Ocular pharmacology

1. OCULAR PHARMACOLOGY
Moderator : Dr Preeti Pandey
Presentor : Dr Shabnam Tanwar

2. Pharmacokinetics
Study of chemical alteration of drug in the body
1. Absorption
2. Distribution
3. Metabolism
4. Excretion

3. Absorption
Absorption is the movement of the drug from its site of
administration to the target tissue (to produce the
desired effect).
Not only the fraction of administered dose that gets
absorbed but the rate of absorption is also important.

4. Factors influencing absorption of drug
 Drug concentration and solubility: higher the
concentration better will be the penetration.
 Viscosity: increases the contact time with the cornea.
Addition of methylcellulose and polyvinyl alcohol
increases the viscosity of drug.
 Lipid solubility: higher the lipid solubility more will
be the penetration.

5.  Surfactants: the preservatives used in ocular
preparations alter cell membrane in the cornea and
increase drug permeability eg- Benzylalkonium and
Thiomersal
 pH:
the normal tear pH is 7.4 and if the drug pH is
different, it will cause reflex tearing.
when an alkaloid drug is put in relatively alkaline
medium, the proportion of the uncharged form will
increase, thus more penetration

6. Barrier for intraocular transport of drugs
Corneal epithelium and stroma: most imp
Blood ocular barriers: blood retinal barrier
blood aqueous barrier
Blink rate
Absorption through conjunctival vessels and mucosa
Nasolacrimal drainage of tears

8. Distribution
 Once the drug is absorbed, it has the potential to
penetrate most compartments of the body known as
distribution.
 Distribution largely depends on the route of
administration.

9. Distribution: Topical
Transcorneal absorption
Accumulation in aqueous humor
Distribution to intraocular structures
Trabecular Meshwork
Distribution in systemic circulation

10. Factors affecting distribution
Physiochemical properties of drug:
 Acidic/basic
 Binding to plasma proteins
 Binding to tissue proteins
 Relative blood flow to different tissues

11. Metabolism
 Drugs are metabolized to facilitate clearance &
activate prodrugs for enhanced permeability
 Enzymatic biotransformation
Eg: Esterases, ketone reductase & phase 1 &2 oxidizing
and conjugating enzymes
Eg. 1. Dipivefrine hydrochloride - Epinephrine
2. Latanoprost (isopropyl ester)- acid
3. Nepafenac 0.1% - Amfenac

12.  Many of the drugs metabolized and excreted via
kidneys or liver mostly
1. Timolol – Liver
2. Mannitol – kidneys
3. Acetazolamide – kidneys
4. Latanoprost (PG)- liver
5. Local anesthetics- liver/ plasma

13. Routes of administration
Topical Periocular Intraocular
Solutions Subconjunctival Intracameral
Gels Subtenon Intravitreal
Ointments Peribulbar
Contact lens Retrobulbar

14. Therapeutic applications

15. DRUGS FORMULATION INDICATION Onset of action&
Duration of action
ATROPINE 0.5%, 1% & 2%
solution.
1% ointment
•Cycloplegia
•Mydriasis
•Cycloplegic
retinoscopy
OA: 30-40 mins
Mydriasis -15 days
Cycloplegia -120
mins
HOMATROPINE 2% & 5% solution Cycloplegia
Mydriasis
Same as above
SCOPALAMINE 0.25% solution Cycloplegia
Mydriasis
Mydriasis-7 days
Cycloplegia-30-60
mins
CYCLOPENTOLATE 0.5% & 1% solution Cycloplegia
Mydriasis
OA: 15-30 mins
Mydriasis -1day
Cycloplegia-20-45
mins
PHENYLEPHRINE 2.5% solution Mydriatic only Mydriasis-4-6 hrs
TROPICANAMIDE 0.5% & 1% solution Cycloplegia
Mydriasis
OA: 15-30 mins
Mydriasis -4-5 hrs
Cycloplegia-15miins
Diagnostic purposes

16. Fluorescein dye
 Corneal epithelial defects & corneal ulcers.
 Applanation tonometry -Goldmann
tonometer/Perkins hand-held tonometer
 Seidel's test: Concentrated fluorescein dye
 Jones dye test for assessment of lacrimal passage
functional potency.
 Fundus fluoroscein angiography: 10%-20% i/v
 Fluorometry
 Tear film break up time(TBUT)

