Methodological quality of the review: Medium confidence

Author: Honrubia F, Garcia-Sanchez J, Martinez de la Casa JM, Soto J

Geographical coverage: Not reported

Sector: Ocular hypertension, glaucoma

Sub-sector: Conjunctival hyperemia, latanoprost, travoprost, bimatropost.

Equity focus: Patients with ocular hypertension or glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: For patients with ocular hypertension or open-angle glaucoma, drug therapy focuses on reducing intra-ocular pressure (IOP) levels to delay or prevent the progression of ocular hypertension to glaucoma, and to slow disease progression in glaucoma patients. First-line treatment usually consists of monotherapy with a topical hypotensive drug. Although ophthalmologists traditionally have prescribed beta-blockers as first-line ocular hypotensive therapy, due to the possibility of producing systematic side effects, other therapeutic options are preferred, with prostaglandin analogues being one of the most widely used. Topical prostaglandins such as latanoprost, bimatoprost and travoprost are similar in that they require once-daily instillation, produce few systematic side effects and reduce IOP levels similarly.

Objectives: To evaluate the development of conjunctival hyperemia after the use of latanoprost versus travoprost and bimatoprost, in patients with ocular hypertension or glaucoma

Main findings: In total, 13 randomised controlled trials (RCTs) involving 2222 patients with ocular hypertension or glaucoma were included, five comparing latanoprost versus travoprost, seven comparing latanoprost versus bimatoprost and one comparing latanoprost versus travoprost and bimatorpost. The combined results showed that latanoprost produced lower occurrence of conjunctival hyperemia than both travoprost (Odds Ratio [OR] = 0.51; 95% CI 039 to 0.67, p<0.0001) and bimatoprost (OR = 0.32; 95% CI 0.24 to 0.42, p<0.0001). No significant heterogeneity was found between the included RCTs. There was no evidence of publication bias. In the sensitivity analysis performed, none of the clinical trials included in the meta-analysis have an important impact in the global estimation of OR.

Authors conclude that based on the available data, the use of latanoprost is associated with a lower incidence of conjunctival hypertension when compared with travoprost and bimatoprost in the treatment of patients with ocular hypertension or glaucoma.

Methodology: The following criteria were used to identify published studies for inclusion:

(a) Study design – RCTs

(b) Population – patients with ocular hypertension and/or glaucoma

(c) Intervention – latanoprost versus other prostaglandins analogues (bimatoprost or travoprost) as monotherapy

(d) Outcome variable – conjunctival hyperemia.

Only articles written in English were included. Abstract without raw data available for retrieval and duplicate publications were excluded.

Authors conducted a computerised literature search in Medline, EMBASE and Cochrane Controlled Trials Register databases from 1995 to April 2007 for relevant articles in English. They used the Medical Subject Heading and the following key words: glaucoma, ocular hypertension, randomisation, trials, latanoprost, bimatoprost, travoprost and conjunctival/ocular hyperemia. References from the reviewed articles were also searched for relevant titles.

Two reviewers independently selected and screened studies for inclusion, extracted data and performed methodological quality assessment of included studies. A customised form was created to record information of selected articles: year of publication, information of study design, length of study, number of subjects, age, sex, type of glaucoma and proportion of conjunctival hyperemia. The primary outcome measure was the incidence of conjunctival hyperemia over treatment visits. Authors used the Jadad tool to quality-assess included studies.

Authors conducted a meta-analysis of included RCTs. For dichotomous outcomes, OR and 95% CI were calculated. The OR was defined as the odds of an outcome in those who received latanoprost therapy compared with the odds in those who received bimatoprost or travotoprost. The ORs of different RCTs were combined by using the fixed-effects model of Mantel and Haenszel and the random-effects model of Der Simonian and Laird. Heterogeneity was explored using the Cochran Q test with calculate I². To exclude the possibility that any one study was exerting excessive influence on the results, authors conducted a sensitivity analysis by systematically excluding each study at a time and then re-running the analysis to assess the change in ORs.

Applicability/external validity: Review authors did not discuss the generalizability of the results.

Geographic focus: Geographical location of included studies was not reported in the review. However, authors note that clinical trials in this meta-analysis were undertaken in many different countries, suggesting that studies published in certain countries may be more likely than others to produce research showing significant effects of interventions.

Summary of quality assessment: There is medium confidence in the conclusions about the effects of this study as limitations were identified. Literature searches are not comprehensive enough, so we can be confident that relevant studies were not omitted. Authors conducted searches on the relevant databases and searched reference lists for published studies written in English. However, searching for unpublished literature and contacting authors or experts for potentially relevant studies were not part of the search strategy.

Authors used appropriate methods to screen studies for inclusion, extract data, quality assess and analyse findings of included studies. Authors used the Jadad instrument to appraise the methodological methods of RCTs, and provided an overall score for each of them. However, authors did not specify limitations of included studies. Therefore, it is not clear how much of an impact these have on the overall findings of the meta-analysis. Overall, authors appropriately reported limitations of the review including the presence of publication and location bias, and did not draw strong conclusions about the effects of this study.