Current Advances in Ocular Surgery (Current Practices in Ophthalmology) 9819916607, 9789819916603

Table of contents :
Preface
Contents
About the Editors
Part I: Surgical Innovations for Adnexal and Oculoplastics
1: Injectables: Aesthetics and Cosmetics
1.1 Soft Tissue Filler
1.1.1 Introduction
1.1.2 Clinical Applications
1.1.3 Categories of Dermal Filler
1.1.3.1 Non-biodegradable Fillers
Poly-Methyl Methacrylate (PMMA)
Silicone
Polyalkylimide
1.1.3.2 Biodegradable Fillers
Collagen
Calcium Hydroxyapatite (CaHA)
Poly-l-Lactic Acid (PLLA)
Hyaluronic Acid Fillers (HA)
Patient Selection and Evaluation
Contraindications
1.1.4 Preparation and Post-Operative Care
1.1.4.1 Antiseptic Technique
1.1.4.2 Post-Procedural Care
1.1.5 Injection Techniques
1.1.5.1 Linear Threading (Anterograde and Retrograde)
1.1.5.2 Serial Puncture and Depot Injections
1.1.5.3 Fanning and Cross Hatching
1.1.6 Anatomical Considerations and Techniques
1.1.6.1 Forehead and Glabellar Furrows
1.1.6.2 Forehead and Temporal Fossa
1.1.7 Periorbital Region
1.1.7.1 Eyebrows
1.1.7.2 Superior Sulcus
1.1.7.3 Tear Troughs
1.1.8 Midface and Nasolabial Folds
1.1.8.1 Cheek
1.1.8.2 Nasolabial Folds Augmentation
1.1.8.3 Nose
1.1.9 Lower Face
1.1.9.1 Perioral Region
1.1.9.2 Marionette Lines and the Oral Commissure
1.1.9.3 Labiomental Fold and the Chin Apex
1.1.9.4 Jawline
1.1.10 Soft Tissue Filler Complications
1.1.10.1 Technique for Reversal
1.1.10.2 Ecchymosis
1.1.10.3 Infection and Biofilm Production
1.1.10.4 Granulomas
1.1.10.5 Improper Filler Placement or Migrated Filler
1.1.10.6 Skin Necrosis
1.1.10.7 Ophthalmic Complications
1.2 Botulinum Toxins
1.2.1 Introduction
1.2.2 Clinical Applications
1.2.3 Mechanism of Action
1.2.4 Patient Selection and Evaluation
1.2.5 Contraindications
1.2.6 Preparation and Post-Operative Care
1.2.6.1 Preparation and Storage
1.2.6.2 Post-Procedural Care
1.2.7 Injection Techniques
1.2.8 Anatomical Considerations and Techniques
1.2.8.1 Frontalis
1.2.8.2 Glabella
1.2.8.3 Orbicularis Oculi
1.2.8.4 Pharmacologic Brow Contouring
1.2.8.5 Nasal Rhytids
1.2.8.6 Perioral Region
1.2.8.7 Masseter
1.2.8.8 Mentalis
1.2.8.9 Platysma
1.2.9 Botulinum Toxins Complications
1.2.10 Injection Site Reactions
1.2.11 Under-Correction
1.2.12 Ptosis
1.2.13 Brow Ptosis
1.2.14 Brow Asymmetry
1.2.15 Diplopia, Lagophthalmos, and Dry Eyes
1.2.16 Lip Ptosis
1.2.17 Dysphagia
1.2.18 Systemic Complications
1.2.19 Future Directions
References
2: Fornix Reconstruction
2.1 Mucous Membrane Substitution
2.1.1 Contralateral Conjunctiva
2.1.2 Buccal or Labial Mucous Membrane
2.1.3 Nasal Mucosa Graft
2.1.4 Hard Palate Graft
2.1.5 Dermis Fat Graft
2.1.6 Temporoparietal Fascial Flap
2.1.7 Tarsoconjunctival Flap
2.1.8 Amniotic Membrane Graft
2.2 Forniceal Deepening
2.3 Maintaining Separation of Healing Surfaces
2.4 Summary
References
Part II: Surgical Innovations for Cataract
3: Capsulotomy and Lens Fragmentation
3.1 Anterior Capsulotomy: Manual Curvilinear Capsulorhexis, Femtosecond Laser Capsulotomy, and Precision Pulse Capsulotomy
3.1.1 Historical Perspective
3.1.2 Adequacy of Capsulotomy for Successful Cataract Surgery
3.1.3 Introduction to Femtosecond Laser Capsulotomy (FSLC)
3.1.4 Applications of Femtosecond Laser Capsulotomy (FLSC)
3.1.5 Introduction to Precision Pulse Capsulotomy (Zepto)
3.1.6 Applications of Precision Pulse Capsulotomy
3.2 Lens Fragmentation: Femtosecond Laser-Assisted and Micro-Interventional Lens Fragmentation
3.2.1 Historical Perspective
3.2.2 Introduction to Femtosecond Laser (FSL) for Cataract Lens Fragmentation
3.2.3 Applications for Femtosecond Laser Lens Fragmentation
3.2.4 Introduction to Micro-Interventional Lens Fragmentation
3.2.5 Applications of the miLOOP
3.2.6 Conclusion and Future Directions
References
4: Scleral-Fixated Intraocular Lenses
4.1 Introduction
4.2 Background
4.3 Indications and Risk Factors
4.3.1 Subluxation/Dislocation of the Lens
4.3.2 Inadequate Capsular Support
4.4 Glued Intrascleral Haptic Fixation of an IOL (Glued IOL)
4.4.1 Lens and Suture Selection
4.4.2 Surgical Technique
4.4.3 Modifications to the Surgical Technique
4.4.4 Outcomes
4.5 Flanged Intrascleral IOL Fixation with Double-Needle Technique (Yamane Technique)
4.5.1 Lens and Suture Selection
4.5.2 Surgical Technique
4.5.3 Outcomes
4.6 Canabrava Four-Flanged Scleral Fixation Technique
4.6.1 Lens and Suture Selection
4.6.2 Four-Flanged Scleral Fixation of a Two-Eyelet Non-Foldable IOL
4.6.3 Four-Flanged Scleral Fixation of a Four-Eyelet Foldable IOL
4.6.4 Outcomes
4.7 McCabe Belt Loop Technique for Scleral Fixation
4.7.1 Lens and Suture Selection
4.7.2 Surgical Technique
4.7.3 Outcomes
4.8 Complications
4.8.1 Complications in Glued SFIOL
4.8.2 Complications in Flanged, Double-Needle SFIOL
4.8.3 Complications in Canabrava and McCabe Belt Loop SFIOL
4.9 Comparisons between Scleral Fixation Techniques
4.10 Conclusion
References
5: Iris Implants
5.1 Indications for Artificial Iris Device Implantation
5.2 Types and Manufacturers of Iris Prostheses
5.2.1 Morcher
5.2.2 Ophtec
5.2.3 HumanOptics
5.2.4 Reper-NN
5.3 Selecting an Appropriate Device
5.4 Surgical Technique
5.5 Complications of Artificial Iris Implantation
5.6 Device Availability
5.7 Future Directions
References
6: New Lenses
6.1 Introduction
6.2 Terminology
6.3 New Classification
6.3.1 Small-Aperture IOLs
6.3.1.1 The IC8-IOL (Acufocus Inc.)
6.3.2 Wavefront-Correcting IOLs
6.3.2.1 The Mini Well IOL (Sifi Medtech)
6.3.2.2 The Vivity IOL DFT015 (Alcon)
6.4 Full Range of Focus Lenses
6.4.1 RAYNER Sulcoflex Trifocal®
References
Part III: Surgical Innovations for Refractive Procedures
7: Laser Surface Ablation Procedures
7.1 Introduction
7.2 Surface Ablation
7.2.1 Photorefractive Keratectomy
7.2.2 Transepithelial PRK
7.2.3 Phototherapeutic Keratectomy
7.2.4 Conclusion
References
8: Small Incision Lenticule Extraction
8.1 Indications of SMILE Surgery
8.2 Preoperative Preparations
8.2.1 Patient Preparations
8.2.2 Instrument Preparation
8.3 Surgical Design and Procedure
8.3.1 Surgical Design
8.3.1.1 Corneal Cap
8.3.1.2 Lenticule
8.3.1.3 Incision
8.3.1.4 Energy Setting
8.3.1.5 Nomogram Adjustment
8.4 Surgical Procedures
8.4.1 Anesthesia
8.4.2 Docking
8.4.3 Centration
8.4.4 Lenticule Creation
8.4.5 Lenticule Separation and Extraction
8.4.6 Surgical Sequence Selection
8.4.7 Incision Management
8.4.8 Postoperative Management
8.5 Complications and Managements
8.5.1 Intraoperative Complications
8.5.1.1 Suction Loss
8.5.1.2 Opaque Bubble Layer (OBL)
8.5.1.3 Appearance of “Black Areas” in the Scanned Area
8.5.1.4 Difficulties in Identifying the Stromal Lenticule
8.5.1.5 Difficulties in Lenticule Separation
8.5.1.6 Tears at the Incision or Cap
8.5.1.7 Lenticular Tear or Remnant
8.5.1.8 Decentered Lenticule
8.5.1.9 Foreign Body Beneath the Cap (Interface Debris)
8.5.1.10 Bleeding
8.5.2 Postoperative Complications
8.5.2.1 Diffuse Lamellar Keratitis (DLK)
8.5.2.2 Corneal Stromal Haze
8.5.2.3 Corneal Striae or Folds
8.5.2.4 Epithelial Island or Epithelial Ingrowth
8.5.2.5 Infection
8.5.2.6 Corneal Sterile Infiltrates
8.5.2.7 Dry Eye
8.5.2.8 Symptoms of Poor Vision: Cloudy Vision, Glare, and Halo
8.5.2.9 Regression or Under-Correction
8.6 Refractive Outcomes of SMILE
8.6.1 Long-Term Outcomes
8.6.2 Outcomes of High Myopia
8.6.3 Outcomes of Myopic Astigmatism
8.6.4 Outcomes of Higher-Order Aberrations
8.7 Advantages of SMILE
8.7.1 Stability of Corneal Biomechanics
8.7.2 Less Corneal Damage and Faster Corneal Nerve Recovery
8.7.3 Wound Healing
8.8 Lenticule Tissue Applications
8.9 Future Directions
References
9: Phakic Intraocular and Implantable Collamer Lenses
9.1 Introduction
9.2 Types of PIOL
9.3 Indications and Contraindications
9.4 Preoperative Evaluation
9.5 Sizing of the ICL
9.6 Surgical Technique
9.7 Outcomes
9.8 Complications
9.8.1 Endothelial Cell Loss
9.8.2 Glaucoma
9.8.3 Cataract
9.9 Future Directions
References
10: Corneal Cross-Linking
10.1 Background
10.2 Indications
10.3 Contraindications
10.4 Procedure
10.5 Postoperative Care
10.6 Complications
10.7 Variations of Standard Technique
10.7.1 Modifications to Riboflavin Delivery
10.7.2 Modifications to UV Exposure
10.7.3 Modifications to Oxygen Availability
10.8 Treatment Outcomes
10.9 CXL-Plus (“Refractive-Plus”)
10.9.1 Conductive Keratoplasty
10.9.2 Surface Ablation
10.9.3 Phakic IOLs
10.9.4 LASIKxtra
10.10 Future Directions/Novel Uses
References
Part IV: Surgical Innovations for Cornea and External Diseases
11: Simple Limbal Epithelial Transplantation
11.1 Introduction and History
11.2 Indications
11.3 Contraindications and Poor Prognostic Factors
11.4 Surgical Technique
11.5 Postoperative Care and Follow-Up
11.6 Advantages
11.7 Complications
11.8 Modifications and Recent Advances
11.9 Outcomes
11.10 Concluding Remarks and Future Directions
References
12: Updates on Therapy for Cornea Edema
References
13: Corneal Neurotization
13.1 Introduction
13.2 Neurotrophic Keratopathy
13.2.1 Anatomy and Pathophysiology
13.2.2 Diagnosis and Clinical Presentation
13.2.3 Management
13.3 Development and Physiology of Corneal Neurotization
13.3.1 History
13.3.2 Corneal Nerve Regeneration and Functionality
13.4 Modern Corneal Neurotization Techniques
13.4.1 Anatomy of Donor Nerves and Coaptation
13.4.2 Direct Approaches (Table 13.1)
13.4.3 Nerve Graft-Based (“Indirect”) Approaches (Table 13.2)
13.4.4 Comparative Analysis and Outcomes
13.5 Current Limitations and Controversies
13.6 Future Directions
References
14: Keratoprosthesis
14.1 Introduction
14.2 Design
14.3 Indications
14.3.1 Inclusion and Exclusion Criteria
14.3.2 Implications of the Underlying Indication on Outcomes
14.3.3 Specific Indications and Considerations for Keratoprosthesis Implantation
14.3.3.1 Prior Graft Failure
14.3.3.2 Limbal Stem Cell Deficiency
14.3.3.3 Primary Keratoprosthesis Implantation
Chronic Hypotony and Pre-Phthisis
14.3.3.4 Pediatric Keratoprosthesis Implantation
14.3.3.5 Bilateral Keratoprosthesis Implantation
14.4 Preoperative Evaluation
14.4.1 Eyelid and Blink Function Assessment
14.4.2 Ocular Surface and Anterior Segment Examination
14.4.3 Evaluation of Glaucoma Status
14.4.4 Posterior Segment Evaluation and Assessment of Potential for Vision
14.5 Surgical Technique and Intraoperative Considerations
14.6 Postoperative Management
14.6.1 Antimicrobial Prophylaxis
14.6.2 Bandage Contact Lens
14.6.3 Glaucoma Management
14.6.3.1 Other Considerations
14.7 Outcomes
14.7.1 Visual Outcomes
14.7.2 Retention Outcomes
14.8 Complications
14.8.1 Retroprosthetic Membrane
14.8.2 Glaucoma
14.8.3 Sterile Corneal Necrosis
14.8.4 Infectious Keratitis
14.8.5 Endophthalmitis
14.8.6 Idiopathic Vitritis
14.8.7 Other Posterior Segment Complications
14.8.7.1 Hypotony
14.9 Future Directions
References
Part V: Surgical Innovations for Glaucoma
15: Microinvasive Glaucoma Surgery
15.1 Introduction
15.2 Schlemm’s Canal Devices/Procedures
15.2.1 Trabectome
15.2.2 iStent and iStent Inject
15.2.3 Kahook Dual Blade
15.2.4 Hydrus Microstent
15.3 Ab Interno Trabeculotomy Procedures and Devices
15.3.1 Gonioscopy-Assisted Transluminal Trabeculotomy
15.3.2 Omni
15.4 Suprachoroidal Devices
15.4.1 Cypass
15.4.2 iStent Supra
15.5 Subconjunctival Devices
15.5.1 XEN® Gel Stent
15.5.2 PRESERFLO (InnFocus) MicroShunt
15.6 Cycloablation Procedures
15.6.1 Endoscopic Cyclophotocoagulation
15.7 Economic and Quality of Life Considerations
15.8 Ethical Considerations
15.9 Quality of Evidence
15.10 Conclusion
References
16: Ahmed ClearPath, PAUL Glaucoma Implant, and Aurolab Aqueous Drainage Implant
16.1 Glaucoma Drainage Devices
16.1.1 Preoperative Considerations
16.1.2 Surgical Technique and Pearls
16.1.3 Postoperative Management and Monitoring
16.2 Ahmed Clearpath Glaucoma Drainage Device
16.2.1 Introduction
16.2.2 Features of the Device
16.2.3 Advantages and Disadvantages
16.2.4 Clinical Studies
16.3 AUROLAB Aqueous Drainage Implant
16.3.1 Introduction
16.3.2 Features of the Device
16.3.3 Advantages and Disadvantages
16.3.3.1 Clinical Studies
16.4 PAUL Glaucoma Drainage Implant
16.4.1 Features of the Device
16.4.2 Advantages and Disadvantages
16.5 Clinical Studies
16.6 Special Populations and Considerations
16.7 Future Directions
References
Part VI: Surgical Innovations for Retina
17: Advances in Vitrectomy
17.1 Introduction
17.2 Advances in Gauge Size
17.3 Advances in Duty Cycle
17.4 Other Advances in Vitreous Cutters
17.5 Advances in Fluidics
17.6 Advances in Forceps and Adjunct Tools
17.7 Advances in Lighting
17.8 Conclusion
References
18: Advancements in Visualization
18.1 Introduction
18.2 Addressing the Media
18.3 Wide-Angle Viewing Systems
18.4 Macula Flat Lenses
18.5 Chromovitrectomy
18.6 Endoillumination
18.7 Three-Dimensional Heads-Up Visualization
18.8 Endoscopic Vitrectomy
18.9 Intraoperative Optical Coherence Tomography
18.10 Conclusion
18.11 Future Directions
References
19: New Avenues of Delivery (Subretinal Gene Therapy, Port Delivery, Suprachoroidal)
19.1 Introduction
19.2 Subretinal Delivery
19.2.1 Surgical Maneuvers
19.2.2 Gene Therapy
19.2.3 Stem Cell Transplantation
19.2.4 Retinal Implants
19.3 Surgically Implanted Extended-Release Therapeutic
19.3.1 Introduction
19.3.2 The Surgical Implantation of the Port Delivery Device
19.3.3 The Usage and Refill of the Port Delivery Device
19.3.3.1 Ranibizumab PDS System
19.3.4 The Results of the Port Delivery System
19.3.5 Discussion of the Port Delivery System
19.4 Suprachoroidal Delivery
19.5 Conclusion
References
Part VII: Surgical Innovations for Strabismus
20: Vessel-Sparing Strabismus Surgeries
20.1 Introduction
20.2 Partial Tenotomy
20.2.1 Surgical Technique
20.3 Plication
20.3.1 Surgical Technique
20.4 Vessel-Sparing Transposition Techniques
20.4.1 Surgical Technique
20.4.1.1 Nishida Procedure
20.4.1.2 Superior Rectus Transposition (SRT)
20.4.1.3 Inferior Rectus Transposition (IRT)
20.4.1.4 Vertical Rectus Transposition (VRT) with Adjustable Technique
20.5 Future Directions
References

Citation preview

Current Practices in Ophthalmology Series Editor: Parul Ichhpujani

Edmund Tsui Simon S. M. Fung Rohan Bir Singh   Editors

Current Advances in Ocular Surgery

Current Practices in Ophthalmology Series Editor Parul Ichhpujani, Department of Ophthalmology, Government Medical College and Hospital, Chandigarh, India

This series of highly organized and uniform handbooks aims to cover the latest clinically relevant developments in ophthalmology. In the wake of rapidly evolving innovations in the field of basic research, pharmacology, surgical techniques and imaging devices for the management of ophthalmic disorders, it is extremely important to invest in books that help you stay updated. These handbooks are designed to bridge the gap between journals and standard texts providing reviews on advances that are now part of mainstream clinical practice. Meant for residents, fellows-in-training, generalist ophthalmologists and specialists alike, each volume under this series covers current perspectives on relevant topics and meets the CME requirements as a go-to reference guide. Supervised and reviewed by a subject expert, chapters in each volume provide leading-edge information most relevant and useful for clinical ophthalmologists. This series is also useful for residents and fellows training in various subspecialties of ophthalmology, who can read these books while at work or during emergency duties. Additionally, these handbooks can aid in preparing for clinical case discussions at various forums and examinations.

