Textbook on Clinical Ocular Pharmacology & Therapeutics SK Gupta, Renu Agarwal, Sushma Srivastava
Page numbers followed by f refer to figure and t refer to table.
Abacavir 314
Abducent nerve 24
Acanthamoeba 68, 259t, 268, 269
ACE inhibitors 310
Acetazolamide 316
Acetylcholine 210, 256
Acinetobacter species 111, 126, 131
Active transport 30f, 36
Acute angle-closure glaucoma 250
Acute conjunctivitis 111
Acute retinal necrosis 140, 141
Adenoviruses 136, 138, 143
Adenylyl cyclase-camp system 52
Adverse drug reactions 63
secondary effects 63
side-effects 63
toxicity 63
carcinogenicity 64
genetically determined 63
idiosyncratic reactions 64
immunologically mediated 63
teratogenicity 64
Age-related macular degeneration 234
laser photocoagulation in 234
nutritional agents in
lutein 235
zeaxanthin 235
photodynamic therapy in 234
verteporfin (visudyne) 234
Agonists 50, 51
Alendronate 311
Allergic conjunctivitis 187
Allopurinol 312
Alprazolam 307
Amblyopia 91
Amino acids 279
cysteine 279
taurine 279
administration 127
adverse effects 127
bacterial resistance 126
classification 125
contraindications 128
dosage 127
therapeutic uses 127
Amiodarone 310
Amitriptyline 307
Amlodipine 310
Amorolfine 153
Amphetamine 306
Amphotericin B 146, 149, 151, 313314
Ampicillin 314
Anidulafungin 152
Annulus of Zinn 15
Antiallergic drugs 182192
antihistamines 184188
mast cell stabilizers 188
Anti-angiogenic agents 235
aflibercept 235
bevacizumab 235
ranibizumab 235
Anti-glaucoma drugs
adverse effects, systemic 213
carbachol 211, 213
adverse effects 213
contraindications 213
therapeutic uses 213
ecothiophate 211, 213
adverse effects 213
contraindications 213
pilocarpine 211, 212
adverse effects 212
ocular adverse effects 212
Antihistamines 184188
Anti-inflammatory therapy, in dry eyes 240
Antioxidants 72
Antiviral drugs 135145, 136f
Aquaporins 10
Aqueous enhancement therapy, in dry eyes 240
Aqueous humor 13f, 23
Aqueous solutions 74
central retinal 16
ciliary 16
dorsal nasal 16
ethmoidal 16
lacrimal 16
maxillary 16
medial palpebral 16
meningeal 16
ophthalmic 3, 16
supratrochlear 16
Aspergillus niger 66
Aspergillus species 147
Aspirin 312
Atopic keratoconjunctivitis (AKC) 207
Atorvastatin 311
Atropine 90, 92
Augmentin 108
Autologous serum 243
Azathioprine 205
B. quintana 123
Bacillus anthracis 106, 120
administration and dosage 130
contraindications of 131
in blepharitis 131
in chronic conjunctivitis 131
in corneal ulcers 131
in keratitis 131
mechanism of action of 130
Bacterial keratitis 111
fragillis 111
species 108, 121
Bartonella henselae 123
Beclomethasone 312
Behçet's disease 205
Benzalkonium chloride (BAK) 66
Benzatropine 306
Beta lactam antibiotics 103
Beta-blockers 306
Betamethasone 178
Bifonazole 150
Bioadhesive hydrogels 77
Bioavailability enhancer excipients 68
BK virus 136
Blastomyces dermatitidis 147, 150
Blepharitis 111
Blepharocolysis 2
Blepharospasm 2
Blood ocular barriers 37
blood-aqueous 37
blood-retinal barriers (BRB) 37
Bordetella pertussis 123
Borrelia burgdorferi 121
Borrelia recurrentis 121
Botulinum toxin 256
Buffers 242
Bullous keratopathy 250
Busulphan 315
Butenafine 153
Butoconazole 150
C. pneumoniae 122
C. psittaci 122
Canal of Schlemm 11, 13
Candida spp. 66, 147152, 154, 268
albicans 66, 268
Canis 153
Carbachol 256
Carbamazepine 308
Carbapenems 111
adverse effects of 112
in bacterial endophthalmitis 112
in prophylaxis of post-operative endophthalmitis 112
Carrier-mediated transport 29
active transport 29
facilitated diffusion 29
Caspofungin 152
Centrimonium 67
Cephalosporins 109,110t, 314
First generation 109
Fourth generation 110
Second generation 110
Third generation 110
Cevimeline 244
Chlamydia spp. 113, 122
pneumoniae 116
trachomatis 122
Chlorambucil 205
Chloramphenicol 112, 314
adverse effects 114
antibacterial spectrum 113
in corneal ulceration 114
in dacryoadenitis 114
in gonococcal conjunctivitis 114
in gonococcal corneal ulcer 114
mechanism of action 112
Chlorhexidine 68
Chloroquine 314
Chlorpheniramine 313
Cholinergic receptors 211, 211t
muscarinic 211
nicotinic 211
Cholinomimetic drugs 211
Chondroitin sulfate 242
Choroidal neovascularization 295
Ciliary body 13f
Ciliary ganglion 17, 24
Clobetasone butyrate (0.1%) 179
Clonazepam 307
Clostridia tetani 121
difficile 111, 122
perfringens 110
tetani 106
Clotrimazole 150
Coccidioides species 147
Codeine 307
Conjunctiva 2, 32
bulbar 32
forniceal 32
palpebral 32
Conjunctival hyperemia 199
Contact lenses 85, 265
cleaning systems 265
disinfection systems
hydrogen peroxide 268
multipurpose disinfecting solutions 268
disinfection systems of 266
enzymatic cleaners for 266
rewetting solutions for 269
storage case for 269
surfactant cleaners for 266
soft hydrogel 265
soft silicone hydrogel 265
Copper 272
deficiency 272
Corneal epithelial defects 199
Corneal herpetic lesions 139
Corneal hydrops 250
Corneal permeability coefficient 32
Corneal ulceration 111
Corneal ulcers 91, 131, 151
adverse effects 176
anti-inflammatory effect 174
classification 172
contraindications 177
immunosuppression effect 174
intraocular use 176
periocular use 175
systemic use of 176
therapeutic uses of 174
topical use of 175
Corynebacterium diphtheria 106, 121, 122
Cotton pledgets 85
Cryptococcus neoformans 147
Crystallin proteins 14
Crystalline lens 14
Cyanocobalamin (vitamin B12) 278
Cyclopentolate 92
Cyclophosphamide 205
Cycloplegia 9091
Cyclosporin A 243
Cyclosporine 205, 316
adverse effects 207
formulations 206
mechanism of action 206f
therapeutic uses 207
Cytomegalovirus 136, 138, 139, 142, 143, 144
infections 141, 142
retinitis 142, 143, 144
Dacryoadenitis 111
Dacryocystitis 111
D-alanyl-D-alanine 106
Demecarium 306
Dendritic herpetic ulcer 140
Dendric ulcer 138
Desferoxamine 316
Dexamethasone 177, 312
Dexmethylphenidate 307, 316
Dextrothyroxine 311
Diabetic retinopathy 25, 230f
drugs used 232t
anti-VEGF drugs 231
bevacizumab 233
corticosteroids 233
dexamethasone 233
fluocinolone acetonide 234
pegaptanib 231
ranibizumab 231
triamcinolone acetonide 233
vitreolytic agent 234
mild NPDR 229
moderate NPDR 229
non-proliferative 229
proliferative (PDR) 229
severe NPDR 229
Diazepam 308
Didanosine 314
Difluprednate 0.05% 179
Digoxin 310
Diltiazem 310
Diphenhydramine 313
Diphenoxylate 316
Diuretics 310
Docetaxel 315
Dornase alfa 316
Dosage forms 74, 77t
Doxazosin 310
Drug absorption 30, 38
ocular 37
systemic route 36
oral 36
parenteral 36
topical route 30
transconjunctival 32
transcorneal 30
transscleral 33
Drug action
chemical reactions 55
inducing antibody formation 56
non-receptor mediated mechanisms 55
physical 56
protoplasmic poisons 56
targeting enzymes 56
Drug administration routes
intraocular 25
intracameral 25
intravitreal 25
periocular 22
peribulbar 24
retrobulbar 24
subconjunctival 22
sub-Tenon's 23
systemic 25
topical 21
Drug affinity 50
Drug effects measurement
graded dose-response curve 56
quantal dose-response curve 57
Drug safety measurement 58
Drug-drug interactions 63
Dry eyes 240
hormonal therapy in 240, 244
syndrome 207
treatment 240, 244
Echothiophate 306
Econazole 150
Endocytosis 30
Endophthalmitis 262
Enfuvirtide 314
