Impact of anti-VEGF treatment for diabetic macular oedema on progression to proliferative diabetic retinopathy: data-driven insights from a multicentre study

Objective To report insights on proliferative diabetic retinopathy (PDR) risk modification with repeated antivascular endothelial growth factor (VEGF) injections for the treatment of diabetic macular oedema (DMO) in routine care. Methods and analysis Multicentre study (27 UK-National Health Service centres) of patients with non-PDR (NPDR) and DMO. Primary outcome was PDR development. Repeated anti-VEGF injections were modelled as time-dependent covariates using Cox regression and weighted cumulative exposure (WCE) adjusting for baseline diabetic retinopathy (DR) grade, age, sex, ethnicity, type of diabetes and deprivation. PDR incidence rates (IRs) were calculated. Results We included 2858 DMO anti-VEGF-treated eyes. Anti-VEGF injections showed a protective effect on PDR risk during the most recent 4 weeks from exposure, which rapidly decreased. Mild-NPDR had a lower PDR risk compared with moderate-NPDR (HR 1.99, 95% CI 1.13 to 3.51, p=0.015) and severe-NPDR (HR 4.63, 95% CI 2.55 to 8.41, p<0.001). Patients with type 1 diabetes showed an increased PDR risk when compared with patients with type 2 diabetes (HR 2.08, 95% CI 1.35 to 3.21, p<0.001). And every 5-year increase in age showed a 9% reduction in PDR hazards (p=0.002). The PDR cumulative IR was 4.45 (95% CI 3.89 to 5.09) per 100 person-years. Conclusions The WCE method is a valuable modelling strategy for repeated exposures in ophthalmology. Injections are protective against PDR predominantly within the most recent 4 weeks. Based on observed data, we show that age and baseline DR severity are relevant predictors of poor outcomes in patients with DMO treated with anti-VEGF.