Methodological quality of the review: Medium confidence
Author: Ford JA, Lois N, Royle P, Clar C, Shyangdan D, Waugh N.
Region: United States of America (USA), United Kingdom (UK), Iran, Hong Kong, Australia, Korea, Brazil, and multicentre international studies.
Sector: Diabetic macular oedema.
Sub-sector: None specified
Equity focus: None specified
Review type: Effectiveness review
Quantitative synthesis method: Meta-analysis
Qualitative synthesis methods: Not applicable
Diabetic macular oedema (DMO) is a complication of diabetic retinopathy (DR) and a leading cause of blindness. Laser photocoagulation has primarily been the prevalent treatment of choice although recently anti-vascular endothelial growth factor (anti-VEGF) drugs and steroids have been introduced as a potential alternative.
To appraise the evidence for the use of anti-VEGF drugs and steroids in DMO as assessed by change in best corrected visual acuity (BCVA), central macular thickness and adverse events.
The authors included 51 articles from 29 studies were included in the review, seven of which were suitable for meta-analysis. Randomized control trials (RCTs) were included to evaluate clinical effectiveness of the use of anti-VEGF, and safety was assessed through both RCTs and observational studies. The quality of the studies varied considerably. The quality of the included studies was, in general good quality.
Authors reported the following results: ‘Anti-VEGF drugs are effective compared to both laser and placebo and seem to be more effective than steroids in improving BCVA. They have been shown to be safe in the short term but require frequent injections. Studies assessing steroids (triamcinolone, dexamethasone and fluocinolone) have reported mixed results when compared with laser or placebo. Steroids have been associated with increased incidence of cataracts and intraocular pressure rise but require fewer injections, especially when steroid implants are used.’
Authors concluded that ‘The anti-VEGFs ranibizumab and bevacizumab have consistently shown good clinical effectiveness without major unwanted side effects. Steroid results have been mixed and are usually associated with cataract formation and intraocular pressure increase. Despite the current wider spectrum of treatments for DMO, only a small proportion of patients recover good vision (≥20/40), and thus the search for new therapies needs to continue.’
Authors searched MEDLINE and EMBASE and the Cochrane Library (from inception to July 2012) as well as a number of websites and conference abstracts. In addition, websites of the European Medicines Agency and the US Food and Drug Administration were searched for data on registration status and safety in July 2012.
RCTs were included provided that they (1) addressed the use of triamcinolone, dexamethasone, fluocinolone, bevacizumab, ranibizumab, pegaptanib or aflibercept in patients with DMO; (2) had a minimum follow-up of 6 months; and (3) had a minimum of 25 eyes per study arm. Among other exclusion criteria, studies were excluded if written in another language other than English. 29 studies from 51 articles were included in qualitative synthesis and seven were included in quantitative synthesis (meta-analysis). Risk of bias of included studies was assessed using the Cochrane risk of bias tool. Study results were narratively described and, where appropriate, data were pooled using random effects meta-analysis.
The authors did not specifically address the external validity of the review. Authors did note that, although anti-VEGFs were clinically effective, they had little effect in a large number of patients and the proportion of patients who demonstrated 10 or more letter gain using anti-VEGFs is between 30%-50% in the trials that demonstrate the greatest effectiveness.
Included studies were from a number of countries including the USA, UK, Iran, Hong Kong, Australia, Korea and Brazil, as well as multicentre international studies. The authors did not focus on the implications of the review for low- to middle-income settings.
This review was attributed medium confidence in the conclusions about the effects of this study as some limitations were identified. The literature search, although covering relevant databases and contacting experts/authors for additional articles, was restricted to published articles written in English only and a search of reference lists in included studies was not part of the strategy. Therefore, we could not be confident that relevant studies were not omitted. Authors used appropriate methods to reduce risk of bias in terms of study selection, data extraction and analysis.