Enterobacter species 108, 110, 112, 126, 129
Epidermophyton floccosum 153
Epithelial keratitis 140
Epstien barr virus 136, 139,142144
Erythromycin 314
Escherichia coli 66, 107, 108, 112,113, 126, 129, 131
Estradiol 311
Estrogen 311
Ethambutol 314
Ethanol 308
Ethinylestradiol 311
Ethosuximide 308
Ethylene glycol dimethacrylate (EGDMA) 206
Etretinate 315
Excimer laser keratectomy 140
Extraocular irrigation 84
Eyeball injuries 5
Eyelid edema 199
Facilitated diffusion 29f
Fas ligands 16
Felbamate 308
Fenticonazole 150
Fluoroquinolones 103, 115- 119, 314
adverse effects 118t
contraindications 119
in acute bacterial conjunctivitis 117
in bacterial endophthalmitis 118
in bacterial keratitis 117
in blepharitis 117
in gonococcal corneal ulcer 117
in prophylaxis for post-operative endophthalmitis 118
interactions 119
Fluorometholone acetate 178
Fluvastatin 311
Folic acid (vitamin B9) 278
Fuch's endothelial dystrophy 250
Fusarium solani 268
Gabapentin 308
Gels 76
Gene therapy applications 292t
in corneal alkali burn 294
in corneal dystrophies 294
in corneal graft rejection 292
in corneal neovascularization 293
in corneal scarring and wound healing 293
in glaucoma 295
in ocular surface disorders 294
Genital herpes infection 141
Gentamicin 314
accessory glands of Krause 3
accessory lacrimal 3
lacrimal 3
Meibomian 1, 245
Glaucoma 14, 248, 249
Glucocorticoids 190
Gold 312
Gonococcal conjunctivitis 111
Gonococcal corneal ulceration 111
Gonococcus 109
Gramicidin 132
Granulomatosis 205
Growth factors 256
epidermal growth factor (EGF) 256
fibroblast growth factor (FGF) 257
transforming growth factors (TGFs) 257
H. influenzae 108
H1 receptor blockers 184
adverse effects of 186t
pharmacological effects 185
anticholinergic effects 185
antiemetic effects 185
antiparkinsonian effects 185
sedation 185
topical ocular use 187
antazoline phosphate (0.5%) 187
pheniramine maleate (0.3 %) 187
pyrilamine maleate (0.1%) 187
mast cell stabilizing combinations 190, 190t
H2 receptor blockers 184t
Haemophilus influenzae 107, 108, 110, 121, 123, 126, 129
Hashish 308
Hepatitis B virus (HBV) 136
infections 136
Helicobacter pylori 107, 121, 123
Hemolytic Streptococcus 109
Hepatitis 262
Heroin 308
Herpes simplex
keratitis 137
keratoconjunctivitis 138
Herpes viruses 144
Herpes zoster 140, 141
Histamine 182
effects of 184t
Histoplasma capsulatum 147, 150
Homatropine 91
Horner's syndrome 2, 89
HSV 136, 141, 135
HSV-1 137139, 141144
HSV-2 137139, 141, 143
Human immunodeficiency virus (HIV) 263
Human recombinant interferon 205
Hyaluronidase 256
Hydralazine 310
Hydrocortisone 312
Hydroxyamphetamine 90, 306
Hydroxyl ethyl methacrylate (HEMA) 206
Hydroxypropyl methylcellulose (HPMC) 255
Hyoscine 91
Hypermetropia 9
Hyperosmotic agents 246t, 247, 247f
glycerol (glycerin) 248
isosorbide 249
mannitol 248
topical 250
glycerol (glycerin) 250
hypertonic saline 250
Hyphema 199
Hypopyon 199
Ibuprofen 312
Indomethacin 312
Infective waste disposal 263
Infraorbital fissure 5
Infraorbital foramen 6
Infraorbital sulcus 5
Insulin 311
Interdigitalis 153
Interferons 208
adverse effects 209
mechanism of action 209
Inverse agonists 51
Ionotropic receptors (type I receptors) 52f
Iopamidol 316
Iritis 139, 140
Isocarboxazid 308
Isoniazid 314
Isosorbide 310
Isotretinoin 315
Keratitis 140, 131, 151
Keratoconjunctivitis 240
treatment approach 240
Ketorolac 190
Ketotifen 190
Klebsiella species 108,112, 126, 129, 131
fossa 5
gland 3, 240, 245
papilla 3
sac 3
Lactamase inhibitor combinations 109
Lactoferrin 4
Lamivudin 314
Lamotrigine 308
L-ascorbate. See L-ascorbic acid
L-ascorbic acid 278
Laser-assisted in-situ keratomileusis (LASIK) 140
Lasik surgery 89
Leber's congenital amaurosis (LCA) 295
Leptospira species 121, 106
Leuprolide 316
Levator palpebrae muscle 1
Levetiracetam 308
Levonorgestrel 311
Levothyroxine 311
Lid scrubs 84
Linezolid 314
Lipid emulsion 243
Lipophilic drugs 31, 32
Listeria 111
Listeria species 106, 121, 122
Lithium 308
Local anesthetic
adverse effects 199
local 199
on cardiovascular system 199
on central nervous system 199
contraindications 200
injectables 196t
local infiltration 201
mechanism of action 197
peribulbar block 201
retrobulbar block 200
sub-Tenon's block 201
topical 195t, 201
Local anterior uveitis 199
Losartan 310
Loteprednol etabonate 178, 190
Lovastatin 311
LSD 308
Lutein 275
Lycopene 274f
M. scrofulaceum 122
adverse effects 124t
contraindications of 124
in bacterial conjunctivitis 123
in blephritis 123
in chronic or recurrent conjunctivitis 123
in trachoma 124
interactions of 124
mechanism of action of 122
Magnesium 272
deficiency 272
Manganese 273
deficiency 273
Marijuana 308
Mast cell stabilizers 188
adverse effects 189
cromolyn 188
disodium chromoglycate (cromolyn) 188
lodoxamide (0.1%) 189
mechanism of action 188
nedocromil sodium (2%) 189
ocular use 189
pemirolast (0.1%) 189
Measurement drug effects measurement 56
Medroxyprogesterone 311
Meibomian gland, dysfunction 2
Mescaline 308
Metabotropic receptors 53f
Methadone 308
Methotrexate 205, 315
Methyl dopa 310
Methyl phenidate 308
Methyl predinosolone 312
Methylphenidate 308
Micafungin 152
Miconazole 150151
audouinii 153
canis 153
gypseum 153
Midazolam 307
Mitomycin C 257
Modified drug responses 59
acquired tolerance 60
acute tolerance 60
drug tolerance 59
natural tolerance 59
pharmacodynamic tolerance 60
pharmacokinetic tolerance 60
Molluscum contagiosum 136
Mometasone 312
Monobactams 112
Morphine 308
Mucoadhesives 69, 69t
Moraxella species 117
Muller's muscle 2, 8889
paralysis of 2
Multiple dose administration and dosing schedule 46
dilator pupillae 12
extraocular 15, 15f, 24
inferior oblique 1, 6, 15, 16
inferior rectus 6,15
lateral rectus 6, 15
medial rectus 6, 6f, 15
levator palpebrae superioris 1, 2, 16
superior oblique 15,6
superior rectus 15,6
Muller’s/superior tarsal 2
orbicularis oculi 1, 2
sphincter pupillae 12
superior tarsal 2
Mycobacterium spp. 117
Mycobacterium kansasii 122
Mycophenolate mofetil 205
Mycoplasma 113, 121
Mydriatics, Contradictions 88t
Mydriatics, indications 88t
Myopia 9
Naftifine 153
Nasolacrimal apparatus 3
Natamycin 147149
Neisseria spp. 110,123, 130
gonorrhoea 106, 108, 110, 120, 126
meningitidis 106, 110, 126, 129
abducent 17
frontal 6, 17
inferior ophthalmic 16
lacrimal 6, 17
maxillary 17
nasociliary 6, 17
oculomotor 2, 17, 24
ophthalmic 16, 17
optic 6, 12, 14, 17
trigeminal 2, 10
trochlear 17
zygomatic 17
Niacin 311
Niacinamide (vitamin B3) 277
Nifedipine 310
Nitrates 310
Nitroglycerine 310
Non-beta lactam antibiotics 112
in acute bacterial conjunctivitis 114
in blepharitis 114
in bacterial keratitis 114
Non-steroidal anti-inflammatory drugs (NSAIDs) 163
adverse effects 167
mechanism of action 164t
pharmacological actions 165
analgesic 166
anti-inflammatory action 166
antiplatelet action 166
therapeutic uses 166
analgesic 166
anti-inflammatory 167
antiplatelet action 167
antipyretic 167
Nonviral vectors
nanoparticles 291
hybrid metal-polymeric 291
metallic 291
polymeric 291
NSAIDs, Topical ocular use 169t
Nystatin 146148
Ocular decongestants 190
adverse effects 191
naphazoline 191
oxymetazoline 191
phenylephrine 191
tetrahydrozoline 191
