ocular pharmacology

1. Ocular Pharmacology
Dr Navodaya Salwe ( junior resident-2)
Guide – Dr Sangeeta Dabhade
Associate professor
BJGMC & SASSOON HOSPITAL.

2. Anatomy of eye

4. Routes of ocular administration

6. Pharmacokinetics
• Rate & extent of absorption of topically
instilled
drugs depends upon –
1. Time the drug remains in the cul-de-sac &
precorneal tear film
2. Elimination by nasolacrimal drainage
3. Drug binding to tear proteins
4. Drug metabolism by tear & tissue proteins
5. Diffusion across cornea & conjunctiva

8. Distribution
Transcorneal absorption
Accumulation in aqueous humor
Distribution to intraocular structures
Distribution to systemic circulation via Trabecular
meshwork pathway

9. • Metabolism
• Biotransformation of ocular drugs may be
significant a variety of enzymes including
esterases, oxidoreductases, lysosomal enzymes,
peptidases etc
• Ex: Development of prodrugs for enhanced
ocular permeability
• 1. Dipivefrine hydrochloride
• 2. Latanoprost

10. Antibacterial agents
Agents Formulation Toxicity Indication for use
Besifloxacin 0.6%
suspension.
H Conjunctivitis
ciprofloxacin 0.3% solution,
0.3% ointment.
H,
D-RCD
Conjunctivitis,Keratitis,
keratoconjunctivitis,
corneal ulcers,
blepharitis,dacryocystitis
Gatifloxacin 0.3&0.5 %
solution.
H Conjunctivitis.
H-hypersensivity, D-RCD-drug related corneal deposit.

11. Agents Formulation Toxicity Indication for use
Levofloxacin 0.5% & 1.5%
solution
H Conjunctivitis,
corneal ulcers
Moxifloxacin 0.5% solu H Conjunctivitis
Ofloxacin 0.3%
solution
H Conjunctivitis,
corneal ulcers
Antibacterial agents

12. Antibacterial agents
Agents Formulation Toxicity Indication for use
Gentamicin 0.3% Solution
0.3%
ointment
H Conjunctivitis ,Keratitis,
keratoconjuctivitis,
corneal ulcers,
blepharitis,dacryocystitis
Tobramycin 0.3% Solution
0.3%
ointment
H External infection of the
eye
sulfacetamide 10% solu,10%
ointment
H Conjunctivitis, Superficial
ocular infection,
Azithromycin 1% solution H Conjunctivitis.

13. Antiviral agents
Agents Formulation Toxicity Indication for use

14. Antiviral agents
Agents Formulation Toxicity Indication for use

15. Antifungal agents.
Agents Administration Indications for use
Amphotericin
B
0.1-0.5% solution
0.8-1 mg Subconjunctival
5 microgram intravitreal
injection
Intravenous
Yeast & fungal
keratitis &
endophthalmitis
Natamycin 5% topical suspension Yeast & fungal
blepharitis
-Conjunctivitis ;
keratitis
Fluconazole Oral & Intravenous Yeast keratitis &
endophthalmitis
Itraconazole Oral Yeast & fungal
keratitis &
endophthalmitis

16. Antifungal agents
Agents Administration Indications for use
Ketoconazole Oral Yeast keratitis &
endophthalmitis
Miconazole 1% topical
solution,
5to 10mg
subconjunctival,
Yeast & fungal
keratitis & fungal
endophthalmitis.
Voriconazole Oral,
Intravenous,
intravitreal.
Yeast & fungal
keratitis & fungal
endophthalmitis.

17. Ophthalmia neonatorum
• Also known as neonatal conjunctivitis
• Any type of conjunctivitis within 1 month of age.
• Causes-1)chlamydia
2)Gonorrhea
3)Herpes simplex virus
4)Staph aureus
Crede’s method- 1% silver nitrate
-topical tetracycline ointment 1 %, erythromycin
ointment 0.5 %, povidone iodone solution 2.5 %,
aminoglycosides, macrolides,fluroquinolone,
chloramphenicol.

18. Glaucoma
Glaucoma is a group of disease characterised by a
progressive form of optic nerve damage.
The therapeutic measure is to lower IOT either by
reducing secretion of aqueous humour or by
promoting its drainage.

