Fundamentals in Ophthalmic Practice [1st ed.] 9783030288402, 9783030288419

Table of contents :
Front Matter ....Pages i-xvi
Ophthalmology as a Career (Adam Lewis)....Pages 1-7
Anatomy of the Eye, Orbit and Visual Pathway (Christopher Schulz, Paul Meredith, Anthony Shinton)....Pages 9-34
Physiology of Vision (George Murphy, Kanwaldeep SinghVijjan)....Pages 35-45
Ocular Symptoms: A Systemic Approach to Diagnosis (George Murphy, Pei-Fen Lin)....Pages 47-55
Adnexal Conditions (Shiu Ting Mak, Hunter K. L. Yuen)....Pages 57-85
Conjunctiva and Cornea (Mehran Zarei-Ghanavati, Mohamed Bahgat Goweida)....Pages 87-112
Glaucoma (Richard M. H. Lee, Christopher Liu, Hanbin Lee)....Pages 113-128
Cataract (Matthew McDonald)....Pages 129-150
Medical Retina and Uveitis (Camille Yvon, Moloy Dey)....Pages 151-178
Vitreous and Retina (Emily Shao, Sui Chien Wong)....Pages 179-194
Ocular Tumours (Bertil E. Damato)....Pages 195-209
Ocular Injuries and Emergencies (Ahmed Bardan, Hanbin Lee)....Pages 211-219
Neuro-ophthalmology and Strabismus (Hanbin Lee, Adam Bates)....Pages 221-232
Back Matter ....Pages 233-239

Citation preview

Fundamentals in Ophthalmic Practice Christopher Liu Hanbin Lee Editors

123

Fundamentals in Ophthalmic Practice

Christopher Liu  •  Hanbin Lee Editors

Fundamentals in Ophthalmic Practice

Editors Christopher Liu Sussex Eye Hospital Brighton and Sussex Medical School Tongdean Eye Clinic Brighton and Hove UK

Hanbin Lee Sussex Eye Hospital Brighton and Hove UK

ISBN 978-3-030-28840-2    ISBN 978-3-030-28841-9 (eBook) https://doi.org/10.1007/978-3-030-28841-9 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

We thank our parents, family and teachers and dedicate the book to apprenticeship.

Foreword

It gives me great pleasure to provide this Foreword to what is clearly an excellent primer in ophthalmology. Professor Christopher Liu is well suited to edit this book that promises to be an excellent textbook for medical students, trainees new to ophthalmology and other professionals who look after patients with problems relating to their eyes or vision. Prof. Liu has made extensive contributions to education, clinical care and research in ophthalmology over many years for which work he was honoured with an OBE in the Queen’s Honours List. The chapters cover important and common areas encountered in ophthalmology. The contributing authors are multi-national and many of them have worked here in the Sussex Eye Hospital and have been close associates with Prof. Liu. Dr. Hanbin Lee, the co-editor is one such excellent doctor who has worked with Prof. Liu. I have no doubt that this book will be an important addition to the existing literature in ophthalmology and I wish it the success that it deserves.

August 2020

Varadarajan Kalidasan Consultant Paediatric Surgeon and Director of Medical Education Brighton and Sussex University Hospitals NHS Trust, Brighton, UK

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Afterword

Fundamentals in Ophthalmic Practice came to being after many years of Professor Liu’s experience as Undergraduate Ophthalmology Lead at the Brighton and Sussex Medical School and successful decades of nurturing and training fellows and registrars. This textbook is a valuable addition to the textbooks available for ophthalmologists in all stages of their career. Interested medical students and junior doctors will find the chapter on pursuing a career in ophthalmology informative. Ophthalmologists-in-training, optometrists and allied health professionals will value its comprehensive coverage of a range of conditions as well as some basic sciences. Consultants will find this a useful aide-memoire. The book has been written with the core tenets of a mentor and mentee relationship in mind that exists in many surgical specialities, and ophthalmology is no exception. The majority of chapters having been written by ophthalmologists-intraining with a supervising consultant making them succinct and easy to follow with core topics and tips that should be a useful guide for anyone working in the ophthalmology department. Editors Prof. Christopher Liu and Dr. Hanbin Lee and the chapter authors are to be congratulated for their work and contribution to this textbook. August 2020 

Bernard Chang President, Royal College of Ophthalmologists London, UK

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Preface

Thank you very much for your interest in this book, a primer in ophthalmology, put together for quite a wide audience. You may well be a medical student, a junior doctor, an optometrist, an optometric student, an ophthalmic nurse, an orthoptist, an orthoptic student or an ophthalmic technician. We hope the book will benefit you in your care of the patient. Eye care is now provided through teamwork. Ophthalmologists alone cannot deliver adequate capacity to treat ageing populations all over the world. Many ophthalmic conditions are age related, e.g. cataract, glaucoma and macular degeneration. Some are chronic and require life-long care, e.g. glaucoma, macular degeneration and diabetic eye disease. In recognition of the need of teamwork for efficient delivery of eye care and increasing capacity, the Royal College of Ophthalmologists website states: “Aspects of clinical work that were previously the domain of the medically qualified ophthalmologist are now being delivered by a broader multidisciplinary team. This new team of qualified optometrists, orthoptists, ophthalmic nurses and ophthalmic clinical scientists has taken on expanded roles, which releases ophthalmologists to make more complex clinical decisions and to deal with the more complex cases. But this has been at the expense of a systematic approach to education and training to ensure standardised and recognised competences across all ophthalmic secondary care locations in the UK. The Royal College of Ophthalmologists (RCOphth), the Royal College of Nursing (RCN), the College of Optometrists (CoO), The British and Irish Orthoptic Society (BIOS), and the Association of Health Professions in Ophthalmology (AHPO) worked together with other contributors to develop “The Ophthalmic Common Clinical Competency Framework (OCCCF)”. I hope this new book will serve as a useful text for acquiring basic and intermediate knowledge in ophthalmology and ophthalmic practice. As Professor and Undergraduate Ophthalmology Lead at the Brighton and Sussex Medical School (BSMS) for many years, I have come to learn the key ophthalmic knowledge students need and wish to learn, for exams and for the rest of their careers. The book highlights ophthalmic knowledge which they need to remember for life, whichever branch of medicine they choose to enter, as they are xi

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either sight threatening or life threatening. Lecture programmes have been developed over the years along with practical skills such as testing vision, pupils, eye movement, visual fields and how to use a direct ophthalmoscope. These concepts have formed part of the brief for contributing authors, many of whom have connections to Brighton. I am extremely grateful to all the contributing authors, many of whom are experts in their field. Many are involved in the ongoing education of medical students and ophthalmologist-in-training. I thank my co-editor Dr. Hanbin Lee. Not only did she support me with student teaching when she was attached to the Sussex Eye Hospital as an ophthalmologist-in-training, but she has also done much of the leg work for this book. After accepting the task, she has worked tirelessly to liaise with chapter authors, and preparing chapters for us to work on together. I further thank Mr. Varadharajan Kalidasan, Director of Education of the Brighton and Sussex University Teaching Hospitals NHS Trust, for writing an inspiring foreword; Professor Bernie Chang, President of the Royal College of Ophthalmologist for his afterword; and Springer for being such an excellent publisher. Finally, I thank Sue Cooper and Professor Bernie Chang for proof reading. Any errors however remain ours as editors. Brighton and Hove, UK  Christopher Liu

Contents

1 Ophthalmology as a Career��������������������������������������������������������������������    1 Adam Lewis 2 Anatomy of the Eye, Orbit and Visual Pathway ����������������������������������    9 Christopher Schulz, Paul Meredith, and Anthony Shinton 3 Physiology of Vision ��������������������������������������������������������������������������������   35 George Murphy and Kanwaldeep SinghVijjan 4 Ocular Symptoms: A Systemic Approach to Diagnosis������������������������   47 George Murphy and Pei-Fen Lin 5 Adnexal Conditions����������������������������������������������������������������������������������   57 Shiu Ting Mak and Hunter K. L. Yuen 6 Conjunctiva and Cornea ������������������������������������������������������������������������   87 Mehran Zarei-Ghanavati and Mohamed Bahgat Goweida 7 Glaucoma��������������������������������������������������������������������������������������������������  113 Richard M. H. Lee, Christopher Liu, and Hanbin Lee 8 Cataract����������������������������������������������������������������������������������������������������  129 Matthew McDonald 9 Medical Retina and Uveitis ��������������������������������������������������������������������  151 Camille Yvon and Moloy Dey 10 Vitreous and Retina ��������������������������������������������������������������������������������  179 Emily Shao and Sui Chien Wong 11 Ocular Tumours ��������������������������������������������������������������������������������������  195 Bertil E. Damato

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12 Ocular Injuries and Emergencies����������������������������������������������������������  211 Ahmed Bardan and Hanbin Lee 13 Neuro-ophthalmology and Strabismus��������������������������������������������������  221 Hanbin Lee and Adam Bates Appendix A ������������������������������������������������������������������������������������������������������  233

About the Editors

Christopher Liu  was born in Hong Kong to a medical family and attended a UK boarding school in the West Country. He first wanted to become an ophthalmologist when he became short sighted at the age of 13. His undergraduate studies at Charing Cross Hospital Medical School and subsequent postgraduate training posts in London at Charing Cross, Western Ophthalmic and Moorfields Eye Hospitals and Higher Surgical Training at Addenbrooke’s in Cambridge, Norwich and Rome led to his appointment as a consultant with an interest in cornea, external eye disease and cataract in Brighton at the Sussex Eye Hospital. He is a world leading expert in the osteo-odonto-keratoprosthesis (OOKP), with patients seeking his expertise from across the globe. He also serves as an Honorary Clinical Professor and Undergraduate Ophthalmology Lead for the Brighton and Sussex Medical School and has designed the curriculum as well as supervising medical students, registrars and fellows in research. His research interests are in the anterior segment of the eye with over 250 publications, over a dozen inventions and a number of patents. He is an active member in the scientific field, having served as president of The Medical Contact Lens and Ocular Surface Association, British Society for Refractive Surgery and Southern Ophthalmological Society and is the current president of Brighton and Sussex Medico-Chirurgical Society. He is also a past Honorary Secretary of the United Kingdom and Ireland Society of Cataract and Refractive Surgeons, and Council Member and Trustee of the Royal College of Ophthalmologists. He holds honorary academic and clinical positions past and present in Japan (Kindai University, Osaka), Hong Kong (Chinese University of Hong Kong), Singapore, India and Alexandria University in Egypt. Christopher held a Silver National Clinical Excellence Award. He was Hospital Doctor of the Year in 2005. He is a Member of Merit of the Barraquer Institute in Barcelona, Spain. He was made honorary Fellow of the Royal College of Surgeons, Edinburgh, and honorary Fellow of the Royal College of Physicians, London, in 2018. He delivered the Kersley Lecture in 2018. He was appointed OBE in 2018 New Year’s Honours list for Services to Ophthalmology. Professor Liu established the Anterior Segment Fellowship at the Sussex Eye Hospital in 1998 and also has honorary fellows who attend for observership. xv

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His fellows have followed on his footsteps becoming clinical and academic consultants in teaching hospitals globally. His passion for education has continued throughout his career, and he is frequently invited as an international speaker at conferences and runs training courses for ophthalmologists. He is also an active philanthropist, supporting young musicians and artists. Outside work, his passion is in music, travel, haute cuisine, cross-cultural understanding and freemasonry. He is married to Vivienne and they have three grown-up children. Hanbin Lee  trained at the University College London and completed her foundation training in the North East Thames region. She is currently towards the end of her Ophthalmology Specialty training in the Kent, Surrey and Sussex regions and works as a registrar at the Sussex Eye Hospital. She has had an interest in medical education throughout her training and is passionate about teaching and education. She has previously held posts as Junior Teaching Fellow during her Foundation Year 1 post, and more recently as Undergraduate Ophthalmology Teaching Co-ordinator and Honorary Clinical Lecturer at Brighton and Sussex Medical School. Outside of work, she enjoys travelling and is an enthusiastic musician.

Photograph of Dr Hanbin Lee with Professor Christopher Liu outside the Brighton and Sussex Medical School Falmer campus

Chapter 1

Ophthalmology as a Career Adam Lewis

1.1  Ophthalmology as a Specialty Ophthalmology is a branch of medicine involving diagnosis and treatment of the eye and visual system. It is unusual in that it is both a medical and surgical specialty, making the ophthalmologist both physician and surgeon. Ophthalmology provides an abundance of opportunities for those with a keen eye for detail, an interest in technology and of course, a steady hand. The combination of both medicine and surgery within one profession has become something of a rarity amongst the medical specialties. The ophthalmologist is privileged to be able to meet the patient, make a diagnosis and treat the patient both medically and surgically, should this be necessary. This builds rapport and improves continuity of care for the patient and job satisfaction for the doctor. The ophthalmologist is required therefore, to have both good diagnostic and interpersonal skills, in addition to surgical dexterity. Ophthalmic practice involves the use of multiple gadgets on a weekly basis. The ophthalmologist in training soon learns to use an array of microscopes, lasers and microsurgical instruments, including the phacoemulsification probe used in cataract surgery. Lasers have a wide range of therapeutic functions in ophthalmology and are used regularly in both clinic and the operating theatre. Ophthalmology, as a specialty, has seen huge technological advancement in recent years in both diagnostic and therapeutic techniques. It is therefore, a very exciting time be an ophthalmologist. Ophthalmology is a visual specialty in more ways than are immediately obvious. In order to diagnose and treat disorders of the visual system, the ophthalmologist must be observant. Much of the ophthalmologist’s clinic time involves using his or her own eyes to view the anatomy of the patient’s eye in microscopic detail. Ophthalmic diagnoses are often made through visual examination as the primary A. Lewis (*) Sussex Eye Hospital, Brighton, UK e-mail: [email protected] © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_1

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diagnostic tool. Radiological and serological tests may be used as a supportive or confirmatory function but are the exception rather than the rule. Commonly used investigations in ophthalmology such as optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) require almost exclusively visual interpretation. For this reason, the ophthalmologist must develop meticulous observational skills and a brain adept at pattern recognition. Many medical students’ and junior doctors’ first and lasting impression of ophthalmology relates to the use of the direct ophthalmoscope. It takes a great deal of practice to become competent at using this instrument. Unfortunately, due to the time pressures created by an extensive medical curriculum, ophthalmology is seldom given more than a 2-week long rotation in most medical schools. This short period does not give students adequate time to fully understand the anatomy of the eye, let alone receive exposure to all that the specialty can offer. Students who may not have previously appreciated ophthalmology as a career through negative formative experiences with the ophthalmoscope, will no doubt be encouraged to hear that this instrument is rarely used in practice by ophthalmologists. Instead, we use a microscopic instrument which allows binocular viewing, known as the slit lamp. By nature of its binocularity, this microscope allows the observer to see a three-­dimensional image of the fine structures within the eye, magnified to reveal exquisite detail.

1.2  Application and Training Structure Ophthalmology is a run-through specialty in the United Kingdom (UK). This means that the applicant need only apply and be accepted once prior to certificate of completion of training (CCT), providing all competencies are met. This is in contrast to most other medical and surgical specialties, which require reapplication after core training. Ophthalmology is a competitive surgical specialty. There are around 95 run-through posts advertised each year throughout the UK. Applicants can apply for a run-through post after Foundation Year 2 through a centralised application system. Whilst no previous experience in ophthalmology is necessary, an elective or Student Selected Component in ophthalmology is a good way to gain experience and show commitment to the specialty prior to applying. Ophthalmology training lasts for 7 compulsory years, although most people go on to do at least one fellowship prior to consultant application. For those with an interest in research there are opportunities for out of programme experiences in research during the training period.

1.3  The Royal College of Ophthalmologists The Royal College of Ophthalmologists (RCOphth) is the professional body that oversees the training curriculum and professional practice of ophthalmologists in the UK.  It received Royal Charter in 1988. Ophthalmic trainees are required to pass a series of professional examinations set by the college in order to become a fellow of the Royal College of Ophthalmologists (FRCOphth). Examinations set

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by the Royal College of Physicians and the Royal College of Surgeons are not required as part of ophthalmic training. The Ophthalmologists in Training Group (OTG) represents the view of ophthalmic trainees to the college. Ophthalmology consistently ranks highly in the annual General Medical Council (GMC) survey for trainee job satisfaction.

1.4  Examination Structure Ophthalmology trainees are required to pass both written and practical examinations. These are currently divided into Part 1 FRCOphth, the Refraction Certificate, and Part 2 FRCOphth. Part 1 FRCOphth covers Basic Sciences and optics and must be passed by the end of specialist trainee year 2 (ST2). Completion of the Refraction Certificate is compulsory before the end of ST3. This certificate allows the ophthalmologist to legally prescribe glasses. Whilst it is quite rare in the UK, with the exception of paediatric ophthalmology, for an ophthalmologist to prescribe glasses, it does remain a mandatory competency. Part 2 FRCOphth consists of written, objective structured clinical examination (OSCE) and viva components and must be passed prior to CCT in ST7, the final year of training.

1.5  Ophthalmic Surgical Training Ophthalmic surgery is often performed under a microscope and is referred to as microsurgery (Fig. 1.1). Cataract surgery is the most common ophthalmic surgical procedure performed and most ophthalmic surgeons, regardless of sub-specialty, perform many cataract operations each year. Cataract surgery is usually carried out under local anaesthesia. Stereopsis (the ability of use both eyes to perceive depth) is no longer a mandatory requirement for application. However, it is strongly advised that candidates do have good eyesight, dexterity and stereopsis. Most surgical procedures do require accurate depth perception and fine hand-eye coordination to be successful. For those considering applying for ophthalmology, stereopsis can be checked using tests available in any ophthalmic department or by consulting an orthoptist (see below). During cataract surgery, the surgeon aims to manually preserve the posterior capsule. This anatomical structure measures only 2  μm at its thinnest point. This is a potent example of the narrow margin between success and failure in ophthalmic surgery. The RCOphth runs a two microsurgical skills courses. Introduction to Ophthalmic Surgery course which is open to anyone who is considering a career in ophthalmology. Introduction to Phacoemulsification course is aimed at ST1 and LAT trainees which offers hands-on practical experience. These courses cover the basics of microscope use, ophthalmic equipment and cataract surgery. The wet-lab courses are highly recommended for foundation doctors wishing to pursue a career in ophthalmology. This serves a number of purposes: firstly, it is a good way of gaining experience in the skills necessary to be an ophthalmologist, prior to committing to a lengthy training programme. Secondly, it is a way of gaining points in the competitive appli-

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Fig. 1.1  An ophthalmic surgeon performing vitreoretinal surgery to repair a retinal detachment. A live image of the retina is projected on screen for other theatre staff to see

cation system. Finally, it allows the trainee to perform surgery from the beginning of the training post. Early application to these courses is advisable as places do tend to fill up quickly. (See ‘Further Reading’ for link to the RCOphth website).

1.6  Ophthalmic Surgical Simulation In recent years the invention of the Eyesi simulator has revolutionised ophthalmic surgical training. Eyesi is a virtual reality ophthalmic surgery simulator which allows the trainee to practise the steps involved in cataract and other forms of eye surgery in the safety of a wet lab situation (Fig. 1.2). The delicate skill of simultaneously coordinating the eyes, hands and feet can be practised prior to the trainee entering a real eye. These simulators are now available in most deaneries throughout the UK.  Any medical student with an interest in ophthalmology should seek out these devices in order to gain a flavour of what ophthalmic microsurgery involves. It is the most authentic surgical simulation experience currently available and is increasingly becoming part of the ophthalmic training curriculum. It can, in fact, be a highly enjoyable and safe way to improve technique at any point during training. Other skills, including suturing and certain steps of corneal, oculoplastic and glaucoma surgery (e.g. trabeculectomy) can be practised in a wet-lab using porcine eyes, which are anatomically similar to human eyes.

1.7  Ophthalmic Sub-specialties Ophthalmology can be broadly divided into eight sub-specialties: • Oculoplastic surgery (plastic surgery around the eye), orbital and lacrimal surgery • Cornea and anterior segment

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Fig. 1.2  Eyesi simulator being used to practise phacoemulsification (cataract) surgery, with permission from VRmagic

• • • • • •

Glaucoma Medical retina Vitreo-retinal surgery Paediatric ophthalmology Neuro-ophthalmology Primary and emergency eye care

Trainees undertake a trainee selected component (TSC) in their ST7 year in a sub-specialty of their choosing. This allows greater preparation for a consultant post in the chosen field, although in most cases further fellowships will be undertaken, often internationally. In addition to ophthalmologists, there are many other allied health professionals in the ophthalmology department. These include ophthalmic nurses, ophthalmic technicians, orthoptists (non-medical professionals trained in eye movement disorders), electrophysiologists, ocular prosthetists and optometrists. There is a wide range of ophthalmic investigations carried out which are unique to ophthalmology, including visual field testing, OCT and corneal topography. Whilst these are usually

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undertaken by ophthalmic technicians, it is advisable that ophthalmic trainees should learn how to carry out these procedures themselves. Ophthalmologists work closely with high street optometrists and often refer patients to them for up-to-­date refraction (glasses) after treating a medical or surgical eye complaint.

1.8  A Day in the Life of an Ophthalmologist Regardless of sub-specialty, the ophthalmologist’s working week is divided between clinic, for medical management, and the operating theatre for surgical management. This is with the exception of a small minority of ophthalmologists who choose not to operate. Ophthalmic conditions can affect all age groups but, as with other specialties, ageing tends to increase incidence of disease. Common conditions in ophthalmology include glaucoma, age-related macular degeneration (AMD), cataract, childhood squint, eyelid tumours and retinal detachment. Ophthalmic trauma can present at any time and most ophthalmologists will be called upon to repair penetrating eye injuries (globe rupture) and eyelid lacerations from time to time in their careers. Ophthalmic surgery makes up a substantial part of the ophthalmologist’s working week and is arguably the most challenging, but also the most rewarding aspect of the job. Each subspecialty involves surgical techniques unique to its field, but there are many skills which are common to all ophthalmic surgeons. These include phacoemulsification (cataract surgery), suturing under a microscope and treatment of ophthalmic emergencies including infection and trauma. Out of hours, the ophthalmic registrar will commonly manage corneal ulcers associated with contact lens use, remove metallic corneal foreign bodies, repair retinal tears using laser and less frequently, repair trauma or treat infection inside the eye (endophthalmitis). This sight threatening condition must be treated as an emergency and a vitreous tap must be taken from the eye using a needle, followed by injection of antibiotics into the vitreous. On-calls can be very busy, as the ophthalmic Ophthalmic Trainee is often the only person from the eye clinic in hospital overnight and at weekends. On-calls are often the best time to see complex pathology and learn to practise with greater independence through the senior years of training. Ophthalmology clinics are very busy. Just under 10% of UK National Health Service (NHS) outpatient appointments take place in the eye clinic. With an ageing population, patient numbers are projected to rise exponentially over the coming decades. Despite this heavy workload, ophthalmology remains a hugely rewarding specialty. There is great scope for research and innovation within ophthalmology, and trainees and consultants are encouraged to incorporate research into their working schedules. Presenting at international conferences is perhaps one of the most enjoyable aspects of the job and provides the opportunity to travel and meet like-­ minded people all over the world. There is great satisfaction in working with different allied health professionals in a multidisciplinary team. Ophthalmologists often have a role in leading and teaching this MDT.

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As a career, ophthalmology offers great job satisfaction and still allows a greater work-life balance than many other medical specialties. Possessing the skills to be able to improve or even restore someone’s sight is a great privilege and brings tremendous joy to both the patient and surgeon alike.

Further Reading Eyesi surgical simulator. https://www.vrmagic.com. The Royal College of Ophthalmologists website. https://www.rcophth.ac.uk.

Chapter 2

Anatomy of the Eye, Orbit and Visual Pathway Christopher Schulz, Paul Meredith, and Anthony Shinton

2.1  Periocular Surface Anatomy and the Eyelids 2.1.1  Eyelids The primary function of the eyelids is to protect the ocular surface. The mechanism of blinking is controlled by both voluntary and involuntary contraction of the orbicularis oculi muscle assisting in the distribution of tears across the ocular surface. Any condition which impairs this function risks ocular surface drying, inflammation or scarring leading to vision loss. In prolonged or extreme cases, impaired eyelid function may lead to a loss of the eye’s structural integrity through corneal ulceration and perforation (Fig. 2.1). The medial and lateral canthi are terms given to the angles where the upper and lower eyelids meet. The eyelid opening (palpebral fissure) is typically 10–12 mm in height centrally, and 30 mm in length. The upper eyelid is larger and contributes more to blinking and eyelid closure than its fellow lower lid. With the eye in primary gaze (looking straight ahead), the upper lid margin rests 1–2 mm below the superior border of the cornea. The lower eyelid rests at the border of the inferior cornea. The anterior surface of each eyelid is covered by a very thin layer of skin that folds easily (Fig. 2.2). The posterior surface is lined by the palpebral conjunctiva which is continuous with the bulbar conjunctiva as it folds back on itself at the upper and lower fornices. The skin and conjunctiva meet at the eyelid margin. Lying in the plane between the skin and conjunctiva of each eyelid is the tarsal plate. The tarsal plate offers structural integrity to the eyelid and houses the meibomian glands, about 20–25 in each of the four eyelids. The meibomian glands open onto the eyelid margin. The secretion of oily meibum onto the surface of the tear film prevents C. Schulz (*) · P. Meredith · A. Shinton Wessex School of Surgery - Ophthalmology, Winchester, UK e-mail: [email protected] © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_2

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Superior lacrimal punctum Caruncle Medial canthus

Lateral canthus

Meibomian glands

Plica semilunaris Inferior lacrimal punctum

Fig. 2.1  Surface anatomy of the eyelid

Periosteum of frontal bone Orbicularis oculi Orbital septum Müller’s muscle Aponeurosis of levator palpebrae superioris Skin Meibomian gland (in tarsal plate)

Orbital fat Levator palpebrae superioris Superior rectus Conjunctival fornix Bulbar conjunctiva Palpebral conjunctiva

Fig. 2.2  The eyelid. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. Cosmetic Facial Anatomy by J. Javier Servat, Eric B. Baylin © (2018))

excess evaporation and ocular dryness. The tarsal plate is continuous with the orbital septum, which is itself an extension of the periosteum of the orbital margin. At their medial and lateral borders, the tarsal plates receive an insertion of the canthal tendons which fix the canthi to the (marginal tubercle formed by the) zygoma laterally and the (lacrimal crest and the frontal process of the) maxilla medially. The upper tarsus receives the aponeurotic insertion of the levator palpebrae superioris muscle (LPS; the primary eyelid elevator) and Müller’s muscle (secondary elevator under sympathetic control). Fibres of the LPS also extend into the eyelid

2  Anatomy of the Eye, Orbit and Visual Pathway Fig. 2.3  Orbicularis oculi. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. Cosmetic Facial Anatomy by J. Javier Servat, Eric B. Baylin © (2018))

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Frontalis muscle Orbital orbicularis Preseptal orbicularis Pretarsal orbicularis Raphe

skin forming the visible skin crease. Involutional changes with age may cause the upper eyelid to droop (ptosis). The LPS receives its innervation from the superior branch of the oculomotor nerve and ptosis is therefore also an important sign in some cases of oculomotor nerve (cranial nerve III) palsy. The lower tarsus receives the insertion of the lower eyelid retractor under sympathetic control. Together, the LPS, Müller’s muscle and the lower lid retractors act to widen the palpebral fissure. The fibres of the orbicularis muscle are elliptical, originating at the medial canthal tendon and the surrounding bone (Fig. 2.3). The muscle traverses anterior to the tarsal plate, the orbital septum and the bones of the orbital margin. These elliptically arranged fibres serve to narrow the palpebral fissure as they contract. The eyelashes (about 150 in the upper lid and 75 in the lower) originate from the skin just anterior to the eyelid margin and are arranged in 2–3 rows. The sebaceous glands of Zeiss open into each lash follicle. Adjacent to the bases of the eyelashes are also modified sweat glands known as glands of Moll. A greyish line separates the anterior portion of the eyelid margin (skin and orbicularis) from the posterior component (tarsal plate and conjunctiva) and is an important surgical landmark for eyelid reconstruction.

2.1.2  Lacrimal Gland The lacrimal gland contributes to production of the tear film. Each lacrimal gland is divided into two lobes (larger orbital part and smaller palpebral part) as it folds around the lateral edge of the fan-shaped levator palpebrae muscle’s aponeurotic insertion into the tarsus. The orbital portion lies above the aponeurosis and beneath the frontal bone just inside the superotemporal orbital margin. The palpebral (eyelid) portion lies beneath the aponeurosis and extends into the upper eyelid.

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Its inferior border is closely related to the lateral aspect of the superior conjunctival fornix and can be visualized when the upper eyelid is everted. The excretory ducts pass from the orbital portion through the palpebral portion to drain into the superior conjunctival fornix.

2.1.3  Tear Drainage Tears spread medially across the surface of the eye (Fig. 2.4). About 5 mm from the medial canthus, the punctum is visible on each eyelid margin as a 0.3 mm opening into the lacrimal canaliculus. Tears drain though the punctum into the upper and lower canaliculi. The canaliculi have a 2 mm vertical portion before turning sharply medially toward the lacrimal sac and continuing horizontally for 7–8 mm. The lacrimal sac is found within a fossa formed by the anterior lacrimal crest of the maxillary bone (easily palpable) and the posterior crest of the lacrimal bone, lying posterior to the medial canthal tendon. In most individuals, the upper and lower canaliculi will fuse to form a common canaliculus prior to opening into the sac. Superior punctum

Superior canaliculus Lacrimal gland

Inferior punctum

Lacrimal sac

Inferior canaliculus Nasal cavity Nasolacrimal duct

Inferior meatus

= Flow of tears

Fig. 2.4  The lacrimal system. Blue arrows denote direction of tear flow

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From the sac, tears will drain through the nasolacrimal duct at the lower border of the lacrimal sac. This duct passes through the nasolacrimal canal, a 12 mm passageway between the maxillary bone and the inferior nasal concha. The duct drains tears into the inferior meatus of the nasal cavity.

2.1.4  Vascular Supply to the Eyelids The eyelids contain a dense network of blood vessels (Fig. 2.5). The lateral palpebral artery emerges from the lacrimal artery, a branch of the ophthalmic artery and anastomoses with the medial palpebral artery via the marginal and (when present) peripheral arcades in each eyelid. The medial palpebral artery is a terminal branch of the ophthalmic artery. The arcades receive contributions from the supraorbital and supratrochlear arteries which are also branches of the ophthalmic artery and thus the internal carotid circulation. The arcade also receives contributory branches from the external carotid system via the facial artery, the infraorbital artery and the temporal artery.

Frontal artery

(branch of temporal a.)

Supraorbital artery

(branch of ophthalmic a.)

Peripheral arcade Lacrimal artery

(branch of ophthalmic a.)

Marginal arcade Medial palpebral artery Angular artery

Transverse facial artery (branch of temporal a.)

Infraorbital artery

(branch of maxillary a.)

Facial artery

(branch of external carotid a.)

Fig. 2.5  Arterial supply to the eyelids. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. Cosmetic Facial Anatomy by J. Javier Servat, Eric B. Baylin © (2018))

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2.2  The Orbit 2.2.1  Osteology of the Orbit Each orbit forms a pyramid-shaped bony cavity to protect the globe and transmit nerves and blood vessels. The medial wall lies in the sagittal plane with the lateral wall orientated at 45° to the medial wall (Fig.  2.6). The apex of the pyramid is directed posteriorly, medially, and slightly superiorly. The orbital aperture forms the base of the pyramid. The four walls of the orbit are formed from seven bones: frontal, zygomatic, maxilla, palatine, lacrimal, ethmoid, and sphenoid (Fig. 2.7). • • • •

Roof: frontal bone, lesser wing of sphenoid Lateral wall: greater wing of sphenoid, zygomatic bone Medial wall: body of sphenoid, maxilla, ethmoid, lacrimal bone Floor: maxilla, zygoma, palatine bone

Fig. 2.6  Geometry of the orbit (Illustration by Muhammed Jawad)

Sagittal plane

Visual axis

Medial orbital wall

Orbital axis

23˚

Lateral orbital wall

45˚

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Frontal bone Lesser wing of sphenoid Superior orbital fissure Greater wing of sphenoid Zygoma Inferior orbital fissure

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Supraorbital notch Trochlear fossa Optic foramen

Ethmoid bone Lacrimal bone

Infraorbital foramen

Maxilla

Fig. 2.7  Osteology of the orbit. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. Anatomy of the Orbit by Mohammad Wakeel Ansari, Ahmed Nadeem © (2016))

The medial wall is the thinnest, being only 0.2–0.4 mm thick (lamina papyracea) and is susceptible to the transmission of infection from the adjacent paranasal sinuses into the orbit (causing orbital cellulitis). Below the floor of the orbit lies the maxillary sinus. A blunt force to the eye may be transmitted to the orbital contents causing a ‘blow-out fracture’ of either the medial wall or floor of the orbit. Although the orbital floor is thicker (0.5–1 mm) than the medial wall it is commonly involved in blow out fractures as the medial wall is buttressed by the ethmoidal air sinuses. The lateral orbital margin is thickest, being the region most susceptible to direct trauma. It should be noted however, that to allow for peripheral horizontal gaze, the globe itself is most exposed from the lateral aspect. 2.2.1.1  Superior Orbital Fissure The superior orbital fissure (SOF) is a gap between the greater (lateral wall) and lesser (roof) wings of the sphenoid bone. It is comma shaped and 22 mm long. It transmits several key structures between the orbit and the intracranial cavity (Fig. 2.8):

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Trochlear nerve

Frontal nerve Lacrimal nerve

L.P.S

Dura mater

S.O. Medial rectus

S.R. Superior ophthalmic vein

III1 III2

Lateral rectus muscle

Optic nerve Central tendon I.R.

Optic foramen Ophthalmic artery Nasociliary nerve 6th cranial nerve Inferior ophthalmic vein

I.O.F.

Two heads of lateral rectus Origin of S.R. - Superior rectus muscle I.R. - Inferior rectus muscle S.O. - Superior oblique muscle L.P.S. - Levator palpebrae superioris

Fig. 2.8  Superior orbital fissure. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. Extraocular and Intraocular Muscles by Mohammad Wakeel Ansari, Ahmed Nadeem © (2016)) 1. Lacrimal nerve (branch of CN V1) 2. Frontal nerve (branch of CN V1) 3. Trochlear nerve (CN IV) 4. Superior ophthalmic vein

5. Superior division oculomotor nerve (CN III) 6. Nasociliary nerve (branch of CN V1) 7. Inferior division of oculomotor nerve (CN III) 8. Abducent nerve

Of these, the latter four structures all enter the orbit inside a common tendinous ‘ring’ found on the orbital aspect of the SOF. This tendinous ring is a thickening of periosteum and forms the origin of the four rectus muscles which fan outward and forward to insert on the globe. This cone-shaped arrangement gives rise to two distinct and clinically important compartments of the orbit: the intraconal and extraconal compartments. 2.2.1.2  Inferior Orbital Fissure The inferior orbital fissure is a gap between the greater wing of the sphenoid (lateral wall) and the maxilla (orbital floor). This provides communication between the orbit and both the infratemporal and pterygopalatine fossae. It transmits the following:

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1. Infraorbital nerve (branch of CN V2) 2 . Zygomatic nerve (branch of CN V2) 3. Branches from pterygopalatine ganglion 4. Inferior ophthalmic vein 5. Infraorbital artery (branch of maxillary artery) The infraorbital nerve and artery pass forwards from the inferior orbital fissure along the orbital floor in the infraorbital groove. As they course forward, they descend into the orbital floor through the infraorbital canal (in the roof of the maxillary sinus). They exit the frontal aspect of the face 4 mm below the orbital margin through the infraorbital foramen. 2.2.1.3  Optic Canal The optic canal lies in the lesser wing of the sphenoid. It measures 4–10 mm long and passes anteriorly, inferiorly and laterally from the middle cranial fossa to the orbital cavity. It contains the optic nerve with surrounding meninges, the ophthalmic artery and sympathetic nerve fibres. The optic canal enters the orbit within the recti muscles’ common tendinous ring, and so these structures are found within the intraconal compartment.

2.2.2  Paranasal Sinuses The paranasal sinuses are air-filled cavities found within the facial bones, lined with mucosa. The paired frontal sinuses are found within the frontal bone behind the superciliary arches (above the orbital margin). They drain into the middle meatus of the nasal cavity. They are innervated by the supraorbital nerve and so pain is localized to the forehead and scalp. The ethmoidal sinuses are thin walled air cells and are grouped into anterior, middle and posterior. They are found abutting the medial wall of each orbit. The posterior ethmoidal cells drain to the superior meatus while both the anterior and middle cells drain to the middle meatus of the nasal cavity. Sensory innervation is via the anterior ethmoidal nerve (a branch of the nasociliary nerve which also provides sensory innervation to the eye), posterior ethmoidal nerve and orbital branch of pterygopalatine ganglion. Pain from any stimulus within the ethmoidal sinus (e.g. inflammation) may be perceived between, in or behind the eyes. The sphenoidal sinus is located within the body of the sphenoid. The pituitary gland and optic chiasm lie above with the cavernous sinuses either side. It drains to the sphenoethmoidal recess within the nasal cavity. Sensory innervation is via the posterior ethmoidal nerve, again a branch of the nasociliary nerve and the orbital branches of the pterygopalatine ganglion.

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The paired maxillary sinuses are the largest of the sinuses, located within the maxillary bone and beneath the orbital floor. They drain to the right and left middle meatus of the nasal cavity. Thus, unlike the other sinuses, this drainage pathway goes against gravity with the head in the erect position. The upper molar teeth project into the sinus. Dental infection can cause a maxillary abscess. Sensory innervation is via the infraorbital nerve and some of its branches to the teeth. Therefore, painful stimuli within the maxillary sinus may be perceived in the cheek, lower eyelid, or teeth.

