- •Preface to the Second Edition
- •Contents
- •List of Abbreviations
- •1: Epidemiology of AMD
- •Core Messages
- •1.1 Introduction
- •1.3 Frequency
- •1.3.1 Prevalence
- •1.3.2 Incidence
- •1.4 Natural Course
- •1.5 Genetic Factors
- •1.5.1 The Complement Pathway Genes
- •1.5.1.1 Complement Factor H (CFH)
- •1.5.1.3 Complement Component 3 (C3)
- •1.5.1.4 Complement Factor I (CFI)
- •1.5.2 The ARMS2 (10q26) Locus
- •1.5.3.1 Apolipoprotein E (APOE)
- •1.5.4 Candidate Gene Association Studies
- •1.6 Environmental Factors
- •1.6.1 Smoking
- •1.6.2 Antioxidants
- •1.6.3 Body Mass Index (BMI)
- •1.6.4 Hypertension
- •1.6.5 Cataract Surgery
- •1.7 Interaction Between Risk Determinants
- •1.7.1 Combined Effects of CFH Y402H and Other Genetic and/or Environmental Factors
- •1.7.2 Combined Effects of 10q26 SNPs and Other Genetic and/or Environmental Factors
- •1.7.4 Combined Effects of the APOE Gene and Other Genetic and/or Environmental Factors
- •References
- •2: Genetics
- •Core Messages
- •2.1 Introduction
- •2.2 Identifying Risk Factors of a Common Disease
- •2.3 Early Findings
- •2.4.1 Functional Implications
- •2.5.1 Functional Implications
- •2.7 Prospects of Genetics in AMD Therapy and Prevention
- •Summary for the Clinician
- •References
- •Core Messages
- •3.1 Introduction
- •3.2 Cause and Consequences of Ageing
- •3.3 Clinical Changes Associated with Retinal Ageing
- •3.4 Ageing of the Neural Retina
- •3.5 Ageing of the RPE
- •3.5.1 Changes in RPE Cell Density
- •3.5.2 Subcellular Changes in the RPE
- •3.5.3 Accumulation of Lipofuscin
- •3.5.4 Melanosomes and Pigment Complexes
- •3.5.7 Antioxidant Capacity of the RPE
- •3.6 Ageing of Bruch’s Membrane
- •3.7 The Association Between Ageing and AMD
- •Summary for the Clinician
- •References
- •Core Messages
- •4.1 Introduction
- •4.2 The Complement System
- •4.3 Evidence for Involvement of the Complement System in AMD Pathogenesis
- •4.4.2 Complement Gene Variants and AMD Subtypes
- •4.4.3 Complement Gene Variants and Progression of AMD
- •4.4.5 Variations of Complement Genes and Response to Treatment: Pharmacogenetics
- •4.5 Emerging Pharmacological Intervention Targeting Complement Dysregulation
- •Conclusions
- •Summary for the Clinician
- •References
- •5: Histopathology
- •Core Messages
- •5.1 Retinal Pigment Epithelium
- •5.1.1 Structure and Function of the Retinal Pigment Epithelium
- •5.1.3 Deposits in the RPE
- •5.2 Bruch’s Membrane
- •5.2.1 Structure of Bruch’s Membrane
- •5.2.3 Deposits in Bruch’s Membrane, Drusen
- •5.3 Choroidal Neovascularization
- •5.4 Detachment of the Retinal Pigment Epithelium
- •5.5 Geographic Atrophy of the RPE
- •Summary for the Clinician
- •References
- •6: Early AMD
- •Core Messages
- •6.1 Introduction
- •6.2 Drusen
- •6.2.3 Fluorescence Angiography and Optical Coherence Tomography
- •6.3 Focal Hypopigmentation and Hyperpigmentation of the Retinal Pigment Epithelium
- •6.4 Abnormal Choroidal Perfusion
- •Summary for the Clinician
- •References
- •Core Messages
- •7.1 Introduction
- •7.2.1 Decreased Visual Acuity
- •7.2.2 Visual Distortion
- •7.2.3 Visual Field Defects
- •7.2.4 Miscellaneous Symptoms
- •7.3 Signs of Choroidal Neovascularization
- •7.3.1 Hemorrhage
- •7.3.2 Macular Edema and Subretinal Fluid
- •7.3.3 Retinal Pigment Epithelial Detachment
- •7.3.4 Miscellaneous Signs
- •7.4 Common Testing Modalities to Diagnose Choroidal Neovascularization
