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<<< < Предыдущая 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169170 / 170170

Index

A1, 230	AG013711, 362	C2 mutations, 45, 48–49, 123
A2E, 19	Age-related changes	copy number variants (CNVs), 49
AART (Anecortave Acetate Risk Reduction	Bruch’s membrane, 20–21	environmental interactions, 52
trial), 212	posterior vitreous detachment, 327	factor B polymorphism, 45, 123
ABCA4 mutations, 6–7, 18, 20, 48	retina, 5	factor H polymorphism, 37, 40, 44–45,
Abetalipoproteinemia (Bassen–Kornzweig	vitreous degeneration, 15	48–49, 123, 293
syndrome), 194	Age-Related Eye Disease Study see AREDS;	factor H Y402H variant, 48–49, 51–52,
Absorption enhancers, 60, 88	AREDS 2	122–123, 128, 365
adverse effects, 61	Age-related macular degeneration, 2, 8, 15,	HtrA serine peptidase 1 (HTRA1)
cyclodextrins, 89	26, 56, 344, 362	mutations, 48–49, 52, 122–123
topical drug delivery, 61	anecortave acetate, 208, 211–212, 212t	LOC387715/PLEKHA1, 123
Acetazolamide, 192	prophylactic treatment, 212	treatment response prediction, 53–54
side effects, 114, 192	bevacizumab, 213–214, 220–221, 232	intravitreal drug delivery, 67
Acetylsalicylic acid, intravitreal with silicone	bevasiranib, 232, 278–280	JSM6427, 363
oil tamponade, 71	CARE study, 279–281, 281t	laser photocoagulation, 129
Acute lymphoblastic leukemia, 252	ranibizumab combined treatment, 281	lipofuscin, 20
Acute posterior pigment placoid	brimonidine, 293	medical therapies, 129–132, 363t
epitheliopathy, verteporfin	Chlamydia pneumoniae infection	combination therapy, 131
photodynamic therapy, 301	relationship, 52	treatments under investigation, 131–132,
Acute retinal necrosis, 10	preventive strategies, 53	364–365
pathogenic mechanisms, 40	choroidal neovascularization, 8, 13, 128,	pathogenesis, 123, 128, 321
Acyclovir, 244	162–164	Bruch’s membrane degeneration, 123
poly(lactic-co-glycolic) acid microparticles,	classification, 128, 129t	choroid circulation theory, 123
63	extrafoveal lesions, 129	immune-inflammatory, 40, 51–52, 123,
Adalimumab, 236, 239–240, 245t	juxtafoveal lesions, 129	128
Adamantiades–Behçet disease, 157	natural history, 128–129	molecular mechanisms, 44–45
adverse effects, 101, 240	subfoveal lesions, 129	oxidative stress, 56, 123, 125, 128
contraindications, 240	type1/type2 subretinal neovascular	vascular endothelial growth factor, 23,
drug interactions, 240	membranes, 128	163, 226, 231
mechanism of action, 239	ciliary neurotrophic factor, encapsulated	pegaptanib, 231–232, 265–267
ophthalmic indications, 240	cell technology (NT-501 implant), 293	PF-04523655, 364
pharmacology, 239	complement activation, 37, 44, 51–52	pharmacologic vitreolysis, 328
systemic indications, 240	alternative pathway, 44–45	prevalence, 122, 128
Adamantiades–Behçet disease see Behçet	therapeutic targeting, 53, 364–365	radiotherapy, 336–337, 339–341
disease	complement factor H replacement therapy,	angiogenesis inhibitor combined
Adaptive immunity, 37–39, 44	53	treatment, 336–337, 341
cellular, 38–39	copaxone, 295	epimacular brachytherapy technique,
humoral, 38	corticosteroids, 203–204	339
Adeno-associated virus vectors, 285–287,	biodegradable implants, 82–83	side-effects, 341
289–290, 293–295	periocular/intravitreal injection, 82	ranibizumab, 213–214, 219, 226, 231–232
Adenosine, 41	diagnosis, 123–124	efficacy, 227
retinal vascular homeostasis, 17	dietary supplements, 56–59, 125–126	National Institute for Health and
Adenosine deaminase deficiency, gene	differential diagnosis, 124t	Clinical Excellence (NICE)
therapy, 287	drusen, 123–125, 128	recommendations, 360
Adenovirus vectors, 285, 289	dry (nonneovascular) form, 8, 51–52,	photodynamic therapy combined
complications, 287	122–127, 231	treatment, 228
Adjuvant chemotherapy, retinoblastoma,	epidemiology, 122	REDD14NP, 283
308–309	new drugs, 364–365	retinal pigment epithelium transplantation,
Administration routes, 2–4, 60	treatment outcome/prognosis, 126	344–345
see also Drug delivery	E10030, 363	rheopheresis, 321–322
AdPEDF.11, 131	gene therapy, 49	MAC-1 trial, 321
Adriamycin see Doxorubicin	pigment epithelial-derived growth factor,	MIRA-1, 321–322
Advance beneficiary notices (ABNs), 354	53	risk factors, 56, 122–123, 128
Advanced glycation receptor (AGE) blockers,	genetic aspects, 48, 51–52, 123, 128	cataract surgery, 123
134	apoE gene polymorphism, 48–49, 123	ethnicity, 122, 128
Aflibercept, 259–260	associated single nucleotide	high BMI/fat intake, 122
AG013764, 362	polymorphisms, 8, 128	smoking, 122, 128

367

Index

Sirna-027, 232, 282	vascular endothelial growth factor	Anthracyclines, uveal metastases, 309
sirolimus (rapamycin), 364	inhibitor comparisons, 213–214	Antibiotics, 313–320
submacular surgery, 129	choroidal neovascularization, 211	endophthalmitis, 173
sustained-release devices, 81	clinical studies, 211–213	nasal administration, 316–317
symptoms/signs, 124–125, 125t	contraindications, 214–216	off-label use, 352, 354
treatment strategies, 41, 125–126	historical background, 208	oral/intravenous, 315–316
value-based treatment analysis, 358,	idiopathic macular telangiectasia, type 2,	prophylaxis, 68–69, 170
360	182	Endophthalmitis Vitrectomy Study (EVS),
vascular endothelial growth factor	idiopathic perifoveal telangiectasia, 212	313–314
inhibitors, 1, 167, 231–232	intraocular tumors, 211	intravitreal delivery, 67
gene therapy approaches, 288–289	intravitreal delivery, 208	gas-phase nanoparticles, 77
vascular endothelial growth factor	mechanism of action, 210	pharmacokinetics/clearance, 70
Trap-Eye, 232, 261–263	pharmacology, 208–209	safety, 96, 99–100, 99t
vatalanib (PTK787), 362	posterior juxtasceral depot administration,	thermo-sensitive hydrogel encapsulation,
verteporfin photodynamic therapy, 1, 231,	208	91
297, 299–300, 300t, 303, 303t	drug reflux prevention, 212	Antibodies, 38
triamcinolone acetonide combined	injection technique, 208	Anticoaguant therapy, intravitreal injection
therapy, 300	preclinical studies, 211	perioperative management, 67
vascular endothelial growth factor	primary open-angle glaucoma, 212–213	Antifungal agents, 317–319
inhibitor combined therapy, 300	retinal angiomatous proliferation, 212	safety of retinal therapy, 100
vitamin supplements	retinopathy of prematurity, 211	Antigen-presenting cells, 37–39
formulations, 57t	structure, 208, 209f	Antimetabolites, 41, 251–255, 253t–254t
safety, 57	toxicity, 214–216, 215t–217t	uveal metastases, 309
wet/exudative (neovascular) form, 8, 40,	see also AART (Anecortave Acetate Risk	Antioxidants
51–52, 128–132, 231	Reduction trial)	macular carotenoids, 17
choroidal neovascularization risk in	Anecortave desacetate, 208	neuroprotection, 292–293
fellow eye, 128–129	mechanism of action, 210	Antisense oligomer therapy, 288
nonpharmacological therapies, 129	pharmacokinetics, 208–209	Anti-vascular endothelial growth factor
AGN211745 see Sirna-027	structure, 208, 209f	therapy see Vascular endothelial
AIPL1 mutations, Leber’s congenital	Angiogenesis, 23–36, 219, 230	growth factor inhibitors
amaurosis, 194	age-related macular degeneration	ApoE gene polymorphism, 48–49, 123
Albumin nanoparticles, 61	neovascularization (wet form), 128,	Apoptosis
intravitreal drug delivery, 86	163	inhibition as neuroprotective strategy,
Aldose reductase inhibitors, 134	delta-like ligand 4, 232	293–295
Alemtuzumab, 236	fibroblast growth factor family, 232	neoplastic ocular disease gene therapy
safety of retinal therapy, 101	inhibitors, 24t, 31–32, 210	approaches, 288–289
uveitis, 244	endogenous, 230	photodynamic therapy immunomodulatory
Alkylating agents, 255–258, 256t–257t	ocular disease pathogenesis, 219	effects, 299
retinoblastoma chemoreduction, 306	placental growth factor, 232, 259	retinal degeneration, 18
uveal metastases, 309	platelet derived growth factor, 25	vascular endothelial growth factor effects,
All-trans retinal, 19	promoters, 23–31, 24t	230
visual cycle, 18	retinal vascular development, 176	Apraclonidine, neovascular glaucoma, 189
All-trans retinol, 18–19	tumors, 219, 231	Aptamers, 1, 265–266
Alpha-chymotrypsin, 327	vascular endothelial growth factor,	ARC1779, 266
Amacrine cells, 5	185–186, 230–232, 259	ARC1905, 46, 365
Amebiasis, 107	Angioid streaks	AREDS (Age-Related Eye Disease Study),
Amikacin	choroidal neovascularization, 162	56–57, 123–126, 128, 292
endophthalmitis, 173	bevacizumab, 167	classification scheme, 124–125, 125t
Endophthalmitis Vitrectomy Study (EVS),	laser photocoagulation, 166	dietary supplements evaluated, 57
313–315	macular translocation surgery, 167	limitations, 126
safety of retinal therapy, 99, 112	pathogenesis, 163	vitamin/mineral supplement formulations,
Aminoglycosides	verteporfin photodynamic therapy, 166,	126t
postoperative endophthalmitis, 313–314	301	AREDS 2 (Age-Related Eye Disease Study 2),
safety of retinal therapy, 96, 99, 112–113	clinical features, 164	56–58, 125–126, 292
Amphotericin B, 318	diagnosis, 163	dietary supplement formulations, 58t, 126t
fungal endophthalmitis, 173–174	risk factors, 162	ARMS2, 52
safety of retinal therapy, 100	Angiopoietins, 26, 29–30	single nucleotide polymorphism, 8
Amsler grid, 124	age-related macular degeneration	Aromatase inhibitors, 309
Anakinra, 236, 245t	neovascularization (wet form), 128	Arrestin (S-antigen), 19
uveitis, 244	angiogenesis, 29–30	Arteriovenous nipping, 17
Anatomical barriers, permeation, 86–87	Angiostatic corticosenes, 208	Arylmethane dyes, chromovitrectomy, 331
ANCHOR, 67, 130, 213–214, 227–228,	Angiostatin, radiotherapy combined	AS1411, 266
231–232	treatment, 336	Aspergillus endophthalmitis, 170–172
Anecortave acetate, 24, 208–218	Angiotensin II, 17	ATG-003, 363
age-related macular degeneration, 208,	Animal models	Atherosclerosis, age-related macular
211–212	intravitreal drug toxicity evaluation, 96–97	degeneration, 122–123
clinical trials, 211–212, 212t	pharmacokinetics, 74–75	Atherosclerosis Risk in Communities Study,
dry form prophylactic treatment, 212	topical drug delivery, 75	137
photodynamic therapy comparisons,	retinal drug delivery, 74–75	Atopic dermatitis, 248, 251
211–213	Ankylosing spondylitis, 236, 240, 252	Atropine, neovascular glaucoma, 189