2.2.3  Orbital Contents Each orbit has a volume of approximately 30 mL, only one fifth of which is occupied by the globe. 2.2.3.1  Extraocular Muscles (Fig. 2.9) There are six extraocular muscles: four recti and two obliques. The four recti originate from the aforementioned common tendinous ring. They pass forwards and fan outwards to insert onto the sclera anterior to the equator in an arrangement known as the spiral of Tillaux (Table 2.1). The rectus muscles are supplied by muscular branches of the ophthalmic artery. As each rectus muscle inserts into the sclera, it Equator

Roof of orbit Trochlea Bend of superior oblique by 51˚ Insertion of superior oblique Lateral rectus

Medial rectus Superior rectus Apex of orbit Annulus of Zinn Inferior rectus

Inferior oblique Floor

Fig. 2.9  Extraocular muscles. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. Extraocular and Intraocular Muscles by Mohammad Wakeel Ansari, Ahmed Nadeem © (2016))

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Table 2.1  Extraocular muscles

Muscle Medial rectus Inferior rectus Lateral rectus Superior rectus Superior oblique Inferior oblique

Primary action (1) Secondary action (2) Tertiary action (3) Origin 1. Adduction CTR 1. Depression 2. Adduction 3. Extorsion 1. Abduction 1. Elevation 2. Adduction 3. Intorsion 1. Depression 2. Abduction 3. Intorsion 1. Elevation 2. Abduction 3. Extorsion

Insertion 5.5 mm from limbus

Innervation Oculomotor nerve (III) Oculomotor nerve (III)

CTR

6.5 mm from limbus

CTR

6.9 mm from limbus

CTR

7.7 mm from limbus

Sphenoid, apex of orbit above CTR Maxilla, behind lacrimal fossa

Upper outer quadrant of Trochlear globe behind equator nerve (IV)

Abducent nerve (VI) Oculomotor nerve (III)

Lower outer quadrant of Oculomotor nerve (III) globe, behind equator, between globe and lateral rectus

CTR common tendinous ring

also transmits two anterior ciliary arteries to supply the anterior segment of the eye (except the lateral rectus which transmits just one). The inferior oblique originates anteromedially on the orbital floor and passes posterolaterally under inferior rectus (extraconally) to insert posterior to the equator. The superior oblique is a long slender muscle that passes forwards from its origin at the orbital apex on the body of the sphenoid above and medial to the common tendinous ring. It runs forward along the superomedial orbital wall to the anterior orbit where it slings around a fibrocartilaginous pulley (the trochlea) to then pass downwards, backwards and laterally. It passes inferior to superior rectus to a fan shaped insertion posterior to the equator. 2.2.3.2  Orbital Fascia The orbital contents are contained within a fascial sac termed the periorbita. This is continuous with the periosteum of the facial bones at the orbital margin and with the septum in each of the eyelids. The orbital contents are further invaginated by a network of fascial septa, interposed by locules of fat. A fibrous intermuscular membrane connects the four recti muscles to separate the intra- and extraconal compartments. Surrounding each of the extraocular muscles is a fibrous sheath that blends with Tenon’s capsule at their insertions to the globe. Tenon’s is a fascial membrane that envelops the globe, overlying the sclera all the way from the optic nerve to just behind where the sclera and cornea meet (the limbus). At the medial and lateral recti insertions, a thickened expansion of Tenon’s forms the medial and

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lateral check ligaments, which are fixed at the medial and lateral orbital margin respectively. These are joined to one another by the suspensory ligament of Lockwood which acts as a fascial ‘hammock’ to suspend the globe. 2.2.3.3  Blood Vessels of the Orbit The ophthalmic artery emerges as the first branch of the internal carotid artery and enters the orbit via the optic canal. The ophthalmic artery travels forward through the orbit, giving off several branches (Fig. 2.10). Key Branches of the Ophthalmic Artery • Central artery of the retina Branches soon after leaving the optic canal. Enters the optic nerve 12 mm behind the globe. • Lacrimal artery Passes along the upper border of lateral rectus to the lacrimal gland. • Ciliary arteries Supratrochlear artery Dorsal nasal artery Short posterior ciliary arteries

Supraorbital artery

Long posterior ciliary artery Anterior ethmoidal artery Ophthalmic artery Posterior ethmoidal artery Canalicular part of ophthalmic artery (crosses under surface of optic nerve within optic canal)

Central retinal artery (CRA) CRA (within optic nerve) Lacrimal artery Long posterior ciliary artery Optic nerve CRA (inferior to optic nerve) Orbital part of ophthalmic artery (crosses optic nerve superiorly)

Fig. 2.10  The ophthalmic artery. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. The Blood Supply to the Eyeball by Mohammad Wakeel Ansari, Ahmed Nadeem © (2016))

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Long and short posterior ciliary arteries supply the globe. • Muscular branches Supply extraocular muscles. Those to the recti muscles continue as the anterior ciliary arteries and supply the anterior segment of the globe. • Supraorbital artery Supplies levator palpebrae superioris, the upper eyelid and skin of the forehead. • Ethmoidal arteries Supplies posterior ethmoidal cells and nasal septum • Supratrochlear artery Supplies the skin of the forehead. • Dorsal nasal artery Supplies lacrimal sac and anastomoses with the facial artery. Gives off medial palpebral artery to eyelids. Venous drainage is into the cavernous sinus via the larger superior ophthalmic vein and smaller inferior ophthalmic vein. The orbital veins are valveless meaning infection can spread from the facial veins to the cavernous sinus via this route. 2.2.3.4  Nerves of the Orbit and Beyond Optic Nerve (Cranial Nerve II) and the Visual Pathway The optic nerve is formed from the axons of retinal ganglion cells. It carries visual information from the retina to the brain and is the only part of the central nervous system that can be directly visualised. The nerve is divided into four portions (below), with all but the intraocular portion being surrounded by the three meningeal layers. • • • •

Intraocular: 1 mm and unmyelinated Orbital: 30 mm with a slight S-shape bend allowing for globe movement Intracanalicular: 10 mm within the optic canal Intracranial: 10–15 mm

The intracranial portion ends at the optic chiasm where nerve fibres from the nasal half of the retina (temporal visual field) decussate (cross) to the contralateral optic tract. Temporal fibres continue without decussating in the ipsilateral optic tract. This crossing occurs just anterior to the pituitary stalk with the pituitary gland and the cavernous sinus sitting immediately below the optic chiasm. Either side of the optic chiasm is the internal carotid artery as it exits the superior part of the cavernous sinus. The optic tracts wind around the cerebral peduncles of the midbrain to the lateral geniculate body. Approximately 90% of fibres take this lateral root and are involved in conscious vision. A smaller medial root is projected to the superior colliculus and the pretectal area. The pretectal area is responsible for the pupillary light reflex, by synapsing with the oculomotor nerve’s parasympathetic fibres at the Edinger-­ Westphal Nucleus (EWN, see below). These fibres serve to constrict the pupil in

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response to light, and each EWN is stimulated by both the ipsilateral (direct light reflex) and contralateral (consensual light reflex) optic tract (more below). Nerve fibres relating to conscious vision pass posteriorly from the Lateral Geniculate Body (LGB) as a large, looping fan shaped optic radiation, that spreads through both temporal and parietal lobes of the brain. The optic radiations pass to the primary visual cortex located in the walls of the calcarine sulcus of the occipital lobe. From here, neurons spread to secondary visual areas in the parietal, temporal and frontal lobes that are responsible for interpreting and responding to the visual inputs. Understanding the visual pathway is important clinically as patterns of visual field deficit can localize the site of insult (Fig. 2.11). Any injury that is pre-chiasmal

Sphincter pupillae

Optic nerve 1 Ciliary ganglion Third cranial nerve 3

2 Edinger-Westphal nucleus

Optic chiasm Crossing of nasal fibres Optic tract

Pupillary fibres

4

Lateral geniculate body Optic radiation

Field defects 1

5

2 3 4 5

ary ex Prim al cor t visu Occipital lobe of brain

Fig. 2.11  The visual pathway (Illustration by Muhammed Jawad)

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(optic nerve) will result in a monocular scotoma. It should be recognized that fibres are topographically arranged within the nerve corresponding to the area of retina they are derived from (e.g. superior fibres serve the superior retina however will receive light from the inferior visual field). Pituitary gland tumours will lead to a bitemporal hemianopia as the decussating nasal fibres will be most affected and these receive light from the lateral visual field. Often, the upper outer quadrant of vision is affected first due to the inferior fibres being compressed by the inferiorly positioned pituitary gland. Any insult that is postchiasmal will lead to a homonymous hemianopia. If the right optic tract or optic radiation is affected, this will affect the non-decussating neurons of the right temporal retina and the decussating neurons of the left nasal retina, leading to a left sided field defect in each eye (left homonymous hemianopia). The upper fibres of the optic radiation transmit visual information from the superior retina (inferior visual field) which travels within the parietal lobe and its inferior fibres carrying inferior retinal information (superior visual field) travel within the temporal lobe. The size of the optic radiations make them particularly susceptible to ischaemia (stroke) and compression from tumours.

Oculomotor Nerve (Cranial Nerve III) The oculomotor nerve carries motor fibres to all the extraocular muscles except lateral rectus and superior oblique, and preganglionic parasympathetic fibres to the eye. Originating at the level of the superior colliculus the nerve emerges from the anterior midbrain at its border with the pons. It passes forwards, laterally and slightly inferiorly between the posterior communicating artery medially, the posterior cerebral artery above and the superior cerebellar artery below. These relationships make it susceptible to compression from an aneurysm. The oculomotor nerve then runs along the lateral wall of the cavernous sinus. It enters the intraconal compartment of the orbit through the SOF (within the common tendinous ring). The nerve divides into a superior division (to supply superior rectus and levator palpebrae superioris) and an inferior division (to medial rectus, inferior rectus, and inferior oblique). Preganglionic parasympathetic fibres originating from the Edinger-Westphal nucleus in the midbrain pass along the oculomotor nerve (III) and enter the orbit on its inferior division. They synapse in the ciliary ganglion and post-ganglionic fibres travel along the short ciliary nerves to supply the sphincter pupillae (pupil constriction) and ciliary muscle (accommodation). As preganglionic fibres are located superficially in the oculomotor nerve they are susceptible to compressive lesions.

Trochlear Nerve (Cranial Nerve IV) The trochlear nerve nuclei lie in the midbrain at the level of the inferior colliculus. It is unusual in that the nerve fibres decussates before they leave the brainstem on its posterior aspect. The nerves wind around the cerebral peduncles of the brainstem to

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pass forwards under the free edge of a dural fold called the tentorium cerebelli. Along with the oculomotor nerve it passes between the posterior cerebral artery above and the superior cerebellar artery below. It enters the lateral wall of the cavernous sinus, initially running beneath the oculomotor nerve. In the cavernous sinus, it crosses the oculomotor nerve and exits above it to enter the superior orbital fissure outside the common tendinous ring. It passes in to the extraconal orbital compartment where it supplies the superior oblique muscle. Trigeminal Nerve (Cranial Nerve V) The trigeminal is the largest cranial nerve and the main sensory nerve of the head. The nucleus spans the entire brainstem, from the midbrain to the medulla. There are three distinct sensory nuclei whose axons course through the sensory root exiting at the level of the pons to the trigeminal ganglion where they are divided among three trigeminal branches: • The ophthalmic nerve (V1) enters the cavernous sinus where it forms three branches: –– The frontal nerve is the largest branch and enters the orbit through the SOF outside the CTR. It is the most superior structure in the orbit, lying just inside the periorbita coursing along the roof of the orbit. It has two terminal branches: the supraorbital branch that passes through the supraorbital notch to supply the conjunctiva and skin of the upper lid, forehead and most of the scalp; and the supratrochlear branch passes above the trochlea to supply the skin of the medial upper lid and forehead. –– The lacrimal nerve is the smallest branch. It enters the orbit through the SOF but outside the CTR.  It travels along the superotemporal orbit to provide sensory innervation to the lacrimal gland, as well as the conjunctiva and skin of the upper outer eyelid. Within the orbit it also receives secretomotor parasympathetic fibres that are responsible for lacrimation. These parasympathetic fibres have a complex course, originating at the superior salivatory nucleus in the pons and ‘hitch-hiking’ with branches of the facial nerve (CN VII) to the pterygopalatine fossa which is a space found posterior to the maxilla and inferotemporal to the apex of the orbit. Here the secretomotor fibres synapse in the pterygopalatine ganglion. Postganglionic fibres ‘hitchhike’ along the zygomatic and then zygomaticotemporal branches of the maxillary nerve (CN V2) as they traverse the lateral wall of the orbit. They finally cross to the lacrimal nerve (V1) in the anterior orbit to reach the lacrimal gland. –– The nasociliary nerve enters the intraconal orbit through the SOF and within the CTR. It supplies the globe (via the long and short posterior ciliary nerves), the sphenoid sinus (via the posterior ethmoidal nerve), the ethmoid sinus, nasal septum and external nose (all via the anterior ethmoidal nerve). Its terminal branch is the infratrochlear nerve that exits the anterior orbit below the

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trochlea and innervates the medial skin and conjunctiva of the eyelids, the lacrimal sac, the caruncle and the skin of the nose. • The Maxillary nerve (V2) provides sensory innervation to the midface. It also enters the lateral wall of the cavernous sinus before entering the pterygopalatine fossa through a small hole in the skull base called the foramen rotundum. An infraorbital branch enters the orbit via the inferior orbital fissure. It passes along the orbital floor in the infraorbital groove and exits via the infraorbital foramen to supply the skin and conjunctiva of the lower lid and midface. • The Mandibular nerve (V3) supplies sensory innervation to the lower face and also receives a small motor root that supplies the muscles of mastication. Abducent Nerve (Cranial Nerve VI) The abducent nerve emerges from the lower border of the pons near the midline. It loops around the anterior inferior cerebellar artery (a branch of the basilar artery as it joins the arterial circle of Willis) and passes up between the brainstem and the clivus. At the upper border of the petrous temporal bone it makes a sharp turn from vertical to horizontal to run forwards in the cavernous sinus lateral to the internal carotid artery. It enters the orbit through the SOF (within the CTR) where it supplies the lateral rectus muscle. It is susceptible to compression from aneurysmal bleeding in the pontine cistern. It is also susceptible to injury in head trauma or raised intracranial pressure due to compression against either the anterior inferior cerebellar artery or the sharp crest of the petrous temporal bone. The medial longitudinal fasciculus runs cranio-caudially in the area just lateral to the oculomotor nucleus. It connects the oculomotor, trochlear and abducens nuclei, co-ordinating the signals between them. Lesions here can cause internuclear ophthalmoplegia. Facial Nerve (Cranial Nerve VII) The facial nerve provides motor supply to the muscles of the face including those responsible for brow depression and elevation, and the orbicularis oculi which acts to close the eyelid. The facial nerve also provides parasympathetic supply to the lacrimal gland and receives taste sensation from the anterior two thirds of the tongue. The facial nerve is frequently paralysed and may lead to incomplete eyelid closure and an exposed ocular surface (Fig. 2.12). Sympathetic Supply of the Orbit The sympathetic nervous system is associated with the ‘fight or flight’ response and supplies the dilator pupillae muscle (pupil dilation), ciliary muscle (relaxation for distance focus), lacrimal gland (reduces lacrimation), and the upper and lower tarsal muscles (widening of palpebral fissure). First order neurons descend from the

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Posterior communicating artery

Anterior communicating artery

Trochlear nerve

Anterior cerebral artery

Trigeminal nerve

Posterior cerebral artery

Middle cerebral artery

Basilar artery Superior cerebellar artery

Internal carotid artery

Facial nerve Pons

Abducent nerve Tentorium cerebelli Medulla

Frontal view

Superior view

Fig. 2.12  Relationships between the cranial nerves and the arterial circle of Willis

hypothalamus to the spinal cord at level C8–T2. Here the second order neuron exits the spinal cord to join the sympathetic chain. The fibres pass over the apex of the lung, and loop under the subclavian artery before synapsing in the superior cervical ganglion at the bifurcation of the common carotid artery. The third order neurons form a sympathetic plexus that follows both the internal and external carotid arteries. Those related to the external carotid artery will innervate the sweat glands of the head, while the main plexus ascends with the internal carotid artery to the cavernous sinus. Third order neurons ‘hitch-hike’ with the superior and inferior divisions of CN III as well as with the nasociliary nerve (branch of CN V2) to reach their sites of action. Horner’s syndrome manifests as loss of sympathetic function due to an insult anywhere along this entire course (including spinal nerve injury, carotid or subclavian artery dissection, apical lung tumours, cavernous sinus thrombosis, carotid-­ cavernous fistula, and orbital compression or inflammation). The syndrome typically presents with a constricted pupil (miosis) and a slight ptosis (Fig. 2.13).

2.3  The Eye The adult eyeball, or globe, is approximately 2.5 cm in diameter. It has three principal layers (Fig. 2.14): • The outer protective layer, comprising the cornea and sclera. • The middle vascular pigmented layer, or uveal tract. This comprises the iris, the ciliary body, and the choroid. • The inner nervous layer, formed by the retina and optic disc.

2  Anatomy of the Eye, Orbit and Visual Pathway Optic Chiasm II

27 Pituitary gland

Internal carotid artery Cavernous sinus

Oculomotor nerve III Trochlear nerve IV

Internal carotid artery Ophthalmic nerve V1

Abducens nerve VI

Maxillary nerve V2 Sphenoid sinus

Fig. 2.13  Image of the cavernous sinus. (Illustration by Kim Yeohun)

Palpebral or tarsal conjunctiva Fornix Ciliary body Angle of anterior chamber Posterior chamber (P.C.)

Iris Comea Anterior chamber (A.C.) Lens Eyelid Tarsus Bulbar conjunctiva

Vitreous in vitreous chamber (V.C.) Physiological cup Optic nerve Dura of optic nerve Fovea

Levator palpebrae superioris (L.P.S.) Fornix

Ciliary processes Zonule Tenon’s capsule Retina Choroid Sclera

Fig. 2.14  Section through the eye. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. The Eyeball: Some Basic Concepts by Mohammad Wakeel Ansari, Ahmed Nadeem © (2016))

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The globe can be divided into anterior and posterior segments, separated by the crystalline lens. The iris further divides the anterior segment into the anterior and posterior chambers.

2.3.1  The Outer Layer 2.3.1.1  Conjunctiva & Tenon’s Capsule The conjunctiva is a thin translucent mucous membrane. It lines the inner surface of the eyelids (palpebral conjunctiva) and then reflects back on itself in the upper and lower fornices to clothe the anterior part of the eyeball (bulbar conjunctiva). Tenon’s capsule is a fascial sheath that encloses the eye, separating the sclera from the conjunctiva anteriorly and the orbital fat posteriorly. There is a potential space between Tenon’s layer and the underlying sclera, although the two are firmly adherent to each other approximately 1.5  mm behind the limbus (the junction between sclera and cornea) and at the entry site of the optic nerve posteriorly. The potential space between Tenon’s layer and the sclera forms a useful site for an anaesthetic (sub-Tenon’s) block. 2.3.1.2  Sclera The sclera, from the Greek meaning “hard”, is the tough outer coat of the eyeball. It is white and opaque, being composed of an irregular arrangement of collagen and elastic fibres. It has a thickness of 0.6–1.0 mm, but is thinner in areas where the four recti muscles insert. The episclera is a fine elastic tissue covering the surface of the sclera. It has a rich vascular supply to nourish the scleral stroma beneath. 2.3.1.3  Cornea The cornea is a transparent dome of tissue, sometimes described as the ‘window’ to the eye. It is slightly elliptical, measuring around 11.7 mm horizontally and 10.6 mm vertically. The average adult cornea has a central thickness of about 540 μm, increasing to 700 μm in the periphery. The limbus is a transitional zone between the cornea, conjunctiva and sclera. The cornea has five layers (Fig. 2.15). They are as follows, from outermost to innermost: • Epithelium: Comprises five to six layers of epithelial cells, and is continuous with the epithelium of the bulbar conjunctiva. It is the only corneal layer that regenerates following trauma. • Bowman’s layer: An acellular layer of connective tissue. • Stroma: Accounts for around 90% of the corneal thickness. Composed of parallel lamellae of collagen fibrils (predominantly type 1 collagen).

2  Anatomy of the Eye, Orbit and Visual Pathway Fig. 2.15  Histology of the cornea (Illustration by Muhammed Jawad)

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Tear film Epithelium Bowman’s membrane

Stroma

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• Descemet’s membrane: The basement membrane of the corneal endothelium. • Endothelium: A single layer of cells, responsible for maintaining the relative dehydration of the corneal stroma (deturgescence). Endothelial repair is limited to enlargement and sliding of existing cells, with little capacity for cell division. Failure of endothelial function leads to corneal oedema. The cornea is the principal refractive component of the ocular optical system. To transmit light rays, the cornea must remain transparent. Corneal transparency is achieved by its uniform structure, avascularity, and relative dehydration. The cornea receives nutrients from the tear film, the aqueous humour, and the limbal capillaries. It receives a profuse nerve supply from the nasociliary nerve of the ophthalmic nerve (CN V1), via the long ciliary branches.

2.3.2  Uveal Tract The uveal tract is the middle vascular pigmented layer of the eye. It comprises the iris, the ciliary body, and the choroid.

2.3.2.1  Iris The iris is a thin, contractile diaphragm with a round central aperture—the pupil. It controls the amount of light entering the eye. The iris is situated in front of the lens, and it separates the anterior chamber from the posterior chamber.

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The anterior stromal layer of the iris includes both the sphincter and dilator pupillae muscles, which control pupil size. Contraction of the circular sphincter pupillae muscle causes pupil constriction, and is stimulated by parasympathetic fibres from the third cranial nerve. Contraction of the radial dilator pupillae muscle causes pupil dilation, and is stimulated by sympathetic fibres via the long ciliary nerves. The iris receives its blood supply from the anterior ciliary arteries and long posterior ciliary arteries, whose capillaries anastomose in an arterial circle. 2.3.2.2  Ciliary Body The ciliary body extends from the iris root to form a 6  mm wide ring that runs around the inside of the anterior sclera. The ciliary body can be divided into the pars plicata anteriorly, and the pars plana posteriorly. The smoother and flatter pars plana is continuous with the choroid at the ora serrata. The pars plicata has a ridged, or plicated, surface due to its 70 or so ciliary processes. These processes are responsible for the production and secretion of aqueous humour. Beneath the ciliary processes is the ciliary muscle, which forms the bulk of the ciliary body. Contraction of the circular muscle fibres reduces the tension on the lens zonules which attach the ciliary body to the lens, increasing its convexity and its refractive power. Light rays can thereby be brought to a focus on the retina for near vision. This process is known as accommodation. The ciliary muscle is innervated by parasympathetic fibres derived from the third cranial nerve, which reach the muscle via the short ciliary nerves. 2.3.2.3  Choroid The choroid represents the posterior part of the uveal tract. It is a thin (100–220 μm), highly vascular layer between the sclera and retina. Choroidal blood vessels serve to nourish the outer layers of the retina. From innermost to outermost, the choroid comprises the choriocapillaris, the vascular layer, and the suprachoroid. The choriocapillaris is a rich network of capillaries, fed by large and medium-sized blood vessels in the vascular layer beneath. The suprachoroid contains thin sheets of connective tissue running through a potential space between the choroid and sclera. The choroid’s arterial blood supply is derived from branches of the long and short posterior ciliary arteries, which are branches of the ophthalmic artery. The short posterior ciliary arteries supply the choroid as far forward as the equator. The long posterior ciliary arteries supply the choroid as far back as the equator. Venous drainage occurs via four large vortex veins that pierce the sclera and drain into the superior and inferior ophthalmic veins in the orbit.

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2.3.3  Lens The crystalline lens is a transparent, biconvex structure measuring about 9 mm in diameter and 4 mm in thickness in adulthood. It contributes around 25% of the total convergent refractive power of the human eye (the majority comes from the air-­ corneal interface). The lens is suspended behind the iris by the suspensory ligaments (zonules). The zonules arise from the ciliary body circumferentially, and insert into the lens equator. The lens is composed of the capsule, lens epithelium, cortex, and nucleus. It contains neither nerves nor blood vessels. The cortex and nucleus both consist of concentric lamellae of lens fibres. Lamellar fibres are continuously produced throughout life, so that the lens becomes gradually larger and less elastic with age.

2.3.4  Aqueous Humour Aqueous humour is a clear fluid produced by the ciliary processes of the ciliary body. It supplies nutrients to the avascular cornea and lens, removes metabolic waste products, and contributes to intraocular pressure. It enters the posterior chamber between the lens and iris, and then flows through the pupil into the anterior chamber. Aqueous circulates in the anterior chamber, before draining away in the angle of the anterior chamber, via the trabecular meshwork and Schlemm’s canal. A small proportion of aqueous humour drains by the alternative uveoscleral pathway (Fig. 2.16).

Limbus Aqueous vein Canal of Schlemm Pars Plicata Sclera Pars plana Ciliary muscle

Scleral spur Ciliary process

Collecting trunks Epithelium Bowman’s membrane Stroma Descemet’s membrane Endothelium Anterior chamber Trabecular meshwork Angle Iris Pupil Zonule Lens Posterior chamber

Fig. 2.16  Anatomy of the anterior segment and aqueous drainage. Red arrows indicate direction of aqueous flow. (Reprinted/adapted by permission from Springer Nature and Copyright Clearance Center: Springer Nature. The Eyeball: Some Basic Concepts by Mohammad Wakeel Ansari, Ahmed Nadeem © (2016))

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2.3.5  Vitreous Humour The posterior segment of the eye, between the crystalline lens and the retina, is filled by a clear gel called the vitreous. It occupies 80% of the volume of the eye. Its composition is 98% water, with an organized scaffold of fine collagen fibrils. The denser vitreous cortex surrounds a more liquid central vitreous. The vitreous cortex is firmly attached to the inside of the globe at the vitreous base. The vitreous base straddles the ora serrata, attaching the vitreous gel to both the pars plana and the anterior retina. There are also moderately firm attachments at the optic disc margin and posterior lens capsule. Weaker attachments exist between the vitreous and the retina. These attachments weaken further with age.

2.3.6  Retina The retina is the innermost layer of the eyeball, and extends from the ora serrata anteriorly to the optic disc posteriorly. It is responsible for photochemical transduction of optical images. The macula is an oval area of retina located temporal to the optic disc, bordered by the temporal vascular arcades. It has a high concentration of cone photoreceptors, and is responsible for precise central vision. At the centre of the macula lies the fovea centralis, a small depression where inner retinal layers are displaced to give incoming light greater access to the photoreceptors. No blood vessels cross the macula and the central 0.5 mm is an entirely avascular zone, receiving its entire blood supply from the underlying choroid. In cross-section, the retina can be divided into the inner neural retina and the outer retinal pigment epithelium (RPE). The neural retina has nine histological layers, from inner (adjacent to vitreous cavity) to outer (adjacent to RPE): • Inner limiting membrane (ILM): The inner foot processes of Müller cells. • Nerve fibre layer: The axons of ganglion cells, converging towards the optic disc to become continuous with the optic nerve. • Ganglion cell layer: The ganglion cell nuclei. • Inner plexiform layer: Synapses between the ganglion and bipolar cells. • Inner nuclear layer: The bipolar cell and Müller cell nuclei. • Outer plexiform layer: Synapses between the bipolar cells and photoreceptors. • Outer nuclear layer: The nuclei of the photoreceptors (rods and cones). • External limiting membrane: The outer foot processes of Müller cells. • Photoreceptor layer: This layer contains the rods and cones. The rods number approximately 120 million in each eye, and function in dim light. They are distributed mainly in the peripheral retina. The cones, in contrast, number around 7 million and are concentrated at the fovea. They provide detailed colour vision in bright light (Fig. 2.17).

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Retinal pigment epithelium

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Fig. 2.17  Layers of the retina

Fig. 2.18 Widefield fundus photograph of right eye. (a) Optic disc; (b) retinal artery (superonasal branch); (c) retinal vein; (d) macula; (e) fovea

c b d

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The RPE is a single layer of cells beneath the neural retina. Its functions include turnover of photoreceptor outer segments and absorption of excess light. Zonula occludentes between adjacent RPE cells contribute to the blood-retina barrier. At the ora serrata the neural retina ends, whereas the RPE is continuous with the pigmented ciliary epithelium. Between the RPE and the choroid lies Bruch’s membrane. It is only a few microns thick, and includes the basement membranes of the RPE and the choriocapillaris. The RPE and outer layers of the neural retina receive their blood supply from the choriocapillaris. The inner layers of the neural retina are supplied by the central retinal artery, and drained by the central retinal vein. The central retinal artery is the first branch of the ophthalmic artery, and travels down the centre of the optic nerve to enter the eyeball at the optic disc. Here the central retinal artery divides into four branches, each supplying a quadrant of the retina. These branches run in the nerve fibre layer, and give rise to a diffuse capillary network as far as the inner nuclear layer. Zonula occludentes between the capillary endothelial cells contribute to the blood-retina barrier (Fig. 2.18).

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2.3.7  Optic Disc Axons from the ganglion cell layer follow an arcuate pattern from the peripheral retina toward the optic disc. The macular axons take a more direct route. The 1.2 million nerve fibres converge at the optic disc and turn posteriorly to enter the intraocular portion of the optic nerve. As they turn posteriorly they form a circumferential ‘neuroretinal rim’ around the optic disc which is pinkish in hue. This arrangement leaves a more central and visibly paler bowl or ‘physiological cup’ into which the central retinal vessels descend. The retinal vessels and unmyelinated nerve fibres pass through a sieve-like structure in the sclera known as the lamina cribrosa, before continuing into the intraorbital portion of the optic nerve. At this point the fibres become myelinated and surrounded by their meningeal sheath (dura, arachnoid and pia). The dura is fixed to both the sclera and Tenon’s fascia.

Further Reading Ansari MW, Nadeem A. Atlas of ocular anatomy. Cham: Springer; 2016. Forrester JV, Dick AD, McMenamin PG, Pearlman E, Pathologist FR. The eye. London: Elsevier Health Sciences; 2015. Snell RS, Lemp MA. Clinical anatomy of the eye. Hoboken, NJ: Wiley-Blackwell; 1997.

Chapter 3

Physiology of Vision George Murphy and Kanwaldeep SinghVijjan

3.1  Physiology of Light Perception Visual perception is as a result of the brain’s visual cortex interpreting rays of visible light from our environment, which are focused on the retina. The main aspects of vision are: visual acuity (resolution), colour vision, night vision, motion detection, and depth perception. The visible light spectrum falls within a narrow band of the electromagnetic spectrum, incorporating wavelengths between 390 and 750 nm (Fig. 3.1). These rays of light are received by the photoreceptors, both rods and cones, within the outer retina.

3.1.1  Photoreceptor Anatomy All photoreceptors are composed of two main portions, an inner segment, and an outer segment. The outer segment contains discs, membrane bound structures containing the photosensitive pigment rhodopsin. These discs are produced at the area joining the inner and outer segments, and slowly migrate down through the outer segment, until they reach the junction with the Retinal Pigment Epithelium (RPE), where they are shed and phagocytosed. Whilst both rods and cones contain photosensitive discs, the outer segments of cones are conical in shape, and the discs are incorporated into the plasma membrane of the cell, rather than contained within (Fig. 3.2). The type of photoreceptor cell you find in the retina depends on the area of retina being looked at. At the fovea, there are only densely packed cone cells, which are then used for fine resolution, spatial resolution, and colour vision. The macula G. Murphy (*) · K. SinghVijjan Sussex Eye Hospital, Brighton, UK e-mail: [email protected] © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_3

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Fig. 3.1  Visible light spectrum. (Image by Philip Ronan, Gringer. Reproduced under Creative Commons Attribution-Share Alike 3.0 Unported license)

c­ ontains predominately cones, with some rod cells, whilst the peripheral retina is almost entirely composed of rod photoreceptors, and thus is responsible for brightness and motion. The retinal pigment epithelium layer is a single continuous layer of cuboidal cells, which play an important function in: the adherence of the retina inside the eye, metabolism of the waste products from the photoreceptors, and absorption of light to reduce scatter and improve vision. For the transmission of the light stimulus in the photoreceptors there are two further steps that must be taken to communicate beyond the eye. The cell bodies of the photoreceptors synapse with bipolar cells in the retina. Bipolar cells are also distributed in varying densities, with the highest concentration being in the fovea, with each photoreceptor having its own bipolar cell. Further in the periphery there will be multiple photoreceptors synapsing with a bipolar cell, which is one of the factors resulting in decreased resolution in the periphery. The bipolar cells then synapse with ganglion cells. The axons from these will join to form the optic nerve and synapse in the lateral geniculate nucleus of the thalamus.

3.1.2  Phototransduction The process of converting photons of light into electrical current that can be processed by the brain occurs at the level of the photoreceptors. Contained within the disc membranes in the outer segments of photoreceptors are chromophores, a special structure that is sensitive to light, and within photoreceptors is most commonly rhodopsin. These are part of a G-protein coupled receptor system responsible for phototransduction, with the transmembrane protein molecule rhodopsin (Fig. 3.3). When a photon of light contacts a molecule of 11-cis retinal (of the rhopdosin), it is absorbed, causing a structural change in the molecule, and converting it to ‘all-­

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disk

Outer Segments

Outer Segments

connecting cillium

mitochondria Inner Segments

Inner Segments nucleus

axon

Synaptic Region

Synaptic Region

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Cone

Fig. 3.2  Photoreceptors. (Illustration by Kim Yeohun)

trans retinal’. This change causes the rhodopsin molecule to activate a G-protein response, causing a hyperpolarisation of the cell, by closing sodium channels in the cell membrane. The termination of this hyperpolarisation is accelerated by a chemical called β-arrestin. This process allows very fast termination of the impulse, as well as an amplification effect. It should be noted that photoreceptors are unique in neural cells, by being able to transmit a localised, graded action-potential, and only once the signal has reached the ganglion cells will it become an all-or-nothing action potential.

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hv visual activated pigment visual pigment (11-cis retinal) (all-trans retinal)

transducin

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phosphorylated visual pigment arrestin activated transducin

cGMP phosphodiesterase

4Na+

activated cGMP phosphodiesterase

GTP

cGMP cGMP

K+, Ca2+

5’-GMP

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outer segment plasma membrane Na+, Ca2+

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Fig. 3.3  Diagram showing the basic process of phototransduction in rods. The visual pigment (rhodopsin) is activated by photons of light, causing transducin to activate GTP. In turn this activation causes phosphodiesterase to catalyse the conversion of cGMP to 5’-GMP, closing the ion channels in the outer segment plasma membrane, due to the lack of cGMP. This causes hyperpolarisation, generating a potential within the photoreceptor that can be transmitted

Following the change from 11-cis retinal to all-trans retinal, the molecule detaches from the opsin, and some is converted back into the 11-cis retinal form, helping to increase the supply of rhodopsin to the photoreceptors. The remainder is degraded as waste by the retinal pigment epithelium.

3.1.3  Image Formation Once the light has been received by the photoreceptors, and an initial impulse generated, this image is further manipulated by the two subsequent steps to help in visual function. There is a degree of summation from both the bipolar and the ganglion cells, but they also perform further modulation of the image. There exist two main types of ganglion cells, each with a characteristic receptive field. Some have an “on-centre” configuration, whereby a stimulus falling within this field will produce an excitatory response, but light falling in the area surrounding the central field will produce an inhibitory response. Inversely, there are also “off-centre” cells, which have a central inhibitory zone, and a surrounding excitatory area. The areas controlled by these cells allow for activation, and nearby inhibition, which will in turn help to improve discrimination of objects as well as increasing contrast on the edges of a stimulus.

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3.1.4  Visual Cortex The visual pathway (see Chap. 2) extends posteriorly to the visual cortex in the occipital lobe of the brain. The location of the synapse prior to the occipital cortex is within the lateral geniculate nucleus of the thalamus. There is an extraordinary degree of orientation of the ganglion cells, maintaining a clear map of the hemi-­retinal surface they correspond to, and leading to six distinct areas of synapse in the lateral geniculate nucleus. Layers 1, 4, and 6 receive nerve fibres from the contralateral eye, whilst 2, 3, and 5 come from the ipsilateral eye. These layers then maintain the orientation of the retinal nerves, and project backwards to the visual cortex, represented as Brodmanns area 17.

3.1.5  Colour Vision Different wavelengths in the visible spectrum create the perception of different colours when they are absorbed by the photoreceptors in the retina. Whilst rod cells have a peak sensitivity within the visible spectrum (around 500 nm), they are not responsible for colour vision. There are three main photoreceptor types when it comes to considering colour vision. These are blue (440 nm), green (541 nm), and red (566 nm), and they form the basis of the trichromatic theory of vision. If only one of these types of photoreceptor is activated then you perceive the colour relating to that photoreceptor. As each photoreceptor has a larger receptive wavelength that overlaps with each other it gives the ability to combine the stimulation between the different types of photoreceptor, and allow further colours to be seen. If two complementary colours are combined then the colour ‘white’ is perceived. Inversely the absence of colour is seen as black, however there is still retinal stimulation with this, distinguishing the sensation from that of a blind eye which is unable to perceive light. As with gross visual perception, there is a layer of processing that occurs within the ganglion cells, prior to transmission posteriorly to the cerebral cortex. It is thought that this occurs through a similar system of on-centre/off-centre receptive areas, with different colours forming excitatory/inhibitory areas. This would allow for better colour mixing, and appreciation of hues of colour in our environment.

3.1.6  Colour Blindness There is a spectrum of colour deficiency that may affect humans. This can range from an absolute inability to distinguish any colours, through to those who have a weakness perceiving one particular colour. The most common method of detecting colour deficiency is through testing with similar hues, or the use of Ishihara plates. These contain numbers that are difficult to distinguish, as the colours used are liable to merge in those with certain colour deficiencies.

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The most common defect is red-green trichromatism, affecting around 10% of males. It produces a spectral shift in either the red or green hues that the sufferer perceives, causing difficulty distinguishing between the two. As it is X-linked it most commonly affects men, only affecting women if they carry two affected copies of the X-chromosome.

3.1.7  Visual Fields and Binocular Vision The visual field is a representation of the receptive area of each eye. Whilst there is the potential for this to be circular, the shape of the eye, and the bony aspects of the orbit limit this. The visual field extends to the greatest extent temporally, and is most limited nasally (by the nose), and by the frontal bone superiorly. The visual field is essential to determine if binocular vision can be achieved, as there is normally a central portion of overlapping field from each eye. The visual field can be affected at any point from the eyelids, through to the occipital cortex, with either a structural or neurological abnormality causing differing areas of visual field loss. The most classical of these are neurological, and it is often possible to localise where in the course of the optic pathway the lesion has occurred by comparing the visual fields of both eyes. Formal visual field testing is commonly performed in ophthalmology units, and normally each eye is tested independently of the other. Such abnormalities will be covered elsewhere in this book (Fig. 3.4). Binocular vision also relies upon the image falling on corresponding points of the retina, and hence the muscular control of the eye is important. To maintain binocularity the eyes are controlled centrally to move in sync with each other, and thus move in complementary directions. Eye movement relies upon each eye both moving independently, but also in an organised manner with each other. For each eye to move each muscle must contract, and its antagonist relax by an equal amount. Eye movements can then be saccadic, which are sudden jerky movements allowing gaze to flick from one focus to another, or smooth pursuit for tracking Fig. 3.4 Diagram demonstrating the human binocular visual field, as seen from above. Each eye contributes half of the overall field, with an overlapping central portion forming the binocular field allowing for stereopsis

Binocular visual field

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objects. All of this is stabilised with assistance from the vestibular system, allowing positioning of the head to alter the movements of the eyes. Binocularity allows for true stereopsis to exist, with depth perception able to be interpreted by the brain from the two slightly disparate images from each eye. The brain is able to process the two images with disparity to derive a three-dimensional structure. Parallax (difference in apparent position of an object viewed through two different lines of slight) allows us to determine the apparent distance of objects. Interestingly rabbits, whose eyes are positioned laterally, lack depth perception and binocular viewing in the majority of their visual field, and they adopt this technique by moving their head side to side. This way, they are able to utilise parallax to identify their surroundings and an object that moves more than other objects will appear closer. This technique can be utilised by a monocular person in a similar way to judge distance and depth of objects. This alongside with the variance in hue allows us to judge distances and function in a three-dimensional space. If these systems fail to develop properly, or there is a weakness in the co-ordinating mechanisms so that a single visual stimulus no longer falls on corresponding retinal points, this is termed strabismus. In young children if there are two separate retinal images in such a case, the brain will preferentially suppress one of these, leading to an eye that is chronically suppressed, termed amblyopia. It is for this reason that there is screening of school aged children to detect such suppression, and to treat early hopefully preventing long term weakness in one eye. It can then also be possible to restore normal orientation of the eyes by selectively lengthening and shortening pairs of muscles to restore normal alignment.

