Ocular pharmacology - from Goodman and gilmann 14th edition.

1. OCULAR PHARMACOLOGY
Dr. Arun S
First Year Post Graduate
Department of Pharmacology
GMC, ATP

2. AT THE END OF THE SESSION THE LEARNER WILL BE ABLE TO KNOW
ABOUT THE FOLLOWING
1. To be aware of the structure of eye.
2. To enumerate various ocular routes of drug administration.
3. To explain the pharmacokinetics of topically administered ocular drugs.
4. To discuss the general principles of local eye therapy.
5. To enumerate the different classes of drugs used in eye with their
indications.
6. To mention the drugs causing ocular toxicity giving type of lesions induced
by them.
2

3. INTRODUCTION
• The eye is a specialized sensory organ that is relatively secluded from systemic access
by the blood-retinal, blood-aqueous, and blood-vitreous barriers.
• As a consequence, the eye exhibits some unusual pharmacodynamic and
pharmacokinetic properties.
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4. EXTRAOCULAR STRUCTURES
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5. EXTRAOCULAR STRUCTURES
1. EYELIDS AND EYELASHES
2. CONJUNCTIVA
3. LACRIMAL APPARATUS
EYELIDS AND CONJUNCTIVA:
• External surface - Thin layer of skin
• Internal surface - lined with the palpebral portion of the conjunctiva, which is a
vascularized mucous membrane continuous with the bulbar conjunctiva.
• At the reflection of the palpebral and bulbar conjunctivae is a space called the fornix,
located superiorly and inferiorly behind the upper and lower eyelids, respectively.
• Topical medications usually are placed in the inferior fornix, also known as the inferior cul-
de-sac.
5

6. LACRIMAL APPARATUS
SECRETORY -
Lacrimal gland located in the temporal outer portion of the orbit, and accessory glands located in
the conjunctiva.
EXCRETORY - Ductal elements
INNERVATION:
• The parasympathetic innervation is clinically relevant because a patient may complain of dry
eye symptoms while taking medications with anticholinergic side effects, such as tricyclic
antidepressants , antihistamines, and drugs used in the management of Parkinson’s disease.
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7. 7

8. TEARS
• Tears form functionally trilaminar lubrication barrier covering the conjunctiva and cornea.
• The anterior tear layer is composed primarily of lipids, produced by the meibomian glands located at
the eyelid margin.
• The middle aqueous layer, produced by the main lacrimal gland and accessory lacrimal glands,
constitutes about 98% of the tear film.
• Adherent to the corneal epithelium, the posterior layer is a mixture of mucins produced by goblet
cells in the conjunctiva.
• Tears also contain nutrients, enzymes, and immunoglobulins to support and protect the cornea.
• The tear drainage system starts through small puncta located on the medial aspects of both the
upper and lower eyelids. With blinking, tears enter the puncta and continue to drain through the
canaliculi, lacrimal sac, nasolacrimal duct, and then into the nasal cavity.
• The nasal cavity is lined by a highly vascular mucosal epithelium; consequently, topically applied
medications that pass through this nasolacrimal system have direct access to the systemic
circulation.
8

9. OCULAR STRUCTURES - ANTERIOR SEGMENT
Anterior segment structures include the cornea, limbus, anterior and posterior chambers,
trabecular meshwork, canal of Schlemm (Schlemm’s canal), iris, lens, ciliary zonule, and
ciliary body.
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10. CORNEA AND DRUG ACCESS
6 LAYERS:
1. Hydrophobic epithelial layer - barrier to foreign bodies and many drugs
2. Bowman’s layer - distinct sheet of collagen fibres
3. Stroma - hydrophilic layer - collagen lamellae - keratocytes - 90% of corneal thickness
4. Dua’s layer - a distinct thin, but strong, collagen layer between the stroma and
Descemet’s membrane
5. Descemet’s membrane - the basement membrane of the corneal endothelium
6. Endothelium - monolayer of cells - tight junctions - hydrophobic barrier - maintains
corneal dehydration by active transport process.
Drug absorption across the cornea requires penetration of the trilaminar hydrophobic-
hydrophilic-hydrophobic domains of the various anatomical layers.
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11. LIMBUS
• Limbal structures include the corneal epithelial
stem cells, conjunctival epithelium, Tenon’s
capsule, episclera, corneoscleral stroma,
canal of Schlemm, and trabecular meshwork
• Limbal blood vessels, as well as the tears,
provide important nutrients and immunological
defense mechanisms for the cornea.
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12. ANTERIOR AND POSTERIOR CHAMBER
• The anterior chamber holds about 250 μL of
aqueous humor.
• The peripheral anterior chamber angle is formed by
the cornea and the iris root.
• The trabecular meshwork and canal of Schlemm
are located just above the apex of this angle.
• The posterior chamber, with about 50 μL of
aqueous humor, is defined by the boundaries of the
ciliary body processes, posterior surface of the iris,
and lens surface.
12

13. IRIS
ANTERIOR SURFACE - consistes of stroma, a
loosely organized structure containing
melanocytes, blood vessels, smooth muscle, and
parasympathetic and sympathetic nerves.
Importance:
• Differences in iris color - individual variation in
the number of melanocytes and their
melanosomes located in the stroma.
• Individual variation may be an important
consideration for ocular drug distribution due to
drug-melanin binding and side effect profile if
melanogenic.
POSTERIOR SURFACE - densely pigmented
bilayer of epithelial cells.
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14. PUPIL
The pupillary size is controlled by two types
of muscle fibres:
a. Radial, innervated by the
sympathetic nerve fibres, causing
dilatation of the pupil (mydriasis)
b. Circular, innervated by the
parasympathetic nerve fibres,
causing constriction of the pupil
(miosis)
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15. CILIARY BODY
The ciliary body serves two very specialized roles:
• Production and secretion of aqueous humor by the epithelial bilayer - Beta-2 receptors
• Accommodation by the ciliary muscle - M3 receptors
ANTERIOR PORTION - Pars plicata - 70-80 ciliary processes with intricate folds
POSTERIOR PORTION - Pars plana
Ciliary muscle:
• The ciliary muscle is organized into outer longitudinal, middle radial, and inner circular layers.
Coordinated contraction of this smooth muscle apparatus by the parasympathetic nervous system
causes the zonular fibers suspending the lens to relax, allowing the lens to become more convex
and to shift slightly forward. This process, known as accommodation.
• Accomodation is pharmacologically blocked by muscarinic cholinergic antagonists through a
process called cycloplegia
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16. AQUEOUS HUMOUR DRAINAGE
16