Ocular drug
bioavailability 38
distribution 39
elimination 41
metabolism and elimination 41
Ocular infection indications 109
Omega-3 fatty acids 240, 245
Omeprazole 313
Opioid (narcotic) analgesics 157
absorption 159
adverse effects 162
classification 159t
contraindications 162
head injury 162
impaired hepatic functions 162
impaired renal functions 162
reduced pulmonary function 162
distribution 159
mechanism of action 157
metabolism 159
pharmacological actions 160
analgesia 160
emesis 161
euphoria 160
histamine release 161
miosis 161
respiratory depression 160
sedation 160
suppression of cough reflex 161
receptor subtypes 158
dynorphins 158t
endorphin 158t
enkephalin 158t
therapeutic uses 161
acute pulmonary edema 162
analgesia 161
cough suppression 162
diarrhea 162
topical ocular use 163
Opium 308
Orbit 4
apperture 6, 7t
dimensions 5f
infection spread in 6
malignancy spread in 6
margins 5
walls 5,6t
fractures 6
inferior 6
lateral 6f
medial 6f
superior 6
Orbital apex syndrome 9
Orphenadrine 313
Oxacephems 112
Oxcarbazepine 308
Oxiconazole 150
Oxybutynin chloride 306
P. aeruginosa 110, 113, 116, 126
Paclitaxel 315
Palpebral fissure 89
Pantothenic acid (vitamin B5) 277
Papillary hypertrophy 199
Parabens 67
Paricalcitol 316
Parkinson's disease 2, 271
Partial agonists 51
Passive diffusion 28f, 31, 36
Pasteurella spp. 131
Penciclovir 140141
Penetration enhancers 70
Penicillin-binding protein (PBP) 106
aminopenicillins 107
antipseudomonal penicillins 108
beta lactamase inhibitor combinations 108
natural penicillins 106
ophthalmic use 108
penicillin G 106
penicillin V 106
penicillinase-resistant penicillins 107
Peptococcus 121
Phagocytosis 3
Pharmacodynamics 5064
Pharmacokinetics 2847
acyclovir 314, 139140
aminoglycosides 125,126
anesthetics, 195, 196, 197
azoles 150, 150t
bacitracin 130, 131
chloramphenicol 113
cidofovir 142,143
corticosteroids 172, 244
cotrimoxazole 129
disodium chromoglycate 188
echinocandins 152
famciclovir 140141
flucytosine 148149, 154
foscarnet 143144
ganciclovir 141,142
griseofulvin 153
H1 receptor antagonists 185
hyperosmotic, 247, 247f
idoxuridine (IDU) 137
macrolides 122, 123
nanoparticle 296
NSAIDs 164
opioids 159
polyenes 146, 147, 147t
polymyxin B 131
terbinafine 154
tetracyclines 121
trifluridine 137
vidarabine 138
Phenobarbitone 308
Phenothiazines 308
Phenylephrine 8890
Phenylephrine (10%), usage guidelines 90t
Phenytoin 308
Phospholipase C-inositol phosphate system 53
Physostigmine 91
Pilocarpine, contraindications 213
Pimecrolimus 208
Pinguecula 3
Pirenzepine 313
Pneumococcus 109, 117
Polyangiitis 205
Polyhexamethylenebiguanide 68
Polymeric gels 77
Polymyxin B
adverse effects 132
in blepharitis 132
in blepharoconjunctivitis 132
in conjunctivitis 132
in corneal ulcers 132
in keratitis 132
mechanism of action 131
Polyquaternium-1 67
Post-herpetic neuralgia 140
Post-operative endophthalmitis 262
Pralidoxime 306
Pravastatin 311
Prazosin 306
acetate 177
sodium phosphate 177
Prednisone 312
Preservatives 65, 66t
Primidone 308
Progestogens 311
Propionibacterium 121
Proteus spp. 110, 126
mirabilis 107
Pseudomonal keratitis 111
Pseudomonas spp. 110, 111, 116
aeruginosa 66, 108, 112, 117, 126, 127, 131, 268
Psilocybin 308
Pterygium 3
Pterygopalatine ganglion 3
Ptosis 2, 89
Pupillary light reflex 19f
direct 18
indirect 18
Pyridoxine (vitamin B6) 277
Quinidine 310
Quinine 314
Quinolones and fluoroquinolones 116t
first generation 116
fourth generation 116
in gonococcal conjunctivitis 117
mechanism of action 116
second generation 116
third generation 116
Ranitidine 313
Receptors 52
actions 55
desensitization 55
down-regulation 55
spare receptors 55
supersensitivity 55
upregulation 55
cytoplasmic receptors 54
enzyme-linked receptors 54
Retina 14
Retinal vein occlusion 235
anti-platelet therapy 236
drugs used 236
hydroxyethyl starch or dextran 236
ticlopidine 236
troxerutin 236
Retinitis 140, 142143
Retinitis pigmentosa (RP) 295
Retinoic acid 316
Reuptake inhibitors 308
Riboflavin (vitamin B2) 276
Rickettsiae species 113, 120, 121,123
Rifabutin 314, 316
Rimexolone 178
Rofecoxib 312
Rosuvastatin 311
S. aureus 107, 108
S. pneumoniae 116
Salbutamol 306
Salmonella species 113, 107, 131
Sclera 11, 33
episclera 33
lamina fusca 33
stroma 33
Scleral spur 11
Scleritis 12
Scopolamine 91, 306
Secretagogues 240, 244
Selective serotonin 308
Selenium 273
Serratia spp. 126
marcescens 268
Sertaconazole 150
Shigella species 107, 113,129, 131
Sildenafil 316
Simvastatin 311
Sirolimus 205, 208
Sjogren's syndrome 244, 274
Smallpox 136
Sodium hyaluronic acid 255
Sodium perborate 68
Solifenacin succinate 306
Sorbic acid 67
Spirochetes 120
Sporothrix schenckii 147
Stabilized oxychloro complex (SOC) 68
Staphylococci 117
Staphylococcus spp. 106, 108, 111,113, 122, 130
aureus 66, 108, 129, 268
pyogenes 109
Sterilization methods 258
Streptococcus species 106,111, 120, 130
pneumoniae 129
pyogenes 129
viridans 129
Stromal keratitis 140
hemorrhage 24
injections 111
Sulconazole 150
Sulfonamides 128, 314
administration and dosage 129
adverse effects 129
local 129
systemic 130
classification 128
contraindications, 130
cotrimoxazole 129
mechanism of action 128
trimethoprim (TMP) 128
Sulfonylureas 311
Surfactants 71
Suspensions 74
Systemic drug 89
elimination half-life 43
excretion 42
first order kinetics 43
metabolism and excretion 41
mixed order kinetics 45
zero-order kinetics 44
Tacrolimus 205, 207
Tadalafil 316
Tamoxifen 311
Tamsulosin 306
Tarsal Meibomian glands 3
Tear film 2, 3, 240
Tenon's capsule 11f
Terazosin 310
Tetracyclines 120, 121, 244, 314
adverse effects 121
bacterial resistance of 121
blepharitis 121
classification 120, 120t
in acute conjunctivitis 121
in bacterial endophthalmitis 121
in bacterial keratitis 121
in corneal ulceration 121
in dacryoadenitis 121
in ophthalmia neonatorum 121
mechanism of action 120
TGF-B2 16
Thiabendazole 149
Thiamine 276
Thimerosal 67
Tiagabine 308
Ticarcillin disodium 108
Timentin 108
Tioconazole 150
Tolterodinet artrate 306t
Topiramate 308
Toxic anterior segment syndrome (TASS) 25
Trachoma 121
Treponema pallidum 106, 121, 123
crateriform 153
gallinae 153
interdigitalis 153
megnini 153
mentagrophytes 153
rubrum 153
schoenleini 153
sulphureum 153
tonsurans 153
verrucosum 153
Trochlear fossa 5
Tropicamide 93
Unasyn 108
Ureaplasma 121
urealyticum 122
Uveitis 91
Vaccinia 138, 143
Valacyclovir 139, 140
Valdecoxib 312, 312
Valganciclovir 141142
Valproic acid 308
Vardenafil 316
Varicella species 139
Varicella zoster virus (VZV) 135, 141142
Vehicles 68
inferior ophthalmic 6, 16
infraorbital 16
superior ophthalmic 3, 6
Venlafaxine 308
Verapamil 310
Vernal conjunctivitis 189
Vibrio cholera 121
Vigabatrin 308
Viral vectors 287, 288f
adeno-associated virus (AAV) 288, 289, 295
recombinant 289
self-complementary 289
adenovirus (AV) 287, 295
lentivirus 290, 295
retrovirus 290
Viscosity enhancers 68
Visual pathway 18f
Vitamin A 274, 316
Vitamin B 276
Vitamin C 278
Vitamin D 275, 316
Vitamin E 276
Vitreous humor 14
Voclosporin 208
VZV 19, 138, 139, 141143
Warfarin 315
Zeazanthin 275
Zidovudine 314
Zinc 271
deficiency 271
toxicity 272
Zoster ophthalmicus 139
