Index

A

A2E, 50–53, 142, 267, 268 ABCA1-gene, 17 ABCA4-gene, 18, 35 ACU-4429, 268

AdPEDF, 229

AD. See Alzheimer’s disease (AD)

Advanced glycation end products (AGE), 79–80, 89 AGE. See Advanced glycation end products (AGE) AG-013958, 229

Age-related eye disease Study (AREDS) alleviation, oxidative stress, 133 beta-carotene, 193

defined, 70–71, 192, 263

Age-related macular degeneration (AMD)

blue fundus autofluorescence image, 179, 180 causes and consequences, and neural retina, 57 caution, 6

choroidal perfusion, 107–108 classification, epidemiologic studies, 4

CNV (see Choroidal neovascularization (CNV)) color fundus and fundus auto fluorescence

images, 179

complement system (see Complement system, AMD) description, 101

diabetic retinopathy, 179 drusen, 102–107

dry (see Dry AMD) environmental factors

antioxidants, 18–19 BMI, 19

cataract surgery, 19–20 hypertension, 19 smoking, 18

FAF, 178

fundus autofluorescence, 57, 58 fundus imaging (see Fundus imaging) GA (see Geographic atrophy (GA)) genetic factors

ARMS2 (10q26) locus, 12–13

candidate gene association studies, 17–18 complement pathway genes, 7–12 lipid-related genes, 13–17

heterogeneous etiological factors, 101 histopathologic studies, 178 incidence rates and risks, 7 interaction, risk determinants

APOE gene, genetic and environmental factors, 21 CFH and ARMS2/HTRA1 SNPs, 21

CFH Y402H, genetic and environmental factors, 20 10q26 SNPs, genetic and environmental factors, 20–21

lipid metabolism, 3 natural course, 7

nutritional supplementation (see Nutritional supplementation, AMD)

NV-AMD (see Neovascular AMD (NV-AMD)) prevalence

geographic atrophy and neovascular, 6 population-based studies, 4–6

quantitative parameters, 102 reading (see Reading, AMD) RPE, 107

smoking, 3

soft drusen and pigmentary abnormalities, 3 stages, 101, 102

TIMP3, 17

treatment (see Treatment, AMD) “wet” and “dry”, 101

Age-related maculopathy (ARM) BM, 165, 166

disorganization retinal layers, 167 drusenoid PED, 165, 166

OS/IS junction, 165, 166 types, drusen, 165

AL-8309B (Tandospirone), 267 Alternative pathway of complement (APC)

activation, 66

AMD donor eyes and genetic Studies, 68 Alzheimer’s disease (AD)

APOE gene, 35 protein isoforms, 35

AMD. See Age-related macular degeneration (AMD) Anticalines, 228

Antioxidants AREDS, 18–19 capacity, RPE

oxidative damage, 55 peripheral, 56

ROS, 55–56 reduction of serum, 18 and zinc

AREDS, 192, 193

categories, disease severities, 192 mortality rates, 192

Anti-VEGF therapy description, 233

diseases management, 235 evidence-based guidelines, 235 fluorescein leakage, 159, 160 macula, thermometer, 160 management, 235–236 NV-AMD

antibody Fab fragment, 234 ‘as needed’ approach, 241–242

continuous monthly treatment, 238, 239 diagnosis, 236

fixed quarterly injection studies, 240–241 lesions, 237–238

long-term considerations, 242 parameters, 238

placental growth factors, 234–235 ranibizumab and bevacizumab, 234, 235 RCT, 234

‘treat-and-extend’ approach, 242 treatment, 240

SNPs, 234

APC. See Alternative pathway of complement (APC) APOE. See Apolipoprotein E (APOE) Apolipoprotein E (APOE)

allele-based meta-analysis, APOe4 and APOe2, 15–16

defined, 13

and genetic/environmental factors, 21 haplotypes, 14, 16

RPE cells and Bruch’s membrane, 16–17 AREDS. See Age-related eye disease study (AREDS) ARM. See Age-related maculopathy (ARM) ARMS2 (10q26) locus

allele-based meta-analysis, 13, 14 AMD, 12–13

haplotypes, 1

HTRA1 meta-analyses, 13 linkage studies, 12

‘As Needed’ approach, NV-AMD bevacizumab, 242

PrONTO, 239, 241 re-treatment criteria, 241 SUSTAIN trial, 239, 241

Atrophy, non-geographical body-mass-index, 128

choroidal neovascularization, 122 clinical manifestations, 111–118 contrast sensitivity, 131

foveal, 131

genetic factors, 127–128 light exposition, 128 reading speed, 131–132 spectral-domain-OCT, 125 therapy, 131

Auto fluorescence imaging emission, light, 142

fundus camera-based systems, 144 lipofuscin, 142

SLO-based systems, 144

B

Barbados-Eye Study, 6

Basal laminar deposits (BLD), 87, 88 Basal linear deposits, 84, 104–105

BDES. See Beaver Dam Eye Study (BDES) Beaver Dam Eye Study (BDES)