17. CILIARY MUSCLE AND IOP LOWERING AGENTS
Contraction of the ciliary muscle (parasympathetic innervation)
↓
Traction on the scleral spur
↓
Widens the spaces within the trabecular meshwork.
↓
IOP-lowering properties of directly acting and indirectly acting
parasympathomimetic drugs
Block of Beta receptors and Carbonic anhydrase enzymes - Decrease production of
aqueous humour
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18. LENS
• The lens is suspended by the ciliary zonular fibers,
specialized strands emanating from the ciliary body.
• The lens is about 10 mm in diameter and is enclosed in a
capsule.
• The bulk of the lens is composed of fibers derived from
proliferating lens epithelial cells located under the anterior
portion of the lens capsule.
• These lens fibers are continuously produced throughout
life.
• Aging, in addition to certain medications, such as
corticosteroids, and certain diseases, such as diabetes
mellitus, cause the lens to become opacified, which is
termed a cataract.
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19. SCLERA AND CHOROID:
Sclera - outermost coat of the eye; covers the posterior part of the globe
• External membrane - episcleral vascular coat, Tenon’s capsule and conjunctiva. The
tendons of the six extraocular muscles insert collagen fibers into the superficial sclera
• Blood vessels pierce the sclera to supply the choroid, ciliary body, iris and optic nerve.
• Internal surface of sclera - vascular choroid - nourishes outer retina
• Choroid - abnormal neovascularization - Target for anti-VEGF drugs
• Blood - retinal barrier - formed by - Bruch’s membrane and retinal pigmental epithelium -
between outer retina and choroid.
• Functions of Retinal pigment epithelium:
a. Vitamin A metabolism
b. Phagocytosis
c. Multiple transport process
OCULAR STRUCTURES - POSTERIOR SEGMENT
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21. 21

22. RETINA
• Thin transparent highly
organised structure - neurons,
glial cells, blood vessels
• It contains photoreceptors
and Rhodopsin based G-
protein singalling system
• Elevated IOP in glaucoma -
death of retinal ganglion cells
• This damage is enhanced by
Glutamate acting on NMDA
receptors
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23. VITREOUS
• Approximately 80% of the eye’s volume is the vitreous.
• Contains collagen type II, hyaluronic acid, proteoglycans, glucose, ascorbic acid, amino
acids, and a number of inorganic salts.
• The vitreous is adherent to the retina and optic nerve, which can result in traction on these
vital structures, and has been the target of enzymatic lysis.
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24. OPTIC NERVE
• Myelinated nerve - 4 segments - Intraocular, Intraorbital, Intracanalicular, Intracranial.
• Various causes of damage:
a. Trauma
b. Toxic drugs (Ethambutol, Methanol, Ethanol)
c. Nutritional (B12 and B9 deficiency)
d. Neoplastic
e. Infections
f. Vascular
g. Inflammatory
• At present, pharmacological treatment of optic neuropathies usually is based on management of the
underlying disease
• Arteritic ischemic optic neuropathy (giant cell arteritis) and optic neuritis is best treated with systemic
intravenous glucocorticoids.
• Glaucomatous optic neuropathy is medically managed by decreasing IOP.
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25. PHARMACOKINETICS AND TOXICOLOGY OF OCULAR
THERAPEUTIC AGENTS
25

26. Topical applied drugs: (eye drops / ointment)
• They target cornea, conjunctiva, sclera, iris and ciliary body and hence used to treat
anterior segment diseases.
• Topically administered solutions get washed away within 15–30 s after instillation,
resulting in less contact time with the absorptive membranes and hence <5% of the
applied dose reaches the intraocular tissues.
Systemic drugs: (oral / parenteral)
• Drugs have to cross the blood–aqueous barrier and blood–retinal barrier to reach the
anterior segment and posterior segment, respectively.
• The drug particle size and lipophilicity play an important role in determining the intraocular
concentration of the drug.
• Usually only 1%–5% reaches the vitreous humour.
OCULAR ROUTES OF DRUG ADMINISTRATION -
Contd..
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27. Periocular route:
• To overcome the inefficiency of topical and systemic routes and to deliver therapeutic drug
concentrations to the posterior segment, periocular routes (periphery of the eye) are
developed.
• These routes include
1. subconjunctival,
2. subtenon,
3. retrobulbar,
4. peribulbar and
5. posterior juxtascleral route.
OCULAR ROUTES OF DRUG ADMINISTRATION -
Contd..
27

28. PERIOCULAR ROUTE OF DRUG ADMINISTRATION
The drug administered by periocular injections can reach the posterior segment by
three different pathways:
1. Trans-scleral pathway
2. Systemic circulation through the choroid plexus and
3. The anterior pathway through the tear film, cornea, aqueous humour and the
vitreous humour.
Periocular injections are as follows;
• Subconjunctival injection
It involves introduction of the drug (e.g., anaesthetic drugs, triamcinolone) beneath the
conjunctiva.
• Subtenon injection
It involves injecting the drug (e.g., lignocaine) into the tenon capsule located around the
upper portion of the eye and into the superior rectus muscle.
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29. PERIOCULAR INJECTIONS - contd..
• Retrobulbar injection
Drug is injected into the conical compartment within the rectus muscles and intramuscular
septa. This route provides high local concentration of drug with no influence on the IOP.
• The peribulbar route
This involves injecting the drug in the extracellular spaces surrounding the rectus muscle.
This route is safe but less effective.
Anaesthetic drugs are administered via retrobulbar and peribulbar routes.
• Posterior juxtascleral route
This involves injecting the drug using blunt tipped curved cannula into the outer surface of
the sclera. This route allows sustained drug delivery to the macula.
Among all periocular routes; retrobulbar route is most efficient but is associated with
complications like retrobulbar haemorrhage, globe perforation and respiratory arrest.
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30. Intracameral route:
• Direct injection of drug (e.g., anaesthetics, antibiotics) can be given into anterior or
posterior chamber of the eye, usually during surgery.
Intravitreal injections
• They are used to deliver drugs (e.g., ranibizumab, bevacizumab) directly into the vitreous
humour to reach the retina and other structures in the back of the eye.
• This route is used to deliver drugs to treat diabetic retinopathy, macular degeneration,
retinal vascular diseases and ocular inflammation without causing systemic toxicity.
OCULAR ROUTES OF DRUG ADMINISTRATION -
Contd..
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31. 31