Edmund Tsui  •  Simon S. M. Fung Rohan Bir Singh Editors

Current Advances in Ocular Surgery

Editors Edmund Tsui Stein Eye Institute University of California, Los Angeles Los Angeles, CA, USA

Simon S. M. Fung Stein Eye Institute University of California, Los Angeles Los Angeles, CA, USA

Rohan Bir Singh Department of Ophthalmology Massachusetts Eye and Ear Harvard Medical School Boston, MA, USA

ISSN 2523-3807     ISSN 2523-3815 (electronic) Current Practices in Ophthalmology ISBN 978-981-99-1660-3    ISBN 978-981-99-1661-0 (eBook) https://doi.org/10.1007/978-981-99-1661-0 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 This work is subject to copyright. All rights are solely and exclusively licensed 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, expressed 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

To our families, mentors, and friends. ~ Edmund Tsui and Simon Fung To my mentor, Dr. Reza Dana, for being a perpetual source of inspiration and not giving up on me! ~ Rohan Bir Singh

Preface

In the last century, the field of ophthalmology has seen remarkable advances in our foundation of knowledge and surgical interventions. The development of microsurgical instrumentation has led to tremendous improvements in the outcomes of surgical procedures. Technological breakthroughs dramatically improved our understanding of ocular anatomy and physiology, allowing innovative surgical approaches to be developed. This book, Current Advances in Ocular Surgery, is a comprehensive guide to the most recent advances in surgical techniques for the treatment of a wide spectrum of ophthalmic disorders. These novel advancements have revolutionized the way we manage ocular conditions: from the use of injectables for aesthetics and cosmetics to new avenues of treatment delivery such as subretinal gene therapy, the advances in ocular surgery have transformed the landscape of eye care, leading to improved patient outcomes and quality of life. Each section of this book delves into the latest surgical techniques and devices used in the field, and each chapter is written by experts in the respective fields, providing a detailed analysis of each surgical technique including the indications, contraindications, advantages, and disadvantages of each. The text is also illustrated with high-quality images, diagrams, and videos that help to illustrate the techniques being discussed. We hope that this book will be a valuable resource for both trainees and seasoned ophthalmologists alike, who are interested in keeping up-to-date with the latest advancements in ocular surgery. Los Angeles, CA, USA Los Angeles, CA, USA  Boston, MA, USA 

Edmund Tsui Simon S. M. Fung Rohan Bir Singh

vii

Contents

Part I Surgical Innovations for Adnexal and Oculoplastics  1 Injectables: Aesthetics and Cosmetics ����������������������������������������������������������   3 Maja Magazin, Marissa K. Shoji, Ann Q. Tran, and Andrea A. Tooley   2 Fornix Reconstruction ������������������������������������������������������������������������������  39 Pallavi Singh and Daniel B. Rootman Part II Surgical Innovations for Cataract   3 Capsulotomy  and Lens Fragmentation����������������������������������������������������  59 Andres Parra, Joseph Tran, and Mitra Nejad   4 Scleral-Fixated Intraocular Lenses����������������������������������������������������������  73 Nhon T. Le and Zaina Al-Mohtaseb   5 Iris Implants ����������������������������������������������������������������������������������������������  89 Justin J. Park and Kevin M. Miller   6 New Lenses ������������������������������������������������������������������������������������������������ 109 Martin Dirisamer Part III Surgical Innovations for Refractive Procedures   7 Laser Surface Ablation Procedures���������������������������������������������������������� 123 Benjamin B. Bert   8 Small  Incision Lenticule Extraction �������������������������������������������������������� 135 Yan Wang, Jiaonan Ma, and Vishal Jhanji   9 Phakic  Intraocular and Implantable Collamer Lenses�������������������������� 157 Shokufeh Tavassoli and Mohammed Ziaei 10 Corneal Cross-Linking������������������������������������������������������������������������������ 175 Minh T. Nguyen, Thomas Meirick, Shu Feng, and Michele D. Lee

ix

x

Contents

Part IV Surgical Innovations for Cornea and External Diseases 11 Simple Limbal Epithelial Transplantation���������������������������������������������� 189 Hiren Matai, Shweta Agarwal, Bhaskar Srinivasan, and Geetha Iyer 12 Updates  on Therapy for Cornea Edema�������������������������������������������������� 201 Kishan Gupta and Sophie X. Deng 13 Corneal Neurotization ������������������������������������������������������������������������������ 217 Angela Y. Zhu, Gregory H. Borschel, and Asim Ali 14 Keratoprosthesis���������������������������������������������������������������������������������������� 241 Reza Ghaffari and Ali Massoudi Part V Surgical Innovations for Glaucoma 15 Microinvasive Glaucoma Surgery������������������������������������������������������������ 271 Annie M. Wu, Courtney L. Ondeck, and Nazlee Zebardast 16 Ahmed  ClearPath, PAUL Glaucoma Implant, and Aurolab Aqueous Drainage Implant �������������������������������������������������������������������������������������� 295 Gregory Fliney, Christopher C. Teng, Ji Liu, and Soshian Sarrafpour Part VI Surgical Innovations for Retina 17 Advances in Vitrectomy���������������������������������������������������������������������������� 313 Saagar Pandit, Yasha Modi, and Nitish Mehta 18 Advancements in Visualization ���������������������������������������������������������������� 325 Lindsay M. Foley and Vaidehi S. Dedania 19 New  Avenues of Delivery (Subretinal Gene Therapy, Port Delivery, Suprachoroidal)������������������������������������������������������������������������������������������ 339 Archana A. Nair, Siyang Chaili, and Janice C. Law Part VII Surgical Innovations for Strabismus 20 Vessel-Sparing Strabismus Surgeries������������������������������������������������������ 355 Yoon H. Lee, Federico G. Velez, and Stacy L. Pineles

About the Editors

Edmund Tsui, MD  is currently an assistant professor of ophthalmology at the UCLA Stein Eye Institute and the David Geffen School of Medicine at UCLA, USA.  He completed his medical training at Dartmouth Medical School, followed by residency training at New York University and a uveitis and ocular inflammation fellowship at the Francis I. Proctor Foundation and UCSF. His research interests are in clinical trials and imaging in ocular inflammatory diseases. He has published over 80 peer-reviewed papers and has given talks at national and international conferences. He is part of the American Uveitis Society Executive Committee. He also serves on the ARVO Professional Development and Education Committee and is Chair of the  Young Uveitis Specialists Communications Committee. Simon  S.  M.  Fung, MD, MA, FRCOphth  is an assistant professor of ophthalmology  at the UCLA Stein Eye Institute and the David Geffen School of Medicine at UCLA, USA. He completed his medical training at the University of Oxford, followed by ophthalmology residency at the Moorfields Eye Hospital in London, England. After a fellowship in adult cornea and external disease at Moorfields, Dr. Fung undertook an additional fellowship in pediatric cornea and external diseases at The Hospital for Sick Children in Toronto, Canada. Dr. Fung’s research interests are in pediatric cornea and ocular surface diseases. He has published over 40 peer-reviewed articles and is on the editorial board of Journal of Pediatric Ophthalmology and Strabismus. He is part of the Young Ophthalmologists Committees of both the American Academy of Ophthalmology and the European Society of Ophthalmology. Rohan Bir Singh, MD  is a fellow at the Laboratory of Corneal Immunology, Transplantation and Regeneration at the Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, USA.  His research interests include immunopathogenesis of dry eye disease, immunology of corneal graft rejection, and epidemiology of corneal disorders in the United States. He is a PhD candidate at the Leiden University Medical Center (The Netherlands) with concentration in ocular immunology. He is also a visiting senior lecturer of Ophthalmology at the University of Adelaide (Australia) and honorary research associate at the Department of Ophthalmology, Great Ormond Street Institute of Child Health, University College London (United Kingdom). He has more than 70 peer-reviewed publications and chapters.

xi

Part I Surgical Innovations for Adnexal and Oculoplastics

1

Injectables: Aesthetics and Cosmetics Maja Magazin, Marissa K. Shoji, Ann Q. Tran, and Andrea A. Tooley

Chapter Summary • Hyaluronic acid fillers, the most commonly used class of dermal fillers, are ­characterized by their hyaluronic acid concentration, degree of cross-linking, hydrophilicity, cohesivity, and particle size, all of which influence their performance, duration, and cosmetic indication. • Indications for soft tissue filler include treatment of static and dynamic facial wrinkles and folds, contour defects, facial scarring, and volume loss caused by chronological aging and medical disease. • The glabella, temples, and nasolabial folds are considered high risk filler ­injection zones due to their proximity to the supratrochlear and supraorbital arteries as improper injection techniques can lead to retrograde occlusion of the ophthalmic artery and irreversible vision loss.

Maja Magazin and Marissa K. Shoji have contributed equally to this work. M. Magazin Department of Ophthalmology, Medical College of Georgia at Augusta University, Augusta, GA, USA M. K. Shoji Department of Ophthalmology, University of Miami, Bascom Palmer Eye Institute, Miami, FL, USA A. Q. Tran Department of Ophthalmology, University of Illinois of Chicago, Illinois Eye and Ear Infirmary, Chicago, IL, USA A. A. Tooley (*) Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA e-mail: [email protected] © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 E. Tsui et al. (eds.), Current Advances in Ocular Surgery, Current Practices in Ophthalmology, https://doi.org/10.1007/978-981-99-1661-0_1

3

4

M. Magazin et al.

• Botulinum toxin (Botox), a naturally occurring bacterial neurotoxin, prevents the release of acetylcholine from presynaptic cholinergic receptors, thus inhibiting contraction of the injected muscle. Various formulations of Botox are available for treatment of facial wrinkles and facial asymmetry, and non-surgical contouring of the eyebrows and lower face. • The muscular effects of Botox are typically seen approximately 1–2 weeks after injection and last approximately 3–4  months depending on the formulation. Complications from Botox are rare and usually related to injection technique.

1.1 Soft Tissue Filler 1.1.1 Introduction Soft tissue fillers have gained tremendous popularity as a minimally invasive intervention for restoring volume loss and facial symmetry due to chronological aging, disease, and trauma [1]. The use of filler for facial reconstruction dates back to the 1830s when the first injectable agent, paraffin was introduced followed by autologous fat in the 1890s. It was not until 1981, when Zyderm®, a bovine collagen filler, became the first Food and Drug Administration (FDA) approved agent for soft tissue reconstruction [2, 3]. Since then, various agents have been developed. In 2003, the FDA approved Restylane®, a product made from hyaluronic acid (HA). Shortly after, the market for dermal fillers experienced rapid growth with over 2.5 million injectable procedures performed in the United States in 2019 alone [4].

1.1.2 Clinical Applications Cosmetic applications of soft tissue dermal filler include facial rejuvenation, contouring, and augmentation to correct superficial and deep defects caused by volume loss. The FDA approved areas of injection include the nasolabial folds, perioral lines, lips, cheeks, chin, and back of the hand, patients with facial lipoatrophy, contour deficiencies, and facial scaring from acne. Many off labeled uses have developed over time. Functional applications include treatment of eyelid retraction in thyroid eye disease, lagophthalmos, eyelid malposition, and anophthalmic enophthalmos [5–8].

1.1.3 Categories of Dermal Filler There are two categories of dermal fillers: non-biodegradable and biodegradable (Table 1.1). Non-biodegradable soft tissue fillers such as silicone and poly-methyl methacrylate (PMMA) are more permanent agents with a longevity of 5 years or more [9]. Biodegradable fillers consist of nonpermanent products that can be further divided into long-acting agents such as calcium hydroxyapatite (CaHA) and

5

1  Injectables: Aesthetics and Cosmetics Table 1.1  Categorization of soft tissue dermal fillers. Various compositions of non-biodegradable and biodegradable soft tissue dermal fillers

Non-biodegradable fillers Silicone Polyalkylimide Poly-methyl methacrylate Harvested fat

Biodegradable fillers Calcium hydroxyapatite Collagen Hyaluronic acid Poly-l-lactic acid

poly-­l-­lactic acid (PLLA) with a duration between 15 and 24 months and shortacting agents such as collagen and hyaluronic acid (HA) with a duration between 3 and 24 months [10].

1.1.3.1 Non-biodegradable Fillers Poly-Methyl Methacrylate (PMMA) Poly-methyl methacrylate (PMMA) consists of non-resorbable microspheres within a collagen vehicle. Artefill® was approved for correction of nasolabial folds in 2006 but was re-branded in 2014 as Bellafill® which is indicated for severe, atrophic acne scars [1, 11]. Malar augmentation in patients with age-related malar lipoatrophy has also been performed with PMMA [12]. It is recommended that patients undergo skin allergy testing prior to treatment [3]. Silicone Silicone, composed of dimethylsiloxanes was one of the first filler agents used for cosmetic volumization in the 1960s. Given the high risk of embolism, granulomatous reactions, and fistula formation, liquid silicone was banned by the FDA in 1991–1992 [3]. Polyalkylimide Polyalkylimide (Aquamid®) is a semi-permanent non-absorbable soft tissue filler [13]. This filler has been used internationally and approved in Europe since 2001 for facial augmentation and minor body contouring. It has been available in 40 countries internationally and currently undergoing pre-market approval with the FDA in the United States.

1.1.3.2 Biodegradable Fillers Collagen The first injectable soft tissue filler used for facial cosmetic enhancement was derived from bovine collagen in the 1980s [3]. In the early 1980s, an injectable collagen filler, Zyderm I® was developed for the correction of superficial rhytids and scars while Zyderm II® and Zyplast® were indicated for deeper rhytids and scars [10, 14]. These bovine derived collagen fillers may require allergy testing prior to use [14, 15]. In 2003, dermal fillers composed of purified human collagen— CosmoDerm® and CosmoPlast®—received FDA approval for correction of superficial and deep contour deficiencies, respectively. Both products had a limited duration of 2–3 months [10, 14].

6

M. Magazin et al.

Calcium Hydroxyapatite (CaHA) Radiesse® is a synthetic, semi-permanent filler composed of calcium hydroxyapatite (CaHA) microspheres suspended in a carboxymethylcellulose gel. It was FDA approved in 2006 for correction of moderate to severe facial rhytids, such as the nasolabial folds, and HIV associated facial lipoatrophy [9]. After injection, the gel reabsorbs over a period of 3 months after which the microspheres stimulate local collagen production leading to volumization for an average duration of 12–18 months [16, 17]. In 2015, the FDA approved Radiesse® for hand rejuvenation. Additionally, it is used in non-surgical rhinoplasty and volume restoration to the temporal fossa, marionette lines, oral commissure, and pre-jowl sulcus [18]. Poly-l-Lactic Acid (PLLA) Poly-l-lactic acid (PLLA) is a synthetic, semi-permanent, nonimmunogenic polymer that stimulates collagen production through local secondary inflammation, leading to gradual volumization [16]. Sculptra® was approved in 2004 for correction of HIV associated facial lipoatrophy and in 2009 for aesthetic volume augmentation in areas such as the nasolabial folds. Sculptra® is indicated for correction of superficial to deep facial wrinkles and folds but has also been used for restoring volume in the maxilla and deep temporal fossa [19, 20]. PLLA is unique in that it must be diluted with 5 mL or more of sterile water at least 2 h prior to injection, with higher volumes allowing for greater particle diffusion. Some injectors advocate for at least 24 h of product hydration to ensure proper particle diffusion and to decrease the risk of nodule formation [21, 22]. Hyaluronic Acid Fillers (HA) Hyaluronic acid is a naturally occurring hydrophilic protein composed of cross-­ linked N-acetyl-glucosamine and glucuronic acid [16]. The structural and water binding properties of HA fillers allow for volumization through hydration, direct fill, and neocollagenesis. Unlike other soft tissue fillers, HA fillers are dissolvable with an injectable enzyme, hyaluronidase (Hylenex®). This is especially important in the setting of post-injection complications such as vascular necrosis. Given their properties, HA fillers have become the most common dermal filler injected within the market with various product choices (Table 1.2). The effect of HA soft tissue filler depends on the HA concentration, degree of cross-linking, hydrophilicity, cohesivity, and particle size. These properties determine the rheologic and viscoelastic properties of HA fillers and subsequently influence their performance, duration, and clinical indication [17]. A higher HA concentration and cross-linking result in higher elastic modulus (G′), creating a “firmer” gel with lower diffusion tendency. Products with a higher G’ have a higher lift capacity and are more suitable for volume replacement and contouring of deeper defects in the mid face, jaw, and temporal fossa [17, 23]. The hydrophilicity is determined by HA concentration and degree of cross-linking. Products with a higher concentration tend to absorb higher degrees of water affecting the hydrophilicity of a product. This effect may be favorable with lip augmentation where a product with higher hydrophilicity may be desired but should be avoided in the tear trough where a lower hydrophilicity product should be used [24].

1  Injectables: Aesthetics and Cosmetics

7

Table 1.2  Hyaluronic acid soft tissue dermal fillers. Types and properties of hyaluronic acid soft tissue dermal fillers HA Year of concentration FDA approval (mg/mL) Trade name Allergan aesthetics/AbbVie 2006 24 Juvéderm 2010 ultra Juvéderm ultra XC

Cross-­ linking technology Hylacross

Juvéderm ultra + Juvéderm ultra +XC

2008 2010

24

Hylacross

Juvéderm Volbella Juvéderm Volbella XC

2011

15

Vycross

Juvéderm Voluma XC

2013

20

Vycross

Juvéderm Vollure Juvéderm Vollure XC Juvéderm Volux Juvéderm Volite

2013

17.5

Vycross

2022

25

Vycross

PMA1

12

Vycross

2003 2012

20

NASHA

2007

12

NASHA

Galderma Restylane Restylane-L

Restylane Lyft

Indications

Duration

Moderate to severe facial wrinkles and folds, lip augmentation, periorbital wrinkles Moderate to severe facial wrinkles and folds, nasal sculpting, jaw line sculpting, nasal sculpting Perioral wrinkles, moderate to severe facial wrinkles and folds, lip augmentation, periorbital lines, tear trough augmentation Cheek and chin augmentation to correct volume loss in the midface, nasal sculpting Moderate to severe facial wrinkles and folds

6–12 months

Chin and jaw volumization Skin smoothing, correction of cutaneous lines

24 months

Moderate to severe facial wrinkles and folds, lip augmentation Upper perioral wrinkles, lip augmentation, cheek augmentation

6–12 months

12 months

18–24 months

12–18 months

6–9 months

6 months

6–12 months

(continued)

8

M. Magazin et al.

Table 1.2 (continued) Year of FDA approval 2014

HA concentration (mg/mL) 20

Cross-­ linking technology NASHA

Restylane Refyne

2016

20

XpresHAn

Restylane Defyne

2016

20

XpresHAn

Restylane Kysse

2020

20

XpresHAn

Restylane Contour

2021

20

XpresHAn

Merz Aesthetics Belotero 2011 Balance

22.5

Revance Therapeutics Teosyal 2017 RHA 2

Trade name Restylane Silk

Indications Perioral wrinkles, lip augmentation, periorbital wrinkles Moderate to severe facial wrinkles and folds, periorbital wrinkles Moderate to severe facial wrinkles and folds, chin augmentation Upper perioral wrinkles, lip augmentation Volume deficiencies in the midface region, cheek augmentation

Duration 6 months

CPM2

Moderate to severe facial wrinkles and folds, tear trough augmentation

6 months

23

Resilient HA3

Moderate dynamic facial wrinkles and fold such as glabella winkles, perioral lines, periorbital lines Moderate to severe deep dynamic facial wrinkles and folds such as nasolabial folds, cheek augmentation Moderate to severe dynamic facial wrinkles and folds, cheek and jaw line augmentation

6 months

Teosyal RHA 3

2017

23

Resilient HA

Teosyal RHA 4

2017

23

Resilient HA

12 months

12 months

12 months

9 months

6 months

6 months

9

1  Injectables: Aesthetics and Cosmetics Table 1.2 (continued)

Trade name Revanesse Revanesse Lips Revanesse Versa Anika Therapeutics Hydrelle/ Elevess Mentor Corporation Prevelle Silk

Year of FDA approval

HA concentration (mg/mL)

Cross-­ linking technology

Indications

Duration

2020

22–28

Thixofix

Lip augmentation

9–12 months

2012

25

Thixofix

Moderate to severe facial wrinkles and folds

12 months

2006

28

BCDI4

Moderate to severe facial wrinkles and folds

12 months

2008

4.5–6

DIS5

Moderate to severe facial wrinkles and folds, infraorbital volume loss

6 months

Moderate to severe facial wrinkles and folds Moderate to severe facial wrinkles and folds Fine lines and wrinkles

3–4 months

Inamed Corporation/Genzyme Corporation Hylaform 2004 4.5–6 DIS5

Hylaform Plus

2004

4.5–6

DIS5

Captique

2004

4.5–6

DIS5

3–4 months

3–6 months

Key: pending market approval Cohesive polydensified matrix 3 Hyaluronic acid 4 p-phenylene bis(ethylcarbodiimide) 5 Di-vinyl sulfone 1 2

The cross-linking technology overtime has evolved to tailor the properties of the filler without compromising duration. Depending on the product and production company, various terms have been used to describe soft tissue filler properties. For instance, Vycross® technology mixes both short and long chain HA for additional cross-linking efficiency. There are smaller amounts of high molecular HA that allow the product to be more cohesive and easier to inject and mold. The Hylacross® technology is cross-linked with longer HA chains to provide a more cohesive product with higher water uptake and hydrophilicity. Patient Selection and Evaluation A holistic approach should be taken during the aesthetic evaluation of a patient. Patients should be asked about previous filler, facial surgeries, especially cosmetic

10

M. Magazin et al.

rhinoplasty, and neurotoxin injections as these factors may influence the injection plan. Baseline asymmetry, skin elasticity, bony prominence, and fat distribution should be identified during assessment. Realistic expectations, anticipated improvement, and longevity should be discussed. Medication history should be reviewed. To help prevent unwarranted bruising, aspirin and NSAID should be discontinued for 7 days if able. Contraindications Acute soft tissue infections, allergy to lidocaine or product components, and history of bleeding disorders are considered absolute contraindications for soft tissue filler. History of keloid formation, dyspigmentation, and hypertrophic scars are relative contraindications. Patients with history of herpetic skin infections should not receive injections during active flares and should be started on prophylactic antiviral therapy prior to injection [25]. The safety of cosmetic filler in pregnancy and lactation are unknown and should therefore be avoided in these patients.

