Authors: Feng Y, Zhu S, Skiadaresi E, McAlinden C, Tu R, Gao R, et al.

Geographical coverage: Saudi Arabia, Spain, Japan, Iran and China

Sector: Biomedical

Sub-sector: Treatment

Equity focus: Not reported

Study population: Patients with diabetic macular edema

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Cataract surgery increases the risk of diabetic retinopathy (DR) and diabetic macular edema (DME). These risks are lowered by using intravitreal anti-vascular endothelial growth factor (VEGF) therapy with cataract surgery. Although several comparative studies assessed efficacy of intravitreal bevacizumab (IVB) with cataract surgery to lower the risk of DR progression, the results were not consistent.

Objectives: To evaluate the clinical effectiveness of intravitreal bevacizumab (IVB) injection combined with cataract surgery in the treatment of patients with cataract and coexisting diabetic retinopathy (DR).

Main findings: A total of 55 articles were identified from the electronic database and manual reference searches, of which six were included in this review. Five of the six included studies were randomised control trials (RCTs) and one was a cohort study. Two of the six studies were conducted in Iran, and one each in Saudi Arabia, Spain, Japan and China. The findings of meta-analysis showed that at one and three months after cataract surgery, corrected distance vision acuity (CDVA) was significantly better in the IVB groups than in control groups (p<0.00001 and p = 0.01); however, CDVA did not differ significantly between the two groups (p = 0.24) at six months post-surgery. Similarly, at one, three and six months after cataract surgery, the central macular thickness (CMT) was significantly thinner in IVB groups than in control groups (p = 0.01, p = 0.0004, and p = 0.01). Sensitivity analyses conducted for CDVA and CMT did not alter the results. The progression of postoperative DR (p = 0.0001) and maculopathy (p<0.0001) occurred more frequently in the control group than in the IVB group.

The authors concluded that IVB injections combined with cataract surgery was safe and effective for patients with coexisting DR for up to six months; and proposed to conduct more randomised, prospective, and large sample-sized studies to assess the long-term effects of intravitreal anti-VEGF therapy at the time of cataract surgery in patients with DR.

Methodology: Searches were conducted in PubMed, EMBASE and Cochrane Controlled Trials Register databases to identify studies comparing cataract surgery with or without IVB therapy in patients with DME. Searches were restricted to articles published in the English language from inception to 1 March 2016. Reference lists of the included studies and relevant review articles were manually reviewed to identify any additional studies.

Randomised controlled and cohort studies conducted on patients aged 18 years and older, with cataract and preexisting DR, who were scheduled for cataract surgery alone (control group) or combined with an IVB injection at the end of surgery (IVB group) were included. In addition, to be included in the study, all patients must have received similar routine medication preoperatively and postoperatively and must not receive further IBV during the minimum three-month follow-up.

The results were synthesised using meta-analysis. Two reviewers conducted screening, data extraction and quality appraisal. The reviewers assessed the risk of bias in the included studies using Cochrane Collaboration’s risk-of-bias tool. Heterogeneity was assessed using Chi² and I² statistics. Sensitivity analysis was conducted by excluding non-randomised control trials or studies including patients without DME. Publication bias was assessed using the funnel plot test.

Applicability/external validity: The review did not discuss generalisability of the results.

Geographic focus: Included studies were conducted in Saudi Arabia, Spain, Japan, Iran and China. Authors did not report how findings of this review may be applicable to low and middle income settings.

Summary of quality assessment:

The conclusions of this review are regarded with low confidence due to the identified shortcomings in the review methodology. The literature search was confined to peer-reviewed articles written solely in English. Furthermore, studies with different levels of bias were not individually reported and analysed based on their bias status.