Keratoconus: Diagnosis and Treatment

Foreword
Foreword
Preface
Contents
About the Editor
1: Epidemiology of Keratoconus
1.1 Introduction
1.2 Epidemiology
1.2.1 Incidence and Prevalence
1.2.2 Age of Onset
1.2.3 Gender
1.2.4 Laterality
1.3 Risk Factors
1.3.1 Genetic
1.3.2 Ethnic Groups
1.3.3 Eye Rubbing
1.3.4 Atopy
1.3.5 Ultraviolet and Sun Exposure
1.3.6 Hormonal
1.3.7 Associated Systemic and Ocular Disorders
1.4 Conclusion
References
2: Etiology and Risk Factors of Keratoconus
2.1 Introduction
2.2 The Genetics of Keratoconus
2.2.1 Genome-Wide Association Studies (GWAS)
2.2.2 GWAS of Central Corneal Thickness (CCT) and Corneal Biomechanical Properties
2.3 KC and Family History
2.4 Functional Studies of Candidate Genes
2.4.1 DOCK9 and PPIP5K2
2.5 Genetic Determinants of Syndromic and Non-syndromic KC
2.6 Transcriptomic and Expression Studies
2.6.1 Noncoding RNA (lncRNAs and miRNAs) Involved in KC
2.7 Environmental Risk Factors
2.7.1 Eye Rubbing
2.7.2 Comorbidities
2.7.3 Contact Lens Wear
2.7.4 Asthma
2.7.5 Allergy
2.7.6 Atopy
2.7.7 UV Exposure
2.8 Conclusion
References
3: Biomechanics of Keratoconus
3.1 Introduction
3.2 Background
3.3 Biomechanical Changes
3.3.1 Biomechanical Changes in KCN
3.3.2 Biomechanical Changes in ffKCN
3.3.3 Biomechanical Changes After Intrastromal Corneal Ring Segments
3.3.4 Biomechanical Changes in CXL
3.3.5 Biomechanics in Refractive Surgery
3.4 Conclusions
References
4: Pathophysiology and Histopathology of Keratoconus
4.1 Introduction
4.2 Pathophysiology of Keratoconus
4.2.1 Composition of the Corneal Stroma in Keratoconus
4.2.2 Alterations in Volume/Stromal Thinning
4.2.3 Alterations in Characteristics
4.2.4 Role of Inflammatory Mediators Including TGF Beta Pathway and Cytokine Dysregulation
4.2.5 Imbalance of Proteolytic Enzymes
4.2.6 Oxidative Stresses
4.2.7 Cellular Hypersensitivity to Apoptosis
4.3 Histopathology
4.3.1 Penetrating Keratoplasty Specimens
4.3.2 Epithelial Changes
4.3.3 Bowman’s Layer
4.3.4 Stroma
4.3.5 Dua’s Layer
4.3.6 Descemet’s Membrane
4.3.7 Endothelial Cells
4.3.8 DALK and Attempted DALK Specimens
4.3.9 Acute Hydrops and Healed Hydrops
4.3.10 Histopathological Changes After Collagen Cross-linking
4.4 Conclusion
References
5: Clinical Diagnosis of Keratoconus
5.1 Introduction
5.2 Symptoms
5.3 History
5.3.1 Past Ocular History
5.3.2 Family History
5.3.3 Medical History and Associated Diseases
5.4 Clinical Examination
References
6: Classifications and Patterns of Keratoconus
6.1 Introduction
6.2 Classification Systems in Keratoconus
6.2.1 KISA Index
6.2.2 McMahon and Colleagues’ Keratoconus Severity Score (KSS)
6.3 Classification of Keratoconus Based on Clinical Characteristics
6.3.1 Based on Severity of the Corneal Curvature
6.3.2 Classification of Keratoconus Based on Morphological Appearance of the Cone
6.4 Amsler–Krumeich Classification
6.4.1 Belin ABCD Classification
6.5 Fourier-Domain OCT Classification