AMD subtypes, age, 6 hypertension, 19 meta-analysis, 18

Bevacizumab, 228

Bevasiranib, 229

BLD. See Basal laminar deposits (BLD) Bleeding

intraretinal, 255 submacular, 279–280

Blindness

definition, 33, 295

Blue Mountains Eye Study (BMES) beta-carotene, 193

intake, lutein/zeaxanthin, 194 vitamin E intake, 196

BM. See Bruch’s membrane (BM) BMI. See Body mass index (BMI) Body mass index (BMI), 19 Brachytherapy

epimacular, 255

Brimonidine tartrate intravitreal implant, 267 Bruch’s membrane (BM)

age-related changes AGE, 79–80

biochemical characteristics, 81, 82 cross-linking, 79

different aged specimens, 80, 81 donor eyes, 81

electron and light microscopic, 79 fatty acids, 81

glycosylations, 79 hydrauic conductivity, 82

immunohistochemical staining, 81 macular ageing, 83

MMP, 82 peroxidized lipids, 82 phospholipids, 82 protein vitronectin, 79

quick-freeze/deep-etch technique, 81 TIMP, 82

unsaturated fatty acids, 82–83 defined, 56

drusen

amorphous and vesicular structure, 84, 85 BLD, 87

choroid, 87 classification, 84, 86 description, 83

histological appearance, 83 hypothesis, 87

lipid contents, 84, 86 LSC, 85–86

macular degeneration, 87 neutral lipids, 85

ophthalmoscope, 83, 84 ophthalmoscopically visible change, 83

pentalaminar structure, 79, 80

C

C3. See Complement component 3 (C3) Candidate gene approach, 34, 38 Carboxyethylpyrrole (CEP), 67 Carboxymethyl lysine, 79

CAREDS, 195

Catalase, 55, 56

Cataract and Age-Related Maculopathy study, 102, 165

Cathepsin D, 54, 55

CCTV. See Closed circuit television systems (CCTV) CDCV-hypothesis, 34

CDRV-hypothesis, 34, 35 CETP-gene, 17 CFB-gene, 37

CFB. See Complement factor B (CFB) CFH. See Complement factor H (CFH) CFI. See Complement factor I (CFI)

Cholesterol, 16–17, 81, 87, 128 Cholesteryl transfer protein, plasma, 39 Chondroitin sulphate, 87

Choriocapillaris (CC), 56, 122, 123, 152, 219 Chorioretinopathy, central, serous, 153 Choroidal neovascularization (CNV)

AGE, 89

autofluorescent image, 116, 117 capillaries growth, 88

clinical differentiation, 88 combination treatments

PDT, anti-angiogenic and anti-inflammatory therapies, 220

steroids, verteporfin therapy, 219 verteporfin PDT, 219

cumulative oxidative stress, 247 description, 87, 111, 203 development, 69

FA, 117

fatty acid metabolism, 91 fibrovascular membranes, 87–88 field defects

dark spot, 113 description, 112–113 microperimetry, 113

fluorescence angiography, 88, 89 foggy vision, 113

hemorrhage

collection, blood, 113 RPE, 113, 114

VEGF levels, 113, 115 hypoxia and lipofuscin, 91 ICG angiography, 117–118 immigrating capillaries, 91 immune system, 88–89

laser photocoagulation (see Laser photocoagulation) leakage, 238

macular edema and subretinal fluid, 113–115 natural fluorophores, 118

occult neovascularization, 88, 90 OCT, 88–90, 118

oxidation processes, 89 pathogenic processes, 247

PDT (see Photodynamic therapy (PDT)) phospholipids, 91

photoreceptor cells, 91

polypoidal choroidal vasculopathy, 116, 117 principles

“extra-foveal” membrane, 203, 204 FA, 203

“juxta-foveal” membrane, 204, 205 perifoveal laser technique, Crétei, 204, 210

retinal microglia cells, 89 retina specialists, 221–222 RPE detachment, 114–116 subfoveal, 72, 237 subtypes, 237

VA

acuity change, 111–112 anticoagulated patients, 111 testing, 112

VEGF, 90, 91, 221 verteporfin, 250 visual distortion

macular diseases, 112 PHP, 112

screening tool, 112 Choroidal perfusion

choriocapillaris, 107, 108 description, 107

fluorescein angiography, 107, 108 Ciliary neurotrophic factor (CNTF)

defined, 266–267 efficacy, 133

mueller glial membranes, 266 retinal degeneration, 266 retinitis pigmentosa, 267

Closed circuit television systems (CCTV) advantages, 303, 304

disadvantages, 304

letters appearance, monitor, 303, 304 mobile electronic reading system, TFT

monitor, 304 specialty, 303

CME. See Cystoid macular edema (CME) CNTF. See Ciliary neurotrophic factor (CNTF) CNV. See Choroidal neovascularization (CNV) Coherence tomography, optical

drusen, 106, 107 frequency-domain-optical, 145

spectral-domain-OCT (see Spectral domain optical coherence tomography (SD-OCT))