368

Autoimmune disorders, 40	Betahexol	Bioactive lipids, 364
Autoimmune regulator (AIRE), 40	ion drug exchange, 2	Biologic therapies, 236–247, 245t
Autoimmune uveitis	neuroprotective activity, 293	Bipolar cells, 5
cyclophosphamide, 255	Betametasone, scleral implants, 3, 63	Birdshot retinochoroidopathy
infliximab, 236–237	Bevacizumab, 1, 24, 83, 167, 219–225	clinical features, 157
Autologous plasmin enzyme, 327–328	adverse effects, 100–101, 223–224	daclizumab, 243
pharmacologic vitrectomy outcome, 329	age-related macular degeneration, 131, 167,	diagnosis, 157
Autosomal-dominant neovascular	213–214, 220–221, 232	ethnic factors, 152
inflammtory vitreoretinopathy, 188	comparative aspects, 223	HLA-A29 association, 152, 157
Avastin see Bevacizumab	radiotherapy combined treatment, 336,	immunosuppressive therapy, 153
Azathioprine, 41, 244, 252–255	341	pharmacotherapy, 157
Adamantiades–Behçet disease, 153–157	cancer therapy, 220, 231	retinitis, 10
birdshot retinochoroidopathy, 157	lung carcinoma, 309	Birth trauma, 11
mechanism of action, 252	choroidal neovascularization, non-age-	Bladder cancer, 220
pharmacology, 252	related macular degeneration-	Blood–aqueous barrier, 15
sarcoidosis, 158	associated, 167	ocular pharmacokinetics, 61
serpiginous choroidopathy, 158	angioid streaks, 167	Blood–retina–vitreous barrier, 15
sympathetic ophthalmia, 160	idiopathic choroidal neovascularization,	Blood–retinal barrier, 15–17
systemic indications, 252	167	disruption, 16–17
use in retinal disease, 252	myopia, 167, 222	drug delivery influence, 81
uveitis, 252	presumed ocular histoplasmosis	drug permeability, 16
Vogt–Koyanagi–Harada disease, 160	syndrome, 167	paracellular transport pathway, 16–17
Azo dyes, chromovitrectomy, 331	contraindications, 223	ocular pharmacokinetics, 61
	costs, 131	tight junctions, 15–16
B7-1 (CD80), 39	cystoid macular edema	Blue Mountains Eye Study, 56–57, 122, 137
B7-2 (CD86), 39	postoperative, 223	Body mass index
B lymphocytes, 38	uveitic, 222	age-related macular degeneration risk,
Bacillus cereus endophthalmitis, 170–172	diabetic macular edema, 223	122
Basic fibroblast growth factor, 18	diabetic retinopathy, 134–135, 221	retinal vein occlusion risk, 137
angiogenesis promotion, 25–26	drug interactions, 224	BOLD chemotherapy, metastatic uveal
neovascular glaucoma pathogenesis,	efficacy, 223	melanoma, 309–310
185–186	historical background, 219, 226	Bone marrow-derived cells, retinal pigment
neuroprotective activity, 293	intravitreal delivery, 81	epithelium replacement, 350
Bassen–Kornzweig syndrome	complications, 69, 170	Brain tumors, 298–299
(abetalipoproteinemia), 194	preoperative, 72	BRAVO, 228
Bcl-2, 230, 292–295	vitrectomized eyes, 71	Breast cancer, 110, 114, 220, 226, 252
BclXL, 293	intravitreal pharmacokinetics, 71	bevacizumab effects, 220
BCNU (carmustine), retinal toxicity, 110–111	half-life, 131	uveal metastases, 309
Beaver Dam Eye Study, 57, 122, 137	mechanism of action, 220	Briard dog, 52–53, 194, 287
Behçet disease, 41, 153–157	neovascular glaucoma, 189–190, 223	Brilliant blue, 331
adalimumab, 240	ocular disease treatment, 219–223	chromovitrectomy, 331, 333–334
azathioprine, 252	ocular surgery adjunctive treatment, 223	Brimonidine, 293
chlorambucil, 255–258	off-label use, 354	Bromfenac, 196
clinical features, 153	pharmacology, 220	pharmacology, 197
cyclophosphamide, 255	photodynamic therapy combined	physicochemical characteristics, 197f
cyclosporin, 248	treatment, 129, 131	use in ocular/retinal disease, 198–200
daclizumab, 243	radiation retinopathy, 223	Bromophenol blue, 331
diagnosis, 153	ranibizumab comparison (CATT study),	Bruch’s membrane, 5
HLA-B51 association, 152–153	131	age-related changes, 20–21
immunosuppressive therapy, 153	retinal telangiectasias, 222–223	cell biology, 20
infliximab, 236–239	idiopathic macular type 1, 181	lipid accumulationm, 20
methotrexate, 252	idiopathic macular type 2, 182–183	matrix dysregulation, 20–21
tacrolimus, 251	retinal vein occlusion, 221–223	matrix metalloproteinases, 21
treatment strategies, 153–157	branch, 139, 143	retinal pigment epithelium transplantation
Benign concentric annular macular	central, 139–140	substrate, 344
dystrophy, 6–7	retinopathy of prematurity, 177–178, 222	structural composition, 20
Benzalkonium chloride, 61, 75, 89, 110	injection technique, 178	tissue engineering/prosthetic replacement
Benzoporphyrin monoacid derivative see	ocular complications, 178	strategies, 346–349
Verteporfin	systemic complications, 178	Budesonide, sub-conjunctival microparticle
Bestrophin, 6–7	vascular endothelial growth factor-A	injection, 86
Best’s disease see Vitelliform dystrophy	binding, 220	Butterfly-shaped pigment dystrophy of fovea,
β cyclodextrins, 88–89	Bevasiranib, 1, 24, 131, 278–284	6–7
Beta-carotene	age-related macular degeneration, 232,
adverse effects of dietary supplementation,	278–279	C2, 8
56	CARE study, 279–281, 281t	mutations, age-related macular
age-related macular degeneration, 56, 125	ranibizumab combined treatment, 281	degeneration, 45, 123
AREDS, 126	diabetic macular edema, 279, 281–282	C3, 8
Beta-receptor antagonists, neuroprotective	historical background, 278	mutations, age-related macular
activity, 293	subfoveal choroidal neovascularization, 279	degeneration, 45, 52
Beta-thalassemia, 287	Bimatoprost, retinal toxicity, 114	therapeutic targeting, 46, 364

Index

369

Index

C3a, 31, 44	Cefazolin, intravitreal pharmacokinetics/	Choroidal hemangioma with retinal
age-related macular degeneration	clearance, 70	detachment, radiotherapy, 338
pathogenesis, 45	Cefipime, oral administration, 316	Choroidal neovascularization, 8, 13, 162
C5, therapeutic targeting, 46, 364	Ceftazidime	anecortave acetate, 211
C5a, 31, 44	endophthalmitis, 173	antiangiogenic therapy, 167
age-related macular degeneration	Endophthalmitis Vitrectomy Study,	bevasiranib, 279
pathogenesis, 45	313–315	ciliary neurotrophic factor-secreting retinal
c-raf kinase, 1	safety of retinal therapy, 99–100	pigment epithelium cell implant, 63
C-reactive protein, 45, 51–52, 123	Ceftriaxone, endophthalmitis, 173	combined sub retinal pigment epithelium/
Calcineurin inhibitors, 248–251, 249t–250t	Celestone Solspan, retinal toxicity, 110	subretinal (type 3), 163
neuroprotection, 294–295	Cell culture models, intravitreal drug toxicity	corticosteroids, 201
Callithrix jacchus (common marmoset	evaluation, 96	differential diagnosis, 163–164
monkey), 97	Cellular adaptive immunity, 38–39	gene therapy approaches, 288
Calpains, 18	Cellulose derivatives	laser photocoagulation, 166
Cancer therapy, vascular endothelial growth	biodegradable ophthalmic inserts, 61	pathogenesis, 163
factor inhibitors, 231	mucoadhesive polymer formulations, 61	vascular endothelial growth factor
Cand5 see Bevasiranib	Central alveolar pigment epithelium	involvement, 23–24, 231
Candida, 10	dystrophy, 6–7	pegaptanib microspheres, transscleral
endophthalmitis, 170–173	Central areolar choroidal dystrophy, 8	delivery, 3
Canthaxanthine, retinal toxicity, 116–117	Central retinal artery, 5	radiotherapy, 336
Capecitabine, uveal metastases, 309	Central serous chorioretinopathy, verteporfin	ranibizumab, 219
Capillary hemangioblastoma, 220	photodynamic therapy, 301–302	risk factors, 162–163
CAPTURE DME study, 365	CEP290 mutations, Leber’s congenital	SIRNA-027, 282
Carbon nanostructure nanotubes, 65	amaurosis, 194	sub retinal pigment epithelium (type 1),
Carboplatin	Cephalosporins	163
lung carcinoma, 309	postoperative endophthalmitis, 313	subretinal (type 2), 163
retinoblastoma, 306, 308–309	safety of intravitreal delivery, 96	surgery, 167
side-effects, 307–308	Chemoreduction, retinoblastoma, 306–307	treatment options, 165–167
uveal melanoma, 309–310	agents, 306–307	verteporfin photodynamic therapy,
Carboxymethylcellulose, mucoadhesive	Chemotherapy, 306–312	166–167, 301
polymer formulations, 61	intraocular lymphoma, 310	Choroidal osteoma, verteporfin photodynamic
Cardiac glycosides, ocular side effects, 118	retinoblastoma, 306–309	therapy, 302
Cardiovascular disease, retinal vein occlusion	adjuvant, 308–309	Choroideremia, 8
risk, 137	intrathecal, 309	retinal pigment epithelium transplantation,
Cardiovascular Health Study, 137	intravitreal, 308	344
CARE, 279–281	metastatic disease, 309	Chromovitrectomy, 72, 331–335
Carmustine, metastatic uveal melanoma,	periocular/subconjunctival, 308	dyes, 331–334
309–310	see also Chemoreduction	biochemistry/pharmacology, 331–332
Carotenoids	side-effects, 307–308	injection technique, 334–335
age-related macular degeneration dietary	uveal melanoma, 309–310	retinal toxicity, 332–333
supplements, 125	Chemothermotherapy, retinoblastoma, 308	VINCE applicator, 335
macular pigments, 17–18, 125	Cherry red spot, 9	historical background, 331
Carotid artery occlusive disease	Chick embryo allantoic membrane model,	indications, 332–334
neovascular glaucoma, 186–187, 189	corticosene angiostatic activity, 208	operative techniques, 334–335
treatment, 189	Child abuse, 11	macular hole protection, 335
Carotid cavernous fistula, 186	Chitosan nanoparticles, 61	rationale, 331
Caspase inhibitors, neuroprotection, 294–295	Chlamydia pneumoniae infection, age-related	Chronic lymphocytic leukemia, 255
Caspases, 18	macular degeneration associaton, 52	Cidofovir, retinal toxicity, 117–118
Cat models	preventive strategies, 53	Ciliary neurotrophic factor, 18
intravitreal drug toxicity, 97	Chlorambucil, 255–258, 256t–257t	encapsulated cell technology (NT501
pharmacokinetic studies, 75	efficacy, 258	device), 3, 63, 83–84, 293
Cataract	pharmacology, 255	age-related macular degeneration, 293
intravitreal triamcinolone acetonide	serpiginous choroidopathy, 158	retinitis pigmentosa, 192–193, 293
complication, 205	sympathetic ophthalmia, 160	neuroprotective activity, 293
radiation-induced, 342	systemic indications, 255	retinitis pigmentosa gene therapy, 53
Cataract surgery	use in retinal disease, 255–258	Cinchonism, 108
age-related macular degeneration risk, 123	uveitis, 255–258	Ciprofloxacin
differential diagnosis of inflammation, 172,	Chloroquine, retinal toxicity (chloroquine	endophthalmitis, 173, 314
172t	retinopathy), 9, 107–108	intravitreal pharmacokinetics/clearance, 70
endophthalmitis complicating, 170	screening guidelines, 108	safety of retinal therapy, 100
retinal detachment, 147	Chlorpromazine, retinal toxicity, 105	11-cis-retinal, 18–19
CATT (Comparison of Age-related macular	Chlorthalidone, retinal toxicity, 114	11-cis-retinol, 18
degeneration Treatment Trial), 131,	Chondroitin sulfate, 327	Cisplatin
223, 354	Chondroitinase, 327	lung carcinoma, 309
Cavernous hemangioma, radiotherapy, 338	Chorioretinal venous anastomosis, central	retinal toxicity, 110–111
CD antigens, 38t	retinal vein occlusion, 143	retinoblastoma chemoreduction, 306
CD4 T lymphocytes, 39	Choroid circulation theory, age-related	Clarithromycin, rifabutin interaction, 117
subsets, 39	macular degeneration pathogenesis,	Claudins, 16, 273
CD8 T lymphocytes, 39	123	CLEAR-IT 1, 261–262
CD59, angiogensis inhibition, 31–32	Choroid, drug permeation, 87	CLEAR-IT 2, 262

