Evidence map›Paper›PMID 41101497›Full record

ArticleOphthalmology. Retina2026

How to Judge Failure: Defining Treatment Resistance to Anti-VEGF Therapy in Exudative Maculopathies-A Systematic Scoping Review.

Geoffrey K Broadhead, Long Phan, Tiarnán D L Keenan, Jennifer Chin, Thomas Hong, Emily Y Chew, Andrew A Chang

Abstract readScoping Review
PubMed Full text at PMC Publisher
In one paragraph

Article in Ophthalmology. Retina, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Defining failure is not enough.Eye (London, England) · 2026
    Article
  5. Article
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

7 authors.

Geoffrey K BroadheadSave Sight Institute, Department of Ophthalmology, The University of Sydney, Sydney, New South Wales, Australia; CUREOS Group, Sydney, New South Wales, Australia; Canberra Eye Surgeons, Deakin, Australian Capital Territory, Australia.
Long PhanCUREOS Group, Sydney, New South Wales, Australia.
Tiarnán D L KeenanDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Jennifer ChinCUREOS Group, Sydney, New South Wales, Australia.
Thomas HongCUREOS Group, Sydney, New South Wales, Australia.
Emily Y ChewDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Andrew A ChangSave Sight Institute, Department of Ophthalmology, The University of Sydney, Sydney, New South Wales, Australia; CUREOS Group, Sydney, New South Wales, Australia. Electronic address: achang@sydneyretina.com.au.

Funding

NEI Intramural Biorepository for Retinal Diseases (12-EI-0042)ZIAEY000514 · NEI · NATIONAL EYE INSTITUTE · PI KEENAN, TIARNAN · 2012 to 2025
$2.0M
Intramural NIH HHS ZIA EY000514
6 · The paper itself

Abstract

topicTo evaluate the currently used definitions of treatment resistance in common retinal vascular diseases (neovascular age-related macular degeneration [nAMD], diabetic macular edema [DME], and retinal vein occlusion [RVO]) through a systematic scoping review of published studies. CLINICAL RELEVANCE: A notable proportion of patients receiving therapy for retinal vascular diseases exhibit suboptimal responses to anti-VEGF therapy, however, currently there are no well-recognized definitions of resistance to treatment in these conditions. Clear definitions of treatment resistance would aid in developing treatment strategies and guiding research studies for these patients.

methodsThe online databases PubMed, EMBASE, and the Cochrane Database of Systemic Reviews were searched on January 5, 2025, and August 16, 2025, for articles relating to treatment resistance in all 3 conditions.

resultsIn total, 402 publications were identified, of which 88 met the eligibility criteria: 30 relating to nAMD, 48 relating to DME, and 10 relating to RVO. Wide heterogeneity exists in the definition of treatment resistance for each condition. Persistent intraretinal fluid and/or subretinal fluid (SRF) on OCT is the most commonly used criterion in each condition. Duration of prior treatment for defining resistance is commonly longest for nAMD, however, treatment frequency of approximately ≤6 weekly injections for defining resistance was generally similar across all 3 conditions.

conclusionThere is wide variability in the definitions used, however, persistent intraretinal and/or SRF on OCT despite regular anti-VEGF therapy of approximately ≤6 weekly intervals are the most common criteria across all 3 conditions. Adoption of these definitions for future studies would help ensure consistency and may potentially improve patient outcomes by improving the validity of future studies and allowing for the development of treatment paradigms to manage this patient subgroup. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Indexed as

Angiogenesis InhibitorsDrug ResistanceMacular EdemaRetinal Vein OcclusionVisual AcuityWet Macular DegenerationHumansIntravitreal InjectionsTomography, Optical CoherenceTreatment FailureVascular Endothelial Growth Factor AAngiogenesis InhibitorsVascular Endothelial Growth Factor AVEGFA protein, humanAge-related macular degenerationAnti-VEGF agentDiabetic macular edemaRetinal vein occlusionTreatment resistance

Identifiers

PMID41101497
PMCPMC12803011

What OpenQuestion holds

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Registered trials

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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.