3.1.8  Refraction and Optics For these visual processes to occur, it is necessary for the environmental light to be brought to focus on the retina, and without it functioning properly the image formed will be blurred. The bending of light by a surface is called refraction, and the power of the surface is measured in Dioptres (D). There are two focusing parts of the eye when thought of in a simplified way, and these refract light to bring it to focus. The majority of focusing done by the eye occurs at the corneal surface. The difference in refractive indices between the air and the tear film of the anterior corneal surface provides the greatest focusing power. The other main source of focusing power within the eye is the lens. As the lens sits within the aqueous humour, the difference in refractive indices is less, and hence the focusing power is less. However, the natural lens can change shape by the action of the ciliary processes contracting or relaxing. In the relaxed state the lens is relatively flatter, but when the ciliary processes contract the lens enlarges in the middle, becoming thicker, and increasing the refractive power (Fig. 3.5). In a simplified version of the eye, considering only two refractive surfaces, the cornea is thought to contribute 43D of focusing power, and the lens 15D (Figs. 3.6 and 3.7).

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Accommodated eye

Fig. 3.5  Diagram demonstrating the effect of the ciliary processes on the natural crystalline lens. Relaxation of the ciliary processes causing flattening of the lens, whilst contraction of the processes allows the curvature to increase, termed accommodation

Emmetropia Normal – Light focuses directly on the retina

Myopia Nearsightedness – Light focuses in front of the retina

Hyperopia Farsightedness – Light focuses behind the retina

Fig. 3.6  Emmetropic eye, hypermetropic eye, and myopic eye

Small changes in the eye, either through corneal pathology or even the natural aging of the lens may affect the ability of the eye to focus and change the overall refractive power. In what is considered a normal (emmetropic) eye, this focusing is sufficient without any further corrective lenses. Refractive error occurs when the light is not brought to a focal point on the retina, and commonly occurs as myopia and hypermetropia. Both can be considered as either axial (where the length of the eye is too long in myopia, or too short in hypermetropia) or as refractive (where the focusing power of the eye is too strong in myopia, or too weak in hypermetropia but the eye is otherwise normal). As such in myopia the rays of light are brought to focus in front of the retina, and to correct it a diverging (concave) lens is used. The opposite is true of hypermetropia, whereby a converging (convex) lens is used to bring rays of

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Power = +60 D H n´ = 1.33 F

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Fig. 3.7  Diagram of a simplified eye. (Illustration by Kim Yeohun)

Myopia

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Fig. 3.8  Hypermetropic eye with convex lens, and myopic eye with concave lens correcting the focus of incident light

light to focus on the retina. When both of these cases exist by t­ hemselves they can be corrected by a spherical lens, which has the same power in all meridians (Fig. 3.8). Astigmatism is where there is more than one refractive power within the eye, and they lie on different angles within the eye. This typically occurs either within the lens or the cornea, and in regular astigmatism the two meridians are separated by 90°. This means that rays of light will be focused at two points, depending on the power of the part of the eye doing the focusing. This can be corrected by using cylindrical lenses, which have their lens power orientated in a complementary meridian. Most commonly if there is co-existing myopia or hypermetropia, this will

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lead to a glasses prescription for a sphero-cylinder lens to correct the two refractive errors in one pair of glasses. Presbyopia is part of the natural aging process, and relates to the loss of ability of the lens to change shape, which is essential for accommodation (Fig. 3.5). As the natural aging of the lens occurs, it stiffens, and is unable to increase in power through the movement of the ciliary processes. This increase in power is necessary for accommodation in younger people, but can be corrected with an additional convex lens. As this will converge the rays of light from an object, it can be used to help bring to focus objects closer to the eye. These lenses are often incorporated into bifocal or varifocal glasses, mostly to allow people to continue reading at a natural distance.

3.2  Anterior Segment Physiology and Vision Maintaining clarity and the health of the anterior segment is essential to allowing light into the eye, and hence vision. The cornea maintains clarity through careful homeostatic mechanisms, with a fine balance of hydration necessary for clarity. The cornea is a five layered structure composed predominately of collagen, regularly aligned to allow for the clear transmission of light. (Refer to Fig. 2.14 in Chap. 2.) There are further glycosaminoglycan molecules that are present in the stroma to help with the hydration of this layer. Further to this the epithelium provides a watertight barrier to prevent dehydration of the stroma, and the endothelium contains a pump that removes water from the stroma into the anterior chamber. This is an active process requiring glucose for an ATP ion pump present in the endothelial cells. If this pump is not functioning properly, as happens in Fuchs endothelial dystrophy, the stroma becomes oedematous and cloudy, adversely affecting the vision. Whilst the epithelium and stroma receive the majority of their nutrients and oxygen through diffusion from the limbal blood vessels, and from the environment, the endothelium must rely on the aqueous humour. Aqueous humour is produced by the epithelial layer of the ciliary bodies, sitting posterior in the uveal tract to the iris. This circulates past the lens and fills the anterior chamber, being responsible for maintaining intraocular pressure. It is composed of low molecular weight compounds and protein, and its glucose content is important for respiration of both the endothelium, and the lens. Further it is used to dispose of waste products from these structures, as well as from the iris. There is circadian fluctuation in the production of aqueous, being lowest at night, but it can also be affected by neuronal control. It is generally formed at a rate of 2–3 μL/min, and the anterior chamber has a volume of roughly 250 μL. To keep a constant pressure of 10–20 mmHg within the eye, there must also be outflow so as to maintain the homeostasis with the constant production of aqueous. There are two methods of outflow, termed the conventional and unconventional. The conventional involves the trabecular meshwork contained within the ‘angle’ of the anterior chamber. The angle is bordered posteriorly by the anterior iris surface, and anteriorly by the corneal endothelium. Indeed it is the corneal endothelium that is continuous with the trabecular meshwork and lines it, creating some degree of outflow

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resistance. From the anterior chamber it is thought that membrane bound vesicles containing aqueous are transported through pores in the meshwork, being delivered through into Schlemm’s Canal. From here they are connected to and drain into the episcleral veins. As roughly 90% of drainage occurs through the conventional route, should something block this pathway, the pressure inside the eye can rise quite dramatically. This most commonly occurs secondary to physical blockage of the meshwork by the iris, in acute angle closure, and may cause rapid glaucomatous optic neuropathy if not reversed. It may also become blocked if there is blood or dense inflammation present within the anterior chamber, which may block the actual trabecular meshwork from draining. The unconventional by comparison requires drainage through the ‘uveoscleral’ method. In this process fluid passes posteriorly into the space around the choroid, and drains through the surface of the eye in episcleral veins. This means of fluid drainage is utilised better in younger patients, but may be enhanced by usage of prostaglandin analogues, a class of pressure lowering glaucoma medication.

Further Reading Elkington AR, Frank HJ, Greaney MJ. Clinical optics. Oxford: Blackwell Science; 1999. p. 124–33. Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The eye e-book: basic sciences in practice. London: Elsevier Health Sciences; 2015. Ganong WF. Ganong’s review of medical physiology. 22nd ed. New York: McGraw-Hill Medical; 2005. Levin LA, et al. Adler’s physiology of the eye. 11th ed. Edinburgh: Elsevier Health Sciences; 2011.

Chapter 4

Ocular Symptoms: A Systemic Approach to Diagnosis George Murphy and Pei-Fen Lin

4.1  Introduction History and examination remain the cornerstone of assessment in approaching a patient’s symptoms for any branch of medicine. In ophthalmology there is a large crossover both with neurology and also with systemic disease that may impact upon the eye. Further to this the ability to examine the eye, inside and out, will often enable you to confirm a diagnosis without further blood tests or scans.

4.2  History The history will follow the same format as a general medical history, with the special inclusion of past ocular history. Discerning what symptoms the patient is suffering from, the laterality of these, duration, and other factors will often then guide your further examination. These may be generally divided into anterior segment conditions (affecting the lids, ocular surface, and anterior segment of the globe), to posterior segment (affecting the ocular contents behind the lens, as well as vascular and neurological problems).

G. Murphy (*) Sussex Eye Hospital, Brighton, UK e-mail: [email protected] P.-F. Lin Moorfield Eye Hospital, Croydon Eye Centre, Thornton Heath, UK e-mail: [email protected] © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_4

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4.2.1  Anterior Segment The majority of anterior segment conditions involve some degree of inflammation of the surface, and as such often cause: pain, localised redness, watering/discharge from the eye, photophobia, blurring of vision, and foreign body sensation. Obvious precipitants, such as a history of foreign body entering the eye or chemical exposure history may point towards a source of the problem. Using an easy to remember set of questions such as: Site, onset, character of the symptom, radiation, associated symptoms (including the effect on vision), timing, exacerbating/relieving factors, and severity can be useful. Past ocular history of a similar symptom and diagnosis may help, with conditions such as anterior uveitis, or Herpes simplex keratitis being recurrent and intermittent with distinct flare episodes, whilst ocular surface dryness and blepharitis are generally persistent with some constant low level irritation between flares. Questions to always ask are about past ocular surgery, and whether the patient wears corrective glasses or contact lenses. If the patient wears contact lenses the risk of infection is increased, and asking about some particular aspects of lens hygiene is important, as well as knowing the type of lenses being worn. Asking for contact with water, hand hygiene, duration of lens wear each day, sleeping/showering/ swimming in lenses, frequency of lens case cleaning/changing, and how old the current lenses are, are all important factors to consider. It is also useful to enquire regarding associated recent or current systemic symptoms such as coryzal symptoms.

4.2.2  Posterior Segment The majority of posterior segment conditions cause fewer pain symptoms than those of the anterior segment, but often provide more varied visual symptoms, up to loss of vision. A systemic medical history is often useful, as vascular risk factors are often responsible for posterior segment conditions, with the most common being diabetes. Further determining the level of vision prior to this presentation may help guide you as to whether this may again be a repeat presentation. Drug history and allergy status should be taken with particular attention paid to eye drops, most commonly for glaucoma or ocular surface disease. Social history is again the same, but with the addition of enquiring about whether the patient drives, and determining their work. Both of these may not be possible depending on what their present acuity and symptoms are. Family history may also give clues to ocular conditions with strong family links such as glaucoma and squints.

4.3  Examination The majority of examination of function comes as the basis of a cranial nerve examination of cranial nerves II–VII and will form the basis of all ophthalmic examinations.

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4.3.1  Optic Nerve The main modalities examined will be: • • • • •

Visual Acuity Visual Fields Colour Vision Pupillary Reaction Fundoscopy

4.3.1.1  Visual Acuity Distance visual acuity is most commonly assessed with a Snellen chart (Fig. 4.1) or a logMar chart, typically viewed at a distance of 6  m. Ensure that the patient is wearing any distance prescription corrective lens before starting, and test each eye independently. Usage of a pinhole may be used after this to see if this improves the best acuity. An improvement with pinhole would suggest that there is a focusing/ refractive problem with the eye, and allows a better estimation of the absolute visual ability independently of glasses. It is also useful to know if there is past ocular history that may impact upon the best acuity the patient can achieve. For documenting Snellen visual acuity, it is presented in a commonly used format of: Distance Patient Is from Chart/Number of the Lowest Correctly Visualised Line If the patient cannot read the chart from 6 m, then the acuity should be checked at 3 m from the chart and further to 1 m if required. Below this the acuity is documented as: • Counting Fingers (CF): Ability to count presented fingers, start at 1 m, and move further away or closer as able, documenting the furthest distance the patient is able to correctly resolve the fingers. • Hand Movements (HM): Able to detect a hand moving in front of their eye in a well-­lit room. • Perception of Light (PL): Able to perceive if a bright light is shone in the eye. May be further modified to determine if different colours of light can be differentiated, and if the direction or quadrant of incoming light can be discerned. • No Perception of Light (NPL): Unable to perceive any light shone in the affected eye. It should be remembered that acuity is a subjective measurement, and it is often useful to encourage the patient to try further than they report being able to manage. 4.3.1.2  Visual Fields Formal visual field testing is useful, and a good way to monitor optic nerve function often also used by neurologists, and the government in assessing fitness to drive. Confrontational field testing is possible with a patient in clinic and provides a

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Fig. 4.1  Snellen chart

useful means to rapidly screen for major defects and neglect. It can either be done grossly, focusing on quadrants, or more formally using a white pin to trace the periphery of a field. A red pin can be useful to assess the blind spot and the central 20° (Fig. 4.2).

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Fig. 4.2  Demonstration of visual field testing to confrontation. (Illustration by Yi-Hwa Lin)

Fig. 4.3  Ishihara colour plate

Sitting directly in front of the patient at the same level, 1 m apart, the four quadrants of each eye should be tested in turn, comparing the patient’s visual field with that of the examiner. It can be helpful to ask the patient to look directly into the examiner’s eye when testing confrontational visual fields. Documentation of the field, and a defect if present, is made from the perspective of the patient looking out onto the environment. Refer to Fig. 2.11 in Chap. 2 for examples of visual field defects. Through careful examination gross field defects may be detected, leading to important neurological diagnoses. Further, in a patient with possible optic nerve damage, a documentation of the fields is essential as a part of the assessment. This will be discussed in further detail in the neuro-ophthalmology chapter.

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4.3.1.3  Colour Vision The most commonly used assessment of colour vision in the eye clinic setting is the Ishihara plates (see Fig. 4.3). Whilst it is intended to detect inheritable colour vision deficiency, it can be applied to those with optic nerve injury and a relative deficiency is often the first sign of impaired optic nerve function. Each eye is tested individually, and the score out of the total number of plates tested recorded for each eye. It does rely on the patient having a minimum visual acuity of 6/36 but does have a trial plate on the first page that even patients with a colour deficiency are able to see. If a patient makes more than three mistakes or has a particularly slow reading speed in comparison to the fellow eye, then consideration should be given to an underlying optic nerve problem. Red desaturation can also be an early sign in optic nerve dysfunction. The patient may report the affected eye to have a washed-out appearance, or the colour red may appear paler. 4.3.1.4  Pupil Size and Response This is a combination of both the optic nerve function as well as the oculomotor nerve. The pupil size should be compared between the two eyes, and a difference between the two is termed an anisocoria. Up to 1 mm of difference is allowed as a physiological variant. If one pupil is significantly larger or smaller than the other, then comparing the sizes in both bright and dark conditions is important. To tell which the affected eye is, a small pupil that does not dilate in the dark, or a large pupil that does not constrict in the light is generally the abnormal side. It is important to note the eyelid height and presence of any extraocular muscle restrictions alongside anisocoria. Comparing pupil response is also essential, and this requires a focused light source such as a pen torch to prevent the light spilling into the fellow eye. A direct and consensual response should be looked for in each eye, comparing size, speed and recovery of each response. Accommodation should also be tested, by first asking the patient to look at a distant object with both eyes, and then holding an object within 10 cm of their eyes to check for the normal accommodative constriction. These tests are often abbreviated to Pupils Equal and Reactive to Light and Accommodation (PERLA). Finally testing for a Relative Afferent Pupillary Defect (RAPD) is important to look for impaired optic nerve function. This is elicited by checking each direct response in turn, and quickly moving between the two eyes. As you will be detecting an afferent or receptive problem in one eye, when moving quickly to the affected eye it will dilate instead of constrict (see Figs. 4.4 and 4.5). 4.3.1.5  Fundoscopy The final stage of optic nerve assessment involves visualisation of the optic nerve to assess its appearance. This can be carried out by direct ophthalmoscopy (which is discussed later in this chapter) or indirect ophthalmoscopy. Assess the appearance of the optic nerve including the colour (pallor), contour (oedema) and presence of any haemorrhages.

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Fig. 4.4 Demonstrating the pupillary light response pathway. Author’s own light stimulus

afferent signal carried through optic nerve

at lateral geniculate body

Both oculomotor nerves are activated thus both pupils are constricted

Afferent signal arrives at Pretectal nucleus stimulates the Edinger-Westphal nucleus on both sides

Fig. 4.5 Demonstrating how to elicit a RAPD. Author’s own

Light source

Both pupils constricted by shining light in RIGHT eye

Both pupils constricted by shining light in LEFT eye

BUT if when the light swings back to the RIGHT EYE it dilates, due to reduced optic nerve input (if normal nerve, the pupil should remain constricted),

In this case the RIGHT eye has the RAPD (optic neuropathy)

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4.3.2  Oculomotor, Trochlear, and Abducens Nerves As previously covered the extraocular muscles are controlled by three different cranial nerves. Each of these will give a different picture of movement deficit. In addition testing the extraocular movements can provide information on the restriction of eye movements, and is important to document when orbital pathology is considered, such as in thyroid eye disease or orbital trauma. Testing takes place from the right of the patient with a physical target or light source for them to focus upon. The testing is done binocularly, and you are looking to demonstrate double vision (diplopia) if it is present. Importantly if there is diplopia whilst in neutral gaze you need to consider if it worsens in a particular direction of movement, and which eye is not functioning correctly. Further if there is double vision it is important to determine if it is monocular or binocular. If it is monocular then the patient will see two images with the affected eye, and the other eye covered, or with both eyes open. If it is binocular then the patient will only experience double vision when both eyes are uncovered. You should aim to ensure the patient keeps their head still, and you move to the extremes of gaze. Monocular diplopia is normally a refractive problem within one eye, and as such tends not to vary, nor have implications for the patient’s general health. Binocular diplopia most commonly arises as an imbalance or weakness in one of the extraocular muscles, and as such may be more considered a neurological problem arising from the cranial nerves. If these do not resolve they generally require further medical investigation. Typical patterns of nerve palsy will give different gaze problems with their affected muscles. A third nerve palsy typically gives the appearance of a ‘down and out’ eye, as the lateral rectus and superior oblique action are unopposed Due to the innervation of the levator palpebrae superioris in the upper lid there is commonly a ptosis on the affected side. An abducens palsy may not be noticeable in primary gaze, but the patient will then develop worsening diplopia on abduction of the affected eye. The two images are horizontal, as this is the plane in which the lateral rectus has its action. A trochlear palsy is often the most subtle of all nerve palsies, and patients may compensate for it with an abnormal head posture. It can cause vertical diplopia which is worse in downgaze and adduction. Patients most often complain of difficulty reading and going down stairs. It can be difficult to see this clinically, as the movement can be quite small.

4.3.3  Trigeminal and Facial Nerve The trigeminal nerve supplies the sensation both to the eyelid skin, and the cornea. Testing corneal sensation may be done in a non-anaesthetised eye by touching a fine piece of cotton to the peripheral cornea, which should normally give a blink reflex. Corneal neuropathy may commonly be found following herpetic infection of the cornea, and is a prognostic sign for future problems. The facial nerve supplies orbicularis oculi, and as such is important in lid tone, and for lid closure. Assessment of the ability to close the lids is especially important for

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corneal hydration and integrity, and may be compromised following facial nerve palsy. The tone of the lids, and ability to resist forced opening are signs to test for laxity that may expose the cornea during sleep, or even whilst awake if particularly lax.

4.3.4  Examination of the Globe and Adnexal Structures Bedside or clinic examination starts with the general principles of using a systematic approach. Inspecting from afar and then moving closer, finishing with fundoscopy. A direct ophthalmoscope may be used during the entire examination, having utility both as a light source and a magnifier. Moving from anterior structure backwards also ensures that a consistent approach will not miss obvious abnormalities. These in order are: Eyelid skin and eyelashes, eyelid margin and puncti, bulbar conjunctiva, everting the lids for palpebral conjunctiva, sclera, cornea, anterior chamber, iris, lens, and finally the retina. Drops are frequently used to aid in both diagnosis and patient comfort. Topical anaesthetic may be used in patients with anterior segment pain, but should not be given to take home with the patient as prolonged use may lead to corneal toxicity and failure of the corneal epithelium. Fluorescein 2% eye drops are also commonly used to stain epithelial defects on the conjunctiva and cornea. This dye coats the surface of the eye, and when a cobalt blue light is shone upon it, will fluoresce a bright yellow/green. Many ophthalmoscopes will have a blue light filter specifically for this purpose. The process of direct ophthalmoscopy involves settling the patient in a dark room. For the purposes of better fundal examination, using dilating drops will enable a larger field of view through the patient’s pupil. Starting a few metres away from the patient you can check the red reflex in both eyes by shining the light in turn at the pupils whilst looking through the eyepiece of the ophthalmoscope. When you wish to move closer then, using the right hand and right eye to examine the patient’s right eye, move closer following the red reflex. It is normal to be very close to the patient’s face during this time, and if you follow the red reflex in close enough the retinal features should start to focus. There is a dial on ophthalmoscopes allowing corrective lenses to be adjusted within the ophthalmoscope, correcting for the patient’s prescription. An examination of the major macular vasculature, optic nerve, macular retina, as well as some of the peripheral retina is possible with a direct ophthalmoscope and would form the structure of your report.

Further Reading 1. Appendix for differential diagnosis, symptom finder and referrals to ophthalmology. 2. Bagheri N, et al. The Will’s eye manual. 7th ed. Philadelphia, PA: Wolters Kluwer; 2017. 3. Denniston AKO, et al. Oxford handbook of ophthalmology. 4th ed. Oxford: Oxford University Press; 2018.

Chapter 5

Adnexal Conditions Shiu Ting Mak and Hunter K. L. Yuen

5.1  Lids 5.1.1  Basic Anatomy of the Lid The lid is a layered structure consisting of skin, orbicularis oculi muscle, tarsal plate, septum, fat pads, lid retractors, and conjunctiva. It serves to protect the structures of the eye. The orbicularis oculi is innervated by the seventh cranial nerve and its function is to close the lids. The upper lid retractors, the levator complex, is innervated by the third cranial nerve and elevates the upper lid. Its lower lid counterpart serves to retract the lower lid in downgaze. Glands exist in the lid margin, including meibomian glands and Glands of Zeis, which are modified sebaceous glands, and Glands of Moll, which are modified sweat glands. These glands may be the source of cyst, mass or occasionally tumour formation.

5.1.2  Benign Lid Lesions 5.1.2.1  Blepharitis Blepharitis (Fig. 5.1) is the inflammation of lid margins. It is associated with seborrhoea, staphylococcal infection, and meibomian gland dysfunction. Demodex S. T. Mak Department of Ophthalmology, United Christian Hospital, Kowloon, Hong Kong H. K. L. Yuen (*) Hong Kong Eye Hospital, Kowloon, Hong Kong Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Shatin, Hong Kong © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_5

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Fig. 5.1  Upper and lower lid blepharitis. Image reproduced from (permission request done, a/w) Auran J., Casper D.S. (2019) Blepharitis and Conjunctivitis. In: Casper D., Cioffi G. (eds) The Columbia Guide to Basic Elements of Eye Care. Springer, Cham

i­nfestation has also been identified as a cause of blepharitis. (Also refer to Chap. 6, External Diseases.) Symptoms of blepharitis include grittiness, irritation, itchiness, burning sensation, redness and crusting of the lid margins. There may be associated formation of hordeolum or chalazion on the lid. Furthermore, because of the close relationship of the lid to the ocular surface, chronic blepharitis may lead to secondary changes in the cornea and the conjunctiva. Blepharitis can be managed by performing regular lid hygiene by applying warm compress (to open up the meibomian glands) and scrubbing the lid margin with water or diluted baby shampoo. Alternatively, there are commercially available heat masks and lid wipes. Staphylococcal blepharitis is treated with antibiotic ointment. Artificial tears are useful in dealing with tear film instability. Occasionally, weak topical steroids and oral tetracyclines are necessary, though the latter should be avoided in children under 12 years old and in pregnant or breast-feeding women. Demodex infestation can be treated with tea tree oil. 5.1.2.2  Chalazion Chalazion (Fig. 5.2) is an idiopathic, chronic lipogranulomatous inflammation of blocked meibomian glands and stagnation of sebaceous secretions. It may occur at any age, and is more common among patients with chronic blepharitis, rosacea or seborrhoeic dermatitis. It is characterized by a painless localised roundish firm swelling. On occasion, there may be superimposed infection with redness, pain and swelling. Systemic antibiotics may be required if there is infection of the chalazion to prevent development of preseptal cellulitis. Small chalazia may resolve spontaneously with time. Warm compresses of the lesion and use of topical antibiotics and steroid may be helpful. Persistent ones will require incision and curettage of the lesion. Intralesional steroid injection may also be useful. Rarely, oral tetracycline may be required as prophylaxis in patients with chalazia, particularly if the patients have associated conditions including rosacea and seborrhoeic dermatitis.

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Fig. 5.2 Chalazion

5.1.2.3  Hordeolum Infection of the glands of the lid is hordeolum. External hordeolum or stye is the acute infection of the Gland of Zeis and the lash follicle. Internal hordeolum is the infection of the meibomian gland. Hordeolum is often caused by staphylococcal infection. It presents as a painful swelling on the lid margin. Treatment of hordeolum involves warm compresses of the lesion. If it does not resolve with conservative management, incision and curettage may be necessary.

5.1.3  Benign Lid Tumours 5.1.3.1  Papilloma Papilloma (Fig. 5.3), or viral wart, is the most common benign lid tumour. It usually occurs in adults. It can be broad based or pedunculated and has a friable surface. It can be treated by excision, cryotherapy or laser ablation. 5.1.3.2  Naevus Naevus (Fig.  5.4) are benign neoplasms or hamartomas composed of epidermal melanocytes. It may be pigmented or non-pigmented, and is usually well-­ circumscribed. Rarely, there is a small chance of malignant transformation. It can be removed by shave excision.

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Fig. 5.3  Left upper lid papilloma

Fig. 5.4  Left lower lid naevus

Fig. 5.5 Xanthelasma

5.1.3.3  Xanthelasma Xanthelasma (Fig. 5.5) is a deposition of lipid-containing histiocytes and appears as yellowish plaques on the surface of the lid. It usually occurs at the inner angle of the eye and is often bilateral. It is more common among patients with high serum

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c­ holesterol, but it may also occur among people with normal lipid level. It can be removed by excision or treated with laser if desired for cosmetic reason, yet patients should be warned that the lesion may recur after removal.

5.1.4  Malignant Lid Tumours To distinguish a malignant from benign lid tumour, there are several warning signs specific to malignant tumours. Attention should be paid to any Asymmetry, Border irregularity, Colour variation, Diameter, and Evolution of new signs or rapid changes, giving the ABCDE mnemonic. As for the lid, attention should be paid to any change in pigmentation, change in visible vessels such as telangiectasis, loss of lashes, chronic conjunctivitis, and lid malposition. 5.1.4.1  Basal Cell Carcinoma Basal cell carcinoma (Fig. 5.6) is the most common malignant lid tumour. It is most commonly found on the lower lid, though it may occur anywhere on the periorbital area. Its incidence rises with increasing age. Other risk factors include solar exposure and white skin. Occasionally, it is associated with certain cutaneous syndromes such as xeroderma pigmentosa and Gorlin-Goltz syndrome. Classically, basal cell carcinoma appears as a firm nodule with rolled pearly edge and fine telangiectasia over an ulcerated surface, often known as rodent ulcer. Sometimes, it may infiltrate beneath the epidermis with minimal overlying surface changes. Basal cell carcinoma is usually locally invasive but seldom metastasises. The main stay of treatment is complete excision with histologically-confirmed clear margins by means of frozen section or Moh’s micrographical technique, followed by eyelid reconstruction for the eyelid defect. In certain selected cases, it can be Fig. 5.6  Lower lid basal cell carcinoma

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treated by cryotherapy or radiotherapy. Vismodegib and Sonidegib are indicated when the tumour has metastasised, relapsed after surgery, or cannot be treated with surgery or radiotherapy. 5.1.4.2  Squamous Cell Carcinoma Squamous cell carcinoma (Fig.  5.7) is less common. It is most common on the lower lid. Similar to basal cell carcinoma, risk factors of squamous cell carcinoma include increasing age, solar exposure, white skin, and xeroderma pigmentosa. Squamous cell carcinoma may arise de novo or from pre-existing actinic keratosis. It initially presents as a hyperkeratotic nodule which eventually becomes ulcerated. It may also present as an erythematous scaly plaque. In addition to being locally invasive, squamous cell carcinoma may metastasize to regional lymph node or exhibit perineural spread via the orbit to involve the intracranial region. Treatment involves wide local excision with histological control. 5.1.4.3  Sebaceous Gland Carcinoma Sebaceous gland carcinoma (Fig. 5.8) arises from the meibomian gland, Gland of Zeis, or sebaceous gland. It is more common on the upper lid where meibomian glands are more abundant. Risk factors include increasing age. There may be difficulty in diagnosing sebaceous gland carcinoma initially because it often resembles chalazion or chronic blepharitis. Recurrent chalazion resistant to treatment should raise the suspicion of sebaceous gland carcinoma. Sebaceous gland carcinoma is an aggressive lid tumour. It exhibits Pagetoid spread, spreading to epithelium that appears to be separate from the main tumour. It often extends into the orbit, lymph nodes, and metastasizes, therefore carrying a

Fig. 5.7  Squamous cell carcinoma

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Fig. 5.8  Sebaceous gland carcinoma

Fig. 5.9 Malignant melanoma

high overall mortality rate of 10%. Map biopsy of the conjunctiva should be performed to determine the extent of the tumour. The aim of treatment is to achieve wide local excision but exenteration is required in cases of orbital involvement. 5.1.4.4  Malignant Melanoma Malignant melanoma (Fig. 5.9) can rarely occur on the lid and is potentially life-­ threatening. Risk factors include increasing age, solar exposure, white skin, and cutaneous syndrome such as xeroderma pigmentosa. Not all malignant melanomas are pigmented, hence leading to a diagnostic challenge. Biopsy is often needed to confirm the diagnosis. Malignant melanoma exhibits lymphatic spread. Prognosis depends on the thickness of lesion or the depth of invasion. Wide local excision of 10 mm margin is recommended. The 5-year survival is around 50% for lesions with thickness >1.5 mm.

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5.1.5  Disorders of Lashes 5.1.5.1  Trichiasis Trichiasis (Fig. 5.10) are lashes arising from their normal position but are misdirected posteriorly. It is often idiopathic but may also be caused by scarring of the lid margin due to chronic blepharitis. Patients often complain of foreign body ­sensation, irritation or grittiness. Trichiasis may cause corneal epithelial erosions. In severe chronic cases, trichiasis may lead to corneal ulceration or scarring. The simplest treatment for trichiasis is epilation. Yet the lashes usually regrow in approximately 4–6 weeks, and repeated epilation is required. Isolated trichiasis may be treated by electrolysis, where an electrocautery needle is inserted down to the lash root and electric current applied to achieve coagulation. However, the procedure is tedious and recurrence is observed in around 40% of cases. Alternatively, argon laser may be used, but recurrence may similarly happen. When trichiasis is extensive, cryotherapy using a double freeze-thaw technique plays its role. Potential complications include depigmentation, scarring, skin necrosis or lid margin notching. In resistant cases, surgery for eyelid margin repositioning may be required. 5.1.5.2  Distichiasis Distichiasis are lashes arising from an abnormal position. Often, an abnormal row of lashes is seen posterior to the meibomian glands. It can be congenital or acquired, the most common cause of which is cicatrizing ocular conditions. Treatment is similar to those for trichiasis.

Fig. 5.10 Trichiasis showing misdirection of eyelashes

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5.1.5.3  Madarosis Madarosis is partial or complete loss of lashes. It can be due to local or systemic causes. Local causes include cicatrizing conjunctivitis, chronic lid margin disease, burns, tumour and post-radiotherapy or cryotherapy for tumour, and iatrogenically following epilation. Systemic causes include alopecia, psoriasis, syphilis and leprosy. 5.1.5.4  Poliosis Poliosis is the premature whitening of the lashes. Causes of poliosis include Vogt-­ Koyanagi-­Harada syndrome, sympathetic ophthalmia, and Waardenburg syndrome.

5.1.6  Disorders of Lid Position 5.1.6.1  Entropion Entropion (Fig. 5.11) is the abnormal in-turning of the lid. The most common cause of entropion is involutional due to ageing. Cicatricial or congenital causes are less common. Involutional entropion almost always affect the lower lid. The pathogenesis lies in the degeneration of elastic and fibrous tissue of the lid, namely laxity of the inferior retractors, upward migration of the orbicularis oculi causing over-riding, and horizontal lid laxity. Cicatricial and congenital entropion, on the other hand, may affect both the upper and lower lids. Cicatricial entropion is caused by scarring of Fig. 5.11  Lower lid entropion

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the conjunctiva as a result of cicatrizing conjunctivitis, trachoma, trauma or chemical injury, hence pulling the lid margin towards the eyeball. Congenital entropion is rare. Entropion may cause the lashes to constantly rub onto the corneal surface, leading to irritation, tearing, photophobia, corneal epithelial erosions, and corneal ulceration or scarring in severe cases. Use of lubricants or taping may provide temporary relief. Definitive treatment of entropion requires surgery. In involutional entropion, the choice of surgery depends on the underlying laxity, for example Jones plication to reattach the dehisced retractor, or lateral tarsal strip to shorten the lid laterally and tighten it at the lateral canthus. In cicatricial entropion, the underlying inflammatory condition leading to the cicatrizing process has to be treated, followed by surgery to reposition the lid margin, for example by tarsal fracture, posterior tarsotomy, or terminal lid margin rotation. In severe cases, grafts may be required to lengthen the scarred and shortened lid tissue. 5.1.6.2  Ectropion Ectropion (Fig. 5.12) is the abnormal eversion of the lid. It principally affects the lower lid. Ectropion can be involutional, cicatricial, paralytic or mechanical in nature. Involutional ectropion is caused by degenerative laxity of the lid, the medial or lateral canthal tendons. Cicatricial ectropion is caused by scarring of skin or underlying tissue, leading to contracture and hence pulling the lid away from the eyeball. It occurs in patients with trauma, burns, radiotherapy or severe dermatitis. Paralytic ectropion commonly occurs in patient with palsy of the seventh cranial nerve (facial nerve) where the orbicularis oculi action is weakened. Mechanical ectropion is a result of tumour or mass growing on the lid causing eversion due to mechanical effect. Patients with ectropion complain of irritation, tearing, and recurrent infection. In cases of facial nerve palsy, there is also inability to close the eye or lagophthalmos with resultant exposure keratopathy. Fig. 5.12  Lower lid ectropion

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Ectropion is treated by surgery targeting at the underlying defect. The most commonly performed surgery involves creation of the lateral tarsal strip to shorten and tighten the lid. It can be combined with other procedures. In cicatricial cases, the underlying cicatrizing condition needs to be controlled, and sometimes skin-gaining procedures or graft is necessary. Mechanical ectropion usually resolves after the culprit lesion is removed. 5.1.6.3  Ptosis Ptosis (Fig. 5.13) is an abnormally low position of the upper lid. Apart from being cosmetically disturbing, severe ptosis may block the superior visual field. Ptosis can be acquired or congenital. Acquired ptosis is by far more common than congenital ptosis. Involutional or senile ptosis is the most common cause of ptosis. With age, there is disinsertion or dehiscence of the levator palpebrae superioris resulting in dropping of the upper lid. It may also occur after ophthalmic surgery, trauma, or long term contact lens use. It is treated by levator complex advancement surgery. Mild cases can be treated by Fasanella-Servat procedure or Muller Muscle Conjunctiva Resection (MMCR). Neurogenic ptosis may occur as part of third cranial nerve palsy or Horner’s syndrome. In third nerve palsy, there is complete ptosis with associated ocular motility abnormalities. The pupil may be dilated. This is an ocular emergency and urgent attention is necessary. In Horner’s syndrome where the ocular sympathetic supply is damaged, there is partial ptosis with a miosed pupil. Aetiology of Horner’s syndrome may lie anywhere along the sympathetic pathway, and common causes include tumour in particular Pancoast tumour of the apical lung, stroke, demyelination, trauma etc. Treatment should be delayed to allow for any spontaneous improvement. Persistent ptosis will eventually require surgery. Myogenic ptosis is often seen in myasthenia gravis. The ptosis can be unilateral or bilateral and is often variable and fatigable. There is also associated bizarre ocular motility disturbances. Myasthenia gravis is a medical disease and should be treated with acetylcholinesterase inhibitors. Surgery should be avoided. However, in cases refractory to medical treatment and where ptosis is disabling to the patient, Fig. 5.13 Ptosis

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surgery may be required for functional correction. Chronic progressive external ophthalmoplegia is a hereditary neuromuscular disease that presents in middle age. The levator complex and extraocular muscles are affected, resulting in bilateral ptosis and ocular motility restriction. Surgery should be delayed until ptosis is visually significant as lid closure is also affected resulting in possibility of exposure keratopathy following ptosis correction surgery. Mechanical ptosis is caused by growth of mass or tumour on the upper lid, oedema or scarring of the upper lid. Treating the underlying cause will lead to resolution of the ptosis. Congenital ptosis happens as a result of developmental myopathy of the levator complex. There is absence of lid crease and often a refractive error. Severe congenital ptosis may lead to deprivation amblyopia. In such cases, early ptosis correction surgery should be performed. In patients with Marcus Gunn jaw-winking syndrome, there is synkinesis of the levator and the ipsilateral pterygoid muscle. The ptotic lid retracts when the pterygoid muscle is stimulated by opening the mouth, chewing, sucking, or moving the jaw to the opposite side. Surgery is performed for functional or cosmetic purposes, though the outcome is often not entirely satisfactory. 5.1.6.4  Epiblepharon Epiblepharon (Fig. 5.14) usually occurs in the lower lid where an extra horizontal fold of skin runs just below the lower lid margin. As a result, the lashes, especially those in the medial side, point vertically and may cause irritation and corneal epithelial erosions. Epiblepharon is more common among Asian and usually presents in childhood or early adulthood. It usually resolves spontaneously with age. However, surgery may be required for symptomatic and persistent cases. Surgical correction is done by excising a thin strip of skin and the underlying orbicularis muscle, with the placement of lash rotating sutures. Fig. 5.14 Epiblepharon

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5.2  Lacrimal 5.2.1  Basic Anatomy of the Lacrimal System The lacrimal system consists of the secretory and the excretory systems. The secretory system is responsible for the production of tears, including the lacrimal gland and other accessory glands. The lacrimal gland is innervated by the parasympathetic system. The excretory system is responsible for the drainage of tears. It starts at the upper and the lower puncti which are located at the medial end of the lid margin. They connect to the superior and inferior canaliculi which join to form the common canaliculus. The common canaliculus opens into the lateral wall of the lacrimal sac. The valve of Rosenmuller lies at the entrance to the lacrimal sac to prevent reflux of tears back into the canaliculi. The lacrimal sac lies in the lacrimal fossa and continues as the nasolacrimal duct inferiorly. The nasolacrimal duct opens into the inferior meatus of the nose. The valve of Hasner lies at the exit of the duct.

5.2.2  Watery Eye Watery eye can be a result of overproduction or under-drainage of tears. Overproduction can be caused by autonomic disturbances, but most commonly it is a reflex hypersecretion secondary to local irritation of the eye by misdirected lashes or foreign body, blepharitis, keratoconjunctivitis sicca, or other ocular ­inflammation or surface diseases. Treatment is usually medical to correct the underlying cause. Under-drainage is often due to obstruction anywhere along the tear drainage system. Punctal obstruction can be congenital, idiopathic, or a result of infection and inflammation. Canalicular obstruction is often idiopathic or due to chronic infection. Nasolacrimal duct obstruction can be congenital but is most commonly idiopathic. Other causes include trauma, post-irradiation, or tumour. Treatment usually requires surgery. In addition to drainage system obstruction, lacrimal pump failure also leads to under-drainage. Lacrimal pump failure is usually seen in patients with lid laxity or weakness of the orbicularis oculi, a common cause of which is facial nerve palsy. Patients with watery eye experience intermittent or persistent tearing from one or both eyes which can be functionally disturbing. It is more common with increasing age. Patients often find the tearing is exacerbated by wind.