370

CLEAR-IT DME, 263	colored, chromovitrectomy, 331–332	Cyclophosphamide, 255, 256t–257t
Clearance, intravitreal drug delivery, 70–71	complications of ocular therapy, 97–99,	Adamantiades–Behçet disease, 153–157
Clofazimine, retinal toxicity, 109	153, 204–205	pharmacology, 255
Coats’ disease, 9	intraocular pressure elevation, 204	retinoblastoma, 308–309
neovascular glaucoma, 186, 188	cystoid macular edema, 202	serpiginous choroidopathy, 158
pegaptanib, 269	diabetic macular edema, 202–203	small-cell lung carcinoma, 309
COBALT, 24, 281	diabetic retinopathy, 134–135	systemic indications, 255
Cobblestone degeneration, 8	endophthalmitis, 173	use in retinal disease, 255
Collagen	guidelines for patients with ocular	uveal metastases, 309
age-related changes, Bruch’s membrane, 20	inflammation, 153	uveitis, 255
biodegradable ophthalmic inserts, 61	historical aspects, 201	Cyclosporine (Ciclosporin), 41, 244, 248
vital dye uptake, 332	idiopathic macular telangiectasia type 2,	Adamantiades–Behçet disease, 153–157
vitreous, 15, 327	182–183	birdshot retinochoroidopathy, 157
Collagen vascular disease, 12–13	implants, 201	childhood uveitis, 248
Collagenase, 72	multofocal choroiditis and panuveitis, 158	pharmacology, 248
Colorectal cancer, 131, 167, 219, 226, 362	neovascular glaucoma, 189	retinal pigment epithelium transplantation,
bevacizumab, 220	periocular/intravitreal injection, 82	345
Commotio retinae (Berlin’s edema), 11	adverse effects, 82	retinoblastoma chemoreduction, 307
Complement inhibitors, 362	photodynamic therapy combination, 131	sarcoidosis, 158
age-related macular degeneration, 364–365	pharmacology, 201–202	serpiginous choroidopathy, 158
Complement system, 37, 44–47	posterior uveitis, 153	sympathetic ophthalmia, 160
activation, 37, 44	relative potency, 202t	systemic indications, 248
age-related macular degeneration, 51–53,	retinal toxicity of formulation vehicles, 110	tacrolimus comparison, 248
123	retinal vein occlusion, 203	use in retinal disease, 248
alternative pathway, 44, 51–52, 123,	branch, 139, 143	Vogt–Koyanagi–Harada disease, 160
364–365	central, 139–140	Cystoid macular edema
classical pathway, 44, 364–365	SCORE study, 205	bevacizumab, 222–223
lectin pathway, 44, 364–365	sarcoidosis, 158	corticosteroids, 82, 202
angiogensis-promoting components, 31	serpiginous choroidopathy, 158	methotrexate intravitreal injection, 252
therapeutic targeting, 46, 53	sympathetic ophthalmia, 160	nonsteroidal anti-inflammatory drugs, 101,
Compounding pharmacies, Food and Drug	thermo-sensitive hydrogel encapsulation,	196, 198
Administration (FDA) regulation, 353	91	off-label drug use, 352
Compstatin see POT-4	use in ocular diseases, 202–205	retinitis pigmentosa, 192
COMS (Collaborative Ocular Melanoma	Vogt–Koyanagi–Harada disease, 160	carbonic anhydrase inhibitors, 192
Study), 337, 339	Cost minimization analysis, 356	systemic medicines toxicity, 114
Cone monochromatism, 6	Cost–benefit analysis, 357	topical drug delivery, 75
Cone–rod dystrophy, 7	Cost–effectiveness analysis, 357	Cytarabine
Cones, macular/foveolar density, 5	Cost–effectiveness standards, 358–359	intraocular lymphoma, 310
CONFIRM-2, 362	Cost–utility analysis, 356–359, 359t	retinoblastoma, 309
Congenital retinal cyst, 6	direct medical costs, 359	Cytokine traps, 259
Conjunctiva	societal costs, 359	Cytomegalovirus retinitis, 10
drug permeation, 87–88	standardization, 359, 360t	anti-vascular endothelial growth factor
topical drug administration, 60	Cost–utility ratio, 356, 358–359	gene-based drugs, 1
Conjunctival in situ squamous cell	Costimulatory molecules, 39	cidofovir, 117–118
carcinoma, verteporfin photodynamic	Coumadin see Warfarin	fomiversen sodium (Vitravene) intraviteal
therapy, 303	Craf kinase antisense oligonucleotide, 3	therapy, 96
Construct validity, 356	CRB1 mutations, Leber’s congenital	ganciclovir
Controlled drug release, 2	amaurosis, 194	intraocular implants (Vitrasert), 3, 81–82
intraocular implants, 3	Criterion validity, 356	intravitreal therapy, 96
microparticles/nanoparticles, 3	Crohn’s disease, 236–237, 239–240, 252,	safety of retinal therapy, 100
thermo-sensitive hydrogels, 91	258	silicone oil tamponade combined
Copaxone, 295	CRUISE, 228	treatment, 71
Copper, 126	CRX mutations, Leber’s congenital	HIV/AIDS-related, 3, 62–63, 81–82, 96
Copy number variants (CNVs), 49	amaurosis, 194	intravitreal drug delivery, 67
Cornea	CRYO-ROP (Cryotherapy for Retinopathy of	polymerase chain reaction diagnosis, 41
drug permeation, 86, 88	Prematurity), 177
paracellular, 86–87	Cryotherapy, retinopathy of prematurity,	Dacarbazine, metastatic uveal melanoma,
transcellular, 86–87	177	309–310
epithelial cell tight junctions, 60–61	Crystalline retinopathy, systemic medicines	Daclizumab, 236, 241–244, 245t
topical drug administration, 60, 75	toxicity, 114–117	adverse effects, 101, 243–244
Corneal neovascularization, verteporfin	CVOS (Central Vein Occlusion Study), 139,	birdshot retinochoroidopathy, 157
photodynamic therapy, 303	323	contraindications, 243
Corticosenes, 208	CX3CR1 single nucleotide polymorphism, 8	dosage, 241
angiostatic activity, 208	Cyanine dyes, chromovitrectomy, 331	drug interactions, 244
lack of glucocorticoid activity, 210	Cyclodextrins, 61, 88–89	mechanism of action, 241
Corticosteroids, 41, 201–207, 248	microparticle drug complexation, 89–90	ophthalmic indications, 242–243
Adamantiades–Behçet disease, 153–157	nanoparticles, 86	pharmacology, 241
age-related macular degeneration	suspensions in eye drops, 90	sarcoidosis, 158
(exudative), 203–204	Cyclooxygenase inhibitors, 196	systemic indications, 241
birdshot retinochoroidopathy, 157	Cyclophilin, 248	uveitis, 242–243, 242t

Index

371

Index

Dark current, phototransduction, 19	iris neovascularization, 185	Drug delivery, 2, 60–66, 74–80, 82t
Daunorubicin, proliferative vitreoretinopathy	laser photocoagulation, 133	animal models, 74–75
adjunctive therapy, 150	neovascular glaucoma, 185–186, 189	intraocular, 61–65
Deferoxamine, retinal toxicity, 109–110	pathogenesis, 133–134, 273	micro/nanotechnological applications, 86
Degenerations, 8–9	inflammatory mechanisms, 41, 133–134	modalities, 75–79
peripheral, 8	vascular endothelial growth factor	properties of ideal system, 74
Delta-like, 29	involvement, 23	topical, 61
Delta-like ligand 4 (Dll4), angiogenesis, 29,	pathology, 12	Drusen
230, 232	pegaptanib, 267–268, 269t	activated complement components, 44, 46
Denali trial, 131	pharmacologic vitreolysis, 328	age-related macular degeneration, 8,
Dendrimers, 61, 65	prevalence, 133	123–125, 128
Dendritic cells, 37–38	retinal blood flow autoregulation	optic nerve head, retinal vein occlusion,
Depo-Medrol, retinal toxicity, 110	impairment, 17	137
Depot formulations, 62	risk factors, 133	Dystrophies, 6–8
Dexamethasone, 201–202	ruboxistaurin, 232, 274–275
endophthalmitis, 173	sustained-release devices, 81	E10030, 363
γ cyclodextrin complexation, 89	symptoms/signs, 134	Eales’ disease, neovascular glaucoma, 186,
microsuspension formulation, 89	treatment outcome/prognosis, 135	188
intraocular implants, 3	treatment strategies, 41, 134–135, 189	Eculizumab, 46, 122
biodegradable, 63, 82–83	vascular endothelial growth factor	Efalizumab
intravitreal delivery, 81, 96	inhibitors, 1, 220	diabetic macular edema, 365
photodynamic therapy combination, 131	Dicer, 278, 288	safety of retinal therapy, 101
Ozurdex implant, 3, 63, 201, 206	Diclofenac, 153, 196	EGb 761 (ginkgo biloba), neuroprotective
central retinal vein occlusion, 203	pharmacology, 196	activity, 293
poly(lactic-co-glycolic) acid microparticles,	physicochemical characteristics, 197f	Ehlers–Danlos syndrome, 162
63	safety of retinal therapy, 101	Eicosapentanoic acid, 292
safety of retinal therapy, 97–99	use in ocular/retinal disease, 198	age-related macular degeneration, 57
structure, 202, 202f	2′,3′-Dideoxyinosine (DDI), retinal toxicity,	Electroporation, 86
subconjunctival/peribulbar injection, 2	109	gene transfer, 287
Diabetes, retinal vein occlusion risk, 137	Dietary factors	ELOVL4 mutations, 6–7
Diabetic macular edema, 26, 133–136, 201,	abetalipoproteinemia (Bassen–Kornzweig	Embryonic stem cells, retinal pigment
362	syndrome), 194	epithelium replacement, 349–350
ATG-003 (topical mecamylamine), 363	age-related macular degeneration, 56–59,	EMD478761, 31
bevacizumab, 223	125–126	Emulsions (creams), micro/nanotechnological
bevasiranib, 279, 281–282	AREDS formulations, 126t	applications, 86
corticosteroids, 202–203	AREDS2 formulations, 126t	Encapsulated cell technology, 3
biodegradable sustained-release implants,	carotenoids, macular pigments, 17	ciliary neurotrophic factor delivery (NT-501
82–83	gyrate atrophy, 194	implant), 192–193, 293
periocular/intravitreal injection, 82, 365	Refsum’s disease, 193	sustained-release devices, 81, 83–84
diagnosis, 134	retinitis pigmentosa, 192	Endometrial cancer, 220
efalizumab, 365	Digoxin, retinal toxicity, 118	Endophthalmitis, 170–175
indocyanine green chromovitrectomy, 332	Diltiazem, neuroprotection, 295	acute-onset, 170, 172–173
inflammatory processes blockade, 365	Dipivefrin, retinal toxicity, 114	causative organisms, 170–172, 171t
laser photocoagulation, 133	Discoid lupus, 109	chronic postoperative, 170
pathogenesis, 133–134	Dispase	diagnosis, 172
pegaptanib, 267–268, 269t	retinal toxicity, 327	differential diagnosis, 172
pharmacologic treatment, 363t	vitrectomy, 72, 327	endogenous, 170–173
PKC412, 274	DNA injection, gene transfer, 287	filtering bleb-associated, 170
ranibizumab, 228	DNA topoisomerase II inhibitors,	fungal, 173, 317
retinal blood flow autoregulation	retinoblastoma, 306	antifungal agents, 173–174, 174t
impairment, 17	DNA viral vectors, 285–286	incidence, 170
rheopheresis, 322–323	Docetaxel	intravitreal antibiotic treatment, 67,
ruboxistaurin, 274	lung carcinoma, 309	99–100
sirolimus (rapamycin), 364	uveal metastases, 309	intravitreal injection-related, 170, 171t,
symptoms/signs, 134	Docosahexaenoic acid	172
treatment options, 134–135	age-related macular degeneration, 57	prevention, 170
vascular endothelial growth factor, 23, 227	neuroprotection, 292–293	triamcinolone acetonide complication,
gene-based drugs, 1	retinitis pigmentosa, 192	204–205
Trap-Eye, 263	Dog models, pharmacokinetics, 75	microbial culture techniques, 172
Diabetic retinopathy, 2, 13, 15, 133–136	Dominant slowly progressive macular	microbial keratitis-related, 170, 172–173
bevacizumab, 221	dystrophy of Singerman–Berkow–Patz,	nasal antibiotics administration, 316–317
blood–retinal barrier disruption, 16	6–7	neovascular glaucoma, 186
diagnosis, 134	Dorzolamide, X-linked juvenile retinoschisis,	ocular symptoms, 172–173
endothelial dysfunction, 17	195	off-label drug use, 352
genetic aspects, 48	Doxorubicin	oral/intravenous antibiotics, 315–316
erythropoietin single nucleotide	poly(lactic-co-glycolic) acid microparticles,	postoperative, 170
polymorphism, 133	63	management strategies, 313
hyperglycemia, 134	retinoblastoma, 308–309	pathogens, 313–314
insulin receptors in retina, 134	small-cell lung carcinoma, 309	post-traumatic, 170, 173
intravitreal drug delivery, 72	uveal metastases, 309	prophylaxis, 67–69, 170

372

risk factors, 170	Eye drops, 2	intravitreal pharmacokinetics/clearance,
systemic manifestations, 173	cyclodextrin-containing formulations,	70
topical fluoroquinolones, 314–315	89–90	microbial resistance, 314
treatment options, 173–174	systemic drug absorption, 87	minimum inhibitory concentration,
treatment outcome, 174	tear fluid dilution, 87–88	315–316, 316t
see also EVS (Endophthalmitis Vitrectomy	Eyegate II Delivery System, 4	5-Fluorouracil
Study)	Eyelash disinfection, endophthalmitis	intravitreal delivery, 96
Endostatin, 230	prophylaxis, 68	combined gas tamponade, 71
Endothelin, 273		combined silicone oil tamponade, 71
retinal vascular homeostasis, 17	Factor B, 44	intravitreal pharmacokinetics/clearance,
Enucleation, retinoblastoma, 306	age-related macular degeneration, 45, 52,	70–71
Enzymatic vitrectomy, 327–330	123	poly(lactic-co-glycolic) acid microparticles,
choroidal neovascularization prophylaxis,	therapeutic targeting, 46, 53	63
328	single nucleotide polymorphism, 8	proliferative vitreoretinopathy adjunctive
complications, 329	Factor H, 31, 37, 44, 364–365	therapy, 150
pharmacology, 327–328	age-related macular degeneration-related	uveal metastases, 309
surgical vitrectomy adjunctive use, 328	mutations, 37, 40, 44–45, 123, 293	Flupirtine, neuroprotection, 295
vitreolysis, 101, 327	single nucleotide polymorphism, 8	FOCUS, 130
Enzymes, safety of retinal therapy, 101	see also Factor H Y402H variant	Fomiversen sodium (Vitravene), 1
Ephrins, 28–29	Factor H related-1, 52	intravitreal delivery, 96
angiogenesis promotion, 26–29	Factor H Y402H variant, 45–46, 48–49, 52	Food and Drug Administration (FDA)
Ephs, angiogenesis promotion, 26–29	age-related macular degeneration, 51–52,	approval process, 352
Epilepsy, 118	122–123, 365	Foreign bodies, 11
Epinephrine, retinal toxicity, 114	FAME (Fluocinolone Acetonide in diabetic	Formivirsen analog nanoparticles, 86
Epirubicin, uveal metastases, 309	Macular Edema), 205–206	Fotemustine, metastatic uveal melanoma,
Epstein–Barr virus, acute retinal necrosis	Familial exudative vitreoretinopathy,	309–310
syndrome, 40	pegaptanib, 269	Foveola, 5
Ergot alkaloids, retinal toxicity, 113	Familiar drusen, 6–7	Foveomacular vitelliform dystrophy, 6–7
Erlotinib, lung carcinoma, 309	Fat intake, age-related macular degeneration,	Free radical damage, 9
Erythropoietic protoporphyria, 116	57, 122	Fuchs’ heterochromic iridocyclitis, 188
Erythropoietin	Fenestrated sheen macular dystrophy, 6	Fuchs spot, 8–9
angiogenesis promotion, 30	Fibrinolytics, safety of retinal therapy, 101	Fundus flavimaculatus, 6–7
diabetic retinopathy-related single	Fibroblast growth factor 2 see Basic fibroblast	Fungal endophthalmitis, 317
nucleotide polymorphism, 133	growth factor	Fungal keratitis, 317–318
ET-ROP (Early Treatment for Retinopathy of	Fibroblast growth factor	Fusarium keratitis, 172, 317–318
Prematurity), 177	angiogenesis, 230, 232	Future developments, 362–366
Etanercept, 236, 240–241, 245t	proliferative vitreoretinopathy pathogenesis,
adverse effects, 101, 241	148	GABAergic neurons, 5
contraindications, 241	Fibroblast growth factor receptors, 362	γ cyclodextrins, 88–89
drug interactions, 241	Fibronectin, 51–52	Gamma irradiation, 65
mechanism of action, 240	vital dye uptake, 332	Ganciclovir, 244
ophthalmic indications, 240–241	vitreous, 327–328	gene therapy combined approach,
pharmacology, 240	FKBP12, 364	retinoblastoma, 289
systemic indications, 240	Fluconazole	intraocular delivery system sterilization, 65
Ethnic factors	rifabutin interaction, 117	intraocular implants (Vitrasert), 3, 62–63,
age-related macular degeneration, 122,	safety of retinal therapy, 100	81–82
128	Flunarizine, neuroprotection, 295	intravitreal delivery with silicone oil
myopia, 162	Fluocinolone acetonide, 201–202	tamponade, 71
posterior uveitis, 152	depot formulations, 62	liposomal prodrug delivery, 63
retinal detachment, 147	intraocular implants	nanoparticles, 86
Vogt–Koyanagi–Harada disease, 158	I-vation, 201	poly(lactic-co-glycolic) acid microparticles,
Ethoxyzolamide, retinal toxicity, 114	Medidur/Iluvien, 63, 83, 201, 205–206	63
Ethylene vinyl acetate, ophthalmic drug	Retisert, 3, 62–63, 82, 157, 201–202,	safety of retinal therapy, 96, 100
inserts, 2–3, 81	205	Ganglion cell layer, 5
Ethylenediamine tetraacetic acid (EDTA), 61	intravitreal delivery with gas tamponade,	Ganglion cells, 5
Ethylvinylacetate, intraocular drug delivery,	71	neuroprotection, 292
62	safety of retinal therapy, 97	memantine, 293
Etoposide	structure, 202, 202f	Gas tamponade, combined intravitreal drug
retinoblastoma, 306, 308–309	see also FAME (Fluocinolone Acetonide in	delivery, 71
small-cell lung carcinoma, 309	diabetic Macular Edema)	Gas-phase nanoparticles, intravitreal drug
Evidence levels, 356, 357t	Fluorescein, 331	delivery, 77–79
Evidence-based medicine, 356	angiography, labeled thermo-sensitive	Gastrointestinal cancer, 220, 298–299
EVS (Endophthalmitis Vitrectomy Study), 72,	hydrogels, 93–94	Gatifloxacin
173–174, 173t, 313–316, 313b	chromovitrectomy, 334	endophthalmitis, 173, 314
diabetic patient subset analysis, 314	Fluoromethalone acetate, chromovitrectomy,	oral administration, 315–316
EXCITE, 227	331–332	minimum inhibitory concentration,
Exfoliation syndrome, 188	Fluoroquinolones	315–316, 316t
EXTEND-1, 227	endophthalmitis, 173	safety of retinal therapy, 100
External limiting membrane, 5	oral, 315–316	structure, 314f, 315
Eye Disease Case-Control Study, 125, 137	topical, 314–315	Gelrite, 61