Chapter Notes

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Anatomical and Physiological Basis of Ocular PharmacotherapyCHAPTER 1

The principles of therapeutics in the treatment of ophthalmic diseases require a comprehensive knowledge of ocular anatomy and physiology. The understanding of drug interactions at molecular, cellular and tissue level leading to pharmacological responses require special consideration due to the unique anatomical and physiological characteristics of eye. This chapter provides a basic account of the ocular anatomy and physiology as a basis of ocular pharmacotherapy.
The eye and orbit contain smooth and striated muscle, epithelial tissues, blood vessels, nerves both autonomic and sensorimotor, connective tissues and the neuronal tissue, i.e. retina. They are arranged in order to provide an optimum path for the transmittance of light to the light sensitive cells of the retina. Supporting tissues aid and enable this function, and also provide nutrition, blood supply and an excretory pathway.
The eyelids or palpebrae cover the anterior surface of the eye protecting it from injury and exposure. The space between the upper and lower lids is called the palpebral fissure, the angle between the lids are called the medial and lateral canthi (Fig. 1.1).
The tarsal plate is the main supporting structure of the lids and is present in both the upper and lower lids. The plate is attached to the orbital septum, which is a thin membranous sheet attached to the rim and continuous with the periosteum of the bony orbit.
zoom view
Figure 1.1: The eye
The layers of the upper eyelid from the facial aspect inwards include—skin, subcutaneous connective tissue, orbicularis oculi, connective tissue, tarsal plate, meibomian glands, connective tissue and conjunctiva. Meibomian glands are the tarsal glands that open at the lid margins behind the mucocutaneous junction. The tarsal plate also receives the insertion of the levator palpebrae muscle. The layers of the lower eyelid consist of skin, orbicularis oculi muscle, connective tissue, orbital septum and fat, retractors of the lower eyelid and palpebral conjunctiva.1 The retractors of the lower eyelid are extensions of the fascia covering the inferior oblique muscle and passing forward to be inserted into the tarsal plate of the lower lid. It may be referred to as the inferior tarsal muscle though it has not been completely characterized yet.
Meibomian glands secrete lipids, mainly wax and steryl ester that are hydrophobic. 2They contribute to the layers of the tear film and its stability. They are expressed from the gland during blinking.
Blood Supply, Lymphatic Drainage and Sensory Nerve Supply of Eyelids
Anastomoses of the medial and lateral palpebral arteries supply the eyelids. Venous drainage is into the facial veins or to the ophthalmic veins. Lymphatics drain into the submandibular, superficial and deep parotid lymph nodes. Sensory innervation is by the ophthalmic and maxillary divisions of the trigeminal nerves.
Motor Nerve Supply and Movements of the Eyelids
Movements of the eyelids are brought about by 2 muscles, the orbicularis oculi, for closure of the lids and the levator palpebrae superioris for opening of the eyelids. Firm closure of the eyelid is achieved by the action of the orbicularis oculi muscle, supplied by the facial nerve. Closure of the eyelid for example in the instance of a blink occurs by inhibition of the levator palpebrae superioris muscle, supplied by the oculomotor nerve and the elastic recoil of the supporting connective tissues.3 The levator palpebrae superioris is responsible for the opening of the eyelid. Maximal eyelid opening is achieved by the added action of the frontalis muscle. Muller's muscle or the superior tarsal muscle arises from the distal part of the levator palpebrae superioris and inserts into the upper margin of the tarsus.3 It is composed of smooth muscle fibers and connective tissue. It is supplied by sympathetic nerves. It is mainly responsible for the width of the palpebral fissure. The motor supply is through the oculomotor nerve, while the motor neurons arise from a single central caudal nucleus of the oculomotor nerve. Thus lesions affecting the nucleus often affect both eyelids.3
Eyelid movements occur in coordination with the movements of the globe in a way that on upward gaze vision may not be disturbed and on downward gaze the eyeball is protected. It appears that the interstitial nucleus of Cajal and the rostral interstitial nucleus of the medial longitudinal fasciculus are the main centers for coordinating eyelid and eye movement.3
Mucous membranes that cover the sclera up to the limbus and the palpebral portions of the eyelids are called conjunctiva. Their main function is protection of the anterior surface of the eye by secreting the mucous layer of the tear film, antibacterial and antiviral substances and providing immune defense. The three main regions of the 3conjunctiva include the palpebral portions covering the inner side of the eyelids, fornicial conjunctiva located at the fornices and the bulbar conjunctiva covering the white of the eyeball up to the limbus.
The conjunctival epithelium, which is non-keratinized squamous epithelium contains goblet cells secreting mucous and has been shown to be capable of phagocytosis.4 Below this layer lies the conjunctival substantia propria. It is composed of loose connective tissue and is highly vascularized, and contains a large number of white blood cells.
The lacrimal gland and accessory lacrimal glands are the main tear-producing structures. The lacrimal gland consists of an orbital part located within the orbital margin in the lacrimal fossa of the zygomatic process of the frontal bone. The palpebral part is located below the palpebral conjunctiva. Numerous accessory glands are located in the upper eyelid and the fornices and probably account for lacrimal secretions after removal of the lacrimal gland. Accessory glands of Krause are located in the superior and inferior fornix, while accessory glands of Wolfring are located on the margin of the superior tarsal plate of the upper eyelid.5 The lacrimal gland is supplied by the lacrimal branch of the ophthalmic artery and drains into the superior ophthalmic vein. It is supplied by parasympathetic fibers from the pterygopalatine ganglion, which are secretomotor to the gland. Acini of the gland are surrounded by myoepithelial cells, which contract to help glandular secretions exit the acini and ductules.
Tears produced by the lacrimal gland bathe the eye and drain through to lacrimal canaliculi (Fig. 1.2). The canaliculi are located in the medial portion of each eyelid near the medial canthus. Each canaliculus begins as a punctum in the lacrimal papilla and drains into the lacrimal sac, which has a closed upper end and in turn drains into the nasolacrimal duct. The duct opens into inferior meatus of the nasal cavity. Secretions from the tarsal meibomian glands also contribute to the tear film by preventing the rapid evaporation of the fluid (Fig. 1.3).