1.1.4 Preparation and Post-Operative Care 1.1.4.1 Antiseptic Technique Topical anesthetics can be used prior to filler placement to mitigate injection site pain. Bupivacaine, lidocaine, and tetracaine are anesthetic agents that should be used at least 15 min prior to injection. Products like Juvéderm Ultra Plus XC® and Restylane-L® contain local anesthetic, avoiding the need for additional injections. Topical lidocaine in a 4 or 5% formulation is also an effective option. Periprocedural cold packs can be used to decrease comfort and bruise formation as well. Patients should be instructed to remove makeup prior to injection. Proper antiseptic and sterile technique during preparation and injection is important in preventing infection. During preparation, the treatment area should be cleaned with alcohol, povidone-iodine, or chlorhexidine. However, chlorhexidine can cause irreversible corneal damage and should never be used around the eyes. Newer studies have looked at dilute solution of hypochlorous acid, both effective and safe to the periocular region [26]. 1.1.4.2 Post-Procedural Care Following injections, most providers recommend ice, elevation, and avoidance of exercise for 24 hours. Patients should be educated on the normal healing course and on potential complications for which they should seek more urgent attention, especially if there is disproportionate pain or post-operative swelling. A one-month follow-­ up should be established at which point touch-ups or corrections can be performed. Patients should be educated on the duration of effects and the need for re-treatment.

1  Injectables: Aesthetics and Cosmetics

11

1.1.5 Injection Techniques Various injection patterns have been described and are usually based on individual preference, experience, and underlying anatomy. Filler injections are packaged with a sharp, hypodermic needle that many injectors use. More recently, blunt-tipped cannulas or microcannulas were introduced as an alternative delivery method. Their design is suggested to mitigate the risk of inadvertent arterial injection by laterally displacing nearby vasculature.

1.1.5.1 Linear Threading (Anterograde and Retrograde) With linear anterograde placement, filler is injected into the target space as the needle is advanced. Conversely, in retrograde threading the needle is incorporated into the target plane and the filler material is injected in a retrograde fashion as the needle is withdrawn. Retrograde injection offers the benefit of increased safety, as intravascular injection can be more easily avoided as the needle is constantly in motion. 1.1.5.2 Serial Puncture and Depot Injections The serial puncture technique involves placement of very small aliquots of filler sequentially along a superficial line or fold such as in lip augmentation and correction of nasolabial folds. In depot injections, larger boluses of filler are placed into deeper planes, utilized in the midface of jaw. The treatment zone should be massaged immediately after both techniques to help blend the filler into the surrounding deep tissue. 1.1.5.3 Fanning and Cross Hatching Fanning and cross hatching involve injections along multiple vectors and can be used for treating large areas. In the fanning technique, filler is injected in a retrograde fashion in multiple, but evenly spaced directions without removing the needle. Cross-hatching involves multiple parallel injections followed by a series of perpendicular injections in the same area to create a grid-like pattern.

1.1.6 Anatomical Considerations and Techniques Careful attention to oculofacial landmarks and complex anastomotic vasculature is important in delivering optimal results and preventing irreversible complications (Fig.  1.1). Soft tissue filler injections can be performed throughout the face (Fig. 1.2). The glabella, temples, and nasolabial folds are considered high risk injection zones given their proximity to high-risk vasculature.

1.1.6.1 Forehead and Glabellar Furrows Hyperdynamic horizontal forehead wrinkles, lower forehead concavity, and the deep vertical lines of the glabella are amendable to filler correction. Often,

12

M. Magazin et al.

Superficial temporal artery (parietal branch) Superficial temporal artery (frontal branch)

Supraorbital artery Supratrochlear artery

Dorsal nasal artery Infraorbital artery Superior labial artery

Angular artery Facial artery

Inferior labial artery

Fig. 1.1  Arterial supply of the face. Image demonstrating the main arterial vasculature of the face. (Made by Rohan Bir Singh using Biorender.com) Fig. 1.2  Soft tissue filler injection zones. Illustration demonstrating anatomic facial zones where soft tissue fillers are commonly injected. (Made by Rohan Bir Singh using Biorender.com)

1  Injectables: Aesthetics and Cosmetics

13

combination therapy with neurotoxin and soft tissue filler is used to achieve a smooth contour while simultaneously lifting the eyebrows. The glabella is considered one of the most high-risk injection zones given its proximity to the supratrochlear and supraorbital arteries which can lead to retrograde occlusion of the ophthalmic artery. Improper injections can result in permanent blindness. The supratrochlear artery lies within the corrugator crease about 17 mm from the midline while the supraorbital artery lies within the supraorbital crease 22 mm from the midline [27]. Superficial injections are considered safer in this area. Products with a low elastic modulus such as Belotero®, Juvéderm Volbella®, Juvéderm Ultra XC®, and Restylane Refyne® are preferred in this area. Volumes of 0.3–0.5  mL should be injected using either retrograde linear threading or cross-­ hatching. The corrugator crease and supraorbital crease where the supratrochlear and supraorbital artery run, respectively, should be avoided.

1.1.6.2 Forehead and Temporal Fossa Temple volumization is indicated for treatment of concavity caused by muscle atrophy and can be achieved with superficial or deep injections. The anatomic layers of the temporal region include the skin, subcutaneous tissue, temporoparietal fascia, superficial temporal fascia, loose areolar tissue, deep temporal fascia, superficial temporal fat pad, temporalis muscle, periosteum, and bone [27]. The frontal branch of the superficial temporal artery, which lies within the superficial temporal fascia, and the middle temporal vein are of particular concern in this region. Anastomosis of the superficial temporal artery with the supraorbital or supratrochlear artery within the frontalis muscle can lead to retrograde emboli [28]. The middle temporal vein runs in the temporal fat pad and has been shown to have great variability in its lumen diameter ranging from 0.5 to 9.1 mm, placing it at risk for accidental puncture. Non-thrombotic pulmonary embolism has been described as a severe complication of inadvertent puncture [29, 30]. Within this region, superficial or deep augmentation can be considered depending on the patient’s anatomy. For superficial injections, HA products with a low elastic modulus can be delivered with a blunt-tipped cannula to prevent inadvertent arterial puncture. For deeper injections, HA products with higher elastic modulus, CaHA, and PLLA are preferred and should be delivered in the supraperiosteal plane. These injections should occur around 10 mm above the lateral orbital rim and 10 mm lateral to the temporal crest [19, 27].

1.1.7 Periorbital Region Within the periorbita, soft tissue fillers can be injected in the eyebrow, upper eyelid, and tear troughs. Care should be taken with the superior neurovascular bundle when injecting along the eyebrow or superior sulcus. Additionally, the volume of filler should be monitored, as too much product may lead to a mechanical ptosis. Infraorbital injections are performed for tear trough deformity correction and cheek

14

M. Magazin et al.

augmentation. Special attention should be paid to the infraorbital artery which has anastomotic connections to the supraorbital and supratrochlear arteries [31]. Tear trough or infraorbital hollow injections should be slightly placed above the periosteum, as the patient may have a complication known as the Tyndall effect, where the product is visible. Care should be taken, as theoretically as an intravascular injection could retrograde into the supratrochlear artery [32].

1.1.7.1 Eyebrows Soft tissue fillers allow for three-dimensional eyebrow contouring and volumization. Elevation of the eyebrow using products with a high elastic modulus such as Restylane-L or Restylane Lyft can help restore volume loss due to chronological aging or excessive fat removal during blepharoplasty. Injections may be performed with retrograde cross-hatching [19]. 1.1.7.2 Superior Sulcus A sunken superior sulcus, also referred to as upper eyelid hollowing, can be seen with aging, chronic prostaglandin use, or after blepharoplasty. Superior sulcus deformities can also be seen following enucleations or eviscerations. Injection of 0.2–0.5 mL of HA may be placed inferior to the supraorbital rim, underneath the orbicularis muscle with a 27-gauge microcannula to mitigate the risk of iatrogenic arterial puncture. 1.1.7.3 Tear Troughs The tear trough and infraorbital hollow can be a challenging area to inject given the anatomical variation and the thin eyelid skin. Products with low water affinity and a low elastic modulus like Restylane-L® and Belotero® are preferred in this region [19]. Volbella XC® is the newest FDA approved agent for treatment of infraorbital volume loss [33]. Small volumes between 0.05 and 0.1 mL depot injections can be placed in the supraperiosteal plane to achieve deeper augmentation [24]. If injections are performed superficially, a linear threading or cross-hatching technique in the suborbicularis plane can be considered. However, care should be taken to avoid too much product, again, to avoid the Tyndall effect. While dynamic lateral periorbital wrinkles also referred to as crow’s feet are usually treated with neurotoxin, static wrinkles can be addressed with a retrograde linear threading technique.

1.1.8 Midface and Nasolabial Folds Within the midface and nasolabial folds, identification of the branches of the facial artery is important to avoid possible complications. The facial artery branches to the angular artery and lateral nasal artery within the nasolabial fold region. The dorsal nasal artery lies about 5 mm superior to the horizontal line of the medial canthus [28]. Within the nasolabial folds, retrograde flow to the ophthalmic artery through anastomotic connections with the dorsal nasal artery and supratrochlear artery can lead to vision loss.

1  Injectables: Aesthetics and Cosmetics

15

1.1.8.1 Cheek Filler placement for cheekbone enhancement should be deep in the supraperiosteal layer of the zygomatic bone. Volume restoration in the midface can indirectly enhance surrounding regions and provide an overall youthful appearance. Injections can be placed supraperiosteal along the zygoma to produce an upward lateral lift after which the anteromedial cheek can be further enhanced through a retrograde or anterograde manner. The lateral, anterior, or medial malar region can all be targeted for cheek augmentation. Products with high elastic modulus such as Restylane Lyft®, Restylane- Defyne®, Juvéderm Voluma®, Juvéderm Vollure® with deep depot injections in volumes of 0.5–1.5 mL per side are recommended [24, 31]. More recently, Restylane Contour®, formulated to provide a lift and smoother cheek contour, was approved in 2021 for cheek augmentation and correction of midface contour deficiencies [34]. Non-hyaluronic acid products such as Radiesse® and Sculptra® can also be used for correction of malar lipoatrophy [35]. Although pending market approval, Juvéderm Volite® (VYC-12L) has been used to treat fine wrinkles and improve hydration and elasticity in the malar region [36]. Volume loss in the sub-malar area can be treated with products such as Juvéderm Vollure® and Juvéderm Ultra Plus® if superficial replacement is desired or with Juvéderm Voluma® for deeper volume deficiencies. Filler can be delivered through depot injections or with the fanning technique. Injectors should be cautious of the facial artery and vein in this region [31]. 1.1.8.2 Nasolabial Folds Augmentation Augmentation of the nasolabial region can be accomplished with superficial injections in the inferior two-thirds of the nasolabial fold or with deep injections in the upper third. Correction of superficial nasolabial folds can be accomplished with Belotero®, Juvéderm Ultra XC®, Restylane-L®, or Restylane Refyne® with a fanning technique. Deep nasolabial fold defects can be corrected with firmer HA products such as Revanesse Versa®, Juvéderm Ultra Plus XC®, Restylane Lyft®, and Restylane Defyne®. Non-hyaluronic acid products like Radiesse® are also effective. Linear retrograde threading and cross-hatching are preferred for deeper defects. Recently, Revance RHA® products (TEXONE, Geneva)—with a technology designed to create high-molecule weight HA chains in a more relaxed configuration—became the first FDA approved class of HA filler for correction of moderate to severe dynamic wrinkles and nasolabial folds [37, 38]. 1.1.8.3 Nose The nasal bridge is commonly injected in cosmetic rhinoplasty as an alternative to invasive surgery. This area is a high-risk region of injection, and even in the most skilled hands, vascular necrosis and blindness can occur. Aspirations should be performed before delivery to avoid injecting into the dorsal nasal artery. Sculpting of the nasal bridge is recommended with Juvéderm Ultra Plus®, Voluma®, or Radiesse®. Injections should be performed with small depot injections or deep retrograde threading with volumes of 0.1–0.25 mL.

16

M. Magazin et al.

1.1.9 Lower Face 1.1.9.1 Perioral Region The lips are a popular region for augmentation and sculpting. Within this region, the superior labial artery can have a variable diameter. Thus, deep injections should be avoided to prevent retrograde flow due to anastamosis of the superior labial artery. The use of a microcannula may be a safer option to prevent upper lip necrosis in this area [29]. For a more subtle lip enhancement, Restylane Silk®, Juvéderm Volbella®, Vollure® are excellent products to reshape and define the lip boarders. The border of the philtrum or anatomical region known as the cupid’s bow is a very sensitive area, therefore injection pressure and rate should be low in this region [39]. For greater volume enhancement, injection of Restylane Kysse® and Juvéderm Ultra XC® with linear threading or serial punctures in the vermillion border is recommended with retrograde vertical injections. Revanesse Lips® is the newest FDA approved product for lip augmentation. Fine perioral lines may also be treated with Juvéderm Volite® or Restylane Silk® [36]. 1.1.9.2 Marionette Lines and the Oral Commissure Descent of the oral commissure and development of marionette lines are hallmarks of facial aging amendable to filler correction. Treatment of marionette lines can be achieved by injecting products such as Juvéderm Ultra Plus®, Juvéderm Vollure®, and Restylane Defyne® or Refyne® with linear threading, fanning, or serial puncture [39, 40]. Lifting the oral commissure can also be achieved with Juvéderm Ultra Plus®, Juvéderm Vollure® or Restylane Defyne® or Refyne® by directly injecting the lines of the commissure, indirectly by injecting superior and inferior to the oral commissure, or with cross-hatching [27]. Given its lifting properties, Radiesse® has also been used in marionette lines and oral commissures [20]. 1.1.9.3 Labiomental Fold and the Chin Apex Hyperdynamic muscle contractions, tissue atrophy, and changes in skin elasticity can lead to the development of a labiomental fold, also known as the mental crease. The mental artery and vein should be avoided. Aspiration should be utilized to avoid vessel penetration within this region. Superficial, slow, linear retrograde placement of Juvéderm Ultra Plus® and Juvéderm Vollure® can restore volume in this area [16, 39]. Injecting the chin apex can improve overall lower facial contour. A recessed chin can be enhanced with deep supraperiosteal injections of Juvéderm Ultra Plus XC®, Juvéderm Voluma®, Restylane Lyft®, Restylane Defyne®, or Radiesse®. Improper or excessive injection can lead to an unwanted “witch chin” appearance. 1.1.9.4 Jawline Chronological aging can lead to atrophy between the corners of the jawline and the chin, also referred to as the pre-jowl sulcus. The jawline is a vascular region; thus, aspiration should be utilized with these injections.

1  Injectables: Aesthetics and Cosmetics

17

Volume can be restored with subcutaneous injections of Juvéderm Ultra Plus® and Juvéderm Voluma® utilizing the fanning technique. Another area to consider in jawline contouring is the mandibular angle which can achieve a youthful lift with supraperiosteal injections of Restylane Lyft®, Juvéderm Voluma®, Juvéderm Ultra Plus XC®, and Radiesse® [39]. A new Juvederm product, Volux® (VYC-25), has shown high efficacy and safety in increasing jaw projection and volume [41].

1.1.10 Soft Tissue Filler Complications 1.1.10.1 Technique for Reversal Hyaluronic acid-based fillers have increased in popularity due to their reversal ability. In any injector’s office, Hylenex® or Vitrase® composed of hyaluronidase should be available. This can be injected directly into the area of filler or can be mixed with 1 cc of Hylenex® and 9 cc of pure 1% lidocaine. Typically, 0.1 mL of hyaluronidase should be used to treated every 0.2 mL of hyaluronic acid filler [42]. 1.1.10.2 Ecchymosis Ecchymosis can occur in 5–10% of patients following filler injection. Some injectors advocate the use of topical arnica. The use of small needles and icing can minimize the ecchymosis. Injection site erythema and edema can also occur but are typically mild. Severe cases can be treated with short course of oral steroids (Fig. 1.3) [25]. 1.1.10.3 Infection and Biofilm Production Reactivation of herpes simplex can occur following filler injection, especially after lip injections. Patients with history of cold sores should be started on prophylactic acyclovir or valacyclovir to prevent outbreaks [25]. Although uncommon, bacterial skin infections with streptococcus pyogenes and staphylococcus aureus can also occur. More recently, biofilms have been described as particles of filler coated with bacteria that can lead to delayed formation of sterile inflammatory nodules [43]. Good antiseptic technique and gloves should be utilized with all filler injections. a

b

Fig. 1.3  Profound edema following lip filler. Patient with (a) edema following lip filler injection, with (b) improvement 1 week later after treatment with Benadryl and Medrol dose pack

18

M. Magazin et al.

1.1.10.4 Granulomas Granulomas, or delayed focal areas of inflammation, have been reported 6–24 months following injections in 0.01–1.0% of patients [44]. CaHA and PLLA are more likely to cause granulomas. Early onset palpable bumps, or nodules, are usually related to suboptimal placement involving overly superficial or intramuscular planes. Gentle massage is initially recommended for the first 1–2 weeks. Injection of hyaluronidase can be considered to dissolve the filler. Persistent irregularities may warrant a combination of intralesional corticosteroids, surgical excision, and/or skin resurfacing. 1.1.10.5 Improper Filler Placement or Migrated Filler Reports of filler migration of improper placement of filler can lead to unwanted contour irregularities. The unforgiving thin skin of the lower eyelid is especially prone to complications from improper filler selection and technique. Hydrophilic fillers or overly superficial placement can lead to excessive fluid accumulation causing the appearance of chronic festoons [27]. In addition, overly superficial placement can lead to a bluish periorbital discoloration, referred to as the Tyndall phenomenon, which may be prevented with pre-injection cooling, displacement of malar fat, and post-injection oral corticosteroid therapy [35, 45]. Under corrections may require additional filler placement and more office visits. Over correction can yield an unnatural appearance but can be reversed with hyaluronidase (Fig. 1.4). However, injection of hyaluronidase may unmask previously treated wrinkles and folds. 1.1.10.6 Skin Necrosis Improper filler injection can lead to vascular occlusion through external vessel compression or intra-arterial obstruction from inadvertent cannulation. Injection induced tissue necrosis is a rare local ischemic complication that may present with blanching, skin duskiness, dull pain, skin break down, and ulceration [46]. The glabella is at highest risk for necrosis as it is supplied by the supratrochlear artery which has minimal collateral circulation [45]. Patient with history of cosmetic rhinoplasty whose native vasculature has been altered may be at a higher risk of filler induced necrosis with lip and nasolabial fold injections [47]. Proficient knowledge of facial and vascular anatomy and variation, especially in patients with altered native vasculature is paramount in preventing irreversible complications. Doppler ultrasound can help visualize arterial vasculature and guide a

b

Fig. 1.4  Overcorrection of superior sulcus filler. Patient with (a) superior sulcus overfilling in an anophthalmic socket on the right side which was (b) reversed with hyaluronidase

1  Injectables: Aesthetics and Cosmetics

19

injections. Selection of the right product, a gentle, low pressure retrograde injection with a large microcannulas, pre-injection aspiration, small injection volumes may mitigate the risk, and manual compression of the vessel pathway of high-risk arteries can prevent severe adverse events [48]. Treatment involves prompt recognition and immediate injection of hyaluronidase. Nitrous oxide paste can be considered. Warm compresses and topical nitroglycerin should be applied, and oral aspirin should be initiated.

1.1.10.7 Ophthalmic Complications Irreversible blindness from vascular occlusion is the most devastating complication of soft tissue filler. Vision loss may vary from no light perception to some vision, depending on the patients’ surrounding anastomosis and presence of a cilioretinal artery to provide additional macular perfusion. Most commonly, retrograde flow of filler particles can occur into the ophthalmic and retinal arteries secondary to high pressure injections [49]. The dorsum of the nose is the most common injection site associated with blindness, followed by the glabella [50]. Ophthalmic artery occlusions are most commonly due to injections in the nose. Retinal artery occlusions occur more frequently with glabellar injections [51]. There are no standard treatments for ocular complications caused by filler injection. The practitioner should immediately check the vision and pupils. Ophthalmology should be consulted. Therapies such as ocular massage, acetazolamide, systemic steroids, systemic vasodilators, anticoagulation, hyperbaric oxygen, and anterior chamber paracentesis have all been attempted with varying degrees of success [8, 50, 51]. The role of an immediate retrobulbar injection of hyaluronidase remains controversial [52]. Additionally, other ophthalmic and neurologic complications have been reported. Blockage of the ophthalmic artery will often present with ophthalmoplegia, ptosis, and severe pain due to ischemia of the choroid and extraocular muscles [27]. Vascular compromise can also lead to ocular ischemic syndrome which can present with corneal edema, ophthalmoplegia, and hypotony [53]. Cerebral infarctions with subsequent neurological deficits following glabellar injections have also been described [52].