17. CORNEAL EPITHELIAL
DEFECT
DRY EYE
APPALANTION
TONOMETER
SEIDELS TEST POSITIVE

18. Rose Bengal dye
 Rose bengal is actually a derivative of fluorescein
 Stains the devitalized cells only
 Unlike fluoroscein, it’s a true histological stain which
binds strongly and selectively to cellular components
 1% liquid rose bengal dye via dry impregnated paper
strips
DRY EYE
SJOGREN’S SYN-
KERATOCONJUNTIVITIS
SICCA

19. DENDRITIC KERATITIS

20. Lissamine green
 Stains membrane-damaged or devitalized cells- GREEN
 There is no stinging or discomfort such as that
associated with rose bengal.
 Stains the edges of the dendritic ulcer while
fluoroscence stains the central bed
 Concentration of 1% lissamine strips.
DRY EYE DENDRITIC ULCER

21. Indocyanine green(ICG)
 Absorbs light at about 805 nm and emits 835nm
infrared radiation
 These frequencies penetrate retinal layers allowing
ICG angiography to image deeper patterns of
circulation then FFA
 Tightly bound to plasma proteins, thus becomes
confined to vascular system.
 40mg in 2ml

22. VERTEPORFIN
 Verteporfin,a benzoporphyrin derivative
 Used as a photosensitizer for photodynamic
therapy to eliminate the abnormal blood vessels in
the eye associated with conditions such as the wet
form of macular degeneration.
CENTRAL SEROUS CHORIORETINOPATHY

23. Ocular infections
Anti bacterials Anti fungals Anti virals
Aminoglycosides
cephalosporins
Fluoroquinolone
Macrolides
Sulfonamides
Others:
Chloramphenicol
Polyenes-
Azoles
Imidazole Triazole
Acyclovir
Valacyclovir
Trifluridine
Gancicyclovir
Cidofovir
Foscarnet
Miconazole
ketoconazole
Fluconazole
Itraconazole
voriconazole
Anti Parasitic:
acanthamoeba
Polyhexamethyl
biguanide 0.02%
Chlorhexidine
0.02%
Hydrogen peroxide
Benzalkonium
chloride(BKC)
Natamycin
Ampho B

24. ANTIBACTERIALS

25. Anti Bacterials
Anti Bacterials MOA Drugs available
Aminoglycosides Protein synthesis
inhibitors
Gentamycin, Tobramycin
& Amikacin
Flouoroquinolones DNA gyrase inhibitors Ciprofloxacin, gati, moxi,
besifloxacin etc
Macrolides Protein synthesis
inhibitors
Azithromycin ,
erythromycin
Sulphonamides Anti folate antibiotics Chloramphenichol,
sulphaacetamide
Cephalosporins Cell wall synthesis
inhibitors
cefazoline

26. Aminoglycoside (cont)
Drugs Dosage Indication Side effects
Gentamycin 0.3% every four hrs Conjunctivitis,
keratitis, corneal
ulcers, dacrocystitis
etc
Ocular burning &
irritation, non
specific conjuntivitis.
Pregnancy & child
Tobramycin 0.3% every four hrs Conjunctivitis,
keratitis, corneal
ulcers, dacrocystitis
etc in children
Tearing, swelling of
eye, stinging or
blurred vision
fortified Amikacin 1.25%- 2.5% Severe bacterial
infection
Eg- mycobacterium
chelonae keratitis
Ototoxicity
Nephrotoxicity
Pregnancy-D

27. Generic name formulations Toxicity Indications
Ciprofloxacin 0.3% solution
0.3% ointment
Hypersensitivities
Drug related
corneal deposits
Conjunctivitis
Keratitis
Corneal ulcer
blephritis
Dacrocystitis
Ofloxacin 0.3% solution Hypersensitivity Conjunctivitis
Corneal ulcers
Fluroquinolones

28. Generic name formulations Toxicity Indications
Gatifloxacin 0.3% solution Hypersensitivity Conjunctivitis,
post op & pre op
prophylaxis,
corneal
pathologies etc
Moxifloxacin 0.5% solution Hypersensitivity same as above
Besifloxacin 0.6% suspension Redness, blurring
of vision, pain,
irritation etc
Same as above

