This review assessed the effectiveness of topical treatments for seasonal allergic conjunctivitis. The authors concluded that topical mast cell stabilisers and topical antihistamines are superior to placebo, but there is insufficient evidence for the superiority of one type of medication. The authors' conclusions appear to be supported by the evidence presented, but many studies were short term and there was evidence of publication bias.

To assess the effectiveness of topical treatments for seasonal allergic conjunctivitis and to compare different treatments.

The Cochrane Eyes and Vision Group Trials Register (contained within the CENTRAL Register, the Cochrane Library, Issue 2, 2001), MEDLINE (from 1966 to 2001) and EMBASE (from 1980 to 2001) were searched in August 2001; the search strategy was reported. The reference lists of relevant reports were checked.

Study designs of evaluations included in the review

Double-blind randomised controlled trials (RCTs) were eligible for inclusion if they met minimum quality criteria (see below). Crossover trials were only included if there was a suitable washout period between treatment. Where reported, the duration of the studies ranged from 20 minutes to 4 months.

Specific interventions included in the review

Studies that compared topical mast cell stabilisers or topical antihistamines with placebo, or topical mast cell stabilisers with topical antihistamines, were eligible for inclusion. In the included studies, the topical mast cell stabilisers were sodium chromoglycate, nedocromil and lodoxamide, while the topical antihistamines were levocabastine, azelastine and emedastine. The included studies were conducted at different times of the year.

Participants included in the review

Studies of participants with seasonal allergic conjunctivitis were eligible for inclusion. The included studies were of children and adults.

Outcomes assessed in the review

Only studies that subjectively assessed treatment efficacy were eligible for inclusion. The review assessed symptom scores, the patients' perceived benefit from treatment and side-effects. The included studies assessed symptoms on ordinal scales or visual analogue scales. Some studies assessed outcomes in response to provocative agents.

How were decisions on the relevance of primary studies made?

One reviewer selected the studies.

Only trials with concealed allocation of treatment and documented inclusion criteria for the participants were eligible. Validity was assessed, but the authors did not state who performed the validity assessment.

Two reviewers independently extracted the data using a standard data extraction form.

Where data allowed, the odds ratios (ORs) and 95% confidence intervals (CIs) of perceived benefit were calculated for each study. Where possible, analyses were based on intention-to-treat data.

How were the studies combined?

The studies were grouped by intervention and combined in meta-analyses where possible. Pooled ORs and 95% CIs were calculated using a fixed-effect method in the absence of significant heterogeneity and a random-effects model when significant heterogeneity was found. Publication bias was assessed using funnel plots, the Egger test and the Begg test.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the chi-squared statistic. Treatment effects for individual topical mast cell stabilisers and topical antihistamines were analysed and discussed.

Forty RCTs were included. The number of participants was not reported for all of the included studies.

No trials were identified that directly compared the use of one mast cell stabiliser with another.

Topical mast stabilisers versus placebo (12 RCTs). The random-effects meta-analysis showed that topical mast cell stabilisers significantly increased the proportion of patients perceiving benefit compared with placebo (OR 4.9, 95% CI: 2.5, 9.6). Statistically significant heterogeneity was detected (P<0.001). Marked evidence for publication bias was found (Egger test, P<0.001; Begg test, P=0.005).

Sodium chromoglycate versus placebo (17 RCTs).

Five of the 8 studies reporting subjective symptoms reported improvements with sodium chromoglycate; the other 3 RCTs found no difference between treatments. A random-effects meta-analysis of 6 RCTs (n=316) found that sodium chromoglycate significantly increased the proportion of patients perceiving benefit compared with placebo (OR 17.2, 95% CI: 3.8, 78.4). Statistically significant heterogeneity was detected (P<0.001). Some evidence for publication bias was found (Egger test, P=0.02; Begg test, P=0.45). No important side-effects with the active treatment were reported.

Nedocromil sodium versus placebo (5 RCTs).

All 5 RCTs found that nedocromil reduced subjective symptoms in comparison with placebo; in 3 RCTs the difference was statistically significant. A fixed-effect meta-analysis of 5 RCTs (n=556) found that nedocromil significantly increased the proportion of patients reporting the allergy as moderately or totally controlled compared with placebo (OR 1.8, 95% CI: 1.3, 2.6). No statistically significant heterogeneity was detected for this outcome (P=0.27). Tests for publication bias were not statistically significant. Apart from an unpleasant taste, no important side-effects were reported.

Lodoxamide versus placebo (1 RCT assessing control of symptoms and 3 RCTs assessing response to provocative tests).

The only RCT (n=27) assessing symptom control found that lodoxamide significantly reduced subjective symptoms in comparison with placebo (P<0.002). Three other RCTs found lodoxamide improved short-term symptoms in response to provocation when compared with placebo.

Topical antihistamines versus placebo (9 RCTs).

The majority of studies did not report adequate data to allow an assessment of the benefit from treatment. Most of the studies found that antihistamines improved symptoms after provocation tests and improved allergic conjunctivitis when compared with placebo. There was no evidence to support the use of one type of topical antihistamine over another.

Topical mast cell stabilisers versus topical antihistamines (8 RCTs).

The majority of studies did not report mean outcome scores and errors. All 6 longer term RCTs (duration: 14 days to 4 months) found no statistically significant difference in outcome scores between treatments. A fixed-effect meta-analysis of 4 RCTs (n=325) found no statistically significant difference between levocabastine and mast cell stabilisers in the proportion of patients perceiving 'excellent' or 'good' treatment outcomes (OR 1.3, 95% CI: 0.8, 2.2). Tests for publication bias were not statistically significant. No side-effects were reported for topical antihistamines.

Topical mast cell stabilisers and topical antihistamines were more effective than placebo for allergic conjunctivitis. There was insufficient evidence to draw conclusions about the relative efficacy of treatment.

The review question was clear in terms of the study design, participants and interventions. The inclusion criteria for outcomes were broadly defined, and the time period considered suitable for adequate washout in crossover studies was not specified. Some attempts were made to minimise publication bias and the possibility of publication bias was assessed. It was unclear whether any language limitations had been applied. Only one reviewer selected the studies and this lack of duplication might have led to errors and bias. Methods were used to minimise bias in the data extraction process but, since the methods used to assess validity were not described, any efforts made to reduce errors and bias cannot be judged. Validity was assessed, although there were some limitations in the criteria used.

Where data permitted, the studies were combined in meta-analyses and statistical heterogeneity was assessed. Meta-analysis graphs showed similar directions of treatment effects for the studies included in one meta-analysis, with significant heterogeneity, but potential reasons for differences in the effect size were not explored. The authors' conclusions regarding topical mast stabilisers versus placebo and mast stabilisers versus topical antihistamines appear to be supported by the evidence presented in the review. Supplementary tables on the British Journal of General Practice website (subscription needed for access) provided evidence for the conclusion for topical antihistamines versus placebo. However, many studies were short term and there was evidence for publication bias; this limits the strength of the evidence.

Practice: The authors stated that the choice of treatment should be based on convenience of use, patient preference and costs. They also stated that prolonged use of medications using antihistamine (antazoline) in combination with a vasoconstrictor (naphazoline) should be avoided since it can cause reactive hyperaemia.

Research: The authors stated that larger trials using standardised methods and standardised presentation of results to compare different topical treatments are required.

Wormald R, Smeeth L, Henshaw K, editors. Evidence based ophthalmology. London: BMJ Books; 2004.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.