Index

373

Index

Gels, micro/nanotechnological applications,	central retinal vein occlusion, 137,	HLA-B51, 152–153
86	185–186, 189	HLA-Drw2, 162
Gemcitabine	diabetic retinopathy, 185–186, 189	Hodgkin’s lymphoma, 255
lung carcinoma, 309	diagnosis, 188	Horizontal cells, 5
metastatic uveal melanoma, 309–310	differential diagnosis, 188	HtrA serine peptidase 1 (HTRA1) single
Gene therapy, 48–49, 86, 285–291	intraocular pressure control, 189	nucleotide polymorphism, 8
antiapoptotic therapy, 294–295	neovascularization process, 186	age-related macular degeneration, 48–49,
dominant diseases, 287–288	pathogenesis, 185–188	52, 122–123
ex vivo gene transfer, 285	pharmacologic therapies, 189–190	Human immunodeficiency virus-1 (HIV-1)
gene silencing strategies, 287–288	photodynamic therapy, 190	gene therapy vector, 286
germline, 285	prevalence, 185	see also HIV/AIDS
historical background, 285	prognosis, 190	Humoral adaptive immunity, 38
in situ gene transfer, 285	radiotherapy complication, 341	Hyaluronan, 327
in vivo gene transfer, 285	retinal detachment, 186, 188	vitreous, 15
Leber’s congenital amaurosis (RPE65 gene	risk factors, 185	Hyaluronic acid
therapy), 194–195, 287, 289–290	symptoms/signs, 188–189	mucoadhesive polymer formulations, 61
nanoparticle vectors, 65	treatment options, 189–190	viscous solutions, 65
neoplastic ocular disease, 288–289	treatment of underlying disease, 189	vitreous, 327
neuroprotection, 293	vascular endothelial growth factor	Hyaluronidase
NIH guidelines, 287	involvement, 23	safety of retinal therapy, 101, 327
nonviral vectors, 287, 288t	primary open-angle, anecortave acetate,	vitrectomy, 72, 327
pathogenic pathway targeting, 53	212–213	Hydrochlorothiazide, retinal toxicity, 114
proliferative ocular disease, 288–289	sustained-release devices, 81	Hydrocortisone, retinoblastoma, 309
recessive diseases, 287	Glioblastoma multiforme, 114, 220	Hydrogels, 91
retinal dystrophies, primary lesion direct	Glioma, 110	thermo-sensitive, 91–95
targeting, 52–53	Glutamate-mediated excitotoxicity, 293	characteristics, 91
retinitis pigmentosa, 288	Glutamatergic neurons, retina, 5	cross-linked systems, 91–92
retinoblastoma, 288–289	Glycinergic neurons, retina, 5	delivery site, 93–94
somatic, 285	Glycosaminoglycans, Bruch’s membrane	drug delivery, 91
viral vectors, 285–286	matrix dysregulation, 21	materials, 91
associated risks, 287	Gold nanoparticles, gene transfer, 287	poly(ethylene glycol)/poly(ethylene glycol)
Gene-based drugs, 1	Graft rejection, 248	diacrylate incorporation, 91
Gene-independent therapy, 53	GTPase-activating protein (RGS9), 19	pore size, 91–92
Genetic factors, 48–55	Guanylate cyclase activating protein, 19	toxicity testing, 94
age-related macular degeneration see	GUCY2D mutations, Leber’s congenital	Hydroporation, gene transfer, 287
Age-related macular degeneration	amaurosis, 194	Hydroxychloroquine, retinal toxicity, 107–108
glossary of terms, 50t	Gyrate atrophy, 194	screening guidelines, 108
historical aspects, 48–49	dietary restriction, 194	Hydroxypropyl cellulose, sustained-release
posterior uveitis, 152	retinal pigment epithelium transplantation,	inserts, 81
presumed ocular histoplasmosis syndrome,	344	Hydroxypropylmethylcellulose
162	vitamin B6 supplementation, 194	biodegradable ophthalmic inserts, 61
retinitis pigmentosa see Retinitis		viscous solutions, 65
pigmentosa	Hard exudates, hypertensive retinopathy, 17	Hypertension
treatment response prediction, 53–54	Head and neck cancer, 252	age-related macular degeneration, 128
see also Hereditary retinal diseases	Helper T cells see Th1 lymphocytes; Th2	choroidal neovascularization risk in
Genetic heterogeneity, 49–51	lymphocytes; Th17 lymphocytes	fellow eye, 128
Leber’s congenital amaurosis, 49, 194	Hemangiomas of infancy, 113	diabetic retinopathy, 133
retinitis pigmentosa, 49–51, 192	Hepatitis C, 113	retinal vein occlusion, 137
Genome-wide association studies, 48–49	Hereditary retinal diseases, 192–195	Hypertensive retinopathy
Genotype-specific treatment, 49	treatment approaches, 192	pathology, 12
Gentamicin	see also Genetic factors	retinal arteriolar changes, 17
adverse effects, 9, 99, 112	Herpes simplex virus	Hypoxanthine guanine phosphoribosyl
intravitreal pharmacokinetics/clearance, 70	acute retinal necrosis, 10, 40	transferase deficiency, 285
Giant-cell arteritis, 12–13	polymerase chain reaction diagnosis, 41	Hypoxia-inducible factor, 231
neovascular glaucoma, 186	Histoplasma capsulatum, 162	age-related macular degeneration
Giant-cell astrocytoma of retina, 188	see also Presumed ocular histoplasmosis	neovascularization (wet form), 128
Ginkgo biloba (EGb 761), neuroprotective	syndrome	retinal vascular development, 176
activity, 293	HIV/AIDS
Glatiramer acetate, 295	cytomegalovirus retinitis	Idiopathic choroidal neovascularization,
Glaucoma, 2	ganciclovir implants (Vitrasert), 62–63	162–163
ciliary neurotrophic factor-secreting retinal	gene-based drugs, 1	bevacizumab, 167
pigment epithelium cell implants, 63	Mycobacterium avium-complex infection,	laser photocoagulation, 166
glutamate-mediated excitotoxicity, 293	109, 117	photodynamic therapy, 166–167
intravitreal drug delivery, 72	retinal toxicity of systemic medications,	Idiopathic intermediate uveitis, daclizumab,
neovascular, 185–191	109	242
bevacizumab, 223	HLA-A29, 152, 157	Idiopathic macular telangiectasia, 181–184
carotid artery occlusive disease, 186–187,	HLA-B7, 162	bevacizumab, 222–223
189	HLA-B27-associated uveitis	type 1, 181
central retinal artery occlusion, 186–187,	chlorambucil, 258	clinical features, 181
189	infliximab, 236, 239	treatment, 181

374

type 2, 181–183	mechanism of action, 236	nanoparticles, 3, 86
disease stages, 182	ophthalmic indications, 236–239, 237t	off-label drug use, 354
nonproliferative, 182–183	pharmacology, 236	particulate systems, 63
proliferative, 183	sarcoidosis, 158	pharmacokinetics/clearance, 70–71
type 3, 181	systemic indications, 236	postoperative, 72
Idiopathic perifoveal telangiectasia	Informed consent, off-label drug use, 353	preoperative, 67, 72
anecortave acetate, 212	Infracyanine green, 331	rationale, 67
bevacizumab, 222–223	chromovitrectomy, 332–333	silicone oil tamponade combination, 71
verteporfin photodynamic therapy, 301	Innate immunity, 37, 44	technique, 67–68
Idiopathic uveitis, chlorambucil, 258	Inner nuclear layer, 5	guidelines, 70
Ifosfamide, retinoblastoma, 309	Inner plexiform layer, 5	needle gauge, 68
Illicit drug usage, talc retinopathy, 111	Inserts, ocular	procedure, 68
Imatinib, ranibizumab combined therapy,	biodegradable, 61	vascular endothelial growth factor
363	micro/nanotechnological applications, 86	inhibitors, 1–2
Immune privilege, 38–40, 345	topical drug delivery, 61	vitrectomized eyes, 71
anterior chamber, 40	Insulin-like growth factor, 363	Intravitreal formulations, 61
Immune-inflammatory processes, 37–44	neovascular glaucoma, 185–186	Investigational new drug (IND) application,
posterior uveitis, 152	retinopathy of prematurity, 176	352–353
see also Inflammation	Insulin-like growth factor receptor inhibitors,	Ion drug exchange, 2
Immunity	363	Iontophoresis, 2, 4, 86
adaptive, 37–39, 44	Integrin inhibitors, 363	Iris neovascularization
innate, 37, 44	Integrins, angiogenesis promotion, 31	vascular endothelial growth factor
pathogenic mechanisms, 40–41	Interferon therapy, 38–39	involvement, 23
Immunosuppressive therapy, 41, 248–258	retinal toxicity, 113	verteporfin photodynamic therapy, 303
Adamantiades–Behçet disease, 153–157	Interferon-α	Iron overload, 109
guidelines for patients with ocular	neovascular glaucoma, 185–186	Irvine–Gass syndrome, 9
inflammation, 153	uveal melanoma, 309	chromovitrectomy, 332
multofocal choroiditis and panuveitis, 158	uveitis, 244	pegaptanib, 269
posterior uveitis, 153	Interferon-γ, 39	Ischemic optic neuropathy, retinal vein
retinal pigment epithelium transplantation,	Interleukin 2 receptor antagonist, 241–244	occlusion, 137
345	Interleukin 12, 39
sarcoidosis, 158	Internal limiting membrane, 5	Jagged1/2, 29
sympathetic ophthalmia, 160	chromovitrectomy, 331–334	JNJ-26076713, 31
Vogt–Koyanagi–Harada disease, 160	enzymatic vitrectomy, 327–328	JPE-1375, 46
IMPDH1 mutations, Leber’s congenital	vitreous adhesion, 15	JSM5562, 31
amaurosis, 194	Interphotoreceptor matrix (glycosaminoglycan	JSM6427, 31, 363
Implants, intraocular, 3	ground substance), 5	JSM7717, 46
adverse effects, 3	Intracranial tumors, 220	Junction adhesion molecules, 16
biodegradable, 3, 63, 81–83	Intramers, 265	Juvenile idiopathic arthritis, 240, 252
corticosteroids, 201	Intraocular drug delivery systems, 61–65	chlorambucil, 258
nonbiodegradable, 3, 62–63, 81	biodegradable, 62–65	Juvenile idiopathic arthritis-associated uveitis
sustained-release devices, 81–83, 84t	nonbiodegradable, 62–63	adalimumab, 236–237
In situ gel systems, topical drug delivery, 61	sterilization, 65	infliximab, 236, 239
Indocyanine green, 331	Intraocular pressure elevation, corticosteroids-	Juvenile rheumatoid arthritis, 152, 236
chromovitrectomy, 331–332	induced, 204
indications, 332	Intrathecal chemotherapy, retinoblastoma,	Kaposi’s sarcoma, 113
photothrombosis, idiopathic macular	309	Ketorolac, 153, 196
telangiectasia, type 2, 182	Intravitreal drug delivery (injections), 2, 60,	pharmacology, 196
retinal toxicity, 332	67–73, 81, 86, 96	physicochemical characteristics, 197f
Infections, 10	adverse effects, 2, 69–70, 81, 96	safety of retinal therapy, 101
choroidal neovascularization, 162–169	anecortave acetate, 208	use in ocular/retinal disease, 198
polymerase chain reaction diagnosis, 41	antibiotics, 68	Klebsiella endophthalmitis, 170–172
Infectious choroiditis, 40	anticoagulated patients, hemorrhagic
Infectious retinitis, 40	complications, 67	Lacrisert (sustained-release hydroxypropyl
Inflammation, 13	chemotherapy, retinoblastoma, 308	cellulose), 81
age-related macular degeneration, 40,	endophthalmitis complicating, 170, 171t,	Laminin, vitreous, 327–328
51–52, 123, 128	172	Laser photocoagulation
choroidal neovascularization, 162–169	prevention, 67–69, 170	choroidal neovascularization, 166
diabetic macular edema, 365	gas tamponade combination, 71	idiopathic macular telangiectasia
diabetic retinopathy, 41, 133–134	gas-phase nanoparticles, 77–79	type 1, 181
neovascular glaucoma, 186	aerosol drug deposition, 74–75, 77–79	type 2, 182–183
see also Immune-inflammatory processes	flow-through method, 78	neovascular age-related macular
Inflammatory diseases, 10	pharmacokinetics, 78–79	degeneration, 129
Infliximab, 26, 236–239, 245t	single-fill method, 74, 78–79	neovascular glaucoma, 189
Adamantiades–Behçet disease, 157	historical background, 67, 96	retinal vein occlusion
adverse effects, 101, 239	injection safety, 67	branch, 139, 143
birdshot retinochoroidopathy, 157	intraoperative, 72	central, 139–143, 189
contraindications, 239	liposomes, 86	retinopathy of prematurity, 177
dosage, 236	local disinfection, 68	sarcoidosis, 158
drug interactions, 239	microparticles, 3	Latanoprost, retinal toxicity, 114