Coherence time, 144 Collagen derivatives, 85–86 Combination therapy, 247–256

Common disease-common variant (CDCV) hypothesis, 34

Common disease-rare variant (CDRV) hypothesis, 34, 35 Complement component 2 (C2) See also Complement

factor B (CFB)

associated variants identification, 36–38 SNPs, 38

Complement component 3 (C3), 11, 12 Complement factor B (CFB)

allele-based meta-analysis, 10 protective haplotypes, 9 proteins, 9

R32Q/IVS10 haplotype, 11 Complement factor H (CFH)

activation, 8–9

allele-based meta-analysis, 8

AMD-associated genes, complement cascade, 37–38 and ARMS2/HTRA1 SNPs, 21

genetic polymorphism, 269 GWAS, 35, 37

and isoform FHL-1, 37

population attributable risk, Y402H, 9 protective haplotypes, 37

RCA, 270

validated AMD susceptibility loci and functional variants, 36, 37

Y402H and genetic/environmental factors, 20 Complement factor I (CFI), 11

Complement system, AMD activation

abnormal, 69 APC, 66, 68

prediction and impact, plasma levels, 68 prophylactic intervention, 69

clinical application, 65–66 dysregulation, 65 evidence, involvement

blood protein levels, 67

genetic component, susceptibility, 67 human studies, pathogenesis, 66–67 in vitro and animal studies, 67

gene variants and subtypes CNV, 69

“cuticular drusen”, 69 PCV, 69–70

immune processes, 66

nutrition, supplementation and smoking, 70–71 pharmacogenetics, 71

pharmacological intervention, dysregulation, 72 progression and gene variants, 70

therapeutics, 72 Copaxone, 272–273 Copenhagen City Eye Study, 7 Corticosteroids, 248, 254, 272

C-reactive protein (CRP), 20, 37, 67 Cystoid macular edema (CME), 113, 114

D

Degeneration

macular degeneration (see Macular degeneration) reticular pigment, 106

DENALI-Study, 219, 253

DHA. See Docosahexaenoic acid (DHA) Disposable soma theory, 52 Docosahexaenoic acid (DHA)

defined, 195 intakes, 196 LCPUFAs, 195

Drusen CFH, 102

classification, 103

fluorescence angiography and OCT hydrophilic fluorescein dye, 106 RPE, 107

late-stage atrophic/neovascular lesions, 102 psychophysical examinations, 103 spontaneous modifications

basal linear deposits, 104–105 cuticular, 104, 105

hard, 103 peripheral, 106

reticular pseudodrusen, 105–106 soft, 104

unilateral/bilateral late AMD, 102 vitronectin, 102

Dry AMD clinical trial

OCT, 265

visual acuity, 264–265 drugs, inflammation

additional complement pathway-modulating drugs, 272 anti-inflammatory drugs, 272–273

ARC-1905, 272 CFH, 269

complement inhibition, factor D, 272 complement pathway, 270 eculizumab, 271–272

POT-4, 270–271 GA, 263

irreversible blindness, 263

oxidative stress and micronutrient depletion antioxidant properties, 268

DHA, 268

drugs, prevent injury, 269 OT-551, 269

photoreceptors and RPE, 265–268 RPE, 263

treatment options antiangiogenic therapies, 264 AREDS, 263 choriocapillaris, 264 cigarette smoking, 264

Dystrophy vitelliform, 150

E

ECM. See Extracellular matrix (ECM) Eculizumab, 72

Eicosapentaenoic acid (EPA) and DHA, 195, 196 serum concentration, 195

Endostatin, 229, 230

Enhanced-Depth-Imaging-OCT, 115, 116, 145 Environmental factors, 18–21

EPA. See Eicosapentaenoic acid (EPA) Epidemiology, AMD, 3–22 Extracellular matrix (ECM)

degradation and maintenance, 39 formation, 33

Eye Disease Case Control Study (EDCCS), 195, 196

F

FA. See Fluorescein angiography (FA)

FAM. See Fundus autofluorescence in age-related macular degeneration (FAM)

FBLN6-gene, 18 FCFD4514S, 72, 272 Fenretinide, 267–268

Fibrovascular pigment epithelial detachment (FVPED), 203–204

Filling-in-phenomenon, 183 Fine matrix mapping, 132 Finnish case-control Study, 21 Fixation

central, 176, 177, 181, 183, 184, 280, 288, 289 clinical evaluation, 176–178

eccentric, 131, 132, 181, 280, 289–291 mostly eccentric, 290, 291

Fixation behaviour, 290–292 Fixation locus, preferred retinal, 289 Fixation stability, 176, 181, 184, 291 Fixed quarterly injection studies

EXCITE trial, 239, 240 PIER trial, 239, 240 SAILOR data, 241 SUSTAIN, 239, 240

Fluorescein angiography (FA) choroidal-based speckled

hyperfluorescence, 204 CNV, 203

FOCUS Study, 252–253 Free radical theory, 46 Fundus angiography

cameras, 147 CNV, 146

fluorescein dye characteristics, 146 fluorescein injection, 148

ICG dye characteristics, 146–147 patient consent and instruction, 147–148 sodium fluorescein, 146

Fundus autofluorescence imaging classification, abnormal FAF, 124, 125 FAM, 124

image analysis software, 124 LF, 123, 124

monitoring, atrophic progression, 124 monogenetic retinal diseases, 123–124

Fundus autofluorescence in age-related macular degeneration (FAM), 124

Fundus imaging angiography, 146–149

anti-VEGF therapy, 159–160

auto fluorescence imaging, 142, 144 color photography, 142

deviations, angiographic appearance age-related macular degeneration, 150 hyperfluorescence, 149

fluorescein angiographic interpretation, 149 indocyanine green angiographic interpretation, 150 monochromatic and color photography, 141 monochromatic photography, 142

neovascular, 152–155 non-neovascular

ophthalmoscopy, 151 vitelliform dystrophy, 150

OCT, 144–146 PDT, 159 perimetry, 132

pigmentary abnormalities, GA fluorescein angiography, 152 focal hyperpigmentation, 151 pigmentary alteration, 152

retinal diseases, 141 retinal PED

choroidal neovascularization, 155, 156 CNV, 155

ICG angiography, 153, 155

intra-and subretinal hemorrhage, 155–158 retinal vascular contribution, exudative process

chorioretinal anastomosis, 158

polypoidal choroidal vasculopathy, 158–159 retinal disease, 158

RVAC, 158 thermal laser, 159

FVPED. See Fibrovascular pigment epithelial detachment (FVPED)