- •7.4.1 Fluorescein Angiography
- •7.4.2 Indocyanine Green Angiography
- •7.4.4 Optical Coherence Tomography
- •Summary for the Clinician
- •References
- •8: Geographic Atrophy
- •Core Messages
- •8.1 Introduction
- •8.3 Histology and Pathogenesis of Geographic Atrophy
- •8.5 Spectral Domain Optical Coherence Tomography in Geographic Atrophy
- •8.7 Risk Factors
- •8.7.1 Genetic Factors
- •8.7.2 Systemic Risk Factors
- •8.7.3 Ocular Risk Factors
- •8.8 Development of CNV in Eyes with GA
- •8.9 Visual Function in GA Patients
- •8.9.1 Measurement of Visual Acuity
- •8.9.2 Contrast Sensitivity
- •8.9.3 Reading Speed
- •8.9.4 Fundus Perimetry
- •8.10 Perspectives for Therapeutic Interventions
- •8.10.2 Complement Inhibition
- •8.10.3 Neuroprotection
- •8.10.4 Alleviation of Oxidative Stress
- •8.10.5 Serotonin-1A-Agonist
- •8.10.6 Perspective
- •Summary for the Clinician
- •References
- •9: Fundus Imaging of AMD
- •Core Messages
- •9.1 Introduction
- •9.2 Color Photography
- •9.3 Monochromatic Photography
- •9.5 Optical Coherence Tomography
- •9.5.2 Coherence Length
- •9.5.3 Time Domain Optical Coherence Tomography
- •9.5.4 Frequency Domain Optical Coherence Tomography
- •9.5.5 Increasing Depth of Imaging
- •9.5.6 General Optical Coherence Tomographic Imaging Characteristics of the Macular Region
- •9.6 Fundus Angiography
- •9.6.1 Fluorescein Dye Characteristics
- •9.6.2 Indocyanine Green Dye Characteristics
- •9.6.3 Cameras Used in Fluorescence Angiography
- •9.6.4 Patient Consent and Instruction
- •9.6.5 Fluorescein Injection
- •9.6.6 Fluorescein Technique
- •9.6.7 Indocyanine Green Technique
- •9.7 Fluorescein Angiographic Interpretation
- •9.7.1 Filling Sequence
- •9.7.2 The Macula
- •9.8 Deviations from Normal Angiographic Appearance
- •9.10.1 Drusen
- •9.12 Neovascular AMD
- •9.13 Retinal Pigment Epithelial Detachments
- •9.14 Retinal Vascular Contribution to the Exudative Process
- •9.15 Follow-up
- •9.15.1 Thermal Laser
- •9.15.2 Photodynamic Therapy
- •9.15.3 Anti-VEGF Therapy
- •Summary for the Clinician
- •References
- •10: Optical Coherence Tomography
- •10.1 Introduction
- •Core Messages
- •10.4 OCT in Geographic Atrophy
- •10.5 OCT in Exudative AMD
- •Summary for Clinician
- •References
- •11: Microperimetry
- •Core Messages
- •11.1 Introduction
- •11.2.1 From Manual to Automatic Microperimetry
- •11.2.2 Automatic Microperimetry
- •11.2.3 Microperimetry: The Examination
- •11.2.4 Microperimetry: Test Evaluation
- •11.2.5 Other Microperimeter
- •11.3 Microperimetry in AMD
- •11.3.1 Early AMD
- •11.3.2 Geographic Atrophy
- •11.3.3 Neovascular AMD
- •11.3.4 Neovascular AMD: Treatment
- •Summary for the Clinician
- •References
- •Core Messages
- •12.1 Introduction
- •12.2 Antioxidants and Zinc
- •12.3 Beta-Carotene
- •12.4 Macular Xanthophylls
- •12.6 Vitamin E
- •12.7 Vitamin C
- •12.8 Zinc
- •12.10 AREDS2
- •Summary for the Clinician
- •References
- •Core Messages
- •13.1 Introduction
- •13.2 Basic Principles
- •13.2.1 Clinical Background
- •13.2.2 Laser Photocoagulation
- •13.2.3 Photodynamic Therapy
- •13.3 Treatment Procedures
- •13.3.1 Laser Photocoagulation
- •13.3.2 Photodynamic Therapy
- •13.4 Study Results
- •13.4.1 Laser Photocoagulation
- •13.4.1.1 Extrafoveal CNV
- •13.4.1.2 Subfoveal CNV
- •13.4.1.3 Meta-analysis
- •13.4.2 Photodynamic Therapy
- •13.4.2.1 Predominantly Classic
- •13.4.2.2 Occult with No Classic Neovascularization
- •13.4.2.3 Minimally Classic
