- •Foreword
- •Preface
- •Contents
- •Contributors
- •Key Points
- •Introduction
- •Etiology
- •A Genetic Cause
- •Family Studies
- •Associations with Race
- •Specific Genes Conferring AMD Risk
- •Complement Factor H
- •C2-CFB Locus
- •Complement Component 3
- •Other Inflammatory Factor Variants
- •Toll-Like Receptor
- •VEGF-A
- •Genetic Variants on Chromosome 10q26
- •LOC387715/ARMS2
- •HTRA1
- •Other Genetic Variants
- •Apolipoprotein E
- •Fibulin 5
- •Hemicentin-1
- •LOC387715/HTRA1 and CFH
- •Genetic Predisposition to a Specific Late Phenotype
- •Conclusion
- •References
- •Key Points
- •Introduction
- •Smoking
- •Alcohol
- •Increased Light Exposure
- •Obesity
- •Exercise
- •Dietary Fat Intake
- •Phytochemicals
- •Ginkgo Biloba
- •Anthocyanins
- •Resveratrol
- •Epigallocatechin Gallate
- •Mineral Supplements
- •Summary
- •References
- •Key Points
- •Introduction
- •Classification
- •Nonexudative (Non-neovascular or Dry) AMD
- •Exudative (Neovascular or Wet) AMD
- •Retinal Angiomatous Proliferation
- •Polypoidal Vasculopathy
- •Diagnosis
- •Differential Diagnosis
- •Nonexudative AMD
- •Central Serous Chorioretinopathy (CSCR)
- •High Myopia
- •Stargardt’s Disease/Fundus Flavimaculatus
- •Cuticular Drusen
- •Pattern Dystrophy
- •Old Exudative AMD
- •Old Laser Scars
- •Other Conditions
- •Exudative AMD
- •Central Serous Chorioretinopathy
- •Idiopathic Polypoidal Choroidal Vasculopathy
- •Retinal Angiomatous Proliferation (RAP)
- •Presumed Ocular Histoplasmosis Syndrome (POHS)
- •Angioid Streaks
- •High Myopia
- •Cystoid Macular Edema
- •Traumatic Choroidal Rupture
- •Macular Hemorrhage
- •CNV Secondary to Laser
- •Idiopathic
- •Summary
- •References
- •Key Points
- •Introduction
- •Color Photography
- •Monochromatic Photography
- •Autofluorescence Imaging
- •Optical Coherence Tomography
- •Enhanced Depth Imaging
- •Fundus Angiography
- •Fluorescein Dye Characteristics
- •Indocyanine Green Dye Characteristics
- •Cameras and Angiography
- •Patient Consent and Instruction
- •Fluorescein Injection
- •Fluorescein Technique
- •Indocyanine Green Technique
- •The Macula
- •Deviations from Normal Angiographic Appearance
- •Indocyanine Green Angiographic Interpretation
- •Drusen
- •Choroidal Neovascularization
- •CNV and Fluorescein Angiography
- •Retinal Vascular Contribution to the Exudative Process
- •Fundus Imaging Characteristics of Therapies for Neovascular AMD
- •Thermal Laser
- •Photodynamic Therapy
- •Anti-VEGF Therapy
- •References
- •Key Points
- •Introduction
- •AREDS
- •Carotenoids
- •Beta-Carotene
- •Macular Xanthophylls
- •Fatty Acids
- •Vitamin E
- •Vitamin C
- •Zinc
- •Folate/B-Vitamins
- •AREDS2
- •Summary
- •References
- •6: Management of Neovascular AMD
- •Key Points
- •Introduction
- •Angiogenesis
- •An Overview of VEGF
- •VEGF-A Isoforms
- •VEGF-A Physiological Response
- •VEGF-A Response in Retinal Diseases
- •Antiangiogenic Drugs
- •Pegaptanib
- •Drug Overview
- •Published Trials
- •Bevacizumab
- •Drug Overview
- •Published Studies
- •Ranibizumab
- •Drug Overview
- •Published Trials
- •Safety Data
- •Upcoming Clinical Trials
- •Promising VEGF Inhibitors
- •Conclusion
- •References
- •Key Points
- •Introduction
- •Antinflammatory Therapy
- •Verteporfin Angioocclusive Therapy