G

GA. See Geographic atrophy (GA) Galilean and Kepler telescopes

binocular vision, 302 calculation, magnification, 302 LVAs, distance, 299, 301 reading, 302, 303

spectacle, reading cap, 301, 302 GAP-Study, 106, 124, 126, 127, 129, 133 GATE-Study, 133

Genetics

ABCA4 and APOE genes, 35 ARMS2/HTRA1

AMD pathogenesis, 39 functional data, 39

linkage signal, chromosome, 38

risk variants, rs1061170 and rs10490924, 38 variants, SNPs, 39

CFH, 35–38

ECM formation, 33 GWAS, 39–40

risk factors identification, disease, 34–35 therapy and prevention, 40

Genome-wide association studies (GWAS) identification, CFH, 39

LIPC and AMD, 17

Geographic atrophy (GA) AMD, 121, 122 clinical characteristics

BM, 122

fundus autofluorescence images, 122, 123 CNV development, eyes, 129–130

defined, 167

fixation site, patient, 180 foveal sparing, 180

fundus autofluorescence imaging, 123–125 genetic factors

AMD pathogenesis, 127 TLR3 variant, 128

histology and pathogenesis choroidal capillaries, 123 inflammatory processes, 123

ocular risk factors, 129 quantification, progression

BDES, 126 GAS, 125–126 risk factors, 127

Stargardt’s macular dystrophy, 27 SD-OCT, 125

sensitivity map, fundus autofluorescence image, 181 SLO microperimetry, 180

systemic risk factors cataract extraction, 128

choroidal neovascularization, 128–129 hypertension, 128

therapeutic interventions alleviation, oxidative stress, 133

anti-inflammatory substances, 132 CNTF, 133

complement inhibition, 133 neuroprotection, 133 serotonin-1A-agonist, 133

visual function

contrast sensitivity, 131 fundus perimetry, 132

measurement, visual acuity, 130–131 reading speed, 131–132

Geographic atrophy Study (GAS), 125–126

GWAS. See Genome-wide association studies (GWAS)

H

High temperature requirement factor A1 (HTRA1) gene meta-analyses, 13

SNPs, 21

Histopathology

BM (see Bruch’s membrane (BM))

CNV (see Choroidal neovascularization (CNV)) detachment

amino acids, 93 BM, 91, 92

fibrovascular tissue, 92 hydrophilic sodium fluorescein, 92 hydrophobic barrier, 92, 94 hydrostatic pressure, 94

integrins, 93

lipids content, 92–93

optical coherence tomography, 92, 93 oxidative damage, 93

pathogenesis, 93, 94 retinal pigments, 91, 92

geographic atrophy atrophic areas, 95 cell death, 95 dry AMD, 94

lipofuscin accumulation, 94

ophthalmoscopy and autofluorescence imaging, 94, 95

RPE (see Retinal pigment epithelium (RPE)) HMCN1-gene, 18

Homocysteine, 197–198 HTRA1-gene, 13, 21, 38–39

HTRA1-SNPs, 21

HtrA serine peptidase, 38 Hyperfluorescence, 149–150, 152, 159, 160 Hyperhomocysteinemia, 198 Hyperpigmentation, focal, 107, 151–152 Hypertonia, 19

Hypofluorescence, 46, 92, 150, 152, 159

I

ICG angiography. See Indocyanine green (ICG) angiography

Iluvien, 271, 272

Imaging, 118, 123–125, 141–160 Imidazo (1,2-A) pyridine, 229

Immune system, native, congenital, hereditary, 66, 89 Indian Study, 10

Indocyanine green (ICG) angiography delineation, 207

direct thermal laser photocoagulation, 212 PCV, 118

Inflammation, 48, 195, 269–273

Inject-and-extend-regimen, 235

Injection, intravitreal, 71, 194, 227–229, 279–280 Integrins, 93

Intravitreal bevacizumab (IVB), 252–254 iPad, 304, 305

IPE. See Iris pigment epithelium (IPE) Iris pigment epithelium (IPE), 277

IVB. See Intravitreal bevacizumab (IVB)

K

Kepler-telescope, 298, 301–302

Krypton red laser, 206, 218

Krypton yellow laser, 206, 218

L

Laser photocoagulation absorption, wavelength, 206 case selection, 207

defined, 205 extrafoveal CNV

post-laser recurrence, 210, 211

recurrences detection, ICG angiography, 211, 212

FA, 209

meta-analysis, 212–213 safety and adverse events, 216

spot size, duration and irradiation intensity, 206 subfoveal CNV, 212

treatment technique, 207–208 types, treatments, 209 wavelengths, 217

LCPUFAs. See Long-chain polyunsaturated fatty acids (LCPUFAs)