1.2 Botulinum Toxins 1.2.1 Introduction Botulinum toxin is a naturally occurring bacterial neurotoxin that can be classified into multiple serotypes with type A predominantly used for cosmetic treatments [54, 55]. Onabotulinum toxin A was first used clinically by Scott in the early 1980s for treatment of blepharospasm, strabismus, and glabellar frown lines [56]. While botulinum toxin was initially approved by the Food and Drug Administration (FDA) for strabismus, blepharospasm, and hemifacial spasm in 1989, Botox was subsequently approved for glabellar frown lines in 2002 [57]. There has been increasing use of botulinum toxin since 2002, as the introduction of neurotoxins has facilitated a less expensive, lower-risk, and minimally invasive alternative for facial rejuvenation. Botulinum toxin injections currently comprise

20

M. Magazin et al.

the most common aesthetic procedure performed in the United States, with more than 4.4 million cosmetic Botox injections performed in 2020 [58]. Understanding of the neurotoxin, its uses, techniques for delivery, and complications is essential to optimize the cosmetic outcome and minimize complications. For the purposes of this chapter, botulinum toxin will be referred to by the commonly known name, “Botox,” although other forms of botulinum toxin including Dysport, Xeomin, and Jeuveau are commercially available.

1.2.2 Clinical Applications The use of Botox can be either cosmetic or functional. Functionally, Botox has been utilized for treatment of migraines, axillary hyperhidrosis, facial paralysis, and spasticity associated with cerebral palsy; it may also be used for esophageal spasms or anal fissures through its alteration of muscle action [59, 60]. Rimabotulinum toxin B (Myobloc, Solstice Neurosciences, San Francisco, CA) is approved for use in the USA and Europe only for the treatment of cervical dystonia and is not currently used for cosmetic purposes [61]. Botox A is currently the only form of botulinum available for cosmetic use in the United States. Common applications of cosmetic Botox include glabellar frown lines, horizontal frontalis lines, and crow’s feet periorbitally as well as to help lift the lateral and medial brow. Additional applications include nasal rhytids, masseter, mentalis, and platysma (Fig. 1.5). Fig. 1.5  Botox injection sites. Illustration demonstrating common facial aesthetic injection sites for neurotoxins. (Made by Rohan Bir Singh using Biorender.com)

1  Injectables: Aesthetics and Cosmetics

21

1.2.3 Mechanism of Action Botox is produced by the gram-positive, anaerobic Clostridium botulinum. Different serotypes (A-G) have been described, of which five (A, B, E, F, and G) have been shown to affect the human nervous system [62]. All serotypes inhibit the release of acetylcholine from the presynaptic terminal of the neuromuscular junction [63]. Botulinum toxin A is a 150 kDa polypeptide comprised of a heavy chain and light chain linked by a disulfide bond that irreversibly attaches to the cholinergic receptor of a presynaptic motor neuron [64]. This neurotoxin is incorporated into the presynaptic nerve terminal through receptor-mediated endocytosis, in which the plasma membrane of nerve cells invaginates around the toxin receptor complex to form a vesicle containing the toxin in the nerve terminal [65]. The disulfide bond is cleaved and the light chain of the toxin is released into the cytoplasm of the nerve terminal. The toxin inhibits the release of acetylcholine by cleaving the cytoplasmic protein SNAP-25 (synaptosome-associated protein of molecular weight 25 kDa), preventing vesicles from attaching to the membrane to release acetylcholine into the synaptic cleft. This blocks the neuron from propagating a nerve impulse, subsequently leading to paralysis of the injected muscles [66]. Muscle function typically recovers within 12 weeks after injection. Various formulations of Botox are in widespread use for facial rejuvenation and may be differentiated by molecular weight, protein size, serotype strain, and preparation process (Table  1.3). Currently available Botox products for cosmetic uses include four formulations with future developments on the horizon. Onabotulinum toxin A (Botox, Allergan, Inc., Irvine, CA) is available worldwide and was the first to be seen on the market. AbobotulinumtoxinA (Dysport, Galderma Laboratories, LP, Fort Worth, TX) is available in more than 65 countries including the USA and Canada. IncobotulinumtoxinA (Xeomin, Merz Aesthetics, Greensboro, NC) is available in the USA, Mexico, and parts of Europe and South America. PrabotulinumtoxinA-xvfs (Jeuveau, Evolus, Newport, CA) is the most recently developed formulation, with the pivotal trial establishing its safety and efficacy in 2015 and is currently available in the USA [66–68]. Due to differences in the molecular size, uniformity of neurotoxin complex, and potency, the dosage of Botox may vary depending on the formulation. Comparing the different products, 1 unit of onabotulinum toxin A (Botox) is thought to equal approximately 3–5  units of abobotulinumtoxinA (Dysport), 1 unit of incobotulinumtoxinA (Xeomin), and 1 unit of prabotulinumtoxinA-xvfs (Jeuveau) [69, 70]. All formulations are currently approved for the treatment of glabellar lines, with additional approval for other uses including blepharospasm, frontalis lines, and cervical dystonia depending on the toxin formulation. A recent systematic review has confirmed the safety and efficacy of prabotulinumtoxinA (Jeuveau) in treatment of moderate to severe glabellar lines, which is notable as it may be approximately 20–30% less per unit compared to onabotulinumtoxinA and therefore may be a more cost-effective option for patients [71, 72].

Abobotulinum toxin A

IncobotulinumtoxinA

PrabotulinumtoxinA

Xeomin

Jeuveau

Toxin component Onabotulinum toxin A

Dysport

Trade name Botox

Human serum albumin, NaCl, lactose, sucrose, disodium succinate, and water

Human serum albumin, sucrose

Human serum albumin, lactose

Other components Human serum albumin, lactose

900

150

300–900

Complex weight (kDA) 900

100

50 or 100

300

Units/ vial 50 or 100

2 cc

1 or 2 cc

1.5 cc

Reconstitution per company recommendations 1 or 2 cc

Freeze-­ dried

Freeze-­ dried

Freeze-­ dried

Final formulation Freeze-­ dried

FDA approved indications Chronic migraines, limb spasticity, neurogenic bladder, cervical dystonia, blepharospasm, axillary hyperhidrosis, strabismus, glabellar lines, crow’s feet frontalis lines Blepharospasm, cervical dystonia, upper and limb spasticity, glabellar lines Blepharospasm, cervical dystonia, glabellar lines, chronic sialorrhea, upper limb spasticity Glabellar lines

Table 1.3  Comparison of botulinum A toxins. Comparison of different neurotoxin formulations and FDA approved indications

22 M. Magazin et al.

1  Injectables: Aesthetics and Cosmetics

23

1.2.4 Patient Selection and Evaluation Prior to Botox injection, it is important to discuss medical and surgical history, goals, and expectations with the patient. History should be obtained including prior experiences with other neurotoxins, fillers, and cosmetic surgeries including overall effects and complications. The patient’s occupation should be considered, as singers and actors may require higher residual facial expression. The use of aspirin, other blood thinners, and herbal medications should be noted to counsel patients on the risk of bruising. Discontinuation can be considered 1–2 weeks prior to injection if not medically contraindicated. Realistic expectations should be discussed with the patient prior to injection; while the neurotoxin may temporarily improve facial rhytids, additional injections are likely to be required in the future as the neurotoxin effect is not permanent, and Botox will not address volume loss, aging spots, or skin texture. On examination, facial asymmetry and animation should be documented and discussed with the patient. Patient goals should be discussed prior to injection with tailoring of the injection sites and dosage based upon the individual aesthetic goals of each patient. The patient should be aware that the maximal effects will be seen in approximately 1–2  weeks after injection and results typically last 3–4  months depending on the formulation.

1.2.5 Contraindications Absolute contraindications for Botox include prior allergic reactions and active cutaneous infections. Dysport contains lactose and therefore should be avoided in patients with a cow milk protein allergy. Patients with neurodegenerative conditions such as myasthenia gravis, amyotrophic lateral sclerosis, and Eaton-Lambert syndrome should avoid Botox due to the risk of neuromuscular blockade [73]. Botox is considered a Category C medication in pregnant patients; therefore, injections should be deferred until after pregnancy and breastfeeding have ended [73]. Caution should be taken in injecting patients with body dysmorphic disorder and history of frequent cutaneous skin infections, inflammatory skin disease, keloid scarring, or immunocompromised status. Botox is not currently indicated for cosmetic uses in patients younger than age 18; additionally, manufacturer’s guidelines recommends Botox use only for adults younger than 65 years of age although careful use in older patients has been suggested [74]. Patients taking medications such as aminoglycosides, cholinesterase inhibitors, calcium channel antagonists, cyclosporine, and penicillamine should avoid Botox due to the risk of drug interactions. Of note, all Botox A formulations contain serum albumin, a human blood product, which may be an important consideration in patients who refuse transfusion of blood products.

24

M. Magazin et al.

1.2.6 Preparation and Post-Operative Care 1.2.6.1 Preparation and Storage Botox vials should be stored at 2–8 degrees Celsius. IncobotulinumtoxinA (Xeomin) is the only toxin that does not require refrigeration prior to reconstitution. All formulations currently require reconstitution, typically with bacteriostatic sterile, preserved or non-preserved saline. The amount of bacteriostatic sterile saline used depends on the amount of units per vial and the desired concentration. Typically, vials with 50 units should be reconstituted with 1–1.25 cc of normal saline, and 100  units can be reconstituted with 2.0–2.5  cc for approximately 4–5 units per 0.1 cc. A 300 unit vial of abobotulinum toxin A (Dysport) per company recommendations should be reconstituted with 1.5  cc of normal saline. However, many practitioners chose to reconstitute abobotulinum toxin A (Dysport) with 2.0–2.5 cc units of normal saline such that 12–15 units per 0.1 cc of abobotulinum toxin A (Dysport) is approximately equal to the strength of 4–5  units per 0.1 cc of onabotulinum toxin A (Botox). For the remaining portion of this chapter, units will be considered in onabotulinum toxin A (Botox) equivalent. Reconstituted solutions should be rolled gently to mix, as vigorous shaking may result in toxin denaturation. Per manufacturers’ recommendations, onabotulinum toxin A (Botox), and abobotulinum toxin A (Dysport), and incobotulinumtoxinA (Xeomin) should typically be used within 24 h; however, storage in the refrigerator and use at up to 1 month following reconstitution may not significantly decrease efficacy or safety [75, 76]. 1.2.6.2 Post-Procedural Care Following injection of neurotoxin, the injection site should be cleaned with standard antiseptic fashion, which can be achieved with a variety of agents including hypochlorous acid [26]. Patients should be instructed to avoid touching the site of injection to limit unintentional diffusion or infection. Patients should avoid exercise for 24  h to minimize the risk of neurotoxin spread. All patients should be seen at 2 weeks to assess if certain areas may require additional treatment. Repeat injections can be considered every 3–4 months.

1.2.7 Injection Techniques Prior to injection, the patient should be seated comfortably in an upright position with proper lighting available. Aseptic technique should always be utilized for injections. The potential injection sites should be cleaned of all external products and makeup and prepped with povidone-iodine, hypochlorous acid, or alcohol. Chlorhexidine should be used with caution around the eyes due to corneal toxicity. Static and dynamic facial lines of the upper face should be assessed, and injection points can be marked. Anesthesia is not routinely used, as injections are well tolerated with 31-gauge insulin needle [77]. However, if the patient’s pain tolerance is low, ice or topical lidocaine 5% or ice may be applied over the prospective injection

1  Injectables: Aesthetics and Cosmetics

25

sites 30 min prior to treatment or vibratory stimulus may be used to minimize the perceived injection discomfort [78, 79]. To select the sites of injection, the patient is asked to squeeze and relax the muscles in the affected areas with the surgeon identifying and marking the location of maximal skin displacement during the contraction of the muscle that is to be treated. The muscles should be relaxed prior to injection to minimize discomfort. The thumb and index finger of the noninjecting hand may be used to pinch and elevate skin at the site of injection, decreasing discomfort and facilitating localization of the injection point. The needle is inserted into the muscle layer or the subdermal tissue just above the muscle. Location, dosage, and formulation of injections should be well-documented.

1.2.8 Anatomical Considerations and Techniques 1.2.8.1 Frontalis The frontalis muscle elevates the eyebrows and the skin of the forehead. The fibers of the frontalis are oriented vertically, causing forehead wrinkles to be oriented horizontally with repeated contracture. Prior to the injection, the patient should raise his or her eyebrows to allow for assessment of the eyebrow height, overall muscle activity, and symmetry. Of note, it is important to identify individuals who use their frontalis muscle to compensate for preexisting brow ptosis or eyelid ptosis. Total paralysis of the frontalis muscle may worsen these features. Injections are performed across the central forehead and above the midline. The classic injection of the frontalis muscle includes a six-point pattern with 2.5-units per injection site. Some providers use only four-point pattern depending on the width of the forehead. For larger foreheads, two injection rows or a staggered injection pattern may be considered [80]. Injections should occur at least 2 cm above the brow, although a microdroplet technique involving the lower frontalis has been reported as a safe and effective treatment [81]. Frontalis injections in conjunction with injection of the brow depressors of the glabella may help avoid brow ptosis and eyelid ptosis. 1.2.8.2 Glabella Glabellar folds develop from the repeated contraction of the corrugator supercilii and procerus muscles. These muscles are innervated by temporal branches of the facial nerve. Both the procerus and corrugator muscles depress the brow and the forehead. The vertical folds are created by the corrugators, while the horizontal folds across the bridge of the nose are formed by the procerus muscle. These lines may be most frequently identified in patients with excessive sun exposure, nearsightedness, and habitual frowning. To assess muscle activity prior to injection, the patient should be asked to frown to highlight the horizontal and vertical folds. The classic injection pattern involves a 5-point pattern across the glabella using approximately 5  units per spot. Some providers utilize a 3-point injection pattern instead, which has been shown to also

26

M. Magazin et al.

be effective with mild glabellar lines [82]. This can be achieved with as little as 2–2.5 units per injection site. Additionally, some patients prefer to only have the corrugators injected, as they notice widening of the eyebrows with procerus injections. Injections are typically made in both the procerus and corrugators muscles in a way to protect the orbital rim and avoid migration of toxin into the levator aponeurosis. The procerus is injected between the two brows just above the bridge of the nose. The corrugators are injected superolaterally to this position. The skin overlying the respective muscle should be pinched and the needle should be angled upward to avoid inducing blepharoptosis. Digital massage may be performed following the injection in an upward direction away from the orbital rim and levator aponeurosis.

1.2.8.3 Orbicularis Oculi Hyperkinetic contraction of orbicularis oculi and hypertrophy of its fibers over time due to repeated smiling and squinting may lead to wrinkles extending radially from the lateral canthus often described as crow’s feet. The classic injection pattern occurs at the lateral aspect of the orbicularis oculi muscle in a 3-point pattern comprised of 5 units per injection site [83]. Some providers use a 2 to 3-point injection pattern with as little as 1–2.5 units per injection site. Prior to the injection, the patient is asked to smile, noting the center of the crow’s feet and assessment of the degree of orbicularis hypertrophy. During injection, the needle position should be superficial to create a subcutaneous wheal at least 1.5 cm lateral to the orbital rim and 1 cm above the zygoma. This will help avoid complications of blepharoptosis and diplopia caused by extravasation of the neurotoxin to the lateral rectus or levator muscle. Care should be taken because excess weakening of the orbicularis oculi may result in lagophthalmos and lid retraction with increased risk of ectropion and keratitis in certain patients. Additionally, many patients, particularly Asian patients, may have orbicularis hypertrophy or “jelly rolls” along the lower eyelid. This is more pronounced when patients smile. Typically, a 2-point pattern with 1–2.5 units per injection site should be given subcutaneous in the pre-tarsal orbicularis below the lower eyelid margin at the level of the medial and lateral corneal limbus. Care should be taken to avoid overdosing, as there is increased risk of lower lid retraction and ectropion. 1.2.8.4 Pharmacologic Brow Contouring Neurotoxins may be utilized to change the brow position and shape. Lateral brow ptosis may occur with aging due to gravity and loss of forehead elasticity in combination with excessive orbicularis oculi activity. Injections may be performed unilaterally or bilaterally to correct asymmetry as needed [84–86]. To elevate the lateral third of the brow, a total of 4–5 units of Botox can be injected into the orbicularis oculi, which functions as a lateral depressor of the brow. This may achieve 1–2 mm of elevation of the eyebrow and an aesthetically pleasing arch of the lateral brow. If flattening of the eyebrows is desired, focal injection of the frontalis 3 cm above the orbital rim can be performed with gradual doses. Medial injection is less common; however, the superomedial orbicularis oculi can be injected in combination with the

1  Injectables: Aesthetics and Cosmetics

27

glabella to allow for 1–2 mm of medial brow elevation. The horizontal male brow is characterized by greater muscle mass compared to females. Thus, more Botox may be needed to achieve the same level of paralysis compared to a female brow.

1.2.8.5 Nasal Rhytids Transverse nasal wrinkles on the dorsum of the nose, described as “bunny lines,” may be treated with neurotoxin. Typically, injections of 2.5–5 units of neurotoxin are given on each side of the lateral nasal bridge into the nasalis, with care to avoid the angular vessels. 1.2.8.6 Perioral Region Signs of aging around the periorbital region include lengthening and sagging of the upper lip leading to vertical wrinkles, nasolabial furrows, and drooping of the corners of the mouth with prominent marionette lines. The vertical ridges extending above and below the vermilion border on the upper and lower lips are produced by contraction of the orbicularis oris muscle. These lines are exacerbated in patients who smoke or have significant sun exposure. Patients are asked to pucker their lips with subsequent injections of 1–1.5 units given superficially above the vermilion border on the lateral side of the crease. Patients should be counseled that they may not be able to drink through a straw or whistle if this region is injected. Botox may also be injected perinasally into the levator labii superioris muscle to lengthen the upper lip and reduce nasolabial folds, which may reduce the appearance of a “gummy” smile [87]. Additionally, injection of 3–8 units into the depressor anguli oris inferior to the lateral commissure may provide elevation of the corners of the lip [88, 89]. 1.2.8.7 Masseter Masseter injections may be used for non-surgical facial contouring, masseteric hypertrophy, bruxism, and temporomandibular joint dysfunction [90–92]. Patients should be asked to clench their teeth to allow for palpation of the anterior and posterior borders of the muscle. Typically, injections of 5–10  units are used in multiple injection points for a total of approximately 25–100  units per muscle. Total doses above 20  units have been shown to achieve satisfactory results, although there may be no significant difference between 25 units and 35 units of neurotoxin injection per muscle [93, 94]. The injection should be below the tragus of the ear, posterior to the anterior border of the masseter, and 1.5 cm or more above the lower border of the mandible, with care to avoid injection into facial nerves or vessels. Injections above the tragus may increase the risk of an asymmetric smile or crooked smile. 1.2.8.8 Mentalis The mentalis muscle is located inferior to the chin wrinkle, at the tip of the chin along the mandible. Irregular dimpling of the chin can be diminished through chemical denervation of the mentalis muscle. A total of 1–2.5 units of Botox is typically injected into each side of the muscle. Care is taken to ensure the injection is both deep and lateral to avoid inadvertent weakening of the depressor labii.

28

M. Magazin et al.

1.2.8.9 Platysma The downward pull of the platysma due to aging may result in vertical fibrous bands, which may be softened through neurotoxin injection. Important anatomic structures within this region include the surrounding vessels and the sternocleidomastoid. Inadvertent injection or diffusion in the sternocleidomastoid may result in neck weakness. Small injections may also be administered along the insertion of the platysma at the jawline to subtly lift the neck [95, 96]. Before the injection, patients are asked to strain their necks to identify the bands. A 2-point pattern of 2–2.5 units per injection site is given in each band approximately 2 cm apart. The band is grasped between the thumb and the forefinger, and the solution is injected into the platysma at the subdermal level.