Tear Film
The tear film is composed of three layers (Fig. 1.4). The outermost layer consists of lipids from the secretions of tarsal glands. It floats on a middle aqueous layer, contributed by the main and accessory lacrimal glands. An inner mucous layer secreted by goblet cells is in contact with the surface of the conjunctiva and cornea.
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Figure 1.2: Nasolacrimal apparatus
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Figure 1.3: Glands secreting the tear film
The mucous layer is hydrophilic and traps particulate matter. The aqueous layer makes up more than 97% of the volume of secretions, and contains most of the proteins, immunoglobulins, lactoferrin and enzymes.
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Figure 1.4: Tear film
The orbit or the “sockets” of the eye are bony cavities that protect the eye and its supporting structures. The orbit also serves as a passage to connect the eye with its blood supply and nerves and also conduct the vessels and nerves that supply other parts of the face. The bony boundaries of the orbit are described below. It is a crowded space filled with numerous vessels, nerves, connective tissue and muscles apart from the eyeball. Anesthetic agents are administered into this space by the retro- and peribulbar route.5
Orbital Margins
Superiorly, the orbital margin is formed by the orbital arch of the frontal bone. Laterally, it is formed by the zygomatic bone and the zygomatic process of the frontal bone. The zygomatic bone and the maxilla form the inferior border of the orbital margin. It is slightly raised above the floor of the orbit. Medially, it is formed by the maxilla and lacrimal bone.
The outer limits of the orbit are formed by bony boundaries. They form a roughly quadrilateral pyramidal shape and accommodate the globe of the eye, the extra-ocular muscles attached to it, surrounding fat, blood vessels and nerves. The orbit is oriented with its apex directed postereo-medially and the base at the front of the skull. The medial walls are almost parallel with each other and to the sagittal plane. The lateral walls are roughly at an angle of 90° to each other. Dimensions of the orbit are shown in Table 1.1.
Table 1.1   Dimensions of the orbit7
50–70 mm
30 mL
Volume of extraocular muscles and eyeball
7 mL
Wall of the Orbit
The orbit has a superior, medial and lateral wall and a floor composed of a number of different bones. They are briefly summarized in the Figures 1.5 to 1.7 and Table 1.2.9
The superior wall is concave anteriorly, where the maximum diameter of the orbit is about 1.5 cm from the orbital margin and more or less flattened posteriorly. It contains the fossa for the lacrimal gland in the anterolateral aspect of the frontal bone. The trochlear fossa lies anteromedially, and contains the trochlea through which the tendon of the superior oblique passes. Anteriorly it is related to the air sinuses of the frontal bone. It separates the orbit from the anterior cranial fossa and the frontal lobes of the brain.
The medial wall contains the lacrimal fossa for the lacrimal sac anteriorly. It is thin and runs almost parallel with medial wall of the other orbit. It separates the orbit from the anterior, middle posterior and sphenoid air cells.
The floor of the orbit separates it from the maxillary sinus. It contains the infraorbital sulcus, which is continuous with the infraorbital fissure.
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Figure 1.5: Left bony orbit
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Figure 1.6: Medial wall of the orbit
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Figure 1.7: Lateral wall of the orbit
Table 1.2   Walls of the orbit
Composing structures
Superior wall
Orbital plate of the frontal bone, sphenoid bone (lesser wing)
Frontal air sinuses and frontal lobes of the brain
Inferior wall
Orbital plate of maxilla, orbital surface of the zygomatic, orbital process of palatine bone
Maxillary air sinus
Medial wall
Maxilla(frontal process), lacrimal bone, ethmoid (orbital plate) and sphenoid body
Sphenoid air sinuses
Lateral wall
Zygomatic and sphenoid greater wing
It runs forward and passes below the surface as the infraorbital canal to open below the orbital margin as the infraorbital foramen.
The lateral walls are composed of the zygomatic anteriorly and the greater wing of the sphenoid posteriorly. They are triangular in shape with base present anteriorly and lie at an approximate angle of 90° with each other.10
The pyramidal structure of the orbit is incomplete due to the presence of a number of apertures (Fig. 1.8).12 These limited spaces are crowed with a number of blood vessels and nerves passing through. Thus lesions often present as a syndrome called “orbital apex syndrome” (Tables 1.3 and 1.4). 10
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Figure 1.8: Apertures in the orbit
Table 1.3   Apertures in the bony orbit
Surgical Importance
Superior orbital fissure
Between the roof and lateral wall of the orbit
Greater and lesser wings of the sphenoid and closed off laterally by the frontal bone
Superior and inferior divisions of the IIIrd, IVth, VIth cranial nerve, the lacrimal, frontal and nasociliary branches of the Vth cranial nerve, superior and inferior branch of ophthalmic vein and sympathetic fibers of the cavernous plexus
Lesions that frequently present with multiple cranial nerve palsies along with loss of vision are called the orbital apex syndrome (OAS) The cavernous sinus syndrome may include features of OAS, and also Vth nerve involvement with also involvement of sympathetic fibers. They may occur in association with injuries to the facial bones, skull fractures, inflammatory conditions and orbital apical tumors
The Superior Oblique fissure or Rochon-Duvigneaud syndrome involves lesions anterior to the apex, including the annulus of Zinn. However, the optic nerve and vision is left intact The optic nerve may also be damaged in its intra canalicular portion of the optic canal
Ethmoid sinus surgery may cause optic nerve damage in cases where ethmoid air cells form the canal wall
Inferior orbital fissure
Lateral wall and the floor of the orbit and ending about 2 cm from the anterior margin of the orbit
Maxilla, the palatine bone and the greater wing of the sphenoid
Optical canal
Apex of the pyramidal orbit structure, directed forwards, downwards and laterally
Roots of the lesser wings of the sphenoid and medially the body of the sphenoid. Posterior ethmoid air cells (Onodi cells) may form the medical wall in certain instances
The optic nerve along with its sheathings of dura, arachno and pia mater, the ophthalmic artery and a few fibers of sympathetic nerves that pass along with the artery
Anterior Ethmoidal Canal
Between the roof and medial walls of the orbit
Frontoethmoidal suture between the medial and superior orbital walls
Anterior ethmoidal vessels and nerves
Posterior Ethmoidal Canal
Between the roof and medial walls of the orbit
Frontoethmoidal suture between the medial and superior orbital walls
Posterior ethmoidal vessels and nerves
Vessels may bleed during extraperiosteal medial wall dissection and thus need to be clipped or cauterized
Table 1.4   Causes of orbital apex syndrome
Infectious **
Traumatic/ Iatrogenic
  1. Sarcoidosis
  2. Systemic lupus erythematosus
  3. Churg-Strauss syndrome
  4. Wegener granulomatosis
  5. Tolosa-Hunt syndrome (THS)*
  6. Giant cell arteritis
  7. Orbital inflammatory pseudotumor
  8. Thyroid orbitopathy
Fungi: Aspergillosis, Mucormycosis
Bacteria: Streptococcus species, Staphylococcus species, Actinomyces species, Gram-negative bacilli, anaerobes, Mycobacterium tuberculosis
Spirochetes: Treponema pallidum
Viruses: Herpes zoster
Head and neck tumors: Nasopharyngeal carcinoma, adenoid cystic carcinoma, squamous cell carcinoma
Neural tumors: Neurofibroma, meningioma, ciliary neurinoma, schwannoma
Metastatic lesions:
  1. Lung, breast, renal cell, malignant melanoma
  2. Hematologic: Burkitt lymphoma, non-Hodgkin lymphoma, leukemia
  3. Perineural invasion of cutaneous malignancy
  1. Penetrating injury
  2. Nonpenetrating injury
  3. Orbital apex fracture
  4. Retained foreign body
  1. Sinonasal surgery
  2. Orbital/facial surgery
  1. Carotid cavernous aneurysm
  2. Carotid cavernous fistula
  3. Cavernous sinus thrombosis
  4. Sickle cell anemia
*THS is a syndrome characterized by painful ophtalmoplegia due to granulomatous inflammation of unknown etiology affecting the cavernous sinus or orbital apex.
