Simmonds Mark, Walton Matthew, Hodgson Rob, Llewellyn Alexis, Walker Ruth, Fulbright Helen, Bojke Laura, Stewart Lesley, Dias Sofia, Rush Thomas, Lawrenson John, Peto Tunde, Steel David
Centre for Reviews and Dissemination, University of York, York, UK.
Centre for Health Economics, University of York, York, UK.
Health Technol Assess. 2025 May 7:1-16. doi: 10.3310/KRWP1264.
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.
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.
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.
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.
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.
This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR132948.
糖尿病视网膜病变是糖尿病患者视力丧失的主要原因，存在黄斑水肿、玻璃体积血或其他并发症的高风险。全视网膜光凝是增殖性视网膜病变的主要治疗方法。抗血管内皮生长因子药物用于治疗各种眼部疾病，可能对增殖性或非增殖性视网膜病变患者有益。
抗VEGF在糖尿病中的应用项目旨在研究与全视网膜光凝或不治疗相比，使用抗血管内皮生长因子预防视网膜病变进展的临床效果和成本效益。对随机对照试验（抗血管内皮生长因子单独使用或与全视网膜光凝联合使用）治疗视网膜病变进行了系统评价和网状Meta分析。数据库检索于2023年5月更新。寻求来自大型试验的个体参与者数据。对非随机研究进行了系统评价。回顾了现有的成本效益分析，并根据个体参与者数据Meta分析建立了一个新的经济模型。该模型还估计了进行进一步研究以解决决策不确定性的价值。
该评价发现，在增殖性视网膜病变患者随访1年后，抗血管内皮生长因子在最佳矫正视力方面比全视网膜光凝产生了轻微但无临床意义的益处（平均差异为4.5个ETDRS字母；95%可信区间为-0.7至8.2）。没有证据表明不同抗血管内皮生长因子之间在有效性上存在差异。抗血管内皮生长因子的益处似乎会随着时间下降。抗血管内皮生长因子治疗对初始视力较差的患者可能更有效。抗血管内皮生长因子对非增殖性视网膜病变患者的视力没有影响。抗血管内皮生长因子可降低黄斑水肿和玻璃体积血的发生率，并可能减缓视网膜病变的进展。预计抗血管内皮生长因子的成本更高，但与全视网膜光凝效果相似，在支付意愿阈值为20000英镑时，净健康效益为-0.214质量调整生命年。只有在非常特殊的情况下，抗血管内皮生长因子才有可能在治疗增殖性视网膜病变方面具有成本效益。通过进一步的初步研究降低不确定性可能具有潜在的重大价值。
抗血管内皮生长因子在保护视力方面与全视网膜光凝相比没有临床意义上的益处，但它可能延迟或预防进展为黄斑水肿和玻璃体积血。抗血管内皮生长因子治疗的长期有效性和安全性尚不清楚，特别是随着时间的推移还需要额外的全视网膜光凝和抗血管内皮生长因子治疗。因此，与全视网膜光凝相比，抗血管内皮生长因子不太可能是早期增殖性视网膜病变的具有成本效益的治疗方法。在各种情况下，它们通常与更高的成本和相似的健康结果相关。由于缺乏长期临床证据，抗血管内皮生长因子的长期成本效益尚不确定。
需要进行随访超过2年的更有力研究，以评估使用抗血管内皮生长因子的长期疗效和安全性，以及随着时间推移额外的抗血管内皮生长因子和全视网膜光凝治疗的效果。关注治疗时视力较差的患者使用抗血管内皮生长因子的临床试验或观察性研究也可能有用。
本综述介绍了由英国国家卫生与保健研究所（NIHR）卫生技术评估项目资助的独立研究，资助编号为NIHR132948。
