Association Between Anti-vascular Endothelial Growth Factor Therapy Exposure and Visual Outcomes in Diabetic Macular Edema and Retinal Vein Occlusion

Summary

In this retrospective cohort, greater injection frequency, longer treatment duration, and earlier treatment initiation were each independently associated with better visual outcomes. Although non-standard treatment patterns were common and associated with poorer unadjusted outcomes, composite standard-treatment classification did not retain independent prognostic value after accounting for these specific treatment-exposure metrics.

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) therapy is first-line treatment for diabetic macular edema (DME) and retinal vein occlusion (RVO), but real-world practice often differs from clinical trial findings. This single-center retrospective cohort study used hospital electronic medical records to evaluate anti-VEGF treatment patterns and associations with visual outcomes. We included 332 adults who received at least one intravitreal injection of ranibizumab, aflibercept, or conbercept between January 2022 and January 2024 and had at least one post-baseline best-corrected visual acuity (BCVA) measurement. The cohort included 180 patients with DME, 138 with RVO, and 14 with other retinal vascular diagnoses. Standard treatment required three monthly loading doses, a treat-and-extend regimen with intervals of 4–16 weeks, no interval >16 weeks, and treatment duration ≥12 months; all other patterns were classified as non-standard. The primary outcome was change in LogMAR BCVA at the last available follow-up. The standard and non-standard groups included 132 and 200 patients, respectively. Treatment interruption for ≥6 months was common in the non-standard group (68.50%). Unadjusted visual outcomes favored the standard group (median ΔBCVA, −0.23 vs. −0.07 LogMAR; improvement rate, 68.18% vs. 35.00%; P<0.001). In adjusted analyses, baseline BCVA, total number of injections, and treatment duration were positive predictors of improvement, whereas longer time to first injection was a negative predictor; standard/non-standard grouping was not significant (P=0.853). Safety events were infrequent, limiting comparison of rare events. Non-standard treatment patterns were common and associated with poorer unadjusted visual outcomes; optimizing injection exposure and treatment timing may improve real-world outcomes.

Introduction

Retinal vascular diseases, particularly diabetic macular edema (DME) and retinal vein occlusion (RVO), are leading causes of global visual impairment^1,2,3. Their incidence is rising due to increasing diabetes prevalence and population aging⁴, placing a heavy burden on public health systems⁵. The IDF reports ~500 million adults with diabetes, one-third of whom have diabetic retinopathy⁶. As its leading cause of vision loss, DME affects up to 5% of patients⁷. RVO, the second most com....

Protocol

This study was approved by the Tianjin Medical University Ethics Committee (Approval number: 2024-025). This study adhered to the principles of the Declaration of Helsinki and the Measures for Ethical Review of Biomedical Research Involving Humans. As this was a retrospective analysis using previously de-identified clinical data, the study protocol was reviewed and approved by the hospital ethics committee, and the requirement for informed consent was waived.

Study design
This single-center, retrospective cohort study used real-world data from our hospital’s electronic medical records and ophthalmic picture arch....

Results

Baseline characteristics of patients
A total of 332 patients were included. Among them, 180 (54.22%) had diabetic macular edema (DME), 138 (41.57%) had retinal vein occlusion (RVO; comprising 72 with central RVO and 66 with branch RVO), and 14 (4.22%) carried other diagnoses, including retinal vasculitis and ischemic retinopathy. Measured baseline characteristics were not statistically different between the standard and non-standard treatment groups, including age, sex, affected side, disease type di.......

Discussion

In this single-center, real-world cohort, we systematically characterized anti-VEGF treatment patterns in patients with retinal vascular diseases and explored their associations with visual outcomes. The main findings are threefold. First, non-standard therapy was common, affecting 60.24% of the cohort, with treatment interruption for ≥6 months being the most frequent manifestation. Second, patients in the standard-treatment group had significantly better unadjusted visual outcomes than those in the non-standard gr.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Aflibercept (Eylea)	Bayer	61755-005-02	Anti-VEGF agent administered by intravitreal injection.
Alternative SD-OCT System	Carl Zeiss Meditec AG	Cirrus HD-OCT 5000	Alternative spectral-domain OCT system used for retinal thickness analysis and retinal imaging.
Best-Corrected Visual Acuity (BCVA) Assessment	Precision Vision, La Salle, IL, USA	Revised 2000 ETDRS Charts	ETDRS charts used for standardized BCVA assessment.
Conbercept (Langmu)	Chengdu Kanghong Biotech	S20130002	Anti-VEGF agent administered by intravitreal injection.
Fundus Fluorescein Angiography (FFA) System	Heidelberg Engineering GmbH	222611 / FDA 510(k): K101223	System used for fluorescein angiography and retinal imaging.
Ranibizumab (Lucentis)	Novartis	50242-080-03	Anti-VEGF agent administered by intravitreal injection.
Slit-Lamp Biomicroscope	Haag-Streit AG, Bern, Switzerland	BQ 900	Slit-lamp biomicroscope used for anterior and posterior segment examination.
Spectral-Domain Optical Coherence Tomography (SD-OCT) System	Heidelberg Engineering, Germany	222611	Used to measure central subfield thickness (CST) and assess macular edema morphology.
SPSS Statistics Software	IBM Corp.	Version 26.0	Used for statistical analyses, including t-tests, Mann-Whitney U tests, chi-square tests, Fisher's exact tests, and logistic regression.