The effects of the topical administration of non-steroidal anti-inflammatory drugs on corneal epithelium and corneal sensitivity in normal subjects.
OBJECTIVE
To study the changes in the corneal epithelium and corneal sensitivity of healthy subjects after the topical administration of non-steroidal anti-inflammatory drugs (NSAIDs; diclofenac, indomethacin, flurbiprofen and ketorolac) frequently used in ocular therapy.


METHODS
A double-masked parallel clinical study was undertaken on 90 subjects (45 men, 45 women; Caucasian; age 21-46 years, mean +/- SD 27.1 +/- 5 years). The subjects were divided into six groups: group 1 was treated with placebo, group 2 with 0.1% diclofenac, group 3 with 0.1% indomethacin, group 4 with 0.03% flurbiprofen, group 5 with 0.5% ketorolac and group 6 with 0.4% oxybuprocaine. One eye was randomly treated with the study drug and the fellow eye was treated with placebo. The medications were instilled four times, at 5 min intervals. Assessment of the corneal epithelium was carried out by vital fluorescein stain before instillation and 5, 15, 30 and 60 min after instillation of the last drop. Subjective burning sensation was assessed by asking participants to rate burning on a scale from 0 (none) to 3 (severe). After 1 week, assessment of corneal sensitivity was carried out by the Cochet-Bonnet method, repeating the above scheme of instillation and measurement times.


RESULTS
None of the study drugs, with the exception of oxybuprocaine, produced evident epithelial damage. All the drugs caused a mean burning sensation greater than the placebo. The diclofenac-treated group showed a statistically significant decrease in corneal sensitivity (p < 0.001) at the measurement carried out 15 min after instillation of the last drop and lasting up to the end of the study, when the corneal anaesthesia was similar to that induced by the topical anaesthetic treatment. No significant changes were demonstrated for the other NSAIDs when compared either with the placebo-treated eyes or with the fellow eyes.


CONCLUSIONS
Despite a similar mechanism of action and analgesic activity to the other NSAIDs tested, diclofenac was able to induce a reduction in corneal sensitivity. More studies are needed to determine the mechanism of action responsible for this effect.
Aragona
P
P
Institute of Ophthalmology, University of Messina, Italy. p.aragona@eniware.it
Tripodi
G
G
Spinella
R
R
Laganà
E
E
Ferreri
G
G
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D003316:Corneal Diseases / Q000139:chemically induced*; D004008:Diclofenac / Q000494:pharmacology; D004311:Double-Blind Method; D019573:Epithelium, Corneal / Q000187:drug effects*; D005260:Female; D005480:Flurbiprofen / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D020910:Ketorolac / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010292:Paresthesia / Q000139:chemically induced*; D011343:Procaine / Q000031:analogs & derivatives / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D011343:Procaine; D005480:Flurbiprofen; C005298:benoxinate; D007213:Indomethacin; D020910:Ketorolac