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5.2.3  Obstruction 5.2.3.1  Punctal Obstruction Punctal obstruction can be congenital, idiopathic, or a result of infection notably herpes simplex infection, and inflammation. Initial treatment is to dilate the punctum using a punctal dilator. However, if repeated dilatation using a dilator is not successful, a snip procedure will be required. During a snip procedure, snips or small cuts are made at the punctum to create a larger opening to facilitate draining of tears. 5.2.3.2  Canalicular Obstruction Canalicular obstruction is often idiopathic or due to chronic infection due to viral, bacterial and fungal infections (most commonly by Herpes simplex, Varicella, adenovirus and Actinomyces). It may also occur in conjunctival shrinkage diseases such as Stevens-Johnson syndrome or ocular pemphigoid. Treatment requires surgery to recanalize the obstruction either by using a lacrimal probe or lacrimal trephine, followed by intubation of the canalicular system. For proximal canaliculi obstruction, a bypass tube known as Jones tube may be used. In common canalicular obstruction, dacryocystorhinostomy (DCR) may be required as well.

5.2.3.3  Nasolacrimal Duct Obstruction Congenital Nasolacrimal Duct Obstruction Nasolacrimal duct obstruction can be congenital but is most commonly idiopathic. In congenital nasolacrimal duct obstruction, there is delayed canalization of the valve of Hasner. Parents may notice the baby suffers from persistent tearing since birth. The tearing is often more common when the baby has concomitant upper respiratory tract infection. The lashes may be matted together, and gentle massage over the lacrimal sac region leads to purulent discharge from the punctum. In babies with watery eye, it is very important to rule out congenital glaucoma. In most children, it resolves spontaneously with time after the valve of Hasner canalizes, with 95% of cases resolving at 1 year of age. Massaging the lacrimal sac increases the hydrostatic pressure within the sac and may help to rupture the valve of Hasner. If tearing persists after 1 year of age, probing can be performed to manually overcome the obstruction at the valve of Hasner. If performed before 2 years of age, probing has a high success rate of more than 90%. Probing can be repeated following one failure. A second probing adds a further 6% success rate. For patients who fail two probings, intubation or DCR (see below) will be required.

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Acquired Nasolacrimal Duct Obstruction Most acquired nasolacrimal obstructions are idiopathic in nature. Other causes include infection, trauma, post-irradiation, tumour including those with nasopharyngeal origin, and inflammatory diseases such as Wegener granulomatosis. Patients present with watery eyes which may be intermittent or persistent. They complain of frequent need for wiping their eyes, which may be functionally disturbing. Sometimes there may be pus-like discharge especially upon compression of the lacrimal sac region. Patients with partial nasolacrimal duct obstruction may benefit from balloon dacryoplasty and intubation using silicone tubes. Patients with complete obstruction will require DCR. In DCR, a new anastomosis is created between the lacrimal sac and the middle meatus of the nose. It can be performed using an external approach, endoscopically inside the nasal cavity, or by laser via the lacrimal punctum. The success rate lies between 70% and 90% depending on the technique used.

5.2.4  Inflammation 5.2.4.1  Dacryoadenitis Dacryoadenitis is inflammation of the lacrimal gland. It may occur as an isolated entity or as a complication of influenza. It may also occur as part of generalized orbital inflammatory disease. Patients present with painful swelling over the lacrimal gland region with a S-shape configuration. Dacryoadenitis may resolve spontaneously without treatment. It also responds well to oral non-steroidal anti-inflammatory drugs or oral steroids.

5.2.5  Infection 5.2.5.1  Dacryocystitis Dacryocystitis (Fig. 5.15) is infection of the lacrimal sac. It usually occurs secondary to nasolacrimal duct obstruction and is caused by staphylococcal or streptococcal infection. In children, it is also commonly caused by Haemophilus influenzae. Patients with dacryocystitis present with an acute painful swelling over the lacrimal sac region. Purulent discharge may be expressed from the lacrimal sac through the punctum. In severe cases, there may be co-existing cellulitis. The presentation is typical and can be easily identified. Systemic and topical antibiotics usually provide relief, though incision and drainage may be required to release the pus collection. However, the condition may recur in view of underlying nasolacrimal duct obstruction. Therefore, the ultimate cure relies on DCR to correct the underlying obstruction. DCR may also be performed in the acute infective phase and shows promising outcome.

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Fig. 5.15 Dacryocystitis. Image courtesy of Mr Huw Oliphant, Sussex Eye Hospital

5.2.5.2  Canaliculitis Canaliculitis is an uncommon, chronic infection of the canaliculus. It is usually unilateral and affects the lower canaliculus more than the upper. It is frequently caused by infection with Actinomyces, Candida albicans, or Aspergillus species. Patients present with a red eye, mucopurulent discharge, swelling at the canaliculus, and a pouting punctum. Sometimes, concretions are expressed from the pouting punctum. Treatment involves use of topical antibiotics, in particular ciprofloxacin eyedrops, but often it can only achieve temporary relief. Concretions should be removed from the canaliculus, followed by irrigation with iodine and antibiotics such as penicillin. Canaliculotomy may be performed to incise the conjunctival side of the canaliculus, but it may lead to scarring and subsequently affecting the function of the canaliculus. If left untreated, canalicular stenosis may result. Nevertheless, recurrence is common despite treatment.

5.3  Orbit 5.3.1  Basic Anatomy of the Orbit The orbit consists of the medial wall, lateral wall, roof and floor. Inside the orbit lies the eyeball, optic nerve, extraocular muscles, blood vessels, cranial nerves, and lacrimal gland. As the orbit is a rigid bony structure, the only room for expansion is anteriorly. As a result, any increase in intraorbital content or pressure will displace the eyeball forward, leading to proptosis. Movement of the extraocular muscles may also be affected, and patients may experience diplopia. Pathologies like space occu-

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pying lesions or inflammatory diseases may also cause mass effect and compress onto the eyeball and optic nerve. It should be remembered that in orbital imaging like CT scan and MRI scan plays an important role in the diagnosis and management of orbital diseases.

5.3.2  Thyroid Eye Disease 5.3.2.1  Aetiology and Clinical Features Thyroid eye disease (also known as Graves Ophthalmopathy or Orbitopathy, Thyroid Associated Orbitopathy) is the most common cause of both unilateral and bilateral proptosis. Most patients with thyroid eye disease suffer from hyperthyroidism or hypothyroidism, although their systemic signs and symptoms may follow a different course from their eye features. Thyroid eye disease may also occur in patients who are clinically euthyroid, at least at the time of presentation. Risk factors for thyroid eye disease (Fig. 5.16) includes female sex, middle age and smoking. All patients with thyroid eye disease must refrain from smoking. Thyroid eye disease is an organ-specific autoimmune reaction in which IgG antibody causes inflammation of the extraocular muscles and inflammatory cellular infiltration of the orbital soft tissue, orbital fat and lacrimal gland. Patients present with red eyes and discomfort—they often describe the pain as retro-orbital. There is lid and periorbital swelling due to soft tissue oedema, lid retraction, chemosis or conjunctival oedema, keratoconjunctivitis sicca secondary to infiltration of the lacrimal gland, proptosis, lagophthalmos, limitation in ocular motility caused by inflammation of the extraocular muscles. In severe cases, optic neuropathy due to compression of the optic nerve or its blood supply by the inflamed and enlarged extraocular muscles. 5.3.2.2  Emergencies in Thyroid Eye Disease Severe thyroid eye disease can lead to permanent visual loss. Emergencies in thyroid eye disease include optic nerve compression, exposure keratopathy and glaucoma. Fig. 5.16  Thyroid eye disease

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Optic nerve compression occurs when extraocular muscles and other orbital soft tissue were severely inflamed leading to enlargement. There may be signs of optic nerve compromise with reduced visual acuity, impaired colour vision, visual field defects, relative afferent pupillary defect and a swollen optic disc. Patients should receive immediate treatment to prevent irreversible visual loss. Early immunosuppression can be given in the form of a systemic steroid, usually via an intravenous route. If this fails, surgical decompression is required to relieve the orbital pressure. Orbital irradiation can be considered for those patients who are not surgical candidates, or those who are at risk of steroid side effects. Exposure keratopathy is often a result of proptosis causing lagophthalmos. Lid retraction may exacerbate the condition. Exposure of the cornea results in erosion, ulcer, and subsequently corneal scar causing permanent visual loss. Therefore it is important to assess a patient’s tear film and ability to close the lids. Treatment starts with adequate lubricants and taping the involved eye. Sometimes, a frost suture may be required to close the lid. In severe cases, systemic steroid and orbital decompression are required to relieve the proptosis and hence the exposure. Increase in intraocular pressure happens due to enlargement of the intraorbital contents, increased episcleral venous pressure due to congestive orbitopathy, and tight recti muscles. The pressure should be controlled medically using pressure-­ lowering eye drops. If this fails, and if severe proptosis exists, surgical decompression may be needed. 5.3.2.3  Assessment of Thyroid Eye Disease It is important to have an accurate assessment of thyroid eye disease because it affects subsequent diagnosis and management. Assessment of thyroid eye disease includes both activity and severity. The Clinical Activity Score (CAS) assesses disease activity. One score is given for each finding present. A score of 4 or more has a high predictive value for the outcome of immunosuppressant treatment for thyroid eye disease. The components of the CAS include the following: • Pain –– Pain, oppressive feeling on or behind the globe, during the last 4 weeks –– Pain on attempted up, side or down gaze, during the last 4 weeks • Redness –– Redness of the eyelid –– Diffuse redness of the conjunctiva • Swelling –– –– –– ––

Swelling of the eyelid Chemosis Swollen caruncle Increase of proptosis of ≥2 mm during a period of 1–3 months

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• Impaired function –– Decrease of eye movements in any direction ≥5° during a period of 1–3 months –– Decrease of visual acuity of ≥1 line on the Snellen chart during a period of 1–3 months The NOSPECS classification assesses disease severity. This is less commonly used now as studies had shown that disease activity rather than disease severity is the prime determinant of therapeutic outcome. The components of NOSPECS classification include the following: • • • • • • •

N = No symptoms or signs O = Only signs, no symptoms S = Soft tissue involvement P = Proptosis E = Extraocular muscle involvement C = Corneal involvement S = Sight loss

The VISA classification was developed which allows various aspects of thyroid eye disease to be evaluated and recorded to allow appropriate management. It ­separates the various clinical features of thyroid eye disease into four parameters, namely: V (vision, optic neuropathy) I (inflammation, congestion) S (strabismus, motility restriction) A (appearance, exposure) Investigations in thyroid eye disease include serum testing: thyroid function tests (TSH, free T4 and T3), thyroid autoantibodies (thyroid hormone stimulating receptor antibodies, anti-thyroid peroxidase and anti-thyroglobulin antibodies). Orbital imaging is important to assess the ocular status and look for any optic nerve compression. The typical finding on imaging is enlarged extraocular muscle bellies with the tendons spared. MRI gives better resolution of the orbital soft tissue, and CT is preferred when planning for decompression of the orbit. 5.3.2.4  Treatment Treatment of thyroid eye disease requires a multi-disciplinary approach involving ophthalmologists, endocrinologists, orthoptists, and radiation oncologists. Management options include supportive treatment such as use of lubricants or prisms to relieve diplopia, medical treatment involving use of immunosuppressants and radiotherapy to relieve tissue oedema, and surgical treatment including orbital decompression and rehabilitative surgery like squint and lid surgeries. The European Group on Graves’ orbitopathy (EUGOGO) published a consensus statement on the management of thyroid eye disease. In short, all patients with

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thyroid eye disease should be referred to specialist centres, encouraged to quit smoking, and receive prompt treatment in order to restore and maintain euthyroidism. Strict follow up of thyroid dysfunction is necessary. In patients with mild thyroid eye disease, local measures and an expectant strategy may be adequate. Use of antioxidants such as selenium may be helpful.

5.3.3  Vascular 5.3.3.1  Cavernous Haemangioma Cavernous haemangioma (Fig. 5.17) is the most common benign orbital tumour in adults. It has a female preponderance and often presents in middle age. If present in the muscle cone, it can lead to axial proptosis, optic disc swelling and choroidal folds. If the haemangioma lies near the orbital apex, it may compress onto the optic nerve causing visual loss. CT and MRI imaging shows a well-circumscribed intraconal lesion with mild or moderate contrast enhancement. The haemangioma can be asymptomatic and is an incidental finding when imaging of the orbits is performed for other reasons. Asymptomatic lesions can be observed but symptomatic lesions should have complete surgical excision. The lesion is usually well-encapsulated allowing complete removal. 5.3.3.2  Capillary Haemangioma Capillary haemangioma (Fig.  5.18) is a common benign tumour in children that may affect the lid and the orbit. The lesion is usually apparent before 6 months of age. It tends to rapidly progress in the first year of life and then gradually regress spontaneously over years. Superficial haemangiomas are reddish and are often known as strawberry naevus, while deeper lesions are more bluish. Haemangiomas on the lid may be cosmetically disfiguring, and may cause astigmatism, obscure visual axis leading to amblyopia. Haemangiomas in the orbit may lead to proptosis which worsens with Valsalva manoeuvre or crying. Patients with large haemangioma may have associated high-output cardiac failure. If the tumour is consumptive, Kasabach-Merritt syndrome, characterized by thrombocytopenia, anaemia and decreased clotting factors, may result. Small superficial lesions can be observed as most may regress spontaneously. If treatment is required, options include intralesional steroid injection, oral ­propranolol, laser therapy, cryotherapy, low-dose radiotherapy, sclerosing agents and surgical resection.

5  Adnexal Conditions Fig. 5.17 (a) Left cavernous haemangioma causing a proptotic appearance. (b) Axial orbital CT showing a well circumscribed intraconal lesion. (c) Excised cavernous haemangioma

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Fig. 5.18  Left capillary haemangioma

5.3.3.3  Orbital Varices Orbital varices are congenital venous malformations. It may present anytime from childhood onwards. Most varices are unilateral and affect the upper medial region of the orbit. Patients present with intermittent proptosis which is exacerbated with Valsalva manoeuvre, straining or coughing. Sometimes, the lesion may be visible on the eyelid and under the conjunctiva. Occasionally, there may be acute haemorrhage and thrombosis from the lesion. Treatment is necessary when there is severe proptosis, pain, optic nerve compression, or recurrent haemorrhage and thrombosis. Treatment is by surgery but complete removal is difficult because the lesion is friable and may bleed excessively at the time of surgery. Use of sclerosing agents or glue embolization may help. 5.3.3.4  Carotid-Cavernous Fistula This is an abnormal vascular communication between the carotid artery and the cavernous sinus. It may be congenital, idiopathic, or secondary to trauma. Patients may present with a red eye due to conjunctival vascular engorgement known as corkscrew vessels. There may be pulsatile proptosis with associated carotid bruit or thrill. Intraocular pressure is raised due to elevated venous pressure and orbital congestion. Ocular motility may be affected with diplopia. Other possible signs include relative afferent pupillary defect, optic disc swelling, retinal venous engorgement and retinal haemorrhage, and anterior segment ischaemia characterized by corneal oedema, anterior chamber cells and flare, cataract, iris atrophy, and neovascularization of the iris. The typical features of carotid-cavernous fistula on imaging include a dilated superior ophthalmic vein and mild swelling of extraocular muscles. Treatment is

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indicated when there is secondary glaucoma, severe proptosis, and diplopia. The fistula is closed by coil or glue embolization using interventional radiology technique by various catheters.

5.3.4  Tumours 5.3.4.1  Lacrimal Gland Tumour Pleomorphic Adenoma Pleomorphic adenoma is a benign mixed-cell tumour of the lacrimal gland. It is the most common lacrimal tumour. The tumour usually arises in middle age as a painless progressive swelling in the lacrimal gland region. Patients present with upper lid swelling or palpable swelling and proptosis. Imaging, preferably CT, shows a well circumscribed tumour with or without calcification, indentation of the globe, and expansion but not destruction of the lacrimal fossa. Pleomorphic adenoma has a small chance of malignant transformation. Therefore treatment involves complete surgical excision of the entire tumour. The capsule must be kept intact to avoid tumour seeding into the adjacent orbital tissue. Lacrimal Gland Carcinoma The most common lacrimal gland carcinoma is the adenoid cystic carcinoma. They present at a similar age as pleomorphic adenoma but with a much shorter history and more acute progression over a few months’ time with rapid proptosis and ocular motility limitation. Orbital pain due to perineural spread is common. CT may reveal a poorly defined lesion at the lacrimal gland region with bony erosion, destruction and in some cases calcification. Prognosis is very poor even with radical surgical excision as the tumour is almost always beyond excision due to perinerual invasion. Orbital exenteration and radiotherapy may be done to prolong life and reduce pain. 5.3.4.2  Optic Nerve Tumour Optic Nerve Glioma Optic nerve glioma is a slow-growing low-grade tumour of astrocytes that usually affects children and has a strong association with neurofibromatosis type 1. Patients usually present with progressive visual loss and optic nerve dysfunction, proptosis and optic atrophy. It may spread intracranially to involve the optic chiasm and hypothalamus.

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Imaging shows fusiform enlargement of the optic nerve. Treatment is controversial. In patients with good vision and small lesion, observation and monitoring with regular imaging are advised. If there is severe proptosis, visual loss, and posterior spread threatening the optic chiasm, treatment is required. It involves radiotherapy which can often stabilize the vision, chemotherapy, and surgical excision. Optic Nerve Sheath Meningioma Optic nerve sheath meningioma is a benign tumour of meningothelial cells of the meninges. It usually affects middle age females and has an association with neurofibromatosis type 2. Patients usually present with unilateral gradual visual loss or transient visual obscurations. There may also be optic atrophy, opticociliary shunt vessels, proptosis, and ocular motility limitation. Imaging shows tubular enlargement of the optic nerve with a typical “tram-track” sign. Sometimes calcification of the optic nerve is present. If visual acuity is good, observation is recommended. Radiotherapy works in selected cases. If the tumour is aggressive or if the eye is blind with severe proptosis, surgical excision can be performed. 5.3.4.3  Malignant Orbital Tumour Lymphoma Lymphoma (Fig. 5.19) may affect both the orbit and the lacrimal gland. It usually occurs in the elderly and is often a low-grade proliferation of B cells, i.e. the non-­ Hodgkin’s type. The most common subtype is the marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Patients usually present with gradual proptosis or lid swelling with a palpable firm rubbery mass. There may also be ptosis. It is usually unilateral, but ­occasionally it can occur bilaterally. It is necessary to refer the patients to an oncologist or physician for systemic workup because systemic involvement is present in up to 40% of cases. The course is variable and depends on the grade and staging of the disease. Treatment involves radiotherapy for localized lesion and chemotherapy for systemic disease. Rhabdomyosarcoma Rhabdomyosarcoma (Fig. 5.20) is the most common primary orbital malignancy in children. It usually presents before 10 years of age. Characteristically, patients present with rapid progressive proptosis. There is ptosis and a mass may be palpable. The acute progressive course may mimic acute inflammatory or infective process such as orbital cellulitis. The tumour may destroy adjacent bones and spread

5  Adnexal Conditions Fig. 5.19 (a) Image of a patient with right orbital lymphoma. Note the slight upward displacement of the globe. (b) Axial orbital CT showing a homogenous orbital mass

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Fig. 5.20 (a) Image of a patient with right rhabdomyosarcoma showing ptosis. (b) Axial T2 MRI showing a hyperintense mass adjacent to the globe

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i­ntracranially. Imaging shows an irregular homogenous mass with or without adjacent bony erosion. The role of ophthalmologists in managing rhabdomyosarcoma lies in early incisional biopsy to confirm the diagnosis, followed by prompt referral to a paediatric oncologist for further workup and management. Treatment involves radiotherapy and chemotherapy. Occasionally surgical excision or exenteration may be required. The prognosis varies and depends on the stage, extent and histological subtype of the tumour. Secondary Tumour Metastatic tumour reaches the orbit by haematogenous spread. The most common source of primary tumour is lung and gastrointestinal in adults, prostate in men, breast in women, and neuroblastoma in children. Metastatic tumour of the orbit usually has an aggressive presentation with rapid proptosis, ocular motility restriction and cranial nerve involvement. Small localized tumours may be debulked or excised; localized secondary orbital tumors extending from surrounding structures may be treated by radical resection and reconstruction. Other tumours may respond to radiotherapy or chemotherapy. Nevertheless, adults with metastatic orbital tumours often have poor prognosis with limited life expectancy. Children with neuroblastomas, on the other hand, have a relatively good prognosis.

5.3.5  Inflammatory Diseases of the Orbit 5.3.5.1  Idiopathic Orbital Inflammatory Disease Idiopathic orbital inflammatory disease (IOID) is an inflammatory process of the orbit with unknown aetiology. The inflammation may involve any of the orbital soft tissues. Histology shows a pure inflammatory response with no cellular atypia followed by reactive fibrosis. It was previously known as orbital pseudotumour as it simulates a neoplastic process. It is important to note that IOID is a diagnosis by exclusion; infective aetiologies such as sinusitis with secondary orbital cellulitis or systemic diseases such as thyroid eye disease, Granulomatosis with polyangiitis (Wegener’s granulomatosis) and other autoimmune diseases have to be excluded. IOID is usually unilateral. Patients present with acute pain, redness, lid swelling, proptosis, ocular motility limitation and diplopia. The course varies among patients. While some patients enjoy spontaneous remission after a few weeks, some suffer from prolonged inflammation resulting in fibrosis of orbital tissue impairing ocular motility.

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Biopsy is required to exclude other diseases to confirm the diagnosis of IOID.  Treatment requires use of systemic immunosuppressants such as systemic steroid or cytotoxic drugs. Occasionally radiotherapy may be considered. Despite treatment, IOID may recur.

5.3.5.2  Orbital IgG4-Related Disease Orbital IgG4-related disease is characterized by IgG4-positive lymphoplasmacytic infiltrations of orbital tissues including the lacrimal gland. The involved tissue will subsequently become fibrotic. It is often associated with elevated serum IgG4 level. Orbital IgG4-related disease usually affects people in middle age and the elderly. Patients present with lid swelling, proptosis, and mild ocular motility restriction. There is usually no visual loss. Imaging shows infiltrative lesions affecting the orbit or the lacrimal gland. Biopsy should be performed which shows IgG4-positive plasma cells on immunohistochemical analysis. Blood tests may show elevated serum levels of IgG4, IgE, and hypergammaglobulinaemia. Around half of the patients have bilateral involvement. In addition to the orbit, IgG4-related disease often affects other organs including the salivary glands, lymph nodes, pancreas (known as autoimmune pancreatitis in the past), and bile ducts. Chronic rhinosinusitis is also possible. Infraorbital nerve enlargement is commonly seen in IgG4-related disease. Treatment of orbital IgG4-related disease involves use of systemic steroids to which the diseases is quite responsive. However, unless the patients remain on long-term steroid, relapse is common after steroid is stopped. Other modalities of treatment include radiotherapy or immunomodulating agents such as rituximab.

5.3.5.3  Orbital Myositis Orbital myositis is an idiopathic, non-specific inflammatory process affecting one or more extraocular muscles, with involvement of the superior and lateral recti being the most frequent. Patients present with acute pain which worsens on attempted gaze controlled by the involved muscle. Patients also present with eye redness and mild proptosis. Imaging shows fusiform enlargement of the affected extraocular muscle together with its tendon. Mild cases of orbital myositis can be controlled by non-steroidal anti-­ inflammatory drugs which helps to relieve discomfort and dysfunction. Systemic steroid is usually required and gives good treatment outcome. Radiotherapy is also effective and is used to prevent subsequent recurrences. It is also important to consider biopsy of the muscle to rule out malignancy in cases that do not respond to treatment or are recurrent.

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5.3.6  Infection of the Orbit 5.3.6.1  Orbital Cellulitis Orbital cellulitis (Fig. 5.21) is a sight and life-threatening condition as it may spread to cause intracranial complications. Orbital cellulitis involves bacterial infection of the soft tissue behind the orbital septum. The most common organisms are Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, and Haemophilus influenzae. The source is often from the nearby sinuses, dacryocystitis, haematogenous, or following trauma or orbital surgery. Patients present with rapid proptosis, chemosis, ocular motility limitation, visual loss, fever and malaise. Extension of the infection to cavernous sinus may cause bilateral involvement of cranial nerves II–VI. Erosion of the orbital roof may cause meningitis and brain abscess and is life-threatening. Imaging is helpful to identify an orbital or subperiosteal abscess formation, and to look for sinusitis. Orbital cellulitis is an ocular emergency and the patient should be admitted to hospital immediately. Wide-spectrum intravenous antibiotics should be administered. Patients who do not respond to intravenous antibiotics or those who develop orbital or subperiosteal abscesses should receive surgery for drainage. Management of patients with orbital cellulitis should be in a multi-disciplinary approach involving ophthalmologists, paediatricians in paediatric cases, otolaryngologists and dental surgeons should the source of infection be sinus or dental in nature respectively as these have to be drained as well.  In the unfortunate event of an intracranial abscess formation which is life-threatening, neurosurgeons should be consulted at once for drainage of the abscess. 5.3.6.2  Pre-septal Cellulitis Pre-septal cellulitis involves infection of the tissue anterior to the orbital septum. Although it is not an orbital condition, it is important to make the distinction between pre-septal and orbital cellulitis. Pre-septal cellulitis has the potential to Fig. 5.21  Patient with right orbital cellulitis with surrounding erythema and ptosis

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progress to an orbital cellulitis. It is more common in children, and risk factors include trauma to skin, hordeolum and upper respiratory tract infections. Patients present with a unilateral swollen and inflamed lid without proptosis and chemosis. Optic nerve function is not impaired. These patients can be initially be managed with oral antibiotics.

Further Reading Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, Perros P, Salvi M, Wiersinga WM. The 2016 European Thyroid Association/European Group on Graves’ orbitopathy guidelines for the management of Graves’ orbitopathy. Eur Thyroid J. 2016;5:9–26. Boboridis KG, Bunce C. Interventions for involutional lower lid entropion. Cochrane Database Syst Rev. 2011;(12):CD002221. https://doi.org/10.1002/14651858.CD002221.pub2. Burton M, Habtamu E, Ho D, Gower EW, et al. Cochrane Database Syst Rev. 2015;(11):CD004008. https://doi.org/10.1002/14651858.CD004008.pub3. Huang J, Malek J, Chin D, Snidvongs K, Wilcsek G, Tumuluri K, Sacks R, Harvey RJ. Systematic review and meta-analysis on outcomes for endoscopic versus external dacryocystorhinostomy. Orbit. 2013;33(2):81–90. Leonardi-Bee J, Batta K, O’Brien C, Bath-Hextall FJ. Cochrane review: Interventions for infantile haemangiomas (strawberry birthmarks) of the skin. Evid Based Child Health. 2012;7:578–626. https://doi.org/10.1002/ebch.1831. Lindsley K, Matsumura S, Hatef E, Akpek EK. Interventions for chronic blepharitis. Cochrane Database Syst Rev. 2012;(5):CD005556. https://doi.org/10.1002/14651858.CD005556.pub2. Lindsley K, Nichols JJ, Dickersin K.  Non-surgical interventions for acute internal hordeolum. Cochrane Database Syst Rev. 2017;(1):CD007742. https://doi.org/10.1002/14651858. CD007742.pub4. Minakaran N, Ezra DG.  Rituximab for thyroid-associated ophthalmopathy. Cochrane Database Syst Rev. 2013;(5):CD009226. https://doi.org/10.1002/14651858.CD009226.pub2. Narayanan K, Hadid OH, Barnes EA.  Mohs micrographic surgery versus surgical excision for periocular basal cell carcinoma. Cochrane Database Syst Rev. 2014;(12):CD007041. https:// doi.org/10.1002/14651858.CD007041.pub4. Petris C, Liu D.  Probing for congenital nasolacrimal duct obstruction (Protocol). Cochrane Database Syst Rev. 2014;(5):CD011109. https://doi.org/10.1002/14651858.CD011109. Rajendram R, Bunce C, Lee RWJ, Morley AMS. Orbital radiotherapy for adult thyroid eye disease. Cochrane Database Sys Rev. 2012;(7):CD007114. https://doi.org/10.1002/14651858. CD007114.pub2.

Chapter 6

Conjunctiva and Cornea Mehran Zarei-Ghanavati and Mohamed Bahgat Goweida

6.1  Infectious Conjunctivitis 6.1.1  Acute Bacterial Conjunctivitis Acute bacterial conjunctivitis can be caused most commonly by the following organisms; Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae. Gonococci may cause hyper-acute conjunctivitis. 6.1.1.1  Clinical Features Red eye, lid swelling, foreign body sensation and discharge are common symptoms. There is conjunctival injection and chemosis. Discharge is watery or mucopurulent. Purulent discharge and peripheral corneal ulceration are seen in gonococcal or meningococcal conjunctivitis. 6.1.1.2  Treatment Microbiological culture and sensitivity testing of conjunctival swab is indicated in hyper-acute and severe forms to exclude gonococcal or meningococcal infection. It should also be done for persistent conjunctivitis. Otherwise, bacterial conjunctivitis is often self-limiting. Topical antibiotics such as chloramphenicol, aminoglycosides, M. Zarei-Ghanavati Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran M. B. Goweida (*) Department of Ophthalmology, Alexandria Main University Hospital, Alexandria, Egypt Faculty of Medicine, Alexandria University, Alexandria, Egypt © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_6

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quinolones and macrolides accelerate recovery. Systemic antibiotic coverage is required for H. influenzae, meningococcal and gonococcal conjunctivitis.

6.1.2  Adult Chlamydial Conjunctivitis Chlamydia trachomatis (variants D–K) causes adult chlamydial conjunctivitis. It is transmitted via eye to eye contact or exposure to genital secretions. 6.1.2.1  Clinical Features Patients may present with unilateral or bilateral redness, lacrimation and discharge which may persist for several months in some cases. Clinical signs include watery or mucopurulent discharge, large follicles in the inferior fornix which may also involve the upper tarsal conjunctiva. There may be changes on the cornea including superficial punctate keratitis, perilimbal corneal infiltrates which may appear after 2–3 weeks. Chronic cases have less prominent conjunctival follicles and commonly develop papillae. Mild conjunctival scarring and superior corneal pannus are not uncommon. Preauricular lymphadenopathy may be present. 6.1.2.2  Investigations Tarsal conjunctival scrapings may be sent for PCR, Giemsa staining and direct immunofluorescence scalpel blade and bacteriological examination. Nucleic acid amplification tests such as PCR are likely to be the investigation of choice. Giemsa staining for basophilic intracytoplasmic bodies is performed by applying scrapings onto a glass slide. Direct immunofluorescence detects free elementary bodies with approximately 90% sensitivity and specificity. 6.1.2.3  Treatment Systemic treatment with azithromycin or doxycycline is very effective. Referral to the genitourinary clinic is mandatory to exclude other sexually transmitted infections and contact tracing. Topical treatment of Azithromycin 1.5% eye drops can be precribed in addition to systemic treatment.

6.1.3  Trachoma Trachoma caused by Chlamydia trachomatis (variants A, B and C) is the most common cause of corneal blindness by infection. It is endemic in developing countries and remote areas in Africa, Asia, Central and South America, Australia and the Middle East. It is related to poor sanitation, crowding and poverty.

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6.1.3.1  Clinical Features Active Stage There is follicular and papillary conjunctivitis with superior pannus formation. Cicatricial Stage It is developed in untreated patients by progressive scar formation. Scar in upper tarsal conjunctiva (Arlt line—horizontal scar), scar of resolved superior limbal follicles (Herbert pits), dry eye, trichiasis and corneal opacity (Figs. 6.1 and 6.2). 6.1.3.2  Treatment The SAFE strategy introduced by WHO includes Surgery for trichiasis and entropion, Antibiotics for active disease, Facial hygiene and Environmental improvement. A single dose of azithromycin (20 mg/kg up to 1 g) is the treatment of choice.

6.1.4  Neonatal Conjunctivitis (Ophthalmia Neonatorum) By definition, neonatal conjunctivitis is conjunctival inflammation which develops during the first month of life. It may be caused by acquiring an infection during vaginal delivery such as C. trachomatis, N. gonorrhoeae, Herpes simplex virus (HSV), etc. Toxicity of topical antibacterial medication may cause chemical conjunctivitis. Gonococcal or chemical conjunctivitis usually presents early in the first few days after birth. Fig. 6.1  Herbert pits seen in patient with trachoma in the past

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Fig. 6.2 Tarsal conjunctival scarring from trachoma (upper). Corneal opacification and entropion with trichiasis (lower). (Reproduced from Burton M.J. (2010) Trachoma. In: Reinhard T., Larkin F. (eds) Cornea and External Eye Disease. Essentials in Ophthalmology. Springer, Berlin, Heidelberg)

6.1.4.1  Clinical Features Watery or mucopurulent discharge is the main presenting sign. However, purulent discharge, severe eyelid oedema and corneal ulceration (later presentation) are seen in gonococcal conjunctivitis. Lid vesicles and dendritic epithelial lesion may be accompanying signs in HSV conjunctivitis. Pseudomembrane may form in chlamydial infection. Signs of systemic infection may coexist. 6.1.4.2  Treatment Conjunctival swab is done for Gram stain and culture, particularly for severe cases. Systemic medication is necessary for gonococcal (third-generation cephalosporin), chlamydia (erythromycin) and HSV conjunctivitis (acyclovir). Topical broad-­ spectrum antibiotic is effective for other infectious causes.

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6.1.5  Adenoviral Conjunctivitis It may cause sporadic conjunctivitis or epidemic in schools, swimming pools or medical facilities. Viral particles can survive on dry surfaces for weeks, and viral shedding may occur for many days before clinical features are apparent which may facilitate the spread of this highly contagious virus. Transmission is generally by contact with respiratory or ocular secretions. 6.1.5.1  Clinical Features Patients complain of acute onset of red eye, foreign body sensation and discharge. Both eyes are usually affected which may be sequential. Lid swelling, follicular conjunctivitis, subconjunctival hemorrhage, chemosis, preauricular lymphadenopathy are seen in adenovirus conjunctivitis. Two clinical presentations of adenovirus conjunctivitis: • Epidemic keratoconjunctivitis (EKC) is caused by adenovirus serotypes 8, 19 and 37. It causes severe conjunctivitis sometimes with membrane formation. Corneal involvement is common in the form of punctate epithelial keratitis. Subsequently, subepithelial infiltration may develop and persist for several months. • Pharyngoconjunctival fever (PCF) is caused by adenovirus serotypes 3, 4 and 7. There is fever and pharyngitis in addition to conjunctivitis. 6.1.5.2  Treatment Conjunctivitis usually resolves spontaneously. Supportive treatment such as lubricants can be given to alleviate symptoms. Patients should be advised to take measures to reduce spread (frequent hand washing, not sharing towels and soaps, avoid touching eyes). Topical steroid may be necessary for corneal involvement of adenovirus and in cases with membrane formation.

6.1.6  Other Viral Conjunctivitis Primary HSV infection may cause a follicular conjunctivitis which is usually unilateral with associated skin vesicles. Systemic viral infections in childhood such as varicella, measles and mumps, can be associated with follicular conjunctivitis. Molluscum contagiosum (a virus in poxvirus family) cause small pearly lesions with central umbilication typically at lid margins. Shedding of virus from lesion in lids can cause chronic follicular conjunctivitis. This can be treated with removal of the lesion with shave excision or cauterization. See Fig. 6.3.

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Fig. 6.3  Image of molluscum contagiosum on the lid margin (upper) and follicular conjunctivitis secondary to molluscum (lower). (Reproduced with permission from: Ali T.K., Pantanelli S.M. (2016) Conjunctivitis. In: Laver N., Specht C. (eds) The Infected Eye. Springer, Cham)

6.2  Allergic Conjunctivitis 6.2.1  H  ay Fever Conjunctivitis and Perennial Allergic Conjunctivitis Hypersensitivity reactions mediated by IgE cause reactions to airborne allergens. There is a release of histamine and other inflammatory mediators from the conjunctival mast cells. Allergens in hay fever conjunctivitis is environmental in the spring or summer but in perennial conjunctivitis exists year-round. 6.2.1.1  Clinical Features The main complaint of patients is itching. There is lid swelling, chemosis and mucoid discharge. Papillary reaction is seen.

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6.2.2  Vernal Keratoconjunctivitis Vernal keratoconjunctivitis (VKC) is a bilateral inflammation of the cornea and conjunctiva which is more common in young males. There is usually a history of atopy. It is more prevalent in areas with hot climates like the Middle East and Africa. The disease duration may be up to several years. 6.2.2.1  Clinical Features Itching, photophobia, red eye and mucoid discharge are common presentations. VKC is categorized to two types with some overlaps: Palpebral VKC: Inflammation is more prominent in upper palpebral conjunctiva in the form of papillary conjunctivitis. Giant papillae (more than 1 mm) may develop and has a cobblestones appearance. Limbal VKC: Inflammation in limbus causes thickened limbus with a gelatinous appearance. Limbal papillae are sometimes seen. Horner-Trantas dots (see Fig. 6.4) are accumulations of eosinophils and epithelial cells may be seen as white dots over limbus. • In cases with poor control of inflammation, punctate epithelial erosions and sometimes an epithelial defect may develop which is called shield ulcer. This ulcer forms more commonly in upper half of the cornea and sometimes a plaque may form over the base of the ulcer. Patients with VKC are at risk of keratoconus and should be screened for it.

6.2.3  Atopic Keratoconjunctivitis Atopic keratoconjunctivitis is a chronic bilateral kerato-conjunctivitis in patients with an atopic background. Inflammation is year-round and develops in adult age. Fig. 6.4 Horner-Trantas dots. (Reproduced from La Rosa, M., Lionetti, E., Reibaldi, M. et al. Ital J Pediatr (2013) 39: 18)

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6.2.3.1  Clinical Features Chronic itching of eye and lids are main complaints. There is also mucoid discharge and photophobia. Conjunctival scarring develops in forms of subepithelial fibrosis or symblepharon. Limbal stem cell dysfunction may be seen in advanced cases. Subcapsular cataract and keratoconus are more common in these patients. These patients are more susceptible to staphylococcal and HSV infections.

6.2.4  G  eneralized Approach for Treatment of Allergic Conjunctivitis Treatment starts with avoidance of allergen exposure if possible. Cold compress and use of artificial tears to wash out allergen are useful. Topical antihistamines, mastcell stabilizers, NSAIDs and short course of topical steroids are commonly prescribed to control inflammation. Topical cyclosporine or tacrolimus are used in steroid dependent or refractory cases of VKC and AKC. Systemic immunosuppressive medications are indicated in severe cases of atopic keratoconjunctivitis.

6.3  S  tevens-Johnson Syndrome and Toxic Epidermal Necrolysis Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous reactions. They are commonly caused by • Drugs such as sulfonamides, penicillin, anticonvulsants, NSAIDs, etc. • Infectious diseases like streptococci, mycoplasma, HSV, HIV, etc.