32. DRUG DELIVERY STRATEGIES
• Several formulations prolong the time a drug remains on the surface of the eye. These
include
a. Gels
b. Ointments
c. Soft contact lenses and
d. Collagen shields.
• Prolong the time a drug remains in the cul-de-sac beneath the eyelid - enhances drug
absorption.
• Ophthalmic gels (e.g., pilocarpine 4% gel) release drugs by diffusion following erosion of
soluble poly- mers.
• Ointments usually contain mineral oil and a petrolatum base and are helpful in delivering
antibiotics, cycloplegic drugs, or miotic agents.
• Drug molecules may also be encapsulated in nanoparticles for controlled release on the
ocular surface.
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33. 33

34. ADME OF OCULAR DRUGS
ABSORPTION:
After topical instillation rate and extent of absorption depends on
1. Dwell time of the drug in the cul-de-sac and precorneal tear film,
2. Elimination by nasolacrimal drainage,
3. Drug binding to tear proteins,
4. Drug metabolism by tear and tissue proteins, and
5. Diffusion across the cornea and conjunctiva.
1. Dwell time of the drug can be prolonged by changing its formulation or vehicle, blocking
the egress of tears from the eye by closing the tear drainage ducts with flexible silicone
(punctal) plugs.
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35. 2. Nasolacrimal drainage:
• Contributes to systemic absorption of topically administered ophthalmic medications.
• Absorption from the nasal mucosa avoids first-pass metabolism by the liver; thus, topical
ophthalmic medications can cause significant systemic side effects, especially when used
frequently or chronically.
3. Diffusion across cornea and conjunctiva:
The drug concentration gradient between the tear film and the cornea and conjunctival
epithelium provides the driving force for passive diffusion across these tissues.
Other factors affecting diffusion:
• Size of the molecule,
• Chemical structure, and
• Steric configuration
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36. Transcorneal absorption:
• The cornea resembles a tril-laminar “fat-water-fat” structure corresponding to the
epithelial, stromal, and endothelial layers, respectively.
• The epithelium and endothelium represent barriers for hydrophilic substances; the stroma
is a barrier for hydrophobic compounds. Hence, an amphipathic agent with both
hydrophilic and lipophilic properties is best suited for transcorneal absorption.
Special conditions:
• Drug penetration into the eye is approximately linearly related to its concentration in the
tear film.
• Certain disease states, such as corneal epithelial defects and corneal ulcers, may alter
drug penetration.
• Medication absorption usually is increased when an anatomical barrier is compromised or
removed.
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37. ADME - DISTRIBUTION
• Topical drugs undergo systemic distribution by nasal mucosal absorption and local ocular
distribution by transcorneal/transconjunctival absorption.
Transcorneal absorption
↓
Aqueous humour accumulates the drug
↓
Trabecular meshwork
↓
Distributed to intraocular structures and systemic circulation
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38. 38

39. MELANIN BINDING
• Melanin binding of certain drugs is an important factor in some ocular compartments.
• For example, the mydriatic effect of α adrenergic agonists is slower in onset in humans
with darkly pigmented irides compared to those with lightly pigmented irides
• Drug-melanin binding is a potential reservoir for sustained drug release.
Clinical importance:
• In the retinal pigment epithelium, accumulation of chloroquine causes a toxic retinal lesion
known as a “bull’s-eye” maculopathy, which is associated with a decrease in visual acuity.
• To reduce the risk of retinal toxicity from chloroquine and related substances (e.g.,
hydroxychloroquine), patients receiving chronic therapy should receive periodic eye
exams, and lifetime cumulative doses should generally be limited to 2.3 mg/kg per day of
chloroquine and 5 mg/kg per day of hydroxychloroquine
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40. ADME - METABOLISM
Enzymes present in eye:
1. Esterases,
2. Oxidoreductases,
3. Lysosomal enzymes,
4. Peptidases,
5. Glucuronide and sulfate transferases,
6. Glutathione conjugating enzymes,
7. Catechol-O-methyltransferase,
8. Monoamine oxidase, and
9. 11β-hydroxysteroid dehydrogenase,
The esterases are of particular interest,
permitting development of ester prodrugs for
enhanced corneal permeability.
Examples:
• Latanoprost is a prodrug for prostaglandin
[PG] F2α used for glaucoma
management.
• Loteprednol is a prednisolone analogue
engineered to have limited systemic
effects due to metabolic inactivation within
the eye
40

41. Routes of excretion:
• Lacrimal tears
• Nasal mucosal absorption and systemic elimination
ADME - EXCRETION
41

42. TOXICITY
• Hypersensitivity reactions
• Direct toxic effects on the cornea, conjunctiva, periocular skin, and nasal mucosa.
• Systemic side effects - All ophthalmic medications are potentially absorbed into the systemic
circulation.
1. Eye drops and contact lens solutions commonly contain anti-microbial preservatives such
as benzalkonium chloride, chlorobutanol, chelating agents, and, rarely, thimerosal.
2. Benzalkonium chloride may cause a punctate keratopathy or toxic ulcerative keratopathy.
42