** Infections may spread from the paranasal sinuses, periorbital structures of the CNS. Cavernous sinus thrombosis may occur by spread of bacterial infections from the paranasal sinuses, while fungal infections should be suspected in patients with immunosuppression, diabetes mellitus, and hematologic malignancies.
Malignancies may spread from a primary ocular or orbital source or from adjacent paranasal sinuses. Metastasis especially in the cavernous sinus may also occur. Local spread from head and neck tumors may also occur.
Surgical intervention in sinonasal and periorbital procedures have also on occasion produced orbital apex syndrome (OAS).
The Globe
The globe is located within the bony orbit. It is roughly spherical in shape, being composed of the transparent cornea anteriorly and the opaque sclera posteriorly. It is 2.5 cm in diameter and has a volume of approximately 25 mL. The cornea has a greater curvature as compared to the sclera, and has a radius of about 7.8 mm. The sclera is the larger of the two components and is part of a sphere of radius about 11.5 cm.
The globe is composed of an external layer made up of the sclera, a middle choroid layer and an inner retina. The sclera consists of dense collagenous tissue mixed with a few elastic fibers. At the limbus or corneoscleral junction, it continues anteriorly as the transparent cornea.
The choroid or “middle” layer of the globe lies in close approximation to the sclera. Anteriorly, behind the transparent cornea, it is present as the iris and ciliary body.
The retina is the light sensitive layer of the eye, containing light receptors and neural tissue.
The globe contains the crystalline lens, the anterior chamber between the cornea and the iris, the posterior chamber between the iris and the ciliary body and the vitreous chamber between the lens and the retina.
The Cornea
The cornea is an avascular 50–60 micron- thick structure composed of 5 layers—corneal epithelium, anterior limiting lamina, substantia propria, posterior limiting lamina and endothelium (Fig. 1.9). Since it is an avascular structure it obtains nutrition by diffusion from neighboring aqueous humor. It is transparent, strong and relatively resistant to abrasions. A tear film covers the surface of the cornea. Corneal epithelial layer is composed of a basal columnar germinal layer, intermediate wing cells and an outer layer of squamous, non-nucleated cells. These cells form a continuous layer over the cornea due to the zona occludens type of tight junctions that they form. Interstices present between these cells communicate directly with the aqueous humor. Adhesion of the basal layer to the anterior limiting membrane or Bowman's membrane is facilitated by network of anchoring fibrils and plaques. Cells from the basal layer are able to regenerate and replace other cells. The rate of corneal epithelial turnover is approximately 5–7 days.11
The main bulk of the substantia propria is composed of type 1 collagen fibers arranged in bundles that help maintain the structure of the cornea. They also form a strong junction with the sclera and thus maintain intraocular pressure and alignment of the visual apparatus including the lens. A network of fibroblast cells called keratocytes, is found in the stroma, connected to each other by gap junctions. These cells have well developed rough endoplasmic reticulum and Golgi apparatus. Their main function is the secretion and maintenance of the stroma. Hydrophilic molecules pass easily through the stroma, whereas the epithelial layers are more permeable to lipophilic molecules. Corneal endothelium lines the inner surface of the cornea. It is composed of a single layer of flattened polygonal cells whose main function is to allow passage of large amount of water, solute and molecules of size 1000000 Da and below. It is also capable of pinocytosis. A fluid pump responsible for the rapid rates of fluid transport is thought to be a HCO3 based transport linked to the Na+ K+ ATPase. It is thought to maintain the amount of fluid in the stroma and prevent stromal edema from occurring.
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Figure 1.9: Cornea
Aquaporins (AQP1) have also been identified in the endothelium and thought to play a role in maintaining corneal thickness.
The absence of blood vessels and the particular arrangement of epithelial cells and the extracellular matrix are largely responsible for the smoothness and transparency of the cornea. Cornea also contributes most of the refractive power of the eye. Changes in its curvature may result in a refractive error called astigmatism.
Though it is avascular, the cornea is well supplied by sensory fibers from the trigeminal nerve. Fibers loose their sheaths near the limbus and run through the cornea radially. As they loose the sheaths there is no interference with the corneal transparency. Corneal epithelium has one of the densest nerve supplies of all epithelia. Loss of innervation of the cornea leads to neurotrophic keratitis and loss of corneal epithelium.
Tenon's Capsule
A fascial membrane called Tenon's capsule surrounds the globe of the eye, separating it from the orbital fat (Fig. 1.10). It extends from the point where optic nerve exits the globe to the corneoscleral junction where it fuses with the conjunctiva. It is pierced by tendons of the extraocular muscles and it becomes continuous with their fascial coverings. It is divided into an anterior and posterior space by the tendons of the extraocular muscles and their fascia. A number of fascial septa arise from the eyeball and are fixed to the periosteum, separating the orbital fat into various compartments. They help in maintaining the position of the eye and the position of the orbital fat and hence assist in binocular vision.
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Figure 1.10: Tenon's capsule
The Sclera
The sclera is a tough, opaque fibrous structure, protecting the contents of the globe. It is continuous with the cornea at a junction known as the limbus. It permits a limited amount of drug absorption, due to its vascularity. It is covered by the conjuctival epithelium reflecting onto it from the inner surface of the eyelids. Posteriorly it is pierced by the optic nerve passing through a sieve like perforated plate. Anteriorly at the limbus, an endothelial canal called the canal of Schlemm is present. Externally, the sclera is covered by Tenon's capsule. Within this layer is present the episclera, followed by scleral stroma. The innermost layer is called lamina fusca, which is closely applied to the choroid. Sclera is composed of Type I and III collagen fibril with small amounts of type V and VI. These fibrils are surrounded by a matrix composed of decorin and biglycan. They are proteoglycans. Collagen fibers are interwoven and are also mixed with fibers from the insertions of the extraocular muscles. This particular arrangement of fibers gives the sclera its physical and mechanical properties. It is able to maintain shape while being subjected to the pull of extraocular muscles as well as accommodate minor changes in shape due to changing intraocular pressure. Interspersed between the collagen fibrils are scleral fibrocytes. They have long cytoplasmic processes that form gap junctions with other fibrocytes and are responsible for secretion and turn over of the extracellular matrix material. They are activated by injury.13
The scleral spur is formed by a ring of deep fibers of the sclera surrounding the limbus. It receives insertions of the trabecular tissue anteriorly, and posteriorly parts of the ciliary muscle are inserted into it. Thus, contraction of the ciliary muscle facilitates opening of the trabecular network. The optic nerve pierces the sclera posteriorly. Outer scleral fibers join the dural covering of the optic nerve. Lamina cribrosa is formed by the remaining fibers. They also form small canals through which fibers of the optic nerve exit the eye. A centrally located canal conveys the central retinal artery and vein.12
Though the posterior ciliary blood vessels and nerve pass through the sclera, the sclera itself receives nutrition by diffusion from Tenon's capsule and episcleral blood vessel networks and also from the choroid. However, the sclera receives an abundant nerve supply. Thus, scleral inflammation is very painful.13
Iris and its Muscles
The uveal tract is the pigmented middle layer of the eye. It is continuous with the pia-arachnoid coverings of the optic nerve. The iris and its muscles form the anterior part of the uveal tract. The iris acts as a diaphragm surrounding the pupil. It is composed of fibroblasts, melanocytes and loose collagenous material that contain its nerves and blood vessels. It lies between the cornea and lens, splitting the anterior segment of the eye into an anterior chamber between the cornea and iris and a posterior chamber between the iris and the lens. The main function of the iris is to control the aperture of the pupil. The larger the pupillary aperture is, the more the amount of light entering the eye and vice versa. The aperture is controlled by the sphincter pupillae and dilator pupillae. The sphincter pupillae is formed at the rim of the pupillary margin of the iris by a concentration of circularly arranged smooth muscle fibers. The pupillary aperture decreases upon contraction of these fibers. The dilator pupillae muscle fibers increase pupillary aperture when they contract as their fibers are arranged radially. The anterior surface of the iris has no epithelial covering. The epithelium of the posterior surface is bilayered, its deeper anterior layer being pigmented to absorb light. The more superficial posterior layer is non-pigmented and is in continuity with the unpigmented layer of the retina. The free surface of the iris contains numerous grooves, which allow movement of fluid from the posterior to the anterior chambers.15 The iris is pigmented and hence absorbs and retains lipophilic drugs. The stored drugs are then released slowly.