Linolenic acid, 83

Lipase, hepatic, 39, 127–128 LIPC-gene, 17, 36, 39–40, 128 Lipid accumulation, 17, 40

Lipid composition, 16, 17, 57, 82–83 Lipid metabolism, 7

Lipid peroxidation, 50, 56, 128 Lipofuscin

accumulation, 50–52, 55, 57 components, 142

Liquid crystal display microperimetry, 175, 178 Liquid, subretinal, 113–114, 159, 167 Logarithm of the minimum angle of resolution

(LogMAR), 236

logMAR. See Logarithm of the minimum angle of resolution (LogMAR)

Long-chain polyunsaturated fatty acids (LCPUFAs) BMES, 196

DHA, 195, 196

“Long-spaced” collagen (LSC), 85–87 Los Angeles Latino Eye study, 6–7 Low-density lipoprotein (LDL) receptors

lipophilic verteporfin, 207 Lu-Tex, 219

Low vision aids (LVAs) distance, optical magnifiers

advantages and disadvantages, 299, 301 and discrete opacification, optic media, 301 folding and illuminated pocket, 301 Galilean and Kepler telescopes, 301–303 half-eye magnifying spectacles, 299

hand magnifier, 300 illuminated stand, 300

magnifying clips, glasses attachment, 300, 301 and magnifying glasses, 298, 299

reading ability, 301

reading, hyperocular magnifying spectacles, 299 electronic

magnifiers, 303–305 reading instruments, 305

evaluation, required magnification, 296–297 illumination, 305–306

magnification methods, 297 magnifiers prescription, 306 optical magnification, distance

advantage and disadvantage, 298 Kepler-type telescope, 297 watching television, 298

principles, prescription, 307 reading table, 305

visual impairment

effects, 296 rehabilitation, 295–296

WHO notation, acuity classification, 295, 296 LPL-gene, 17

LSC. See “Long-spaced” collagen (LSC) Luminescence test, 149

Lupus erythematosus, 69 Lutein, 194–195, 199, 264

Lutetium texaphyrin (Lu-Tex), 219 Lu-Tex. See Lutetium texaphyrin (Lu-Tex) LVAs. See Low vision aids (LVAs)

M

Macroautophagocytosis, 54 Macula

fluorescein angiography, 149 Macular degeneration, age-related

age, 295–307 antioxidants, 18–19 classification, 4

clinical manifestations, 117–118 diagnostics, 117–118, 236

dry, 263–273, 280–282 early, 101–108

early stage, 87, 102, 233, 276 environmental factors, 18–20 etiology, 34, 38, 195 exudative, 167–170, 249–256 frequency, 4–7

genetic factors-hypertonia, 7–18 imaging, 141–160

incidence, 6–7

late, 4, 6–16, 19–20, 69–72 microperimetry, 173–186 neovascular, 152–155 non-neovascular, 150–151 pathogenesis, 66–68 pathomechanism, 282 photodynamic therapy, 203–222 prevalence, 4–6

prevention, 40 progression, 70

risk factors, 127–129 smoking, 18, 70–71

spectral-domain-OCT, 163–165 surgical therapy, 275–282 therapy, 40, 233–243, 249–256 therapy control, 9, 35, 37, 67 visual disability, 112

Macular dystrophy surgical therapy, 282

Macular-mapping-test, 292 Macular edema and subretinal fluid

accumulation, subretinal fluid, 114, 115 CME, 113

CNV, 114

cystoid changes, 113–114

Macular photocoagulation Study (MPS) disc areas, 213

VA, 212

Macular translocation

advantages and disadvantages, 276 pigment epithelium, 277

PVR, 276 retinotopy, 276

Maculoplasty AMD, 275

photoreceptor transplantation, 275 visual improvement, 276

Magnification methods, 297 Malattia leventinese, 150 Malondialdehyde, 50

Matrix metalloproteinases (MMP), 82 Matrix proteins, extracellular, 18, 79, 81, 102 MC-1101, 265–266

Melanin, 6, 52, 56, 95, 113, 117, 142 Melanolipofuscin, 52

Melanosomes reduction, 52 loss, 46, 49, 52

Membrane extraction, submacular, 279 Membrane, fibrovascular, 87–88 Mendelian diseases, 34 MERITAGE-I-Study, 255 Metalloproteinases, 17, 79 Metalloproteinse inhibitor 3, 17, 39 Metamorphopsy, 167, 209 Microperimetry

AMD, 178–185

psychophysical visual function testing, 173 psychophysics, 173

SLO, 174

technologic evolution, 174–178 automatic microperimetry, 174–175 fixation test, 176

manual, automatic microperimetry, 174 SLO/OCT, 178

stimulus, 175

test evaluation, 176–178 Mitochondrial theory, 46

MMP. See Matrix metalloproteinases (MMP) Monochromatic photography

fluorescein angiography, 142

modern digital color imaging, 142, 143 SLO, 142

subretinal drusenoid deposits, 142, 143 MONT-BLANC-Study, 253

Morbus Stargardt (Stargardt’s disease) surgical therapy, 282

MP1-Microperimeter, 174, 175, 178, 181 Muenster-Aging-and-Retina-Study, 18

N

Ng-YAG-laser, 206 Neovascular AMD (NV-AMD)