6.6 Topographic Patterns in Keratoconus
6.7 Conclusion
References
7: Differential Diagnosis of Keratoconus
7.1 Introduction
7.2 True Corneal Ectasias
7.2.1 Pellucid Marginal Degeneration (PMD): Keratotorus
7.2.2 Keratoglobus
7.2.3 Isolated Keratoconus Posticus
7.2.4 Regular Astigmatism
7.2.5 Post-LASIK Ectasia
7.2.6 Superior Keratoconus and Superior Pellucid Marginal Degeneration (PMD)
7.3 Corneal Diseases with Pseudokeratoconic Tomography
7.3.1 Epithelial Basement Membrane Dystrophy (EBMD)
7.3.2 Scar-Associated Irregular Astigmatism
7.3.3 Central Fuchs Endothelial Corneal Dystrophy
7.4 Differential Diagnosis of Corneal Hydrops
7.4.1 Salzmann’s Nodular and Peripheral Hypertrophic Subepithelial Corneal Degeneration (PHSCD)
References
8: Keratoconus in Children
8.1 Introduction
8.2 Epidemiology
8.3 Genetics
8.4 Ocular Allergy
8.5 Syndromes
8.6 Risk Factors
8.7 Clinical Features and Diagnosis
8.8 Adult vs. Pediatric Keratoconus
8.9 Treatment
8.10 Contact Lens
8.11 Surgical Procedures
8.11.1 Collagen Cross-linking
8.11.1.1 Indications and Timing of the Procedure in Children vs. Adolescent
8.11.2 CXL Standard Dresden Protocol
8.11.3 Transepithelial CXL (TE CXL)
8.11.4 Accelerated Cross-linking Protocol
8.11.5 Other Methods
8.11.6 Safety
8.11.6.1 Epithelial Defect
8.11.6.2 Endothelial Cell Loss
8.11.6.3 Limbal Cell Loss
8.11.6.4 Efficacy of Standard Protocol
8.11.6.5 Efficacy of Transepithelial CXL (EPI-ON) and Accelerated Protocol
8.11.7 Intracorneal Ring Segments
8.11.8 Keratoplasty
References
9: Allergic Eye Disease and Keratoconus
9.1 Introduction
9.2 Association between Allergic Eye Diseases and Keratoconus
9.3 Etiopathogenesis
9.3.1 Causative Factors
9.3.2 Genetic Factors
9.3.3 Environmental Factors
9.3.4 Role of Inflammation
9.3.5 Role of Enzymes
9.3.6 Role of Oxidative Stress
9.3.7 Role of Hormones
9.4 Role of Early Topography in Allergic Eye Diseases
9.5 Role of Allergic Eye Diseases in KC Progression
9.6 Role of Allergic Eye Diseases in Acute Corneal Hydrops and Perforation
9.7 Management of Allergic Eye Disorders
9.7.1 Treatment Options for Ocular Allergy
9.7.1.1 Avoidance of Allergen
9.7.1.2 Cold Compresses
9.7.1.3 Artificial Tear Substitutes
9.7.1.4 Topical Antihistamine
9.7.1.5 Topical Vasoconstrictors
9.7.1.6 Topical Mast Cell Stabilizers
9.7.1.7 Multimodal Anti-Allergic Agents
9.7.1.8 Topical Corticosteroids
9.7.1.9 Topical Immunomodulatory Agents
9.7.1.10 Systemic Agents
9.8 Prevention of Eye Rubbing
9.9 Surgical Treatment
9.9.1 Surgical Outcome in Cases with Allergic Eye Diseases and KC
9.10 Conclusion
References
10: Topography and Tomography of Keratoconus
10.1 Introduction
10.2 Topography Vs. Tomography
10.2.1 Historical Background
10.3 Placido-Based Corneal Topographer
10.3.1 Principle
10.3.2 Features
10.3.3 Application Tools for Keratoconus Management
10.4 Scheimpflug-Based Tomography
10.4.1 Principle
10.4.2 Features
10.4.3 Application Tools for Keratoconus Management