1.2.9 Botulinum Toxins Complications While Botox is generally considered to be safe and tolerable, complications have been documented. In a recent review of the FDA Adverse Event Reporting System, the top 10 most commonly reported adverse events included pain (9.3%), swelling (6.4%), eyelid/brow ptosis (6.1%), headache (4.3%), allergy (3.4%), vision changes (3.4%), fatigue (2.8%), facial paresis (2.6%), rash (2.3%), and dizziness (1.8%) [97]. These complications are discussed by category below: complications at the site of injection, due to technique, or systemic effects. Careful technique is essential to reduce complications of neurotoxin injection, including undertreatment, facial asymmetry, or complications due to iatrogenic muscle weakening or unintended diffusion to non-target muscles (Table 1.4). Table 1.4  Neurotoxin complications and management. Complications and management of neurotoxins. Typical re-treatment varies based on the initial neurotoxin used, but between 1 and 5 units of Botox may be required Injection area Forehead

Complication Brow ptosis Uneven treatment Ptosis

Glabella

Blepharoptosis

Brow Crow’s Feet

“Spock” Brow Ectropion Dry eye Diplopia Lip drop Facial droop Dysphagia, dysphonia, inability to use straw Dysphagia or dysphonia Neck weakness

Nasal Masseter Perioral Platysma

Management Observation or treatment of brow depressors at lateral orbicularis Treatment of non-weakened areas to provide symmetry Apraclonidine 1% two times a day Observation or treatment with apraclonidine drops Treat lateral aspect of ipsilateral frontalis Observation with lubrication Observation with lubrication Observation, temporary Fresnel prisms Observation Observation Observation Close observation Observation

1  Injectables: Aesthetics and Cosmetics

29

1.2.10 Injection Site Reactions Injection site reactions include local ecchymosis, edema, erythema, and pain at the injection and adjacent sites. Bruising can be limited by using a small gauge needle, such as an insulin syringe, and paying close attention to the superficial vessels. This is important when injecting the crow’s feet, as 10% of patients noticed bruising in this region in early clinical trials [98]. Stopping aspirin or herbal products prior to treatment may help decrease the risk of ecchymosis if not medically contraindicated. The application of cold compression following injection can also reduce bruising. Erythema and edema are rare, occurring in less than 0.06% and 0.09% of patients, respectively [99]. Pain may be due to improper injection, using diluents other than sterile saline, or injecting into an off-label site [100]. Pain may be minimized by pinching the skin and underlying muscle during injection, maintaining a slow and constant injection speed, and utilizing a distracting technique including taping of the forehead, vibration anesthesia, or a cold icepack [78, 79].

1.2.11 Under-Correction Undertreatment of an area can be mitigated by discussing expectations with a patient prior to the injection. Follow-up should occur 2 weeks later to assess for regions of undertreatment. This can be corrected by providing additional neurotoxin. Rarely, repeated neurotoxin injections may lead to decreased response to the agent through creation of neutralizing antibodies [101]. The prevalence of patients developing neutralizing antibodies after long-term treatment Botox depends on the condition to be treated and the cumulative dosage [101, 102]. While switching to a different formulation of Botox may circumvent this decreased response, secondary treatment failure has also been reported [103]. Thorough history regarding prior neurotoxin injection should be elicited from the patient.

1.2.12 Ptosis Botox-induced blepharoptosis may result from diffusion of the neurotoxin beyond the orbital septum to the levator palpebrae superioris muscle [104]. Blepharoptosis may be more commonly associated with glabellar injections [105]. The overall incidence of eyelid ptosis has decreased over time, and found to be as low as 0.71%, due to increased clinical experience and improved injection techniques [99]. Blepharoptosis can be minimized by protecting the orbital rim during these injections and utilizing an upward digital massage immediately afterwards. Apraclonidine may be used as a treatment option to reverse blepharoptosis through stimulation of Müller’s muscle to allow for 1–2 mm of eyelid elevation (Fig. 1.6) [106, 107].

30

M. Magazin et al.

1.2.13 Brow Ptosis Brow ptosis and loss of expressivity are the most common complaints of frontalis injection. These complications are reported to occur in 13.4% of patients [99]. Injections in the frontalis muscle should be 2 cm above the supraorbital margin or eyebrow. Injections may be modified to occur subcutaneously rather than intramuscularly into the frontalis to weaken rather than paralyze the muscle [108]. If brow ptosis does occur, injection of the lateral orbicularis oculi may lift the brow.

1.2.14 Brow Asymmetry Brow asymmetry may also occur; thus, brow asymmetry should be noted at the time of initial evaluation (Fig. 1.7). The “Spock” brow occurs when there is continued function of the lateral frontalis, resulting in raising of the brow tail. This may be corrected by injection 1–1.25 units along the lateral frontalis below the midline of the forehead and above the lateral eyebrow.

1.2.15 Diplopia, Lagophthalmos, and Dry Eyes Complications from injection of the lateral orbicularis oculi to address crow’s feet rhytids may include diplopia, lagophthalmos, and dry eyes. Injections should be placed 1.5 cm lateral to the lateral canthus to limit diplopia due to extravasation of neurotoxin to the lateral rectus muscle [105]. Dry eye or ectropion may result from a

b

Fig. 1.6  Botox induced blepharoptosis. Image demonstrating (a) left sided blepharoptosis following Botox injection that (b) resolved with apraclonidine 1% drops Fig. 1.7  Brow asymmetry following Botox injection. Image demonstrating brow asymmetry that was unmasked after injection of the frontalis and glabella

1  Injectables: Aesthetics and Cosmetics

31

paralysis of the lower orbicularis oculi with resulting incomplete eyelid closure. Lower eyelid laxity and preexisting dry eye symptoms should be assessed prior to neurotoxin injection.

1.2.16 Lip Ptosis Injection of the nasalis and perioral region may lead to perioral ptosis or asymmetry. Injection of the nasalis may lead to lip ptosis if injected too inferiorly, which may result in weakening of the levator labii superioris. Similarly, Botox injections below the upper margin of the zygomatic arch may also affect the levator labii superioris, leading to upper lip asymmetry and weakening of the zygomatic major muscle, leading to a Bell’s palsy appearance [109]. An asymmetric smile may result from muscle weakening of adjacent muscles during depressor anguli oris, mentalis, or masseter injections, including the depressor labii inferioris, which is responsible for lowering the lip. Additional Botox injections may be given to counteract asymmetry. However, with observation, these results will minimize over the next 3–4 months.

1.2.17 Dysphagia Dysphagia and dystonia are rare complications. Dysphagia has been reported as a side effect of lip ptosis due to weakening of the orbicularis oris [110]. Additionally, this may be seen in platysma band injections, if migration or inadvertent injection of the sternocleidomastoid occurs [111, 112]. Close observation over the next 3–4 months is required.

1.2.18 Systemic Complications Systemic complications are rare but may include headache, fatigue, or rarely local allergy [97]. Headaches may occur in approximately 4.3% of patients, possibly due to muscle spasm from the neurotoxin or trauma from the needle insertion [97]. This can typically be treated with oral NSAID medication. However, some cases may be intractable and require neuroimaging to assure no other underlying causes are present. Patients may present with pruritus and unspecified rashes, with approximately 3.4% of patients reporting allergy, urticaria, or pruritis, with an additional 2.3% with local rash [97]. These patients may benefit from an oral anti-histamine or a short course of an oral Medrol dose pack. Anaphylactic reactions from Botox have been rarely reported, and more so related to allergies with lidocaine. Rarely, cutaneous zoster reactivation may reoccur following injection. This may occur with injections in the perioral region. Prophylactic antiviral medication may be needed in patients with a prior known history of cutaneous herpes infections [113].

32

M. Magazin et al.

The rate of adverse events appears to be similar between each Botox formulation [114]. A prospective clinical trial found no statistically significant differences in the adverse events between onabotulinum toxin A (Botox) and the prabotulinumtoxinA (Jeuveau) [98].

1.2.19 Future Directions Over the past few decades, soft tissue fillers and neurotoxins have shown to be safe and effective in treating a variety of cosmetic and functional soft tissue defects caused by chronological aging, trauma, and medical disease. The science of soft tissue fillers and neuromodulators continues to evolve as products with new technology emerge and expand clinical applications. With new products and new clinical indications, a thorough understanding of facial anatomy and the unique characteristic of each injectable product is crucial in delivering safe and satisfactory outcomes.

References 1. Jones DH, Bacigalupi R, Beleznay K. Injectable soft tissue augmentation. Bolognia Dermatol. 2018:2649–59. 2. Eppley BL, Dadvand B. Injectable soft-tissue fillers: clinical overview. Plast Reconstr Surg. 2006;118(4):98–106. https://doi.org/10.1097/01.prs.0000232436.91409.30. 3. Kontis TC, Rivkin A.  The history of injectable facial fillers. Facial Plast Surg. 2009;25(2):67–72. https://doi.org/10.1055/s-­0029-­1220645. 4. Aesthetic Plastic Surgery National Databank Statistics.; 2019. Accessed August 1, 2021. https://www.surgery.org/sites/default/files/Aesthetic-­Society_Stats2019Book_FINAL.pdf 5. Kotlus BS, Dryden RM. Correction of Anophthalmic Enophthalmos with injectable calcium hydroxyapatite (Radiesse). Ophthal Plast Reconstr Surg. 2007;23(4):313–4. https://doi. org/10.1097/IOP.0b013e31806ada5c. 6. Tan P, Kwong TQ, Malhotra R. Non-aesthetic indications for periocular hyaluronic acid filler treatment: a review. Br J Ophthalmol. 2018;102(6):725–35. https://doi.org/10.1136/bjophth almol-­2017-­310525. 7. Hassan Hussien M, Abd El-Wahed Hassan E, El-Haddad NSE-DM.  Comparison between hyaluronic acid filler and botulinum toxin type A in the treatment of thyroid upper eyelid retraction. Ther Adv Ophthalmol. 2020;12:251584142097911. https://doi. org/10.1177/2515841420979113. 8. Carruthers J, Humphrey S.  Injectable soft tissue fillers: Overview of clinical use.; 2021. https://www.uptodate.com/contents/injectable-­soft-­tissue-­fillers-­overview-­of-­clinical-­use/ print?source=history_widgetwww.uptodate.com 9. Jones DH.  Semipermanent and permanent injectable fillers. Dermatol Clin. 2009;27(4):433–44. https://doi.org/10.1016/j.det.2009.08.003. 10. Funt D, Pavicic T.  Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol. 2013;6:295–316. https://doi.org/10.2147/ CCID.S50546. 11. Bellafill-Instructions for Use. Accessed 1 Aug 2021. https://www.accessdata.fda.gov/cdrh_ docs/pdf2/P020012S009c.pdf 12. Liberati A, Altman D, Tetzlaff J, et  al. Malar augmentation with polymethylmethacrylate-­ enhanced filler: assessment of a 12-month open-label pilot study. Aesthetic Surg J. 2013; 33(3):539–47.

1  Injectables: Aesthetics and Cosmetics

33

13. Aquamid. Published 2019. https://www.aquamid.com/wp-­content/uploads/2019/11/ Aquamid-­Brochure_Physician.pdf 14. Fallacara A, Manfredini S, Durini E, Vertuani S. Hyaluronic acid fillers in soft tissue regeneration. Facial Plast Surg. 2017;33(1):87–96. https://doi.org/10.1055/s-­0036-­1597685. 15. Sapijaszko MJ. Dermal fillers: ever-expanding options for esthetic use. Skin Therapy Lett. 2007;12(8):4–7. 16. Kontis TC.  Contemporary review of injectable facial fillers. JAMA Facial Plast Surg. 2013;15(1):58–64. https://doi.org/10.1001/jamafacial.2013.337. 17. Heitmiller K, Ring C, Saedi N. Rheologic properties of soft tissue fillers and implications for clinical use. J Cosmet Dermatol. 18. Gupta N, Spiegel OL, Spiegel JH.  Radiesse™ calcium hydroxyapatite injectable filler. Neurotoxins Fill Facial Esthet Surg. 2019:71–4. https://doi. org/10.1002/9781119294306.ch5. 19. Montes JR, Santos E, Amaral C.  Eyelid and periorbital dermal fillers: products, techniques, and outcomes. Facial Plast Surg Clin North Am. 2021;29(2):335–48. https://doi. org/10.1016/j.fsc.2021.01.003. 20. Lee JC, Lorenc ZP.  Synthetic fillers for facial rejuvenation. Clin Plast Surg. 2016;43(3):497–503. https://doi.org/10.1016/j.cps.2016.03.002. 21. Herrmann JL, Hoffmann RK, Ward CE, Schulman JM, Grekin RC. Biochemistry, physiology, and tissue interactions of contemporary biodegradable injectable dermal fillers. Dermatol Surg. 2018;44:S19–31. https://doi.org/10.1097/DSS.0000000000001582. 22. Lighthall JG. Rejuvenation of the upper face and brow: neuromodulators and fillers. Facial Plast Surg. 2018;34(2):119–27. https://doi.org/10.1055/s-­0038-­1637004. 23. Lee W, Hwang SG, Oh W, Kim CY, Lee JL, Yang EJ.  Practical guidelines for hyaluronic acid soft-tissue filler use in facial rejuvenation. Dermatol Surg. 2020;46(1):41–9. https://doi. org/10.1097/DSS.0000000000001858. 24. Rohrich RJ, Bartlett EL, Dayan E.  Practical approach and safety of hyaluronic acid fillers. Plast Reconstr Surg Glob Open. 2019;7(6):e2172. https://doi.org/10.1097/ gox.0000000000002172. 25. Lemperle G, Rullan PP, Gauthier-Hazan N.  Avoiding and treating dermal filler complications. Plast Reconstr Surg. 2006;118(3 suppl):92S. https://doi.org/10.1097/01. prs.0000234672.69287.77. 26. Tran AQ, Topilow N, Rong A, et  al. Comparison of skin antiseptic agents and the role of 0.01% hypochlorous acid. Aesthetic Surg J. 2021;41(10):1170–5. https://doi.org/10.1093/asj/ sjaa322. 27. Lee WW, Watson C, Topilow NJ, Pirakitikulr N, Tran AQ. Botulinum toxins and soft tissue fillers. Albert Jakobiec’s Princ Pract Ophthalmol. 2020:1–23. https://doi.org/10.1007/978-­3 -­319-­90495-­5_92-­1. 28. Tran AQ, Staropoli P, Rong AJ, Lee WW. Filler-associated vision loss. Facial Plast Surg Clin North Am. 2019;27(4):557–64. https://doi.org/10.1016/j.fsc.2019.07.010. 29. Wollina U, Goldman A.  Facial vascular danger zones for filler injections. Dermatol Ther. 2020;33(6) https://doi.org/10.1111/dth.14285. 30. Kapoor KM, Bertossi D, Li CQ, Saputra DI, Heydenrych I, Yavuzer R.  A systematic literature review of the middle temporal vein anatomy: ‘venous danger zone’ in temporal fossa for filler injections. Aesthet Plast Surg. 2020;44(5):1803–10. https://doi.org/10.1007/ s00266-­020-­01791-­2. 31. De Maio M, DeBoulle K, Braz A, Rohrich RJ. Facial assessment and injection guide for botulinum toxin and injectable hyaluronic acid fillers: focus on the midface. Plast Reconstr Surg. 2017;140(4):540E–50E. https://doi.org/10.1097/PRS.0000000000003716. 32. Hufschmidt K, Bronsard N, Foissac R, et  al. The infraorbital artery: clinical relevance in esthetic medicine and identification of danger zones of the midface. J Plast Reconstr Aesthetic Surg. 2019;72(1):131–6. https://doi.org/10.1016/j.bjps.2018.09.010. 33. Sharad J.  Treatment of the tear trough and infraorbital hollow with hyaluronic acid fillers using both needle and cannula. Dermatol Ther. 2020;33(3):e13353. https://doi.org/10.1111/ dth.13353.

34

M. Magazin et al.

34. Restylane Contour. Published 2021. Accessed 9 Nov 2021. www.fda.gov/medical-­devices/ recently-­approved/restylaner-­contour-­p140029s032 35. Trinh LN, Grond SE, Gupta A.  Dermal fillers for tear trough rejuvenation: a systematic review. Facial Plast Surg. 2021;38:228. https://doi.org/10.1055/s-­0041-­1731348. 36. Ogilvie P, Thulesen J, Leys C, et al. Expert consensus on injection technique and area-specific recommendations for the hyaluronic acid dermal filler VYC-12L to treat fine cutaneous lines. Clin Cosmet Investig Dermatol. 2020;13:267–74. https://doi.org/10.2147/CCID.S239667. 37. FDA executive summary general issues panel meeting on dermal fillers. Published online 2021:1–38. https://www.fda.gov/media/146870/download 38. Monheit G, Kaufman-Janette J, Joseph JH, Shamban A, Dover JS, Smith S.  Efficacy and safety of two resilient hyaluronic acid fillers in the treatment of moderate-to-severe nasolabial folds: a 64-week, prospective, multicenter, controlled, randomized, double-blinded, and within-subject study. Dermatol Surg. 2020;46(12):1521–9. https://doi.org/10.1097/ DSS.0000000000002391. 39. De Maio M, Wu WTL, Goodman GJ, Monheit G. Facial assessment and injection guide for botulinum toxin and injectable hyaluronic acid fillers: focus on the lower face. Plast Reconstr Surg. 2017;140(3):393E–404E. https://doi.org/10.1097/PRS.0000000000003646. 40. Allemann IB, Baumann L. Hyaluronic acid gel (Juvéderm™) preparations in the treatment of facial wrinkles and folds. Clin Interv Aging. 2008;3(4):629–34. https://doi.org/10.2147/ CIA.S3118. 41. Ogilvie P, Benouaiche L, Philipp-Dormston WG, et al. VYC-25L hyaluronic acid injectable gel is safe and effective for long-term restoration and creation of volume of the lower face. Aesthetic Surg J. 2020;40(9):NP499–510. https://doi.org/10.1093/asj/sjaa013. 42. King M, Convery C, Davies E. The use of hyaluronidase in aesthetic practice (v2.4). J Clin Aesthet Dermatol. 2018;11(6):E61–8. 43. Alijotas-Reig J, Fernández-Figueras MT, Puig L. Inflammatory, immune-mediated adverse reactions related to soft tissue dermal fillers. Semin Arthritis Rheum. 2013;43(2):241–58. https://doi.org/10.1016/j.semarthrit.2013.02.001. 44. Christensen L. Normal and pathologic tissue reactions to soft tissue gel fillers. Dermatologic Surg. 2007;33(suppl. 2) https://doi.org/10.1111/j.1524-­4725.2007.33357.x. 45. Lafaille P, Benedetto A.  Fillers: contraindications, side effects and precautions. J Cutan Aesthet Surg. 2010;3(1):16. https://doi.org/10.4103/0974-­2077.63222. 46. Witmanowski H, Błochowiak K.  Another face of dermal fillers. Postep Dermatologii i Alergol. 2020;37(5):651–9. https://doi.org/10.5114/ada.2019.82859. 47. Robati RM, Moeineddin F, Almasi-Nasrabadi M. The risk of skin necrosis following hyaluronic acid filler injection in patients with a history of cosmetic rhinoplasty. Aesthetic Surg J. 2018;38(8):883–8. https://doi.org/10.1093/asj/sjy005. 48. Zein M, Tie-Shue R, Pirakitikulr N, Lee WW.  Complications after cosmetic periocular filler: prevention and management. Plast Aesthetic Res. 2020;7:44. https://doi. org/10.20517/2347-­9264.2020.133. 49. Rayess HM, Svider PF, Hanba C, et  al. A cross-sectional analysis of adverse events and litigation for injectable fillers. In: JAMA facial plastic surgery, vol. 20. American Medical Association; 2018. p. 207–14. https://doi.org/10.1001/jamafacial.2017.1888. 50. Lee W, Koh IS, Oh W, Yang EJ. Ocular complications of soft tissue filler injections: a review of literature. J Cosmet Dermatol. 2020;19(4):772–81. https://doi.org/10.1111/jocd.13213. 51. Sito G, Manzoni V, Sommariva R. Vascular complications after facial filler injection: a literature review and meta-analysis. J Clin. 2019;12(6):e65–72. 52. Ansari ZA, Choi CJ, Rong AJ, Erickson BP, Tse DT. Ocular and cerebral infarction from periocular filler injection. Orbit (London). 2019;38(4):322–4. https://doi.org/10.1080/0167683 0.2018.1537287. 53. Kim YJ, Kim SS, Song WK, Lee SL, Yoon JS. Ocular ischemia with hypotony after injection of hyaluronic acid gel. Ophthal Plast Reconstr Surg. 2011;27(6):e152–5. https://doi. org/10.1097/IOP.0b013e3182078dff.