antibody Fab fragment, 234 ‘As Needed’ approach, 241–242 beam radiation for CNV, 155 chorioretinal scar, 182

classic CNV, 152

continuous monthly treatment

MARINA and ANCHOR trials, 238, 239 ranibizumab, 238

CSC, 153 diagnosis

classification, 236 FA, 236

ICG, 236 logMAR, 236 OCT, 236 PCV, 236 RAP, 236

fixed quarterly injection studies, 240–241 fluorescein angiography, 153

lesions characteristics, 237 CNV, 237

MARINA data, 237 ranibizumab, 237 RCOphth guidelines, 237

sub-foveal haemorrhage, 238

linear scan spectral domain-OCT, 181, 182 long-term considerations, 242

macular diseases, 183 MARINA and ANCHOR, 234 parameters

‘active’ disease, 238 extracellular fluid, 238 RPE tears, 238

placental growth factors, 235 polypoidal choroidal vasculopathy, 155 ranibizumab and bevacizumab, 234, 235 RCT, 234

‘treat-and-extend’ approach, 242 treatment, 239, 240

vascular ingrowth, 152 visual impairment, eyes, 181

Nerve fibre layer, retinal, 47 Neuroprotection, 133, 266–267 Neuroretina, ageing, 182 Neutrazimab, 272

Non-synonymous coding SNPs (nscSNPs) APOE variants, 35

CFB, 38

nscSNPs. See Non-synonymous coding SNPs (nscSNPs) Nutritional supplementation, AMD

antioxidants and zinc, 192–193 AREDS2

micronutrients role, 198–199 objective, 199

beta-carotene, 193–194 defined, 191

folate and B-vitamins, 197–198 hyperhomocysteinemia, 199 macular xanthophylls

AREDS formulations, testing, 195 degeneration, 194, 195

FDA, 195 Western diet, 194

omega-3 LCPUFAs, 195–196 pathogenesis, macular degeneration, 192

vitamin C, 196–197 vitamin E, 196 zinc, 197

Nutritional supplementation, 191–199 NV-AMD. See Neovascular AMD (NV-AMD)

O

OCT. See Optical coherence tomography (OCT) Omega-3-fatty acids, 19, 70, 133, 192, 193, 195–196, 198, 264 Optical coherence tomography (OCT)

analyses, postmortem eyes, 47 ARM, 165–167

assessment, 236 CNV, 163

cystoid change, 113–114 drusenoid detachments, RPE, 107 exudative AMD

anti-VEGF therapy, 167

retinal thickness maps, 168, 169 SD-OCT scans, 167, 168, 170

frequency domain, 145 GA, 167

ICG leakage and fluid accumulation, 216, 217, 220 imaging characteristics, macular region, 145–146 increasing depth, imaging, 145

length, 144

noninvasive method, 85, 88 SD-OCT, 163–165 TD-OCT, 144–145 wave-like nature, light, 144

OT-551, 133, 269

Oxygen, reactive, 46, 50–52, 55–57, 128, 142

P

Palomid, 229 Paraoxonase 1, 18 Pars-plana vitrectomy, 255 Patch, 277–278 Pazopanib, 229

PCV. See Polypoidal choroidal vasculopathy (PCV) PDGF, 225, 226, 229

PDT. See Photodynamic therapy (PDT)

PEDF. See Pigment epithelium derived factor (PEDF) Pegaptanib sodium, 227

Perfluorocarbon liquids (PFCL), 278 Perimetry

fundus controlled, 132 microperimetry (see Microperimetry)

PFCL. See Perfluorocarbon liquids (PFCL) Pharmacotherapeutic approach, 221 Phospholipids, 79, 81, 82, 85, 91 Photodynamic therapy (PDT)

anti-VEGF monotherapy, 220 case selection, 209

CFH Y402H genotype and response, 71 combination therapy, 221

fluorescein leakage, 210 ICG angiography, 207, 217 laser, 207

mechanism, 206 minimally classic

prevention, laser photocoagulation, 214 VPDT, 213

neovascularization, 159 photosensitizer and light, 218–219 predominantly classic, 213–215 reduced fluence, 219

safety and adverse events

calcium channel blockers and polymyxin B, 216 ICG angiography, 216, 217

subfoveal CNV, 217 “selective” verteporfin therapy, 219

subepithelial occult, no classic neovascularization, 213 tissular effect, 207

treatment technique, 209 verteporfin, 206–207 VPDT, 213

Photocoagulation

laser photocoagulation (see Laser photocoagulation) perifoveal, 106, 212, 213

treatment technique, 207–208 Photofrin, 218

Photoreceptors density, 47

loss, 47, 123, 265 transplantation, 275

Photosensitizers, 50, 206, 209, 218

PHP. See Preferential hyperacuity perimetry (PHP) Phthalocyanine, 218

Physicians’-Health-Study, 18, 193, 194, 196 Pigment epithelial detachment (PED)

CNV, visualized, 116 fibrovascular, 114 serous, 115

Pigment epithelium-choroid translocation ICG angiography, 277

immune reactions, 277 PFCL, 278 retinotomy, 278

Pigment epithelium derived factor (PEDF), 229 Pigment epithelium, retinal

ageing, 45–59 cell density, 49–50

depigmentation, 19 deposits, 79

detachment, 114–116, 155–158 irregular pigmentation, 102 rupture s.a. tear, 278–279 spectral-domain-OCT, 165, 167 tear, 101, 116, 155–156