10.5 Anterior Segment OCT
10.5.1 Principle
10.5.2 Feature
10.5.3 Application Tools for Keratoconus Management
10.6 Combined Systems with a Wavefront Aberrometer
10.7 Tips for the Measurements
10.8 Tips at Reading the Maps
10.9 Final Practical Comment from Specialists
References
11: Newer Diagnostic Technology for Diagnosis of Keratoconus
11.1 Introduction
11.2 Corneal Topography
11.2.1 Types of Topographic Indices
11.3 Epithelial Mapping in Keratoconus
11.3.1 Classification of OCT-Based Devices
11.3.1.1 RTVUE®
11.3.1.2 CASIA 2
11.3.1.3 MS-39: A Hybrid Tomographer
11.3.2 Importance of Epithelial Mapping in Diagnosis of Subclinical Keratoconus
11.3.3 Imaging the Bowman’s Layer in Subclinical and Clinical Keratoconus
11.3.4 Epithelial Changes in Keratoconus
11.3.5 True Progression in Keratoconus
11.3.6 Pseudoprogression in Keratoconus
11.3.7 Epithelial Remodeling Post-Cross-Linking
11.3.8 Importance of Epithelial Imaging in Identifying Keratoconus Masquerades
11.3.9 Clinical Applications
11.4 Corneal Biomechanics
11.4.1 Introduction
11.4.2 Ocular Response Analyzer
11.4.2.1 Application in Keratoconus
11.4.3 Corvis ST
11.4.3.1 Vinciguerra Screening Report
11.4.3.2 TBI (Tomographic/Biomechanical Index)
11.4.3.3 Biomechanics Comparative Display
11.4.4 Clinical Applications
11.5 Confocal Microscopy
11.5.1 Introduction
11.5.2 Principle
11.5.2.1 Tandem Scanning Confocal Microscope (TSCM)
11.5.2.2 Scanning Slit Confocal Microscope (SSCM)
11.5.2.3 Confocal Laser Scanning Microscope (CLSM)
11.5.3 Confocal Microscopy in Normal
11.5.3.1 Corneal Epithelium
Superficial Cells
Wing Cells
Basal Cells
11.5.3.2 Bowman’s Membrane
11.5.3.3 Corneal Stroma
11.5.3.4 Descemet’s Membrane
11.5.4 Confocal Microscopy in Keratoconus
11.5.4.1 Corneal Epithelium
Superficial Cells
Basal Cells
11.5.4.2 Bowman’s Membrane
11.5.4.3 Corneal Stroma
11.5.4.4 Corneal Nerves in Keratoconus
11.5.4.5 Descemet’s Membrane
11.5.5 Clinical Applications
11.6 Polarization-Sensitive Optical Coherence Tomography (PS-OCT)
11.6.1 Introduction
11.6.2 Principle of PS-OCT
11.6.3 Corneal Imaging Using PS-OCT
11.6.4 Clinical Applications
11.6.4.1 Normal Patients
11.6.4.2 Keratoconus
11.6.4.3 Post-Corneal Collagen Cross-Linking
11.7 Brillouin Microscopy
11.7.1 Introduction
11.7.2 Principle of Brillouin Microscopy
11.7.3 Clinical Applications [73]
11.7.3.1 Screening/Diagnosis of Corneal Disease
11.7.3.2 Monitoring Response to Corneal Cross-Linking
11.7.3.3 Advantages
11.8 MMP-9 Kit Useful in the Diagnosis of Molecular Markers for Keratoconus
References
12: Acute Corneal Hydrops: Etiology, Risk Factors, and Management
12.1 Introduction
12.2 Etiology
12.2.1 Primary Corneal Ectasia
12.2.2 Secondary Corneal Ectasia
12.2.2.1 Post-Laser in Situ Keratomileusis (LASIK)
12.2.2.2 Post-Radial Keratotomy (RK)
12.2.2.3 Post-Penetrating Keratoplasty
12.2.2.4 Post-Anterior Lamellar Keratoplasty
12.2.2.5 Post-Corneal Trauma or Degeneration
