Ophthalmic Anti Inflammatory Drugs

Ophthalmic anti-inflammatory drugs treat inflammation of the lids, ocular surface, cornea and uvea, and prevent inflammation after surgery. They include topical corticosteroids, topical non-steroidal anti-inflammatory drugs (NSAIDs), mast cell stabilisers and antihistamines, and topical calcineurin inhibitors. Corticosteroids are the most effective but carry the greatest risks.

Mechanism. Corticosteroids inhibit phospholipase A2 and cytokine transcription, reducing prostaglandins, leukotrienes and cell infiltration. NSAIDs inhibit cyclo-oxygenase and prostaglandin synthesis. Antihistamines block H1 receptors; mast cell stabilisers prevent degranulation. Ciclosporin and tacrolimus block calcineurin and T-cell activation.

Pharmacokinetics. Drops reach the anterior chamber through the cornea; acetate and alcohol forms penetrate better than phosphate. Systemic absorption is small. Corticosteroid suspensions need shaking before use.

• Corticosteroids: prednisolone acetate 1 percent and difluprednate 0.05 percent (potent; uveitis, post-operative); dexamethasone 0.1 percent (potent); loteprednol 0.5 percent and fluorometholone 0.1 percent (less pressure effect, weaker).
• NSAIDs: ketorolac 0.5 percent, diclofenac 0.1 percent, nepafenac 0.1 or 0.3 percent, bromfenac 0.09 percent; for post-operative inflammation, cystoid macular oedema prevention, and pain after surface surgery.
• Mast cell stabilisers and dual agents: sodium cromoglicate 2 percent, olopatadine 0.1 to 0.2 percent, ketotifen 0.025 percent, azelastine 0.05 percent; for allergic conjunctivitis.
• Calcineurin inhibitors: ciclosporin 0.05 to 0.1 percent drops and tacrolimus 0.03 to 0.1 percent ointment; for vernal and atopic keratoconjunctivitis and dry eye.

Regimens.

• Anterior uveitis: prednisolone acetate 1 percent every 1 to 2 hours while awake in severe disease, tapering over 4 to 8 weeks as inflammation clears, with a cycloplegic.
• After cataract surgery: prednisolone acetate 1 percent or dexamethasone 0.1 percent four times daily, tapering over 3 to 4 weeks; add an NSAID once daily to four times daily in patients with diabetes or risk of macular oedema.
• Allergic conjunctivitis: olopatadine 0.1 percent twice daily or ketotifen twice daily, with cold compresses and lubricants; short course of low-potency steroid for flares.
• Vernal keratoconjunctivitis: dual-action drops plus ciclosporin 0.05 to 0.1 percent four times daily or tacrolimus 0.1 percent ointment twice daily; pulses of potent steroid for exacerbations and shield ulcers.
• Episcleritis and mild non-infectious inflammation: lubricants, with a weak steroid or NSAID for a short course.
• Do not prescribe steroid drops for an undiagnosed red eye. Stain the cornea with fluorescein before starting.

Selection. Use the weakest steroid that controls inflammation, for the shortest time; taper rather than stop abruptly to prevent rebound. NSAIDs avoid pressure rise and cataract but do not control severe uveitis. For chronic surface inflammation, use ciclosporin or tacrolimus to spare steroids.

Contraindications. Corticosteroids: untreated bacterial, fungal, viral (herpes simplex epithelial) and acanthamoeba infection, corneal epithelial defect, tuberculosis of the eye; NSAIDs: aspirin and NSAID hypersensitivity, corneal thinning.

Effects. Corticosteroids: raised intraocular pressure (steroid responders, in 5 percent strongly and about 30 percent moderately; children and relatives of people with glaucoma at risk), posterior subcapsular cataract, worsening of herpes simplex, bacterial and fungal keratitis, delayed wound healing, corneal thinning and perforation, ptosis and mydriasis. NSAIDs: stinging, punctate keratitis, delayed epithelial healing, corneal melt with prolonged use. Antihistamines: stinging and dry eye. Calcineurin inhibitors: burning, transient redness.

Interactions. Topical steroids with CYP3A4 inhibitors have little systemic effect. Combining a topical NSAID and steroid in the presence of corneal thinning increases melt risk.

Monitoring. Check pressure, lens and cornea at 2 to 4 weeks when steroids exceed 2 weeks, and every 3 months in prolonged use; arrange early review in children; stop steroid and treat infection if the corneal epithelium breaks down.

Special groups.

• Pregnancy: topical steroids acceptable with occlusion of the tear duct; avoid NSAIDs in late pregnancy.
• Children: steroids raise pressure quickly and cataract risk is higher; use under specialist care.
• Region: vernal keratoconjunctivitis is common in East African children and teenagers and responds poorly to short courses; chronic use of over-the-counter steroid-containing eye drops and the use of herbal preparations for red eye cause steroid glaucoma, cataract and corneal infection; counsel families and limit steroid supply to supervised courses.