29. Macrolides
Generic name formulations Toxicity Indications
Azithromycin 1% ointment Hypersensitivity Superficial
infection
involving cornea
and conjunctiva
Erythromycin 0.5% ointment Hypersensitivity Superficial
infection
involving cornea
and conjunctiva
MOA: Inhibits Protein synthesis by inhibiting
the translocation on 50S ribosome

30. Sulphonamides
Generic name Formulations Dosage Indications
Chloramphenicol 0.5% solution 4-6 times daily Conjuntivitis
Keratitis
Sulfacetamide
sodium
10%, 15% and
30% w/v
Two hourly (for
trachoma)
Conjuntivitis,
trachoma and
other superficial
ocular infections
MOA: These are Anti folate antibiotics which
inhibit folic acid synthesis

31.  The use of fluoroquinolones as monotherapy for
bacterial keratitis has proved as effective as combined
fortified antibiotics
 However, serious complications such as corneal
perforation, evisceration, or enucleation of the
affected eye were more common with
fluoroquinolone therapy (16.7%) compared with the
fortified therapy (2.4%, p= 0.02).
 Caution should be exercised in using
fluoroquinolones in large, deep ulcers in the elderly
Gangopadhyay N, Daniell M, Weih L,Taylor HR. Fluoroquinolone
and fortified antibiotics for treating bacterial corneal ulcers; Br J
Ophthalmol 2000;84:378–384

32. Antibiotic Resistance
 Moxifloxacin resistance rates of coagulase negative
(70% of endophthalmitis in cataract surgey) are
increasing. The mean resistance of moxi at a large
university centre over past six years were almost 60%.
-JAMA Ophthalmology, November 2014
 “ Recent studies suggest that repeated short courses of
post injection topical antibiotic do not decrease the
risk of endophthalmitis but also actually increase
antibiotic resistance among conjunctival flora
-American Journal Of Ophthalmology, March 2014

33.  “Use of only povidone iodine at the time of
intravitreal injection without topical antibiotics
appears to have the lowest risk of contributing to the
wide spread problem of increasing endophthalmitis.”
-American Journal of Ophthalmology, March 2014
For topical agents, the MIC value is considered the
Gold standard measurement of antibiotic efficacy

34. Antifungal agents
Drug Administration Toxicity Indications
Natamycin 5% suspension
2hourly
Hypersensitivity
Irritation
Yeast & fungal
keratitis
Amphoteracin B 0.1-0.5% solution
0.8-1mg
subconjuctival
5 mcg intravitreal
Hypokalemia
Infusion related
toxicity
Yeast & fungal
keratitis and
endophthalmitis
Ketoconazole Topical 1-2%
Oral 200-600mg/d
Allergic rash
teratogenic
Yeast keratitis &
endophthalmitis
Fluconazole Topical 1-2%
Oral 200mg/d
Allergic rash
teratogenic
Yeast keratitis &
endophthalmitis
Itraconazole Topical 1-2%
Oral 200-400 mg
Poor penetration
so used in
combination
Yeast & fungal
keratitis &
endophthalmitis
Voriconazole Extemporaneously
prepared
No damage to the
eye
Invasive
Aspergillosis
P
O
L
Y
E
N
S
A
Z
O
L
E
S

35. Antiviral agents
Generic name Route of
administration
Ocular toxicity indications
Trifluridine Topical 1%
solution
Punctate
keratopathy
hypersensitivity
Herpes simplex
keratitis,
keratoconjtivitis
Acyclovir Oral(200mg cap/
800mg tab)
Herpes zooster
ophthalmicus,
HS iridocyclitis
Valacyclovir Oral (500-
1000mg)
HS Keratitis
HZ ophthalmicus
Famicyclovir Intravenous
intravitreal
HS Keratitis
HZ ophthalmicus
Vidarabine 3% ointment Lacrimation,
foreign body
sensation, photo-
phobia etc
HS Keratitis
HZ ophthalmicus
ACUTE
&RECURRENT
Gua-
nosine
nucleo
side
analog
yes