12.2.3 Primary Infantile Glaucoma
12.3 Natural History of Disease
12.4 Histopathology of Corneal Hydrops
12.5 Clinical Presentation
12.6 Investigative Modalities
12.6.1 Ultrasound Biomicroscopy (UBM)
12.6.2 Anterior Segment Optical Coherence Tomography (AS-OCT)
12.6.3 In Vivo Confocal Microscopy
12.7 Management
12.7.1 Conservative Management
12.7.2 Surgical Management
12.7.2.1 Thermokeratoplasty (TKP)
12.7.2.2 Intracameral Air or Gas Injection
12.7.2.3 Compression Sutures with Intracameral Gas Injection
12.7.2.4 Amniotic Membrane Transplantation with Cauterization
12.7.2.5 Penetrating Keratoplasty (PK)
12.7.2.6 Deep Anterior Lamellar Keratoplasty (DALK)
12.7.2.7 Endothelial Keratoplasty (EK)
12.8 Visual Rehabilitation Post-Corneal Hydrops
12.9 Summary and Conclusion
References
13: Contact Lenses for Keratoconus
13.1 Introduction
13.2 Prerequisite for Fitting
13.2.1 Clinical Examination
13.3 Investigations
13.3.1 Corneal Topography
13.4 Selection of a Lens
13.4.1 Soft Lenses
13.4.2 Rigid Gas Permeable Lenses
13.5 Fitting Philosophies
13.5.1 Apical Clearance
13.5.2 Apical Bearing
13.5.3 Three-Point Touch or Divided Support
13.5.4 Fitting RGP Lenses
13.6 Lens Designs
13.6.1 Rose K Lenses
13.6.2 Assessment of Fitting
13.6.3 Intralimbal Lenses
13.6.4 Piggybacking Lenses
13.6.5 Hybrid Lenses
13.6.6 Scleral Lenses
13.7 Assessment of Fitting
13.8 Contact Lenses in Special Scenarios
13.8.1 Keratoconus with Vernal Keratoconjunctivitis or Allergic Conjunctivitis
13.8.2 After Collagen Cross-Linking
13.8.3 After Intracorneal Ring Segment Surgeries
13.8.4 Keratoconus with Stevens-Johnson Syndrome
13.8.5 Warpage or Progression after RGP Fitting
13.9 Conclusion
References
14: Corneal Cross-Linking in Keratoconus
14.1 Introduction
14.2 CXL to Arresting Keratoconus Progression
14.3 Epi-on Versus Epi-off CXL
14.4 Accelerated CXL Protocols
14.5 Attempts to Overcome the Rate-Limiting Effects of Oxygen
14.6 CXL in Thin Corneas
14.6.1 Artificial Thickening Approaches
14.6.2 Choosing a Protocol that Delivers the Desired Cross-Linking Depth
14.6.3 Individualizing Fluence to each Patient’s Corneal Thickness
14.6.4 Cross-Linking Corneal Infections
14.6.5 The Future of CXL
References
15: Penetrating Keratoplasty in Keratoconus
15.1 History of Keratoplasty in Keratoconus
15.2 Long-Term Results of Penetrating Keratoplasty in Keratoconus
15.3 Indications for PK in the Era of DALK
15.4 Surgical Steps of PK
15.5 Femto-Assisted PK
15.6 Deep Anterior Lamellar Keratoplasty (DALK) Versus PK
15.6.1 Learning Curve
15.6.2 Visual Acuity
15.6.3 Refractive Astigmatism
15.6.4 Topographic or Keratometric Astigmatism
15.6.5 Spherical Equivalent
15.6.6 Q Value
15.6.7 Corneal Densitometry
15.6.8 Contrast Sensitivity
15.6.9 Endothelial Cell Loss
15.6.10 Graft Survival
15.6.11 Graft Rejections
15.6.12 Corneal Biomechanics
15.6.13 Miscellaneous
15.6.14 Complications
15.6.15 Conclusion