Innervation of the iris
The muscles of the iris are supplied by autonomic nerves. The constrictor pupillae muscle is innervated by parasympathetic fibers arising from the ciliary ganglia. When stimulated the pupil constricts, reducing its diameter and causing a five-fold decrease in the amount of light entering the eye. The dilator pupillae muscle is supplied by sympathetic autonomic fibers that originate in the T1 segment of the spinal cord. Preganglionic fibers pass to the superior sympathetic cervical ganglion. Postganglionic fibers pass along with blood vessels and supply the muscle fibers. When stimulated, the radial fibers of the dilator pupillae constrict and the pupillary diameter increases.
Ciliary Body
The ciliary body is continuous with the choroid layer of the eye. Its main function is the suspension of the crystalline lens and the secretion of aqueous humor. It is attached to the scleral spur and passes around the eyeball in the irdiocorneal angle. Hence, anteriorly it is continuous with the tissues of the iris, while posteriorly it forms the ora serrata and continues as the choroid. It is brown in color due to the pigment contained in its epithelial layers. It has the following parts (Fig. 1.11)—pars plicata, present anteriorly, which is ruffled and pars plana present more posteriorly, which is smooth and continues with the ora serrata. Suspensory ligaments of the lens pass into the pars plana, anchoring the lens firmly. The ciliary body is covered by a bilayer of epithelial cells, a superficial unpigmented layer and an inner pigmented layer.
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Figure 1.11: Lens and ciliary body
Ciliary body stroma is composed of loose collagen bundles and the ciliary muscle. The ciliary muscle is a ring of muscle tissue. It contains circular, radial and meridional fibers. Nerve supply to the ciliary body and muscle is predominantly parasympathetic from the ciliary ganglion. Upon stimulation, it contracts towards the optical axis, relaxing the suspensory ligaments causing the lens to bulge and accommodate.16
Aqueous Humor
It is a fluid formed by the ciliary body and occupies the anterior and posterior chambers. It is secreted in the posterior chamber and flows through the pupil into the anterior chamber (Fig. 1.12). It drains through the canal of Schlemm into the episcleral veins. Some fluid may also leave the anterior segment through the surface of the iris. It provides nutrition to the avascular cornea, vitreous and lens. It also plays a major role in the regulation of intraocular pressure and the general shape of the eyeball. Any alteration to its drainage and/or secretion causes raised intraocular pressure.
Secretion of Aqueous Humor: It is secreted continuously by the epithelium of the ciliary processes of the pars plicata. They have a large surface area due to the presence of a number of folds, as well as an extensive capillary network. Fluid secretion is a result of active as well as passive processes. Fluid is essentially filtered out of the ciliary capillaries into the stroma and is then secreted by the pigmented and unpigmented epithelium of the ciliary processes into the posterior chamber of the eye. Here, the unpigmented epithelium actively secretes Na+ ions into the lateral intracellular spaces. Cl and HCO3 ions follow the positively charged Na+ ions. Water is drawn out due to the osmolar forces developed by these ions.
Fluid then flows into the posterior chamber and over the edge of the iris in the pupil to enter the anterior chamber. The rate of secretion of aqueous is influenced by intraocular pressure and blood pressure in the ciliary vessels.
Outflow of Aqueous Humor: Fluid exits the anterior chamber through outflow tracts in the iridiocorneal angle (Fig. 1.12). It passes through the trabecular meshwork and then enters the canal of Schlemm. From here, it drains into the extraocular veins.
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Figure 1.12: Outflow of aqueous
Though it is not a primary route, aqeuous also drains through uveoscleral outflow, which involves aqueous reabsorption by the ciliary body and iris and ultimately drains into the veins of the ciliary body, choroid and sclera.
Trabecular meshwork: It is the main site of resistance to the flow of aqueous and has a unique system to maintain its patency and prevent occlusion by debris. A population of phagocytic cells is found on the trabecular meshwork and also within the canal of Schlemm that removes debris and other molecules and keeps the drainage pathway clear.
Crystalline Lens
The lens is a transparent biconvex structure, with a slightly flattened anterior surface and a more curved posterior surface that is in contact with the vitreous. It is devoid of any blood vessels or nerve fibers that may impede its transparency. Its refractive or diopteric power is less than that of the cornea and tears film. The importance of the lens is its ability to alter its shape and hence diopteric power. The lens is encircled by zonular fibers that attach to the ciliary processes of the ciliary body (Fig. 1.11). Changes in tension in this tissue are transferred to the lens, and result in the change in its shape and accommodative power.
The lens is composed of lens fibers which contain crystallin proteins. Crystallins are responsible for the transparent, refractile and elastic properties of the lens. Fibers toward the center of the lens form the nucleus of the lens, while those towards its margin (equator) form the cortical portion of the lens. Fibers terminate in sutures found on the anterior and posterior surfaces of the lens.
A capsule surrounds the lens that prevents entry of hydrophilic molecules into the lens, however, lipophilic molecules enter and pass through the lens slowly. Hence the lens acts as a barrier to the movement of substances from the aqueous to the vitreous humor. After the lens is removed, rates of transport are higher between the aqueous and the vitreous humor.17
Vitreous Humor
The vitreous accounts for about 80% of the mass of the eyeball and fills the vitreous chamber. It is composed of hyaluronan; that is long chains of glucosaminoglycan and a few type II collagen fibers. The fibers are anchored to the basal lamina of the ciliary body. It forms the suspensory ligaments of the lens. At the periphery, it is in a gel like state and towards the center it is in a more fluid state. Hyalocytes are found within the vitreous and they produce substance of the vitreous. The hyaloid canal occupies a central position in the vitreous and is the remnant of the hyaloids artery. It runs from the posterior surface of the lens to the optic disc. Rupture of the hyaloids artery may sometimes form structures called “floaters” that may interfere with vision.
Retina and Optic Nerve
The retina is the sensory layer of the eyeball. It lies between the choroid and the vitreous. It is continuous with the optic nerve at the optic disc and continues anteriorly to cover the iris and ciliary body. It is composed of the pigment layer in opposition to the choroid, followed by the rods and cones, external limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, 15nerve fiber layer and an inner limiting membrane, in contact with the vitreous.
The blood retinal barrier: Cells of the pigment layer form zona occludens type tight junction with each other and prevent movement of a number of particles between the vitreous and the choroid. This function is somewhat in continuation of the function of the blood–brain barrier as the retina may be considered to be part of the brain. The blood retinal barrier properties are also determined by the endothelial cells of its capillaries. They are of the continuous type and provide a barrier to the transport of metabolites and toxins in the blood. It is a barrier to hydrophilic drugs but lipophilic drugs cross easily. Therefore, orally administered drugs and other systemic agents may be present in the eye and sometimes cause retinal toxicity, e.g. digitalis, phenothiazines, methyl alcohol, quinoline derivaties, sildenafil.
Extraocular Muscles
There are 7 extraocular muscles in total (Fig. 1.13). There are 4 rectii (superior, inferior, medial and lateral), and 2 obliques (superior and inferior) that attach to the globe and allow its movements, while the seventh is the levator palpebrae superioris that attaches to the upper eyelid. Individual muscles and their actions are described below.
The Rectii
They arise from a common tendinous ring around the margins of the optic canal called the annulus of Zinn. Each muscle passes anteriorly in positions corresponding to their names and attach onto the sclera behind the corneoscleral junction. They receive their blood supply from the ophthalmic artery and its branches. The lateral rectus is supplied by the abducent nerve, while the oculomotor nerve supplies the others.
The Superior Oblique
Its origin is superomedial to the optic canal on the body of the sphenoid. It passes forward through the trochlea on the superior orbital margin. It passes posterior and laterally and inserts into the sclera between the insertions of the superior and lateral rectii. It is supplied by the trochlear nerve and ophthalmic artery and the maxillary artery.
The Inferior Oblique
It arises from the orbital surface of the maxilla, lateral to the nasolacrimal groove.
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Figure 1.13: Extraocular muscles
It passes posteriorly, laterally and upwards to insert between insertions of the inferior and lateral rectii.