- •13.5 Safety and Adverse Events
- •13.5.1 Laser Photocoagulation
- •13.5.2 Photodynamic Therapy
- •13.6 Variations
- •13.6.1 Laser Photocoagulation: Different Wavelengths
- •13.6.2 Photodynamic Therapy
- •13.6.3 Combination Treatments
- •13.7 Present Guidelines
- •13.7.1 Laser Photocoagulation
- •13.7.2 Photodynamic Therapy
- •13.8 Perspectives
- •Summary for the Clinician
- •References
- •Core Messages
- •14.1 Introduction
- •14.2 Vascular Endothelial Growth Factor (VEGF)
- •14.3 Targets Within the VEGF Pathway
- •14.3.1 Sequestration of Released VEGF
- •14.3.2 Inhibition of VEGF and VEGF Receptor Synthesis by Small Interfering RNA (siRNA)
- •14.3.3 Inhibition of the Intracellular Signal Cascade
- •14.3.4 Natural VEGF Inhibitors
- •14.4 New Methods of Drug Delivery
- •14.5 Combined Strategies
- •Summary for the Clinician
- •References
- •Core Messages
- •15.1 Introduction
- •15.1.1 Anti-VEGF Therapies for NV-AMD
- •15.2.1 How Should Neovascular AMD be Diagnosed?
- •15.2.4.1 Results with Continuous Monthly Treatment
- •15.2.4.2 How Should Treatment be Started?
- •15.2.4.3 What Flexible Approaches Are Reported?
- •Fixed Quarterly Injection Studies
- •Flexible Dosing Regimens: Two Approaches
- •Flexible Dosing Regimens: ‘As Needed’ Approach
- •Flexible Dosing Regimens: ‘Treat-and-Extend’ Approach
- •Summary for the Clinician
- •References
- •Core Messages
- •16.1 Introduction
- •16.3 Current Limitation of Therapy in the Treatment of Exudative AMD
- •16.4 Rationale for Combination Therapy in the Treatment of Exudative AMD
- •16.5 Clinical Data Examining Combination Therapy for Exudative AMD
- •16.5.3 Triple Therapy for Exudative AMD
- •16.5.4 Combination Therapy with Radiation
- •Summary for the Clinician
- •References
- •Core Messages
- •17.1 Introduction
- •17.2 Current Treatment Options for Dry AMD
- •17.3 Targeting the Cause of AMD
- •17.4 Preclinical and Phase I Drugs in Development for Dry AMD
- •17.4.1 Clinical Trial Endpoints in Dry AMD
- •Trimetazidine
- •17.4.2.2 Neuroprotection
- •Ciliary Neurotrophic Factor (CNTF/NT-501)
- •AL-8309B (Tandospirone)
- •Brimonidine Tartrate Intravitreal Implant
- •17.4.2.3 Visual Cycle Modulators
- •Fenretinide
- •17.4.2.4 Other
- •17.4.3 Drugs to Prevent Injury from Oxidative Stress and Micronutrient Depletion
- •17.4.4.1 Complement Inhibition at C3
- •17.4.4.2 Complement Inhibition at C5
- •Eculizumab
- •17.4.4.3 Complement Inhibition of Factor D
- •FCFD4514S
- •Iluvien
- •Glatiramer Acetate (Copaxone)
- •17.5 Summary
- •Summary for the Clinician
- •References
- •18: Surgical Therapy
- •Core Messages
- •18.1 Maculoplasty
- •18.2 Macular Translocation
- •18.3 Single Cell Suspensions
- •18.5 Indications for Surgery
- •18.5.1 Non-responder
- •18.5.2 Pigment Epithelium Rupture
- •18.5.3 Massive Submacular Bleeding
- •18.5.5 Macula Dystrophies
- •Summary for the Clinician
- •References
- •19: Reading with AMD
- •Core Messages
- •19.1 Introduction
- •19.2 Physiological Principles
- •19.3 Reading with a Central Scotoma
- •19.3.1.2 The Reading Visual Field Related to the Fundus (Fig. 19.4b)
- •19.3.1.3 The Reading Visual Field Related to the Text (Fig. 19.4c)
- •19.3.1.4 Eccentric Fixation Related to the Globe (Fig. 19.5)
- •19.3.3 Examination of Fixation Behaviour
- •19.3.4 Motor Aspects
- •19.4 Methods to Examine Reading Ability
- •19.5 Rehabilitation Approaches to Improve Reading Ability
- •Summary for the Clinician
