Topical ophthalmic anesthetics for corneal abrasions

Despite potential analgesic benefits from topical ophthalmic amides and esters, their outpatient use has become of concern because of the potential for abuse and ophthalmic complications.

To assess the effectiveness and safety of topical ophthalmic anesthetics compared with placebo or other treatments in persons with corneal abrasions.

We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase.com; Latin American and Caribbean Health Sciences (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), without restriction on language or year of publication. The search was performed on 10 February 2023.

We included randomized controlled trials (RCTs) of topical ophthalmic anesthetics alone or in combination with another treatment (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs)) versus a non-anesthetic control group (e.g. placebo, non-treatment, or alternative treatment). We included trials that enrolled participants of all ages who had corneal abrasions within 48 hours of presentation.

We used standard Cochrane methodology.

We included nine parallel-group RCTs with a total of 556 participants (median number of participants per study: 45, interquartile range (IQR) 44 to 74), conducted in eight countries: Australia, Canada, France, South Korea, Turkey, New Zealand, UK, and USA. Study characteristics and risk of bias Four RCTs (314 participants) investigated post-traumatic corneal abrasions diagnosed in the emergency department setting. Five trials described 242 participants from ophthalmology surgery centers with post-surgical corneal defects: four from photorefractive keratectomy (PRK) and one from pterygium surgery. Study duration ranged from two days to six months, the most common being one week (four RCTs). Treatment duration ranged from three hours to one week (nine RCTs); the majority were between 24 and 48 hours (five RCTs). The age of participants was reported in eight studies, ranging from 17 to 74 years of age. Only one participant in one trial was under 18 years of age. Of four studies that reported funding sources, none was industry-sponsored. We judged a high risk of bias in one trial with respect to the outcome pain control by 48 hours, and in five of seven trials with respect to the outcome complications at the furthest time point. The domain for which we assessed studies to be at the highest risk of bias was missing or selective reporting of outcome data. Findings The treatments investigated included topical anesthetics compared with placebo, topical anesthetic compared with NSAID (post-surgical cases), and topical anesthetics plus NSAID compared with placebo (post-surgical cases). Pain control by 24 hours In all studies, self-reported pain outcomes were on a 10-point scale, where lower numbers represent less pain. In post-surgical trials, topical anesthetics provided a moderate reduction in self-reported pain at 24 hours compared with placebo of 1.28 points on a 10-point scale (mean difference (MD) -1.28, 95% confidence interval (CI) -1.76 to -0.80; 3 RCTs, 119 participants). In the post-trauma participants, there may be little or no difference in effect (MD -0.04, 95% CI -0.10 to 0.02; 1 RCT, 76 participants). Compared with NSAID in post-surgical participants, topical anesthetics resulted in a slight increase in pain at 24 hours (MD 0.82, 95% CI 0.01 to 1.63; 1 RCT, 74 participants). One RCT compared topical anesthetics plus NSAID to placebo. There may be a large reduction in pain at 24 hours with topical anesthetics plus NSAID in post-surgical participants, but the evidence to support this large effect is very uncertain (MD -5.72, 95% CI -7.35 to -4.09; 1 RCT, 30 participants; very low-certainty evidence). Pain control by 48 hours Compared with placebo, topical anesthetics reduced post-trauma pain substantially by 48 hours (MD -5.68, 95% CI -6.38 to -4.98; 1 RCT, 111 participants) but had little to no effect on post-surgical pain (MD 0.41, 95% CI -0.45 to 1.27; 1 RCT, 44 participants), although the evidence is very uncertain. Pain control by 72 hours One post-surgical RCT showed little or no effect of topical anesthetics compared with placebo by 72 hours (MD 0.49, 95% CI -0.06 to 1.04; 44 participants; very low-certainty evidence). Proportion of participants with unresolved epithelial defects When compared with placebo or NSAID, topical anesthetics increased the number of participants without complete resolution of defects in trials of post-trauma participants (risk ratio (RR) 1.37, 95% CI 0.78 to 2.42; 3 RCTs, 221 participants; very low-certainty evidence). The proportion of placebo-treated post-surgical participants with unresolved epithelial defects at 24 to 72 hours was lower when compared with those assigned to topical anesthetics (RR 0.14, 95% CI 0.01 to 2.55; 1 RCT, 30 participants; very low-certainty evidence) or topical anesthetics plus NSAID (RR 0.33, 95% CI 0.04 to 2.85; 1 RCT, 30 participants; very low-certainty evidence). Proportion of participants with complications at the longest follow-up When compared with placebo or NSAID, topical anesthetics resulted in a higher proportion of post-trauma participants with complications at up to two weeks (RR 1.13, 95% CI 0.23 to 5.46; 3 RCTs, 242 participants) and post-surgical participants with complications at up to one week (RR 7.00, 95% CI 0.38 to 128.02; 1 RCT, 44 participants). When topical anesthetic plus NSAID was compared with placebo, no complications were reported in either treatment arm up to one week post-surgery (risk difference (RD) 0.00, 95% CI -0.12 to 0.12; 1 RCT, 30 participants). The evidence is very uncertain for safety outcomes. Quality of life None of the included trials assessed quality of life outcomes.

Despite topical anesthetics providing excellent pain control in the intraoperative setting, the currently available evidence provides little or no certainty about their efficacy for reducing ocular pain in the initial 24 to 72 hours after a corneal abrasion, whether from unintentional trauma or surgery. We have very low confidence in this evidence as a basis to recommend topical anesthetics as an efficacious treatment modality to relieve pain from corneal abrasions. We also found no evidence of a substantial effect on epithelial healing up to 72 hours or a reduction in ocular complications when we compared anesthetics alone or with NSAIDs versus placebo.