6.3.1  Clinical Features Skin and the mucous membrane are affected in SJS and TEN.  TEN is the more severe form and more than 30% of body surface area is involved in TEN. There is flu-illness with fever, malaise and respiratory symptoms. Bullous lesions form in skin and mucous membrane of eyes, mouth and genitalia. Red eyes and discharge are presenting symptoms. There is membranous conjunctivitis. Conjunctival and corneal epithelial defect is present in severe cases. Conjunctival scarring and symblepharon develop in these cases.

6.3.2  Treatment Patients should be admitted. There is controversy about the use of systemic steroid or other immunosuppressive medications. Systemic treatment is mainly guided by physicians. Ophthalmologist’s examination should be done at the beginning of

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patients’ admission. Irrigation of the eyes and gentle removal of membranes are recommended. Topical lubricant, antibiotics, steroid are prescribed for all patients with ocular involvement. Amniotic membrane transplantation for covering the cornea, conjunctiva and lid margin is proven to decrease chronic sequel of SJS in patients with moderate to severe ocular involvement (epithelial defect of cornea or conjunctiva) when it is done within the first week of onset of ocular disease. The chronic phase of ocular disease is treated with lubricants and topical anti-­inflammatories. Surgical treatment of distichiasis, entropion and lid margin keratinization is necessary. Scleral contact lens wear is helpful for patients with severe dry eye. Corneal transplantation, limbal stem cell transplantation and artificial keratoplasty are last resorts for corneal blindness in these patients.

6.4  Mucous Membrane Pemphigoid Mucous membrane pemphigoid (MMP), which was formerly called ocular cicatricial pemphigoid, is more common in women and patients older than 60 years. The pathogenesis of MMP is autoimmune reaction against antigens in the basement membrane.

6.4.1  Clinical Features There are recurrent attacks of non-specific conjunctival inflammation with bullae formation. It leads to subepithelial fibrosis and shortening of the fornices. Symblepharon, surface keratinization and ankyloblepharon are seen in advanced cases (Fig. 6.5).

6.4.2  Diagnosis Conjunctival and/or oral biopsy should be done for direct immunofluorescent examination. Negative results do not rule out this disease. Fig. 6.5 Mucous membrane pemphigoid. Advanced stage with keratinization

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6.4.3  Treatment Topical lubricant is used for treatment for dry eyes. Topical anti-inflammatory drops are not effective in this disease. Systemic immunosuppressive medication is needed to control inflammation. Dapsone or mycophenolate mofetile are best choices for mild cases. Cyclophosphamide may be necessary in severe disease. Systemic steroid is used in these severe cases waiting to see the effect of cyclophosphamide. Artificial keratoplasty is the only available option for advanced cases with corneal opacity.

6.5  Ocular Graft vs Host Disease (GVHD) GVHD is a complication of bone-marrow transplantation that is caused by attack of donor T cell lymphocytes against patient’s tissues including eyes. Eye involvement causes severely dry eyes.

6.5.1  Treatment Application of topical artificial tears and topical anti-inflammatory is necessary. Punctal occlusion is available. Systemic immunosuppression is effective for control of inflammation in eyes and other organs. Scleral contact lens is prescribed in cases with severe dry eye. Artificial keratoplasty is the last option.

6.6  Degenerations 6.6.1  Pinguecula Yellow–white nodular lesions in conjunctiva near limbus which are common in nasal side. The main etiology is sun exposure. Sun glasses can be worn by patients. Surgical treatment is usually not necessary.

6.6.2  Pterygium A triangular growth of conjunctival tissue onto the cornea more commonly in patients with chronic sun exposure (Fig. 6.6).

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Fig. 6.6 Pterygium

6.6.2.1  Clinical Features Small lesions are usually asymptomatic. Recurrent irritation and foreign body sensation may exist. The indications for surgery include symptomatic lesions, cosmetic appearances, induced astigmatism and large pterygium approaching the centre of the cornea. 6.6.2.2  Treatment Pterygium excision with conjunctival autograft is the gold standard treatment. Conjunctival flaps and amniotic membrane graft are sometimes used. Intraoperative application of Mitomycin C is effective but there is chance of late onset scleral necrosis.

6.7  Subconjunctival Haemorrhage There is an accumulation of blood under the conjunctiva. The red appearance of eye is daunting for patients. Causes of subconjunctival haemorrhage include trauma, vascular fragility due to age, diabetes or hypertension, increased venous pressure due to coughing or vomiting, bleeding disorders and medications such as warfarin (Fig. 6.7).

6.8  Dry Eye Diseases Tear Film and Ocular Surface Society Dry Eye Workshop (DEWS II) defines dry eye as: “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which

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Fig. 6.7 Subconjunctival haemorrhage. (Reproduced with permission from: Huang B. (2018) Acute Redness of the Eye. In: Yan H. (eds) Ocular Emergency. Ocular Trauma. Springer, Singapore)

tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” Dry eye is one of the most common eye disorders especially in patients older than 40s. Its effect on patients’ quality of life is compared with angina. It is classified as: • Aqueous-deficient –– Sjögren syndrome (SS) dry eye (primary or secondary) –– Non-Sjögren syndrome dry eye • Evaporative –– The most common reason is meibomian gland dysfunction (MGD).

6.8.1  Clinical Features The patients’ symptoms are foreign body sensation, grittiness, burning, transient visual loss, photophobia, discharge and tearing. There is no single test for diagnosis of dry eye. Schirmer test without anaesthesia (less than 10 mm), corneal staining with fluorescein, conjunctival staining with Rose Bengal or lissamine green and decrease in tear meniscus may be present. Change in quality of lipid from meibomian glands by digital expression by ophthalmologists is the main sign for diagnosis of MGD.

6.8.2  Treatment Artificial tear is the mainstay of treatment. Drops with higher viscosity or gels are used for more severe dry eye. Ointment is usually applied at night time due to its blurring effect on vision. Punctal occlusion increases tear retention.

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Anti-­inflammatory drops should be used in moderate or severe dry eye. Cyclosporine drop is commonly used for this purpose. Oral tetracyclines or macrolides are effective for treatment of MGD in combination with lid hygiene and massage. Autologous serum eye drops and scleral contact lens should be considered for severe dry eye.

6.9  Infectious Keratitis A wide range of infectious pathogens may infect the cornea including virides, bacteria, fungi and amoebae. Infectious keratitis is an ophthalmic emergency. Any delay in treatment is a main risk factor for poor prognosis.

6.9.1  Bacterial Keratitis Although there are many bacteria that may cause keratitis; Staphylococcus aureus and Pseudomonas aeruginosa are the most common pathogens involved in microbial keratitis. 6.9.1.1  Risk Factors It is important to detect any risk factors for keratitis in patients. These include contact lens wear, trauma (including surgical trauma), ocular surface disease such as dry eye, blepharitis, allergic eye disease, reduced corneal sensation and corneal exposure. 6.9.1.2  Clinical Features Patients will report decreased vision, red eye, pain, photophobia, lid swelling and discharge. On slit lamp examination there will be an epithelial defect with stromal ulceration and infiltration. Severe stromal thinning may lead to Descemetocoele and perforation. Corneal oedema around infected site is more common in Gram negative bacteria (e.g. Pseudomonas aeruginosa). Conjunctival injection and variable amount of anterior chamber cells is almost always seen (Fig. 6.8). 6.9.1.3  Treatment A corneal scrape should be taken from the corneal ulcer for smear and culture. Empirical broad-spectrum fluoroquinolones or fortified antibiotics drops such as cefazolin and gentamicin are started hourly. The treatment for microbial keratitis requires intensive topical antibiotics in the initial 48 h. Contact lens wear should be

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Fig. 6.8 Pseudomonas corneal ulcer. (Pantanelli S.M., Ali T.K. (2016) Corneal Infection and Ulceration. In: Laver N., Specht C. (eds) The Infected Eye. Springer, Cham)

halted. If the infection is severe, or a risk of poor compliance with intensive treatment is present patient’s admission should be considered. Choice of topical medications may be revised based on culture results and response to treatment after 48 h. Systemic antibiotics will be needed for scleral involvement and infection with N. meningitidis, N. gonorrhoeae and H. influenzae. Keratoplasty may be needed for perforation or unresponsive cases to medical treatment. Cycloplegics (cyclopentolate 1%) can be added for photophobia and relief of ciliary spasm which causes discomfort. Steroid drops should be avoided.

6.9.2  Fungal Keratitis Fungal keratitis is a major cause of infectious keratitis in tropical and developing countries. Two main types of fungal keratitis are yeasts (e.g. Candida) and filamentous fungi (e.g. Fusarium and Aspergillus). 6.9.2.1  Risk Factors Trauma with vegetative material, chronic ocular surface disease, use of topical steroids, systemic immunosuppression and diabetes are risk factors.

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6.9.2.2  Clinical Features Patients’ symptoms are similar to bacterial keratitis but with more gradual onset. Yellow–white suppurative infiltrate similar to Gram positive bacteria is seen in Candida keratitis. Infiltration (sometimes pigmented) with feathery margin or satellite lesions are typical for filamentous keratitis. However, differentiation of bacterial and fungal keratitis is not possible based on slit lamp examination. 6.9.2.3  Treatment Corneal scraping and biopsy should be done before starting topical medication. Treatment is based on hourly application of topical antifungals such as natamycin, Amphotericin B, and voriconazole. Treatment should be continued for several weeks. Recurrence and the need for keratoplasty is more common than bacterial keratitis.

6.9.3  Herpes Simplex Keratitis Herpes simplex virus (HSV) keratitis is the main infectious cause of corneal blindness in developed countries. There are two types; HSV1, which is airborne, most commonly affecting the eyes, face and trunk. HSV2 is sexually transmitted and usually causes genital lesions. • Primary infection Most HSV primary infections are subclinical but they may cause blepharitis or follicular conjunctivitis. Primary HSV infections are self-limiting, although treatment such as topical antivirals (aciclovir or ganciclovir ointment) may be used. • Recurrent infection Patient symptoms are decreased vision, discomfort and redness. History of recurrent episode of similar symptoms and previous diagnosis of HSV keratitis are very helpful for diagnosis. 6.9.3.1  Epithelial Keratitis Clinical Features Linear branching (dendritic) ulcer with terminal buds are seen. Incorrect use of topical steroid treatment may facilitate enlargement of the ulcer to a geographical configuration (Fig. 6.9).

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Fig. 6.9  Dendritic ulcer due to herpes simplex seen staining with fluorescein with a blue cobalt light. (Reproduced from Gerstenblith A.T., Uhler T. (2012) Herpes Simplex Virus. In: Schmidt-Erfurth U., Kohnen T. (eds) Encyclopedia of Ophthalmology. Springer, Berlin, Heidelberg)

Treatment Aciclovir 3% ointment or ganciclovir 0.15% gel are applied five times daily. Some advocate epithelial debridement which may accelerate healing. Oral antiviral such as aciclovir and valaciclovir are effective treatments in children and immune-­ deficient patients. 6.9.3.2  Non-epithelial Keratitis Stromal Keratitis Clinical Features Stromal infiltration and vascularization are main signs of HSV stromal keratitis. Endotheliitis Clinical Features Patients may report blurred vision, and there may be a history of epithelial keratitis. Endotheliitis can present with stromal oedema, keratic precipitates, Descemet’s membrane folds and raised intraocular pressure. There may be signs of previous episodes with stromal scarring and corneal vascularization. It may exist in three forms; disciform, linear and diffuse categorized based on distribution of corneal oedema and keratic precipitates. Necrotizing Stromal Keratitis Clinical Features Progressive stromal necrosis and melting make differentiation from bacterial keratitis difficult.

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6.9.3.3  Treatment of Non-epithelial HSV Keratitis Systemic antiviral medication in the form of tablets rather than topical preparations are preferred, in addition to topical steroid is main part of treatment.

6.9.4  Herpes Zoster Ophthalmicus Varicella-zoster virus (VZV) may become dormant after an episode of chickenpox. Reactivation of VZV in the ophthalmic division of trigeminal nerve can cause Herpes zoster ophthalmicus (HZO). It is more common in patients older than 60 or immunocompromised patients. 6.9.4.1  Clinical Features Acute Eye Disease Vesicular rash may be seen on the face, lids or nose on the same side of the involved eye. Epithelial, stromal and endotheliitis keratitis due to VZV may occur similarly to HSV. VZV epithelial keratitis are typically in the periphery and are small in size. It causes dendrites which stain with Rose Bengal. The dendrites are elevated dendritic appearance with minimal central staining and without terminal bulb in contrast to HSV epithelial keratitis. Follicular conjunctivitis, episcleritis and scleritis may also be the presenting features of VZV. It can also be a cause of anterior uveitis with elevated intraocular pressure. Chronic Eye Disease There is chronic or persistent replication of VZV in addition to inflammation in this stage of disease. Corneal sensation may be severely affected by VZV and a neurotrophic ulcer may occur. Patients who have had skin involvement also commonly report postherpetic neuralgia, and scarring of the involved skin is common. 6.9.4.2  Treatment Systemic acyclovir (typically 800 mg five times per day) should be started. Topical or systemic steroid may be necessary to suppress inflammation. Topical lubricants and on occasion a tarsorrhaphy is indicated for neurotrophic keratopathy.

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6.9.5  Acanthamoeba Keratitis Acanthamoeba is a free-living protozoon which has two forms; the cystic (the dormant form) which is highly resilient and the trophozoites (the active form) which causes infection. Acanthamoeba keratitis is most commonly associated with contact lenses, such as prolonged lens wear, poor hygiene and swimming or showering with lenses in situ. 6.9.5.1  Clinical Features Severe pain that is disproportionate to the lesion on slit lamp examination is characteristic for this disease. Patients may also report blurred vision, red eye and photophobia. Epithelial pseudo-dendrites may be early signs of this keratitis. These pseudo-dendrites can mimic Herpetic epithelial keratitis. There is no terminal bulb and typical branching patterns in acanthamoeba. Therefore, a branching pattern ulcer in a contact lens wearer should alert one to acanthamoeba. Perineural infiltrates are pathognomonic. Stromal infiltration and ring abscess are late presentations. Limbitis, scleritis and secondary bacterial keratitis can be late complications. 6.9.5.2  Diagnosis Corneal epithelial sheet biopsy and scrapes can be stained with periodic acid–Schiff or calcofluor white and culture in non-nutrient agar with E. coli overlay are helpful. Corneal biopsy is sometimes necessary to confirm diagnosis. Acanthamoeba cysts can be detected in the stroma with confocal microscopy. 6.9.5.3  Treatment Start of topical steroid before anti-amoebic treatment and late diagnosis are risk factors for poor prognosis. Topical biguanides such as polyhexamethylene biguanide (PHMB) 0.02% or chlorhexidine (0.02%) with or without a diamidine (propamidine isethionate - brolene) are started hourly alongside cycloplegics and oral analgesia. Treatment continued for several months to decrease the chance of recurrence.

6.9.6  Bacterial Hypersensitivity-Mediated Corneal Disease 6.9.6.1  Marginal Keratitis Marginal keratitis occurs as a result of a hypersensitivity reaction against exotoxins produced by staphylococcal blepharitis. Rosacea and atopy both of which are chronic skin diseases may be the background of this disease.

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Clinical Features Epiphora, pain and foreign body sensations are common presenting symptoms. Blepharitis with collarettes and peripheral white corneal marginal infiltration are the main signs. Infiltration is separated from the limbus by a clear corneal zone. Epithelial defect that is smaller than the infiltrate may exist. 6.9.6.2  Phlyctenulosis Phylctenulosis can occur as a result of a delayed hypersensitivity reaction to microbial antigens such as Staphylococcus aureus, Chlamydia trachomatis, tuberculosis and helminthic organisms. Patients may present with epiphora and photophobia. Clinical Features Conjunctival phlyctenules are nodular lesions with surrounding marked injection. It may ulcerate and then heals without scar. Corneal phlyctenules start at the limbus and progress centrally with a bundle of vessels. It heals with wedge-shaped scar. Treatment The aim is to suppress corneal inflammatory reaction by topical steroid. Blepharitis and overgrowth of commensal bacteria is treated by lid hygiene and topical antibiotics. Systemic tetracyclines such as doxycycline may be necessary for rosacea. Episcleritis Episcleritis is a common and benign condition where inflammation of the episclera occurs. This most commonly affects young females, who may present with sectoral redness of the conjunctiva which blanches with topical phenylephrine and mild discomfort. The disease usually spontaneously recovers and supportive treatment in the form of cold compress, ocular lubricants can be given. Topical NSAIDs and corticosteroids are also often used. Systemic NSAIDs can also be given for recurrent cases. Scleritis Scleritis is a potentially severe and blinding inflammatory condition of the sclera. It has systemic associations including rheumatoid arthritis, and vasculitic conditions such as Granulomatosis with Polyangitis and Systemic Lupus Erythematosus. Symptoms include moderate to severe pain, redness, epiphora and photophobia.

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Patients complain of severe gnawing pain which is also retrobulbar in nature. The pain may radiate to the brow, forehead and temples and can be confused with GCA. The severe nature of the pain may wake the patient up at night, and their globe is also tender to touch. The visual and systemic prognosis of scleritis can vary depending on the type. Please refer to the table below.

6.9.7  Peripheral Ulcerative Keratitis (PUK) PUK is an aggressive form of inflammatory peripheral corneal ulceration which is caused by an autoimmune mechanism. Scleritis may accompany PUK. Rheumatoid arthritis is the most common systemic disease in these patients. Other autoimmune diseases such as granulomatosis with polyangiitis (formerly known as Wegener’s), systemic lupus erythematosus and polyarteritis nodosa may be associated. Delay in diagnosis of underlying disease may be life-threatening (Fig. 6.10).

6.9.7.1  Treatment Peripheral infectious keratitis should be excluded. Oral or intravenous steroid can suppress inflammation rapidly. Immunosuppressive treatment is chosen based on systemic disease. Topical lubricants and steroids may also be used. Tectonic patch graft may be necessary in case of severe thinning or perforation.

6.9.8  Recurrent Corneal Erosion There is a periodic detachment of an area of the corneal epithelial layer. There are two main causes for this disease: previous superficial corneal trauma and corneal dystrophies. The pathogenesis is lack of robust adherence of epithelium to the Fig. 6.10 Peripheral ulcerative keratitis

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basement membrane and stroma. Patients complain of recurrent episodes of pain on awakening or in the middle of the night. They also report photophobia, redness, blepharospasm and tearing that may last from hours to days.

6.9.8.1  Clinical Features On slit lamp examination an epithelial defect, or an area of loose epithelium may be detected or there may be no signs due to the healing of the epithelial defect. Careful examination of both eyes may reveal signs of coexisting corneal dystrophy such as anterior basement membrane dystrophy.

6.9.8.2  Treatment Treatment is initiated with topical lubricants with or without sodium chloride drops for several months. Bandage contact lenses may also be used in the acute phases. If medical treatment fails, surgical options include debridement of epithelium, alcohol delamination, stromal puncture and phototherapeutic keratectomy (PTK).

6.9.9  C  orneal Diseases Due to Failure of Its Protection Mechanism 6.9.9.1  Neurotrophic Keratopathy Corneal innervation is essential for maintenance of corneal health. Any impairment in corneal sensation may lead to punctate epithelial erosions, persistent epithelial defect, ulceration and ultimately perforation. Both central and peripheral neuropathy may cause neurotrophic keratopathy. Causes include stroke, tumour, diabetes and HSV keratitis. 6.9.9.2  Exposure Keratopathy Incomplete lid closure (lagophthalmos) may cause corneal ulceration mainly in the inferior area of the cornea. It may be due to mechanical (lid scarring) or neurogenic (facial nerve palsy) causes. Effects range from punctate epithelial erosions to frank epithelial defects, ulceration and even perforation. Treatment Artificial tear drops with high viscosity and ointments are mainstay of treatment. Taping of lids at night, gold weight and temporary or permanent tarsorrhaphy are necessary for patients not responsive to medical treatment.

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6.9.10  Corneal Ectasias There are three primary disorders in this entity; keratoconus, pellucid marginal degeneration and keratoglobus. They share two features in common: corneal thinning and bulging. The reported prevalence of keratoconus ranges from 54 per 100,000 to 265 per 100,000. The onset of keratoconus is usually around puberty and progress till the third or fourth decades of life. There is also around 10% chance that offspring of those affected may have the disorder. The main symptom is progressively decreasing vision due to myopia and irregular astigmatism. Keratoconus is associated with systemic diseases such as Down’s, Ehlers–Danlos and Marfan syndromes and ocular diseases including atopic keratoconjunctivitis, vernal keratoconjunctivitis and persistent eye rubbing. 6.9.10.1  Clinical Features These signs can be seen on slit lamp examination: • Iron deposit in epithelial layer around the base of the cone more visible by cobalt blue filter by slit lamp (Fleischer ring) • Deep vertical stress line (Vogt striae) which disappears by pressure on globe • Corneal thinning and steepening may be detectable in more advanced cases Munson’s sign is a bulging of lower lid when patients with advanced keratoconus gaze downwards. Essential imaging device for diagnosis of keratoconus is corneal topography which shows increased steepening with corneal irregularity of corneal curvature (Figs. 6.11 and 6.12).

Fig. 6.11 Schematic diagram showing the shape of a normal cornea versus keratoconus. (Illustration by Kim Yeohun)

Normal Cornea

Keratoconus

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Fig. 6.12  A keratoconic eye showing central corneal thinning

6.9.10.2  Treatment Essential step in treatment is managing the allergic background if it exists. Patients should be advised not to rub their eyes. Visual rehabilitation can be provided with glasses for early cases and rigid contact lens for more advanced cases. Intracorneal ring segment implantation may improve vision in patients who do not tolerate contact lens. Corneal collagen cross-linking (CXL) is very effective in halting progression of disease. Younger patients are more prone to progression. A corneal graft may be necessary for advanced cases. 6.9.10.3  Acute Hydrops Acute hydrops refers to a sudden rupture of the Descemet membrane which can occur in advanced keratoconus. In this situation, there is penetration of the aqueous humour into corneal stroma. Patient experiences sudden decreased vison, pain and photophobia. Treatment is medical with lubricants and cycloplegic drops. 6.9.10.4  Other Corneal Ectatic Disease Pellucid marginal degeneration presents in older patients than keratoconus. There is peripheral corneal thinning (mostly inferiorly) and corneal steepening above the thinned area. Treatment modalities are similar to keratoconus. Keratoglobus onset is at birth. There is generalized thinning of cornea and risk of corneal rupture with minor trauma. Protective eyewear should be worn by these patients.

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6.9.10.5  Corneal Transplantation Corneal grafting dates back to a century ago and was the first transplant surgery in medicine. It is now also the most common form of transplantation. One of the most pivotal factors in success of corneal transplantation is the immune privilege of cornea. Therefore, there is no need for systemic immunosuppressive therapy after corneal grafts in most cases. In recent years, there have been advancements in corneal transplantation techniques from penetrating keratoplasty in which all layers of the cornea are replaced to lamellar keratoplasty in which selective diseased layer or layers of cornea are replaced. In deep anterior lamellar keratoplasty (DALK) recipient stroma is replaced by donor stroma. This technique has several advantages for patients with keratoconus. Grafting of thin lenticule of posterior stromal layer with Descemet and endothelial layers in Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) and Descemet and endothelial layers in Descemet membrane endothelial keratoplasty (DMEK) is referred to as endothelial keratoplasty. The outcomes of endothelial keratoplasty for patients with endothelial dysfunction such as Fuchs’ endothelial dystrophy or pseudophakic bullous keratopathy have been very encouraging (Fig. 6.13). Fig. 6.13  Images of patient following corneal transplantation. (a) Corneal transplantation with continuous sutures. (b) Corneal transplant with interrupted sutures

a

b

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There are multiple eye bank facilities in the world that make corneal transplantation possible but unfortunately there is a lack of this service in developing countries due to both shortage of resources and cultural barriers. This highlights significance of public awareness about eye donation. Corneal epithelial cells are generated from the limbus where the stem cells are located in crypts. In certain diseases and following trauma, stem cells can be depleted causing the quality of the corneal epithelium to deteriorate, allowing the conjunctival epithelium to migrate to the cornea. This can result in reduced vision, sensitivity to light and gritty sensation. In unilateral cases such as unilateral chemical injury, it is possible to transplant stem cells either directly or following laboratory amplification from the good eye to bad. Bilateral stem cell deficiency is much more difficult but may be treated with limited success with allogeneic stem cell sourced from living related donors or cadaveric tissues. Allogeneic grafting requires systemic immunosuppression. Investigations should include FBC, ESR, RF, anti-CCP, ANA, ANCA, CRP, LFTs, U&E, ACE, uric acid, syphilis, serologic tests for TB. CXR and urinalysis should also be included as part of the work up. Anterior Scleritis

Non-Necrotizing

Diffuse

Nodular

Necrotizing

Posterior Scleritis

With inflammation (Complications – globe perforation, peripheral ulcerative keratitis, uveitis) Without inflammation (Complications – globe perforation)

• Diffuse injection • Does not blanch with phenylephrine • Tender globe • Treat with oral NSAID, can use corticosteroid if not controlled • Red nodule from the sclera, adherent to underlying tissue • As above • Red sclera surrounded by white avascular areas • Treat with systemic immunosuppression • Patient is usually asymptomatic • Gradual reduction of vision due to astigmatism • Necrotic sclera with underlying uvea visible in a quiet eye • Systemic immunosuppression • Blurry vision or loss of vision • Pain on eye movement • Choroidal folds • Exudative retinal detachment • Uveal effusion • Treat with systemic immunosuppression

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Further Reading Bowling B. Kanski’s clinical ophthalmology. A systematic approach. 8th ed. London: Elsevier; 2016. Hallerman W, Wilson EJ.  Genetische betrachtungen uber den keratoconus. Klin Monatsbl Augenheilkd. 1977;170:906–8. Mas Tur V, MacGregor C, Jayaswal R, O’Brart D, Maycock N. A review of keratoconus: diagnosis, pathophysiology, and genetics. Surv Ophthalmol. 2017;62(6):770–83. World Health Organisation Trachoma Strategy. https://www.who.int/trachoma/strategy/en/

Chapter 7

Glaucoma Richard M. H. Lee, Christopher Liu, and Hanbin  Lee

7.1  Introduction Glaucoma is defined as a group of optic neuropathies characterised by progressive degeneration of retinal ganglion cells. This results in damage to the optic nerve head and loss of visual field [1, 2] and is often associated with raised intra-ocular pressure (IOP) [2]. Glaucoma is usually asymptomatic at an early stage as only the peripheral visual field is affected but will subsequently lead to loss of visual acuity and irreversible blindness if left untreated [1]. Glaucoma can also have an impact on a person’s ability to drive and there are restrictions set by the Driver and Vehicle Licensing Agency on visual field defects and driving. Glaucoma is the leading cause of irreversible blindness with an estimated 70 million people affected by glaucoma worldwide, 10% being bilaterally blind [1, 3]. More recent estimates suggest these numbers will increase to over 110 million people worldwide by 2040, with a predominance affected in Asia and Africa [4]. The biological basis of glaucoma is not fully understood although several risk factors have been identified (Table 7.1). Genes including myocilin (MYOC, GLC1A), optineurin (OPTN, GLC1E) and WD repeat domain 36 (GLC1G) are also associated with glaucoma but account for less than 10% of cases [2]. Due to the insidious nature in presentation of glaucoma and the risk of irreversible visual loss screening is carried out for glaucoma. Screening can be carried out by the multi-disciplinary team including ophthalmologists, optometrists, orthoptists, R. M. H. Lee (*) Chelsea and Westminster Hospital NHS Foundation Trust, London, UK C. Liu Sussex Eye Hospital, Brighton and Sussex Medical School Tongdean Eye Clinic, Brighton and Hove, UK H. Lee Sussex Eye Hospital, Brighton, UK © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_7

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114 Table 7.1  Risk factors for glaucoma

R. M. H. Lee et al. Risk factors for glaucoma Increasing age Raised intraocular pressure (IOP) Black ethnicity Family history in a first degree relative Myopia

ophthalmic nurses and technicians. Patients who are seen for routine eye examinations should have visual acuity, IOP, fundal assessment and perimetry performed.

7.2  Pathophysiology Axons of retinal ganglion cells exit the eye through the lamina cribrosa, a collagenous structure with sieve-like openings at the optic nerve head [5]. It is thought that raised IOP may result in damage to retinal ganglion cells at the lamina cribrosa via direct mechanical or ischaemic effects. Raised IOP may cause a decrease in axonal transport resulting in reduced retrograde axoplasmic flow, leading to cell death due to lack of neurotrophic factors [5]. Reduced blood perfusion to the optic nerve head leads to formation and accumulation of reactive oxygen species in the retina resulting in cellular stress and malfunction. Activated glial cells (microglia and astrocytes) in the optic nerve head synthesize molecules such as tumour necrosis factor α (TNF-α) that result in degradation and remodelling of the extracellular matrix that have a biomechanical effect on the optic nerve head increasing stress on retinal ganglion cell axons [5]. Optic nerve head cupping occurs due to loss of prelaminar tissue and posterior deformation of the lamina cribrosa. In combination with microglial proliferation, the lamina cribrosa bows posteriorly, prelaminar tissue is lost and the cup gets larger and deeper, straining the retinal ganglion cell axons further compromising their function [5]. The morphological changes in the optic nerve head are associated with changes in the extra-cellular matrix including increased synthesis of collagen type IV, proteoglycans, adhesion molecules and matrix metalloproteinases (MMPs) [5]. Retinal ganglion cell death loss occurs through apoptosis as observed using non-­ invasive direct imaging of apoptotic cell death in rat models of glaucoma [5]. Mononuclear cell infiltration does not occur but the presence of retinal antigen autoantibodies indirectly suggest an inflammatory process has occurred. It is thought that neuroinflammation occurs with phagocytosis of cellular debris by glial cells and development of a subsequent scar response [5]. Glial expression of major histocompatibility-­complex (MHC) class II molecules and synthesis of components of the complement cascade occur as retinal ganglion cell death continues, further contributing to retinal ganglion cell degeneration [5]. Factors other than raised IOP may also contribute to retinal ganglion cell and optic nerve fibre death, with local ischaemia-hypoxia secondary to blood-flow

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autoregulation dysfunction thought to play a role [6]. Excessive stimulation of the glutamatergic system, specifically the N-methyl-d-aspartate (NMDA) subtypes, is thought to contribute to retinal ganglion cell death but there is debate as to whether excess glutamate has a positive or negative effect [6]. Poorly functioning cellular pumps and glutamate transporters, oxidative stress and formation of free radicals, inflammatory cytokines and aberrant immunity are thought to play a role [6]. It is also thought that the primary insult may not directly affect all cells and fibres, but alters the neuronal environment that in turn increases the vulnerability of spared neurons leading to secondary neurodegeneration [6].

7.3  Types of Glaucoma Glaucoma can be classified as open or closed angle glaucoma depending on the appearance and obstruction to the drainage pathway at the iridocorneal angle (trabecular meshwork) [2]. Open angle glaucoma occurs when the anterior chamber angle is open and can be classified as primary (idiopathic) or secondary. Primary open angle glaucoma (POAG) is the most common form of glaucoma accounting for over 70% of cases and is associated with elevated IOP [2]. Normal tension glaucoma (NTG or otherwise known as low tension glaucoma, LTG) is when patients develop glaucomatous optic neuropathy in the presence of an open angle but normal IOP. Secondary glaucoma is when the anterior chamber angle is open but drainage is prevented by another cause. This includes pseudoexfoliation; pigment dispersion glaucoma; angle recession following trauma; lens related; rubeosis associated with ocular ischaemia due to vascular occlusion or diabetes; uveitis; or after ocular surgery, such as retinal detachment surgery [2]. Primary angle closure glaucoma (PACG) occurs when the anterior chamber angle is closed due to the lens pushing the iris forward as it enlarges with age. It is more common in hyperopic patients when the eye is smaller. Acute angle closure glaucoma (AACG) is an ophthalmic emergency and patients present with headache, ocular pain, nausea, vomiting and blurred vision with transient symptoms of blurred vision and halos around lights also being reported. This is often due to a pupil block mechanism whereby aqueous humour is unable to drain from the posterior portion through to the anterior portion of the anterior chamber due to lens and iris contact. Urgent treatment with medications that may include intravenous acetazolamide together with topical pilocarpine and beta-blockers are required. In such situations a laser peripheral iridotomy with or without lens extraction may be necessary subsequently (see Sect. 7.5.2). Primary congenital glaucoma typically presents in the neonatal or infantile period with epiphora, blepharospasm, and photophobia. There may also be a cloudy cornea and an enlarged corneal diameter. Horizontal folds in the Descemet’s membrane called Haab’s striae may be visible. Intraocular pressure will be raised.

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Primary congenital glaucoma is thought to occur due to a developmental disorder of the anterior chamber and its structures leading to a fault in the outflow through the trabecular meshwork. The mainstay of treatment is surgical, in the form of a goniotomy or a trabeculotomy with the use of medical adjuncts.

7.4  Monitoring of Glaucoma Patients can often have good visual acuity despite advanced glaucomatous optic nerve damage. Therefore, clinical examination is vital to monitor disease progression and direct treatment to reduce the risk of blindness. Monitoring of the patient may include assessment the anterior chamber angle, IOP measurement, fundus examination and a visual field test.

7.4.1  Gonioscopy Gonioscopy is a technique for visualization of the anterior chamber developed in the late 1800s by Trantas [7]. Lenses either allow direct (Koeppe, Barkan) or indirect (Posner, Sussman, Zeiss, and Goldmann) views of the angle structures (Figs. 7.1 and 7.2). A number of guidelines exist to try and develop a consensus internationally on how to assess the anterior chamber angle [8]. Imaging devices may allow for a more objective assessment of the anterior chamber angle and include high frequency ultrasound biomicroscopy (UBM), optical coherence tomography (OCT), Scheimpflug photography and scanning peripheral anterior chamber depth analyzer (SPAC) [8].

Fig. 7.1  View seen through gonioscopy revealing the structures of the angle and a Micro-Invasive Glaucoma Surgery Device

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Fig. 7.2  Goldmann single mirror gonioscopy lens

7.4.2  IOP Measurement IOP measurement (tonometry) has been known since the sixteenth century when Bannister described a cohort of patients with blind eyes that were firm to the touch [9]. Goldmann applanation tonometry (GAT) (Fig. 7.3) introduced in the 1950s is widely regarded as the ‘gold standard’ [9]. Limitations of the technique include variations in the central corneal thickness (CCT) amongst individuals and other sources of error including Valsalva’s manoeuvre, astigmatism, corneal curvature, inappropriate amounts of fluorescein, eyelid squeezing and indirect pressure on the globe [9]. CCT can be measured using a pachymeter (Fig. 7.4). Errors may also be induced by corneal refractive surgery and other alterations in the normal biomechanical behaviours of the cornea. A number of approaches have been developed to rectify some of the limitations of GAT. Noncontact or ‘air puff’ tonometry (NCT), commonly used in community optometry practices, employs a calibrated column of compressed air to briefly flatten the corneal apex and detect the exact moment of apical flattening to extrapolate IOP by determining the force of air required to deform the cornea at the point of flattening [9]. It does not require direct contact with the eye (as required with GAT) and can be used without topical anaesthesia, in children and poorly co-operative adults. However, it is also influenced by biomechanical factors such as CCT, ocular pulse amplitude and ocular rigidity [9]. Other devices have been developed that include the ocular response analyzer (ORA) and dynamic contour tonometry (DCT) to minimise the effect of these biomechanical factors.

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Fig. 7.3 Goldmann applanation tonometer for measurement of intraocular pressure

Fig. 7.4  Pachymeter for measurement of central corneal thickness

One of the main limitations of current forms of tonometry is the isolated nature of readings, being limited to office visits and not reflecting changes in IOP over a 24 hour period [10]. Current technologies for continuous 24 hour IOP monitoring include a permanent implantable telemetric pressure transducer system and a temporary implantable sensor via a contact lens approach.

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7.4.3  Optic Disc Assessment Examination of the optic disc is the most valuable method of diagnosing early glaucoma because patients are often asymptomatic and changes in disc appearance can occur before detectable visual field loss [6]. Studies have demonstrated that half of retinal ganglion cells and their axons can be lost before visual field testing demonstrates any evidence of glaucoma [6]. Typical optic disc changes are listed in Table 7.2 [6]. Figure 7.5 representing an example of a glaucomatous optic disc. Several objective and quantitative methods have been developed to assess the optic disc and retinal nerve fibre layer (RNFL). Scanning laser polarimetry assesses the thickness of the RNFL by measuring the retardation (phase shift) of a polarized laser light passing through the eye possessing the physical property of form birefringence. This occurs in tissue composed of parallel structures with a smaller diameter than the wavelength of light used to image it. This occurs in the RNFL due to microtubules within individual nerve fibres, therefore giving an indirect assessment of nerve fibre layer thickness [6]. Confocal scanning laser ophthalmoscopy measures the optic disc topography layer-by-layer providing a quantitative area of the disc and neuroretinal rim. More recently OCT analysis of the optic nerve head has become more widespread. OCT allows for the measurement of RNFL and additional parameters of the optic nerve that aid assessment [11] (Fig. 7.6).

7.4.4  Visual Field Assessment Automation of visual field assessment (perimetry) in the 1970s led to its widespread use in patients with glaucoma, standard achromatic perimetry (SAP) remaining the most frequently used test for measuring peripheral visual field in glaucoma [12]. The predominant system used clinically is the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA) and it determines threshold measurements at various points covering a central 10°, 24° or 30°. SAP utilizes a white target against a white background but given that structural damage in early glaucoma may not result in glaucomatous

Table 7.2  Typical optic nerve changes in glaucoma

Typical optic nerve changes in glaucoma Large cup to disc ratio with a thin neuroretinal rim Progressive optic disc cupping Asymmetric optic disc cupping (>0.2 difference) Optic disc haemorrhages Acquired optic nerve pits Peripapillary retinal nerve fibre layer loss

120 Fig. 7.5 (a) Normal and (b) glaucomatous optic nerve showing greater cup disc ratio. Courtesy of Keith Barton MD FRCP FRCS, Moorfields Eye Hospital

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a

b

Fig. 7.6  OCT centred around the optic nerve. Retinal Nerve Fibre layer analysis

field loss until a substantial number of retinal ganglion cells and axons are lost, alternative perimetry techniques have been assessed including short-­wavelength automated perimetry (SWAP) and frequency doubling technology (FDT) perimetry [12–15] (Fig. 7.7).

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Fig. 7.7  Humphrey visual field analyzer

7.5  Management of Glaucoma Glaucoma treatment aims to enhance the patient’s health and quality of life by preserving visual function without causing untoward effects from treatment. Specific goals include [6]: • Documentation of optic nerve appearance and visual function at presentation and follow-up • Maintenance of IOP at a level that minimises the risk of further optic nerve damage • Minimise the side-effects of treatment and their effect on patient’s vision, general health and quality of life • Educate and engage the patient in the management of their disease Current management aims to lower IOP, which is the only proven and treatable risk factor for the disease [6].

7.5.1  Medical Management A range of medications exists in order to reduce IOP either by suppressing aqueous humour secretion or increasing aqueous humour outflow (Table 7.3) [6]. These are usually applied directly to the corneal surface as a topical eye drop.