43. GENERAL PRINCIPLES OF LOCAL EYE THERAPY
• Non - Pharmacological treatment
• Pharmacological treatment
Nonpharmacological modalities:
1. Eye rest and bed rest
2. Proper lighting
3. Protection from strong light, infection and trauma;
4. Hot or cold compresses;
5. Eye exercises; and
6. Nutritional management.
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44. PHARMACOLOGICAL TREATMENT - PRINCIPLES
1. Choice of drug depends on
a. Assessment of potential / actual threat to vision.
b. Presence of local condition or systemic disease.
Example: Beta-adrenergic receptor blocker eye drops can aggravate bronchial asthma.
Persons with a family history of open angle glaucoma are more likely to develop
glaucoma during glucocorticoid therapy.
2. The health care giver and the patient should strictly observe hygienic and aseptic
practices while applying the medication to the eye.
3. The ophthalmic formulation should be used as purchased and no attempt should be
made to dilute it or otherwise modify it.
4. The remnant after the patient gets well should not be stored for future use
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45. 5. Eye drops and ointments usage:
• Eye drops are convenient for ambulatory patients. Their main disadvantage is their short
duration of action and hence the necessity of frequent instillation.
• Only one drop should be instilled into an eye at one time because that is the capacity of
the conjunctival sac. The patient should then lie down with the eye(s) closed.
• If a drop of another medication needs to be instilled at the same time, then 5 min should
be allowed to elapse before adding the second drop.
• Ointments act as reservoir of the drug and have a prolonged action. They may cause
blurring of vision.
6. Associated conitions:
Diabetes mellitus and Hypertension should be treated
PHARMACOLOGICAL TREATMENT - PRINCIPLES
45

46. 7. Systemic drug therapy may have to be employed in serious ocular conditions and in
those which have failed to respond to topical drug therapy.
8. Corneal ulcers and keratitis require treatment by an ophthalmologist
PHARMACOLOGICAL TREATMENT - PRINCIPLES
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47. CLASSIFICATION OF DRUGS USED IN THE EYE
1. ANTI-MICROBIALS: Anti-bacterial, Anti-viral, Anti-fungal, Anti-protozoals
2. AUTONOMIC AGENTS
3. PROSTANOIDS
4. CARBONIC ANHYDRASE INHIBITORS
5. RHO KINASE INHIBITORS
6. ANTI-INFLAMMATORY DRUGS - Glucocorticoids, NSAIDs, Anti-histamines and Mast
cell stabilizers.
7. IMMUNOMODULATORY AGENTS
8. ANTI-MITOTIC DRUGS
9. AGENTS USED IN OPHTHALMIC SURGERY
10. DIAGNOSTIC AGENTS
11. ANESTHETICS IN OPHTHALMIC PROCEDURES
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48. 1. ANTI-MICROBIAL AGENTS
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49. BACTERIAL INFECTIONS OF EYE
• Dacryoadenitis
• Dacryocystitis
• Hordeolum
• Blepharitis
• Conjunctivitis
• Keratitis
• Endophthalmitis
• Panophthalmitis
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50. DACRYOADENITIS
• It is an infection of the lacrimal gland
• Most common in children and young adults;
• Causative agents:
• Bacterial (typically Staphylococcus aureus, Streptococcus spp.)
• Viral (seen in mumps, infectious mononucleosis, influenza, and
herpes zoster).
• When bacterial infection is suspected, systemic antibiotics usually
are indicated.
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51. DACRYOCYSTITIS
• It is an infection of the lacrimal sac.
• In infants and children, the disease usually is unilateral and secondary to an obstruction of
the nasolacrimal duct.
• In adults, dacryocystitis and canalicular infections may be caused by S. aureus,
Streptococcus spp., diphtheroids, Candida spp., and Actinomyces israelii.
• Any discharge from the lacrimal sac should be sent for smears and cultures.
• Systemic antibiotics typically are indicated.
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52. HORDEOLUM
• It is an infection of the meibomian, Zeis, or Moll glands in the eyelids.
• The typical offending bacterium is S. aureus
• Treatment consists of warm compresses and topical antibiotics (gel, drops, or ointment)
52

53. BLEPHARITIS
• It is a common bilateral inflammatory process of the eyelids characterized by irritation and
burning sensation.
• Usually associated with Staphylococcus spp.
• Local hygiene is the mainstay of therapy, although topical antibiotics frequently are used.
• Systemic tetracycline, doxycycline, minocycline, erythromycin, and azithromycin often are
effective in reducing severe eyelid inflammation but must be used for weeks to months.
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54. CONJUNCTIVITIS
• It is an inflammatory or infectious process of the conjunctiva.
• The more common causes of conjunctivitis include allergies, viruses, environmental
irritants, contact lenses, and chemicals.
• Less common causes include other infectious pathogens, immune-mediated reactions,
associated systemic diseases, and tumors of the conjunctiva or eyelid.
• Commonly reported infectious agents are adenovirus and herpes simplex virus, followed
by other viral (e.g., enterovirus, coxsack- ievirus, measles virus, varicella zoster virus) and
bacterial (e.g., Neisseria spp., Streptococcus pneumoniae, Haemophilus spp., S. aureus,
Moraxella lacunata, and chlamydial spp.) sources.
• Rickettsia, fungi, and parasites, in both cystic and trophozoite form, are rare causes of
conjunctivitis.
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55. • Effective management is based on selection of an appropriate antibiotic for suspected
bacterial pathogens.
• Unless an unusual causative organism is suspected, bacterial conjunctivitis is treated
empirically with a broad-spectrum topical antibiotic without obtaining a culture.
CONJUNCTIVITIS - contd..
55

56. KERATITIS
• Corneal inflammation or infection
• Several bacteria, viruses, fungi, fungi and spirochetes
• Mild cases - Broad spectrum topical antibiotics
• Severe cases - Intensive hourly topical fortified antibiotics (preferably after a culture
report)
• In the case of culture-proven bacterial keratitis that has been treated with appropriate
topical antibiotics for several days but still has significant inflammation, judicious topical
steroids can be used with close follow-up to decrease corneal scarring.
56

57. ENDOPHTHALMITIS AND PANOPHTHALMITIS
• Potentially severe and devastating inflammatory, and usually infectious, process involving
the intraocular tissues.
• When the inflammatory process encompasses the entire globe, it is called pano-
phthalmitis.
• Endophthalmitis usually is caused by bacteria or fungi or, rarely, by spirochetes.
• Common causes:
1. Post operative after intraocular surgery - Prompt vitreous tap followed by emperical
injection of intravitreal antibiotics
2. Traumatic open globe injury - Systemic antibiotics
3. Endogenous seeding in an immunocompromised host / IV drug abuser - Parenteral
antibiotics. Vitrectomy in rare cases.
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58. OPHTHALMIA NEONATORUM
Causative agents:
• Chlamydia trachomatis
• Neisseria gonorrhoeae
• Haemophilus species
• Streptococcus pneumoniae
• Staphylococcus aureus
• Staphylococcus epidermidis
• Streptococcus viridians
• Escherichia coli
• Pseudomonas aeruginosa
• Klebsiella pneumonia
• Adenovirus
• Herpes simplex virus
58