20. Aim of treatment
PG analogues

22. Prostaglandin Analogues
• First- line medical therapy for Glaucoma
• PGF2α analogues - Good efficacy , once daily
application & absence of systemic side effects
1.Latanoprost 2. Travoprost 3.Bimatoprost
• MOA – Facilitate aqueous outflow through
uveoscleral outflow pathway
• Side effects - Ocular irritation & pain, Blurring
of vision, increased iris pigmentation, Macular
edema

23. β Adrenergic blockers
• Nonselective β blockers – Timolol maleate
- Levobunolol
- Metipranolol
- Carteolol
• β -1 antagonists - Betaxolol

24. • Lower IOT by reducing aqueous formation
• MOA-
Production of aqueous humour seem to be
activated by a β recp mediated C-AMP PK-A
pathway.β blocker blunt adrenergic activation
for aqueous production.
β blocker decreases ocular blood flow which
decreases the ultrafiltration responsible for
aqueous production.

25. 1)Timolol
• 20-35% fall in IOT within 1 hour & lasts for 12
hours. 30% patients additional medication.
• s/e –Exacerbation of resp problems, bradycardia.
2) Betaxolol
• Less efficacious than Timolol
• Protective effect on retinal neurons by blocking
some calcium channels & reducing reducing
Na2+/Ca2+ influx

26. Timolol Betaxolol carteolol
Non selective Β1 selective Non selective
20-35% fall in iop Less effective than
timolol
Less effective than
timolol
Iot fall within 1hr
and last for 12hrs
30% patients require
additional
medication.
Protective effect on
retinal neurons
β-agonist property

27. Adverse Effects of Ocular
β Adrenergic blockers
• Ocular
• 1. Stinging, redness &
dryness of eye
• 2. Corneal hypoesthesia
• 3. Allergic
blepharoconjunctivitis
• 4. Blurred vision
• Systemic
• 1. Bronchospasm in
asthmatics & COPD
patients
• 2. Bradycardia &
accentuation of Heart
block

28. Adrenergic Agonists
Dipivefrine
• Prodrug of Adrenaline
• Reduces aqueous
production
• Augments uveoscleral
outflow
• Ocular burning
• used as add on therapy
Apraclonidine
• Selective α2 agonist
• Highly ionized at
physiological pH
• Do not cross BBB
• Reduces aqueous
production
• Enhance uveoscleral
outflow

29. Carbonic anhydrase Inhibitors
• Topical CAI – Dorzolamide , Brinzolamide
• MOA – Inhibit carbonic anhydrase on ciliary
body epithelium → Reduces formation of
bicarbonate ions → Reduces fluid transport →
Reduces aqueous formation → Decrease IOP
• Use – Only as add on drug to topical β
blockers or PG analogs
• S/e – stinging, burning, itching,
corneal edema & bitter taste.

30. Topical Miotics
• MOA - Ciliary muscle contraction
• Increase drainage through trabecular
meshwork
• Drugs----Pilocarpine
• Less useful drugs – Numerous side effects &
three to four times a day dosing

31. Angle closure Glaucoma

32. Angle closure Glaucoma
• 1. Hypertonic Mannitol ( 20%) – IV infusion
1.5 -2 g/kg
• 2. Acetazolamide - 0.5 g iv followed by oral
twice daily started concurrently
• 3. Miotic - Pilocarpine (1-4%) instilled every 10
min
• 4. Timolol 0.5 % - instilled 12 hourly.
• 5. Latanoprost 0.005%
• Definitive treatment –
Surgical/ Laser iridotomy

33. Topical glucocorticoids
Agent indication
Dexamethasone
0.1%suspension.
Palpebral and bulbar conjunctiva, cornea,
post inflammation, corneal injury from
chemical, radiation or thermal burns.
Difluprednate
0.05% emulsion.
Ocular pain, postoperative ocular
inflammation, uveitis.
Fluorometholone
0.25% suspension
0.1% ointment.
Allergic conjunctivitis, giant papillary
conjunctivitis, keratitis, ocular burns, vernal
keratoconjunctivitis, uveitis

34. Topical glucocorticoids
Agent indication
Loteprednol
0.2%suspension
0.5% gel.
Allergic conjunctivitis, giant papillary
conjunctivitis, iritis, keratitis, ocular pain,
uveitis.
Prednisolone
Acetate
1%solution.
Allergic conjunctivitis, marginal corneal
ulcer,anterior segment inflammation, bacterial
conjunctivitis
Rimexolone
1% suspension.
vernal keratoconjunctivitis, uveitis,
postoperative ocular inflammation