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Table 7.3  Medication used to lower IOP (Adapted from Weinreb and Khaw [6]) Category Examples Agents that suppress aqueous inflow Beta adrenergic Betaxolol, carteolol, blockers levobunolol, metipranolol, timolol Alpha adrenergic Apraclonidine, agonists brimonidine

Side-effects

Ocular irritation and dry eyes. Contraindicated in patients with bradycardia, heart block, heart failure, asthma or obstructive airway disease Red eye and ocular irritation. CNS effects and respiratory arrest in young children (brimonidine). Caution in patients with cerebral or coronary insufficiency, Raynaud’s, postural hypotension, hepatic or renal impairment Oral form can cause transient myopia, nausea, Dorzolamide and Carbonic brinzolamide (topical), diarrhoea, loss of appetite and taste, paraesthesia, anhydrase lassitude, renal stones, and haematological acetazolamide and inhibitors methazolamide (oral) problems. Topical forms much less likely to cause systemic side-effects but can cause local irritation and redness Agents that increase aqueous outflow Brown discolouration of iris, lengthening and Latanoprost, Prostaglandin darkening of eyelashes, ocular irritation and travoprost, analogues redness, macular oedema or iritis in susceptible unoprostone, (prostamide) individuals (bimatoprost) Cholinergic Pilocarpine, carbachol Ciliary spasm leading to headaches especially in agonists younger patients, myopia, dim vision (small pupil). Cataracts and iris-lens adhesions in long term

7.5.2  Laser Treatment Topical eye drop medication can sometimes result in undesirable side effects or may not reduce glaucoma progression or IOP adequately. In such instances laser treatment may be more appropriate for patient management. Laser trabeculoplasty utilises a laser directed at the trabecular meshwork to reduce the resistance to aqueous humour outflow. ALT was introduced in the 1970s although there is a shift towards the newer selective laser trabeculoplasty (SLT) that offers similar IOP-lowering effects but has less post-laser anterior chamber inflammation, leaving the trabecular meshwork intact with minimal damage to the endothelial cells or development of peripheral anterior synechiae (PAS) [16]. Advantages of laser treatment over eye drops include more consistent IOP control as medication adherence can sometimes be a challenge for patients, many of whom are elderly or have other health co-morbidities such as arthritis making it difficult using eye drop bottles. More recent studies suggest that SLT may be a costeffective first line treatment with similar efficacy to drop medication therapy. Treatment of patients with primary angle closure (PAC) can either be in the form of a peripheral iridotomy (PI) or a peripheral iridoplasty (ALPI). Pupil block creates an anterior chamber/posterior chamber pressure difference resulting in forces that

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push the iris towards the trabecular meshwork [17]. A PI will often relieve this pressure difference and prevent further attacks of acute angle closure but narrowing of the drainage angle can persist. ALPI is a procedure where the peripheral iris stroma is shrunk to ‘pull’ iris tissue away from the trabecular meshwork. However a Cochrane review found only one randomized controlled trial compared ALPI with PI with no discernible differences in IOP control between the two techniques and found no evidence for its role in the treatment of angle closure [18].

7.5.3  Glaucoma Filtration Surgery When topical medication and/or laser therapy does not control IOP adequately or disease progression continues despite adequate IOP control, surgical options may need to be considered. The trabeculectomy or guarded external fistulisation procedure was first presented by Cairns in the 1970s and has proven to be the most effective treatment for lowering IOP [19]. A surgical tunnel is created between the anterior chamber and the subconjunctival space with removal of part of the trabecular meshwork resulting in a controlled area for aqueous humour outflow, the filtration bleb [20] (Fig. 7.8). While trabeculectomy was safer in the immediate post-operative period compared to full thickness filtration procedures, they were more likely to undergo scarring over time resulting in reduced filtration and higher long-term IOP readings. Therefore techniques to titrate aqueous outflow included laser suture lysis or releasable sutures, the application of anti-inflammatory agents post- or intra-operatively to slow the healing and scarring response of the conjunctiva and Tenon’s capsule [21]. A number of other approaches have been developed for all surgical steps of the surgical technique from choice of anaesthesia to wound closure. While some of these approaches have been created as a result of patient factors, they also assist in Fig. 7.8  Image showing a trabeculectomy bleb and a peripheral iridotomy. (Image courtesy of Amanda Lewis, Sussex Eye Hospital)

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improving long-term outcomes and reducing post-operative complications of the procedure [22, 23].

7.5.4  Glaucoma Drainage Devices (GDD) Glaucoma drainage implants have been increasingly used in the management of glaucoma since their introduction by Molteno in 1969. They were traditionally used in eyes considered to be at high risk of failure for standard trabeculectomy including neovascular glaucoma, uveitic glaucoma and iridocorneal endothelial syndrome due to the increased risk of fibroblast proliferation and episcleral scarring [24]. Eyes with a history of prior conjunctival incisional surgery (trabeculectomy, extracapsular cataract extraction, paras plana vitrectomy, scleral buckling surgery) or a history of conjunctival cicatricial disease or trauma were also considered at higher risk of failure [24]. However, increasingly positive results of glaucoma drainage device surgery have resulted in their increased usage in lower risk patients as well. A recent Medicare study claimed that data showed a 43% decrease in the number of trabeculectomies and a 184% increase in aqueous shunt surgery performed between 1995 and 2004 [25]. Early attempts to drain fluid from the anterior chamber externally to sites such as the vortex veins and nasolacrimal duct were generally unfavourable or too poorly documented to evaluate [26]. Subsequent devices were developed to drain fluid from the anterior chamber to the subconjunctival space and were composed of materials including silk thread, gold, tantalum and platinum thread/wire but were also associated with lack of flow control, hypotony associated with full thickness unguarded glaucoma filtration surgery and a foreign body chronic inflammatory stimulus [26]. Subsequent designs led to the development of devices that drained fluid more posteriorly by utilising a tube and plate design, the plate acting to maintain patency of the subconjunctival filtration reservoir with ongoing subconjunctival fibrosis [26]. Contemporary drainage devices consist of a tube that enters the eye through a scleral fistula and shunts aqueous humour to the episcleral end plate in the equatorial region of the globe. Fibrous encapsulation of the end plate produces a reservoir in which aqueous humour pools and forms the major resistance to aqueous outflow in these devices [25]. Commonly used devices include the Ahmed glaucoma valve (New World Medical, Rancho Cucamonga, California, USA), Baerveldt glaucoma implant (Abbott Medical Optics, Santa Ana, California, USA), Krupin slit valve (Hood Laboratories, Pembroke, Massachusetts, USA), and Molteno implant (Molteno Ophthalmic Limited, Dunedin, New Zealand). The final IOP is governed by the resulting capsular thickness as a result of differences in material, dimensions and surface characteristics of each device [25].

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Devices can also either be valved (Ahmed, Krupin) or non-valved (Baerveldt, Molteno) depending on the presence of a flow restriction mechanism that limits aqueous outflow if the IOP drops too low. Non-valved implants require a temporary restriction of flow by tube ligation or occlusion during surgical implantation to allow the development of fibrous encapsulation around the end plate, reducing the risk of early postoperative hypotony [25]. Non-valved implants have the advantage of having a larger end plate surface area that may provide increased IOP-reducing efficacy but are at greater risk of hypotony-related complications and delayed functioning while plate encapsulation occurs. Valved implants allow for immediate IOP reduction, reduced risk of hypotony-related complications and are easier to implant due to their smaller surface area but have a higher rate of bleb encapsulation, increased risk of reduced IOP-lowering efficacy and valve malfunction may result in hypotony or obstructed outflow [27]. While studies have demonstrated that glaucoma filtration and device surgery can control IOP to levels that reduce the risk of optic nerve damage and visual field progression, the increased demand for procedures that are less invasive has led to the development of a number of surgical procedures generally referred to as micro-­ invasive glaucoma surgery (MIGS).

7.5.5  Micro-invasive Glaucoma Surgery (MIGS) MIGS are a group of surgical procedures that are usually inserted via an ab interno microincisional approach with minimal trauma to the target tissue, high safety profile compared to conventional glaucoma drainage surgery and allows for rapid recovery with minimal impact on the patient’s quality of life [28]. MIGS devices either modulate Schlemm’s canal to improve trabecular outflow, facilitate the uveoscleral outflow by the development of a connection between the anterior chamber and the suprachoroidal space or create an alternative outflow pathway into the subconjunctival space (Fig. 7.9) [28]. Devices include InnFocus/PreserFlo MicroShunt, iStent and Xen gel Stents.

7.6  Conclusion Glaucoma is one of the leading causes of blindness and numbers are only set to increase as we face an increasing population with a greater age demographic of elderly patients. In order to meet the healthcare demands of these patients it is important to improve efficiency in the healthcare service to optimise clinic utilisation and to make use of the latest innovations to provide patients with the most appropriate diagnostic tools and treatments.

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a Cornea

Conjunctiva

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Fig. 7.9 (a) Schematic diagram showing MIGS drainage route via the subconjunctival and suprachoroidal pathways. (b) Gonioscopic image of G2 istents. Courtesy of Keith Barton MD FRCP FRCS, Moorfields Eye Hospital

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References 1. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901–11. 2. King A, Azuara-Blanco A, Tuulonen A. Glaucoma. BMJ. 2013;346:f3518. 3. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–7. 4. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081–90. 5. Kwon YH, Fingert JH, Kuehn MH, Alward WL. Primary open-angle glaucoma. N Engl J Med. 2009;360(11):1113–24. 6. Weinreb RN, Khaw PT.  Primary open-angle glaucoma. Lancet (London). 2004;363(9422):1711–20. 7. Friedman DS, He M.  Anterior chamber angle assessment techniques. Surv Ophthalmol. 2008;53(3):250–73. 8. Smith SD, Singh K, Lin SC, Chen PP, Chen TC, Francis BA, et al. Evaluation of the anterior chamber angle in glaucoma: a report by the American Academy of Ophthalmology. Ophthalmology. 2013;120(10):1985–97. 9. Okafor KC, Brandt JD.  Measuring intraocular pressure. Curr Opin Ophthalmol. 2015;26(2):103–9. 10. Mansouri K, Weinreb RN. Ambulatory 24-h intraocular pressure monitoring in the management of glaucoma. Curr Opin Ophthalmol. 2015;26(3):214–20. 11. Bussel II, Wollstein G, Schuman JS. OCT for glaucoma diagnosis, screening and detection of glaucoma progression. Br J Ophthalmol. 2014;98(Suppl 2):ii15–9. 12. Nouri-Mahdavi K. Selecting visual field tests and assessing visual field deterioration in glaucoma. Can J Ophthalmol. 2014;49(6):497–505. 13. Turalba AV, Grosskreutz C. A review of current technology used in evaluating visual function in glaucoma. Semin Ophthalmol. 2010;25(5–6):309–16. 14. Jampel HD, Singh K, Lin SC, Chen TC, Francis BA, Hodapp E, et al. Assessment of visual function in glaucoma: a report by the American Academy of Ophthalmology. Ophthalmology. 2011;118(5):986–1002. 15. Liu S, Yu M, Weinreb RN, Lai G, Lam DS, Leung CK. Frequency-doubling technology perimetry for detection of the development of visual field defects in glaucoma suspect eyes: a prospective study. JAMA Ophthalmol. 2014;132(1):77–83. 16. Tsang S, Cheng J, Lee JW.  Developments in laser trabeculoplasty. Br J Ophthalmol. 2015;100(1):94–7. 17. Ng WT, Morgan W. Mechanisms and treatment of primary angle closure: a review. Clin Exp Ophthalmol. 2012;40(4):e218–28. 18. Ng WS, Ang GS, Azuara-Blanco A. Laser peripheral iridoplasty for angle-closure. Cochrane Database Syst Rev. 2012;2:Cd006746. 19. Cairns JE.  Trabeculectomy: preliminary report of a new method. Am J Ophthalmol. 1968;66(4):673–9. 20. Van Bergen T, Van de Velde S, Vandewalle E, Moons L, Stalmans I. Improving patient outcomes following glaucoma surgery: state of the art and future perspectives. Clin Ophthalmol (Auckland, NZ). 2014;8:857–67. 21. Rafuse PE.  The optimal trabeculectomy: patient and procedure. Can J Ophthalmol. 2014;49(6):523–7. 22. Salim S.  Current variations of glaucoma filtration surgery. Curr Opin Ophthalmol. 2012;23(2):89–95. 23. Khaw PT, Chiang M, Shah P, Sii F, Lockwood A, Khalili A. Enhanced trabeculectomy: the Moorfields Safer Surgery System. Dev Ophthalmol. 2012;50:1–28.

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24. Aref AA, Gedde SJ, Budenz DL.  Glaucoma drainage implant surgery. Dev Ophthalmol. 2012;50:37–47. 25. Gedde SJ, Panarelli JF, Banitt MR, Lee RK. Evidenced-based comparison of aqueous shunts. Curr Opin Ophthalmol. 2013;24(2):87–95. 26. Lim KS, Allan BD, Lloyd AW, Muir A, Khaw PT. Glaucoma drainage devices; past, present, and future. Br J Ophthalmol. 1998;82(9):1083–9. 27. Gedde SJ, Parrish RK 2nd, Budenz DL, Heuer DK. Update on aqueous shunts. Exp Eye Res. 2011;93(3):284–90. 28. Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr Opin Ophthalmol. 2012;23(2):96–104.

Chapter 8

Cataract Matthew McDonald

8.1  Introduction Half of global blindness is caused by cataract, which is the most common surgical procedure worldwide. Cataracta, which means waterfall in Latin, is caused by abnormalities in the lens fibre cell membranes and space between lens cell fibres. Aggregate molecules and changes to the crystalline proteins of the lens fibres’ cytoplasm lead to denaturation of proteins. Subsequently, cross-linking between adjacent molecules form clusters that scatter light. The separation of fibres may also be caused by changes in osmotic potential. Classically in diabetes mellitus, increased blood glucose levels lead to an increase in the water content of the lens due to the osmotic pressure gradient, causing an increase in the glucose content of the lens. Excessive glucose is metabolised by the polyol pathway in cells to form sorbitol, preventing sufficient glutathione from being produced (a vital anti-oxidant). This cycle causes more water influx into the lens, resulting in swelling, lenticular myopia, and further cataract formation. The lens is unique in both development and growth. During its lifespan, equatorial stem cells elongate, degrading their intracellular organelle to leave behind pristine crystalline proteins which permit the passage of light through the vitreous humour to the retina. Akin to concentric rings observed in the cross section of a tree trunk, the lens is the only organ in the body which does not shed its non-viable cells. In fact, with increasing age, a large lens (intumescent cataract) may cause phakic glaucoma, compressing the eye’s drainage angle and requiring surgical replacement of the lens (Fig. 8.1). With age-related changes, accumulation of yellow-brown protein pigments will cause brunescence and loss of transparency through light absorption (Fig.  8.2). Oxygen-free radicals (oxidants) play a major role in cataract formation. These are M. McDonald (*) The Humane Research Trust, Stockport, UK Norfolk and Norwich University Hospital Trust, Norwich, UK © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_8

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130 Fig. 8.1  Cross section of the lens. (Reproduced with permission from ‘Phaco Fundamentals’, courtesy of J. Butcher, M. Anderson, and J. Ross)

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Fig. 8.2  Nuclear sclerotic cataract. This patient also has pseudoexfoliation syndrome (PXF), which is evidenced by pseudoexfoliative (fibrillar, amyloid-like) material deposited on the anterior capsule of the lens. (Image courtesy of Dr. J. Sukhija, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India)

released through a multitude of cellular processes in the body, particularly excessive UV radiation, smoking, infection, or toxins (e.g. alcohol or medications such as corticosteroids). It is further postulated that barriers develop in an aging lens (e.g. fibrosis of lens capsule) that prevents glutathione from protecting the lens from oxidative stress. Patient risk factors for development of cataracts: • • • • • • • •

Age (>60) Gender (women face a moderately increased risk) Family history (i.e. genetics) Race and ethnicity (patients of African descent are at twice the risk compared to Caucasian counterparts, along with Hispanic patients) Comorbid ocular conditions (e.g. glaucoma or uveitis) Previous intra-ocular procedures (e.g. vitrectomy, laser photocoagulation) Systemic conditions (e.g. diabetes, autoimmune conditions, metabolic disease) Sunlight exposure (ultraviolet radiation)

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• Smoking • Alcohol

8.2  Cataract Classification and Assessment 8.2.1  Classification Cataracts are best classified through their aetiology: acquired or congenital. Each cataract, depending on its aetiology, is then classified morphologically: subcapsular (anterior/posterior), nuclear, and cortical. 8.2.1.1  Acquired These include the most common age-related cataract, followed by cataracts secondary to: • Ocular disease –– chronic anterior uveitis –– acute angle-closure • High myopia • Hereditary fundus dystrophies • Pharmacological therapies (e.g. corticosteroids, amiodarone, statins, and some anti-psychotics) • Systemic disease (e.g. diabetes mellitus, myotonic dystrophy, atopic dermatitis, and neurofibromatosis type 2) • Traumatic cataracts, usually from blunt force, will cause a flower-shaped “rosette” opacity, which occasionally show Vossius’ ring from iris pigments on the pupillary margin. Nuclear sclerotic, cortical (‘spoking’), and subcapsular cataracts will comprise the vast majority of those seen in clinic. 8.2.1.2  Nuclear Nuclear cataracts are the most common age-related cataract, characterised by opacification of the central portion of the lens. This can progress to such a degree that it becomes brunescent (yellow/brown), which leads to poor colour discrimination, particularly in the blue spectrum. In hyperopic (‘long-sighted’) eyes, the gradual hardening of the lens will lead to a myopic shift, known as ‘second sight’, when a hyperope no longer requires reading glasses.

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8.2.1.3  Cortical Known as ‘cortical spoking’ cataracts, these opacities vary greatly from nuclear cataracts for their appearance of a bicycle wheel. The membranes of mature lens fibre cells are disrupted, resulting in protein oxidation and precipitation of cellular material. These begin with the formation of small vacuoles and clefts. Wedge-­ shaped, or cuneiform (‘cone-like’) opacities of a cortical cataract develop when this phenomenon occurs in fibre cells travelling across posterior to anterior lens suture lines. On retroillumination of the lens (using a slit lamp or direct ophthalmoscope), these spokes will appear black as they block light. Patients may complain of increased glare (especially from car headlights) as this cataract begins at the lens periphery and travels inward (opposite to a nuclear cataract). Diabetic patients are at greatest risk (Fig. 8.3). 8.2.1.4  Subcapsular (Anterior and Posterior) In a subcapsular cataract, patients will often complain of glare, halos, or a disproportionate deterioration in vision to what is seen on slit lamp examination at first-­ glance (retro-illuminate and examine closely). A direct ophthalmoscope will visualise these best in the red reflex. A posterior subcapsular cataract in the centre of the visual axis causes profound deterioration in vision as this is where light rays converge before reaching the retina. Produced by degenerative lens fibre material and globular vacuoles, posterior subcapsular cataracts pose a challenge in cataract surgery due to the discoid opacity adhering to a weak posterior capsule. This, in turn, leads to an increased risk of Fig. 8.3  Cortical cataract. Note the wedge-shaped opacities, ‘spokes’, and small vacuoles along the periphery. (Image courtesy of Dr. J. Sukhija, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India)

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Fig. 8.4 Posterior subcapsular cataract. (Reproduced with permission from Eyerounds.org, University of Iowa. Authors: Weed, A., Johnson, T., Thurtell, M.)

posterior capsule rupture intra-operatively (see ‘risks of cataract surgery’ below). With recent advances in genomics, ocular scientists have found an array of genes and single nucleotide polymorphisms (SNPs) associated with posterior subcapsular cataracts. Anterior subcapsular cataracts occur following lens epithelial cell necrosis which may result from iritis, atopic dermatitis (worsened by topical corticosteroid use), keratitis, use of amiodarone (a cardiac anti-arrhythmic medication) and (albeit rare) electrical or alkali burns. Myofibroblast formation as part of a wound healing response results in lens epithelial cell migration to affected areas in an attempt to regenerate portions of the lens capsule. These myofibroblasts form an extracellular matrix which contracts, worsening an anterior subcapsular cataract over time (Fig. 8.4). 8.2.1.5  Traumatic Cataracts These occur suddenly with blunt force trauma, or gradually, depending on cause. Perforating injury will lead to immediate disruption of lens fibre material. Contusion (‘blunt-force’) can lead to a Vossius ring (iris pigment deposition on the anterior lens capsule), rosette-shaped opacity, or occasionally subluxation (dislocation) of the lens from torn zonular ligaments. With torn zonular ligaments, a different type of cataract procedure must be carried out, securing a new intra-ocular lens (IOL) in either the ciliary sulcus or anterior chamber (in front of the iris). Radiation injury can occur from ultraviolet ray exposure, ionizing radiation (X-ray or radiotherapy), and even infra-red radiation (‘glass blower’s cataract’). Chemicals, such as alkali damage, which cause a caustic burn to the lens. Chalcosis, often from copper deposition (foreign body >90% copper or Wilson’s disease) results in a sunflower cataract. Siderosis, from iron deposition (foreign body or

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Fig. 8.5 Traumatic cataract. Note the central stellate pattern surrounded by dense opacification, anterior capsule furrowing (i.e. wrinkling), and corneal laceration. (Image courtesy of Dr. J. Sukhija, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India)

haemachromatosis) will cause opacification of lens material or deposits on the lens capsule itself. Electrical injury, albeit rare, will also cause immediate opacification of the lens (Fig. 8.5). 8.2.1.6  Other Forms of Cataract –– ‘Christmas tree’ cataracts are characterised by polychromatic needle-like opacities in the cortex and nucleus of the lens (associated with myotonic dystrophy) –– Metabolic syndromes: galactosemia, hypoglycaemia, Fabry’s disease, Lowe syndrome, hypocalcaemia, and mannosidosis all cause their own unique cataracts –– Congenital. Occur in 3–4/10,000 births. Most are from genetic variations, but can also be caused by metabolic disease, intra-uterine infection (e.g. rubella), chromosomal abnormalities, or sporadic with no cause found. There are many different forms of congenital cataract (e.g. sutural, ‘blue dot’, coronary, nuclear, anterior/posterior polar, central oil droplet, membranous, and lamellar which is often ‘Y-shaped’) which exceeds the scope of this text. Surgical management will also vary (Fig. 8.6). 8.2.1.7  Cataract Maturity Immature cataracts are characterised by only partial opacities with areas of the lens remaining clear. These are ‘softer’ when using phacoemulsification and much easier to remove, resulting in a lower incidence of complication.

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Fig. 8.6  Posterior polar cataract. Albeit rare, this is often inherited in an autosomal dominant fashion and can arise from the end of a hyaloid artery remnant, producing a characteristic pyramid-like shape or circular plaque. (Image courtesy of Dr. J. Sukhija, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India)

Mature cataracts are those in which the entire lens is opaque. When this occurs, osmotic barriers break down and the lens begins to absorb more water, swelling to eventually become Morgagnian (hypermature) where the nucleus moves freely around a liquefied cortex inside the lens capsule. Hypermature cataracts result from broken down lens fibres leaving protein globules in-between cortical lamellae fibres. As the cortex degenerates, these globular proteins coalesce to form a liquid protein around the remaining nucleus. The lens swells, becoming tense. Occasionally lens protein can even leak through microscopic openings in the lens capsule, leading to ‘phacolytic glaucoma’, which is a non-granulomatous inflammatory reaction resulting in intra-ocular pressure (IOP) rise. These cataracts may burst when attempting a capsulorhexis intra-operatively if conventional surgical techniques are attempted. Instead, the liquid cortex must first be needle-aspirated (with the lens capsule stained blue for visualisation) before cataract surgery can proceed. The brunescent nucleus may even be seen dislocated, floating in the bath of liquid, white protein. If left long enough, water will eventually leave the lens and the capsule will appear wrinkled with the lens shrunken (Figs. 8.7 and 8.8).

8.2.2  Grading of Cataract Severity There is no universally accepted grading system for cataract density, other than broad groups of immature, mature, and hypermature cataracts. However, in the UK and in many Western countries, the majority of cataracts seen in clinic will be immature. Therefore, a grading system of some calibre must be used for these ‘immature cataract’ patients. The World Health Organisation released such a grading system for nuclear and cortical cataracts in 2002 (see ‘further reading’ for full article).

136 Fig. 8.7 Morgagnian (‘hypermature’) cataract with 4+ brunescent nuclear sclerosis. The nucleus is sunken inferiorly in surrounding liquefied cortex. Image below is under slit lamp examination. (Reproduced with permission from Eyerounds.org, University of Iowa)

Fig. 8.8  Injection of Trypan Blue for improved visualisation of lens capsule against a uniformly white, mature cataract

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Nuclear sclerotic (NS) grading: • NS tr or 1+: nucleus clearer than anterior/posterior sections • NS 2+: nucleus equal to the anterior/posterior section (uniform opacity throughout) • NS 3+/4+: nucleus denser than anterior/posterior sections • Dense white/brunescent: cataract complete opaque/brown Cortical spoking (CS) grading (on retroillumination): • CS 1+: 1/8 to ¼ of the total area (as divided into slices) • CS 2+: ¼ to ½ of the total area • CS 3+: ½ or more of the total area Posterior subcapsular (PS) grading (on retroillumination): • PSC 1+: 1–2 mm in cataract height on posterior aspect of lens • PSC 2+: 2–3 mm • PSC 3+: >3 mm If a patient has more than one type of cataract, these grades can be combined as follows: E.g. Patient has a nuclear cataract of low density with posterior subcapsular opacity of 2 mm: 1+ NS, 2+ PSC

8.3  Cataract Surgery 8.3.1  When to Refer for Surgery All surgery entails risk. One should refer when benefit outweighs risk, in consultation between the healthcare professional and the patient (see Appendix for cataract decision-making resources). After a patient’s vision is optimised with corrective glasses or contact lenses, and all other causes of visual impairment excluded, referral may be necessary. This applies when: • Cataract is interfering with the patient’s lifestyle • Comorbidity benefits from surgery (e.g. risk of falls decreased with improved vision) • Another ocular condition where a clear lens would provide better treatment and monitoring (e.g. those with diabetes mellitus who undergo regular retinal screening, or glaucoma)

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8.3.2  Pre-operative Assessment As with any surgical procedure, it is important to know the patient. Understand their general medical history and risk-stratify accordingly. Pre-optimisation is ideal. Below are a few examples: –– Ischaemic heart disease/stroke: defer surgery for 6  months after a myocardial infarction or stroke. For angina patients, bring their GTN spray to the operating theatre –– Hypertension: pre-optimise with anti-hypertensives to decrease risk of suprachoroidal haemorrhage –– Diabetes mellitus: ensure adequate blood glucose control prior to surgery –– Respiratory disease: can the patient lie flat? Have them bring their regular inhalers –– High risk infections (e.g. HIV, Hepatitis C): surgical team may consider extra precautions

8.3.3  Ophthalmic Assessment 1. Detailed ophthalmic and medical history: (a) Past ocular surgeries and other co-morbidities which adversely affect outcome (e.g. diabetes mellitus, glaucoma, disorders of corneal endothelium, macular oedema) 2. Drug history: (a) Allergies (b) Use of α-1 adrenergic receptor antagonists, such as tamsulosin, which lead to ‘floppy iris syndrome’ where the iris becomes incarcerated in the corneal wound or billows during surgery which can cause damage if caught in surgical instruments (e.g. phacoemulsification tip) 3. Examination: Baseline visual acuity. Ocular alignment. Ocular adnexa. Lid position, blepharitis, lacrimal discharge Tear film. Dry eyes may delay wound healing and cause excessive discomfort post-operatively (e) Conjunctiva. Any possible signs of infection or stigmata of anterior disease? (f) Anterior chamber. Deep or shallow? This has implications for instrument manipulation during surgery and pressure management (a) (b) (c) (d)

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(g) Corneal status. A clear view is ideal in cataract surgery. The surgeon must also know the patient’s endothelial cell count. These cells are responsible for maintaining adequate hydration of the cornea, and, if the patient has a low endothelial cell count, surgical technique may alter (e.g. instilling dispersive viscoelastic for intraoperative protection, in addition to altered ­phacoemulsification techniques to reduce the traumas of surgery within the anterior chamber) (h) Iris. Synechiae (adhesions of iris to lens capsule) will invariably lead to more complex surgery, along with pupil size and sensitivity to dilating drops (e.g. tropicamide/phenylephrine). Iris hooks or specialised iris expanders for mechanical dilatation may be necessary (i) Intraocular pressure. Record pre-operatively to monitor any post-operative changes that may require intervention (j) Dilated fundus exam. Presence of retinal pathology can be a contraindication, unless stabilised pre-operatively (e.g. retinal tears, oedema, haemorrhage). If a cataract is so dense the retina cannot be visualised, ultrasound technology can rule out vitreous haemorrhage, detachment, or optic nerve abnormalities. (k) Refractive status of the eye. This will guide intraocular lens (IOL) selection. Data from keratometry should be taken into consideration as the location of surgical incision (i.e. wound placement) may affect the cornea’s refraction. This can be used to flatten a steep corneal meridian to decrease astigmatism.

8.3.4  Biometrics 1. Keratometry The cornea has the greatest impact on refraction in the eye. Keratometry determines the curvature of the cornea in detail. This is important for understanding any axis of astigmatism and associated stability of this refractive surface. Corneal topography is able to produce a colour map of the exact contours of a cornea. For cataract surgery, this has implications for wound placement and lens choice. 2. Optical coherence biometry This machine is essential in any cataract operation. It is able to ascertain the depth of one’s anterior chamber, in addition to total axial length (from cornea to retina), and keratometry to assist with choosing an intra-ocular lens specific to an individual. The IOL Master (Carl Zeiss) is most commonly used, employing infrared laser light to discern these measurements. In particularly dense cataracts, ultrasound technology may also need to be used to ascertain the above measurements. All these tools are used in an IOL power calculation pre-operatively, using various algorithms for the surgeon to select. The patient must remove any contact lenses before any cataract measurements. Regular contact

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Fig. 8.9  The IOL Master® used pre-operatively for biometry calculations

lenses must be removed 1 week prior to biometry (for corneal stabilisation) and rigid ones 3 weeks prior (e.g. those used for keratoconus) (Fig. 8.9).

8.3.5  Post-operative Considerations for Refraction • Emmetropia. Most patients desire this outcome. Spectacles will still be required for near-vision activity as cataract surgery results in the loss of accommodation with conventional lenses. The future holds accommodative IOLs—those which preserve or restore the ability of accommodation. • Monovision. Some patients can function with one eye being left 2 dioptres (2.0D) myopic for near vision, whilst being emmetropic in the fellow eye for distance. • Lens type. –– Monofocal IOLs are most common for high quality single focal point vision. –– Multifocal IOLs provide vision over near, intermediate, and far distance, but of arguably lesser overall quality, with some patients experiencing difficulty with glare and halos. –– Toric lenses are designed for those with astigmatism and must be dialled into a precise position (marked with laser-engraved markings) within the lens capsule in order to leave the patient emmetropic, or with significantly less astigmatism –– For all of the above types of IOLs, there are an array of different materials and designs for specific outcomes (e.g. for reduction of posterior capsule opacification post-operatively). Note: More than 2.0D difference between both eyes may lead to diplopia (double vision). There is also an argument for immediate sequential bilateral cataract surgery to reduce the risk of falls in the older population, amongst other reasons.

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8.3.5.1  Surgical Considerations Anaesthesia Choices for anaesthesia in cataract surgery are topical (most common), intracameral (i.e. within anterior chamber), subtenon anaesthesia, peribulbar, and general anaesthesia. Topical These patients must be cooperative, uncomplicated (no serious comorbidities— ocular and systemic), and expected to have a procedure of short duration. This is occasionally combined with intracameral anaesthesia (e.g. 1% non-preserved lidocaine injected into the anterior chamber) if there is any manipulation of the iris or ciliary body. Dilating agents (mydriatics) such as phenylephrine can be added to this solution for improved visualisation of the lens. Sub-Tenon’s Anaesthesia Tenon’s capsule (also known as the bulbar sheath, ‘fascia bulbi’) is a fibrous layer of connective tissue that enables ocular movement by encasing the eye and separating it from extra-orbital tissue. A blunt cannula is used to inject an anaesthetic mixture into this space after dissecting through conjunctiva inferonasally (to avoid the insertion of superior and inferior oblique muscles). This facilitates the spread of anaesthesia along the extraocular muscle sheaths toward the retrobulbar space, which anaesthetises the lids and nerves supplying the globe. Risks include subconjunctival haemorrhage or inadequate pain relief if the cannula is not advanced far enough into this space. With such anaesthesia the eye must also be patched afterward, as the blink reflex may be reduced and the patient will experience diplopia from anaesthetised extraocular muscles. This technique has replaced the need for retrobulbar anaesthesia. Retrobulbar anaesthesia is rarely used in modern practice due to significant risks (e.g. retrobulbar haemorrhage, globe or optic nerve perforation, infection, extraocular muscle injury, longer recovery, and, in extreme circumstances, brainstem anaesthesia/death if injected into the dura of the optic nerve). General Anaesthesia Around 1  in 20 patients may require general anaesthesia for cataract surgery, in which case a general medical examination (including blood tests and an ECG) are indicated for ASA (American Society of Anaesthesiologists) grade (1–6) for surgical fitness.

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A general anaesthetic is indicated in: –– –– –– –– –– –– ––

Children (e.g. congenital/traumatic cataract surgery) Tremor/movement disorders Chronic cough Epilepsy Extreme anxiety Deafness Claustrophobia

Cataract Surgery with Phacoemulsification Surgery begins with instillation of a povidone iodine 5% drop, cleaning the eyelids with a skin prep (i.e. iodine preparation) and placing a sterile drape which fits around the patient’s eye, held open by an ocular speculum (Fig. 8.10). The procedure begins with a main incision along the limbus and one or two sideport incisions depending on the surgeon’s preference. The larger incision which is used for the phacoemulsification probe and intra-ocular lens injector, is made in three steps (Figs. 8.11 and 8.12). At this point, viscoelastic is injected into the anterior chamber, increasing its depth to prepare for a continuous curvilinear capsulorhexis (Fig. 8.13). This tears a circle in the anterior aspect of the lens capsule, exposing the lens. Next, hydrodissection separates the cortex from the lens capsule to safely rotate the lens nucleus (Fig. 8.14). This involves injecting a small amount of BSS (balanced saline solution) under the lens capsule to separate the cortex from the capsule. This will also allow for more efficient cortical clean up during irrigation and aspiration. Fig. 8.10  The surgeon has cleaned his operating site and is now draping the patient

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Fig. 8.11  Cross-section of a 3-stepped, self-sealing corneal incision. (Reproduced with permission from ‘Phaco Fundamentals’, courtesy of J. Butcher, M. Anderson, and J. Ross)

3 1

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Fig. 8.12  Image of clear corneal incision at the limbus. Forceps are used to grip the conjunctiva on the opposite side for stabilisation and precision of wound construction

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Fig. 8.13 (a, b) Continuous curvilinear capsulorhexis. A cystotome tears the lens capsule, which is then used to create a flap. This is grasped by forceps or dragged circumferentially using the cystotome to create a circular opening in the lens capsule, exposing the lens for subsequent phacoemulsification. (Reproduced with permission from ‘Phaco Fundamentals’, courtesy of J. Butcher, M. Anderson, and J. Ross)

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Fig. 8.14  Separating the lens cortex from its capsule by injecting BSS through a blunt cannula. (Reproduced from ‘Phaco Fundamentals’, courtesy of J. Butcher, M. Anderson, and J. Ross)

Fig. 8.15  Phacoemulsification probe

Fig. 8.16 Initial phacoemulsification groove. Initial sculpting should be deep centrally, and shallow peripherally. (Reproduced with permission from ‘Phaco Fundamentals’, courtesy of J. Butcher, M. Anderson, and J. Ross)

A phacoemulsification probe (Fig. 8.15) follows, aspirating the epinucleus and fragmenting the lens into multiple pieces using ultrasound and peristaltic (or Venturi) vacuum technology (Figs. 8.16 and 8.17).

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Fig. 8.17  Removal of lens using phacoemulsification probe (and mushroom manipulator to rotate fragments)

Fig. 8.18  Removal of cortex during irrigation and aspiration. (Reproduced with permission from ‘Phaco Fundamentals’, courtesy of J. Butcher, M. Anderson, and J. Ross)

Irrigation and aspiration of the lens cortex follows as the final step of lens extraction. This probe removes the fibrous web-like material of the outer lens (Fig. 8.18). An intraocular lens (IOL) is subsequently inserted into a cartridge and injected into the now-empty lens capsule. It unfolds slowly by itself (Fig. 8.19). The surgeon will ensure the IOL is rotated and positioned correctly. Toric lenses, used to counteract astigmatism, must be positioned precisely in the bag and are always marked along the axis for surgical alignment. Lastly, the surgeon removes the previously injected viscoelastic (Fig. 8.20). If the remaining viscoelastic is not removed including under the implant, it can lead to intraocular pressure rises in the eye causing pain and discomfort and potential damage to the optic nerve.

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Fig. 8.19  Intra-ocular lens inserted in lens capsule. Image is an ex-vivo model illustrating the ciliary body (black frond-like shadows) with zonules supporting the lens capsule with an IOL in-situ

Fig. 8.20  Removal of viscoelastic using irrigation and aspiration (I/A) probes after new lens (IOL) is safely inside the lens capsule

8.4  Risks of Surgery As mentioned previously, cataract surgery is not without risk. Occasionally, complications occur. These are best classified perioperatively and post-operatively.

8.4.1  Perioperative 8.4.1.1  Wound Construction In small incision cataract surgery, a stepped (self-sealing) incision is made to avoid the need for sutures, which risks post-operative astigmatism requiring optical correction. If a wound is made too shallow, aqueous humour can leak, causing a drop in intraocular pressure and increased risk in post-operative infection. A risk exists of

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the iris prolapsing through the incision or focal detachment of corneal endothelium (imperative for osmotic homeostasis of the cornea). 8.4.1.2  Capsule Complications The capsular bag gives unrivalled stability for an IOL.  One of the most delicate steps in cataract surgery is the continuous curvilinear capsulorhexis, which enables access to the lens (for evacuation through phacoemulsification) by tearing away a circular piece of tissue from the anterior lens capsule. During this step, a tear toward the equator would compromise the entire lens capsule, leading to IOL instability upon implantation. This complication is best managed through an IOL placed in the ciliary sulcus, or occasionally the anterior chamber. During removal of lens fragments within the lens capsule, a risk of rupturing the posterior lens capsule exists due to its action as a natural barrier between the anterior chamber (containing aqueous humour) and vitreoretinal segment (containing vitreous humour). If ruptured, vitreous may prolapse into the anterior chamber causing several potential complications: • Blockage of drainage angles leading to a high-pressure emergency in the eye • Traction on the retina leading to detachment  • Blockage of the corneal wound and adverse effects on the corneal endothelium, leading to corneal oedema • Cystoid macular oedema • Bacterial endophthalmitis (Fig. 8.21) • “Dropped nucleus”, when lens material is pushed through a posterior capsule rupture, entering the posterior segment of the eye. This may cause an inflammatory reaction, leading to intraocular inflammation and pressure rise. Circumferential tearing of the lens zonules will also lead to a dropped nucleus. Exercise caution in those at risk of weak lens zonules (e.g. homocysteinuria and connective tissue disease such as Marfan’s Syndrome) by using a capsule tension ring or planning for a lens to implant in the ciliary sulcus, anterior chamber, or by other means (e.g. supported by scleral tissue) 8.4.1.3  Suprachoroidal Expulsive Haemorrhage (SEH) SEH is an exceedingly rare but devastating outcome. When intraocular pressure drops so low that haemodynamic stability of the eye is compromised, rapid effusion of venous fluid to the suprachoroidal space (between choroid and sclera) stretches ciliary arteries, resulting in rupture (specifically of the long or short posterior ciliary artery). The surgeon may notice a change in the red reflex as the eye suddenly  feels tense.  This dramatic event, in the most extreme circumstances, may result in extrusion of uveal contents through a corneal excision, causing irreversible blindness. Since the advent of self-sealing wounds and smaller corneal incisions, suprachoroidal haemorrhage incidence is rare and often limited when it does occur.