Index

375

Index

Lattice degeneration, 8	Macular holes	Methanol, retinal toxicity, 118
Lebercilin mutations, Leber’s congenital	chromovitrectomy, 331–333	Methazolamide, 192
amaurosis, 194	protection from direct dye injection, 335	Methotrexate, 41, 239–241, 251–252
Leber’s congenital amaurosis, 52–53,	enzymatic vitrectomy, 329	intraocular lymphoma, 310
194–195	surgical adjunctive treatment, 328	intravitreal injection, 252
gene therapy, 48, 52–53, 192, 194–195,	Macular hypoplasia/aplasia, 6	juvenile idiopathic arthritis-associated
287, 289–290	Macular Photocoagulation Study, 128, 166	iridocyclitis, 252
genetic aspects, 48	Macular pigments, 17–18, 56, 125	mechanism of action, 251
heterogeneity, 49, 194	age-related macular degeneration protective	pharmacology, 251
retinal pigment epithelium transplantation,	action, 56	retinoblastoma, 309
344	functions, 17–18	safety of retinal therapy, 101–102
Lecithin-retinol acetyl transferase, 18	Macular translocation surgery, choroidal	sarcoidosis, 158
(LEI)-DNase II, 18	neovascularization, 167	small-cell lung carcinoma, 309
Lentivirus vectors, 286	Magnetofection, gene transfer, 287	systemic indications, 252
Leprosy, 109	Major histocompatibility complex (MHC), 37	use in retinal disease, 252
Lesch–Nyhan syndrome, 285	class I molecules, 37–39	uveal metastases, 309
Leukemia, 12, 137, 255, 298–299	class II molecules, 37–39	uveitis, 252
Lid disinfection, endophthalmitis prophylaxis	retinal pigment epithelium transplant	Vogt–Koyanagi–Harada disease, 160
for intravitreal drug deliver, 68	rejection, 345	Methoxyflurane, retinal toxicity, 117
Light-induced system, 3	Malaria, 107–108	Metipranolol, neuroprotective activity, 293
Linkage analysis, 48	Mammalian target of rapamycin (mTOR)	Metronidazole, retinal toxicity, 114
Linoleic acid, age-related macular	inhibitor, 364	Micelles, 65
degeneration, 57	Mannan-binding lectin, 37	Microarrys (gene chips), 48–49
Lipofuscin, 19–20	Mannose receptor, 37	Microcannula technology, suprachoroidal
age-related macular degeneration, 20	Mannose-binding lectin-associated proteases	drug delivery, 76–77
formation, 19	(MASP-1/2), 44	Microemulsions, 61, 86
retinal pigment epithelium atrophy, 19	MARINA, 67, 130, 227–228, 231	drop size, 86
Stargardt’s disease, 20	Matrix biology, 20–21	Microparticles, 3, 86, 87t
Lipopolysaccharide-binding protein, 37	Matrix metalloproteinase 2 (MMP-2), 21, 26,	biodegradable, 63
Liposomes, 3, 61, 65, 86	327–328	cyclodextrin–drug complexes, 89–90
biodegradable, 61, 63	Matrix metalloproteinase 3 (MMP-3),	size, 86
gene therapy, 53, 287	vascular endothelial growth factor165	sustained-release devices, 81, 83
sustained-release devices, 81, 83	isoform cleavage, 230	Microplasmin, 328
Lomerizine, neuroprotection, 295	Matrix metalloproteinase 9 (MMP-9), 21, 26	safety of retinal therapy, 101
LRAT mutations, Leber’s congenital	Matrix metalloproteinases, 23	vitrectomy, 72, 328–329
amaurosis, 194	anecortave acetate effects, 210	operative technique, 329
Lucentis see Ranibizumab	angiogenesis promotion, 30–31	outcome, 329
Lung cancer, 220, 226, 252	Bruch’s membrane, 21	see also MIVI-I (Microplasmin in
bevacizumab effects, 220	vascular endothelial growth factor165	Vitrectomy); MIVI-IIT; MIVIIII
uveal metastases, 309	isoform cleavage, 230	Microspheres, 86–90
Lutein, 17–18, 56, 292	Matrix structures, intraocular drug delivery,	Migraine, 114
Age-Related Eye Disease Study 2	62	Mineral supplements, age-related macular
(AREDS2), 57–58	Mecamylamine, 363	degeneration, 125–126
age-related macular degeneration	Medical Outcomes Short-Form-36 (SF-36),	MIRA-1, 321–322
dietary supplementation, 56, 125	357	MIVI-I (Microplasmin in Vitrectomy),
protective action, 56	Medicare, off-label drug use coverage,	101
LY333531 see Ruboxistaurin	353–354	MIVI-IIT, 328
Lymphatic vessels, 37	clinical trials, 354	MIVI-III, 328
Lymphoma, 137, 255	national coverage determination, 354	Modifier genes, 49, 51
intraocular, 310	Medidur see Fluocinolone acetonide	Monoclonal antibodies
radiotherapy, 338	Melanoma, 113, 298–299	intravitreal pharmacokinetics/clearance,
treatment options, 310	anecortave acetate, 211	70–71
	choroidal	safety of retinal therapy, 100–101
MAC MPS, 129	radiotherapy, 336–337, 339	Mont Blanc trial, 131
MAC-1 trial, 321	verteporfin photodynamic therapy, 303	Moxifloxacin
Macaca fascicularis (cynomolgus monkey),	gene therapy approaches, 288–289	endophthalmitis, 173, 314
97	neovascular glaucoma, 188	collagen shield administration, 315
Macaca mulatta (rhesus monkey), 97	uveal, 309–310	oral, 315–316
Macrophages, 37–38	metastases, 307	topical, 315
Macroretinal dysytophy of retinal pigment	treatment options, 309	intravitreal pharmacokinetics/clearance,
epithelium, 6–7	Memantine, 293	70
Macula, 5	Menkes syndrome, 6	minimum inhibitory concentration,
Macular dystrophy, verteporfin photodynamic	6-Mercaptopurine, 252	315–316, 316t
therapy, 301	MERTK mutations, Leber’s congenital	safety of retinal therapy, 100
Macular edema, 9	amaurosis, 194	structure, 314f, 315
corticosteroids, 201	Meso-zeaxanthin, 17–18	Mucoadhesion, topical drug delivery, 88
retinal vein occlusion, 137–138	Metabolic storage diseases, 12	Mucoadhesive polymers, topical drug
treatment, 139–140, 143	Metarhodopsin II, 18–19	delivery, 61
see also Cystoid macular edema	deactivation, 19	Mucolipidoses, 12
Macular heterotopia, 6	Metastatic tumors, radiotherapy, 338	Mucopolysaccharidoses, 12

376

Müller cells, 5	definitions, 292	Omega-3 fatty acids
Multifocal choroiditis and panuveitis,	gene therapy, 293	abetalipoproteinemia (Bassen–Kornzweig
157–158, 162	glutamate-mediated excitotoxicity, 293	syndrome), 194
clinical features, 157, 165	intravitreal gas-phase nanoparticle drug	Age-Related Eye Disease Study 2
diagnosis, 157, 163	delivery, 77	(AREDS2), 57–58
pharmacotherapy, 158	neurotrophic factors, 293	age-related macular degeneration, 56–57,
verteporfin photodynamic therapy, 301	Neuroretina, 5	122
Multiple myeloma, 137	Neurotrophic factors	neuroprotection, 292
Mupirocin, nasal administration	neuroprotection, 293	retinitis pigmentosa, 192
Gram-positive organisms eradication,	poly(lactic-co-glycolic) acid microparticles,	Onchocerciasis, 10
316	63	Opsin, 18–19
intraocular surgical infections prophylaxis,	Nevanac, 196	Optic disc heterotopia, 6
316–317	pharmacology, 196–197	Optic nerve head drusen, retinal vein
Mycobacterium avium-complex infection,	Nicardipine, neuroprotection, 295	occlusion risk, 137
109, 117	Nicotinic acetylcholine receptor antagonists,	Optic neuropathy, radiotherapy complication,
Mycophenolate mofetil, 41, 244, 251	363	341–342
birdshot retinochoroidopathy, 157	Nicotinic acid, retinal toxicity, 114	Optical filtering, macular carotenoids, 17–18
mechanism of action, 251	Nifedipine, neuroprotection, 295	Oral contraceptives
pharmacology, 251	Nilvadipine, neuroprotection, 295	retinal toxicity, 111–112
sarcoidosis, 158	Nipradilol, neuroprotection, 293	retinal vein occlusion risk, 137
systemic indications, 251	Nitric oxide, 23	Organ transplant rejection, 241
use in retinal disease, 251	retinal vascular homeostasis, 17	Ornithine aminotransferase deficiency, 194
Vogt–Koyanagi–Harada disease, 160	Nitric oxide synthase, 17	Ornithine transcarbamylase deficiency, gene
Myopia	Nitrofurantoin, retinal toxicity, 117	therapy, 287
choroidal neovascularization, 162–169	Non-Hodgkin’s lymphoma, 252, 255,	Outer nuclear layer, 5
bevacizumab, 167, 222	298–299	Outer plexiform layer, 5
clinical features, 164	Nonsteroidal anti-inflammatory drugs,	Ovarian cancer, 220
diagnosis, 163	196–200	Oxidative stress, age-related macular
laser photocoagulation, 166	contraindications, 200	degeneration, 56, 123, 125, 128
pathogenesis, 163	historical aspects, 196	Ozurdex see Dexamethasone
pegaptanib, 269	mechanism of action, 196–197
risk factors, 162	pharmacology, 196–197	Paclitaxel
surgery, 167	posterior uveitis, 153	lung carcinoma, 309
verteporfin photodynamic therapy, 166,	safety of retinal therapy, 101	uveal melanoma, 309
297, 300–301	toxicity, 200	uveal metastases, 309
prevalence, 162	Notch, angiogenesis promotion, 29	Paget’s disease, 162
retinal detachment, 147	NT-501 implant, 3, 63, 83–84, 192–193, 293	Panuveitis, autoimmune pathogenesis, 40–41
Myristyl gamma-picolinium chloride, 110	retinitis pigmentosa, 293	Paracellular signaling pathway, 273
		Patches, topical drug delivery, 61
N-retinylidene phosphatidylethanolamine,	Occludins, 16, 273	Patent blue, 331
19–20	Ocular albinism, 6	chromovitrectomy, 331, 333
Nanocapsules, 86	Ocular cicatricial pemphigoid	retinal toxicity, 333
Nanoparticles, 3, 65, 86, 87t	cyclophosphamide, 255	Pattern dystrophy of pigment epithelium of
biodegradable, 63	daclizumab, 243	Marmot–Beyers, 6–7
cyclodextrin suspensions in eye drops,	Ocular ischemia syndrome/carotid	Pattern recognition receptors, 37
90	insufficiency, neovascular glaucoma,	Pazopanib, 131
gas-phase, intravitreal drug delivery,	186	Pegaptanib, 24, 265–272
77–79	Ocular penetration, 2	adverse effects, 270–271
gene therapy, 53	Ocuphor, 4	age-related macular degeneration, 130,
intravitreal injection, 86	Ocusert see Pilocarpine	231–232, 265–267
size, 86	Off-label drugs, 352–355, 353t	value-based treatment analysis, 358
sustained-release devices, 81, 83	advance beneficiary notices (ABNs), 354	verteporfin photodynamic therapy
topical formulations, 61	Amercian Medical Association (AMA)	combined treatment, 300
Nanospheres, 86	policy, 352	Coats’ disease, 269
Nanotechnology, 86–90	compounding pharmacy formulations, 353	contraindications, 269
Natamycin, fungal keratitis, 318	definition, 352	cytomegalovirus infection in HIV/AIDS
Nattokinase (subtilisin NAT), 328	FDA guidance, 352	patients, 1
NDP mutations, 9	historical aspects, 352–354	diabetic retinopathy, 267–268, 269t
Needles, intravitreal injections, 68	informed consent, 353	drug interactions, 271
NEI-25, 357	investigational use, 353	familial exudative vitreoretinopathy, 269
Nepafenac, 153	marketing issues, 352–353	historical background, 265
physicochemical characteristics, 197f	medical payment/coverage, 353–354	intravitreal delivery, 81
use in ocular/retinal disease, 198	clinical trials, 354	endophthalmitis complicating, 170
Nephrotic syndrome, 255	national coverage determination, 354	Irvine–Gass syndrome, 269
Nerve fiber layer, 5	risk management issues, 353	mechanism of action, 266
Neuroprotection, 292–296	standard of care, 352–353	microspheres, transscleral delivery, 3
antiapoptotic therapy, 293–295	Oguchi disease, 6	myopic choroidal neovascularization, 269
antioxidant therapy, 292–293	Ointments	off-label use, 354
calcium channel blockers, 295	micro/nanotechnological applications, 86	pharmacokinetics, 265
clinical trials, 294t	topical formulations, 61	intravitreal, 71