- •Antiangiogenic Therapy
- •Rationale for Combination Therapy in the Treatment of Exudative AMD
- •Clinical Data Examining Combination Therapy for Exudative AMD
- •Verteporfin Therapy in Combination with Triamcinolone
- •Verteporfin PDT Therapy in Combination with Anti-VEGF Agents
- •Triple Therapy for Exudative Age-Related Macular Degeneration
- •Summary
- •References
- •Key Points
- •Drusen
- •Geographic Atrophy
- •Imaging Modalities in Dry AMD
- •Clinical Trials for Dry AMD
- •Study Design
- •Risk Reduction in Dry AMD
- •AREDS
- •Laser/CAPT
- •Anecortave Acetate
- •Control of Disease Progression
- •Visual Cycle Inhibition: Antioxidants
- •Antioxidants
- •Complement
- •Neuroprotective Agents
- •Modulators of Choroidal Circulation
- •Recovery
- •Gene Therapy
- •Stem Cell Therapy
- •Retinal Prostheses
- •Summary
- •References
- •Key Points
- •Introduction
- •Emerging and Future Therapies
- •Ranibizumab
- •Bevacizumab
- •VEGF Trap-Eye
- •Bevasiranib
- •Vatalanib
- •Pazopanib
- •Sirna-027
- •Anti-VEGFR Vaccine Therapy
- •Radiation
- •Epi-Rad90™ Ophthalmic System
- •IRay
- •Infliximab
- •Sirolimus
- •Gene Therapy
- •AdPEDF.11
- •AAV2-sFLT01
- •Other Pathways
- •Squalamine Lactate
- •Combretastatin A4 Phosphate/CA4P
- •Volociximab
- •NT-501, Ciliary Neurotrophic Factor
- •Sonepcizumab
- •Summary
- •References
- •Key Points
- •Introduction
- •Evidence-Based Medicine
- •Interventional Evidence
- •Masking
- •Dropout Rate
- •Validity
- •Risk Reduction
- •Pharmacoeconomic Analysis
- •Cost-Minimization Analysis
- •Cost-Benefit Analysis
- •Cost-Effectiveness Analysis
- •Quality-of-Life Instruments, Function-Based
- •Quality-of-Life Instruments, Preference-Based
- •Utility Acquisition
- •Utility Gain
- •Decision Analysis
- •Comparative Effectiveness (Human Value Gain)
- •Value Trumps Cost
- •Costs
- •Cost Basis
- •Cost Perspective
- •Cost-Utility Ratio
- •Cost-Effectiveness Standards
- •Discounting
- •Standardization
- •Patient Respondents
- •Cost Perspective
- •The Future
- •Macroeconomic Costs and AMD
- •Employment and Wage Loss
- •Gross Domestic Product (GDP)
- •Other Costs
- •Financial Return on Investment (ROI)
- •References
- •Index
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Fig. 3.12 (a) Color photo and (b) fluorescein angiogram of two patients with Stargardt’s disease/Fundus flavimaculatus highlighting retinal flecks and a silent choroid with macular hyperfluorescing lesions
Pattern Dystrophy
Patients with this condition present with yellow, vitelliform lesions in the macula with reticular hyperpigmentation. Key differentiating features include younger patients with pattern dystrophy and the FA findings. FA shows early hypopigmentation and surrounding hyperpigmentation with late staining of vitelliform areas [51–54].
Old Exudative AMD
CNV that has either been treated or involutes can leave atrophic changes. Old subretinal or subRPE tissue as seen on clinical exam or on OCT may help to differentiate old CNV from geographic atrophy.
Old Laser Scars
The history of prior laser treatment should be obtainable in these cases. In addition, FA should reveal areas of hypofluorescence that correspond to the laser scars, as opposed to areas of atrophy in AMD that usually are hyperfluorescent.
