Update: Do ophthalmic nonsteroidal anti-inflammatory drugs reduce the pain associated with simple corneal abrasion without delaying healing?☆

In 1999, Brown et al1 published an evidence-based emergency medicine (EBEM) review of the efficacy of ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) to reduce the pain associated with simple corneal abrasions. We performed an updated review on this topic using the methods described by the original authors.

We searched MEDLINE, using the Ovid interface, between January 1, 1999, and April 2002 using the search strategy and selection criteria previously described.1 We identified 4 randomized controlled trials2, 3, 4, 5 that were not considered in the original review but that fulfilled the authors' inclusion criteria (Figure).

We also screened the bibliographies of the 4 articles and found no additional relevant studies.

We searched the Cochrane Database of Systematic Reviews on the Ovid search engine for systematic reviews evaluating ophthalmic NSAIDs in the treatment of corneal abrasions. Our search terms were “cornea or eye injuries or ophthalmic NSAID,” which identified 11 articles, none of which were relevant. The same search on the Cochrane DSR, ACP Journal Club, and DARE database was also negative. On searching the Cochrane Controlled Trials Registry, we identified 4 of the 5 studies included in this review using the single search term “corneal abrasions.” The study by Alberti et al2 was not identified.

Patrone et al4 studied the use of indomethacin 0.1% NSAID drops in patients with traumatic corneal abrasions. Patients were randomized to treatment either with or without indomethacin. Neither investigators nor research subjects were masked to treatment allocation. Among the cointerventions, the investigators included the use of soft contact lenses for 24 hours in all patients. Because of the use of contact lenses as a cointervention, we excluded this study from further review. A total of 5 studies therefore meet the inclusion criteria of the original review1; they are summarized in the Table.2, 3, 5, 6, 7

Alberti et al2 studied the use of an ophthalmic solution containing a fixed combination of indomethacin 0.1% and gentamicin sulfate compared with gentamicin sulfate alone in 123 patients with traumatic corneal abrasions. Patients were randomized, and the study was double-masked. The participants completed a visual analog scale (VAS) at 5 intervals during the 4- to 5-day study period. Although control subjects on average had deeper corneal abrasions and reported a higher global score for associated symptoms, the 2 groups had similar baseline pain scores. Eye patching was allowed if pain was “unbearable.” Research subjects were given either indomethacin 0.1% combined with gentamicin eyedrops or gentamicin eyedrops alone, which they were instructed to instill 4 times a day for 5 to 6 days. Of the initial 123 patients, 111 were followed up to completion. The investigators found a statistically significant pain reduction at all measured times in the indomethacin group. At 1 hour posttreatment, patients receiving indomethacin had a mean pain intensity reduction (P =.007 for comparison between the 2 groups). There was no statistically significant difference in associated symptoms or in the number of patients taking supplemental analgesics. Four patients in each group took paracetamol for pain rescue. There was no difference in time to healing. Four adverse events led to treatment discontinuation, 3 in the study group and 1 in the control group.

Goyal et al3 studied the use of ketorolac trometanol 0.5% NSAID solution in 85 patients with traumatic corneal abrasions or foreign body removal compared with placebo artificial tears (Liquifilm). The practice setting is poorly described, and the applicability of the results to emergency care settings is potentially open to question. Patients were randomized to treatment groups in this double-masked study and were followed up daily until healing was complete. All patients were asked at presentation to complete a questionnaire that included a somewhat atypical VAS of 0 to 5 (0 being no symptoms, 5 being worst symptoms). The authors provided no further details regarding the measurement instrument. Of an initial 88 patients, 3 were ultimately excluded from the study. The groups were similar at the beginning of the trial. Patients were released with a masked bottle of either ketorolac trometanol 0.5% or placebo, which they were instructed to instill 4 times a day until the abrasion healed. Cointerventions administered to both groups included cycloplegics (cyclopentolate 0.5%) at the initial visit and chloramphenicol eye ointment 4 times daily for 24 hours. Oral analgesics were permitted, and the amounts were reported. Patients receiving ketorolac had a clinically and statistically insignificant pain reduction at 24 hours compared with patients in the control group (P =.76 for comparison between the 2 groups). There was no statistically significant difference in associated symptoms. However, there was an important decrease in the number of patients receiving ketorolac using supplemental oral analgesics. There was no difference in the rate of healing in either group, and no patients in either group had adverse events at 24 hours.