- •References
- •20: Low Vision Aids in AMD
- •Core Messages
- •20.2 Effects of Visual Impairment in AMD
- •20.5 Optical Magnifying Visual Aids for Distance
- •20.5.1 Aids for Watching Television
- •20.8 Electronic Reading Instruments
- •20.9 Additional Aids
- •20.10 Noteworthy Details for the Provision of Low Vision Aids
- •20.11 Basic Information on Prescription
- •Summary for the Clinician
- •References
- •Index
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0.4 |
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Minimal reading |
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40° |
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Fig. 19.1 Visual acuity is dependent on eccentricity. With increasing eccentricity visual acuity decreases rapidly. The range of reading ability is limited on the one hand by the minimum size of the reading visual field (2° each, right and left of fixation), on the other hand by the resolution (for newspaper print in 25 cm approximately 0.4 is required). This acuity is found at the margin of the fovea. It becomes clear that measuring foveal visual acuity is not sufficient for gauging reading ability, because this assesses single optotype recognition (Modified after [6, 7])
extent is required: 2° each to the right and left of fixation, and 1° each above and below [8]. This minimum reading visual field corresponds approximately to the ‘visual span’ [9] and the ‘word identification span’ [10]. Its extent is more or less in accordance with the size of the fovea. Therefore, visual acuity alone is an insufficient measure for reading ability, because it tests only one optotype at a time (Fig. 19.1). The range of reading ability is limited on the one hand by the resolution of the retinal area used and on the other hand by its minimum extent, the minimum reading visual field. The total perceptual span during one fixation, in the following called ‘reading visual field’, can exceed this minimum up to 5° (or 15 letters) in reading direction [11].
Figure 19.2 shows a fundus image which was produced by a Scanning Laser Ophthalmoscope (SLO), with different morphological and functional data: The proportion of foveola and fovea, visual acuity and cone-density depend on eccentricity. The blue oval displays the minimum reading visual field.
In order to see the next group of letters clearly, the eye has to make a saccade. The eye movements during reading are characterized by a regular sequence of saccades and fixations, which results in a typical staircase pattern (Fig. 19.3).
Fig. 19.2 Relationship between morphological and functional data, drawn on an SLO-fundus image: The proportions of foveola and fovea, the minimum size of the reading visual field (blue oval), visual acuity (yellow curve) and cone density (black curve) dependent on eccentricity (Modified after [6])
Saccade
Return sweep
Fixation
Fig. 19.3 Eye movements during reading (schematic): regular sequence of saccades and fixations, return sweeps – resulting in a typical staircase pattern
19.3Reading with a Central Scotoma
19.3.1The Reading Visual Field Related to Other Parameters
(Figs. 19.4 and 19.5)
19.3.1.1The Reading Visual Field Related to the 30° Visual Field (Fig. 19.4a)
On the left, the minimum reading visual field (required for newspaper print) is displayed. It is obvious that visual field defects in the centre disturb the reading process significantly.