Index

377

Index

pharmacology, 265	PKC412, 273	corticosteroid implants, 82–83
retinal vein occlusion, 268–269	diabetic macular edema, 274	diagnosis, 153
retinitis pigmentosa, 269	microspheres, transscleral delivery, 3	differential diagnosis, 156t
retinopathy of prematurity, 269	poly(lactic-co-glycolic) acid microparticles,	ethnic factors, 152
tamoxifen-related macular edema, 269	63	fluocinolone acetonide implants (Retsert),
use in retinal disease, 266–269	toxicity, 274	62–63
von Hipple-Lindau angioma, 269	Placental growth factor, 259	genetic factors, 152
Penicillin, intravitreal delivery, 67	angiogenesis, 230, 232, 259	immune-inflammatory pathogenesis, 152
Pentoxifyllin, central retinal vein occlusion,	Plasmin	pharmacotherapy, 153, 156t
139–140	safety of retinal therapy, 101	prevalence, 152
Peribulbar injection, 2, 60	vitrectomy, 72, 327–329	risk factors, 152
Pericentral cone–rod dystrophy (inverse	operative technique, 329	viral, 99
retinitis pigmentosa), 6	Plasminogen activator, 23	Posterior vitreous detachment, 15
Periocular injection, 60	Platelet derived growth factor, 231	age-related, 327
chemotherapy, retinoblastoma, 308	angiogenesis promotion, 25	pathological consequences, 15
microspheres, 3	neovascular glaucoma pathogenesis,	pharmacologic vitreolysis see Enzymatic
Peripheral cystoid degeneration, 8	185–186	vitrectomy
Peripheral ulcerative keratitis, infliximab,	Platelet derived growth factor receptor	Posttranscriptional gene silencing, 278
236, 239	inhibitors, 362–363	POT-4, 46, 353, 365
Peripherin/retinal degeneration slow (RDS)	Platelet derived growth factor-B, 25	Potassium currents, phototransduction, 19
mutations, 7	PLEKHA1	Potassium iodine, retinal toxicity, 111
retinitis pigmentosa, 49, 51	age-related macular degeneration, 123	Povidone-iodine, 68
Permeation	single nucleotide polymorphism, 8	cover for intravitreal injection, 178
anatomical barriers, 86–87	Pneumatic retinopexy	endophthalmitis prevention, 170
enhancers see Absorption enhancers	intravitreal gas-phase nanoparticle drug	Powders for solutions, micro/nanotechnology,
theoretical aspects, 88	delivery, 77	86
Pexelizumab, 46	retinal detachment management, 147, 149	Pralnacasan, 294–295
PF-03491390, 294–295	success rates, 150	Presumed ocular histoplasmosis syndrome,
PF-04523655, 364	Polyacrylamide, biodegradable ophthalmic	162
Phakomatoses, 10	inserts, 61	bevacizumab, 167
Pharmacoeconomic analysis, 356–359	Polyacrylic acids (carbopol)	choroidal neovascularization
Pharmacoeconomics, 356–361	mucoadhesive polymer formulations, 61	clinical features, 164
Pharmacokinetics, 60–61	nanoparticles, 61	pathogenesis, 163
animal models, 74–75	Polyarteritis nodosa, 12–13	diagnosis, 163
intravitreal drug delivery, 70–71	Polycythemia vera, 137	HLA associations, 162
gas-phase nanoparticles, 78–79	Poly-ε-caprolactone nanoparticles, 61	laser photocoagulation, 166
study methods, 74	Poly(ethylene glycol) diacrylate	prevalence, 162
suprachoroidal drug delivery, 76	poly(N-isopropylacrylamide) hydrogel	risk factors, 162
Phenothiazines, retinal toxicity, 9, 104–105	incorporation, 91	verteporfin photodynamic therapy, 301
Phenylpropanolamine, retinal toxicity, 113	thermo-sensitive hydrogels, 91–93	Primate models
Photodynamic therapy see Verteporfin	Polylactic acid (polylactide)	intravitreal drug toxicity, 97
photodynamic therapy	intraocular devices, 63	pharmacokinetics, 75
Photoreceptors, 5	microparticles/nanoparticles, 3, 83	Prodrugs, topical drug delivery, 61
apoptosis, 16, 18	Polylactic co-glycolic acid (PLGA)	Prolactin peptides, retinopathy of
neuroprotection, 292	intraocular implants, 3, 63	prematurity, 176–177
phototransduction, 18–19	toxicity/biocompatibility, 63	Proliferative vitreoretinopathy, 147–151
retinoid cycle, 18	microparticles/nanoparticles, 3, 63, 83	adjunctive therapies, 150–151
Photosensitive eczema, 116	sterilization, 65	classification, 148–149, 149t
Phototransduction, 18–19	microspheres, adverse reactions, 65	diagnosis, 148–149
Phytanic acid, Refsum’s disease, 193	Polymerase chain reaction, 41	incidence, 147
Picropodophyllin, 363	Poly(N-isopropylacrylamide) hydrogels, 91	intravitreal gas-phase nanoparticle drug
PIER, 130, 227–228	cross-linked systems, 91	delivery, 77
Pig models	crosslinker density, 91–92	pathogenesis, 147
intravitreal drug toxicity, 97	poly(ethylene glycol)/poly(ethylene glycol)	risk factors, 147–148
intravitreal gas-phase nanoparticle drug	diacrylate incorporation, 91–93	surgical management, 147, 149–150
delivery, 78	pore size, 91–92	treatment outcomes, 150
pharmacokinetics, 75	toxicity testing, 94	PrONTO, 130–131
Pigment epithelial dystrophy of Noble–Carr–	Polypoidal choroidal vasculopathy, verteporfin	Prostaglandin analogues, retinal toxicity, 107
Siegel, 6–7	photodynamic therapy, 301–303	Prostanoids, retinal vascular homeostasis,
Pigment epithelial-derived factor	Polyvinyl acetate, intraocular implants, 3	17
angiogensis inhibition, 31	Polyvinyl alcohol, intraocular drug delivery	Prostate cancer, 298–299
gene therapy, 293	systems, 62	Protein kinase C, 273
age-related macular degeneration, 53,	Posaconazole, 317	effects of activation, 273
289	Posterior juxtasceral administration, 60	isoenzymes, 275t
neoplastic ocular disease, 288–289	depto anecortave acetate delivery, 208	therapeutic inhibition, 273–274
neuroprotective activity, 293	Posterior segment disease, 2	diabetic complications management,
Pilocarpine, ophthalmic inserts, 2, 81	Posterior uveitis, 152–162	134, 274
Ocusert, 61, 81	autoimmune pathogenesis, 40–41	see also PKC412
Piperidyl-chlorophenothiazine hydrochloride	clinical features, 154t–155t	vascular endothelial growth factor
(NP-207), 104	complement activation, 37	expression stimulation, 273

378

Protein kinase C family, 273	choroidal neovascularization, 219	Retinal degeneration, 2
Proteoglycan, vitreous, 15	non-age-related macular degeneration-	apoptosis, 18
Pseudomonas endophthalmitis, 170–173	associated, 167	Retinal detachment, 10–11, 13, 77, 147–151
Pseudotumor cerebri, retinal vein occlusion,	clinical trials, 228t–229t	adjunctive therapies, 150–151
137	dosing strategy, 130–131	etiology, 147
Pseudoxanthoma elasticum, 162, 167	monotherapy/combined therapy	incidence, 147
Psoriasis, 109, 116, 248, 252, 299	comparisons, 131	intravitreal corticosteroid injection-related,
Psoriatic arthritis, 236, 240, 252, 299	safety/efficacy, 130	205
Psychosis, 104	contraindications, 228	neovascular glaucoma, 186, 188
Punctate inner choroidopathy, verteporfin	costs, 131	nonrhegmatogenous, 10
photodynamic therapy, 301	diabetic macular edema, 228	proliferative vitreoretinopathy risk,
Purtscher’s traumatic retinopathy, 11	efalizumab combined therapy, 365	147–148
Pyoderma gangrenosum, 109	drug interactions, 228	radiotherapy complication, 341
	historical background, 226	retinal pigment epithelium transplantation-
Quality of life measures, 357	imatinib combined therapy, 363	related, 350
function-based instruments, 357	intravitreal delivery, 81	rhegmatogenous, 10
preference-based instruments, 357	endophthalmitis complicating, 170	risk factors, 147
Quality of Well-Being Scale, 357	mechanism of action, 227	surgical treatment, 147, 149–150
Quinine sulfate, retinal toxicity, 108–109	off-label use, 354	symptoms/signs, 148
Quinolones, safety of retinal therapy, 100	pharmacodynamics, 226	treatment options, 149–150
	pharmacokinetis, 226	treatment outcomes, 150
R28 cells, intravitreal drug toxicity	intravitreal, 71, 131	vital dyes application during par plana
evaluation, 96	pharmacological design, 226	vitrectomy, 72
Rabbit models	retinal vein occlusion, 228	Retinal disruption, systemic medications
intravitreal drug toxicity, 96–97	use in retinal disease, 227	toxicity, 104–111
pharmacokinetics, 75	verteporfin photodynamic therapy	Retinal dysplasia, 6
RACE, 279, 281–282	combined treatment, 131, 228,	Retinal edema, systemic medicines toxicity,
Radial optic neurotomy, central retinal vein	300	114
occlusion, 139, 143	Rapamycin see Sirolimus	Retinal folds, systemic medicines toxicity,
Radiation choroidopathy, 341	Ravuconazole, 317	114
Radiation retinopathy, 341	RB1 mutations, 289	Retinal hemorrhages, hypertensive
bevacizumab, 223	RD3 mutations, Leber’s congenital	retinopathy, 17
neovascular glaucoma, 186	amaurosis, 194	Retinal ischemia, hypertensive retinopathy,
Radiation-induced optic neuropathy, 341–342	RDH12 mutations, Leber’s congenital	17
Radiotherapy, 336–343	amaurosis, 194	Retinal pigment epithelium, 5, 19–20
age-related macular degeneration,	REDD14NP, 278–284	age-related macular degeneration, 123–124,
exudative, 337, 339–341	historical background, 278	128
epimacular brachytherapy technique,	toxicity, 283	cells, ciliary neurotrophic factor-secreting
339	Refsum’s disease, 193–194	implants, 63
biological effects, 336–337	dietary restriction, 192–193	disruption, systemic medications toxicity,
cavernous hemangiomas, 338	plasmapheresis, 194	104–111
choroidal hemangioma with retinal	Regulatory T lymphocytes (Tregs), 39	liposome/nanoparticle uptake, 3
detachment, 338	Reiter syndrome, 252	photoreceptor outer segment degradation,
choroidal melanoma, 337, 339	Relapsing polychondritis, 239	19
complications, 341–342	Renal cell carcinoma, 113, 231	poly(lactic-co-glycolic) acid microparticle
focal epimacular delivery (VIDION	Reservoir ocular devices, 62	uptake, 65
brachytherapy system), 337	RESOLVE, 228	proliferative vitreoretinopathy pathogenesis,
historical background, 336	Restless leg syndrome, 108	148
indications, 337–338	RESTORE, 228	tight junctions, ocular pharmacokinetics,
intraocular lymphoma, 338	Restriction fragment length polymorphism,	61
metastatic tumors, 338	48	visual cycle, 18
outcomes, 339–341	Retina	Retinal pigment epithelium adenocarcinoma,
plaque placement technique, 338–339	age-related changes, 5	10
retinoblastoma, 306, 338	anatomy, 5	Retinal pigment epithelium adenoma, 10
vascular endothelial growth factor inhibitor	congenital abnormalities, 6	Retinal pigment epithelium atrophy, 19
combined therapy, 336–337	pathology, 5–13	Retinal pigment epithelium transplantation,
Ranibizumab, 1, 24, 46, 83, 167, 219,	vascular caliber, 17	344–351
226–229	Retinal angiomatous proliferation, anecortave	autologous treatment, 345–346
adverse effects, 100–101, 228	acetate, 212	iris pigment epithelium, 345
age-related macular degeneration, 129–131,	Retinal arterioles	retinal pigment epithelium, 345–346
167, 213–214, 219, 226–227, 231–232	blood pressure elevation response, 17	Bruch’s membrane as substrate, 344
bevasiranib combined treatment, 281	caliber changes, 17	historical background, 345
National Institute for Health and	Retinal artery occlusion, 9	immune response, 345
Clinical Excellence (NICE)	neovascular glaucoma, 186–187, 189	indications, 344
recommendations, 360	Retinal astrocytoma, verteporfin	retinal detachment-related phenomena,
anticoagulated patients, 67	photodynamic therapy, 302	350
beta-irradiation combined therapy,	Retinal blood flow, 17	stem cells, 349–350
131–132	autoregulation impairment, 17	tissue engineering strategies, 346–350
bevacizumab comparison (CATT study),	Retinal cavernous hemangioma, 10	Bruch’s membrane, 346–349
131	Retinal coloboma, 6	carrier substrates, 347, 348t