The Levator Palpebrae Superioris
It arises above the optic canal, passes anteriorly and inserts into the skin and the tarsal plate of the upper eyelid. It has a component of smooth muscles, which receive sympathetic innervation (Muller's muscle). Its other fibers are supplied by the oculomotor nerve. It receives its blood supply from the ophthalmic artery.
Movements of the Globe
Together, the rectii and obliques are responsible for elevation, depression, adduction and abduction of the eyeball. Individual muscles may require to be tested to ensure that a particular nerve has been blocked by application of an anesthetic agent.
Blood Supply and Lymphatic Drainage
Arterial Supply
The ophthalmic artery, a branch of the internal carotid artery, and its branches supply blood to the orbit and its structures, along with branches of the maxillary artery. The important branches of the ophthalmic artery include the central retinal artery, branches to the muscles, the ciliary arteries (anterior and long and short posterior branches), the lacrimal artery, supraorbital branch, the anterior and posterior ethmoidal arteries, the meningeal, medial palpebral, supratrochlear and dorsal nasal artery.
Venous Drainage
Superior and inferior ophthalmic veins and the infraorbital vein are the main veins of the orbit. The superior ophthalmic vein is formed by the facial and the supraorbital vein. It also receives the central retinal vein and drains into the cavernous sinus. The inferior ophthalmic vein is formed on the floor of the orbit, anteriorly and receives tributaries from the inferior rectus and oblique, the nasolacrimal sac and eyelids, and also from the eyeball. It drains into the cavernous sinus, sometimes joining the superior ophthalmic vein. It also communicates with the pterygoid plexus and the facial vein.
Lymphatic Drainage and Immune Privilege of the Eye
Lymphatics draining the conjunctive only have been identified. Furthermore, the eye is a site of immune privilege. That is, potentially immunogenic tissues in the eye survive over prolonged intervals of time without provoking an immune reaction. It is believed that such a phenomenon occurs in order to protect an organ or tissue essential for the survival of the host, since loss of sight may have life-threatening consequences.
Factors that may explain this privilege is the presence of a relatively robust blood-ocular barrier that prevents mechanically entry of antigens and proteins from the blood stream. There is also a lack of lymphatic vessels within the eye, and aqueous humor drains directly into venous blood and not to regional lymph nodes. However, even though there is an absence of any defined anatomic lymphatic drainage pathway in the eye; there appears to be a functional pathway as has been recently shown. Aqueous humor is itself rich in inflammatory molecules such as TGF-β2. Anterior chamber-associated immune deviation (ACAID) is also quoted to demonstrate that immunosuppressive environments operate in the eye. That is, antigen-presenting cells derived from the eye are altered by exposure to various cytokines in the eye and that suppress any future exposure to a similar antigen derived from the eye. Ocular tissues also express Fas ligands that induce apoptosis of Fas+ immune cells that may enter the eye. It appears that neural input also facilitates the immune privilege of the eye.14
The structures of the orbit receive motor innervation from fibers that are somatic as well as 17autonomic. The optic nerves carry the sense of sight while other structures in the orbit are receiving somatic sensory innervation by the ophthalmic division of the trigeminal nerve. The ophthalmic nerve has three main branches; the lacrimal nerve, the frontal nerve and the nasociliary nerve. The conjunctiva and the skin covering the lateral part of the upper eyelid are supplied by the lacrimal nerve. The frontal nerve supplies the skin of the upper eyelid and conjunctiva. The skin of the lower eyelid is supplied by the infraorbital branch of the zygomatic nerve, which is a branch of the maxillary nerve. The cornea, sclera, iris and ciliary body are supplied by the nasociliary nerve.
Somatic motor innervation is provided by the oculomotor, abducent and trochlear nerves to the extraocular muscles. The lateral rectus muscle is supplied by the abducent nerve, the superior oblique by the trochlear nerve while all others are supplied by the oculomotor nerve.
The ciliary ganglion: The ciliary ganglion is located in the orbital fat near the apex. It has three main roots; they are the sensory, sympathetic and motor or parasympathetic. The sensory root arises as branches from the nasociliary nerve and passes through the ganglion to supply the sclera, cornea, iris and ciliary body. The sympathetic root arises from postganglionic neurons around the sympathetic plexus of the internal carotid arteries, and passes through the ganglion emerging as short ciliary nerves to supply the blood vessels of the eyeball and the dilator pupillae muscles of the iris. The parasympathetic root is derived from preganglionic fibers of the Edinger-Westphal nucleus and travels with the oculomotor nerve to the orbit. Here a branch separates and joins the ciliary ganglion. Postganglionic parasympathetic fibers arise from the ganglion and pass with the short ciliary nerves and supply the sphincter pupillae and the ciliary body.
Sympathetic stimulation causes pupillary dlilation via α1 adrenergic receptors in the dilator pupillae fibers of the iris. The pupillary aperture increases as also the amount of light entering the eye.
On the other hand, stimulation of the parasympathetics causes pupillary constriction via the action of the constrictor pupillae. This action is mediated via the muscarinic receptors. Parasympathetic stimulation also leads to accommodative changes in the lens. Stimulation of the parasympathetics to the eye causes contraction of the ciliary muscle. Contraction of the ciliary muscles provides a sphincter-like action, reducing its diameter around the suspensory ligaments of the lens. The ciliary ligaments then relax and the lens assumes a more spherical shape with a higher refractive power. The eye is thus able to adjust focal length and view near objects clearly. Since the ciliary body receives predominantly parasympathetic nerve supply, accommodation is controlled by parasympathetic autonomic nerves. A concomitant reduction in the pupillary size accompanies accommodative changes in the ciliary body and lens, due to stimulation of the constrictor pupillae.
Impulses generated by the rods and cones of the retina leave each eye via the optic nerve. Fibers carrying impulses from the nasal halves of each retina cross over to the opposite sides at the optic chiasma, while fibers from the temporal halves of each retina pass on uncrossed. Thus fibers from the right halves of both the retinae pass in the right optic tract, while the fibers of the left halves both the retinae are carried in the left optic tract (Fig. 1.14). Fibers continue on in the optic tract, and relay at the lateral geniculate body of the thalamus. Fibers from this nucleus pass on to the occipital cortex via the optic radiations (geniculocalcarine fibers) to the primary visual cortex.
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Figure 1.14: Visual pathway
Impulses also enter various other pathways: fibers from the optic chiasma; pass on to the suprachiasmatic nucleus; the pretectal nucleus to coordinate the pupillary reflexes, superior colliculus for eye movements and also to the ventral lateral geniculate body.18
Direct reflex: When light is shone in one eye, the pupil constricts. The diagram representing the pupillary light reflex pathways is shown in Figure 1.15. Impulses travel to the pretectal nucleus, and from here to the Edinger-Westphal nucleus, parasympathetic fibers arise here and pass back to the constrictor pupillae muscle with the oculomotor nerve, and through the ciliary ganglion. Alteration of the pupillary diameter grossly affects the amount of light that enters the eye by a factor of about 1 to 30 and hence aids in dark adaptation. Dilator pupillae muscle fibers are supplied by sympathetic fibers originating from the intermediolateral gray horn of T1 thoracic segment, through the superior cervical ganglion. Postganglionic fibers pass along with blood vessels and supply the muscle (Fig. 1.15).
Indirect reflex: When light is shone in one eye, a pupillary reflex is observed in the unilluminated eye as well. It is called the consensual or indirect pupillary reflex. Fibers from the pretectal nucleus supply the Edinger-Westphal nucleus of both sides, hence leading to the consensual or indirect pupillary reflex.19
Accommodation and Pupillary Aperture
A high degree of visual acuity is permitted by the accommodation mechanism. This mechanism involves the contraction or relaxation of the ciliary muscle, and adjustments in the focal length of the lens allowing the eye to maintain acuity of vision at all times.
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Figure 1.15: Pupillary and accommodation reflex pathways
There appears to be a feedback mechanism related to chromatic aberration, where a difference in the ability of the lens to focus red and blue light acts as a signal to correctly adjust the focal power of the lens. Also, convergence of both eyes occurs at the same time. Pupillary diameter also adjusts along with the accommodation process.
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