Pigment epithelium rupture, 278–279 PLEKHA1-gene, 12, 38

Polypoidal choroidal vasculopathy (PCV) Caucasian population, 69–70

ICG, 236

Posterior segment drug delivery system (PS DDS), 267 Preferential hyperacuity perimetry (PHP), 112 Preferred retinal locus (PRL)

defined, 289 eccentric, 290

PRL. See Preferred retinal locus (PRL) Proliferative vitreoretinopathy (PVR), 276, 277 Proton irradiation, 249

PS DDS. See Posterior segment drug delivery system (PS DDS)

Pseudodrusen, reticular, 105–106, 142 Psychophysical visual function testing, 173 PVR. See Proliferative vitreoretinopathy (PVR)

R

Radiation therapy

combination with VEGF inhibitors, 248, 249 epiretinal, 249

RADICAL-Study, 220, 255

Randomized controlled trial (RCT), 234, 235 Ranibizumab, 227–228

RAP. See Retinal angiomatous proliferation (RAP) RBP. See Retinol-binding protein (RBP)

RCT. See Randomized controlled trial (RCT) Reactive oxygen species (ROS)

generation, 50–55, 57 lipofuscin, 50 mitochondria, 46, 56

Reading, AMD ability, 287, 288 fixation behavior

clinical assessment, 291

eccentric, scotoma shift direction, 290, 291 SLO-fundus, 290, 291

fixation stability, 291 methods, ability, 291–292 physiological principles

eye movements, 289 retinal area, 288 SLO-fundus, 289

VA, eccentricity, 287–288 preconditions, ability, 293 rehabilitation approaches, 292–293 visual field

eccentric fixation, 289, 290 fundus, 289

margin, scotoma, 288–289

Recombinant tissue plasminogen activator (rTPA), 279, 280

“Red-free” photography, 142

Rehabilitation approaches, reading ability, 292–293 Resequencing technology, 35

Retina and RPE, ageing aging process, 45, 46 and AMD, 57–58

antioxidant capacity, 55–56 BM, 56–57

changes, cell density, 49–50 clinical changes

color fundus, 46 electrophysiological studies, 47 retinal function, 47

cumulative damage, 48–49 defined, 45

functions, 48

lipofuscin accumulation

A2E concentrations, 50–51 lysosomal dysregulation, 52 and photoreactivity, 50, 51

lysosomal-autophagy axis enzyme activity, 54, 55 lipofuscin, 54–55

macromolecules degradation, 53, 54 mitochondria, 55

melanosomes and pigment complexes, 52 mitochondrial changes, 52–53

neural

decrease, photoreceptor cells density, 47, 48 inflammatory pathways, 48

OCT, 47 RPE, 48–56

stochastic and grammed theories, 45–46 subcellular changes, 50

Retinal angiomatous proliferation (RAP), 236, 237 Retinal nerve fiber layer (RNFL), 47

Retinal pigment epithelium (RPE) See also Retina and RPE, ageing

age-related changes accumulation, lipofuscin, 78 degenerative changes, 79 functional processes, 78

phagocytosis and degradation, 77–78 CFB and C2, 38

CFH and FHL-1 risk variant, 37 choroidal neovascularizations, 107 detachment

fibrovascular PED, 114, 115 ICG fluoresces, 115, 116

indocyanine green angiography, 115, 116 SD-OCT, 115

focal hyperpigmentations, 107 injuries, 33

and photoreceptors

choroidal circulation, 265–266 neuroprotection, 266–267 RN6G, 268

visual cycle modulators, 267–268 structure and function, 77, 78 vision-threatening lesions, AMD, 263

Retinal vascular anomalous complexes (RVAC), 158 Retinol-binding protein (RBP), 267–268

Ring scotoma, 290, 292 Risk factors

genetic, 127–128

environmental, 11, 18, 40, 71, 264 ocular, 129

systemic, 128–129

RNFL. See Retinal nerve fiber layer (RNFL) RN6G, 266, 268

ROS. See Reactive oxygen species (ROS) Rotterdam Study (RS)

dietary intake, 20 dose-dependent association, 19

interaction, CFH and cataract surgery, 20 meta-analysis, 18

population-based, 70

RS. See Rotterdam Study (RS)

rTPA. See Recombinant tissue plasminogen activator (rTPA)

S

Saccades, 288, 291

Scanning laser ophthalmoscope (SLO) commercial systems, 144

FP, 132

fundus image, 288

Scar, disciform, 87, 88, 90–91, 129, 130 Scatter photocoagulation, 213

Scotoma

absolute, 130, 182, 184 central, 288–291

Scottish and English case-control Study, 11 sCR1, 272

SD-OCT. See Spectral domain optical coherence tomography (SD-OCT)

Serotonin 1A agonist, 133 sFLT01, 228

Single nucleotide polymorphisms (SNPs) candidate gene approach, 34

CFH and ARMS2/HTRA1, 21 evaluation, 9

functional, 12 information, 34

10q26 and genetic/environmental factors, 20–21 siRNA. See Small interfering RNA (siRNA) Sirolimus, 132

SLO. See Scanning laser ophthalmoscope (SLO) Small interfering RNA (siRNA)