59. TREATMENT OF OPHTHALMIA NEONATARUM
Chlamydial infection (Trachoma)
• Best treated with topical tetracycline plus systemic erythromycin (50 mg/kg/d - divided in 4
doses) for 14 days. Milder cases - Topical erythromycin.
• Alternate therapy - oral azithromycin (20 mg/kg once daily for 3 days)
Gonococcal Ophthalmia neonatorum
• Frequent irrigation of the conjunctiva and intravenous or intramuscular administration of
ceftriaxone (25 to 50 mg/kg, to a maximum dose of 125 mg)
Herpetic Ophthalmia Neonatorum
• Systemic acyclovir (60 mg/kg in divided doses 3 times a day) for 14 days, coupled with
topical ophthalmic solution (ie, 1% trifluridine, 0.1% iododeoxyuridine, or 3% vidarabine)
Prophylaxis:
• Tetracycline ointment may be applied to the conjunctivae prophylactically in neonates at
risk.
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60. 60

61. VIRAL INFECTIONS OF THE EYE
1. Viral Keratitis
2. Herpes Zoster Ophthalmicus
3. Viral retinitis
61

62. VIRAL KERATITIS
• Infection of the cornea that may involve the epithelium, stroma, or endothelium.
• Causative agents: Herpes simplex type I and Varicella-zoster viruses, Herpes simplex
type II, Epstein-Barr virus, and Cytomegalovirus (CMV).
• The topical antiviral agents trifluridine, acyclovir, and ganciclovir are indicated for the
treatment of epithelial disease due to herpes simplex infection, but trifluridine is more toxic
to the corneal epithelium than the other two.
• Topical glucocorticoids are contraindicated in herpetic epithelial keratitis due to active viral
replication.
• In contrast, for herpetic disciform (or endothelial) keratitis, topical glucocorticoids often
accelerate recovery.
• For recurrent herpetic stromal keratitis, there is clear benefit from treatment with an oral
antiviral such as acyclovir in reducing the risk of recurrence.
62

63. HERPES ZOSTER OPHTHALMICUS
• Due to latent reactivation of a varicella-zoster infection in the first division of the trigeminal
cranial nerve.
• Systemic acyclovir, valacyclovir, and famciclovir are effective in reducing the severity and
complications of herpes zoster ophthalmicus
63

64. VIRAL RETINITIS
• Causative agents: Herpes simplex virus, CMV, and Varicella-zoster virus.
• Treatment - long-term parenteral administration of antiviral drugs.
• Intravitreal ganciclovir, injected or implanted as an insert, is an effective alternative to
systemic use.
• The ganciclovir intravitreal implant provides a zero-order rate of delivery by steady-state
diffusion, whereby drug is released at a more constant rate over a prolonged period of
time rather than as a bolus.
• Acute retinal necrosis and progressive outer retinal necrosis, most often caused by
varicella-zoster virus is treated with combinations of oral, intravenous, and intravitreal
administration of antiviral medications
64

65. 65

66. FUNGAL INFECTIONS OF THE EYE
Fungal infections can involve the cornea, sclera, intraocular structures, canaliculi, and orbit.
FUNGAL KERATITIS:
• Treatment is typically prolonged due to the generally poor ocular penetration of these
medications and more resistant nature of these pathogens to antimicrobial agents.
• Consequently, topical anti-fungal therapy is frequently supplemented with systemic
antifungal drugs to improve access to deeper infections
66

67. 67

68. PROTOZOAL INFECTIONS OF THE EYE
• They cause uveitis, conjunctivitis, keratitis and retinitis
ACANTHAMOEBA KERATITIS:
Causes:
Poor contact lens hygiene, wearing contact lenses in a pool or hot tub, and ocular trauma.
Treatment:
• Topical Polyhexamethylene biguanide (0.02%) or chlorhexidine (0.02%) with propamidine
(0.1%) or hexamidine (0.1%).
• oral miltefosine has also been used adjunctively in the treatment of Acanthamoeba
keratitis.
• Oral imidazoles (e.g., itraconazole, fluconazole, ketoconazole, voriconazole) are
sometimes used in addition to topical medications
• The duration of therapy may last six months to a year.
• Pain control can be helped by topical cyclopegic solutions and oral nonsteroidal
medications. 68

69. OCULAR TOXOPLASMOSIS
Treatment is indicated when inflammatory lesions encroach on the macula and threaten
central visual acuity.
Several regimens can be tried with concurrent use of systemic steroids.
(1) pyrimethamine, sulfadiazine, and folinic acid (leucovorin);
(2) pyrimethamine, sulfadiazine, clindamycin, and folinic acid;
(3) sulfadiazine and clindamycin;
(4) clindamycin; and
(5) trimethoprim-sulfamethoxazole with or without clindamycin.
69

70. 2. AUTONOMIC AGENTS
Autonomic drugs are used extensively for diagnostic and surgical purposes and for the
treatment of
• Glaucoma,
• Uveitis, and
• Strabismus.
70

71. MYDRIASIS AND CYCLOPLEGIA
• Mydriasis and cycloplegia - paralysis of accommodation, of the human eye occurs after
one drop of
a. Atropine 1%,
b. Scopolamine 0.5%,
c. Homatropine 1%,
d. Cyclopentolate 0.5% or 1%, and
e. Tropicamide 0.5% or 1%.
• Recovery of mydriasis is defined by return to baseline pupil size to within 1 mm.
• Recovery of cycloplegia is defined by return to within 2 diopters of baseline
accommodative power.
• The maximal mydriatic effect of homatropine is achieved with a 5% solution, but
cycloplegia may be incomplete.
• Maximal cycloplegia with tropicamide may be achieved with a 1% solution.
71