35. Agents Method of
administration
Indications
Triamcinolone subtenon’s,
intracameral
Intravitreal
Ocular inflammation, ocular
surgery,uveitis.
Betamethasone Sub-Tenon’s Corticosteroid-responsive
ophthalmic disorders: allergic
Conjunctivitis, marginal
corneal ulcer, anterior
segment inflammation,
chorioretinitis, conjunctivitis,
iritis, keratitis, postoperative
ocular inflammation, optic
neuritis, vernal
keratoconjunctivitis
GLUCOCORTICOIDS FOR SUB-TENON’S, INTRAVITREAL, AND SYSTEMIC USE

36. Agents Method of administration Indications
Dexamethasone
0.7 mg ophthalmic
implant
Intravitreal Ocular inflammation
due to macular edema
following retinal vein
occlusion or central
retinal vein occlusion ,
noninfectious uveitis
Methylprednisolone
2-32mg tabs
40-1000 mg injection.
Oral, intravenous,
Intramuscular
allergic conjunctivitis,
allergic marginal
corneal ulcer, anterior
segment inflammation,
chorioretinitis,
endophthalmitis,
optic neuritis,
diffuse posterior uveitis,
or vernal
keratoconjunctivitis

37. Agents Method of administration Indications
Fluocinolone
acetonide
0.19 mg implant.
Intravitreal Diabetic macular
edema
Prednisone
1mg/ml solution
20-50 mg tabs.
Oral Inflammatory
conditions such as
endophthalmitis,a
optic neuritis,
allergic
conjunctivitis,
keratitis, allergic
corneal ulcer, iritis,
chorioretinitis,

38. Toxicity of Steroids
• 1. Posterior subcapsular cataracts
• 2. Secondary infections
• 3. Secondary open-angle glaucoma
-- Positive family history of glaucoma

39. Nonsteroidal Anti-inflammatory Agents
• Five topical NSAIDs are approved for ocular use: flurbiprofen,
ketorolac,diclofenac, bromfenac, and nepafenac.
• To reduce ocular inflammation and cystoid macular edema.
• Ketorolac – seasonal allergic conjunctivitis.
• Diclofenac - postoperative inflammation ,pain.
• ketorolac and diclofenac - treating cystoid macular edema
occurring after cataract surgery and in controlling pain after
corneal refractive surgery.
• S/E --Topical and systemic NSAIDs associated
--corneal melts and perforations, especially in older patients
with ocular surface disease, such as dry eye syndrome.

40. IMMUNOSUPPRESSIVE AND
ANTIMITOTIC AGENTS FOR OCULAR
Agent Formulation Indication comments
Cyclosporine 0.05% emulsion Dry eye
Lifitegras 5% solution Dry eye
5-Fluorouracil 50-mg/mL
solution
Glaucoma
surgery
Used intraoperatively and
postoperatively to
prevent subconjunctival
scarring
Inhibits corneal epithelial
healing

41. Agent Formulation Indication comments
Mitomyc
in
0.2 mg/mL for
topical
application
Glaucoma
surgery
Pterygium
surgery
Corneal scarring
and surface
ablation surgery
used as a
subconjunctival
application
intraoperatively
to prevent
scarring
Used topically on
the cornea

42. Drugs for ocular daignosis
Agent Formulation Indication Side effect
Atropine 1% solution Cycloplegia,mydriasis,
fundoscopic examination
Photo sensetivity,
blurred vision.
Homatropine 2% &5%
solution
Cycloplegia,mydriasis, iritis Photo sensetivity,
blurred vision
Cyclopentolat
e
0.5% & 2%
solution
Cycloplegia,mydriasis Photo sensetivity,
blurred vision
Tropicamide 0.5% & 1%
solution
Cycloplegia,mydriasis Photo sensetivity,
blurred vision
Scopolamine 0.25%solution Cycloplegia,mydriasis, iritis Photo sensetivity,
blurred vision

43. • Fluorescein ,rose bengal, lissamine green dye -
surface problems of cornea & conjunctiva.
• Fluorescein - patency of nasolacrimal ducts,
applanation tonometry, in determining the proper fit
of rigid & semirigid contact lens.( ant segment)
• Integrity of blood retinal and retinal pigment
epithelial barriers by retinal angiography.( post
segment)

44. Treatment of Retinal Neovascularization, Macular
Degeneration, and Vitreomacular Traction
1) Verteporfin ( Intravenously )
• Light activation by non-thermal laser
• Free radical generation
• Vessel damage
• Platelet activation & thrombosis
• Occlusion of choroidal neovascularization
• 2-mg/mL reconstituted solution for intravenous
infusion
• Causes photosensitization and propensity for
sunburn

