Background: Diabetic retinopathy is a major cause of sight loss in people with diabetes. The most severe form, proliferative diabetic retinopathy, carries a high risk of vision loss, vitreous haemorrhage, macular oedema and other harms. Panretinal photocoagulation is the primary treatment for proliferative diabetic retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with diabetic retinopathy.
Objective: To investigate the efficacy and safety of anti-vascular endothelial growth factor therapy for the treatment of diabetic retinopathy when compared to panretinal photocoagulation.
Methods: A systematic review and network meta-analysis of all published randomised controlled trials comparing anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to panretinal photocoagulation in people with diabetic retinopathy. The database searches were updated in May 2023. Trials where the primary focus was treatment of macular oedema or vitreous haemorrhage were excluded.
Results: A total of 14 trials were included: 3 of aflibercept, 5 of bevacizumab and 6 of ranibizumab. Two trials were of patients with non-proliferative diabetic retinopathy; all others were in proliferative diabetic retinopathy. Overall, anti-vascular endothelial growth factor was slightly better than panretinal photocoagulation at preventing vision loss, measured as best corrected visual acuity, at up to 2 years follow-up [mean difference in the logarithm of the minimum angle of resolution -0.089 (or 3.6 Early Treatment Diabetic Retinopathy Study letters), 95% confidence interval -0.180 to -0.019]. There was no clear evidence of any difference between the anti-vascular endothelial growth factors, but the potential for bias complicated the comparison. One trial found no benefit of anti-vascular endothelial growth factor over panretinal photocoagulation after 5 years. Anti-vascular endothelial growth factor was superior to panretinal photocoagulation at preventing macular oedema (relative risk 0.29, 95% confidence interval 0.18 to 0.49) and vitreous haemorrhage (relative risk 0.77, 95% confidence interval 0.61 to 0.99). There was no clear evidence that the effectiveness of anti-vascular endothelial growth factor varied over time.
Conclusions: Anti-vascular endothelial growth factor injections reduce vision loss when compared to panretinal photocoagulation, but the benefit is small and unlikely to be clinically meaningful. Anti-vascular endothelial growth factor may have greater benefits for preventing complications such as macular oedema. Observational studies extending follow-up beyond the 1-year duration of most trials are needed to investigate the longer-term effects of repeated anti-vascular endothelial growth factor injections.
Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.
Keywords: ANTI-VEGF; DIABETIC RETINOPATHY; META-ANALYSIS; PANRETINAL PHOTOCOAGULATION; SYSTEMATIC REVIEW.
People with diabetes are at risk of gradually losing their sight. This is because blood vessels in the part of the eye called the retina may become damaged, leading to sight loss. This condition is called diabetic retinopathy. People with a more severe type of retinopathy, called proliferative diabetic retinopathy, are usually offered laser treatment to reduce the risk of further sight loss. Recently, drugs called anti-vascular endothelial growth factor drugs, which are injected directly into the eye, have been used to treat other eye conditions, and might be useful to treat retinopathy. This project investigated whether anti-vascular endothelial growth factor therapy is effective by identifying and re-analysing all the clinical trials that used the three main anti-vascular endothelial growth factor drugs (called aflibercept, bevacizumab and ranibizumab) to treat diabetic retinopathy. We identified 14 relevant clinical trials, including approximately 1800 persons. Our analyses found that anti-vascular endothelial growth factor injections were slightly better than laser therapy at maintaining vision. After 1 year, people with proliferative retinopathy who received anti-vascular endothelial growth factor injections could, on average, read three or four more letters on a standard eye test chart than people who had received laser therapy. This difference may be too small to make anti-vascular endothelial growth factor injections worthwhile. People with less severe forms of retinopathy saw no benefit in vision after receiving anti-vascular endothelial growth factor therapy. We did find that people who received anti-vascular endothelial growth factor injections were substantially less likely to experience some of the more severe consequences of vision loss, including where vision is lost in the centre of the eye (called diabetic macular oedema), and where blood leaks into the eye (called vitreous haemorrhage). Most of the trials lasted for 1 year or less, so the long-term impact of using anti-vascular endothelial growth factor injections is still not well understood. This long-term impact of anti-vascular endothelial growth factor use requires further clinical research.