1  Injectables: Aesthetics and Cosmetics

35

54. Shone C, Appleton N, Wilton-Smith P, et al. In vitro assays for botulinum toxin and antitoxins. Dev Biol Stand. 1986;64:141–5. 55. Peck MW, Smith TJ, Anniballi F, et  al. Historical perspectives and guidelines for botulinum neurotoxin subtype nomenclature. Toxins. 2017;9(1):38. https://doi.org/10.3390/ toxins9010038. 56. Scott AB.  Development of botulinum toxin therapy. Dermatol Clin. 2004;22(2):131–3. https://doi.org/10.1016/S0733-­8635(03)00019-­6. 57. Botulinum toxin type A—product approval information—licensing action. Accessed 6 Sep 2021. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2002/botuall041202L.htm 58. 2020 Plastic surgery statistics report. Plast Surg. Published online 2020:26. 59. Persaud R, Garas G, Silva S, Stamatoglou C, Chatrath P, Patel K. An evidence-based review of botulinum toxin (Botox) applications in non-cosmetic head and neck conditions. JRSM Short Rep. 2013;4(2):1–9. https://doi.org/10.1177/2042533312472115. 60. Vanuytsel T, Bisschops R, Farré R, et  al. Botulinum toxin reduces dysphagia in patients with nonachalasia primary esophageal motility disorders. Clin Gastroenterol Hepatol. 2013;11(9):1115–1121.e2. https://doi.org/10.1016/j.cgh.2013.03.021. 61. Marsili L, Bologna M, Jankovic J, Colosimo C.  Long-term efficacy and safety of botulinum toxin treatment for cervical dystonia: a critical reappraisal. Expert Opin Drug Saf. 2021;20(6):695–705. https://doi.org/10.1080/14740338.2021.1915282. 62. Coffield JA, Bakry N, Zhang RD, Carlson J, Gomella LG, Simpson LL.  In vitro characterization of botulinum toxin types A, C and D action on human tissues: combined ­electrophysiologic, pharmacologic and molecular biologic approaches. J Pharmacol Exp Ther. 1997;280(3):1489–98. 63. Niemann H, Binz T, Grebenstein O, et al. Clostridial neurotoxins: from toxins to therapeutic tools? Behring Inst Mitt. 1991;89:153–62. 64. Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature. 1992;359(6398):832–5. https://doi.org/10.1038/359832a0. 65. Brin MF.  Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve Suppl. 1997;6:S146–68. 66. Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthetic Dermatol. 2014;7(2):31–9. 67. Klein AW, Carruthers A, Fagien S, Lowe NJ.  Comparisons among botulinum toxins: an evidence-based review. Plast Reconstr Surg. 2008;121(6):413e. https://doi.org/10.1097/ PRS.0b013e318170813c. 68. Won CH, Kim HK, Kim BJ, et al. Comparative trial of a novel botulinum neurotoxin type a versus onabotulinumtoxinA in the treatment of glabellar lines: a multicenter, randomized, double-blind, active-controlled study. Int J Dermatol. 2015;54(2):227–34. https://doi. org/10.1111/ijd.12627. 69. Ravenni R, De Grandis D, Mazza A. Conversion ratio between Dysport and Botox in clinical practice: an overview of available evidence. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol. 2013;34(7):1043–8. https://doi.org/10.1007/s10072-­013-­1357-­1. 70. Scaglione F. Conversion ratio between Botox®, Dysport®, and Xeomin® in clinical practice. Toxins. 2016;8(3):65. https://doi.org/10.3390/toxins8030065. 71. Gadarowski MB, Ghamrawi RI, Taylor SL, Feldman SR. PrabotulinumtoxinA-xvfs for the treatment of moderate-to-severe glabellar lines. Ann Pharmacother. 2021;55(3):354–61. https://doi.org/10.1177/1060028020943527. 72. What is Jeuveau and Can It Beat Botox? | Faces PLLC.  Faces, PLLC in Ridgeland, MS.  Published July 30, 2019. Accessed September 6, 2021. https://www.facesdr.com/ what-­is-­jeuveau-­and-­can-­it-­beat-­botox/ 73. Klein AW. Complications, adverse reactions, and insights with the use of botulinum toxin. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2003;29(5):549–56; discussion 556. https://doi.org/10.1046/j.1524-­4725.2003.29129.x.

36

M. Magazin et al.

74. Cheng CM.  Cosmetic use of botulinum toxin type a in the elderly. Clin Interv Aging. 2007;2(1):81–3. 75. Hexsel DM, De Almeida AT, Rutowitsch M, et  al. Multicenter, double-blind study of the efficacy of injections with botulinum toxin type a reconstituted up to six consecutive weeks before application. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2003;29(5):523–9; discussion 529. https://doi.org/10.1046/j.1524-­4725.2003.29121.x. 76. Hui JI, Lee WW. Efficacy of fresh versus refrigerated botulinum toxin in the treatment of lateral periorbital rhytids. Ophthal Plast Reconstr Surg. 2007;23(6):433–8. https://doi. org/10.1097/IOP.0b013e31815793b7. 77. Sami MS, Soparkar CNS, Patrinely JR, Hollier LM, Hollier LH. Efficacy of botulinum toxin type a after topical anesthesia. Ophthal Plast Reconstr Surg. 2006;22(6):448–52. https://doi. org/10.1097/01.iop.0000248989.33572.3c. 78. Kuwahara H, Ogawa R.  Using a vibration device to ease pain during facial needling and injection. Eplasty. 2016;16:e9. 79. Sharma P, Czyz CN, Wulc AE. Investigating the efficacy of vibration anesthesia to reduce pain from cosmetic botulinum toxin injections. Aesthet Surg J. 2011;31(8):966–71. https:// doi.org/10.1177/1090820X11422809. 80. Ahn BK, Kim YS, Kim HJ, Rho NK, Kim HS. Consensus recommendations on the aesthetic usage of botulinum toxin type a in Asians. Dermatol Surg. 2013;39(12):1843–60. https://doi. org/10.1111/dsu.12317. 81. Zhang X, Cai L, Yang M, Li F, Han X.  Botulinum toxin to treat horizontal forehead lines: a refined injection pattern accommodating the lower frontalis. Aesthet Surg J. 2020;40(6):668–78. https://doi.org/10.1093/asj/sjz174. 82. Rzany B, Ascher B, Fratila A, Monheit GD, Talarico S, Sterry W. Efficacy and safety of 3and 5-injection patterns (30 and 50 U) of botulinum toxin A (Dysport) for the treatment of wrinkles in the glabella and the central forehead region. Arch Dermatol. 2006;142(3):320–6. https://doi.org/10.1001/archderm.142.3.320. 83. Lowe PL, Patnaik R, Lowe NJ. A comparison of two botulinum type a toxin preparations for the treatment of glabellar lines: double-blind, randomized, pilot study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2005;31(12):1651–4. https://doi.org/10.2310/6350.2005.31303. 84. Frankel AS, Kamer FM.  Chemical browlift. Arch Otolaryngol Head Neck Surg. 1998;124(3):321–3. https://doi.org/10.1001/archotol.124.3.321. 85. Huang W, Rogachefsky AS, Foster JA. Browlift with botulinum toxin. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2000;26(1):55–60. https://doi.org/10.1046/j.1524-­4725 .2000.99147.x. 86. Ahn MS, Catten M, Maas CS.  Temporal brow lift using botulinum toxin A.  Plast Reconstr Surg. 2000;105(3):1129–35; discussion 1136–1139. https://doi. org/10.1097/00006534-­200003000-­00046. 87. Hwang WS, Hur MS, Hu KS, et al. Surface anatomy of the lip elevator muscles for the treatment of gummy smile using botulinum toxin. Angle Orthod. 2009;79(1):70–7. https://doi. org/10.2319/091407-­437.1. 88. Fabi SG, Massaki AN, Guiha I, Goldman MP.  Randomized Split-face study to assess the efficacy and safety of abobotulinumtoxinA versus onabotulinumtoxinA in the treatment of melomental folds (depressor Anguli Oris). Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2015;41(11):1323–5. https://doi.org/10.1097/DSS.0000000000000501. 89. Carruthers A, Carruthers J.  Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1998;24(11):1189–94. https://doi.org/10.1111/j.1524-­4725.1998.tb04097.x. 90. Andrade NN, Deshpande GS. Use of botulinum toxin (botox) in the management of masseter muscle hypertrophy: a simplified technique. Plast Reconstr Surg. 2011;128(1):24e–6e. https://doi.org/10.1097/PRS.0b013e3182174463. 91. Long H, Liao Z, Wang Y, Liao L, Lai W.  Efficacy of botulinum toxins on bruxism: an evidence-­ based review. Int Dent J. 2012;62(1):1–5. https://doi.org/10.1111/j.1875-­595X .2011.00085.x.

1  Injectables: Aesthetics and Cosmetics

37

92. Pihut M, Ferendiuk E, Szewczyk M, Kasprzyk K, Wieckiewicz M. The efficiency of botulinum toxin type a for the treatment of masseter muscle pain in patients with temporomandibular joint dysfunction and tension-type headache. J Headache Pain. 2016;17:29. https://doi. org/10.1186/s10194-­016-­0621-­1. 93. Choe SW, Cho WI, Lee CK, Seo SJ. Effects of botulinum toxin type A on contouring of the lower face. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2005;31(5):502–7; discussion 507–508. https://doi.org/10.1111/j.1524-­4725.2005.31151. 94. Kim JH, Shin JH, Kim ST, Kim CY. Effects of two different units of botulinum toxin type a evaluated by computed tomography and electromyographic measurements of human masseter muscle. Plast Reconstr Surg. 2007;119(2):711–7. https://doi.org/10.1097/01. prs.0000239453.67423.99. 95. Zhou R, Fei Y, Sun L, Guo J, Zhou X, Zhang X.  BTX-A rejuvenation: regional botulinum toxin-a injection of the platysma in patients with facial sagging. Aesthet Plast Surg. 2019;43(4):1044–53. https://doi.org/10.1007/s00266-­019-­01396-­4. 96. Levy PM.  Neurotoxins: current concepts in cosmetic use on the face and neck—jawline contouring/platysma bands/necklace lines. Plast Reconstr Surg. 2015;136(5 Suppl):80S–3S. https://doi.org/10.1097/PRS.0000000000001841. 97. Lee KC, Pascal AB, Halepas S, Koch A. What are the most commonly reported complications with cosmetic botulinum toxin type a treatments? J Oral Maxillofac Surg. 2020;78(7):1190. e1–9. https://doi.org/10.1016/j.joms.2020.02.016. 98. Ascher B, Rzany BJ, Grover R. Efficacy and safety of botulinum toxin type A in the treatment of lateral crow’s feet: double-blind, placebo-controlled, dose-ranging study. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2009;35(10):1478–86. https://doi.org/10.1111/j.1524-­47 25.2009.01261.x. 99. Sethi N, Singh S, DeBoulle K, Rahman E. A review of complications due to the use of botulinum toxin A for cosmetic indications. Aesthet Plast Surg. 2021;45(3):1210–20. https://doi. org/10.1007/s00266-­020-­01983-­w. 100. Coté TR, Mohan AK, Polder JA, Walton MK, Braun MM. Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases. J Am Acad Dermatol. 2005;53(3):407–15. https://doi.org/10.1016/j. jaad.2005.06.011. 101. Naumann M, Carruthers A, Carruthers J, et al. Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications. Mov Disord Off J Mov Disord Soc. 2010;25(13):2211–8. https://doi.org/10.1002/mds.23254. 102. Albrecht P, Jansen A, Lee JI, et  al. High prevalence of neutralizing antibodies after long-­ term botulinum neurotoxin therapy. Neurology. 2019;92(1):e48–54. https://doi.org/10.1212/ WNL.0000000000006688. 103. Torres S, Hamilton M, Sanches E, Starovatova P, Gubanova E, Reshetnikova T. Neutralizing antibodies to botulinum neurotoxin type A in aesthetic medicine: five case reports. Clin Cosmet Investig Dermatol. 2014;7:11–7. https://doi.org/10.2147/CCID.S51938. 104. Ferreira MC, Salles AG, Gimenez R, Soares MFD. Complications with the use of botulinum toxin type a in facial rejuvenation: report of 8 cases. Aesthet Plast Surg. 2004;28(6):441–4. https://doi.org/10.1007/s00266-­004-­0031-­7. 105. Hanke CW, Narins RS, Brandt F, et al. A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2013;39(6):891–9. https://doi.org/10.1111/dsu.12160. 106. Omoigui S, Irene S. Treatment of ptosis as a complication of botulinum toxin injection. Pain Med Malden Mass. 2005;6(2):149–51. https://doi.org/10.1111/j.1526-­4637.2005.05029.x. 107. Yazici B, Beden U. Use of 0.5% apraclonidine solution in evaluation of blepharoptosis. Ophthal Plast Reconstr Surg. 2008;24(4):299–301. https://doi.org/10.1097/IOP.0b013e31817f526a. 108. Kim YJ, Lim OK, Choi WJ. Are there differences between intradermal and intramuscular injections of botulinum toxin on the forehead? Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2020;46(12):e126–31. https://doi.org/10.1097/DSS.0000000000002379.

38

M. Magazin et al.

109. Matarasso SL, Matarasso A. Treatment guidelines for botulinum toxin type a for the periocular region and a report on partial upper lip ptosis following injections to the lateral canthal rhytids. Plast Reconstr Surg 2001;108(1):208–214; discussion 215–217. doi:https://doi. org/10.1097/00006534-­200107000-­00033. 110. Carruthers J, Carruthers A. Botulinum toxin A in the mid and lower face and neck. Dermatol Clin. 2004;22(2):151–8. https://doi.org/10.1016/s0733-­8635(03)00118-­9. 111. Brandt FS, Bellman B. Cosmetic use of botulinum a exotoxin for the aging neck. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 1998;24(11):1232–4. https://doi.org/10.1111/j.1524­4725.1998.tb04103.x. 112. Obagi S, Golubets K. Mild to moderate dysphagia following very low-dose Abobotulinumtoxin A for Platysmal bands. J Drugs Dermatol JDD. 2017;16(9):929–30. 113. Graber EM, Dover JS, Arndt KA. Two cases of herpes zoster appearing after botulinum toxin type A injections. J Clin Aesthetic Dermatol. 2011;4(10):49–51. 114. Cavallini M, Cirillo P, Fundarò SP, et al. Safety of botulinum toxin A in aesthetic treatments: a systematic review of clinical studies. Dermatol Surg Off Publ Am Soc Dermatol Surg Al. 2014;40(5):525–36. https://doi.org/10.1111/dsu.12463.

2

Fornix Reconstruction Pallavi Singh and Daniel B. Rootman

Ocular surface conditions requiring significant fornix reconstruction are varied in etiology and include traumatic injury such as chemical and thermal burns, inflammatory disorders including Stevens–Johnson syndrome (SJS) (Fig. 2.1) and ocular cicatricial pemphigoid (OCP) as well as degenerative or iatrogenic conditions such as pterygium, postsurgical eyelid retraction, and the contracted socket. Rarer indications including adenoviral membranous conjunctivitis, trachoma, Sjögren’s syndrome, sarcoidosis, and rare congenital disease such as abortive cryptophthalmos are also to be considered [1, 2]. The various etiologies can be associated with unique medical and surgical management challenges, though they are unified in the requirement for conjunctival replacement in some form, either through flaps or grafts, or a combination of both. Auto-immune disease such as SJS and OCP might get activated upon manipulation of the ocular surface, so it is essential that these patients are on systemic immunosuppression at the time of reconstructive surgery. The common goals of surgery are to expand mucous membrane surface area, create free and independent motion of the eyelid and bulbar surfaces, and create adequate depth of the fornices for eyelid closure, and/or prosthetic/contact lens maintenance. These objectives can be achieved by a variety of techniques involving mucous membrane substitution, flap construction, blood supply management, and forniceal molding. Critically important in all of these aspects of reconstruction is the maintenance of distinct surfaces during healing.

P. Singh · D. B. Rootman (*) Stein Eye Institute, Los Angeles, CA, USA © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 E. Tsui et al. (eds.), Current Advances in Ocular Surgery, Current Practices in Ophthalmology, https://doi.org/10.1007/978-981-99-1661-0_2

39

40

P. Singh and D. B. Rootman

Fig. 2.1  Advanced stage of Stevens–Johnson syndrome (SJS) with total upper and lower symblepharon, poor ocular surface, and leucomatous corneal opacity

2.1 Mucous Membrane Substitution Shortening of the fornix results from tissue loss and/or contracture, leading to insufficient mucous membrane length for coverage of both the bulbar and palpebral surfaces, and/or maintenance of an adequate forniceal reflection. Tissue transfer from another location can be used to manage this insufficiency. Grafts can be obtained from a variety of donor sites including contralateral bulbar conjunctiva, buccal mucous membrane, nasal mucous membrane, hard palate, and temporoparietal fascia. Dermis grafts from hairless sources with debrided epithelium, and allogenic commercially available dermal matrix substitutes are additional options. Commercially available amniotic membrane grafts have also been utilized as a substitute for mucous membrane, and as a protective barrier during healing [1]. Each of these sources has distinct benefits and particular uses in reconstructive surgery.

2.1.1 Contralateral Conjunctiva The use of healthy conjunctiva from a contralateral unaffected eye or from distant locations on the ipsilateral side may be considered ideal in the appropriate circumstances. For unilateral or localized processes, for instance, iatrogenic or traumatic cicatrization, conjunctiva is preferred particularly for the bulbar portions of the reconstruction. Progressive or bilateral disease processes would require significant caution in utilizing autografts in this way, as it may worsen the situation in the source location leading to an exacerbation of donor site morbidity. Conjunctival autografts provide the advantage of being native tissue with matching histochemical and structural properties to the host location. Additionally, conjunctiva is less bulky and provides goblet cells to facilitate lubrication. Being thinner with less tissue and cell burden may lead to reduced requirement for blood supply and decreased contracture during fibrovascular proliferation and graft integration, relative to lager buccal and nasal grafts. Additionally, the color match is superiorly compared to other grafts.

2  Fornix Reconstruction

41

Fig. 2.2 Schematic diagram showing the most common location for harvesting conjunctival grafts

The graft is obtained usually from the superior quadrant of the healthy eye, although lateral and inferior options are available as well (Fig.  2.2). It is recommended to avoid the medial bulbar conjunctiva so as not to disturb the plica semilunaris. The donor site can be closed directly or with flaps. Healing by secondary intent is a reasonable option, with or without amniotic membrane placement [3]. Avoiding harvest of tenons capsule can assist in providing a matrix for epithelial regeneration/sliding and also avoids the exposure of bare sclera that can lead to scleral thinning and necrosis [4]. The size of the graft may be limited by risk of conjunctival insufficiency, however healthy secondary intention healing can be achieved for surprisingly large grafts in the range of 10 × 20 mm or larger [5]. The graft harvest is limited by the epithelial limbal cells in the corneal region and the conjunctival reflection in the fornix, which can be difficult to reconstruct functionally. It may be useful to leave 5  mm from each of these structures as a safety margin [6]. Healthy epithelium harvested from the contralateral healthy eye is placed over the areas of conjunctival deficiency in the diseased eye. Preference is given for the perilimbal regions. Securing the graft can be with sutures or sutureless, using fibrin glue or patient’s own blood as bioadhesive [7, 8]. We tend to prefer at least cardinal sutures to maximize coverage, as the graft can stretch significantly when splayed out with mild tension. Conjunctival grafts are preferred on the bulbar surface for a number of reasons. Initially, these are cosmetically superior and utilizing them in visible areas may be preferred. Additionally, the palpebral surface is more forgiving for thicker grafts, both in terms of greater blood supply for integration and a naturally thicker configuration, hiding potentially bulky grafts. Further, though mostly based on anecdotal experience, conjunctival scarring and contraction appear to be less exuberant than other mucous membrane substitutes, which is beneficial for the more delicate bulbar recipient site.

42

P. Singh and D. B. Rootman

Additionally, conjunctival autografts have also been used as limbal grafts and utilize the process of transdifferentiation to replace limbal corneal epithelium in eyes with limbal stem cell dysfunction [9, 10]. This may be useful in cases of monocular chemical or thermal burns, advanced or recurrent pterygia, ocular surface squamous neoplasia, aniridia, and contact lens- induced ocular surface disease [6].

2.1.2 Buccal or Labial Mucous Membrane Mucous membrane grafts were first used in 1912 by Denig for ocular surface reconstruction following chemical burns and later by weeks for correction of trichiasis and symblepharon [11]. It has since then been the mainstay of ocular reconstruction in cases of cicatrizing diseases [12–14]. Buccal or labial mucous membrane grafts function as the “workhorse” of ocular surface reconstruction and can be used to replace any surface other than the tarsus. Grafts can be harvested from inferior lip and buccal regions. Oral mucous membrane grafts are relatively easy to harvest, provide abundant mucous membrane, and tend to heal extremely well. On the buccal surface, very large grafts up to 8 cm * 1.5 cm can be harvested, taking care to avoid Stenson’s duct posteriorly and maintaining the red-white junction at the oral commissure [15]. Lower lip grafts are limited in size inferiorly by the frenulum and superiorly by the wet-dry vermillion border, to avoid lip entropion. The donor area is typically marked 20%–30% larger than the recipient site area to account for graft contracture [16]. Split-thickness grafts contract more than full thickness grafts and should be sized accordingly. The graft can then be separated from the underlying tissue using en glove or open dissection, ensuring that the submucosal and minor salivary glands are removed from the graft surface and avoiding damage to the buccinator muscle (Fig.  2.3). Split-thickness a

b

c

d

Fig. 2.3  Surgical series showing injection of local anesthesia at the donor site (a), en glove undermining of the buccal mucosal graft (b), removal of fatty tissue and salivary gland from the graft (c), and final appearance of the buccal mucosal graft (d)

2  Fornix Reconstruction

43

grafts can be harvested using a microtome. Wounds can be left to heal by secondary intent, closed primarily or closed partially [17]. They tend to heal well in any case, primary closure may reduce the duration of discomfort for the patient. In many cases, obtaining a second graft from the same position at a later date is possible [18]. Minor salivary glands can be harvested along with mucous membrane, particularly in keratinized sockets. These glands are present in the labial mucosa, the buccal mucosa, the base of the tongue, and the posterior hard palate. They are obtained at the time of dissection by making full thickness incisions at the margins of the graft and lifting the graft to get a direct view of the submucosal lobular glands, the dissection is then carried out in the plane below them or by taking a partial thickness muscular plane with the graft [19, 20]. Patients affected by unhealthy buccal mucosa, secondary to smoking, alcohol abuse or medications such as clindamycin, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory drugs may not be the best candidates for this graft source [21]. Additionally, as many of the ocular cicatrizing diseases can also affect other mucosal membranes, the donor site should be inspected for signs of cicatrization pre-operatively and avoided if present. Graft contracture is the most common complication. Other issues including displacement, infection, necrosis, granuloma formation, and thickened mucosa at the recipient site may also be noted [22]. Complications at the donor site include non-­ healing of graft bed, infection, necrosis, hematoma and granuloma formation, perioral numbness, and wound contracture causing restricted mouth opening. Rarely, parotid duct injury can lead to salivary insufficiency [23].

