# Comparable choroidal thickness between treated eyes and untreated fellow-eyes in patients with unilateral neovascular AMD: a paired-eyes comparative study

## TL;DR

This study found no significant difference in choroidal thickness between eyes treated with anti-VEGF and their untreated counterparts in patients with AMD.

## Contribution

The study challenges the hypothesis that anti-VEGF treatment causes choroidal thinning and subsequent atrophy in AMD patients.

## Key findings

- There was no statistically significant difference in choroidal thickness between treated and untreated eyes.
- The number of anti-VEGF injections did not correlate with choroidal thinning.
- Age was the only variable that significantly influenced choroidal thickness.

## Abstract

To investigate the potential effect of anti-VEGF treatment on choroidal thickness (CT) in unilateral neovascular age-related macular degeneration (AMD) patients.

This is a cross-sectional study where patients were included as part of an ongoing prospective study which included patients with unilateral neovascular (n) AMD. The fellow-eye served as control. All patients had spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) done at every visit. CT was measured independently by two graders at five locations: subfoveal, 1500 micron temporal and nasal, 3000 micron temporal and nasal. The average of the measurements was used after statistical verification of their accuracy. CT differences were initially analysed via a paired T-test and later via multiple linear regression. Variables such as number of injections were studied and presence of geographic atrophy (GA) in fellow-eyes was evaluated via SD-OCT.

A total of 112 patients met the inclusion criteria (Female 67%). The median (IQR) years of treatment was 2.6 (4.1). The subfoveal choroidal thickness (SFCT) in the neovascular (NV) eye appeared thinner in the NNV eye initially (-11.0 μm difference between NV and NNV SFCT (CI -23.4 to 1.3). However, after age-adjustment this trend disappeared (CI -29.8 to 4.6). In fact, apart from age (CI -6.2 to -0.1)), no other variable including number of anti-VEGF injections (CI -1.5 to 1.4) predicted SFCT. Presence of GA in fellow eyes did not influence the SFCT compared to non-GA fellow eyes, difference (CI -59.7 to 46.6).

This study shows no statistically significant CT difference in NV versus NNV eyes. There was no relationship between number of injections and CT.

What is known
Intravitreal injection with anti-vascular endothelial growth factors (anti-VEGF) is the mainstay treatment for exudation secondary to neovascular AMD. One quarter of anti-VEGF treated neovascular AMD patients will develop signs of macular atrophy within 2 years, possibly related to anti-VEGF treatment.

Intravitreal injection with anti-vascular endothelial growth factors (anti-VEGF) is the mainstay treatment for exudation secondary to neovascular AMD. One quarter of anti-VEGF treated neovascular AMD patients will develop signs of macular atrophy within 2 years, possibly related to anti-VEGF treatment.

What this study adds
A hypothesized mechanism for atrophy induction is the effect of anti-VEGF on choroidal thickness. In this cross-sectional study, we found a non-significant 11 micron difference between anti-VEGF treated eyes and non-treated eyes in long-term follow-up neovascular AMD patients. A relationship between choroidal thinning and the number of anti-VEGF injections was furthermore not shown.

A hypothesized mechanism for atrophy induction is the effect of anti-VEGF on choroidal thickness. In this cross-sectional study, we found a non-significant 11 micron difference between anti-VEGF treated eyes and non-treated eyes in long-term follow-up neovascular AMD patients. A relationship between choroidal thinning and the number of anti-VEGF injections was furthermore not shown.

How this study might affect research, practice or policy
There is no significant choroidal thickness difference between anti-VEGF treated and non-treated long-term follow-up neovascular AMD. We therefore suggest that atrophy induction through choroidal thinning secondary to anti-VEGF injections is of limited concern.

There is no significant choroidal thickness difference between anti-VEGF treated and non-treated long-term follow-up neovascular AMD. We therefore suggest that atrophy induction through choroidal thinning secondary to anti-VEGF injections is of limited concern.

The online version contains supplementary material available at 10.1007/s00417-025-06751-7.