Evidence map›Paper›PMID 40915541›Full record

ArticleDiabetes research and clinical practice2025

Intravitreal anti-VEGF therapy and risk of limb complications in individuals with diabetic eye disease.

Alexander T Hong, Ivan Y Luu, Forest Lin, Tze-Woei Tan, Brian C Toy

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PubMed Full text at PMC Publisher
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Article in Diabetes research and clinical practice, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Alexander T HongKeck School of Medicine at the University of Southern California, Los Angeles, USA.
Ivan Y LuuKeck School of Medicine at the University of Southern California, Los Angeles, USA.
Forest LinKeck School of Medicine at the University of Southern California, Los Angeles, USA.
Tze-Woei TanKeck School of Medicine at the University of Southern California, Los Angeles, USA.
Brian C ToyRoski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: Brian.Toy@med.usc.edu.

Funding

Southern California Clinical and Translational Science InstituteUL1TR001855 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Thomas A Buchanan, Michele D. Kipke · 2016 to 2026
$81.3M
Investigating the Development, Persistence, and Progression of Uveitis and Ocular Inflammation in the United StatesK23EY032985 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOY, BRIAN · 2021 to 2025
$820k
NCATS NIH HHS UL1 TR001855NEI NIH HHS K23 EY032985
6 · The paper itself

Abstract

aimsTo evaluate the association between intravitreal anti-VEGF therapy and lower extremity complications in diabetic eye disease (DED), and compare risks among ranibizumab, aflibercept, and bevacizumab.

methodsThis retrospective cohort study used a U.S. electronic health records network. Adults with DED receiving ≥3 intravitreal anti-VEGF injections (IVI) were compared to those receiving ≤2 (controls). Outcomes included diabetic foot ulcer (DFU) and lower extremity amputation (LEA). Propensity score matching (1:1) balanced baseline characteristics. Cox models estimated hazard ratios (HRs) with 95 % confidence intervals (CIs) for LEA, above-ankle LEA, and DFU in the overall cohort and subgroups with proliferative diabetic retinopathy (PDR), peripheral artery disease (PAD), end-stage renal disease (ESRD), or prior DFUs.

resultsOf 448,100 individuals with DED, 35,269 received ≥3 injections; 34,070 remained in each group after matching. IVI was associated with higher risk of LEA (HR 1.54 [95 % CI 1.38-1.72]), above-ankle LEA (HR 1.31 [1.08-1.59]), and DFU (HR 1.36 [1.30-1.42]) versus controls. LEA risk was greater in IVI versus control subgroups with PDR, PAD, ESRD, or DFUs. Risks were similar across agents.

conclusionsAnti-VEGF therapy in DED was linked to increased DFU and LEA risk, especially in high-risk subgroups. Prospective studies are needed for confirmation.

Indexed as

Angiogenesis InhibitorsDiabetic FootDiabetic RetinopathyVascular Endothelial Growth Factor AAgedAmputation, SurgicalBevacizumabFemaleHumansIntravitreal InjectionsMaleMiddle AgedRanibizumabReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsRetrospective StudiesafliberceptAngiogenesis InhibitorsBevacizumabRanibizumabReceptors, Vascular Endothelial Growth FactorRecombinant Fusion ProteinsVascular Endothelial Growth Factor ADiabetic foot ulcerDiabetic retinopathyIntravitreal injectionsLower extremity amputationMacular edema

Identifiers

PMID40915541
PMCPMC12459292

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.