2.1.3 Nasal Mucosa Graft Nasal mucosal grafts are typically used for reconstruction of the fornix and palpebral conjunctiva as they can be thicker than buccal mucosa and these locations are more forgiving. This mucosa provides the additional benefits of relative rigidity and presence of intraepithelial goblet cells, making these grafts histologically similar to conjunctival epithelium [24]. Like buccal membrane grafts, they have the advantage of being in ample supply and can be re-harvested after healing. The inferior turbinate and nasal floor are typical harvest sites. The former has an extremely rich supply of goblet cells, especially in the anterior half, and thus may be preferred for goblet cell-deficient syndromes [25]. Long-term studies have shown that grafts can preserve functional goblet cells even up to 10 years after transplantation, making them suitable for mucosal replacement in severe-deficiency syndromes. Nasal mucosal grafts have been shown to bring symptomatic improvement and increase visual acuity by replenishing the mucus components of the tear film [26]. For effective nasal mucosal harvesting, adequate vasoconstriction and anesthesia are critical. Various strategies can be utilized to this end. Topical vasoconstrictors such as cocaine, dilute epinephrine, and oxymetazoline are all effective, differing

44

P. Singh and D. B. Rootman

Fig. 2.4  Site for harvesting nasal floor grafts, below the inferior turbinate and over the maxillary and palatine crests, is shown using a black arrow

a

b

Fig. 2.5  Endoscopic retrieval of nasal floor grafts includes vertical and horizontal incisions in the nasal floor mucosa (a) followed by separating the mucosa from the underlying bone using a periosteal elevator (b)

mostly in their chronotropic effects. Risk stratification is critical [27]. Submucosal anesthesia with epinephrine infused formulations can be augmented this hemostatic approach. Harvest can be direct or endoscopic, our group preferring the latter. Turbinate grafts are obtained by a horizontal excision of the free edge of the inferior turbinate [28]. Floor grafts can be acquired by making medial incisions at the lateral wall of the nasal cavity under the inferior turbinate and at the medial wall of the nasal cavity overlying the maxillary and palatine crests (Figs. 2.4 and 2.5). Care is taken to avoid cartilage exposure medially. The posterior margin is the hard-soft palate junction and anteriorly at the mucocutaneous junction of the vestibule. Complications include donor site hemorrhage and hematoma formation, and nasal crusting. There is also a theoretical risk of nasal vestibular stenosis [29]. In the past, inferior turbinate mucosal grafts had shown growth of corynebacteria, S. viridans, and S. aureus in conjunctival swabs after transplants [28]. Nasal floor grafts provide a lower risk of hemorrhage and donor site morbidity as compared to turbinate grafts. They are also safer and easier to harvest.

2  Fornix Reconstruction

45

2.1.4 Hard Palate Graft Grafts harvested from the hard palate have classically functioned as a tarsal substitute and are thought to provide tectonic support to the upper and lower eyelid in case of loss of tarsus. However, it is noteworthy that they share few similar structural or histologic similarities and modern research suggests that they may function similarly to buccal or nasal floor grafts [30]. In any case they are typically utilized for palpebral reconstruction in cases of tarsal loss and can be used in conjunction with other grafts for ocular surface reconstruction [31]. Palatal mucosa is characterized by orthokeratinized or parakeratinized epithelium with submucosal tissue containing glands and fat [32]. The epithelium retains this true keratin layer even many years after transplant and does not transdifferentiate to non-keratinized epithelium [33]. Upper eyelid palatal mucosal transplantation in marginal or tarsal position should be considered with caution. In the lower eyelid, with less corneal touch, this graft is more commonly applied. Harvest from the roof of the mouth begins with effective anesthesia. A greater palatine nerve block through the greater palatine foramen located medial to the third molar tooth can be effective alone, however is often supplemented with direct infiltration (Fig. 2.6). The incision is to bone deep and typically is located medial to the second or third molar tooth and extended anteriorly and medially as needed. Traditionally, the incision is not extended past the midline; however, the anatomic consequences of transgressing this rule are questionable (Fig. 2.7). The graft is then dissected off the underlying bony palate. The donor site can be packed using surgical gauze or a palatal stent. The latter ensures a faster return to normal food intake for the patient. Donor site complications most commonly include hemorrhage, and rarely infection, and oro-nasal fistula formation [34, 35]. Fig. 2.6  Inferior view of the hard palate in the skull showing the greater palatine foramen through which the greater palatine nerve runs, which needs to be anesthetized to harvest hard palate grafts

46

a

P. Singh and D. B. Rootman

b

Fig. 2.7  The surgical site for the incision to harvest a hard palate graft should be started medial to the second or third molar tooth (a) and the dissection should be carried down to the bone to release the graft (b)

2.1.5 Dermis Fat Graft Dermis graft tissue can be harvested both with and without associated deep fat. The most superficial keratinized squamous epithelium is debrided from the surface of the graft and it then can be used as a conjunctival substitute, presuming the residual conjunctiva will expand across the deep dermal matrix. Typically the dermis graft is utilized for areas that do not typically come in contact with the cornea, as conjunctivalization can be variable, and periodically hairs can persist despite best efforts to remove adnexal structures. The deep fat graft has an additional advantage of adding volume to the graft [36]. The addition of volume is particularly useful in socket reconstruction, as these individuals are often volume deficient in the orbit. The inferior fornix is additionally a common location for dermis fat grafting, as the fat can offer volume support for a retracted lower eyelid [37]. However, dermis and dermis fat grafts both have the disadvantages of keratin-laden discharge, possible hair growth, and higher rates of tissue contraction [38, 39]. For this reason, they are typically reserved for severe, multilayer lower eyelid retraction with conjunctival contraction and in anophthalmic socket cases. Dermis fat grafts can be harvested from multiple sites including the buttocks, abdomen, hip, thigh, and groin. The post-auricular region is often used for dermis only grafts [36, 40]. In general, any hairless region with thick dermis tissue that can maintain a hidden scar can be utilized. The donor site injected with a lidocaine-epinephrine solution intradermally to ensure blanching of the overlying skin. The planned resection is the scored with a blade to the mid dermal level. The epithelium can then debrided using a blade or a burr (Fig. 2.8) [41]. Care should be taken to remove all epithelial appendages and reach the point of petechial bleeding, indicating dissection to the mid dermal layer. A dermis only grafts can be harvested by dissecting the dermis free from the underlying fat. A dermis fat graft is harvested including a variable amount of the underlying fatty tissue by dissecting in the mid fat plane. The amount of fat harvested

2  Fornix Reconstruction

a

47

b

Fig. 2.8  Scoring the epidermis while harvesting a dermis fat graft using blade (a) and burr (b) Fig. 2.9 Anophthalmic socket 6 months post dermis fat graft showing mild keratinization of socket

should be greater than the amount needed at the recipient site as it tends to shrink by almost a third to half over the course of wound healing [41–43]. The donor site is closed in layers. Complications include hematoma, infection, and wound dehiscence at the donor site. Recipient site complications are granulomas, keratinization of socket, keratinous discharge, cilia retention, fat atrophy, and volume loss.(Fig. 2.9) [44–46].

2.1.6 Temporoparietal Fascial Flap The temporoparietal fascial flap is a vascularized pedicle flap based on the superficial temporal artery. As it can be a bulky graft with no insignificant donor site morbidity, it is typically used for cases of severe socket contraction and keratinization, in addition to salvage type procedures involving leaking keratoprostheses. The intention in these cases is to replace the entire socket surface with a vascularized flap. It can be left to conjunctivalize by secondary intent if there is a source of healthy local conjunctiva, or grafted primarily with another mucous membrane source. It is a large and pliable flap that can stretch to drape the mucous membrane-­ deficient areas of the socket. It has the benefit of being vascularized and abundant,

48

P. Singh and D. B. Rootman Pericranium

a

Superficial temporoparieta fascia

Deep temporal fascia Deep layer of deep temporal fascia

b

Temporal line of fusion Superficial layer of deep temporal fascia

Superficial temporal fat pad Temporalis muscle and tendon Frontal branch of facial nerve Deep temporal fat Zygoma

Periosteum

Fig. 2.10  Schematic diagram showing the anatomic location of the superficial temporal fascia in relation to surrounding structures (a) and T-shaped temporoparietal fascial flap (b)

allowing for large areas to be reconstructed. The increased vascularity makes it a good substitute for irradiated and severely scarred recipient sites [47]. It does however, have increased morbidity at donor site, is bulky in nature, has higher rates of contraction, and may cause restriction of motility of the socket. The superficial temporalis fascia or temporoparietal fascia (TPF) is located in the layer immediately below the dermis and subcutaneous fat of the temporal region and is the superior extension of the SMAS.  It is attached to the deep temporalis fascia at the superior temporal line or conjoint tendon and to the zygomatic arch inferiorly. This is distinguished from the thicker deep temporalis facia covering the temporalis muscle, though they are fused at the temporal line and the zygomatic attachments [48]. The classic dissection involves a pre-auricular vertical incision extended as a “T” near the superior temporal line. (Fig. 2.10) Starting superiorly avoids damage to the base of the pedicle. The superficial and deep layers are dissected free, in order. The posterior extent of the flap can be designed based on tissue replacement needs. Anteriorly care is taken to avoid the temporal branch of the facial nerve as it courses from deep layers into the superficial temporalis fascia above the zygomatic arch. There are various algorithms for the determination of a “safe zone” [49]. Often it is cited as being anterior to a line from the tragus to 1.5 cm posterior to the tip of the brow. Dissecting posterior to the hairline is typically safe. Ideally the nerve would be identified and avoided during dissection, depending on the width of the desired flap. The flap is then rotated toward the orbit and tunneled above the deep temporalis plane. A bone window including or posterior to the rim laterally is often required to prevent kinking of the graft over the rim. It can be secured edge to edge with residual conjunctiva and grafted accordingly if desired [50, 51]. Complications include graft necrosis and dehiscence, donor site hematoma, and granuloma formation. Damage to the temporal branch of the facial nerve is the most functionally significant.

2  Fornix Reconstruction

49

2.1.7 Tarsoconjunctival Flap Rotational tarsoconjunctival flaps can be fashioned from the ipsilateral palpebral conjunctiva [52]. These flaps can be utilized with severe bulbar surface disease sparing the palpebral conjunctiva, for instance, postsurgical or in cases of scleral melt (iatrogenic or otherwise). In the latter case, this flap may be combined with a scleral or pericardial patch grafting, supplying a blood supply to the deeper levels. As a random flap, there is a limit to the available length and some defects may require upper and lower simultaneous flaps to cover extended midline bulbar defects. The flap is elevated on the palpebral side of the forniceal reflection and based medially to laterally as appropriate. Care is taken to allow for a wide base, and using a 3:1 length to base ratio may be appropriate for sizing, although 4:1 is often effective as the tip acts as a free graft if there is adequate deep vascularization for integration. It can be interpolated or inset, based on the location and dimensions of the defect. Interpolated flaps can be dissected free after integration, though this is often unnecessary. The secondary defect is managed with a free mucous membrane graft. The palpebral surfaces provide an excellent bed for free graft survival (Fig. 2.11). a

b

c

d

Fig. 2.11  Schematic diagram showing the conjunctival surface (a), marking the location of the tarsoconjunctival flap (b), dissection and transposition to bulbar conjunctival surface (c), and grafting a mucous membrane graft to the primary donor site (d). (Source: Rootman, D.B., et al., Ocular surface, fornix, and eyelid rehabilitation in Boston type I keratoprosthesis patients with mucous membrane disease. Ophthalmic Plast Reconstr Surg, 2015. 31(1): p. 43–9)

50

P. Singh and D. B. Rootman

The obvious disadvantage of this flap is the formation of symblepharon, leading to sectoral forniceal shortening and limitation of ocular motility. Thus can be useful in visually monocular patients and likely should be avoided in socket reconstruction in order to avoid poor prosthesis fit.

2.1.8 Amniotic Membrane Graft The amniotic membrane (AM) is the innermost layer of the placenta and consists of a thick basement membrane and an avascular stroma. It produces growth factors, downregulates TGF-β expression, and suppresses anti-inflammatory cytokines. The therapeutic effect of AM may be due to these mechanisms that act together to decrease inflammation, suppress fibrosis, and promote epithelialization [1, 3]. Though the presence of these biologic factors has been established, their in vivo effect has been debated, as some AM products carefully remove these substances and provide similar results [53–55]. Though some studies have suggested it is comparable to buccal membrane grafts in reconstruction of contracted anophthalmic sockets, it is non-cellular and would ideally be thought of as a substrate for secondary intent healing rather than a conjunctival substitute [56]. It provides the additional advantage of acting as a barrier membrane, assisting in the separation of healing surfaces to prevent palpebral-bulbar symblepharon formation. The anti-inflammatory and pro-healing effects of AM transplant may be debated [57]. Further utility can be found in protecting the cornea from palpebral sutures or forniceal foreign bodies using bolster techniques. The amniotic membrane is removed from the filter paper after thawing, or if freeze dried, simply removed from the package. It is classically described as best oriented with the stromal side facing the ocular surface bed, though the necessity of particular orientation is debated [58]. It has many uses. There is ample evidence for utility in the acute stages of SJS progression [59]. In reconstruction, it can be used to cover secondary donor conjunctival defects after graft harvest. There may be utility in covering sites of complex flap and graft reconstruction as a protective layer for comfort and perhaps gaining benefit from pro-healing factors in the AMT [1, 3]. It is also useful as a barrier to symblepharon formation in fornix reconstruction and as a comfort layer over fornix bolsters. In this case can be sutured to the limbal region on the bulbar side and over the lashes to the skin on the palpebral side. Disadvantages of AM transplant include cost, lack of widespread availability, and lack of rigidity. Complications include recurrence of symblepharon, pyogenic granuloma, entropion.

2.2 Forniceal Deepening Mucosal membrane replacement surgery makes up for tissue deficiency. However, contraction of tissues during the healing process draws the bulbar and palpebral surfaces together, leading to a flat eyelid-globe configuration. After the loss of a

2  Fornix Reconstruction

51

normal forniceal reflection, it is extremely difficult to create the mobile redundancy of the natural fornix. The goals of reconstruction are then to create independent motility of the eyelid and the globe, allow for adequate motility of the eyelids for ocular surface protection, prevent keratinization of the palpebral conjunctiva and in the case of anophthalmic socket, to allow for comfortable prosthetic maintenance. In general, the principles of fornix reconstruction are threefold: to provide adequate mucous membrane on both the palpebral and bulbar surfaces, to form and maintain a palpebral to bulbar reflection, and to maintain separation of the eyelid and the globe during healing. The first goal is discussed in the mucous membrane replacement section above, the latter two are described here. Formation of eyelid-bulbar reflection (fornix) 1. Fornix deepening sutures These sutures are intended to pull the forniceal reflection of conjunctiva into position. These are useful as a single intervention in cases of mild shortening of the fornix where adequate mucosal tissue on at least one side is present. Mild or localized cases, for instance, trauma or iatrogenic injury, would be appropriately selected. In this technique, after mucous membrane grafting, full thickness double-­ armed sutures are passed from the deepest point in the fornix to the lid externally and are tied with or without bolsters (Fig. 2.12) [60]. The deep edge of the palpebral graft can be captured and then rotated into place deeply with this technique. Placement of AM in this manner can be adjunctively applied to appropriately fold the AM deep into the reflection. Fig. 2.12 Fornix deepening sutures, performed by passing full thickness double-armed sutures from the deepest point in the fornix to the lid externally and tying with or without bolsters

52

P. Singh and D. B. Rootman

Inferior fornix bolster Cotton Bolster Mucous membrane graft

Fig. 2.13  A bolster provides an additional barrier to formation of eyelid-bulbar conjunctiva adhesions. It may be cylindrical in shape to fit the forniceal shape and is ideally made of inert material. It is usually combined with a fornix deepening suture

Limitations include cheese wiring of the sutures and tissue remodeling secondary to vector forces. 2. Bolsters Bolsters are considered in more significant cases of scarring, where the fornix shortening is extensive and in the case of a known progressive disease where there is an expectation of at least partial recurrence. Bolsters are intended to provide a physical barrier to scar formation, in addition to providing a “mold” for the shape of the new fornix (Fig. 2.13). Various materials can be utilized. Typically, they should have the characteristics of being inert, soft and moldable in order to be customized in shape and maintained in the fornix comfortably for an extended period of time. Surgical gloves, silastic sheet, polytetrafluoroethylene, and retinal sponges are all reasonable choices for this purpose [61]. After mucous membrane grafting, fornix deepening sutures are placed through the material and externalized over bolsters. A second protective layer of AMT can be placed below this material to add further comfort and protection. Often a complete temporary tarsorrhaphy is placed to limit eyelid motility d­ uring healing. Bolsters can be left in place for 2–4 weeks depending on severity of the defect/disease and patient comfort. 3. Conformer A conformer is a piece of inert plastic fashioned to fit to the shape of the ocular socket (Fig. 2.14). It has the same indications for use in fornix reconstruction bolsters. Conformers can maintain the shape of the whole fornix and can be used in anophthalmic socket reconstruction and in cases with complete conjunctivalization of the cornea (post Gunderson flap or due to disease process). Custom conformers have been designed to allow for an opening over the cornea, however there is some residual risk of discomfort and/or poor oxygenation of the cornea if the conformer moves during healing. Tissue remodeling during healing can cause conformers to extrude. They also provide limited over correction pressure for directing the final forniceal shape. To address this, some authors have also sutured the edges of the conformer to the orbital rim or combine conformer placement with bolsters [62]

2  Fornix Reconstruction

53

Fig. 2.14  Conformers of various sizes

2.3 Maintaining Separation of Healing Surfaces Fornix reconstruction surgery often acts as a double-edged sword, since on the one hand the purpose of the surgery is to replace tissue lost due to scarring, but on the other hand any surgical intervention itself leads to more scarring. The third goal of ocular surface reconstruction is to prevent recurrent scarring, or at least manage the location and extent of this natural process. Providing a scar-resistant mechanical or chemical barrier has the dual goals of repelling apposed raw surfaces during the process of re-epithelization and biochemically modifying the scarring process. As described earlier, bolsters and conformers can be utilized in isolation or combination for this purpose. The addition of layered AM may assist in the latter goal of modifying the healing process. In addition, antimetabolites such as MMC and 5-FU have been used intraoperatively, for topical application and as injections, and in the early postoperative course to alter the biology of wound healing [63–68]. Severity and extent will dictate these augmented procedures. Typically, for inflammatory and recurrent cases, it is recommended to have a low threshold for injection of 5-FU in the postoperative period as early recurrence is identified and focally managed.

2.4 Summary Ocular surface reconstruction can be complicated, and often multiple stages are required for rehabilitation. Careful, appropriately selected mucous membrane grafting forms the backbone of reconstruction, utilizing vascular flaps is prudent in more severe and/or ischemic cases. Formation of an eyelid-globe reflection is required in cases of forniceal shortening to maintain independent movement of the eyelid and globe, promote ocular surface protection and for the placement of a prosthesis in anophthalmic cases. The principles of this surgery involve mucous membrane grafting, forniceal shaping or molding and maintain a barrier between the reconstructed surfaces during healing.