36. Anti Parasitic : Protozoal keratitis
 Acanthamoeba Keratitis
 Specific treatment include
Topical agents DRUGS
Diamidines Propamidine isethionate 0.1%
Hexamidine 0.1%
Biguanides Polyhexamethyl biguanide 0.02%
Chlorhexidine 0.02%
Aminoglycosides Neomycin
paromycin
Imidazoles Clotrimazole
Miconazole

37. Anti acanthamoeba for contact lens care
Anti acanthamoeba
agents (in contact lens
solution)
Presevatives Type of contact lens
Polyaminopropyl
biguanide,
Sodium borate
0.11% disodium
edentate
soft
Polyhexamethyl
biguanide
Preservative free soft
Polyvinyl alcohol
0.004%
BKC, sodium edeate Gas permeable
Polyvinyl alcohol (25.0) 0.004% BKC Gas permeable & hard
Hydrogen peroxide 3% soft

38. Drugs for CMV RETINITIS
 Cytomegalovirus infection can occur in general
population but CMV retinitis occur usually with
advanced immunosuppression (CD4+ cells<100/mm3)
 Treatment
Anti viral agents Route Toxicity
Ganciclovir &
valganciclovir
Topically, IV,
intravitreal
Headache, convulsion,
behavioural change
Cidofovir intravitreal Vitritis, hypotony &
vision loss
Foscarnet Intravitreal, IV Headache, tremors etc
Fomiversen Intravitreal Iritis, vitritis, cataract
& rise in IOP

39. Ocular inflammation
 Inflammation is a characteristic response of the
mammalian tissue to injury
 Anti inflammatory agents:
1. Steroidal Anti Inflammatory Drugs
2. Non-Steroidal Anti Inflammatory Drugs

40. Action of steroids
INCREASE THE SYNTHESIS OF
LIPOCORTIN
(-)PHOSPHOLIPASE A2
(-)ARACHIDONIC ACID
(-) PROSTAGLANDIN &
LEUKOTRIENE PATHWAYS
(-) PROSTAGLANDINS:
Inflammation, conjunctival
hyperemia, change in IOP, break
down of blood ocular barrier etc

41. PHOSPHOLIPIDS
ARACHIDONIC ACID
LIPOXYGENASES CYCLOOXYGENASE,
COX-1 & COX-2
LEUKOTRINES
LTB4, LTC4, LTD4
& LTE4
PROSTAGLANDINS
PGD2, PGE2, PGF2,
PGI2 & TXA2
STEROIDS
NSAIDS

42. Steroids
Inhibits
1. Bradykinin
2. Nitric oxide
3. Antigen presenting cells & T-cell macrophages
4. Histamine production
5. Eosinophil release

43. Corticosteroids
 CLASSIFICATION
CLASSIFICATION Steroid
Short acting Hydrocortisone, cortisone, prednisolone
Intermediate acting Triamcinolone , fluprednisolone
Long acting Dexamethasone & Betamethasone

44. Steroidal Anti Inflammatory agents
Corticosteroids Strength (%) Indications
Steroid
responsive
inflammatory
condition of
conjunctiva,
cornea & ant seg
of eye like
Uveitis, allergic
conjunctivitis,
SPK, episcleritis,
Corneal
abrasion, ocular
inflammation,
corneal injury
from diff burns,
optic neuritis etc
Dosage
Prednisolone
acetate,
prednisolone
soduim phophate
0.125 & 1.0 In tapering doses
Dexamethasone
sodium phosphate
0.1 In tapering doses
Fluromethalone
acetate
0.1 In tapering doses
Loteprednol
etabonate
0.5 & 0.2 In tapering doses
Methyl
prednisolone
1mg/kg IV

45. Side effects of steroids
OCULAR SYSTEMIC
 Glaucoma Peptic ulcer
 Cataract Hypertension
 Activation of infection increases blood sugar
 Delayed wound healing Activation of TB
Osteoporosis