Index

379

Index

Retinal telangiectasias	Retinoblastoma, 10	zone II, 177
bevacizumab, 222–223	anecortave acetate, 211	zone III, 177
see also Idiopathic macular telangiectasia	chemoreduction, 306–307	Retinoschisis, 8
Retinal vascular development, 176	agents, 306–307	Retisert see Fluocinolone acetonide
Retinal vein occlusion, 9, 137–146	failure, 307	Retrobulbar administration (injection), 60
bevacizumab, 221–223	focal consolidation treatment, 307	Retrolental fibroplasia see Retinopathy of
branch, 9, 137	results, 307	prematurity
diagnosis, 138	side-effects, 307–308	RGD peptides, vitrectomy, 72
medical treatment, 139, 143, 221–222,	chemotherapy, 306–309	Rheopheresis, 321–326
228	adjuvant, 308–309	age-related macular degeneration, 321–322
neovascular glaucoma, 186	choroidal involvement, 308	MAC-1 trial, 321
surgical treatment, 143–144	intrathecal, 309	MIRA-1, 321–322
central, 9, 137	metastatic disease, 309	central retinal vein occlusion, 323
chorioretinal venous anastomosis, 143	optic nerve involvement, 308–309	complications, 324–325
chromovitrectomy, 332	periocular/subconjunctival, 308	diabetic maculopathy, 322–323
diagnosis, 137–138	chemothermotherapy, 308	high-molecular-weight plasma proteins
hemodilution, 140	classification, 307t	elimination, 321
ischemic, 137	enucleation, 306	historical background, 321
medical treatment, 139–143, 221–222,	gene therapy, 49, 288–289	mechanism of action, 321
228	neovascular glaucoma, 188	nanopore hollow-fiber membrane, 321
neovascular glaucoma, 185–186, 189	radiotherapy, 306, 338	uveal effusion syndrome, 323–325
nonischemic, 137	treatment options, 306	Rheumatoid arthritis, 107, 236, 239–240,
prognosis, 139	selection guidelines, 306	248, 252, 294–295, 299
rheopheresis, 323	tumor seeding, 307–308	Rhodopsin, 19
risk factors, 185	verteporfin photodynamic therapy, 303	gene mutations, 7
surgical management, 143	Retinocytoma, 10	retinitis pigmentosa, 16
treatment options, 189	Retinoic acid, poly(lactic-co-glycolic) acid	phosphorylation, 19
classification, 137	microparticles, 63	visual cycle, 18–19
corticosteroids, 203	Retinoid cycle, 18–19	Rhodopsin kinase, 19
periocular/intravitreal injection, 82	chaperones, 18–19	Rifabutin, retinal toxicity, 117
SCORE study, 205	Retinoid hydrolase, 18	RISE/RIDE, 228
laser photocoagulation, 139–143	Retinoid isomerase, 18	Rituximab
pathogenesis, 137	Retinol-binding protein, 18	intraocular lymphoma, 310
vascular endothelial growth factor, 227	Retinopathy of prematurity, 6, 13, 15,	intravitreal pharmacokinetics/clearance,
pegaptanib, 268–269	176–180	70–71
prevalence, 137	aggressive posterior, 177	safety of retinal therapy, 101
ranibizumab, 228	anecortave acetate, 211	uveitis, 244
risk factors, 137	bevacizumab, 222	RNA interference see Small interference RNA
risk for second eye, 185	classification, 177	(siRNA)
symptoms/signs, 138–139	cryotherapy, 177	RNA-based viral vectors, 286
treatment outcomes, 139–144	diagnosis, 177	RNA-induced silencing complex, 278, 288
treatment strategies, 139	differential diagnosis, 177	Rod monochromatism, 6
vascular endothelial growth factor	intravitreal antiangiogenic agents, 177–178,	Rod–cone dystrophy, 7
involvement, 23	220	Rodent models
Retinal venules, caliber changes, 17	injection technique, 178	intravitreal drug toxicity, 96
Retinitis, 10	ocular complications, 178	retinal drug delivery, 74–75
Retinitis pigmentosa, 7, 192–193	systemic complications, 178	Rods, retinoid cycle, 18–19
apoptosis, 16	laser therapy, 177	ROM1, 49
autosomal-dominant form, 7, 49	neovascular glaucoma, 186, 188	Rotterdam Study, 122
brimonidine, 293	pathogenesis, 176–177	RPE65 gene, 18, 48
ciliary neurotrophic factor, 3, 192–193	abnormal retinal vascularization, 176	gene therapy, 48, 52–53, 194–195, 287,
encapsulated cell technology delivery	growth factors, 176–177	289–290
(NT-501 implant), 83–84, 192–193,	“plus” disease, 176–177	mutations, Leber’s congenital amaurosis,
293	stage 1 (hyperoxic vascularization arrest),	194
cystoid macular edema, 192	176–177	RPGRIP1 mutations, Leber’s congenital
carbonic anhydrase inhibitor treatment,	stage 2 (hypoxic retinal astrocyte	amaurosis, 194
192	degeneration), 176–177	RS1 mutations, 6
dietary factors, 192	stage 3 (new vessel formation), 176–177	RTP801 gene, 278
docosahexaenoic acid therapy, 292–293	stage 4 (partial retinal detachment),	REDD14NP inhibition of expression,
gene therapy, 288	176–177	282–283
small interfering RNAs, 293	stage 5 (total retinal detachment), 176–177	small interfering RNA silencing, 364
genetic aspects, 48	pegaptanib, 269	Ruboxistaurin, 273–277
copy number variants (CNVs), 49	prevalence, 176	contraindications, 275
digenic forms, 49	risk factors, 176	diabetic macular edema, 274
heterogeneity, 49–51	“threshold”, 177	diabetic neuropathy/nephropathy studies,
modes of inheritance, 192	treatment options, 177	274
modifier genes, 49, 51	vitamin A therapy, 292–293	diabetic retinopathy, 134–135, 232,
pegaptanib, 269	vitrectomy, 177–178	274–275
vitamin A therapy, 292–293	enzymatic, 329	drug interactions, 275
X-linked form, 7	zone I, 176–177	mechanism of action, 274

380

pharmacology, 273	Smoking	historical background, 81
protein kinase Cβ inhibition, 273–274	age-related macular degeneration	liposomes, 83
structure, 276f	association, 56, 122, 128	microparticles, 83
toxicity, 275	retinal venular dilatation, 17	nanoparticles, 83
	Sodium channel antagonists, neuroprotective	Sympathetic ophthalmia, 160
SAILOR, 228	activity, 293	chlorambucil, 255, 258
Sarcoidosis, 137, 152, 158, 162	Sodium currents, phototransduction, 19	diagnosis, 160
choroidal neovascularization, verteporfin	Soft contact lenses, topical drug delivery, 61	treatment, 160
photodynamic therapy, 301	Soluble ophthalmic drug inserts, 2	verteporfin photodynamic therapy, 301
clinical features, 158	Soluble vascular endothelial growth factor	Syphilis, 137, 162
diagnosis, 158	receptor 1, angiogensis inhibition, 31	Systematic evolution of ligands by
pharmacotherapy, 158	Solutions, ophthalmic, 86	exponential enrichment (SELEX), 265
retinitis, 10	intravitreal formulations, 61	Systemic administration, 2–3
uveitis	topical formulations, 61	Systemic disease, 12–13
daclizumab, 242	Sorsby’s fundus dystrophy, 6–7, 21	Systemic lupus erythematosus, 12–13, 107,
infliximab, 236–237, 239	Sphingolipidoses, 12	252, 255
SB-267268, 31	Sphingosine 1-phosphate, 364
Schizophrenia, 104	monoclonal antibody inhibition, 364	T lymphocytes, 37–39
Scleral buckling, retinal detachment	Sphingosine 1-phosphate receptors, 364	calcineurin inhibitor actions, 248
management, 147, 149	Sphingosine kinases, 364	neuroprotective activity, 295
success rates, 150	SST (Submacular Surgery Trial), 129, 167	subsets, 39
Scleral drug permeation, 87–88	Staphylococcus aureus endophthalmitis,	T-cell receptor (CD3), 38–39
Scleral implants, 3	170–172	TA106, 46, 53
Scleral necrosis, radiotherapy complication,	Staphylococcus epidermidis endophthalmitis,	Tac, 241
341	314	Tacrolimus, 41, 248–251
Scleral plugs, 63	Stargardt’s disease, 6–7	Adamantiades–Behçet disease, 153–157
Scleritis	genetic aspects, 48	cyclosporin comparison, 248
cyclophosphamide, 255	lipofuscin, 20	pharmacology, 251
daclizumab, 243	Stem cells, retinal pigment epithelium	sympathetic ophthalmia, 160
infliximab, 236, 239	replacement, 349–350	systemic indications, 251
mycophenolate mofetil, 251	Stickler’s syndrome, 188	use in retinal disease, 251
SCORE study, 205	Streptococcus endophthalmitis, 170–172	Vogt–Koyanagi–Harada disease, 160
Seizures, 114	SU5416, radiotherapy combined treatment,	Takayasu’s disease, neovascular glaucoma, 186
Serpiginous choroiditis, 158, 162	336–337	Talc, retinal toxicity, 111
azathioprine, 252	SU6668, radiotherapy combined treatment,	Tamoxifen
chlorambucil, 255	336–337	adverse effects, 9, 114–116
cyclophosphamide, 255	Sub-Tenon’s capsule administration	intravitreal delivery, nanoparticles, 86
diagnosis, 158	(injection), 60	uveal metastases, 309
treatment options, 158	anecortave acetate, 208	Tamoxifen-related macular edema,
verteporfin photodynamic therapy, 301	Subconjunctival administration, 2, 60	pegaptanib, 269
SERPING1, age-related macular degeneration,	chemotherapy, retinoblastoma, 308	TAP (Treatment of Age-related macular
45	drug release implants, 2	degeneration with Photodynamic
Severe combined immunodeficiency, 287	microspheres, 3	therapy), 129–130, 299–300
Sickle cell disease, 12–13, 162	Subfoveal choroidal neovascularization	Taxanes, uveal metastases, 309
neovascular glaucoma, 186	bevasiranib, 279	Tear fluid (lacrimal fluid), 87
Sickness Impact Profile (SIP), 357	Sirna-027, 282	eye drop dilution, 87–88
Sildenafil, retinal toxicity, 118	Submacular surgery	Temozolomide
Silicone, intraocular drug delivery systems, 62	choroidal neovascularization, 167	uveal melanoma, 309
laminate implants, 3	myopia, 167	uveal metastases, 309
Silicone oil tamponade, combined intravitreal	presumed ocular histoplasmosis	Teniposide, retinoblastoma chemoreduction,
drug delivery, 71	syndrome, 167	306
Silver wiring (retinal arteriolar wall	see also SST (Submacular Surgery Trial)	Th1 lymphocytes, 39
opacification), 17	idiopathic macular telangiectasia, type 2, 183	Th2 lymphocytes, 39
Single nucleotide polymorphisms (SNPs),	Subtilisin NAT (nattokinase), 328	Th17 lymphocytes, 39
48–49	Sulfa antibiotics, retinal toxicity, 114	Thalidomide, safety of retinal therapy,
Sirna-027 (AGN211745), 1, 24, 131, 278–284	Sulfanilamide, intravitreal delivery, 67	101–102
age-related macular degeneration, 232, 282	Suprachoroidal drug delivery, 76–77	Thiopurine methyltransferase polymorphism,
historical background, 278	complications, 76–77	41
subfoveal choroidal neovascularization, 282	microcannula technology, 76–77	Thioridazine, retinal toxicity, 104
Sirolimus, 41, 364	Surodex, 3, 63	Ticlopidine, cental retinal vein occlusion,
multofocal choroiditis and panuveitis, 158	Survivin, 230	139–140
Skin disinfection, endophthalmitis	Suspensions, ophthalmic	Tie2, 29
prophylaxis for intravitreal drug	intravitreal formulations, 61	Tight junctions, 16, 273
delivery, 68	micro/nanotechnological applications, 86	blood–retinal barrier, 15
Small interference RNA (siRNA), 278–284,	topical formulations, 61	cornea, 61
288, 293, 364	SUSTAIN, 227	drug passage, 60
historical background, 278	Sustained-release devices, 3, 81–85	molecular components, 16
vascular endothelial growth factor	biodgradable implants, 82–83	ocular pharmacokinetics, 60–61
inhibition, 1, 24, 278–279	encapsulated cell technology, 83–84	paracellular transport pathway, 16–17
use in retinal diseases, 279–283	existing devices, 81–82	structure, 16

