Anti-VEGF drugs compared with laser photocoagulation for the treatment of diabetic retinopathy: a systematic review and economic analysis.

Background: Diabetic retinopathy is a major cause of sight loss in people with diabetes, with a high risk of macular oedema, vitreous haemorrhage or other complications. Panretinal photocoagulation is the primary treatment for proliferative retinopathy. Anti-vascular endothelial growth factor drugs are used to treat various eye conditions and may be beneficial for people with proliferative or non-proliferative retinopathy.

Methods: The Anti-VEGF In Diabetes project sought to investigate the clinical and cost-effectiveness of using anti-vascular endothelial growth factor to prevent retinopathy progression when compared to panretinal photocoagulation or no treatment. A systematic review with network meta-analysis of randomised controlled trials of anti-vascular endothelial growth factor (alone or in combination with panretinal photocoagulation) to treat retinopathy was conducted. The database searches were updated in May 2023. Individual participant data from larger trials were sought. A systematic review of non-randomised studies was performed. Existing cost-effectiveness analyses were reviewed, and a new economic model was developed, informed by the individual participant data meta-analysis. The model also estimated the value of undertaking further research to resolve decision uncertainty.

Results: The review found that anti-vascular endothelial growth factors produced a slight, and not clinically meaningful, benefit over panretinal photocoagulation in best corrected visual acuity, after 1 year of follow-up in people with proliferative retinopathy (mean difference of 4.5 ETDRS letters; 95% credible interval -0.7 to 8.2). There was no evidence of a difference in effectiveness among the different anti-vascular endothelial growth factors. The benefit of anti-vascular endothelial growth factor appears to decline over time. Anti-vascular endothelial growth factor therapy may be more effective in people with poorer initial visual acuity. Anti-vascular endothelial growth factor had no impact on vision in people with non-proliferative retinopathy. Anti-vascular endothelial growth factor reduces rates of macular oedema and vitreous haemorrhage and may slow down the progression of retinopathy. Anti-vascular endothelial growth factors were predicted to be more costly but similarly effective to panretinal photocoagulation, with a net health benefit of -0.214 quality-adjusted life-years at a £20,000 willingness-to-pay threshold. Only under very select conditions might anti-vascular endothelial growth factors have the potential for cost-effectiveness to treat proliferative retinopathy. There is potentially significant value in reducing uncertainty through further primary research.

Conclusions: Anti-vascular endothelial growth factor has no clinically meaningful benefit over panretinal photocoagulation for preserving visual acuity, but it may delay or prevent progression to macular oedema and vitreous haemorrhage. The long-term effectiveness and safety of anti-vascular endothelial growth factor treatment are unclear, particularly as additional panretinal photocoagulation and anti-vascular endothelial growth factor treatment will be required over time. Anti-vascular endothelial growth factors are therefore unlikely to be a cost-effective treatment for early proliferative retinopathy compared to panretinal photocoagulation. They are generally associated with higher costs and similar health outcomes across various scenarios. The long-term cost-effectiveness of anti-vascular endothelial growth factor is uncertain due to the lack of long-term clinical evidence.

Future work: Further, robust studies with more than 2 years follow-up are required to evaluate the long-term efficacy and safety of anti-vascular endothelial growth factor use, and the effect of additional anti-vascular endothelial growth factor and panretinal photocoagulation therapy over time. Clinical trials or observational studies focusing on the use of anti-vascular endothelial growth factor in people with poorer vision at time of treatment may also be useful.

Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.