Other Conditions
Some other conditions that may mimic drusen or dry AMD include:
Hard exudates Cotton wool spots
Type II membranoproliferative glomerulonephritis [55]
Exudative AMD
Central Serous Chorioretinopathy
Patients with CSCR may have serous retinal detachments or sub-RPE fluid (RPE detachment) and can be mistaken for RPE detachments in wet AMD. Differentiating factors include age (usually ages 25–50), lack of drusen, absence of hemorrhage, and multiple areas of hyper and hypoflourescence on ICGA. The natural history is significantly different with visual recovery being common in CSR [42–46].
Idiopathic Polypoidal Choroidal Vasculopathy
Patients with IPCV are typically elderly and suffer from hypertension just as in wet AMD. Differentiating factors include darkly pigmented individuals, lack of drusen, multiple serosanginous RPE detachments with a significant lipid component (rare variant of neovascular AMD, as well), minimal fibrous component (rare disciform scar formation), red-orange color of complex (as opposed to grey-green), and choroidal vascular channels terminating in polyp-like structures on ICGA [28–31].
Retinal Angiomatous Proliferation (RAP)
Retinal angiomatous proliferation is often difficult to be fully differentiated from exudative AMD especially in stage 3 and is largely considered a
3 Diagnosis of Age-Related Macular Degeneration |
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Fig. 3.13 (a) Color photo, (b) late phase fluorescein angiogram, and (c) ICG highlighting the hot spot in a patient with retinal angiomatous proliferation
subset of AMD. Typical features include retinal hemorrhages, prominent cystoid macula edema, elderly (85 years), and Caucasian. ICGA can detect hot spots (Fig. 3.13) [25–27].
Presumed Ocular Histoplasmosis Syndrome (POHS)
Patients with POHS have punched out yellowwhite chorioretinal scars in the midperiphery, chorioretinal scarring adjacent to optic nerve/ peripapillary atrophy, and CNV. It is more common in the Ohio-Missippi River Valley and in younger individuals (20–50) (Fig. 3.14) [10].
Angioid Streaks
Angioid streaks are bilateral reddish-brown subretinal bands radiating from the optic disc representing calcified Bruch’s membrane. About 50% of the time, an associated condition such as Ehlers– Danlos, pseudoxanthoma elasticum, Padget’s
Fig. 3.14 A patient with presumed ocular histoplasmosis syndrome with punched out chorioretinal lesions, peripapillary atrophy, and CNV
disease, and sickle cell disease can be found. Key differentiating features are the peripapillary streaks, which show as window defects on FA due to overlying atrophy (Fig. 3.15) [56, 57].
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Fig. 3.15 (a) Fundus photo and (b) fluorescein angiogram CNV due to angioid streaks in a patient with Ehlers–Danlos syndrome
High Myopia
Patients with myopic degeneration may develop macular CNV. The key differentiating feature of this condition is the history of significant myopia (at least 6 diopters). Other features include lack of drusen, lacquer cracks (yellow subretinal streaks), macular hyperpigmented spots representing nonprogressing CNV (Fuchs spot), and optic nerve anomalies including an oblique insertion (tilted) of the optic nerve and an area of white sclera and/or choroidal vessels (myopic crescent) surrounding the nerve (Fig. 3.16) [47, 48].
Cystoid Macular Edema
Patients with neovascular AMD may develop CME. However, some patients diagnosed with cystoid macular edema have undiagnosed occult CNV lesions. This is specifically relevant in patients with the diagnosis of idiopathic CME or post-cataract surgery CME. FA is particularly useful in these patients.
Pearl
Rule out occult CNV in cases of CME of unknown etiology or CME in the postoperative setting.
Fig. 3.16 Fundus photo of old CNV due to myopic degeneration
Traumatic Choroidal Rupture
Acutely there is often subretinal hemorrhage in or adjacent to the rupture and CNV can later form on the edge of the rupture site. These patients typically have unilateral findings and a history of significant trauma.
Macular Hemorrhage
Hemorrhage secondary to retinal arterial macroaneurysm, valsalva retinopathy, and trauma can be confused with hemorrhage from AMD. Differentiating features include lack of associated AMD findings, history, and unilateral findings.
