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

## TL;DR

Repeated anti-VEGF injections for diabetic macular oedema reduce the risk of developing proliferative diabetic retinopathy, especially within four weeks of treatment.

## Contribution

The study introduces a weighted cumulative exposure method to model repeated anti-VEGF injections and identifies key predictors of PDR progression.

## Key findings

- Anti-VEGF injections show a protective effect against PDR for up to four weeks post-treatment.
- Patients with mild NPDR have a significantly lower PDR risk compared to moderate and severe NPDR.
- Age and baseline DR severity are strong predictors of PDR progression in DMO patients.

## Abstract

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.

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.

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.

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.