Index

381

Index

Tilted optic nerve head, retinal vein occlusion	complications of ocular therapy, 69, 97,	Uveal effusion syndrome, rheopheresis,
risk, 137	140, 204	323–325
Time tradeoff utility values, 357, 358t	cataract, 205	Uveal metastases, 309
Timolol, neuroprotective activity, 293	endophthalmitis, 170, 204–205	chemotherapy, 309
Tissue engineering, retinal pigment	cystoid macular edema, 202	prognosis, 309
epithelium replacement strategies,	depot formulations, 62	treatment options, 309
346–350	diabetic macular edema, 202–203, 365	Uveitis
Tissue inhibitors of matrix	diabetic retinopathy, 134–135	adalimumab, 240
metalloproteinases (TIMPs), 21	idiopathic macular telangiectasia	alemtuzumab, 244
Tissue plasminogen activator	type 1, 181	anakinra, 244
central retinal vein occlusion, 139	type 2, 182–183	azathioprine, 252
intravitreal delivery, 96, 139	intravitreal delivery, 67, 81, 202	biologic therapies, 236
safety of retinal therapy, 101, 139	off-label use, 354	chlorambucil, 255–258
vitrectomy, 72, 101	photodynamic therapy combination, 131	ciliary neurotrophic factor-secreting retinal
Tobramycin, retinal toxicity, 112	postoperative, 72	pigment epithelium cell implants, 63
Tolerance, 40	preoperative, 72	cyclophosphamide, 255
Toll-like receptors, 37	retinal toxicity, 334	cyclosporine, 248
Topical drug delivery, 60, 75, 86	vitrectomized eyes, 71	daclizumab, 242–243, 242t
barriers, 74–75, 88	neovascular glaucoma, 189–190	etanercept, 240–241
formulations, 61	pharmacokinetics, 71, 202	fluocinolone acetonide (Retisert), 3, 82
pharmacokinetic studies, 60–61	poly(lactic-co-glycolic) acid microspheres,	infliximab, 236–239, 237t
systemic drug uptake, 61	63, 65	interferon-α, 244
Topiramate, retinal toxicity, 114	retinal vein occlusion, 140, 143, 203	methotrexate, 251–252
Toxic anterior segment syndrome, 172	SCORE study, 205	mycophenolate mofetil, 251
Toxicity, 9–10	structure, 201, 201f	off-label drug use, 352
animal studies, 96–97	subconjunctival/peribulbar injection, 2	rituximab, 244
cell culture models, 96	suprachoroidal delivery, 76–77	systemic medicines toxicity, 117–118
cystoid macular edema, 114	Triamterene, retinal toxicity, 114	tacrolimus, 251
evaluation methods, 96	Troxerutin, central retinal vein occlusion,	see also Posterior uveitis
retinal edema/folds, 114	139–140	Uveitis–glaucoma–hyphema syndrome, 186
retinal therapy, 96–103	Trypan blue, 331
systemic medicines, 104–121	chromovitrectomy, 331, 333	Value gain, 358, 359t
crystalline retinopathy, 114–117	Tryptophanyl-tRNA fragment, angiogensis	Value-based medicine, 356–361
disruption of retina/retinal pigment	inhibition, 31–32	definition, 359
epithelium, 104–111	TT30, 53	discounting, 359
patterns of damage, 105t	Tuberculosis, 41	historical background, 356
uveitis, 117–118	TULP1 mutations, Leber’s congenital	implications for retinal pharmacotherapy,
vascular damage/occlusion, 111–113	amaurosis, 194	360
Toxoplasma gondii, 10	Tumor necrosis factor receptors (TNFr1/2),	patient respondents, 359
polymerase chain reaction diagnosis,	236	Vancomycin
41	Tumor necrosis factor-α	endophthalmitis, 173
Toxoplasmosis	angiogenesis promotion, 26	Endophthalmitis Vitrectomy Study (EVS),
choroidal neovascularization, verteporfin	gene polymorphism, 38–39	313–314
photodynamic therapy, 301	Tumor necrosis factor-α antagonists,	intravitreal pharmacokinetics/clearance, 70
posterior uveitis, 40	236–241, 245t	safety of retinal therapy, 100
Transducin, 19	Adamantiades–Behçet disease, 157	Varicella zoster virus
Transforming growth factor α, age-related	safety of retinal therapy, 101	acute retinal necrosis, 10, 40
macular degeneration	Tumors, 10	polymerase chain reaction diagnosis, 41
neovascularization (wet form), 128	anecortave acetate, 211	Vascular diseases, 9
Transforming growth factor β, age-related	angiogenesis, 219, 231	Vascular endothelial growth factor, 23–24,
macular degeneration	chemotherapy, 306–312	230–235
neovascularization (wet form), 128	gene therapy approaches, 288–289	age-related macular degeneration
Transplant rejection, 251–252	neovascular glaucoma, 186, 188	pathogenesis, 128, 163, 226
Transpupillary thermotherapy, idiopathic	radiotherapy see Radiotherapy	anecortave acetate actions, 210
macular telangiectasia type 2, 183	vascular endothelial growth factor,	angiogenesis, 23–24, 185–186, 230–232, 259
Transscleral drug delivery, 2–3, 60–61,	230–231	pathological, 220, 259
75–76	vascular endothelial growth factor	retinal vascular development, 176
barriers, 60	inhibitors, 231	tumors, 231
iontophoresis, 4	vasoproliferative, verteporfin photodynamic	biological effects, 230–232
microparticles/nanoparticles, 3	therapy, 302	developmental role, 230
Trauma, ocular, 11	Tumstatin, 230	diabetic retinopathy pathogenesis, 273
neovascular glaucoma, 186	Tyrosine kinase inhibitors, 362–363	historical background, 185–186, 219
retinal detachment, 147		hypoxia (oxygen tension) regulation, 231
Travoprost, retinal toxicity, 114	Ulcerative colitis, 236, 248, 251	intraocular neovascular syndrome
Triamcinolone acetonide, 201	Ultrasound, gene transfer, 287	pathogenesis, 231
Adamantiades–Behçet disease, 157	Urokinase, central retinal vein occlusion,	isoforms, 23, 230
age-related macular degeneration, 203–204	139–140	neovascular glaucoma pathogenesis,
verteporfin photodynamic therapy	Urokinase plasminogen activator, anecortave	185–186
combined treatment, 300	acetate inhibition, 210	ocular neovascular disease pathogenesis,
chromovitrectomy, 331–332, 334	Utility analysis, 357	23–24

382

protein kinase C-stimulated expression,	oncologic formulation (aflibercept),	retinal astrocytoma, 302
273	259–260	retinoblastoma, 303
ranibizumab actions, 227	ophthalmic formulation (VEGF Trap-Eye),	sarcoidosis, 301
retinopathy of prematurity pathogenesis,	259–260	serpiginous choroiditis, 301
176–177	age-related macular degeneration,	sympathetic ophthalmia, 301
small-interference RNA targeting, 278–279	exudative, 232, 261–263	toxoplasmosis, 301
use in retinal diseases, 279–283	diabetic macular edema, 263	vascular endothelial growth factor inhibitor
therapeutic targeting, 1	pharmacology, 260	combined therapy, 129, 131
Vascular endothelial growth factor113 isoform,	preclinical animal studies, 261	see also VIP (Verteporfin In Photodynamic
230	toxicity, 261	therapy); VOH (Verteporfin in Ocular
Vascular endothelial growth factor165 isoform,	VEGF-A/B and placental growth factor	Histoplasmosis)
23–24, 230	binding, 259–260	VF-14, 357
pegaptanib inhibition, 265–266	Vascular endothelial growth factorxxxb	VHL mutations, 10
therapeutic targeting, 130	isoforms, angiogensis inhibition, 31	VIDION brachytherapy system, 337
Vascular endothelial growth factor family,	Vascular toxicity of systemic medicines,	VIEW, 262–263
128, 230, 259	111–113	VIEW 2, 262–263
Vascular endothelial growth factor inhibitors,	Vasculogenesis, 176	Vigabatrin, retinal toxicity, 118
1–2, 24, 230–231, 362	Vasostatin, 230	Vinca alkaloids, retinoblastoma
adverse effects, 362	Vatalanib (PTK787), 131, 362	chemoreduction, 306
age-related macular degeneration, 130–131,	adverse effects, 362	VINCE applicator, 335
231–232	Verteporfin, 3	Vincristine
verteporfin photodynamic therapy	excitation spectrum, 297, 298f	retinoblastoma, 306, 308–309
combined treatment, 300	liposomal formulation, 61	small-cell lung carcinoma, 309
anecortave acetate comparisons, 211–213	pharmacokinetics, 297	Vinorelbine, lung carcinoma, 309
cancer therapy, 231	pharmacology, 297	VIO (Visudyne in Occult CNV), 300
choroidal neovascularization, non-age-	photodynamic therapy see Verteporfin	VIP (Verteporfin In Photodynamic therapy),
related macular degeneration-	photodynamic therapy	129–130, 299–300
associated, 167	structure, 297, 298f	Viral vectors
combination therapy, 131, 362	Verteporfin photodynamic therapy, 1,	associated risks, 287
diabetic retinopathy, 134–135	166–167, 297–305	gene therapy, 285–286
gene therapy approaches, 287–288	acute posterior pigment placoid	Viscous solutions, 61, 65
historical background, 219	epitheliopathy, 301	VISION (VEGF Inhibition Study in Ocular
idiopathic macular telangiectasia	adverse effects, 303–304, 304t	Neovascularization), 130, 170, 231,
type 1, 181	age-related macular degeneration, 1,	266–267, 270–271
type 2, 182–183	129–130, 231, 299–300, 300t, 303,	Visitrec vitrectomy unit, 172
intravitreal delivery, 67	303t	Visual cycle, 18–19
pharmacokinetics, 71	ranibizumab combined treatment, 228	inactivation, 19
vitrectomized eyes, 71	value-based treatment analysis, 358	Visudyne see Verteporfin
vitrectomy combination, 72	anecortave acetate comparisons, 211–213	Visulex, 4
neovascular glaucoma, 189	angioid streaks, 301	Vital dye use see Chromovitrectomy
off-label use, 354	antitumor effects, 298–299	Vitamin A
radiotherapy combined treatment,	central serous chorioretinopathy, 301–302	abetalipoproteinemia (Bassen–Kornzweig
336–337, 341	choroidal melanoma, 303	syndrome), 194
retinopathy of prematurity, 177–178	choroidal neovascularization, 166–167	neuroprotection, 292–293
ocular complications, 178	choroidal osteoma, 302	retinitis pigmentosa, 192
systemic complications, 178	conjunctival in situ squamous cell	Vitamin B6, gyrate atrophy, 194
safety of retinal therapy, 100	carcinoma, 303	Vitamin C, age-related macular degeneration,
thermo-sensitive hydrogel encapsulation,	contraindications, 303	56, 125
91	corneal neovascularization, 303	AREDS, 126
tyrosine kinase inhibitors, 362–363	drug interactions, 304	Vitamin E
Vascular endothelial growth factor receptors,	efficacy, 303	abetalipoproteinemia (Bassen–Kornzweig
220, 230–231, 259	historical background, 297, 352	syndrome), 194
angiogenesis inhibitor targeting, 362	idiopathic macular telangiectasia type 2,	age-related macular degeneration, 56–57,
neoplastic ocular disease gene therapy	182–183	125
approaches, 288	immunomodulatory effects, 299	AREDS, 126
SIRNA-027 mechanism of action, 282	intraocular vasoproliferative tumors, 302	neuroprotection, 292–293
sphingosine 1-phosphate interactions,	iris neovascularization, 303	retinitis pigmentosa, 192
364	laser systems, 297	Vitamin K, abetalipoproteinemia (Bassen–
vascular endothelial growth factor	macular dystrophy, 301	Kornzweig syndrome), 194
inhibition, 259	mechanism of action, 297–298	Vitamin supplements, age-related macular
vascular endothelial growth factor-Trap,	multifocal choroiditis and panuveitis, 158,	degeneration, 56–59
259	301	formulations, 57t
Vascular endothelial growth factor-A see	myopic neovascularization, 300–301	safety, 57
Vascular endothelial growth factor	neovascular glaucoma, 190	Vitelliform dystrophy (Best’s disease), 6–7
Vascular endothelial growth factor-A gene,	ocular histoplasmosis syndrome, 301	retinal pigment epithelium transplantation,
220	off-label use, 354	344
Vascular endothelial growth factor-Trap, 1,	parafoveal telangiectasia, 301	Vitiligo, 116
24, 131, 232, 259–264	polypoidal choroidal vasculopathy,	Vitrase see Hyaluronidase
historical background, 259–260	301–303	Vitrasert see Ganciclovir
mechanism of action, 260–261	punctate inner choroidopathy, 301	Vitravene see Fomiversen sodium

Index

383

Index

Vitrectomy, 67–73	specimens for endophthalmitis diagnosis,	Voriconazole, 317, 319
endophthalmitis complicating, 170,	172	fungal endophthalmitis, 173–174
173–174	Vitreous hemorrhage	intravitreal delivery, 317
Endophthalmitis Vitrectomy Study (EVS),	complicating intravitreal injection in	structure, 317f
313–314	anticoagulated patients, 67	topical administration, 318–319
enzymatic see Enzymatic vitrectomy	radiotherapy complication, 341	VP22, light-induced drug delivery system, 3
intravitreal drug delivery, 72	retinal vein occlusion, 137
clinical experience, 71	vitreous gel liquefication, 72	Wagner–Stickler’s syndrome, 188
gas-phase nanoparticles, 77–78	Vitreous lacunae, 15	Warfarin
historical aspects, 67	Vitreous substitutes, intravitreal	central retinal vein occlusion, 139–140
intraoperative, 72	formulations, 61–62	intravitreal injection hemorrhagic
postoperative, 72	Vitreous tap, endophthalmitis diagnosis, 172	complications, 67
preoperative, 72	Endophthalmitis Vitrectomy Study,	Wegener’s granulomatosis, 239, 255
pharmacologic vitreolysis adjunctive use,	313–314	Wyburn–Mason syndrome, 10
328	VMD2(hBEST1) mutations, 6–7
retinal detachment/proliferative	Vogt–Koyanagi–Harada disease, 158–160	X-linked inhibitor of apoptosis, gene therapy,
vitreoretinopathy, 147, 149–150	adalimumab, 240	294–295
retinopathy of prematurity, 177–178	azathioprine, 252	X-linked retinoschisis, 6, 188, 195
Vitreomacular traction syndrome,	daclizumab, 242	enzymatic vitrectomy, 329
chromovitrectomy, 332	diagnosis, 158–160	treatment, 195
Vitreoretinal interface	ethnic factors, 152, 158	Xanthene dyes, chromovitrectomy, 331
age-related changes, 15	immunosuppressive therapy, 153	XLRS1 mutations, 195
physiological/pathological changes, 15	pharmacotherapy, 160
Vitreous	VOH (Verteporfin in Ocular Histoplasmosis),	Zeaxanthin, 17–18, 56, 292
age-related degeneration, 15	166	age-related macular degeneration, 56, 125
biochemistry, 15, 327	Volociximab, 363	AREDS2, 57–58
clouding	Von Hipple–Lindau disease, 10, 338	Zinc, age-related macular degeneration,
following liposome injection, 83, 86	pegaptanib, 269	56–57, 125–126
following microparticle/nanoparticle	Von Hipple–Lindau tumor suppressor gene,	AREDS, 126
injection, 83	231	Zonula occludens-1 (ZO-1), 16, 273

384

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