45. • Pegaptanib
• Approved for neovascular (wet ) ARMD
• Selective Vascular endothelial growth factor
(VEGF ) antagonist.
• VEGF 165 – Angiogenesis & increase vascular
permeability- Progression of wet ARMD
• 0.3 mg once every 6 weeks by intravitreous
route
• Patients should be monitored for elevation in IOP
and for endophthalmitis.
• cases of anaphylaxis/anaphylactoid reactions
have been reported

46. • Bevacizumab
• Monoclonal antibody against Vascular
Endothelial Growth Factor (VEGF)
• Inhibits vascular proliferation & tumor growth
• Intravitreal injection weekly/monthly
Off label Uses of Bevacizumab
1. Proliferative Diabetic Retinopathy
2. Macular edema
3. Retinopathy of Prematurity
4. ARMD

47. • Aflibercept
• recombinant fusion protein
• approved for the neovascular (wet) form of
ARMD as well as macular edema following
retinal vein occlusion or associated with
diabetic retinopathy
• 2 mg administered once every month by
intravitreous injection into the eye for 3–5
months, followed by 2 mg once every 8
weeks
• eye pain, redness, swelling, vision problems,
photosensitivity, headaches, sudden
numbness, confusion, problems with speech
and balance.

48. Anesthetics In Ophthalmic Procedures
• Proparacaine & tetracaine drops –
Uses 1) Tonometry
2) Removal of foreign bodies on conjunctiva &
cornea
3)Superficial corneal surgery
• Lidocaine & Bupivacaine – Retrobulbar block
anaesthesia

49. • Agents Used in Ophthalmic Surgery
1. Povidone iodine
2. Viscoelastic substances
3. Ophthalmic Glue
4. Anterior Segment Gases
5. Vitreous Substitutes

51. Tear Substitutes
• Hypotonic or isotonic solutions – electrolytes,
surfactants, preservatives & viscosity
increasing agent ( Carboxymethylcellulose,
Hydroxyethylcellulose, polyethylene glycol,
Polyvinyl alcohol)

52. Therapeutic Uses of Tear Substitutes
• Eye diseases – Blepharitis
- Corneal dystrophies
- Chemical Burns
• Systemic diseases – Sjogren’s syndrome
- Rheumatoid arthritis
- Vitamin A deficiency
- Stevens-Johnson syndrome

53. Systemic Agents with Ocular Side Effects
1.Topiramate- -Angle Closure Glaucoma
2. Hydroxychloroquine/Chloroquine --Chloroquine amblyopia
( Bull’s eye Maculopathy )
3. Tamoxifen --Crystalline Maculopathy
4. Vigabatrin --Progressive & Permanent bilateral concentric
visual field constriction
5. Sildenafil/Vardenafil/tadalafil --Nonarteritic Ischemic Optic
Neuropathy(NAION )
6. Ethambutol, Chloramphenicol ,Rifampin--Toxic Optic Neuropathy
(Progressive bilateral central scotomas & vision loss )
7. Ocular Steroids-- Elevated IOP & Glaucoma
8. Steroids– Cataract
9.Amiodarone --Drug deposits in cornea ( Cornea verticillata )
10. Chlorpromazine & Thioridazine --Brown pigmentary deposits in the
cornea
11. Gold-- Chrysiasis ( gold deposits in cornea & conjunctiva

54. Deficien
cy
Effects in Anterior
Segment
Effects in Posterior
Segment
Vitamin
A
Conjunctiva(Bitot’s spot,
xerosis)
Cornea (Keratomalacia ,
Punctate keratopathy)
Retina(Nyctalopia)
Retinal pigment
epithelium
(hypopigmentation
Vitamin
B1
Optic nerve (Visual field
defects)
Vitamin
B6
Cornea(Neovascularizatio
n)
Retina (Atrophy
Vitamin
B12
Optic nerve (Visual field
defects)
Vitamin
C
Lens (Cataract formation)

55. Deficiency Effects in Anterior
Segment
Effects in Posterior Segment
Vitamin E Retina & retinal pigment
epithelium ( Macular
degeneration)
Folic acid Vein occlusion
Vitamin K Conjunctiva
(Hemorrhage)
Retina (Hemorrhage)
Zinc Retina & retinal pigment
epithelium (Macular
degeneration)