72. Times to development of maximal mydriasis and to recovery, respectively, are as follows:
• Atropine, 30–40 min and 7–10 d
• Scopolamine, 20–130 min and 3–7 d
• Homatropine, 40–60 min and 1–3 d
• Cyclopentolate, 30–60 min and 1 d
• Tropicamide, 20–40 min and 6 h.
Times to development of maximal cycloplegia and to recovery, respectively, are as follows:
• Atropine, 60–180 min and 6–12 d
• Scopolamine, 30–60 min and 3–7 d
• Homatropine, 30–60 min and 1–3 d
• Cyclopentolate, 25–75 min and 6 h to 1 d
• Tropicamide, 30 min and 6 h.
72

73. 73

74. 74

75. 75

76. AUTONOMIC AGENTS IN UVEITIS
• Inflammation of the uvea, or uveitis, has both infectious and noninfectious causes, and medical
treatment of the underlying cause (if known), in addition to the use of topical therapy.
TREATMENT:
• Cyclopentolate, tropicamide, or sometimes even longer-acting antimuscarinic agents such as atropine,
scopolamine, and homatropine frequently are used to prevent posterior synechia formation between
the lens and iris margin and to relieve ciliary muscle spasm that is responsible for much of the pain
associated with anterior uveitis.
• If posterior synechiae already have formed, an α adrenergic agonist may be used to break the
synechiae by enhancing pupillary dilation.
• Various combinations of an α adrenergic agonist and antimuscarinic agent (e.g., 10% phenylephrine
with 0.3% scopolamine; 1% hydroxyamphetamine hydrobromide with 0.25% tropicamide; 1%
phenylephrine with 0.2% cyclopentolate; and 2.5% phenylephrine with 1% tropicamide) are available
for the induction of mydriasis.
• Topical steroids usually are adequate to decrease inflammation but sometimes must be supplemented
with local steroid injections or systemic steroids.
76

77. STRABISMUS
• Ocular misalignment - can occur at any age - causes diplopia.
• In children can cause amblyopia - occlusion therapy, orthoptics, optical devices, and
pharmacological agents.
• Treatment:
1. Atropine (1%) instilled in the preferred seeing eye produces cycloplegia and the inability
of this eye to accommodate, thus forcing the child to use the amblyopic eye.
2. Echothiophate iodide - in accomodative strabismus. Used in conjunction with mydriatic
to reduce formation of iris cycts associated with echothiophate use.
77

78. MYOPIA
• Myopia, or nearsightedness, is a condition in which near objects appear clear, while
objects farther away are blurred because light entering the eye is not focused properly
onto the retina.
• Routine treatment: spectacles, contact lenses, or refractive surgery.
• Pharmacological treatment:
1. Low- dose atropine ranging from 0.01% to 0.5% can be used to slow and even reverse
myopia progression in children, although the exact mechanism of action remains
unclear.
• Side effects:
1. Dose dependent and include allergic reactions, dilated pupils requiring sunglasses, and
loss of accommodation.
78

79. 79

80. 80

81. 3. ANTI-INFLAMMATORY AGENTS IN EYE
1. Glucocorticoids
2. NSAIDs
3. Anti-histamines and Mast cell stabilizers
81

82. GLUCOCORTICOIDS
82

83. 83

84. 84

85. TOXICITY OF TOPICAL GLUCOCORTICOIDS
• Posterior subcapsular cataracts,
• Secondary infections, and
• Secondary open-angle glaucoma. There is a significant increase in the risk for developing
secondary glaucoma when there is a positive family history of glaucoma. In the absence of
a family history of open-angle glaucoma, only about 5% of normal individuals respond to
topical or long-term systemic steroids with a marked increase in IOP.
• Certain corneal infections can be worsened by topical steroids, especially from herpes
simplex virus, fungus, and acanthamoeba.
85

86. NSAIDS IN EYE
• Five topical NSAIDs are FDA - approved for ocular use: flurbiprofen, ketorolac, diclofenac, bromfenac,
and nepafenac.
• Available as solutions and suspensions.
• Indications:
1. Flurbiprofen - to counter unwanted intraoperative miosis during cataract surgery.
2. Ketorolac - Seasonal allergic conjunctivitis
3. Ketorolac + Phenylepherine combination - intraoperative ophthalmic irrigation solutions to decrease
miosis during cataract surgery.
4. Diclofenac - Post-operative inflammation and pain
5. Ketorolac / Diclofenac - ketorolac and diclofenac are effective in treating cystoid macular edema
occurring after cataract surgery and in controlling pain after corneal refractive surgery.
6. Bromfenac and nepafenac - treating postoperative pain and inflammation after cataract surgery.
• Adverse effects:
Sterile corneal melts and perforations, especially in older patients with ocular surface disease such as dry
eye syndrome or autoimmune conditions
86

87. ANTI-HISTAMINES AND MAST CELL STABILIZERS
Anti-Histamines:
• Pheniramine / antazoline + naphazoline - Allergic conjunctivitis
• emedastine difumarate - Allergic conjunctivitis
• Cromolyn sodium - vernal conjunctivitis
Mast cell stabilizers:
• lodoxamide tromethamine - Vernal conjunctivitis and keratitis
Anti-Histamine plus Mast cell stabilizing action:
• Nedocromil (also has some anti-histamine action) - Vernal conjunctivitis and keratitis.
• Lopatadine hydrochloride, ketotifen fumarate, bepotastine, azelastine, and alcaftadine are
H1 antagonists with mast cell–stabilizing properties.
• Epinastine antagonizes H1 and H2 receptors and exhibits mast cell–stabilizing activity.
87

88. 4. IMMUNOSUPPRESSIVE AND ANTI-MITOTIC AGENTS
88

89. 5. AGENTS USED IN OPHTHALMIC SURGERY
PRESURGICAL ANTISEPTICS:
• Povidone iodine - 5% sterile ophthalmic solution for use prior to surgery to prepare
periocular skin and irrigate ocular surfaces, including the cornea, conjunctiva, and
palpebral fornices. Following irrigation, the exposed tissues are flushed with sterile saline.
• Povidone iodine can cause local irritation and should be avoided in patients with a history
of prior reaction to it.
• Hypochlorous acid is an effective skin preparation agent and can be used for ophthalmic
surgery when povidone iodine is contraindicated.
89