15.7 Complications of PK in Keratoconus (KC)
15.8 Graft-Host Misalignment
15.9 Wound Healing in Keratoconus
15.10 Post-PK Refractive Errors
15.11 Post-PK Astigmatism
15.11.1 Spectacles and Contact Lenses
15.11.2 Suture Removal or Adjustments
15.11.3 Relaxing Incisions
15.11.4 Astigmatic Keratotomy
15.11.5 Wedge Resection
15.11.6 Intraocular Lens
15.11.7 Intrastromal Ring Segments
15.12 Recurrence/Progression of Keratoconus Following PK
15.13 Rejection
References
16: Lamellar Keratoplasty in Keratoconus
16.1 Introduction
16.2 Anterior Lamellar Keratoplasty
16.2.1 Manual ALKP
16.2.2 Automated ALKP/Microkeratome-Assisted ALKP (MALKP)/Automated Lamellar Therapeutic Keratoplasty (ALTK)
16.2.3 Procedure
16.2.3.1 Recipient Preparation
16.2.3.2 Donor Preparation
16.2.4 Excimer Laser-Assisted LKP (ELLKP)
16.2.5 Femtosecond Laser-Assisted ALK (FALK)
16.3 DALK Surgical Techniques
16.3.1 Layer-by-Layer Manual Dissection
16.3.2 Visco-Delamination
16.3.3 Hydro-Delamination
16.3.4 Pneumo-Delamination
16.3.5 Modifications of Big Bubble Technique
16.3.5.1 Small Bubble-Guided Big Bubble Technique
16.3.5.2 Microbubble-Assisted Baring of DM
16.3.5.3 Femtosecond Laser-Assisted DALK (FS-DALK)
16.3.5.4 DALK after ICRS
16.3.5.5 DALK after Resolved Hydrops
16.3.6 Outcomes
16.3.6.1 Visual Refractive and Graft Success
16.3.6.2 CDVA
16.3.6.3 Spherical Equivalent (SE)
16.3.6.4 Astigmatism
16.3.6.5 Endothelial Cell Density (ECD)
16.3.6.6 Graft Rejection Episodes
16.3.6.7 Graft Survival
16.3.6.8 Complications
16.4 Perforation of DM
16.4.1 Double Anterior Chamber (AC)/Pseudo AC
16.4.2 Pupillary Block and Fixed Dilated Pupil (Urrets-Zavalia Syndrome)
16.4.3 Graft Rejection
16.4.4 Interface Complications
16.5 Conclusion
References
17: Intracorneal Ring Segments in Keratoconus
17.1 Introduction
17.2 Mechanism of Action of the Intracorneal Ring Segments and Effects on the Cornea
17.2.1 Types of Intracorneal Ring Segments
17.3 Nomograms for Intracorneal Ring Segments Implantation
17.4 Surgical Techniques for Intracorneal Ring Segments Implantation
17.5 Efficacy and Complications of Intracorneal Ring Segments Implantation
References
18: Intraocular Lens (IOL) Implantation in Kertaoconus
18.1 Introduction
18.2 Phakic Intraocular Lens Implantation (pIOLs)
18.2.1 Anterior Chamber pIOLs
18.2.1.1 Acrysof Cachet
18.2.1.2 Artisan/Verisyse
18.2.1.3 Artiflex/Veriflex
18.2.2 Posterior Chamber pIOLs
18.2.2.1 Visian ICL
18.2.3 Phakic Intraocular Lens Implantation (pIOLs) in Keratoconus
18.3 Patient Selection
18.3.1 Preoperative Evaluations and Considerations
18.4 pIOL Sizing and Power Calculations
18.4.1 WTW Distance and the Anterior Chamber Depth (ACD)-Based Sizing Formula
18.4.2 NK-Formula Version 2 (NK-Formula V2)
18.4.3 Safe Ranges of Vault
18.5 The Key Points for Successful pIOL Surgery in Keratoconus
18.5.1 Stable Keratoconus (KC) with Low Irregularity
18.5.2 Unstable Keratoconus with Low Irregularity
