Authors: Dascalu AM, Rizzo M, Rizvi AA, Stoian AP, Iancu RC, Stana D, et al.

Geographical coverage: Not reported

Sector: Biomedical

Sub-sector: Treatment

Equity focus: Not reported

Study population: Patients with diabetes

Review type: Effectiveness review

Quantitative synthesis method: Not applicable

Qualitative synthesis method: Narrative synthesis

Background: Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent due to sedentary lifestyles and consumption of processed food. One common complication of T2DM is diabetic retinopathy (DR), which is the main cause of preventable blindness. Diabetic macular edema (DME), a complication of DR, affects patients’ quality of life and visual acuity (VA), and can lead to irreversible visual impairment. The intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab, ranibizumab and aflibercept are used as first-line treatment for DME. This review focused on aflibercept only.

Objectives: To assess the outcomes and safety of the intravitreal use of aflibercept in DME.

Main findings: A total of 1,140 articles were identified from the electronic database and manual reference searches, of which 25 were included in this review. All the studies included in the analysis demonstrated a significant overall improvement in both anatomical and functional aspects. In individuals receiving five IVA injections monthly at the onset of the treatment, the visual improvement at the week-52 mark ranged widely from 5 to 18.9 EDRS letters, with an average of 9.48 letters. Treatment-naïve patients, characterised by poorer visual acuity and increased central subfield thickness at the baseline, exhibited the highest gains. Conversely, patients previously treated with anti-VEGF showed a comparatively lower improvement. Notably, there was no statistically significant difference in Anti-Platelet Trialists’ Collaboration-defined arterial thromboembolic events between the aflibercept group and the laser group. In conclusion, intravitreal aflibercept therapy provides a good safety profile and significant improvement in visual acuity. The review authors highlighted the need for more randomised controlled trials (RCTs) to learn the optimal frequency of intravitreal injections to reduce treatment burden and improve clinical outcomes in diabetic patients with ophthalmic complications.

Methodology: Searches were conducted in PubMed and Web of Science databases to identify randomised and quality prospective studies, conducted on patients with DME, and comparing intravitreal aflibercept with observation, laser or other anti-VEGF agents, with at least 12 months’ follow-up. Searches were restricted to those published in the English language between 2014 and 2021. Reference lists of the relevant review articles were manually reviewed to identify any additional studies. The data extraction and quality assessment of the included studies were assessed by two reviewers independently. The findings were synthesised narratively.

Applicability/external validity: The authors did not discuss the applicability or external validity of the results.

Geographic focus: The authors did not report the geographic regions of included studies. This review does not explicitly address the applicability of its findings to low and middle income countries.

Summary of quality assessment:

Important limitations were identified in the approach employed to conduct this review. The searches were not thorough enough in indicating the presence of publication bias. Furthermore, it is not clear if authors used rigorous methods to screen studies for inclusion, and findings did not account for the risk of bias and heterogeneity of included studies. For these reasons, a low confidence was placed in the conclusions in this review.