90. VISCOELASTIC SUBSTANCES:
• The viscoelastic substances are agents that assist in ocular surgery by maintaining spaces,
moving tissue, and protecting surfaces.
• These substances are prepared from hyaluronate, chondroitin sulfate, and hydroxypropyl
methylcellulose
• Adverse effect: Transient increase in IOP
OPHTHALMIC GLUE:
• Cyanoacrylate tissue adhesive (not FDA-approved for the eye), is widely used in the
management of corneal ulcerations and perforations.
• Fibrin sealants are increasingly being used on the ocular surface to secure tissue such as
conjunctiva, amniotic membrane, and lamellar corneal grafts.
INTRAOPERATIVE VISUALIZATION:
• Trypan blue - 0.06% and 0.15% ophthalmic solutions to facilitate visualization of the anterior
lens capsule during cataract surgery, for staining of Descemet’s membrane that is inserted into
the eye during Descemet’s stripping endothelial keratoplasty
• Staining the retinal surface during surgical vitrectomy to guide the excision of tissue. 90

91. ANTERIOR SEGMENT GASES:
• Sulfur hexafluoride (SF6) and perfluoropropane (C3F8) gases are used as vitreous substitutes during
retinal surgery.
• SF6 - Given after endothelial keratoplasty to help the lamellar graft adhere to the posterior cornea.
• SF6 may also be used to treat Descemet’s detachments, typically after cataract surgery.
VITREOUS SUBSTITUTES:
• Primary use is reattachment of the retina following vitrectomy and membrane-peeling procedures for
complicated proliferative vitreoretinopathy and traction retinal detachments.
• Side effects - elevated IOP, subretinal gas, corneal edema, and cataract formation.
• The liquid perfluorocarbons - denser than vitreous and are helpful in flattening the retina when vitreous is
present.
• Their use is limited to intraoperative settings due to long-term toxicity to the retina.
• Silicone oil (polydimethylsiloxanes) is used for long-term tamponade of the retina.
• Complications from silicone oil use include glaucoma, cataract formation, corneal edema, corneal band
keratopathy, and retinal toxicity.
• Combinations of silicone oil and partially fluorinated alkanes have been approved for clinical use, which
may have benefit over silicone oil alone for certain types of retinal breaks 91

92. 92

93. SURGICAL HEMOSTASIS AND THROMBOLYTIC AGENTS:
• Intravitreal administration of thrombin can assist in controlling intraocular hemorrhage
during vitrectomy.
• When used intraocularly, a potentially significant inflammatory response may occur that
can be minimized by thorough irrigation after hemostasis is achieved.
• During intraocular surgeries to assist evacuation of a hyphema, sub-retinal clot, or
nonclearing vitreous hemorrhage, tissue plasminogen activator has been used off-label.
tPA also has been administered subconjunctivally and intracamerally (i.e., controlled
intraocular administration into the anterior segment) to lyse blood clots obstructing a
glaucoma filtration site.
• The main complication related to the use of tPA is bleeding.
93

94. 6. AGENTS USED TO TREAT BLIND AND PAINFUL EYES
• Retrobulbar injection of either absolute or 95% ethanol may provide relief from chronic
pain associated with a blind and painful eye when topical steroids and cycloplegics fail.
• Retrobulbar chlorpromazine also has been used off-label. This treatment is preceded by
administration of local anesthesia.
• Local infiltration of the ciliary nerves provides symptomatic relief from pain, but other
nerve fibers may be damaged. This may cause paralysis of the extraocular muscles,
including those in the eyelids, or neuroparalytic keratitis.
94

95. 7. DIAGNOSTIC AGENTS
1. Anterior Segment and External Diagnostic Uses:
Epiphora (excessive tearing) and surface problems of the cornea and conjunctiva are
commonly encountered external ocular disorders. The dyes fluorescein, rose bengal, and
lissamine green are used in evaluating these problems.
Fluorescein - 10% and 25% solutions for injection and as an impregnated paper strip,
• Reveals epithelial defects of the cornea and conjunctiva and aqueous humor leakage that
may occur after trauma or ocular surgery.
• In epiphora, fluo- rescein is used to determine the patency of the nasolacrimal system.
• Also used in applanation tonometry (IOP measurement)
• To assist in determining the proper fit of rigid and semirigid contact lenses.
• Fluorescein in combination with proparacaine or benoxinate is available for procedures in
which a disclosing agent is needed in conjunction with a topical anesthetic.
95

96. • Fluorexon, a high-molecular-weight fluorescent solution, is used when fluorescein is
contraindicated (as when soft contact lenses are in place).
• Rose bengal and lissamine green (available as saturated paper strips) stain devitalized
tissue on the cornea and conjunctiva.
2. Posterior Segment Diagnostic Uses:
fluorescein sodium or indocyanine green - intravenous administration - in Retinal
angiography - To check the integrity of the blood-retinal and retinal pigment epithelial
barriers.
96

97. 8. Treatment of Retinal Neovascularization, Macular
Degeneration, and Vitreomacular Traction
97

98. 9. ANESTHETICS IN OPHTHALMIC PROCEDURES
• These agents are used topically to anaesthetise the ocular surface: Drops / gels
1. To remove foreign bodies from the cornea and conjunctiva.
2. Prior to tonometry.
3. For pre-operative preparation. Usually, proparcaine and tetracaine are used.
4. In the manipulation of the nasolacrimal system (tetracaine or lignocaine)
5. During the use of excimer laser for surgery for refractive errors (tetracaine)
6. For infiltration and retrobulbar block anaesthesia (lignocaine and bupivacaine)
• Local anaesthetics should never be used for management of ocular pain.
• Most inhalational anesthetic agents and CNS depressants are associated with a reduction
in IOP.
• An exception is ketamine - elevation in IOP.
• In the setting of a patient with a ruptured globe, the anesthesia should be selected
carefully to avoid agents that depolarize the extraocular muscles, which may result in
expulsion of intraocular contents
98