18.5.3 Stable Keratoconus with High Irregularity
18.5.4 Unstable Keratoconus with High Irregularity
18.6 Surgical Technique
18.6.1 Artiflex/Veriflex
18.6.2 Visian ICL
18.7 Results of pIOLs in KCN
18.7.1 Refractive Outcomes
18.7.1.1 Efficacy
18.7.1.2 Predictability
18.7.1.3 Safety
18.7.1.4 Stability
18.7.2 Visual Quality Outcomes
18.7.2.1 HOAs
18.7.2.2 Glare
18.7.3 Corneal Biomechanical Effects of pIOLs Implantation
18.7.4 Complications of pIOLs in KCN
18.8 ICL Replacement
18.8.1 Cataract
18.8.2 Pigment Dispersion Glaucoma
18.8.3 Endothelial Cell Loss
18.9 Conclusion
References
19: Stromal Augmentation Techniques for Keratoconus
19.1 Introduction
19.2 Corneal Stroma-Applied Surgical Anatomical Considerations
19.3 Bowman’s Membrane Transplant (BLT)
19.4 Surgical Technique
19.4.1 Graft Preparation
19.4.2 Surgery in the Recipient
19.4.3 Clinical Outcomes
19.5 Stromal Lenticule Addition Keratoplasty (SLAK)
19.5.1 Surgical Technique
19.5.1.1 Clinical Outcomes
19.6 Cellular Therapy of the Corneal Stroma
19.7 Autologous Adipose-Derived Adult Stem Cells (ADASCs) Isolation and Intrastromal Implantation Techniques
19.7.1 Clinical Outcomes
19.8 Conclusion
References
20: Cataract Surgery in Keratoconus
20.1 Introduction
20.2 Preoperative Evaluation
20.3 CXL and ICRS Prior to Cataract
20.4 Intraocular Lens Power Calculation Formulas
20.5 Intraocular Lens Choice
20.6 Surgical Technique
20.7 Vision Recovery Following Cataract Surgery
20.7.1 Lens-Based Surgeries
20.7.2 Corneal-Based Surgeries
20.7.3 Contact Lens
20.8 Conclusion
References
21: Refractive Surgery in Management of Keratoconus
21.1 Introduction
21.2 Corneal Therapeutic Laser Refractive Surgery
21.2.1 Combined Protocols: Efficacy and Safety
21.2.2 PRK + CXL: Simultaneous or Sequential?
21.2.3 Transepithelial PTK + CXL with Better Results Compared to Manual Epithelial Debridement
21.2.4 Wavefront-Guided PRK
21.2.4.1 Surgical Technique
21.2.4.2 Outcomes
21.3 Therapeutic Refractive Surgery of Keratoconus with Phakic IOLs
21.3.1 Implantation Criteria
References
22: Artificial Intelligence in the Diagnosis and Management of Keratoconus
22.1 Introduction
22.1.1 Machine Learning and Keratoconus
22.2 Introduction to Machine Learning and Artificial Intelligence
22.2.1 Machine Learning Terminology
22.3 Neural Networks in Deep Learning
22.3.1 Multiperceptron (MLP) Neural Network
22.3.2 Convolutional Neural Networks (CNNs)
22.3.3 Recurrent Neural Networks (RNNs)
22.3.4 Limitations of Artificial Intelligence Programs
22.3.5 Open-Source Vs Purpose-Built?
22.3.6 Keratoconus and Artificial Intelligence
22.4 AI for Keratoconus Detection
22.5 AI for Keratoconus Classification
22.6 AI for Keratoconus Progression
22.7 Surgery Optimization
22.8 Summary
References
23: Changing Paradigm in the Diagnosis and Management of Keratoconus
23.1 Introduction
23.2 Epidemiology
23.3 Diagnosis
23.4 Evolution in Topography
23.5 Treatment
23.6 Summary
References