Ophthalmic anti-inflammatory agents

Definition
Ophthalmic anti-inflammatory agents are topical formulations applied directly to the eye to suppress or modulate inflammation resulting from surgery, trauma, infection, allergy, or chronic eye conditions such as uveitis or dry eye disease. These medications target different components of the ocular inflammatory response, such as prostaglandins, cytokines, immune cells, and vascular permeability.

They encompass several subclasses, including:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Corticosteroids

• Immunomodulators (e.g., cyclosporine, lifitegrast)

• Biological agents (rarely used topically)

They are formulated primarily as ophthalmic solutions or suspensions, and less commonly as ointments or gels. Administration is typically topical, although in severe cases, adjunctive systemic or periocular anti-inflammatory therapy may be required.

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1. Mechanism of Action

Subclass	Mechanism
NSAIDs	Inhibit cyclooxygenase (COX-1 and COX-2) enzymes → ↓ prostaglandin synthesis
Corticosteroids	Inhibit phospholipase A2 → ↓ arachidonic acid → ↓ prostaglandins and leukotrienes; suppress immune cell activation
Immunomodulators	Suppress T-cell activation and proinflammatory cytokines
Biologic agents	Bind inflammatory mediators (rare in topical ophthalmology)

2. Indications

• Postoperative inflammation (cataract surgery, LASIK, glaucoma surgery)

• Uveitis (anterior, intermediate, posterior)

• Allergic conjunctivitis (severe or chronic)

• Episcleritis, scleritis

• Corneal injury or abrasion

• Dry eye disease with inflammation

• Cystoid macular edema (CME) prophylaxis

• Herpetic stromal keratitis (with antiviral cover)

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3. Ophthalmic NSAIDs

Used to manage mild to moderate inflammation, especially in postoperative settings or cystoid macular edema prevention. They are non-immunosuppressive and offer a good alternative to corticosteroids in some settings.

Common NSAIDs (topical ophthalmic)

Generic Name	Brand Names	Key Indications
Ketorolac tromethamine	Acular, Acuvail	Post-op inflammation, allergic conjunctivitis
Nepafenac	Nevanac, Ilevro	Post-cataract CME prophylaxis
Bromfenac	Prolensa, Bromday	Postoperative pain and inflammation
Diclofenac sodium	Voltaren Ophtha	Pain, inflammation, photophobia
Flurbiprofen	Ocufen	Intraoperative miosis inhibition

Characteristics

• Onset: Rapid (within hours)

• Duration: Short to moderate

• Dosing: 1–4 times daily depending on agent

• Side Effects: Burning, stinging, corneal thinning or melting (rare), delayed healing

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4. Ophthalmic Corticosteroids

Potent anti-inflammatory agents used in moderate to severe ocular inflammation. Risk of serious side effects makes monitoring essential.

Common Corticosteroids (topical ophthalmic)

Generic Name	Brand Names	Potency Level
Prednisolone acetate	Pred Forte, Omnipred	High
Dexamethasone	Maxidex, Ozurdex (implant)	High
Fluorometholone	FML, Flarex	Medium
Loteprednol etabonate	Lotemax, Alrex	Low to medium (soft steroid)
Rimexolone	Vexol	Medium
Difluprednate	Durezol	Very high
Hydrocortisone	Cortisporin Eye Ointment	Low (rare use)

Characteristics

• Onset: Fast (within hours)

• Duration: Varies by agent and dose

• Dosing: Typically 1–4 times daily, tapering based on clinical response

• Side Effects:

  • Increased intraocular pressure (IOP)

  • Cataract formation (posterior subcapsular)

  • Secondary infection (fungal, viral)

  • Delayed epithelial healing

Note: Loteprednol is a “soft steroid” designed for lower IOP elevation risk.

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5. Immunomodulators (Calcineurin Inhibitors and LFA-1 Antagonists)

Used for chronic inflammatory conditions, such as dry eye disease, where long-term control with low systemic risk is desired.

Common Agents

Generic Name	Brand Names	Mechanism
Cyclosporine A	Restasis, Cequa	Calcineurin inhibitor (T-cell suppression)
Lifitegrast	Xiidra	LFA-1 antagonist – inhibits T-cell adhesion
Tacrolimus (compounded)	No commercial brand	Calcineurin inhibitor

Indications

• Moderate to severe dry eye disease (keratoconjunctivitis sicca)

• Sjögren’s syndrome-related dry eye

• Off-label: vernal keratoconjunctivitis, graft-versus-host ocular disease

Side Effects

• Burning, foreign body sensation

• Taste disturbance (lifitegrast)

• Immunosuppressive effects are localized with negligible systemic absorption

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6. Combination Products (Steroid + Antibiotic)

Used in postoperative or infectious inflammation to address both inflammation and infection risk. Commonly used after cataract surgery or ocular surface trauma.

Steroid Component	Antibiotic Component	Brand Examples
Dexamethasone	Tobramycin	TobraDex, Tobradex ST
Dexamethasone	Neomycin + Polymyxin B	Maxitrol
Prednisolone	Gentamicin	Pred-G
Loteprednol	Tobramycin	Zylet

7. Routes of Administration

Form	Use
Eye drops	First-line for anterior segment inflammation
Ointments	Nighttime use or for eyelid/eyelash involvement
Injectables (subconjunctival, intravitreal)	Severe inflammation or posterior segment disease
Implants	Sustained release (e.g., Ozurdex dexamethasone implant for uveitis or CME)

8. Adverse Effects and Monitoring

NSAIDs	Corticosteroids	Immunomodulators
Burning/stinging	Raised IOP	Local irritation
Corneal thinning/melting (rare)	Posterior subcapsular cataracts	Delayed effect (weeks)
Delayed epithelial healing	Secondary infections (HSV, fungi)	Dysgeusia (lifitegrast)
Allergic conjunctivitis	Delayed healing	Rare systemic effects

Monitoring Required:

• IOP monitoring (especially with steroids)

• Infectious symptoms (viral/fungal activation)

• Response to treatment (efficacy within 7–14 days for most)

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9. Patient Counseling Points

• Shake suspensions (e.g., prednisolone acetate) before use

• Use drops before ointments if using both

• Wait 5–10 minutes between different eye drops

• Discontinue if pain, photophobia, or vision changes occur

• Never share eye drops – risk of contamination

• Use punctal occlusion to reduce systemic absorption

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10. Examples of Brand Products by Class

A. NSAIDs

Generic	Brand
Ketorolac	Acular, Acuvail
Nepafenac	Nevanac, Ilevro
Bromfenac	Prolensa, Bromday
Diclofenac	Voltaren Ophthalmic

B. Corticosteroids

Generic	Brand
Prednisolone	Pred Forte
Dexamethasone	Maxidex, Ozurdex
Loteprednol	Lotemax, Alrex
Difluprednate	Durezol

C. Immunomodulators

Generic	Brand
Cyclosporine	Restasis, Cequa
Lifitegrast	Xiidra

D. Combinations

Brand	Components
TobraDex	Tobramycin + Dexamethasone
Zylet	Loteprednol + Tobramycin
Maxitrol	Neomycin + Polymyxin B + Dexamethasone
Pred-G	Gentamicin + Prednisolone

11. Prescribing Considerations

• Prefer loteprednol or fluorometholone in patients at risk of IOP elevation

• Nepafenac and bromfenac have better ocular penetration into the posterior segment

• Use restasis or xiidra in long-term dry eye where steroids are not sustainable

• Avoid prolonged steroid use without supervision due to risk of glaucoma and cataracts

• Consider combination therapy when infection risk is high (e.g., corneal abrasion)