NSAID Keratopathy: Corneal Melt From Eye Drops

NSAID keratopathy is damage to the cornea caused by topical nonsteroidal anti-inflammatory drops.

These drops are widely used after cataract surgery to prevent macular edema, and they are safe in most eyes.

In a small number of susceptible eyes, they cause epithelial defects, stromal melting, and even perforation.

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How NSAID Keratopathy Develops

NSAID drops block cyclooxygenase, which reduces prostaglandins and inflammation.

They also lower corneal sensation, slow epithelial healing, and may increase the activity of matrix metalloproteinases, which break down the stroma (see the references).

Together, these effects can turn a small defect into a melt in an eye that is also already at risk.

NSAID Keratopathy: Who Is at Risk?

• Eyes with dry eye disease and a fragile surface
• Patients with diabetes, especially with neuropathy and poor corneal sensation
• Rheumatoid arthritis and other autoimmune diseases that affect the cornea (see corneal melt in collagen vascular disease)
• Previous herpetic keratitis and neurotrophic cornea (see neurotrophic keratitis)
• Eyes with existing epithelial defects, or after multiple surgeries
• Use of NSAIDs for long periods, beyond the usual few weeks, or at high frequency
• Concurrent use of topical steroids and preserved drops

Reports describe melts with diclofenac, ketorolac, nepafenac, and bromfenac (see the references).

Clinical Course

• Early signs: punctate keratopathy and a decrease in comfort or tear stability
• Progression to epithelial defects, with a gray rim, in the central or paracentral cornea
• Stromal thinning, infiltration, and a sterile ulcer
• Perforation, in advanced cases

Pain may be less than expected because the cornea is less sensitive.

Infection may be mimicked or may follow, so take cultures when there is doubt (see stromal corneal ulcers).

Differential Diagnosis of NSAID Keratopathy

• Infectious keratitis, including herpes and fungus
• Toxic keratopathy from preservatives or other drops (see toxic epitheliopathy)
• Dry eye with exposure
• Corneal melt from systemic disease
• Persistent epithelial defect from another cause (see persistent epithelial defect)

A clear history of NSAID use, with a timeline, makes the diagnosis likely.

Management for NSAID Keratopathy

• Stop the NSAID drop at once, and review the other medications
• Use preservative-free lubricants and ointment, frequently
• Add a bandage lens or other protection (see bandage contact lens)
• Use a prophylactic antibiotic if there is an epithelial defect
• Consider autologous serum for slow healing
• Use a low-dose steroid carefully, if inflammation is present, once infection is excluded
• Perform glue, patch, or graft for perforation or impending perforation

Most defects heal after the drug is stopped, though scars may remain.

Prevention for NSAID Keratopathy

• Screen patients before prescribing, and avoid or limit NSAIDs in high-risk eyes (see NSAIDs for macular edema)
• Use the shortest effective course, and the lowest frequency
• Examine the cornea at each postoperative visit, and stop the drug at the first sign of epithelial problems
• Treat dry eye before surgery
• Educate patients about symptoms

Counselling

Explain that the drugs are helpful for most patients, but that the cornea needs watching.

Tell them to report increasing pain, redness, or blurred vision, and not to continue drops if the eye is worse.

A Typical Case

A 70-year-old woman with rheumatoid arthritis and dry eye has cataract surgery and is given a topical NSAID four times daily for six weeks, plus a steroid.

At week five she complains of foreign body sensation, and examination shows a central epithelial defect with a gray rim and mild thinning.

The team stops the NSAID and starts preservative-free lubricants and a bandage lens, and the defect heals over two weeks, with a small residual haze.

Choosing Alternatives

• For macular edema prophylaxis in patients at risk of surface problems, consider a shorter NSAID course, or a single daily dose, with close review
• Use a steroid alone when the risk of macular edema is low
• Use an intravitreal or sub-Tenon steroid in high-risk diabetic patients, where appropriate (see intravitreal triamcinolone)
• Apply dropless techniques to avoid exposure to preserved drops

Reporting

Report cases to the manufacturer and the regulator, since data on rare events come from these reports, and share the experience with colleagues.

Related Conditions

Preservatives in drops, such as benzalkonium chloride, can add to the damage, and so can a combined use of several drugs (see keratitis medicamentosa).

Also, always review the full list of drops that the patient is using, and simplify the regimen where possible.

When to Resume an NSAID

If macular edema develops after the surface heals, the drug can be restarted in a limited course, with weekly checks of the epithelium, or another route of treatment can be chosen, such as a sub-Tenon steroid.

Document the previous reaction in the chart and in the patient’s records, so that the information is available to other surgeons.

Patients who have had a melt should be flagged as high risk before any later eye surgery.

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References

1. Guidera AC, Luchs JI, Udell IJ. Keratitis, ulceration, and perforation associated with topical nonsteroidal anti-inflammatory drugs. Ophthalmology. 2001;108:936-944.
2. Flach AJ. Corneal melts associated with topically applied nonsteroidal anti-inflammatory drugs. Trans Am Ophthalmol Soc. 2001;99:205-210.
3. Gaynes BI, Fiscella R. Topical nonsteroidal anti-inflammatory drugs for ophthalmic use: a safety review. Drug Saf. 2002;25:233-250.
4. American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8: External Disease and Cornea. AAO; current edition.