99. 10. TREATMENT OF DRY EYE AND CORNEAL EDEMA
• Tear substitutes: hypotonic / isotonic - contains electrolytes, surfactants, preservatives,
and some viscosity-increasing agent that prolongs the residence time in the cul-de-sac
and precorneal tear film.
• Common viscosity agents include cellulose polymers, polyvinyl alcohol, polyethylene
glycol, polysorbate, mineral oil, glycerin, and dextran.
• Some tear formulations also are combined with a vasoconstrictor, such as naphazoline,
phenylephrine, or tetrahydrozoline.
• A hydroxypropyl cellulose ophthalmic insert that is placed in the inferior cul-de-sac and
dissolves during the day is available to treat dry eyes.
• Appropriate treatment of the symptomatic dry eye includes treating the accompanying
disease and possibly the addition of tear substitutes, punctal plugs (see Absorption),
ophthalmic cyclosporine, or ophthalmic lifitegrast.
99

100. • Ophthalmic cyclosporine/lifitegrast can be used to increase tear production in patients
with ocular inflammation associated with keratoconjunctivitis sicca.
• Doxycycline is often used to treat blepharitis due to its anti–matrix metalloproteinase
activity.
Corneal edema is a clinical sign of corneal endothelial dysfunction, and topical osmotic
agents may effectively dehydrate the cornea.
NaCl is available in either aqueous or ointment formulations.
Topical glycerin also is available; however, because it causes pain on contact with the
cornea and conjunctiva, its use is limited.
Rho kinase inhibitors, including netarsudil and ripasudil, promote adhesion, survival, and
proliferation of corneal endothelial cells. These medications have been used in conjunction
with Descemet’s stripping only surgery in patients with Fuchs endothelial corneal dystrophy
100

101. 11. TREATMENT OF NEUROTROPHIC CORNEA
• Corneal nerves mediate protective blinking and tearing reflexes and also provide trophic
support, releasing neuropeptides to promote corneal epithelial proliferation, migration, and
adhesion.
• Neurotrophic keratopathy can result from multiple underlying causes including herpetic
infection, chemical injury, long-term diabetes, prior ocular surgery, long-term contact lens
use, or an intracranial mass or neurosurgery.
TREATMENT:
• Artificial tear lubrication, autologous serum tears, tarsorrhaphy, or amniotic membrane
transplantation.
• Cenegermin, a recombinant human nerve growth factor topical eye drop, was approved
for the treatment of neurotrophic keratopathy in the U.S. in 2018.
101

102. 102

103. 12. THERAPEUTIC USES OF VITAMIN A
• Nutritional vitamin A deficiency causes xerophthalmia, a progressive disease
characterized by nyctalopia (night blindness), xerosis (dryness), and keratomalacia
(corneal thinning), which may lead to corneal perforation.
• Vitamin A therapy can reverse xerophthalmia; however, rapid, irreversible blindness
ensues once the cornea perforates. Vitamin A also is involved in epithelial differentiation
and may have a role in corneal epithelial wound healing.
• The current recommendation for retinitis pigmentosa - 15,000 IU of vitamin A palmitate
daily under the supervision of an ophthalmologist and to avoid high-dose vitamin E.
• Clinical studies suggested a reduction in the risk of progression of some types of AMD
(Age related Macular Degeneration) by high doses of vitamin C (500 mg), vitamin E (400
IU), β-carotene (15 mg), cupric oxide (2 mg), and zinc (80 mg).
103

104. OCULAR SIDE EFFECTS OF SYSTEMIC AGENTS
IOP AND GLAUCOMA:
• Topiramate (anti-seizure drug) - choroidal effusions leading to angle-closure glaucoma.
• Inhaled, systemic, or ocular steroids can cause elevated IOP and glaucoma.
RETINA:
• Hydroxychloroquine and Chloroquine - Central retinal toxicity
• Tamoxifen - Crystalline maculopathy
• Cisplatin and Carmustine - Pigmentary retinopathy
• Vigabatrin - progressive and permanent bilateral concentric visual field constriction.
OCULAR SURFACE:
Isotretinoin - Dry eye and severe dysfunction of the meibomian gland.
104

105. OPTIC NERVE:
• The phosphodiesterase (PDE) 5 inhibitors sildenafil, vardenafil, and tadalafil inhibit PDE5 in the
corpus cavernosum to help achieve and maintain penile erection. They are also used to treat
pulmonary arterial hypertension.
• The drugs also mildly inhibit PDE6, which controls the levels of cyclic GMP in the retina, causing a
bluish haze or light sensitivity.
• Ethambutol, chloramphenicol, and rifampin, can cause toxic optic neuropathy characterized by
gradually progressive bilateral central scotomas and vision loss.
ANTERIOR SEGMENT:
• Steroids, Tamoxifen - Cataract
• Rifabutin + clarithromycin or fluconazole for Myco-bacterium avium complex opportunistic infections
in human immuno-deficiency virus–positive persons, is associated with an iridocyclitis and even
hypopyon.
OCULAR SIDE EFFECTS OF SYSTEMIC AGENTS - contd..
105

106. CORNEA, CONJUNCTIVA AND EYELIDS:
• Amiodarone - Corneal microdeposits - Cornea verticillata
• Chlorpromazine and thioridazine - brown pigmentary deposits in the cornea, conjunctiva, and
eyelids.
• Gold- and silver-containing medications can be used to treat rheumatoid arthritis - pigmented
deposits in the cornea and conjunctiva.
• Cytarabine -temporary corneal toxicity.
• Tetracyclines - yellow discoloration of the light-exposed conjunctiva.
• Systemic minocycline - blue-gray scleral pigmentation that is most prominent in the interpalpebral
zone.
• Dupilumab, (a monclonal antibody that inhibits pro-inflammatory signaling by IL-4 and IL-13, is used
to treat moderate to severe eczema) - conjunctivitis, keratitis, blepharitis, and dry eye.
OCULAR SIDE EFFECTS OF SYSTEMIC AGENTS - contd..
106

107. REFERENCES
Goodman & Gilman's: The Pharmacological Basis of Therapeutics - 14th edition.
Pharmacology and Pharmacotherapeutics by R.S. Satoskar - 26th edition.
107

108. 108