Topical non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain in traumatic corneal abrasions

What is the aim of this review?
The aim of this Cochrane Review was to find out if topical (applied directly to the surface of the eye) non-steroidal anti-inflammatory drugs (NSAIDs) for traumatic corneal abrasions reduce pain. Cochrane researchers collected and analysed all relevant studies to answer this question. We found nine studies.

Key messages
It is unclear if using topical NSAIDs is helpful in traumatic corneal abrasions. Topical NSAIDs cost more to use than alternative treatments such as oral pain-killing tablets.

What was studied in the review?
A corneal abrasion is a scratch on the cornea of the eye. The cornea is the clear window that is in front of the iris, which is the coloured part of the eye. The cornea is important both for vision and for protecting the eye. When a corneal abrasion occurs, it causes significant pain and discomfort. A traumatic corneal abrasion is a corneal abrasion caused by an injury, such as the eye being poked or something like dirt or sand being trapped under the eyelid and scratching the cornea.

NSAIDs are one form of pain management for people with corneal abrasions.They may reduce the pain.

What are the main results of the review?
The Cochrane researchers found nine relevant studies. Three studies each were from the UK and the USA, one from Italy, one from Israel and one from France/Portugal. These studies used five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac). The studies compared the topical NSAIDs with antibiotic eye drops, artificial tears, eye patching and dummy (placebo) eye drops. Three of the studies were funded by the manufacturer while the other six studies did not report their funding source.

The results of the review show that:
∙ It is unclear if people treated with topical NSAIDs experience a clinically meaningful reduction in pain compared with people being treated with placebo or standard care (antibiotic eye drops, artificial tears, eye patching) but they may use less oral pain killers.

∙ Where drug-related side effects, and complications of corneal abrasion (e.g. poor healing or infection) were reported (in two trials), the numbers were low.

How up-to-date is this review?
Cochrane researchers searched for studies that had been published up to March 2017.

Authors' conclusions: 

The findings of the included studies do not provide strong evidence to support the use of topical NSAIDs in traumatic corneal abrasions. This is important, since NSAIDs are associated with a higher cost compared to oral analgesics. None of the trials addressed our primary outcome measure of participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours.

Read the full abstract...
Background: 

Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the clinical efficacy and safety profile of topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal abrasions.

Objectives: 

To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017), Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March 2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 30 March 2017. We did not use any date or language restrictions in the electronic searches for trials.We checked the reference lists of identified trials to search for further potentially relevant studies.

Selection criteria: 

RCTs comparing topical NSAIDs to placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions.

Data collection and analysis: 

Two review authors independently performed data extraction and assessed risks of bias in the included studies. We rated the certainty of the evidence using GRADE.

Main results: 

We included nine studies that met the inclusion criteria, reporting data on 637 participants.The studies took place in the UK, USA, Israel, Italy, France and Portugal. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of ‘rescue’ analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours.

One trial (28 participants) reported on the proportion of abrasions healed after 24 and 48 hours. These outcomes were similar in both arms of the trial. (at 24 hours RR 1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence). In the control group nine out of 10 abrasions were healed within 24 hours and all were healed by 48 hours. Complications of corneal abrasions were reported in 6 studies (609 participants) and were infrequently reported (4 complications, 1 in NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible drug-related adverse events (AEs) were reported in two trials (163 participants), with the number of adverse events low (4 AEs, 3 in NSAID group, including discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria, and 1 in the control group, corneal abscess) very low-certainty evidence.