46. Non-Steroidal Anti Inflammatory agents
NSAIDS OCULAR USES
Indomethacin To prevent miosis & CME after cataract sx
Diclofenac Post operative inflammation
Ketorolac Seasonal conjunctivitis, CME after cataract
sx
Nepafenac It’s a prodrug, 6 times faster permeation
Flurbiprofen To counter unwanted intraoperative miosis
during cataract surgery
Piroxicam Activity is comparable & tolerance is better
than diclofenac sodium(0.1%)
INDOLE DERIVATIV
ARYL ACETIC ACID
DERIVATIVE
ARYL PROPIONOC
ACID DERIVATIVE
ENOLIC ACID
DERIVATIVE
ANTI-INFLAMMATORY, ANALGESIC, ANTI-PYRETIC, FREE
RADICAL SCAVENGING ACTIVITY etc

47. Ocular anti Allergic drugs
Classification Drugs Allergy
Seasonal allergic
conjuntivitis(SAC)
Perennial allergic
conjuntivitis(PAC)
Vernal
keratoconjunctivitis
(VKC)
Atopic kerato
conjunctivitis( AKC)
Giant Papillary
conjunctivitis(GPC)
Anti histamines Pheniramine,
antazoline, emedastine
etc
Mast cell stabilizers Cromolyn sodium,
nedocromil,
pemirolast, ketotifen
Dual action anti
allergic drugs
Olapatidine,, azelatine
& epinastine
NSAIDS Ketorolac
Corticosteroids Loteprednol,
fluromethalone,
dexamethasone,
prednisolone etc

48. ANTI GLAUCOMA DRUGS
AIM OF TREATMENT
DECREASE THE
FORMATION OF IOP
-Beta blockers
-Alpha agonist
-Carbonic anhydrase inhibitors
INCREASE AQUEOUS
DRAINAGE
-Prostaglandins
-Topical miotics

49. Cholinergics
 MOA : stimulates the muscarinic receptors producing
increased aqueous outflow.
 Indiacation : pupillary block glaucoma
 Dosage : Pilocarpine 0.25%, 0.5%
one drop two to three times a day

50. Anti cholinergics
 MOA : block the response of response of acetylcholine
at the receptor
 Agents :
1. Atropine
2. Cyclopentolate
3. Tropicanamide
 Not used routinely in glaucoma treatment
 Use: Inflammatory & Malignant glaucoma

51. Alpha adrenergics agonist
 MOA: stimulate alpha 2 receptors in the ciliary
epithelium and thereby decrease the rate of aqueous
production.
 Agents :
1. Dipivefrin 0.1%, one drop 2-3 times a day
2. Brimonidine 0.15% one drop 2-3 times a day

52. Beta blockers
 Mechanism of action: lower IOP by reducing aqueous
formation
 Also reduces ocular outflow
Non selective betablocker Selective beta 1 blockers
Timolol maleate betaxolol
Levobunolol
Metipranolol
Carteolol

53.  TIMOLOL
 BETAXOLOL
20-35% fall in IOP within 1hr and
last for 12 hours.
30% patients- additional
medications
Less efficacious than Timolol
Protective effect on retinal
neurons by blocking calcium
channels

54. Adverse effects
Ocular
 Stinging, redness &
dryness of eyes
 Corneal hypothesia
 Allergic
blephroconjuntivitis
 Blurred vision
Systemic
 Bronchospasm in
asthamatics & COPD
patients
 Bradycadia and
accentuation of heart
block

55. Prostaglandins
 First line medical therapy for open angle glaucoma
 PGF2 alpha analogs

 Good efficacy, once daily, No systemic sideeffects
 MOA: facilitate aqueous outflow through uveoscleral
outflow pathway

56.  Agents :
1. Latanoprost : 0.005% HS
2. Bimatoprost: 0.03% HS
3. Travoprost
 Adverse effects:
 Ocular irritation & pain
 Blurring of vision
 Increased iris pigmentation
 Macular edema

57. Carbonic anhydrase inhibitors
 Add on drugs to topical beta blockers or PG analogues
 MOA: inhibits carbonic anhydrase enzyme on ciliary
body epithelium
reduces formation of bicarbonate ions
reduces fluid transport
reduces aqueous formation
decrease in IOP

58.  Topical CAI:
1. Dorzolamide
2. Brinzolamide
 Systemic CAI: Acetazolamide 125-250 mg, two to
four times a day
 Indication : open & closed angle glaucoma