In the middle, a patient with an absolute central scotoma is shown. With central fixation, the reading visual field is completely covered by the scotoma and is functionless. Most of these patients develop a valuable adaptive strategy (Fig. 19.4 right): The patient uses a
19 Reading with AMD |
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289 |
normal |
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absolute central scotoma |
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minimal size |
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central fixation |
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eccentric fixation |
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30° visual field |
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2° |
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20° 30° |
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4° |
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a
Fundus
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Fig. 19.4 The reading visual field related to other parameters:
Related to the 30° visual field (a): Left: minimum size under normal conditions. Middle: In absolute central scotoma and central fixation, the reading visual field is covered by the scotoma and functionless. Right: In absolute central scotoma and eccentric fixation, the scotoma and the blind spot are shifted. The new reading visual field is located on a healthy retinal area with a lower resolution. Related to the fundus (b): Left: the normal situation. Middle: macular degeneration and central fixation. Right:
eccentric fixation above the lesion corresponds to the fixation below the scotoma. Related to the text (c): Left: the normal situation: only within the marked area (within the central 4°) is the text perceived clearly. Middle: in absolute central scotoma and central fixation there is no reading ability. Right: absolute central scotoma and eccentric fixation: the new reading visual field does not have sufficient resolution. When the text is magnified, reading ability is regained (Modified after [12])
new, healthy visual field area on the margin of the scotoma. This new reading visual field becomes the centre of the visual field. Therefore, the scotoma is shifted, as well as the blind spot. The blind spot serves as a reference scotoma and shows the extent of the shift.
19.3.1.2 The Reading Visual Field Related to the Fundus (Fig. 19.4b)
On the left the normal situation, in the middle and on the right the macular degeneration is displayed. Fixation below the scotoma means fixation above the lesion. The eccentric retinal fixation area, also called ‘preferred retinal locus (PRL)’, has a lower resolution than a healthy fovea. (The term ‘eccentric fixation’ is here
used for any non-foveolar fixation, independent of the subjective gaze direction of the patient).
19.3.1.3 The Reading Visual Field Related to the Text (Fig. 19.4c)
On the left the normal situation: due to the visual acuity curve, only in the marked area ( the central 4°) the text is perceived clearly. Middle: In absolute central scotoma and central fixation, there is no reading ability.
Right: In eccentric fixation, a healthy visual field area at the margin of the scotoma is used. Therefore, the scotoma is shifted. The new retinal fixation locus at the edge of the scotoma does not have a sufficient solution for reading newspaper print. When the text is
290 |
S. Trauzettel-Klosinski |
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Fig. 19.5 Demonstration of central (a) eccentric (b) fixation related to the eye globe position. In central fixation, the object falls directly into the scotoma. In eccentric fixation above the
lesion, i.e. below the scotoma, gaze direction is shifted upwards as well as the scotoma, the object becomes free and is seen with an eccentric retinal locus
magnified, reading ability is regained. This is the basis for the efficiency of magnifying visual aids.
19.3.1.4 Eccentric Fixation Related to the Globe (Fig. 19.5)
Figure 19.5 demonstrates eccentric fixation related to the globe. Fixation above the lesion, i.e. below the scotoma, causes a shift of the scotoma and of the gaze position upwards.
19.3.2The Significance of Fixation Behaviour
Patients with eccentric fixation show preferred directions of scotoma shift (Fig. 19.6): In own studies using SLO and Tübingen Manual Perimetry, approximately 80% of the patients shifted the scotoma upwards, 14% to the right [12, 15]. Similar results were reported by Aulhorn [16] based on perimetric investigations. In contrast, other authors described a shift to the right
to occur much more frequently – up to 63% [13, 14]. The corresponding retinal fixation loci are therefore located mostly above or left of the lesion, i.e. in the upper left quadrant in both eyes. This should be considered before retinal surgery. A shift of the scotoma into the upper visual field seems to be the best condition for reading, because then the line is free and the lower visual field is not impaired in orientation on the page. The choice of a PRL-location is not only dependent on the best local retinal resolution at the margin of the scotoma, but is also influenced by focal visual attention [17, 18].
Figure 19.7 shows the SLO-fundus image of a patient with AMD: She reads the text with an eccentric PRL above the lesion. She is fixating the ‘i’. The patient sees the text upright.
In case of an incomplete absolute central scotoma – a ring scotoma – central fixation persists, but the central island is too small for reading. This explains a discrepancy between visual acuity and reading ability. Often, reading ability can be regained in a later