Szucs et al5 compared diclofenac 0.1% ophthalmic NSAID solution to a control vehicle (Natural Tears) in 49 patients with corneal abrasion. The treatment assignment was randomized, and the study drugs were double-masked. Baseline characteristics of the 2 groups were similar. In the emergency department, patients were treated with a topical anesthetic (proparacaine hydrochloride 0.5% solution), 2 drops of a topical antibiotic (gentamicin 0.3% solution), and either diclofenac or the control vehicle. Some patients also received 1 drop of a cycloplegic (cyclopentolate) at the discretion of the treating physician. Patients were discharged with a masked bottle of either diclofenac or the control vehicle (Natural Tears), with instructions to instill 1 drop every 6 hours while awake for 24 to 36 hours. Patients also received a bottle of topical gentamycin with instructions to instill 2 drops every 2 hours while awake for 24 hours. All patients were given rescue analgesics in the form of 3 tablets containing 5 mg of oxycodone and 325 mg of acetaminophen, in addition to a prescription for 10 more tablets. One control subject had incomplete follow-up. Patients completed a pain diary that reported the amount of rescue medication taken, as well as Numeric Pain Intensity Scale scores and were followed up to study completion. The authors reported a significantly greater improvement in the 2-hour mean Numeric Pain Intensity Scale score in the diclofenac group compared with the control group (P =.002). Patients in the diclofenac group were only half as likely to take oxycodone-acetaminophen rescue medication (20% versus 42%), although the 95% confidence interval (CI) for the difference includes the possibility of greater use in the diclofenac group. There were no adverse events noted other than transient mild stinging.

These 3 randomized trials, combined with the 2 trials included in the original review of ophthalmic NSAIDs, support the use of these agents as analgesics for acute corneal abrasion. All 5 trials were randomized and double-blinded, and except for the study by Alberti et al,2 in which patients in the control group had more severe abrasions and a higher global score for associated symptoms, the groups were well balanced at the start of the trial. Follow-up rates ranged from 88% to 100% and were more than 90% in all but 1 study. Cointerventions were variable but were equally administered in the individual trials.

Important differences among these studies in both the timing and means of assessing pain reduction in treatment and control groups render a statistical pooling of their results inappropriate. It is therefore necessary for the clinician to settle for a qualitative summary of the evidence to date. All 5 studies reported a reduction in pain intensity of variable clinical and statistical significance compared with controls in patients treated with ophthalmic NSAIDs. As noted in the original review,1 a change of 1.3 cm on a 10-cm VAS has been empirically perceived by patients to be a clinically important difference. Three of the 5 studies of ophthalmic NSAIDs2, 5, 6 reported complete data on pain reduction measured by means of a 10-cm VAS at least one point in time after administration of the study drug. Of these, only 25, 6 report a difference between the study groups of this magnitude or larger and in neither case did the 95% CI around the difference exclude a value below this threshold. Fewer patients in the treatment group reported subjective symptoms in 2 of the studies.6, 7 One study reported significantly earlier return to work.6 Two of the 3 studies that reported analgesic use3, 5 observed a decrease in the use of supplemental analgesia. No study identified a change in time to healing, and no serious adverse events or serious infections occurred in the treatment groups.

Although these data support the use of ophthalmic NSAIDs in the treatment of pain from corneal abrasion injuries, the results of these trials must be translated to the individual patient in a given practice locale. Ophthalmic NSAIDs have not been compared with oral opioids alone or to oral NSAIDs. In addition, ophthalmic NSAIDs are more expensive than these alternative oral analgesics. In clinical practice, the evidence gained from clinical trials must be placed in the context of clinician experience. The clinician must also consider a patient's values, preferences, and rights. Can the patient afford an ophthalmic NSAID? Is there a compelling reason to prescribe NSAID eye drops over an oral analgesic? Does the patient need to return to work immediately? Patients who can afford the medication, must return to work immediately, and for whom potential opioid-induced sedation is intolerable are the most likely candidates for the administration of ophthalmic NSAIDs during the first 24 hours after a traumatic corneal abrasion.