5 · Factors delaying or impairing healing
Topical NSAIDs — epithelial delay & melting risk
Review — modulators of corneal healing › 5 · Factors delaying or impairing healing › Topical NSAIDs — epithelial delay & melting risk
Topical NSAIDs — epithelial delay & melting risk
Ketorolac 0,4/0,5 %, diclofenac 0,1 %, bromfenac, nepafenac, flurbiprofen
Oxford I–III
Negative · Strong
Present · FDA warning
MechanismCOX inhibition → ↓prostaglandins (analgesia, ↓macular edema). However, COX products (e.g., 12-HHT via the BLT2 receptor) are required for epithelial migration → NSAIDs delay re-epithelialization; loss of prostaglandin-mediated cytoprotection combined with unchecked MMP/collagenase activity can precipitate sterile stromal melting, ulceration, and perforation (classically generic diclofenac; dry/rheumatoid/diabetic/postoperative corneas, combination with corticosteroids).
ContextAnalgesia after cataract/refractive surgery, prophylaxis of cystoid macular edema, allergic inflammation — used with caution and for a limited duration on a healing epithelium. Avoid in the presence of an epithelial defect, dry eye, connective tissue disease, or neurotrophic cornea.
Route & dosageTopical 2–4×/day; limited duration (typically ≤3–4 days after PRK) to reduce melting risk.
Level of evidenceOxford II–III (melting: large series/pharmacovigilance data, FDA warnings); I–II experimental (delay) · Scale: Strong.
| FDA / EU MA | Approved with an explicit warning (keratitis, thinning, erosion, ulceration, perforation). Generics available worldwide. The reformulation of generic diclofenac (Falcon) caused the historic melting cluster. |
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Key studies: Gabison EE, Chastang P, Menashi S, Mourah S, Doan S, Oster M, Mauviel A, Hoang-Xuan T. "Late corneal perforation after photorefractive keratectomy associated with topical diclofenac: involvement of matrix metalloproteinases," Ophthalmology 2003;110(8):1626-31 — PMID 12917183 (demonstrating the involvement of MMPs in diclofenac-induced melting); Congdon/Flynn et al., Ophthalmology 2001; delay via ↓12-HHT/BLT2 (Sci Rep 2017) — PMID 29038497; FDA Acular (ketorolac) prescribing information.
See also: Gabison E. “Corneal wound-healing agents”. In: SFO 2023 Report — Médicaments et biothérapies en ophtalmologie, chapter 21. Full text, open access (in French).