54

P. Singh and D. B. Rootman

References 1. Solomon A, Espana EM, Tseng SC. Amniotic membrane transplantation for reconstruction of the conjunctival fornices. Ophthalmology. 2003;110(1):93–100. 2. Ding J, et  al. Eyelid and fornix reconstruction in abortive cryptophthalmos: a single-center experience over 12 years. Eye (Lond). 2017;31(11):1576–81. 3. Tseng SC, Prabhasawat P, Lee SH. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol. 1997;124(6):765–74. 4. Ucar F, et  al. Facilitated tenon-free conjunctival autograft preparation and limited tenon removal technique in pterygium surgery. Klin Monatsbl Augenheilkd. 2021; 5. Lee JS, et  al. Efficacy and safety of a large conjunctival autograft for recurrent pterygium. Korean J Ophthalmol. 2017;31(6):469–78. 6. Shimazaki J, Shinozaki N, Tsubota K. Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated with symblepharon. Br J Ophthalmol. 1998;82(3):235–40. 7. Marticorena J, et al. Pterygium surgery: conjunctival autograft using a fibrin adhesive. Cornea. 2006;25(1):34–6. 8. Singh PK, et al. Conjunctival autografting without fibrin glue or sutures for pterygium surgery. Cornea. 2013;32(1):104–7. 9. Shapiro MS, Friend J, Thoft RA.  Corneal re-epithelialization from the conjunctiva. Invest Ophthalmol Vis Sci. 1981;21(1 Pt 1):135–42. 10. Kenyon KR, Tseng SC.  Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96(5):709–22; discussion 722–3. 11. Henderson HWA, Collin JRO. Mucous membrane grafting. Dev Ophthalmol. 2008;41:230–42. 12. Osaki TH, et al. Management of severe cicatricial entropion with labial mucous membrane graft in cicatricial ocular surface disorders. J Craniofac Surg. 2018;29(6):1531–4. 13. Singh S, Narang P, Mittal V. Labial mucosa grafting for lid margin, anterior lamellar, and posterior lamellar correction in recurrent cicatricial entropion. Orbit. 2021;40(4):301–5. 14. Koreen IV, Taich A, Elner VM. Anterior lamellar recession with buccal mucous membrane grafting for cicatricial entropion. Ophthalmic Plast Reconstr Surg. 2009;25(3):180–4. 15. BhalaguruIyyan A, et al. Evaluation of the extent of primary buccal mucosal graft contracture in augmentation Urethroplasty for stricture urethra: a prospective observational study at a tertiary healthcare Centre. Adv Urol. 2021;2021:9913452. 16. Lauer G, Schimming R, Frankenschmidt A. Intraoral wound closure with tissue-engineered mucosa: new perspectives for urethra reconstruction with buccal mucosa grafts. Plast Reconstr Surg. 2001;107(1):25–33. 17. Muruganandam K, et  al. Closure versus nonclosure of buccal mucosal graft harvest site: a prospective randomized study on post operative morbidity. Indian J Urol. 2009;25(1):72–5. 18. Wood DN, et al. The morbidity of buccal mucosal graft harvest for urethroplasty and the effect of nonclosure of the graft harvest site on postoperative pain. J Urol. 2004;172(2):580–3. 19. Geerling G, Raus P, Murube J.  Minor salivary gland transplantation. Dev Ophthalmol. 2008;41:243–54. 20. Sant’ Anna AE, et al. Minor salivary glands and labial mucous membrane graft in the treatment of severe symblepharon and dry eye in patients with Stevens-Johnson syndrome. Br J Ophthalmol. 2012;96(2):234–9. 21. Saluja G, Patel BC, Gupta P.  Mucous Membrane Graft. In: StatPearls, Treasure Island (FL); 2022. 22. Grixti A, Malhotra R.  Oral mucosa grafting in periorbital reconstruction. Orbit. 2018;37(6):411–28. 23. Neuhaus RW, Baylis HI, Shorr N.  Complications at mucous membrane donor sites. Am J Ophthalmol. 1982;93(5):643–6. 24. Kuckelkorn R, et  al. Autologous transplantation of nasal mucosa after severe chemical and thermal eye burns. Acta Ophthalmol Scand. 1996;74(5):442–8.

2  Fornix Reconstruction

55

25. Halama AR, et al. Density of epithelial cells in the normal human nose and the paranasal sinus mucosa. A scanning electron microscopic study. Rhinology. 1990;28(1):25–32. 26. Wenkel H, Rummelt V, Naumann GO. Long term results after autologous nasal mucosal transplantation in severe mucus deficiency syndromes. Br J Ophthalmol. 2000;84(3):279–84. 27. Ross GS, Bell J. Myocardial infarction associated with inappropriate use of topical cocaine as treatment for epistaxis. Am J Emerg Med. 1992;10(3):219–22. 28. Naumann GO, et al. Autologous nasal mucosa transplantation in severe bilateral conjunctival mucus deficiency syndrome. Ophthalmology. 1990;97(8):1011–7. 29. Suh JD, Ramakrishnan VR, DeConde AS. Nasal floor free mucosal graft for skull base reconstruction and cerebrospinal fluid leak repair. Ann Otol Rhinol Laryngol. 2012;121(2):91–5. 30. Weinberg DA, et al. Eyelid mucous membrane grafts: a histologic study of hard palate, nasal turbinate, and buccal mucosal grafts. Ophthalmic Plast Reconstr Surg. 2007;23(3):211–6. 31. Lee AC, et al. Socket reconstruction with combined mucous membrane and hard palate mucosal grafts. Ophthalmic Surg Lasers. 2002;33(6):463–8. 32. Beatty RL, et  al. Intraoral palatal mucosal graft harvest. Ophthalmic Plast Reconstr Surg. 1993;9(2):120–4. 33. Goldberg RA, et al. Management of severe cicatricial entropion using shared mucosal grafts. Arch Ophthalmol. 1999;117(9):1255–9. 34. Cohen MS, Shorr N. Eyelid reconstruction with hard palate mucosa grafts. Ophthalmic Plast Reconstr Surg. 1992;8(3):183–95. 35. Kim JW, Kikkawa DO, Lemke BN. Donor site complications of hard palate mucosal grafting. Ophthalmic Plast Reconstr Surg. 1997;13(1):36–9. 36. Schmitzer S, et  al. The Anophthalmic socket—reconstruction options. J Med Life. 2014;7 Spec No. 4:23–9. 37. Korn BS, et al. Treatment of lower eyelid malposition with dermis fat grafting. Ophthalmology. 2008;115(4):744–751 e2. 38. Bhattacharjee K, et  al. Comparative analysis of use of porous orbital implant with mucus membrane graft and dermis fat graft as a primary procedure in reconstruction of severely contracted socket. Indian J Ophthalmol. 2014;62(2):145–53. 39. Inchingolo F, et al. Use of dermal-fat grafts in the post-oncological reconstructive surgery of atrophies in the zygomatic region: clinical evaluations in the patients undergone to previous radiation therapy. Head Face Med. 2012;8:33. 40. Gupta H, et al. Dermis fat graft for pediatric exenteration-challenging but rewarding. Saudi J Ophthalmol. 2017;31(3):169–72. 41. Jovanovic N, et al. Reconstruction of the orbit and Anophthalmic socket using the dermis fat graft: a major review. Ophthalmic Plast Reconstr Surg. 2020;36(6):529–39. 42. Leaf N, Zarem HA.  Correction of contour defects of the face with dermal and dermal-fat grafts. Arch Surg. 1972;105(5):715–9. 43. Davis RE, Guida RA, Cook TA.  Autologous free dermal fat graft. Reconstruction of facial contour defects. Arch Otolaryngol Head Neck Surg. 1995;121(1):95–100. 44. Bonavolonta G, et al. Orbital dermis-fat graft using periumbilical tissue. Plast Reconstr Surg. 2000;105(1):23–6. 45. Shore JW, et al. Management of complications following dermis-fat grafting for anophthalmic socket reconstruction. Ophthalmology. 1985;92(10):1342–50. 46. Quaranta-Leoni FM, et  al. Dermis-fat graft in children as primary and secondary orbital implant. Ophthalmic Plast Reconstr Surg. 2016;32(3):214–9. 47. Collar RM, et al. The versatility of the temporoparietal fascia flap in head and neck reconstruction. J Plast Reconstr Aesthet Surg. 2012;65(2):141–8. 48. Wormald PJ, Alun-Jones T.  Anatomy of the temporalis fascia. J Laryngol Otol. 1991;105(7):522–4. 49. Hashmi A, et al. Safe zone for dissection in frontotemporal region to avoid injury to the temporal branch of facial nerve. J Craniofac Surg. 2021;32(7):2322–5. 50. Ellis DS, Toth BA, Stewart WB. Temporoparietal fascial flap for orbital and eyelid reconstruction. Plast Reconstr Surg. 1992;89(4):606–12.

56

P. Singh and D. B. Rootman

51. Sahin I, et al. Total lower eyelid reconstruction with superficial temporal fascia flap and porous polyethylene implant: a case report. J Plast Reconstr Aesthet Surg. 2012;65(1):110–3. 52. Rootman DB, et  al. Ocular surface, fornix, and eyelid rehabilitation in Boston type I keratoprosthesis patients with mucous membrane disease. Ophthalmic Plast Reconstr Surg. 2015;31(1):43–9. 53. Koizumi N, et al. Comparison of intact and denuded amniotic membrane as a substrate for cell-suspension culture of human limbal epithelial cells. Graefes Arch Clin Exp Ophthalmol. 2007;245(1):123–34. 54. Fernandes M, et  al. Amniotic membrane transplantation for ocular surface reconstruction. Cornea. 2005;24(6):643–53. 55. Lee HS, Kim JC. Effect of amniotic fluid in corneal sensitivity and nerve regeneration after excimer laser ablation. Cornea. 1996;15(5):517–24. 56. Bajaj MS, et al. Evaluation of amniotic membrane grafting in the reconstruction of contracted socket. Ophthalmic Plast Reconstr Surg. 2006;22(2):116–20. 57. Dua HS, Maharajan VS, Hopkinson A. Controversies and limitations of amniotic membrane in ophthalmic surgery. In: Reinhard T, Larkin DFP, editors. Cornea and external eye disease. Berlin, Heidelberg: Springer Berlin Heidelberg; 2006. p. 21–33. 58. Hao Y, et al. Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane. Cornea. 2000;19(3):348–52. 59. Shanbhag SS, Chodosh J, Saeed HN. Sutureless amniotic membrane transplantation with cyanoacrylate glue for acute Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf. 2019;17(3):560–4. 60. Neuhaus RW, Hawes MJ.  Inadequate inferior cul-de-sac in the anophthalmic socket. Ophthalmology. 1992;99(1):153–7. 61. Demirci H, Elner SG, Elner VM. Rigid nylon foil-anchored polytetrafluoroethylene (Gore-Tex) sheet stenting for conjunctival fornix reconstruction. Ophthalmology. 2010;117(9):1736–42. 62. Putterman AM, Scott R.  Deep ocular socket reconstruction. Arch Ophthalmol. 1977;95(7):1221–8. 63. Lama PJ, Fechtner RD. Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol. 2003;48(3):314–46. 64. Khaw PT, et al. Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-­ term effects on human Tenon's capsule fibroblasts. Arch Ophthalmol. 1992;110(8):1150–4. 65. Priel A, et al. Use of antimetabolites in the reconstruction of severe anophthalmic socket contraction. Ophthalmic Plast Reconstr Surg. 2012;28(6):409–12. 66. Tawfik HA, et  al. Revisiting the role of the myofibroblast in socket surgery: an Immunohistochemical study. Ophthalmic Plast Reconstr Surg. 2016;32(4):292–5. 67. Kamal S, et al. Serial sub-conjunctival 5-fluorouracil for early recurrent anophthalmic contracted socket. Graefes Arch Clin Exp Ophthalmol. 2013;251(12):2797–802. 68. Mattout HK, Fouda SM, Al-Nashar HY. Evaluation of topical mitomycin-C eye drops after reconstructive surgery for anophthalmic contracted socket. Clin Ophthalmol. 2021;15:4621–7.

Part II Surgical Innovations for Cataract

3

Capsulotomy and Lens Fragmentation Andres Parra, Joseph Tran, and Mitra Nejad

Summary • An adequately sized, centered anterior capsulotomy is essential for predictable and safe outcomes, and adjunct technology such as precision pulse capsulotomy or femtosecond laser capsulotomy can help achieve reproducible results. • Pre-phacoemulsification lens fragmentation can decrease phacoemulsification time and energy, potentially reducing postoperative complications. • Femtosecond laser lens fragmentation can be beneficial in cases when endothelial cell damage or zonular stress avoidance is a priority, but can be time and cost prohibitive. • A micro-interventional lens fragmentation device is particularly helpful in reducing phacoemulsification energy in dense cataracts, as well as both spatially and economically advantageous in resource-limited settings.

A. Parra Diagnostic Eye Center, Houston, TX, USA J. Tran University of Southern California, Roski Eye Institute, Los Angeles, CA, USA e-mail: [email protected] M. Nejad (*) Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 E. Tsui et al. (eds.), Current Advances in Ocular Surgery, Current Practices in Ophthalmology, https://doi.org/10.1007/978-981-99-1661-0_3

59

60

A. Parra et al.

3.1 Anterior Capsulotomy: Manual Curvilinear Capsulorhexis, Femtosecond Laser Capsulotomy, and Precision Pulse Capsulotomy 3.1.1 Historical Perspective Cataract surgery has undergone incredible transformation and progressive iterations through the past centuries. One of the most notable changes which revolutionized cataract surgery occurred around the eighteenth century, with the advent of the first attempts to extract the nucleus altogether rather than pushing the cataract into the vitreous. In conjunction with this development, techniques to create a capsular opening in order to extract the lens became a necessary and important step. This need paved the way for techniques and approaches that included a linear opening proximal to the main corneal incision, which was enlarged following clearance of removed lens material; a triangular “Christmas tree” capsulotomy; and a “can opener” capsulotomy with serrated edges. However, all of these approaches left something to be desired due to inconsistency, largely due to capsulotomy edges that were highly susceptible to radialization and tearing [1]. The manual continuous curvilinear capsulorhexis (CCC), the surgical standard in modern cataract surgery, addresses many of these limitations and associated complications. This technique has been historically credited to Thomas Neuhann in Germany, and Howard Gimbel in Canada, as their technique was the first to appear in peer-reviewed literature [2]. However, both Kimiya Shimizu and Calvin Fercho have also been noted to have a similar technique around the same time. This technique included some variation in using either a cystotome, 30 gauge or 26 gauge needle to create a capsular tear and a subsequent flap, which was then either folded or pulled to complete a curvilinear capsulorhexis [1].

3.1.2 Adequacy of Capsulotomy for Successful Cataract Surgery The importance of an adequate and reproducible capsulotomy during cataract surgery cannot be overstated, both for optimizing and stabilizing the position of the intraocular lens to achieve the desired refractive outcome, as well as for withstanding intraoperative forces required to extract the cataract with minimal complications. Surgical steps during cataract surgery inevitably build on each other, with each successive step depending on the success of previous steps. An adequate capsulotomy technique resists tearing and forces associated with hydrodissection, nuclear disassembly, capsular polishing, and intraocular lens implantation [2]. A circular capsulorhexis with good centration has been found to be of paramount importance, given that radial tears during capsulorhexis increase the rate of complications during cataract surgery [3]. The importance of capsulotomy size is highlighted by evidence that capsulotomies smaller than 4 mm or larger than 6 mm were both associated with increased rates of posterior capsular opacification [4, 5]. Small

3  Capsulotomy and Lens Fragmentation

61

capsulotomies are also associated with anterior capsular fibrosis, which can progress to a progressive hyperopic shift due to posterior movement of the intraocular lens [6]. Meanwhile, inadequate capsulotomy centration can lead to refractive shifts up to a year postoperatively [7].

3.1.3 Introduction to Femtosecond Laser Capsulotomy (FSLC) Given the importance of a reproducible, adequately sized, circular, and centered capsulotomy, it should come as no surprise that a well-performed continuous curvilinear capsulorhexis (CCC) is regarded as one of the most challenging steps of cataract surgery to novice surgeons [8]. For this reason, the advent of femtosecond laser technology, and in particular, femtosecond laser capsulotomy (FSLC), has garnered special attention as it allows surgeons to automate anterior capsulotomy and eliminate the inherent variability associated with CCC (Fig. 3.1). A description on how femtosecond laser technology works to fragment lens tissue can be found in the femtosecond laser lens fragmentation section of this chapter. Capsulotomies performed with femtosecond laser have been found to be more precise in size and shape and more reproducible than manual CCC [9]. However, although capsulotomy performed by FSLC was significantly more circular than CCC, no statistical differences have been found in capsulotomy diameter nor rates of anterior capsular tear between FSLC and manual CCC [10]. Despite this geometric advantage, FSLC has not been associated with improvement in refractive outcomes compared to CCC [11]. In addition, FSLC has been associated with high rates of early PCO [12], and lens capsule tissue prepared for scanning electron microscopy in FSLC has been noted to have irregularity at the capsule margin, as well as misplaced laser pits in normal parts of tissue [13]. a

b

Fig. 3.1 (a) A centered, 5 mm, circular capsulotomy created by a femtosecond laser (FSL) and (b) the FSL capsulotomy cap being removed

62

A. Parra et al.

3.1.4 Applications of Femtosecond Laser Capsulotomy (FLSC) Femtosecond laser-assisted cataract surgery presents a substantial additional cost, disruption in workflow, and unique challenge in certain eyes. FLSC requires a separate laser platform with a higher upfront capital cost, as well as higher procedural cost, and national regulations may differ in terms of the ability to bill for the additional costs associated with FSLC [14]. Furthermore, the procedure of docking the eye requires deviation from the normal workflow of standard cataract surgery, disrupting surgical flow and adding procedural time. FSLC also requires a clear media, which may present challenges in pterygia and corneal opacities, not to mention difficulties with certain orbital anatomy and small pupils [15]. Regardless, FSLC still maintains some distinct advantages. White intumescent cataracts pose a unique challenge due to the increased pressure within the capsule, which increases the risk of capsulotomy radialization and tears. Femtosecond laser use has shown relative success in creating capsulotomies in white cataracts, with very low incidence of anterior capsular tears and none with posterior extension. Despite a high rate of incomplete capsulotomies for white cataracts, FSLC allowed for intraocular lens placement within the capsular bag [16, 17]. FSLC may also provide an advantage in cases with weak zonules, as seen with pseudo-exfoliation syndrome; zonular dehiscence, often seen with traumatic cataracts; and lens subluxation, as seen in Marfan’s syndrome. An ex  vivo, experimental study done by Yaguchi et al. demonstrated that FSLC showed favorable results compared to manual CCC in cases of zonular dehiscence simulations—resulting in fewer decentered, ovalized capsulotomies [18]. A retrospective review of 72 eyes with subluxed cataracts managed with FSLC demonstrated successful preservation of the lens capsule in 90% of cases [19].

3.1.5 Introduction to Precision Pulse Capsulotomy (Zepto) Precision pulse capsulotomy (PPC), under the trade name Zepto (Mynosys Cellular Devices, Fremont, CA) was developed in 2015 and approved by the FDA in 2017. The device is powered by a small console and consists of a disposable handpiece with a nanoengineered capsulotomy tip designed to enter through a small clear corneal incision as small as 2.2  mm, to create a capsulotomy meant to be perfectly circular with a 5–5.5 mm diameter, instantaneously to all 360 degrees. The tip consists of a circular nitinol ring covered by a thin, clear, silicone suction cup. The nitinol is self-expanding with memory, which allows entry through a small corneal incision via a retractable push rod, which once retracted, allows the compressed tip to return to its native circular shape. The ring and suction cup are then positioned over the anterior capsule surface, and a small amount of suction is applied via the external console. A series of electrical pulses of 4 ms duration and subsequent phase transition of water molecules trapped between the capsule and nitinol edge cause mechanical cleavage of the stretched capsular membrane circumferentially and simultaneously. Collateral damage is minimized by limiting application of energy

3  Capsulotomy and Lens Fragmentation

63

to this microscopic edge of the nitinol ring in a brief fashion, and insulation is further provided by the suction cup and surrounding ophthalmic viscoelastic device (OVD) [14]. In a study of 38 eyes using PPC through a 2.2 mm corneal incision, all resulted in complete 360 degree round capsulotomies averaging 5.5 mm in diameter with no associated complications intraoperatively nor at 3–8 month follow-up [20]. When comparing complication rates and residual refractive error between manual CCC and PPC, one retrospective study of 243 eyes found no difference in complications. However, PPC had a significantly higher percentage of eyes with refractive cylinder  0.05), an intense anterior chamber inflammation was observed occurring 1–3  months postoperatively in 14 of the 27 cases undergoing AADI while none occurred in the Baerveldt group. Of note, only 4 resolved with medical treatment; the remaining 10 required surgical intervention for various sequelae. As such, Rateb et  al. recommended caution in using AADI in pediatric populations, especially those at higher risk for inflammation. This inflammatory reaction was not reported as significant in other trials [31–33]. A retrospective trial conducted in India by Senthil et  al. including 36 pediatric eyes with refractory glaucoma undergoing AADI and 85 undergoing Ahmed glaucoma implant found that overall qualified success (IOP control with topical medications) was similar between the groups at 3  years (81% in AADI vs. 84% in Ahmed, p = 0.81) [33]. Notably, they found that mean final IOP (12.7 mmHg vs. 17.6 mmHg, p = 0.001), median medication burden (1 medication vs. 2 medications, p