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Fig. 8.21  Six days post phacoemulsification and IOL placement. Severe injection, corneal oedema, and fibrin strands in the anterior chamber are present. (Reproduced with permission from Eyerounds.org, University of Iowa, 2005. Author: J. Maassen, MD)

8.4.1.4  Retinal Detachment Rhegmatogenous (rhegma is Greek for breakage; -gen for producing) retinal detachment is a retinal detachment from a tear or rupture of a segment of retina. This occurs in patients with pre-existing retinal tears before cataract surgery, high myopia (larger eye and thinner retina), or those with lattice degeneration (the peripheral retina becomes atrophic over time). As previously mentioned, if the posterior capsule or vitreous humour is disrupted at any point, this also increases the risk of retinal detachment.

8.4.2  Post-operative Risks These are best described from anterior to posterior: 1. Bruising of the eyelids 2. Conjunctival haemorrhage 3. Corneal decompensation secondary to excessive damage to endothelial cells (patients with Fuchs’ corneal dystrophy are particularly at risk) 4. Refractive surprise, resulting in prescription glasses afterward or further refractive surgery 5. Lens dislocation/decentration (e.g. movement of lens in capsular bag after surgery) 6. Posterior capsule opacification (see below) 7. Raised intraocular pressure from inflammation or remnant viscoelastic which blocks the trabecular meshwork of the eye’s drainage angle

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8. Infectious endophthalmitis 9. Retinal detachment 10. Cystoid macular oedema The most common post-operative complication is posterior capsule opacification (PCO). 8.4.2.1  Posterior Capsule Opacification PCO arises after a number of weeks to many years. Occurring in up to half of patients post-operatively, younger patients or those with inflammatory ocular conditions are at highest risk. After a cataract procedure, where an intra-ocular lens (IOL) is inserted into the lens capsule, lens epithelial cells on the anterior capsule remain despite enduring the rigors of surgical trauma (Fig.  8.22). This resilient group of cells colonize the previously cell-free posterior capsule as a form of wound healing response. A thin cover of cells is insufficient to affect the light path, but subsequent changes to their extracellular matrix and cell organisation give rise to light scatter and clinically significant visual deterioration. If these changes are sufficiently severe, corrective laser treatment is required (specifically using the Nd:YAG laser).

Anterior capsule

Residual lens cells

I n t r a o c u la r L e n s Supporting loops ((haptics)

Posterior capsule

Capsular wrinkling

Fig. 8.22  A diagrammatic representation of a post-surgical capsular bag and PCO development. (This article was published in Experimental Eye Research, Vol 88, by I.M. Wormstone, Wang, L., Liu, C.S.C., entitled Posterior Capsule Opacification, p. 258, © Elsevier, 2009)

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Further Reading Cataracts in Adults: Management This includes guidance for patients, when to refer, pre-op assessment, lens errors, surgical technique, complications, and post-operative assessment, courtesy of NICE (National Institute for Health and Care Excellence), London. https://www.nice.org.uk/guidance/NG77.

Grading of Cataracts Thylefors B, Chylack LT, Konyama K, Sasaki K, Sperduto R, Taylor HR, West S. A simplified cataract grading system. Ophthalmic Epidemiol. 2002;9(2):83–95. https://doi.org/10.1076/ opep.9.2.83.1523.

Cataract Surgery in Depth Anderson M, Butcher J. Phaco fundamentals: a guide for trainee ophthalmic surgeons. Leicester: Troubador Publishing Ltd.; 2011.

Chapter 9

Medical Retina and Uveitis Camille Yvon and Moloy Dey

9.1  Age Related Macular Degeneration Age Related Macular Degeneration (AMD) is the principal cause of blindness in the elderly population in the developed world. Risk factors comprise age, smoking, female preponderance, Caucasian ethnicity, poor diet, cardiovascular risk factors and hypermetropia [1]. UV light and cataract surgery may also exacerbate the condition. There have been numerous studies determining if genetic predisposition plays a role, such as factor H [2–5]. AMD causes a reduction in central vision or scotomas (blind spot) and metamorphopsia (distorted vision). Peripheral vision is preserved; therefore, patients are able to navigate independently. It can be subdivided into dry and wet or neovascular AMD. Both entities vary in their pathophysiology and treatment.

9.1.1  Dry AMD Dry AMD represents 90% of all AMD. Symptoms can be mild, but can potentially cause severe visual impairment, especially in cases of geographic atrophy. Visual loss tends to be progressive. Pathophysiology shows loss of the retinal pigment epithelium (RPE), photoreceptor layers, thinning of the outer plexiform layer (OPL), and thickening of Bruch’s membrane. Drusens are deposited between the RPE and Bruch’s membrane (Fig. 9.1). Examination reveals hard drusen (small, well defined), as well as soft drusen (large, pale yellow, poorly defined, which can become confluent) (Fig.  9.2). In advanced disease, RPE atrophy and geographic atrophy can be noted (Fig. 9.2). A C. Yvon (*) · M. Dey Maidstone and Tunbridge Wells NHS Trust, Tunbridge Wells, UK © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_9

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DAMAGED PHOTORECEPTORS and RPE

LOSS OF NORMAL RETINAL STRUCTURE OEDEMA

RODS AND CONES RPE BRUCH’S MEMBRANE CHOROID DRUSEN BLOOD VESSEL

DRY AMD

WET/NEOVASCULAR AMD

Fig. 9.1 (a) Schematic diagram of dry and wet AMD pathophysiology. (b) Image of a normal macula OCT (ILM internal limiting membrane, RNFL retinal nerve fibre layer, GCL ganglion cell layer, IPL inner plexiform layer, INL inner nuclear layer, OPL outer plexiform layer, ONL outer nuclear layer, ELM external limiting membrane, IS/OS inner segment/outer segment, EZ ellipsoid zone, RPE retinal pigment epithelium)

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wide range of investigations facilitates the diagnosis (see Table  9.1). Optical ­coherence tomography (OCT) enables the visualisation of drusen and absence of intraretinal/subretinal fluid. Fundus fluorescein angiography (FFA) is not usually necessary in dry AMD. OCT-angiography (OCT-A) has also emerged recently but is not widely available. It uses laser light reflectance of the surface of moving red blood cells, thus eliminating the need for intravascular dyes. Treatment is often supportive and aimed to slow progression. It includes advice (smoking cessation, vitamin supplementation), which has been suggested by the Age-Related Eye Disease Studies (AREDS) [6–8]. The low visual aid clinic can Fig. 9.2  Colour fundal photographs showing dry AMD hard drusen (a), soft drusen (b), and geographic atrophy (c)

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Fig. 9.2 (continued) Table 9.1  OCT and FFA Special investigations OCT

FFA

Technique (non-contact, non-invasive) • Measures accurately the retinal thickness (micrometre-resolution and obtains two- and three-dimensional images) • Based on low-coherence interferometry, typically employing near-infrared light • Useful to detect disorders such as macular oedema, macular holes and neovascular AMD •  Examines the circulation of the retina and choroid • Involves injection of sodium fluorescein (fluorescent dye) into the systemic circulation, and then an angiogram is obtained by photographing the fluorescence emitted after illumination of the retina with blue light (wavelength of 490 nm) • Hypofluorescence will highlight abnormalities such as ischaemia, or masking by blood; whereas hyperfluorescence is suggestive of “leaky” vessels and oedema

offer further support, such as devices (magnifying glasses, good lighting, etc.) Patients need to be given warning symptoms (such as worsening of metamorphosis) and an Amsler grid (see Fig. 9.3).

9.1.2  Neovascular (Wet) AMD Neovascular (wet) AMD may lead to sudden reduction of vision. It is less common than dry AMD.  Pathology differs from dry AMD as new capillaries grow through the choriocapillaris and Bruch’s membrane (see Fig. 9.1). Examination

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Fig. 9.3  Amsler grid. The patient focusses on the central target with one eye closed wearing their reading correction. Any distortion or blank areas are suggestive of macular disease

typically shows haemorrhages (subretinal/sub-RPE), as well as possible exudation, RPE detachment, macular oedema or subretinal fibrosis (disciform scar) (Fig. 9.4). FFA is critical for diagnosis, as it reveals hyperfluorescence with progressive leakage. The introduction of anti-vascular endothelial growth factor (anti-VEGF) has radically changed treatment. There are different drugs available including ranibizumab (Lucentis®), aflibercept (Eyelea®) and bevacizumab (Avastin®), which work by inhibiting angiogenesis, vascular permeability and inflammation. The aim of treatment is the resolution of intra and sub retinal fluid, and subsequent restoration of normal anatomy and vision. Injections are typically administered every 4–8 weeks depending on the drug. More recently, the “treat-and-extend” dosing regimen is being adopted in clinical practice, where the aim is to increase the interval between injections [9].

9.2  Diabetic Eye Disease Diabetes is a condition that affects over 200 million people and carries high incidence of morbidity and mortality. It is subdivided into type 1 (typically of juvenile onset, insulin deficiency) and type 2 (usually adults and insulin resistance). Retinopathy due to diabetes can be sight threatening. Severity will depend on duration of the disease, type of disease, glycaemic control, evidence of hypertension, nephropathy, pregnancy, etc. Type 1 diabetics tend to have more severe disease with retinopathy present in over 90% after 15 years.

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Hyperglycaemia is thought to be the main cause of microvascular complications and retinopathy. Glycosylation of tissue proteins, small vessel occlusion, changes in vessel wall, loss of pericytes and increased permeability all contribute to the pathophysiology. VEGF plays a key role as it is released in response to ischemia and may induce neovascularisation. Retinopathy can be detected during routine screening, even when the patient is asymptomatic. However, visual loss in diabetes is usually caused by diabetic maculopathy. In addition, cataract develops earlier in diabetic patients. Other ocular conditions may be exacerbated in diabetics and comprise dry eyes, anterior uveitis, rubeosis, neovascular glaucoma, ocular ischemic syndrome, papillitis, anterior ischemic optic neuropathy (AION), orbital infection and cranial nerve palsies.

Fig. 9.4 Fundal photographs (a, b) and OCT (c) of wet AMD

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Fundal examination to grade the retinopathy is critical. Table 9.2 shows a classification adopted by the National Screening Service. Patients have a fundal photograph taken yearly, and are generally referred to the hospital if there is any evidence of maculopathy or moderate to severe signs of disease (Figs. 9.5 and 9.6). Treatment includes lifestyle advice (smoking cessation, weight control, exercise, etc.); systemic management (good glycaemic and blood pressure (BP) control). Proliferative disease is treated with pan retinal photocoagulation (PRP) ± anti-­ VEGF therapies. Maculopathy is treated with focal or grid laser (very low power to avoid scarring, unlike PRP) and intravitreal injections (anti-VEGF or steroid

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Table 9.2  Diabetic retinopathy classification used by the screening service Retinopathy R0 Background (R1) Pre proliferative (R2) Proliferative (R3a and R3s)

Maculopathy M0 M1

Findings None Micro aneurysm (focal capillary dilatations), small haemorrhages ± exudates Venous beading or loop, intraretinal microvascular abnormality (IRMA), multiple deep or blot haemorrhages in all four quadrants, cotton wool spots (swollen axons) New vessels on disc (NVD) or elsewhere (NVE), pre retinal haemorrhage or vitreous haemorrhage, pre-retinal fibrosis ± tractional retinal detachment. Subdivions of R3 include R3a - active growing fronds and R3s - stable longstanding fronds No maculopathy Exudate within one 1 disc diameter (DD) of the centre of the fovea, circinate/ group of exudates within the macula, retinal thickening less than 1 DD, micro aneurysm or haemorrhage less than 1 DD and VA of less than or equal to 6/12.

Fig. 9.5  Fundal photographs showing moderate non proliferative diabetic retinopathy with microaneurysms, dot/blot haemorrhages, cotton wool spots and exudates

9  Medical Retina and Uveitis Fig. 9.6  Colour fundal photographs showing NVD (a) and NVE (b)

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implants). Vitreous haemorrhages need to be monitored with ultrasounds to confirm the absence of a retinal detachment. Previous PRP in these cases are reassuring; however, if the vitreous haemorrhage persists, then vitrectomy ± endolaser ± anti-­ VEGF therapy may be necessary.

9.3  Retinal Vein Occlusion Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy. It is often associated with atherosclerotic risk factors (hypertension, hypercholesterolaemia diabetes, smoking, obesity); haematological

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causes (e.g. protein S, C or antithrombin deficiency, factor V Leiden, myeloma, antiphospholipid syndrome); inflammatory conditions (e.g. Behcet’s disease, sarcoidosis, systemic lupus erythematous) and other ophthalmic conditions (such as glaucoma and direct trauma). Thrombosis occurs within the lumen of the vessel due to the predisposing factors of Virchow’s triad (hypercoagulability, stasis and endothelial damage). Depending on the location of the occlusion, it is broadly classified as either a central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Additionally, it can be subdivided into ischaemic and non-ischaemic types (based on FFA and certain clinical findings). This is important to counsel the patient with regards to visual prognosis and subsequent complications.

9.3.1  Central Retinal Vein Occlusion CRVOs are less common than BRVOs. Patients typically present with painless reduction of vision. Fundoscopy shows dilated tortuous veins with retinal haemorrhages in all four quadrants, with possibly some cotton wool spots (CWS) and optic disc oedema (Fig. 9.7). Ischaemic CRVO tends to have greater visual loss and more CWS.  In addition, a relative afferent pupillary defect may be noted. Collateral vessels may develop at the optic disc in chronic cases and represent a better visual prognostic factor. Complications comprise cystoid macular oedema (CMO) and neovascularisation (which occurs first at the iris, then disc then retina). When the new vessels block the anterior chamber angle, this may subsequently lead to a severe form of secondary glaucoma, known as neovascular glaucoma Fig. 9.7  Colour fundal photograph showing a CRVO

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(NVG). This process typically develops after an average period of 90 days; hence it is often referred to as the “90  days-glaucoma.” However, it may also appear sooner so should not be missed. All patients should be investigated with BP measurements, blood glucose, full blood count (FBC) and erythrocyte sedimentation rate (ESR). Other blood tests such as urea and electrolytes (U&Es), lipids may be indicated but are not mandatory. If clinically indicated (e.g. young patient), then further blood tests may be needed such as C reactive protein (CRP), serum angiotensin converting enzyme (ACE), anticardiolipin, lupus anticoagulant, autoantibodies, thrombophilia screen and chest X-ray. OCT can confirm the presence of CMO. FFA will aid in the differentiation of non-ischaemic and ischaemic CRVO, as the latter may show large areas of capillary closure. Management initially involves treatment of risk factors in order to prevent an occlusion in the contralateral eye; as well as reducing morbidity and mortality especially if a vascular disease has been diagnosed. PRP may be necessary if there is any evidence of neovascularisation [10]. Anti-VEGF injections or intravitreal steroid implant injections (Ozurdex®) can also be administered in the presence of CMO.  Prognosis is variable with better outcomes in the non-ischaemic type. However, a third of non-ischaemic cases become ischaemic by 3 years, and a third of ischaemic cases develop rubeosis [11].

9.3.2  Branch Retinal Vein Occlusion Branch retinal occlusions are more common and usually occur supero-temporally. Patients may be asymptomatic, or may complain of a reduction of vision, metamorphopsia or visual field defect. The dilated veins and haemorrhages tend to be distributed in an arcade (Fig.  9.8). Complications, investigations and management are similar to CRVOs. Treatment options include intravitreal anti VEGF injections, intravitreal steroid implants in the presence of macular oedema; in addition to macular grid laser. Prognosis is significantly better than CRVO with more than half achieving 6/12 vision, and the risk of neovascularisation is very low.

9.4  Retinal Artery Occlusions Arterial occlusions tend to cause more severe visual loss than vein occlusions. Like venous occlusions, they can be classified as a central retinal artery occlusion (CRAO) or branch retinal artery occlusion (BRAO). The commonest pathology is embolization, where the embolus originates from the carotid artery and is typically made of cholesterol, or calcific deposits. Inflammation within the vessel wall may also cause occlusion.

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Fig. 9.8  Colour fundal photograph showing BRVO

9.4.1  Central Retinal Artery Occlusion CRAO is an ophthalmic emergency and the ocular analogue of cerebral stroke. The incidence is estimated to be 1 in 100,000 people and may lead to profound visual loss by inducing hypoxia of the inner retina, followed by death of the nerve fibre layer, ganglion cell layer and inner plexiform layer. The retina is very susceptible to ischaemia and animal models have demonstrated irreversible damage after 90 min of occlusion [12–15]. Patients typically present with sudden painless unilateral loss of vision. Examination may show in the early stages a white swollen retina with a “cherry red spot” (as the unaffected highly vascular choroid is visualized). In addition, the vessels are typically attenuated and there may be evidence of “cattle trucking” (segmentation of the blood column in the arteries). The emboli may be noted in 25% cases. After approximately 6  weeks, the cherry red spot fades and optic pallor becomes apparent due to death of the retinal ganglion cells (Fig. 9.9). A cilio-retinal artery is present in 30% cases and represents a better prognostic factor. In effect, the blood supply to the macular area will be maintained in those individuals with such a cilioretinal artery. Complications include neovascularisation (mainly at the iris), rubeotic glaucoma, optic atrophy and ocular ischaemic syndrome. It is crucial to rule out giant cell arteritis (GCA) if the patient is above 50 years old, as the condition may cause a CRAO. Bloods tests including FBC, ESR, and CRP should be done promptly. Most commonly, CRAO is associated with atherosclerosis, therefore close monitoring of BP, blood glucose and cholesterol are critical (Table  9.3). Carotid Dopplers may also be necessary to detect occult cardiovascular disease. Patients younger than 50 should have a hypercoagulable workup including thrombophilia screen (e.g. protein C and S, antithrombin, factor

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Fig. 9.9  Colour fundal photographs showing a CRAO

Table 9.3  Associations of CRAO Sources Embolic Haematological

Examples Carotid artery disease, aortic disease, cardiac vegetations Protein C, protein S, antithrombin deficiency, antiphospholipid, leukaemia, lymphoma Inflammatory GCA, granulomatosis with polyangiitis, systemic lupus erythematous (SLE), Susac’s, Behcets Infective Toxoplasmosis, syphilis Pharmacological Oral contraceptive pill, cocaine Ophthalmic Trauma, optic nerve drusen, migraine

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V), antiphospholipid antibody syndrome, vasculitis autoantibodies (e.g. antinuclear antibody, ANA; antineutrophil cytoplasmic antibody, ANCA; rheumatoid factor, RF and syphilis serology). In a young patient with multiple or recurrent BRAOs, Susac syndrome should be considered (which is a rare autoimmune disorder characterized by encephalopathy, BRAOs and hearing loss). There is limited evidence regarding immediate treatment. If the patient presents within 24 hours, it is common practice to try to dislodge the clot further down the arterial tree hence causing less damage. Routine measures include 500 mg IV acetazolamide, ocular massage and anterior chamber paracentesis, which work by reducing intraocular pressure and subsequently displace the embolus. Increasing carbon dioxide concentration induces vasodilation; therefore, breathing into a bag to increase carbon dioxide concentration has also been recommended. If there is any evidence of GCA, then steroids need to be administered to prevent visual loss in the non-affected eye. Referral to the stroke/TIA team is critical and regular prophylactic aspirin should be prescribed if no contraindication is found. The use of clot busting tissue plasminogen activator (tPA) is not widely available and debatable, as it carries a high risk of intracranial hemorrhage (without evidence of visual benefit). Prognosis is poor, especially in the absence of a cilioretinal artery. The majority of patients are counting fingers at presentation and only about a third of cases show some mild improvement.

9.4.2  Branch Retinal Artery Occlusion Patients are typically asymptomatic or present with a sudden painless unilateral field defect. The pale and swollen retinal area is noted along a branch retinal artery, in addition to arteriolar attenuation and cattle-trucking and possible emboli. In contrast, neovascularisation is very rare in branch retinal artery occlusion (BRAO) (Fig. 9.10). It is important to identify the cause of the BRAO. GCA is rarely associated with BRAO and does not need to be ruled out if the clinical suspicion is low. There is no proven treatment for BRAO, but a referral to the stroke team is typically made to identify risk factors.

9.5  Hypertensive Retinopathy Hypertension is associated with cardiovascular risk and systemic target organ damage, including the eye. It affects 60% of those aged over 60 years (approximately one billion worldwide). It can be subdivided into chronic and accelerated/malignant hypertension (>220 mmHg systolic or 120 diastolic). There are two distinct components in the pathophysiology: the vasospastic reaction to acute pressure rise, and the

9  Medical Retina and Uveitis Fig. 9.10  Colour fundal photographs showing a BRAO (a) caused by a calcific emboli (b)

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arteriolosclerotic response to chronic high pressure. Hypertension is usually essential and not secondary to another disease process. Risk factors include age, male gender, obesity and ethnic origin (African-Caribbean). Patients are usually asymptomatic in chronic hypertension; but may experience visual loss and headaches in accelerated hypertension. Numerous classifications have been recommended to grade hypertensive retinopathy (one example illustrated in Table 9.4). Clinical features include narrowing and irregular arterioles (“copper and silver” wiring), arteriovenous nipping, CWS, blot or flame haemorrhages (Fig. 9.11). Complications include macroaneurysms, AION, vein and artery occlusions. Malignant hypertension is characterized by papilloedema with fundal haemorrhages and exudates (Fig.  9.11). Other features comprise choroidal infarcts, known as Elschnig spots when local, and Siegrist’s streaks when linear (along choroidal arteries).

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Table 9.4  The Keith, Wagener, and Barker hypertensive retinopathy classification (grade I–IV), based on the level of severity of the retinal findings Grade I II

III IV

Features •  Mild generalised retinal arteriolar narrowing or sclerosis •  Definite focal narrowing and arteriovenous crossings •  Moderate to marked sclerosis of the retinal arterioles •  Exaggerated arterial light reflex •  Retinal haemorrhages, exudates and CWS •  Sclerosis and spastic lesions of retinal arterioles •  Severe grade III and papilloedema

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Lowering the BP is crucial, and the patient may even need admission in cases of accelerated hypertension (as rapid reduction of BP can be deleterious). Untreated, mortality at 1 year is 90% for malignant hypertension.

9.6  Retinitis Pigmentosa Retinitis pigmentosa (RP) is an inherited, degenerative disease characterized by abnormalities of the photoreceptors (rods > cones). The patients complain of reduced peripheral vision (tunnel vision) and night blindness. It affects approximately 1 in 4000 people and can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. Most cases are isolated, but it may also occur as part of a syndrome, such as Usher syndrome (RP with deafness), Kearns-Sayre syndrome (RP with ophthalmoplegia, ataxia, and cardiac conduction defects) and abetalipoproteinemia (RP with ataxia, red blood cells abnormalities and steatorrhoea). It is clinically and genetically heterogeneous with up to 60 different associated genes. Examinations may reveal mid-peripheral bony spicules, waxy pallor of the optic disc, arteriolar attenuation and early cataracts (Fig. 9.12). Genetic testing may be difficult in atypical cases in view of the high number of genes associated with RP. There is no proven management till date. Treatment involves supportive measures (counselling, low visual aids, etc.). A 15,000 IU daily dose of vitamin A was shown to have a small protective effect on the progression of RP, as was the intake of the carotenoids lutein and β-carotene [16–20]. However, toxicity can occur with high doses of vitamin A and the evidence is very scarce. Patients with RP have increased risk of CMO following cataract surgery. Fig. 9.12  Colour fundal photograph of a patient with retinitis pigmentosa

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9.7  Posterior Uveitis Posterior uveitis, also known as choroiditis, refers to inflammation of the choroid, the posterior part of the uvea. It may also affect the retina and/or the optic nerve and may lead to permanent visual loss. Causes of posterior uveitis may involve underlying systemic disease and hence history taking is essential (Fig. 9.13). Patients often complain of floaters (vitreous opacities consisting of debris and inflammatory cells) and blurry vision. Ophthalmic features of posterior uveitis include vitritis, vasculitis, CWS, macular oedema, optic disc swelling and foci of chorio-retinal inflammation. Investigations are summarized in Table 9.5. Anterior chamber activity is treated with topical steroids, as discussed in previous chapters. Periocular or systemic steroids should be considered in posterior disease, in addition to immunosuppressants and intraocular steroids (e.g. steroid implant (Ozurdex®)) are occasionally given if disease is localized (e.g. CMO); however, carry risk of glaucoma and cataract. Fig. 9.13  Key points to ask during history taking • SOB • Chest pain • Bowel problems • Ulcers (mouth/ genital) • Joint pain • Skin rashes • Fever • Recent travel • Pets

Table 9.5  Principal investigations in posterior uveitis Investigation FFA OCT ESR FBC and U&E ACE Syphilis serology Toxoplasma serology T spot test Chest X-ray

Purpose To detect occult vasculitis, macular oedema (hyperfluorescence) or ischemia (hypofluorescence) To detect evidence of macular oedema or epiretinal membrane indicating chronic inflammation Non-specific increase in inflammatory disorders General work up and systemic involvement (e.g. kidney) Raised in sarcoidosis Can be treated with penicillin Negative results excludes toxoplasmosis exposure Tuberculosis (TB)—treatable and giving steroids without anti-TB medication can be detrimental To detect sarcoidosis and TB

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9.7.1  Sarcoidosis Sarcoidosis is a granulomatous multisystem disorder which involves the eye in 25% cases. The prevalence of sarcoidosis varies widely between studies [21–24]. It is more common in females and peaks in the third and sixth decades. It tends to affect African-Caribbean, Irish and Scandinavian populations. The cause has not yet been fully elucidated, but it is thought to be associated with genetics, infectious agents (e.g. mycobacteria, fungi, borrelia, and rickettsia) and autoimmune disorders. Ophthalmic manifestations can be isolated or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. 60% can have anterior uveitis and 25% may have posterior uveitis (Table 9.6 and Figs. 9.14 and 9.15). It may cause e­ piscleritis/ Table 9.6  Clinical features of ocular sarcoidosis Anterior uveitis Circumlimbal injection, AC cells or flare, mutton fat keratic precipitates (KPs), iris granulomas and nodules Intermediate Vitreous cells, aggregates of inflammatory cells in the vitreous uveitis (snowballs), white exudates (snowbanking) Posterior uveitis CMO, periphlebitis (patchy sheathing + “candle wax dripping”), occluded vessels, neovascularization, nodules/granuloma, disc swelling, small punched-out atrophic spots (multi focal choroiditis) Complications Cataract, glaucoma, CNV Fig. 9.14 Anterior segment photos showing mutton fat keratic precipitates (a) and posterior synechiae and iris nodules (b)

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170 Fig. 9.15  Wide field fundal photograph (a) and FFA (b) of a patient with sarcoidosis and colour fundal photographs showing periphlebitis (patchy sheathing + “candle wax dripping”) (c, d)

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Fig. 9.16  Systemic features of sarcoidosis

scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Systemic features can be varied (Fig. 9.16). Investigations that facilitate diagnosis comprise serum ACE (elevated due to active macrophages), serum calcium (less sensitive), imaging (chest X-ray or high-­ resolution CT scan) and if possible a sarcoid proven biopsy. If neurosarcoid is suspected, then MRI brain/optic nerves and lumbar puncture may be needed.

9.7.2  Behcet’s Disease Behçet’s disease (BD) is a multisystem inflammatory disorder characterized by major symptoms of aphthous and genital ulcers (Fig. 9.17), uveitis, and skin lesions (erythema nodusum, pseudofolliculitis). A higher prevalence is noted in the population along the Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1–10 patients in 10,000 people are affected; in contrast to only 1–2 patients in 1,000,000 people in UK and North America [25]. Although aetiology of the disease is still unknown, a link has been made with the HLA B51 allele (which is more prominent in Japan). Clinical features include anterior uveitis (with a hypopyon), posterior uveitis (with possible vitritis, CMO, retinal infiltrates, occlusive periphlebitis, neovascularization, etc.) (Fig. 9.18) The condition can lead to optic and retinal atrophy in the advanced stages.

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Fig. 9.17  Photograph of a mouth ulcer in a patient with BD

Fig. 9.18  Wide field fundal photograph (a) and FFA (b) of a patient with BD with an inflammatory BRVO

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Investigations comprise a positive pathergy test (where a sterile pustule forms 1–2 days at the site of needle puncture) and MRI/MRV if any evidence of neurological deficit. Systemic steroids are used for acute flare ups, in addition to steroid sparing agents (ciclosporin, azathioprine, anti-tumour necrosis factor therapies and alpha interferon) for long-term management.

9.7.3  Tuberculosis Tuberculosis (TB) is an infectious disease usually caused by the bacterium Mycobacterium tuberculosis. It is still one of the major causes of mortality, and has re-emerged as a significant public health problem in recent years. The disease primarily affects the lungs due to the deposition of Mycobacterium tuberculosis (a facultative intracellular bacterium), found in aerosol droplets, onto lung alveolar surfaces. It can also be extrapulmonary and affect the central nervous, skeletal and cardiovascular system. Ocular TB is rare, but has been reported in approximately 1% cases [26, 27]. Hallmark of the disease comprises caseating granulomas. Clinical features include vasculitis, periphlebitis, vein occlusions, ischemia, CMO, multiple choroidal granulomas (typically at the posterior pole) and optic neuropathy (Fig.  9.19). Eales disease (characterised by vasculitis, ischemia, retinal ­neovascularization and recurrent vitreous hemorrhages) has been linked to TB and hypersensitivity to tuberculoprotein. It typically affects males in the second decade and has a higher prevalence in India [28–30]. Other ophthalmic features include lid abscesses, conjunctival nodules, scleritis, keratitis, granulomatous anterior uveitis with mutton fat keratic precipitates, iris granulomas, etc. TB remains one of the differentials of posterior uveitis. There are multiple investigations that can facilitate the diagnosis of TB (Table 9.7), but all have their own advantages and disadvantages. Treatment requires a multidisciplinary approach involving the help of respiratory specialists. Multi-drug anti-tuberculous regimen comprises the four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol). Standard treatment (and if compliance is likely to be adequate) include all the above drugs for 2 months, followed by rifampicin and isoniazid for 4 months. Combination tablets do exist to make it easier for the patients (e.g. rifater). Disseminated disease may require higher doses and treatment for up to 9 months. It is important to check their kidney and liver function before starting these drugs, as well as visual acuity with ethambutol. Additional treatment like steroids can be given to treat inflammatory changes like CMO, but only if the patient is also receiving TB medication.

174 Fig. 9.19  Colour fundus photographs of a patient with ocular TB

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Table 9.7  Diagnostics tools for TB Investigation Microbiology Chest X-ray Tuberculin testing, e.g. Mantoux

Interferon-Gamma (IFN-γ) Release Assays. E.g. QuantiFERON-TB Gold test/T spot

Interpretation Early morning sputum (positive when stains with Ziel-Nielsen) Apical infiltrates/cavitation, consolidation, pleural effusions, hilar lymphadenopathy Intradermal injection of tuberculin followed by measurement of induration at 48–72 h (in mm). The size is deemed positive depending on risk factors (e.g. 5 mm induration if immunocompromised versus 15 mm in healthy patients). High false negative rates (17%) and false positives post BCG vaccination. Measures the amount of IFN-γ released from sensitized lymphocytes after overnight incubation with purified protein derivative (PPD) from M. tuberculosis and antigens. More specific than Mantoux test; but still cannot distinguish between latent and active infection.

9.7.4  Syphilis Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. There are four stages of syphilis as shown in Table 9.8. It can also be subdivided into acquired and congenital. Ocular findings include anterior uveitis (commonest feature), as well as posterior uveitis (choroiditis/chorioretinitis), which can affect one or both eyes. Yellow plaque lesions with associated vitritis can also be noted in posterior segment disease (Fig. 9.20). Neuro-ophthalmic complications of syphilis include Argyll Robertson pupils (small pupils with light-near dissociation), papilloedema, retrobulbar neuritis, ocular motility disorders, etc. Congenital syphilitic chorioretinitis results in pigmentary retinopathy (“salt and pepper pattern”). Blood tests are divided into non-treponemal and treponemal tests. Non-­ treponemal tests are used initially and include venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR) tests. Due to false positives, confirmation is required with a treponemal test, such as treponemal pallidum particle haemagglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-Abs). Treponemal antibody tests usually become positive 2–5 weeks after the initial infection. Neurosyphilis is diagnosed by finding high numbers of leukocytes and proteins in the cerebrospinal fluid, when the primary diagnosis of syphilis is already known. Dark ground microscopy of serous fluid from a chancre may be used to make an immediate diagnosis. It is also important to rule out HIV, which often coincides with syphilis. Management is usually led by the genitourinary physician. The first-choice treatment is typically a single dose of intramuscular benzathine benzylpenicillin. Doxycycline and tetracycline are alternative choices for those allergic to penicillin. Due to the risk of birth defects, these are not recommended for pregnant women.

176 Fig. 9.20  Wide field fundal photograph with a patient with positive syphilis blood tests presenting with acute syphilitic posterior placoid chorioretinitis (ASPPC) and appropriately treated with benylpenicillin

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Table 9.8  Stages of syphilis Stage Primary

Timing 2–6 weeks after primary infection Secondary 4–10 weeks after primary infection Latent Tertiary

3–15 years after primary infection

Clinical features Painless ulcer (chancre); regional lymph node enlargement Disseminated rash (maculopapular or pustular); fever, malaise, generalised lymphadenopathy Recurrence of secondary syphilis symptoms in up to 25% of individuals Gumma, cardiovascular syphilis (aortic regurgitation), late neurological complications (meningitis, CNS vasculitis, tabes dorsalis, etc.)

9.8  Conclusion Both age related macular degeneration and diabetic retinopathy represents a large proportion of visual loss and morbidity across the population. This is set to rise as both life expectancy and obesity continues to rise. Prompt diagnosis with careful history and appropriate use of investigations are key in medical retina related conditions. As the technology improves with regards to diagnostic tests we are now able to offer appropriate treatment, which allows visual stability and improvement with certain medical retina conditions. This is currently an exciting time for the specialty with ever expanding diagnostic tools and treatments which are now available for the patient.

References 1. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age-Related Eye Disease Study report number 3. Ophthalmology. 2000;107(12):2224–32. 2. Donoso LA, Vrabec T, Kuivaniemi H. The role of complement factor H in age-related macular degeneration: a review. Surv Ophthalmol. 2010;55(3):227–46. 3. Toomey CB, Johnson LV, Bowes Rickman C. Complement factor H in AMD: bridging genetic associations and pathobiology. Prog Retin Eye Res. 2018;62:38–57. 4. Klein RJ, Zeiss C, Chew EY, Tsai J-Y, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science (New York). 2005;308(5720):385–9. 5. Thakkinstian A, Han P, McEvoy M, Smith W, Hoh J, Magnusson K, et al. Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration. Hum Mol Genet. 2006;15(18):2784–90. 6. The Age-Related Eye Disease Study Research Group. The age-related eye disease study (AREDS): design implications AREDS report no. 1. Control Clin Trials. 1999;20(6):573–600. 7. Age-Related Eye Disease Study Research Group. A randomized placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417–36.

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8. Chew EY, Clemons T, SanGiovanni JP, Danis R, Domalpally A, McBee W, et  al. The age-­ related eye disease study 2 (AREDS2): study design and baseline characteristics (AREDS2 report number 1). Ophthalmology. 2012;119(11):2282–9. 9. Rufai SR, Almuhtaseb H, Paul RM, Stuart BL, Kendrick T, Lee H, et al. A systematic review to assess the ‘treat-and-extend’ dosing regimen for neovascular age-related macular degeneration using ranibizumab. Eye. 2017;31:1337. 10. The Central Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995;102(10):1434–44. 11. The Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol (Chicago, IL: 1960). 1997;115(4):486–91. 12. Hayreh SS, Zimmerman MB, Kimura A, Sanon A. Central retinal artery occlusion. Retinal survival time. Exp Eye Res. 2004;78(3):723–36. 13. Hayreh SS, Kolder HE, Weingeist TA. Central retinal artery occlusion and retinal tolerance time. Ophthalmology. 1980;87(1):75–8. 14. Hayreh SS, Weingeist TA.  Experimental occlusion of the central artery of the retina. I.  Ophthalmoscopic and fluorescein fundus angiographic studies. Br J Ophthalmol. 1980;64(12):896–912. 15. Hayreh SS, Jonas JB.  Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: an experimental study in rhesus monkeys. Am J Ophthalmol. 2000;129(6):786–95. 16. Brito-Garcia N, Del Pino-Sedeno T, Trujillo-Martin MM, Coco RM, Rodriguez de la Rua E, Del Cura-Gonzalez I, et al. Effectiveness and safety of nutritional supplements in the treatment of hereditary retinal dystrophies: a systematic review. Eye (London). 2017;31(2):273–85. 17. Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol (Chicago, IL: 1960). 1993;111(6):761–72. 18. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol (Chicago, IL: 1960). 2004;122(9):1306–14. 19. Bahrami H, Melia M, Dagnelie G. Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289]. BMC Ophthalmol. 2006;6:23. 20. Rotenstreich Y, Belkin M, Sadetzki S, Chetrit A, Ferman-Attar G, Sher I, et al. Treatment with 9-cis beta-carotene-rich powder in patients with retinitis pigmentosa: a randomized crossover trial. JAMA Ophthalmol. 2013;131(8):985–92. 21. Park JE, Kim YS, Kang MJ, Kim CJ, Han CH, Lee SM, et al. Prevalence, incidence, and mortality of sarcoidosis in Korea, 2003–2015: a nationwide population-based study. Respir Med. 2018;144S:S28–34. 22. Erdal BS, Clymer BD, Yildiz VO, Julian MW, Crouser ED. Unexpectedly high prevalence of sarcoidosis in a representative U.S. Metropolitan population. Respir Med. 2012;106(6):893–9. 23. Gerke AK, Judson MA, Cozier YC, Culver DA, Koth LL. Disease burden and variability in sarcoidosis. Ann Am Thorac Soc. 2017;14(Suppl 6):S421–8. 24. Gribbin J, Hubbard RB, Jeune IL, Smith CJP, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006;61(11):980–5. 25. Suzuki Kurokawa M, Suzuki N. Behcet’s disease. Clin Exp Med. 2004;4(1):10–20. 26. Thompson MJ, Albert DM. Ocular tuberculosis. Arch Ophthalmol. 2005;123(6):844–9. 27. Shakarchi FI.  Ocular tuberculosis: current perspectives. Clin Ophthalmol (Auckland, NZ). 2015;9:2223–7. 28. Das T, Pathengay A, Hussain N, Biswas J. Eales’ disease: diagnosis and management. Eye (London). 2010;24(3):472–82. 29. Atmaca LS, Batioglu F, Atmaca Sonmez P.  A long-term follow-up of Eales’ disease. Ocul Immunol Inflamm. 2002;10(3):213–21. 30. Biswas J, Sharma T, Gopal L, Madhavan HN, Sulochana KN, Ramakrishnan S.  Eales disease—an update. Surv Ophthalmol. 2002;47(3):197–214.