Bevasiranib, 229 defined, 228

Smoking, 18, 70–71

SNPs. See Single nucleotide polymorphisms (SNPs) Sodium fluorescein, 92, 117, 146, 147

Sorby’s fundus dystrophy, 17, 107

Spectral domain optical coherence tomography (SD-OCT) disease stages, 125

3D scan, 164, 165

Fourier transformation, optical spectrum, 164 interferometric imaging technique, 163–164 normal retina, 165

progression, GA, 125, 126 SLD, 164

thickness map, 164, 165 Squalamine, 229

Stargardt diseases, 35, 123–124, 268 “Stars in the sky” appearance, 105 Stress, oxidative, 133, 268–269 Sudan black, 81, 86

Surgical therapy dry AMD

BM, 280

fluorescein and ICG angiography, 280, 281 geographic atrophy, 281

OCT, 280

pigment epithelium choroid translocation, 280, 281 macula dystrophies, 282

macular translocation, 276–277

maculoplasty, 275–276 massive submacular bleeding

rTPA, 280 vitrectomy, 279

non-responder, 278 photodynamic therapy, 278

pigment epithelium-choroid translocation, 277–278 pigment epithelium rupture, 278–279

single cell suspensions

Bruch’s basal membrane, 277 IPE, 277

Superoxide dismutase, mitochondrial, 53 Susceptibility genes, 7, 35, 39, 40 Swept source OCT, 145

T

TA106, 271, 272

TD-OCT. See Time domain optical coherence tomography (TD-OCT)

Teletherapy, 249

TG100801, 229

TG101095, 229 Thalidomide analogs, 229

Time domain optical coherence tomography (TD-OCT) measurement technique, 145

periodic waveforms, 144 TIMP3-gene, 17, 39

Tin ethyl etiopurpurin, 218

Tissue inhibitor of metalloproteinases-3 (TIMP3) AMD susceptibility genes, 39

candidate gene analyses, 17 TLR3. See Toll-like-receptor 3 (TLR3) Toll-like-receptor 3 (TLR3), 128

‘Treat-and-Extend’ approach, NV-AMD, 242 Treatment, AMD

ageing process, 247 antiangiogenic monotherapy, 248 anti-VEGF agents

combination therapy, VPDT, 251–252 IVB, 253

bevacizumab, 248

choroidal hypoperfusion, 183 CNV, 247

combination therapy, radiation

effect, neovascular membranes, 255 pharmacotherapies, 256 subconjunctival hemorrhage, 256

cortiocosteroids, 248 FA, 184

intraocular epiretinal probe, 249 intravitreal anti-VEGF therapies, 249

microperimetry fixation site and sensitivity map, 184, 185 OCT, 184

radiation therapy, 249 rationale

neovascularization matures, 249 verteporfin, 250

VPDT, 250 RPE, 185

systemic bevacizumab, 183–184

Treatment, AMD (cont.) triple therapy

bevacizumab, 254 CNV, 254

ranibizumab monotherapy, 255 VEGF, 248

visual function, 183 VPDT, 250–251

Triamcinolone, 248, 250–251 Trimetazidine, 265

V

VA. See Visual acuity (VA)

Vascular endothelial growth factor (VEGF) angiogenesis, 225

binding, family members, 225, 226 drug delivery methods, 230 hemorrhages and telangiectasis, 113

inhibition, unrelated and physiologic processes, 230 pathway

inhibition, cascade, 227

intracellular signal cascade inhibition, 229 natural inhibitors, 229–230

receptor synthesis and inhibition, siRNA, 228–229

sequestration, released, 227–228

synthesis and degradation, matrix molecules, 90, 91 vasculopathy, polypoid, choroidal (PCV), 236, 237 VECAT, 196

VEGF-A, 225, 226

VEGFR, 226–227

VEGF. See Vascular endothelial growth factor (VEGF) Verteporfin, 206–207

Verteporfin photodynamic therapy (VPDT) angiogenic signals, modification, 248 angio-occlusive effect, 250

benefits, 213

safety and efficacy, 213 triamcinolone

intraocular pressure, 251 IVTA, 250

small pilot studies, 251 Vision, central

loss, 87–88, 264 VISION Study, 252

Visual acuity (VA) mean LogMAR, 237 outcomes, 241 response, 240 stability, 242

Visual aid for short distance, 298–303 electronically magnifying, 303–305 for the distance, 297–298 magnifying, 292, 297–298 magnifying need, 291–292, 298

possibilities of magnification, 297, 298 prescription, 306–307

Visual cycle modulators, 267–268 Visual field

central, 47, 104, 113, 178, 183, 292 peripheral, 47, 112, 296

Visual impairment classification, 295, 296 definition, 295–296

Vitamin B, 197–198

Vitamin C, 196–197 Vitamin E, 196

Vitrectomy, 117, 249, 255, 279 Vitronectin, 66, 79, 102

VPDT. See Verteporfin photodynamic therapy (VPDT)

W

WAFACS. See Women’s antioxidant and folic acid cardiovascular study (WAFACS)

Women’s antioxidant and folic acid cardiovascular Study (WAFACS), 191, 198

X

Xanthophyll, macular, 194–195, 198, 206

Y

Y402h-gene, 20, 21

Z

Zeaxanthin, 71, 194–195, 199

Zinc, 192–193, 197