59. Immunosuppressive & Anti
Mitotic agents
Agents commonly used
1. 5- fluorouracil
2. Mitomycin C
 Indications :
 Intermediate uveitis
 Peripheral ulcerative keratitis
 Ocular surface squamous neoplasia(OSSN)
 Trabeculectomy
 GVHD

60. Immunomodulators
TOPICAL CYCLOSCPORINE
-Approved for the treatment of Chronic dry eye
associated with inflammation.
Decreases inflammatory markers in lacrimal gland
& increases tear production

61. Angle closure glaucoma
 Hypertonic Mannitol 20% IV infusion- 1.5-2 g/kg
 Acetazolamide 0.5g iv followed by oral twice daily
started cncurrently
 Miotic : Pilocarpine 1-4%
 Timolol 0.5%
 Latanoprost
DEFINITIVE
TREATMENT:
Surgical or Laser
Iridotomy

62. Anti Angiogenic drugs
VEGF Inhibitors ANGIOSTATIC
STEROIDS
•BEVACIZUMAB
•RANIZUMAB
•PEGATINIB
•siRNA
•VEGF TRAP
•ANECORTAVE ACETATE
•SQUALINE

63. VEGF Inhibitors
 MOA:
These are anti VEGF anti bodies that bind the VEGF
receptors thereby blocks both increased vascular
permeability and angiogenesis

64. VEGF Inhibitors Administration Indications
Bevacizumab Intravitreal injection
1.25 mg/0.05ml
WET ARMD
Ranizumab Intravitreal injection
every four wks
Choroidal
neovascularization
due to ARMD
Pegatanib Intravitreal injection
every six wks
WET ARMD
Diabetic macular
edema
siRNA
VEGF Trap
Under clinical trail for
WET ARMD

65. Ocular Lubricants
Polymer composition of Artificial tears
Hydroxymethyl cellulose/ carboxy methyl cellulose
Carbomers (polyacrylic acid)
Hypomellose (hydroxypropylmethyl cellulose)
Liquid paraffin
Polyvinyl alcohol
Polyvinyl pyrrolidone
polycarbophil
Indications: Ocular irritation
Dry Eyes

66. Preservatives
 Ophthalmic solutions and ointments must be sterile
so wide variety of preservatives are used for anti-
microbial activity
PRESERVATIVES
Benzalkonium chloride
Chlorbutol
Phenyl mercuric nitrate
Stabilized oxychloro compound
Thiomersal
Chlorhexidine
Sorbic acid

67. Adverse effects of preservatives
 Toxic to precorneal tear film and epithelium, thus
impedes epithelial healing and disrupting the tear
film
 Direct cellular damage
 Reduces oxygen utilization of cornea
 Hypersensitivity reaction
1. Papillary conjunctivitis
2. Punctate keratitis
3. Corneal edema

68. Ophthalmic Anesthesia
Requirements for ophthalmic surgeries
 Akinesia
 Profound analgesia
 Minimal bleeding
 Avoidance of oculocardiac reflex
 Control of IOP

69. Anaesthesia Techniques
 General
 Local : 1. Topical
2. Regional

70. Local Anaesthesia
According to chemical nature
ESTER group
Procaine
Cocaine
Tetracaine
Benzocaine
AMIDE group
Lidocaine
Bupivacaine
Ropivacaine
Mepivacaine

71. LA ONSET OF
ACTION
DURATION OF
ACTION
CONCENTRATIO
N
Lignocaine 5-10 mins
10-35 secs
30-60 mins
15-20 mins
Infiltration(1/2/3%)
Topical 4%
Proparacaine 15-30 secs 15-20 mins Topical (0.5%)
Bupivacaine Moderate 75-90 mins Infiltration (0.25-
0.75%)
Ropivacaine Moderate 1.5-6hrs Infiltration 1%

72.  In patients with uncomplicated cataract at high risk
for thromboembolic events, phacoemulsification
cataract surgery under topical anaesthesia was safely
performed without discontinuing systemic
anticoagulant and antiplatelet treatment.
 40 pts of mean age 72yrs on anticoagulants had phaco
surgery done and none had any hemmorhagic
complications or a thromboembolic event during
surgery or at 1 week followup
Barequet IS etal,Risk assesment of simple phacoemulsification in patients on combined
anticoagulant and antiplatelet therapy: J Cataract Refractive surgery, 2011

73. Thank you