Chapter 10

Vitreous and Retina Emily Shao and Sui Chien Wong

10.1  Vitreous and Vitreoretinal Interface Disorders The vitreous is a transparent gel inside the eye that supports embryological growth of the eye, enables unobstructured light transmission to the retina with a structured network of collagen fibrils and reduces oxidative stress on the lens. It consists of 98% water, with the remaining 2% made up of collagen fibrils, soluble proteins and hyaluronic acid.

10.1.1  Floaters Visual phenomena where patients may report a cobweb or flies in their vision are commonly referred to as floaters. These are best seen on a light background and move with eye movements. Floaters are common and it is usually a benign condition which is predominantly caused by condensations or remnants in the vitreous gel casting a shadow on the retina. Symptoms of floaters improve as they move further anteriorly in the eye, and as the patient goes through a period of neuro-adaptation during which floaters become less noticeable. A sudden increase in floaters is most commonly associated with posterior vitreous detachment (PVD).

E. Shao (*) Department of Ophthalmology, Sussex Eye Hospital, Brighton, UK S. C. Wong Great Ormond Street Hospital for Children, London, UK Moorfields Eye Hospital, London, UK Royal Free Hospital, London, UK © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_10

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10.1.2  PVD PVD describes the phenomenon when the posterior vitreous cortex separates from the neurosensory retina. Its prevalence increases with age, occurring spontaneously in 70% of adults by the age of 70. However, it can occur secondary to myopia, trauma, intraocular surgery, diabetes and retinal vascular disorders such as retinal vein occlusion, pan-retinal photocoagulation and uveitis. It is asymptomatic in 75% of the population, with the remaining 25% experiencing floaters, due to collagen fibrils disintegrating and aggregating, with or without flashing lights, which occur as the vitreous separates from the neurosensory retina, traction stimulating and leading to flashing lights. The majority of PVDs occur without complications. A minority can present with associated retinal tear, a proportion of which can lead to retinal detachment and sight loss if left untreated (refer to Sect. 10.2). In 90% of cases, the fellow eye will develop PVD within 3 years, of which 11% of them will exhibit similar problems to the first eye such as retinal tears or detachment. PVD have also been implicated in the development of macula holes and epiretinal membranes (please see Sect. 10.3). On clinical examination, the presence of a Weiss ring on fundal exam confirms the diagnosis of PVD (Fig. 10.1). This consists of epipapillary glial tissue, which has avulsed from the disc during PVD. However, clinicians need to be aware that a Weiss ring can be difficult to visualise or apparently absent in around 13% of PVDs. Highly myopic eyes can present with vitreous opacities which can be similar to Weiss rings in appearance but are in fact vitreoschisis (a split in the posterior vitreous cortex) rather than PVD. Shafer sign or tobacco dust sign is an important clinical finding to look for in the anterior vitreous in all patients with a suspected PVD and is highly predictive (around 90%) of the presence of associated retinal tear. When a retinal tear occurs, Fig. 10.1  Weiss ring. (Reproduced from Williamson T.H. (2013) Posterior Vitreous Detachment. In: Vitreoretinal Surgery. Springer, Berlin, Heidelberg)

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retinal pigment epithelial (RPE) cells are released from the sub-retinal to the pre-­ retinal space, visible in the anterior vitreous as tiny pigmented cells, elicited by asking the patient to move their eye quickly away from and back to the primary position.

10.1.3  Vitreous Haemorrhage Vitreous haemorrhage presents with varying symptoms depending on severity, from diffuse blurring of vision (mild) to severe sight loss. Dense vitreous haemorrhage may result in a reduced red reflex on fundoscopy. Causes of vitreous haemorrhage include: • PVD associated with retinal capillary rupture or retinal tear with avulsed retinal vessel • Proliferative retinopathy, most commonly secondary to retinal ischaemia due to diabetic retinopathy and retinal vein occlusions (refer to Chap. 13) • Macroaneurysms • Trauma • Bleeding diathesis All cases of vitreous haemorrhage should be referred to an ophthalmologist urgently to exclude sight-threatening retinal tear or detachment. Where an acute PVD-related retinal tear cannot be excluded, urgent pars plana vitrectomy (PPV) is required to prevent retinal detachment and subsequent loss of sight. In patients with known proliferative retinopathy, the most likely cause of haemorrhage is traction of the vitreous on retinal neovascularisation during a PVD. In such patients who have previously been treated with pan-retinal photocoagulation (PRP), the ­ophthalmologist may observe the haemorrhage with a B-scan ultrasound for several weeks to see if it resolves spontaneously. Non-clearing vitreous haemorrhage after several weeks needs to be referred to a vitreoretinal surgeon for PPV to decrease the risk of complications including erythroclastic glaucoma (secondary to red blood cells and macrophages clogging up the trabecular meshwork decreasing aqueous drainage), and the rarer ‘synchysis scintillans’ (refer to Sect. 10.1.4). In such patients who have previously not undergone PRP treatment, PPV is recommended sooner (usually within a couple of weeks) to clear the blood and enable intra-operative PRP laser to prevent the secondary complications of untreated retinal ischaemia including rubeotic glaucoma and traction retinal detachment. Retinal arterial macroaneurysms are acquired, focal dilations of retinal arterial branches associated with old age, hypertension and a female preponderance. They are more often associated with retinal haemorrhages (80%) than vitreous haemorrhages (30%), although break-through bleeds of retinal haemorrhages into the vitreous cavity can occur. The majority self-resolve over weeks to months without treatment with a good visual prognosis and therefore can be observed.

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If visual function is threatened due to macular oedema, focal laser to the aneurysm can be carried out. PPV is the treatment of choice for fundus obscuring vitreous haemorrhages whereby the diagnosis is uncertain. The most likely cause of haemorrhagic PVD is a retinal tear in over 90% of cases in the absence of predisposing conditions such as diabetes, previous documentation of vein occlusions, systemic disorders such as sickle cell or trauma. The retinal tear can lead to a retinal detachment and subsequent sight loss if left untreated. In the presence of a vitreous haemorrhage where the fundal view is obscured, a B-scan ultrasound of the eye should be attempted to identify retinal detachments and retinal tears. This will help indicate the urgency of vitreoretinal involvement and subsequent surgery (Fig. 10.2). All suspected cases of haemorrhagic PVD should therefore be referred to vitreoretinal surgeons with the view of surgical intervention urgently. Fig. 10.2 Ultrasound B-Mode images of eyes with deviated gaze (a) PVD with dense intra-gel vitreous haemorrhage (IGH) and mild retrohyaloid haemorrhage (b) PVD with IGH ; Sub-total rhegmatogenous RD with vitreous gel inserting into anterior edge of a nasal retinal tear (green arrow): Courtesy Dr. Marie Restori

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Retinal detachments always insert at the optic disc. This can be useful in differentiating between retinal and posterior vitreous detachments.

10.1.4  Asteroid Hyalosis Asteroid hyalosis is a common degenerative process in which particles formed of calcium, phosphorus and oxygen are deposited in the vitreous gel. The prevalence is greater with increasing age, in men and in diabetes mellitus. The vast majority of people are asymptomatic.

10.1.5  Synchysis Scintillans Synchysis scintillans are seen as golden-brown refractile particles in the vitreous, and occasionally seen in the anterior chamber of the eye. They are composed of cholesterol crystals derived from degraded erythrocytes, as a consequence of chronic vitreous haemorrhage. It is an indication of end stage disease and the affected eye is often already blind.

10.2  Retinal Tears and Detachment 10.2.1  Retinal Tears Retinal tears develop as a result of vitreous traction on the neuroretina during PVD, the vast majority developing soon after the onset of PVD symptoms of floaters and flashing lights. Tears associated with PVD most commonly occur in the superior temporal retina and enable retrohyaloid or pre-retinal fluid to migrate into the sub-­ retinal space through the retinal tear. If a tear is surrounded by a cuff of sub-retinal fluid (SRF) of one disc diameter or more, then a retinal detachment (RD) is said to be present. Retinal tears is one of several types of full-thickness retinal breaks which include: Horseshoe (retinal) tear—a U-shaped flap with its base attached to the vitreous base and its apex pulled anteriorly by the detaching vitreous (PVD). This needs referral to an ophthalmologist for retinopexy (retinal laser) to decrease the risk of progression to retinal detachments (Fig. 10.3). Operculated tear—this is when the flap on the horseshoe tear has been completely torn off the retina leaving a separated piece of retina in the detached vitreous (the operculum) and a residual round or oval hole in the neuro-retina (Fig. 10.4). If the patient is asymptomatic and the retinal break is flat then these do not generally require treatment as there is no longer vitreous traction on the retinal break.

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Fig. 10.3  Horseshoe tear. (Williamson T.H. (2013) Posterior Vitreous Detachment. In: Vitreoretinal Surgery. Springer, Berlin, Heidelberg)

Fig. 10.4  Operculated tear. (Role of retinal image-based counseling in the treatment of peripheral retinal lesions. Sharma et al. Eye volume 33, pages 161–163 (2019))

Retinal hole—these are smaller than the average retinal tear and round. They are synonymous with round holes or atrophic holes. They typically occur in younger myopic patients without a PVD, and can be associated with peripheral lattice degeneration. Risk of retinal detachment is very low and treatment is not required. Dialyses—typically large peripheral retinal breaks more anteriorly where the vitreous base meets the ora serrata without PVD, often associated with blunt ocular trauma (Fig. 10.5). This requires specialist vitreoretinal intervention with either retinopexy in the absence of RD, or retinal detachment repair.

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Fig. 10.5 Dialysis. (Williamson T.H. (2013) Different Presentations of Rhegmatogenous Retinal Detachments. In: Vitreoretinal Surgery. Springer, Berlin, Heidelberg)

Fig. 10.6  Giant retinal tear. (Reproduced with permission from: Henry C.R. (2016) Retinal Tears. In: Medina C., Townsend J., Singh A. (eds) Manual of Retinal Diseases. Springer, Cham)

Giant retinal tear—is a large horseshoe tear involving 90° (3 clock hours) or more of the retinal circumference located most commonly immediately posterior to the oraserrata (Fig. 10.6). They have a high incidence of retinal detachment if left untreated. In addition to the type of retinal tear, the risk of progression to retinal detachment is higher in those with: • • • • • •

Myopia—there is a higher incidence of progression to RD in myopes Past history of RD Family history of RD Previous intraocular surgery Aphakia Systemic conditions such as Marfan’s, Stickler’s and Ehlers-Danlos syndromes

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• S  ymptomatic retinal breaks (e.g. flashing lights and floaters) have higher risk of RD progression than asymptomatic retinal tears/holes • Larger size of tear • U tears—higher risk than round holes • Persistent vitreoretinal traction—thus U-tears with traction on the apex of the tear have higher risk than operculated tears whereby the traction is gone. • Superior breaks—higher risk than inferior breaks

Management of retinal tears without RD can be divided into: • • • •

Conservative Retinopexy Laser retinopexy Cryo retinopexy

Operculated tears and asymptomatic flat round holes all have a low risk of progression to RD, and therefore can be observed with conservative management. Both laser- and cryo-retinopexy reduce the risk of RD progression by causing inflammation with subsequent enhanced adhesion of surrounding retina to the RPE around the tear to prevent retrohyaloid fluid from entering the subretinal space. Adequate adhesion of the retina is induced around 5  days after cryotherapy and 3 days after laser retinopexy. Laser retinopexy is more precise and causes less collateral retinal damage and thus lower risk of epiretinal membrane formation. Therefore, laser retinopexy is generally the preferred technique. However. cryoretinopexy is preferred in retinal tears difficult to treat with laser, for example, if the tear is very peripheral, if there are extensive retinal breaks, or multiple contiguous tears, and those with small pupils or hazy media. After retinopexy treatment patients are advised to avoid strenuous exercise and an ophthalmology review is recommended at 1–2 weeks after treatment to check that adequate scarring around the tear has started to form (Fig. 10.7). Full scar maturation is seen at about 6 weeks.

10.2.2  Retinal Detachment Retinal detachment can be classified into three groups; rhegmatogenous, tractional and exudative retinal detachment. 10.2.2.1  Rhegmatogenous Retinal Detachment Rhegmatogenous retinal detachment (Fig. 10.8) is the most common form of retinal detachment. This group is associated with full thickness retinal break such as PVDrelated tears. Patients thus generally present with the symptoms of an acute PVD

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Fig. 10.7  Retinal tear with surrounding laser burns. (Galloway N.R., Amoaku W.M.K., Galloway P.H., Browning A.C. (2016) Retinal Detachment. In: Common Eye Diseases and their Management. Springer, Cham)

Fig. 10.8 Rhegmatogenous retinal detachment. (Williamson T.H. (2013) Rhegmatogenous Retinal Detachment. In: Vitreoretinal Surgery. Springer, Berlin, Heidelberg)

(flashing lights, sudden increase in floaters) followed by a ‘curtain-like effect’ or loss of peripheral vision from one side as the RD occurs. Suspected cases require urgent same-day referral to an ophthalmologist with subsequent referral for vitreoretinal surgery.

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10.2.2.2  Tractional Retinal Detachment Tractional retinal detachment (TRD) is caused by contraction of fibrovascular membrane caused by proliferative retinopathy over an area of vitreo-retinal adhesion (Fig. 10.9). It is most commonly secondary to proliferative diabetic retinopathy, but other pathologies such as retinopathy of prematurity and penetrating eye injuries can also lead to tractional retinal detachment. Photopsia and floaters are usually absent as it is not precipitated by a PVD. Patients generally experience progressive loss of central or peripheral vision depending on where the TRD develops, although in contrast to rhegmatogenous retinal detachment this tends to occur slowly over weeks, months or even years, instead of a matter of days.

Fig. 10.9 (a) Tractional retinal detachment. Tranos P, Gemenetzi M, Papandroudis A, Chrisafis C, Papadakos D. Progression of diabetic tractional retinal detachment following single injection of intravitreal Avastin. Eye (Lond). 2008 Jun;22(6):862. Epub 2007 Nov 16. (b) Ma K., Zhou N., Wei W. (2018) Introduction of Retinal Detachment. In: Wei W. (eds) Atlas of Retinal Detachment. Springer, Singapore

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10.2.2.3  Exudative Retinal Detachment Exudative RD is characterised by RD in the absence of retinal breaks or traction. It is vital when exudative RD is diagnosed to exclude a neoplastic or inflammatory cause, which can cause fluid to leak out of retinal vessels to accumulate in the subretinal space. Common neoplastic causes include choroidal melanomas and metastasis. Unlike rhegmatogenous or tractional RD, exudative RD can cause both eyes to be affected simultaneously when there is a precipitating systemic cause. Photopsia is absent as it is not associated with PVD but floaters may be present in cases of uveitis or neoplastic seeding in the vitreous.

10.2.3  Retinal Detachment Surgery Both rhegmatogenous and tractional RD are surgically managed. Surgery may be done internal or external to the eye. Pars plana vitrectomy (PPV) is an internal procedure involving the removal of vitreous to release traction on the retina. In rhegmatogenous RD, the surgery is accompanied by flattening the RD with an expanding gas bubble or silicone oil, and retinopexy of the retinal tear to prevent a re-detachment. In tractional RD the fibrovascular membranes would be peeled by the vitreo-retinal surgeons to release the traction on the retina. Scleral buckling is an alternative external procedure. Buckles are most frequently considered in rhegmatogenous RDs in the absence of PVD (where PPV has a higher risk of inducing iatrogenic retinal break), and in young patients so that unwanted side effects of PPV such as the earlier development of a cataract can be avoided. Combined vitrectomy and scleral buckling are sometimes undertaken for RD with inferior breaks, proliferative vitreoretinopathy, multiple small breaks at the ora serrata, and traumatic retinal detachments. Management of exudative RD depends on identifying and treating the cause.

10.3  Surgical Retina and Other Conditions 10.3.1  Epiretinal Membrane An epiretinal membrane (ERM) is a thin sheet of fibrous retinal glial and retinal pigment epithelial tissue that develops over the macula, where contraction of the membrane leads to wrinkling of the retina, which can result in visual disturbance such as blurring of vision and metamorphopsia (straight lines appearing wavy) (Fig. 10.10).

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Fig. 10.10 Epiretinal membrane. (Reproduced from Tibbetts M.D., Duker J.S. (2017) Vitreomacular Traction and Epiretinal Membranes. In: Meyer C., Saxena S., Sadda S. (eds) Spectral Domain Optical Coherence Tomography in Macular Diseases. Springer, New Delhi)

ERM signs include: • • • •

An irregular translucent sheen seen at the macula on fundal exam Retinal wrinkling and striae at the macula Distortion of retinal blood vessels around the macula ERM can be accompanied by macula pseudo-hole or lamellar hole, cystoid macula oedema and retinal telangiectasia.

Causes of ERM include: • I diopathic—the commonest cause of ERM. It is thought to be triggered by PVD, which damages the internal limiting membrane of the retina, thus stimulating gilal cell proliferation with subsequent fibrosis. ERM is bilateral in 10% of idiopathic cases. • Previous retinal detachment • Cryotherapy • Retinal laser • Ocular Trauma • Previous intraocular surgery • Ocular inflammation

When ERM is suspected in symptomatic patients, a non-urgent referral to ophthalmologists can be made for further management. A complete dilated fundal examination should be conducted including examination of the peripheral retina to look for retinal breaks. ERM can be either observed or surgically managed. Mild ERM with limited or no symptoms can be observed for progression and worsening symptoms in particular distortion. Rarely, spontaneous resolution of symptoms can occur as progression to full PVD can pull the ERM off the retinal surface. ERM can predispose patients

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to cystoid macular oedema following cataract surgery. In patients with significant blurred vision, central visual distortion or reduced visual acuity, surgery can be considered. This involves pars plana vitrectomy (PPV) and the peeling of the ERM off the retinal surface. Careful consultation for surgery is required, and patients need to be made aware that surgery frequently improves but does not ameliorate distortion and visual acuity will not normalise. Cataract development is accelerated by vitrectomy, with over 50% of patients requiring cataract surgery within 2 years.

10.3.2  Macular Hole Macular hole can be classified into full thickness and partial thickness holes. With a prevalence of 3:1000, full thickness macular holes (FTMH) are a relatively common cause of central scotomas. Risk factors for developing FTMH include increasing age, female sex, blunt ocular trauma and high myopia. Symptoms of FTMH include metamorphopsia and reduced central vision in one eye. Fundoscopy will reveal round or oval defect at the fovea with a red base. Diagnosis of FTMH is confirmed on optical coherence tomography (OCT), which is also used in the grading of FTMH into The Vitreomacular Traction Study Group, and Gass grading systems. The Vitreomacular Traction Study (IVTS) Group grades macular holes (MH) as: • Vitreomacular adhesion (VMA)—perifoveal (within 3 mm) PVD without retinal distortion • Vitreomacular traction (VMT)—distortion of the foveal contour associated with perifoveal PVD • Small or medium FTMH with VMT—a FTMH less than 400 μm in diameter at its base • Medium or large FTMH with VMT—a FTMH greater than 400 μm in diameter at its base • FTMH without VMT—FTMH with a complete PVD (suggested by the presence of a Weiss ring and absence of VMT on OCT)

The Gass Grading system grades macular holes (Fig. 10.11): • • • • •

Grade 1A—foveal intraretinal cyst, clinically seen as a yellow spot Grade 1B—foveal ring of intraretinal cysts, clinically seen as a ring of yellow spots Grade 2—FTMH less than 400 μm Grade 3—FTMH more than 400 μm Grade 4—FTMH with posterior vitreous detachment

Management strategies for macular holes include observation, pharmacological vitreolysis and surgical. Around 50% of VMT resolve spontaneously so therefore it can be observed. Ocriplasmin has been used as an intravitreal injection to stimulate complete PVD, which has been reported to lead to resolution of VMT and VMA stage macular holes. However, significant side effects in decreasing order of frequency include floaters, conjunctival haemorrhage, eye pain, photopsia, blurred vision, macular hole, reduced visual acuity, and retinal oedema. These have limited its use.

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Fig. 10.11 (a) OCT images illustrating the evolution from stage IA macular hole. (b) Stage 2 macular hole. (Reproduced from Bazvand F., Roohipoor R., Hajizadeh F. (2018) Epiretinal Membrane, Macular Hole and Vitreomacular Traction (VMT) Syndrome. In: Hajizadeh F. (eds) Atlas of Ocular Optical Coherence Tomography. Springer, Cham)

The mainstay of FTMH management is surgical, by PPV and peeling of the internal limiting membrane (ILM) and injection of gas tamponade by a vitreoretinal surgeon. Overall, surgery leads to successfully hole closure in over 90%, with improvement in vision in over 80%. Prognosis is dependent on size and chronicity of FTMH, with smaller FTMH and prompt surgery associated with higher rates of both structural and functional success.

10.3.3  Retinopathy of Prematurity Retinopathy of prematurity (ROP) occurs in premature infants with low gestational age and low birth weight. In premature infants the retinal vascular network is not fully developed. Though it continues to develop after birth, it can do so in a disorganised manner which can lead to fibrovascular proliferation, vitreous haemorrhage, retinal detachment and visual loss. Previously in the 1940s and 50s when ROP began to be reported, high or highly variable oxygen tension was attributed as a risk factor in addition to low gestational age and birth weight.

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12

Clock Hours

Zone III

Zone III

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3 Macula

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Fig. 10.12  Zones for classification of retinopathy of prematurity. (Reproduced from Yang M.B. (2016) Retinopathy of Prematurity. In: Traboulsi E., Utz V. (eds) Practical Management of Pediatric Ocular Disorders and Strabismus. Springer, New York, NY)

A screening programme exists in the United Kingdom in which all infants born at less than 31 weeks gestational age and birth weight of less than 1251 g must be screened, and infants born at less than 32  weeks and weight of less than 1501  g should be screened. Patients are screened 4–5  weeks postnatally at 1–2 weekly intervals. ROP is classified according to zones of the retina (see Fig. 10.12), and stages defined by the International Classification of Retinopathy or Prematurity Revisited. Stages 1–5, with 1 being the presence of a demarcation line and stage 5 being total retinal detachment. Treatment is carried out in specialist centres with photocoagulation using transpupillary diode laser to prevent sight threatening traction retinal detachment. Treatment criteria are dependent on the zones of retina involved, and presence of plus disease (significant venous dilatation and arteriolar tortuosity in the posterior retina in two or more quadrants). Patients who have been treated for ROP should be followed up long term. Further details are beyond the scope of this textbook but can be found in the further reading.

Further Reading Akiba J, Ishitko S, Yoshida A. Variations of Weiss’s ring. Retina. 2001;21(3):243–6. American Academy of Ophthalmology. Retina and vitreous. San Francisco, CA: American Academy of Ophthalmology; 2015. Hikichi T, Yoshida A. Time course of development of posterior vitreous detachment in the fellow eye after development in the first eye. Ophthalmology. 2004;111(9):1705–7.

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International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991–9. Kakehashi A, Inoda S, Shimizu Y, Makino S, Shimizu H. Predictive value of floaters in the diagnosis of posterior vitreous detachment. Am J Ophthalmol. 1998;125(1):113–5. Novak MA, Welch RB. Complications of acute symptomatic posterior vitreous detachment. Am J Ophthalmol. 1984;97(3):308–14. Williamson TH. Vitreoretinal surgery. London: Springer; 2013.

Chapter 11

Ocular Tumours Bertil E. Damato

There are many different ocular tumours, all with a wide variety of manifestations. Only a few are mentioned in this chapter. Diagnosis of intraocular tumours is based on ophthalmoscopy, autofluorescence imaging, optical coherence imaging, ultrasonography, fluorescein angiography, indocyanine angiography and/or biopsy. Conjunctival tumours are diagnosed by slit-lamp examination and, if necessary, biopsy. The first priority of treatment is to save life, if possible conserving a comfortable eye with useful vision. Therapeutic modalities include various forms of surgical excision, radiotherapy, laser therapy, cryotherapy, chemotherapy, and immunotherapy, which are usually administered in various combination to ensure local tumour control while avoiding collateral damage to healthy tissues. Treatment of the primary tumour is followed by long-term surveillance to detect and treat any local recurrence and metastasis as well as any side effects and complications. Essential aspects of care include counselling, informed consent, prognostication, and psychological support addressing the needs both of the patient and close relatives. Patients with an ocular tumour have increasingly been managed by ocular oncologists, working as part of a multidisciplinary team comprising specialist nurses, medical oncologists, radiotherapists, pathologists, geneticists, psychologists and others, usually at a supra-regional centre. Because of COVID-19, some aspects of care (e.g., diagnosis and monitoring) may shift from ocular oncology centres to local hospitals, and from hospital clinics to community optometrists, with expert advice from virtual specialist clinics. This trend will be facilitated by improved imaging, secure electronic communications, artificial intelligence, and video-conferencing. Whenever possible, patients are enrolled in clinical trials, which usually involve multicentre collaboration under the auspices of organisations such as the European Ophthalmic Oncology Group and the International Society of Ocular Oncology B. E. Damato (*) Nuffield Department of Clinical Neurosciences, University of Oxford, West Wing, John Radcliffe Hospital, Oxford, UK e-mail: [email protected] © Springer Nature Switzerland AG 2020 C. Liu, H. Lee (eds.), Fundamentals in Ophthalmic Practice, https://doi.org/10.1007/978-3-030-28841-9_11

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as well as patient advocacy groups such as the Melanoma Research Foundation, CureOM, and A Cure in Sight. This collaboration requires standardised methods of examination, treatment, and disease definition using the TNM (Tumor, Node, Metastasis) staging system of the American Joint Committee on Cancer (AJCC), International Retinoblastoma Classification, and others.

11.1  Uveal Tumours 11.1.1  Naevus Choroidal naevus (Fig. 11.1) is a benign tumour composed of uveal melanocytes. It occurs in up to 10% of the Caucasian population. It is usually asymptomatic and found on routine eye examination. Clinical features include: • • • • •

Flat tumour, with some showing slight thickening. Featureless surface, with some lesions showing drusen, especially if dome shaped. Grey appearance, although a few are amelanotic (i.e., yellow or white). Small size, usually less than three disc diameters (DD) (i.e., 4.5 mm) in diameter. Surround of normal choroid, but with an amelanotic halo in a few cases.

Iris naevus (Fig. 11.2) is rare. Clinical features include: • Flat tumour, with some showing slight thickening. • Diameter usually less than 3 mm.

Fig. 11.1 Typical choroidal naevus of the right eye

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Fig. 11.2  Pigmented iris naevus inferiorly in the left eye, with a small freckle supero-temporally

Fig. 11.3 Choroidal melanoma involving the left optic disc, showing a dome shape and confluent clumps of orange pigment

11.1.1.1  Management Patients should be informed of any naevi that are discovered so that they will know that these are not new when these are noted at any subsequent examinations. All lesions should be documented by photography if possible, to make it easier to detect any growth at a later date. The risk of malignancy is extremely low with naevi that do not show any features of melanoma (listed in next section).

11.1.2  Melanoma Choroidal melanomas (Fig. 11.3) are the most common primary ocular malignancy in adults. Presentation peaks around the age of 60 years and is rare before adulthood. In about 30% of patients, the tumour is detected on routine fundus examination before symptoms develop; otherwise, symptoms include blurred vision, metamorphopsia, photopsia, visual field loss or visible tumour in the iris or subconjunctivally.

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Early treatment of choroidal melanoma improves any opportunities for conserving vision and may prevent metastasis in some patients; however, differentiating small choroidal melanomas from naevi can be difficult. 11.1.2.1  Diagnosis Damato has devised the acronym, MOLES, to help diagnose and manage patients with choroidal melanocytic tumours of unknown malignancy: Mushroom shape Orange pigment Large size

Enlargement over time Subretinal fluid (SRF)

0 if absent; 1 if uncertain; 2 if definite. 0 if absent; 1 if dusty or uncertain; 2 if confluent. 0 if diameter 2 mm. (Ignore thickness if this cannot be assessed). 0 if absent or unknown; 1 if uncertain; 2 if definite. 0 if absent; 1 if trace or uncertain; 2 if definite. (Assume SRF if unexplained blurred or distorted vision)

A protocol is currently under evaluation for categorizing tumours and managing patients according to the total score: • • • •

If score is 0, ‘common naevus’—optometry review at every routine checkup. If score is 1, ‘low-risk naevus’—monitoring with photos, OCT and autofluorescence imaging. If score is 2, ‘high-risk naevus’—refer non-urgently to local ophthalmologist. If score is >2, ‘probable melanoma’—refer urgently to ophthalmologist.

Features raising suspicion of the presence of a choroidal melanoma include: • Metamorphopsia (i.e., distorted vision), caused by foveal disturbance by SRF or tumour • Eccentric visual phenomena, such as photopsia (flashing lights) or visual field loss • Lens abnormalities, such as cataract or astigmatism, caused by tumour pressing on the lens • Afferent pupillary defect, caused by retinal damage from detachment or tumour • No improvement in visual acuity with optical correction • Ocular hypertension, if new vessels in the iris, tumour cells or macrophages blocking aqueous outflow • Melanoma visible externally (i.e., extraocular or anterior chamber tumour spread) • Asymmetric episcleral ‘sentinel’ vessels, if the tumour involves ciliary body

Iris melanomas are less common than other uveal melanomas (Fig. 11.4). They can be pigmented or amelanotic and nodular or diffuse.

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Fig. 11.4 Nodular, pigmented, iris melanoma

11.1.2.2  Management Ocular treatment is aimed at conserving a comfortable and seeing eye, possibly preventing metastasis in some patients. The most widely used modalities are: 1. Brachytherapy, administered by a saucer-shaped radioactive applicator, which is sutured to the globe adjacent to the tumour and removed a few days later, once the prescribed dose of radiation has been administered. 2. Proton beam radiotherapy, administered with a cyclotron, which precisely delivers a fine beam of protons, which can be collimated to match the shape of the tumour. The beam is targeted at the tumour using radio-opaque markers that are sutured to the sclera at known distances from the tumour before the radiotherapy. 3. Stereotactic radiotherapy, with multiple fine beams of radiation focused on the tumour from different directions, either simultaneously or sequentially. 4. Infra-red laser therapy that either heats the tumour (transpupillary thermotherapy) or activates a photosensitizer, such as verteporfin (photodynamic therapy). 5. Local tumour resection, either en-bloc through a scleral trapdoor (exoresection) or by nibbling and aspirating the tumour with a vitrector passed through a hole in the retina. 6. Ocular amputation (enucleation) or, if there is extensive extraocular spread, exenteration of the entire orbital contents. Treatment is selected according to the tumour size, location and extent and often combines different modalities (e.g., brachytherapy with adjunctive laser therapy, exoresection followed by adjunctive brachytherapy, or endoresection preceded by neoadjuvant proton beam radiotherapy). After radiotherapy, some choroidal melanomas leak fluid into the macula and subretinally or cause iris neovascularization and painful glaucoma; such ‘toxic tumour syndrome’ can be treated with intra-vitreal injections of anti-­angiogenic agents or by lasering or resecting the toxic tumour.

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11.1.2.3  Prognosis Despite successful excision or ablation of the choroidal melanoma, almost 50% of patients develop metastatic disease, which usually becomes apparent months or years after apparent good health. Metastases develop almost exclusively in patients whose tumour shows chromosome 3 deletion, a class 2 gene expression profile, and/or BAP1 gene inactivation, all of which are more prevalent in large tumours. Prognostic tumour biopsy is therefore being performed routinely in a growing number of centres. An online prognostic tool is available at www.LUMPO.net. Metastatic disease almost always involves the liver, which is examined by ultrasonography or magnetic resonance imaging before ocular treatment and then every 6–12 months, indefinitely. Metastatic disease from uveal melanoma carries a poor prognosis, unless amenable to a partial hepatectomy, although encouraging results have recently been achieved with IMCgp100 (Tebentafusp), which binds cytotoxic T cells to melanoma cells, and with isolated liver perfusion with melphalan.

11.1.3  Haemangioma Choroidal haemangiomas (Fig. 11.5) are rare, benign, vascular tumours, which can be circumscribed or diffuse. Diffuse choroidal haemangiomas are almost always associated with Sturge Weber Syndrome, whereas circumscribed choroidal haemangiomas (CCH) have no systemic associations. These tumours are characterised by: • • • •

pink colour, posterior location, indistinct margins, and exudative retinal detachment, which can become total.

Fig. 11.5 Choroidal haemangioma inferior to the left optic disc. Note the pink colour

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Treatment consists of photodynamic therapy or low-dose radiotherapy and is primarily aimed at conserving the eye and useful vision, although improvement in visual acuity occurs only in a few cases.

11.1.4  Metastases Choroidal metastases (Fig. 11.6) are becoming more common as patients with cancer live longer. They mostly arise in breast or lung. Not unusually, the ocular metastasis is the presenting feature of lung cancer, unlike metastases from breast carcinoma, which arise in patients with a previous history of the disease. Many patients have metastases in other organs when they present with ocular disease. The clinical features of choroidal metastases are: • • • • • • • •

location in posterior choroid in most cases yellow or white colour, except for metastases from skin melanoma placoid shape indistinct margins lack of visible tumour vessels (unlike amelanotic melanomas) serous retinal detachment multiple tumours affecting one or both eyes in some patients rapid tumour growth, which necessitates urgent referral and treatment

In patients with a solitary choroidal metastasis and no evidence of concurrent or previous extraocular malignancy, the clinical diagnosis may need to be established by intraocular tumour biopsy, which may also help to identify the site of the primary tumour. Choroidal metastases usually respond dramatically to radiotherapy, which can be administered in the first instance or if there is no tumour regression with systemic therapy. Metastases to retina and vitreous are rare. Fig. 11.6 Multiple choroidal metastases from the lung in a middle-aged woman. The right eye showed similar appearances

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11.2  Retinal Tumours 11.2.1  Vitreoretinal Lymphoma Retinal lymphoma (Fig. 11.7) is rare but becoming more common. It is usually of the diffuse, large, B-cell type. In most patients, retinal lymphoma is associated with CNS involvement, which can present before or after the ocular disease. Most patients are elderly, except for those with immunodeficiency. The clinical features are: • vitreous infiltrates, resembling uveitis unresponsive to steroids, and/or • yellow or white subretinal infiltrates, accumulating under the retinal pigment epithelium • size of subretinal infiltrates ranging from very small flecks or drusenoid deposits to large, irregular tumours • multiple subretinal deposits in most cases, usually affecting both eyes • other features, such as retinal vascular sheathing and occlusion, epiretinal membrane formation, macular oedema and optic disc swelling

Diagnosis is confirmed by vitreous or tumour biopsy. The lymphoma cells are fragile so that specimens must reach the laboratory within an hour unless special transport medium is used. Steroid therapy must be stopped as long as possible before biopsy as it can cause a false negative result. Ocular treatment consists of low-dose radiotherapy or intravitreal injections of methotrexate or melphalan, but is often followed by fatal CNS lymphoma. In some centres, systemic therapy is therefore preferred, especially in view of encouraging survival data in studies combining chemotherapy with immunomodulatory agents Fig. 11.7 Subretinal infiltrates of lymphoma cells in a patient with CNS/ retinal lymphoma. Vitreous infiltrates are not shown in this figure

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such as lenalidomide. The efficacy of such systemic therapy is enhanced by therapeutic vitrectomy.

11.2.2  Retinal Capillary Angioma Retinal capillary angioma (also known as haemangioblastoma) (Fig. 11.8) can be sporadic or hereditary, the latter arising as part of Von-Hippel Lindau disease. This syndrome is inherited in an autosomal dominant fashion and causes a wide variety of tumours, which include CNS haemangioblastoma, renal cell carcinoma, phaeochromocytoma, renal and pancreatic cysts, islet cell tumours, cystadenoma of the epididymis in men and the broad ligament of the uterus in women, and endolymphatic cell tumour. This syndrome should be suspected in patients with a positive family history, more than one retinal angioma or one retinal angioma and systemic evidence of this disease. The features of retinal capillary angioma are: • Peripheral retinal location, especially temporally, in most cases. • Tiny red spot (similar to microaneurysm) growing into an orange-red nodule with a prominent feeder vessel from the optic disc. • Secondary effects—hard exudates, possibly forming a macular star; retinal haemorrhage, traction retinal detachment. • Optic disc location in some cases. • Spontaneous regression, with reduction in size of feeder vessel and resolution of exudation. • Multiple lesions in one or both eyes if associated with VHL disease. • Sessile or exophytic growth in some optic disc tumours.

Fig. 11.8  Retinal capillary angioma, with dilated feeder vessel and hard exudates

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Patients with VHL need screening for retinal angiomas and vice versa. The detection of retinal lesions can be aided by wide-angle fluorescein angiography. Systemic disease can be revealed by genetic testing, palpitations, headaches, deafness, hypertension, haematuria, urinary catecholamines, and tumours found on CNS and abdominal imaging. Depending on their size and location, retinal angiomas are treated by photocoagulation, photodynamic therapy, cryotherapy or radiotherapy, and possibly intra-­ vitreal anti-angiogenic agents.

11.2.3  Retinoblastoma Retinoblastoma (Fig. 11.9) is almost always caused by mutation of both the maternal and paternal copies of the RB1 gene (i.e., ‘two-hit hypothesis’). The RB1 gene is located on chromosome 13. The disease depends on when the mutation occurs: If the two RB1 mutations both occur in the same retinal cell, then a solitary, somatic, non-hereditary retinoblastoma develops. If one copy of the retinoblastoma gene is mutated during embryonic life, then every cell in part of the body carries the mutation (i.e., mosaicism). If a germline mutation from one parent is inherited, then it is present in all cells throughout the body of the patient. Malignancy develops whenever and wherever the homologous gene from the other parent mutates so that both copies of the gene become abnormal. Patients with such hereditary, germline retinoblastoma tend to develop multiple retinoblastomas in one or both eyes as well as pineoblastoma, osteosarcoma, melanoma and a wide variety of other cancers. The mutation is

Fig. 11.9 Multiple retinoblastomas in the left eye of a baby with germline disease

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autosomal dominant, so that it is inherited by 50% of the patient’s children, 90% of whom will develop retinoblastoma. With regards to the clinical features of retinoblastoma: • • • • • • • •

When very small, the tumour is translucent, pearly, flat or dome-shaped. When larger, the tumour is nodular or multinodular, yellow-white, with visible blood vessels. When tumour necrosis occurs, a craggy, white, irregular, calcified mass develops. Vitreous seeding has the appearance of white dust, pearls or clouds. Subretinal seeding appears as tiny, yellow or white tumours, which become confluent. Anterior chamber seeds form white tumours or a pseudohypopyon. Extra-ocular spread into the orbit causes proptosis if advanced. Secondary effects include retinal detachment, vitreous haemorrhage, glaucoma and panophthalmitis. • Diffuse retinoblastomas infiltrate the retina without forming a discrete mass.

Patients usually present: • at birth or in the first year of life if bilateral disease is present, • in the second or third year of life if only one eye is affected, and • in later childhood if there is diffuse retinoblastoma affecting only one eye.

Modes of presentation include leukocoria, strabismus, glaucoma, buphthalmos, orbital cellulitis and proptosis. Management involves: • I nduction of labour at 38 weeks if family history of retinoblastoma, to detect and treat any tumours as early as possible. • Full ocular examination, commencing ocular treatment 1 or 2 days after birth. • For small tumours (