ReviewInvestigative ophthalmology & visual science2023
Mechanisms of Acquired Resistance to Anti-VEGF Therapy for Neovascular Eye Diseases.
Review in Investigative ophthalmology & visual science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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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.
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.
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Who cites it
50 citing papers in PubMed, 83 citations in OpenAlex.
- Targeted Fluorescence Imaging of Bevacizumab-800CW in Patients with Neovascular Age-Related Macular Degeneration.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Trial
- Comparative outcomes of aflibercept 8 mg and faricimab in neovascular AMD refractory to aflibercept 2 mg.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Pharmacological Targeting of Angiogenesis in Head and Neck Cancer: Molecular Mechanisms and Emerging Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Acridine-derived small molecule associates with VEGF and is linked to reduced CAM vascularization: a combined in silico and CAM study.BMC pharmacology & toxicology · 2026Article
- Article
- FTO-modulated mJournal of translational medicine · 2026Article
- Efficacy, Durability, and Safety of Faricimab for Diabetic Macular Edema: 1-Year Results from the China RHINE Subpopulation.Ophthalmology and therapy · 2026Article
- Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.Investigative ophthalmology & visual science · 2026Review
- Anti-vascular endothelial growth factor therapy for posterior segment diseases: Progress, challenges, and the road ahead.Indian journal of ophthalmology · 2026Review
- The Short-Term Outcomes of Intravitreal Faricimab for Treatment-Naïve and -Refractory Neovascular Age-Related Macular Degeneration: A Real-World Study.Medicina (Kaunas, Lithuania) · 2026Article
- PTP4A3 contributes to pathological retinal neovascularization and vascular leakage partly through the PI3K-AKT signalling pathway.Scientific reports · 2026Article
- An APE1 Redox Inhibitor Attenuates Pathological Retinal Vascularization by Suppressing FGF2 Angiogenic Signaling.Investigative ophthalmology & visual science · 2026Article
- Icariin alleviates corneal neovascularization by regulating inflammation through inhibition of macrophage polarization and the NF-κB pathway.Journal of translational medicine · 2026Article
- AIF-1 Drives Corneal Neovascularization by Promoting Inflammatory Macrophage Activation via the MAPK and PI3K/AKT/mTOR Signaling Pathways.Investigative ophthalmology & visual science · 2026Article
- Article
- Silencing of lncRNA HOTAIR Using Eyedrops as a Potential Treatment for Diabetes-Associated Retinal Dysregulation and Dysfunction.Investigative ophthalmology & visual science · 2026Article
- miR-15a-5p outperforms anti-VEGF drug in ocular neovascularization by providing dual anti-angiogenic and neuroprotective effects.Theranostics · 2026Article
- Selective phosphoinositide 3-kinase inhibitors and implication in diabetic retinopathy as pharmacological tools.Frontiers in pharmacology · 2026Review
- Atypical p38 Kinase Signaling in Retinal Vascular Damage and Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: The purpose of this study was to evaluate clinical reports of response-loss in patients with neovascular eye diseases, such as neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME), after repeated anti-vascular endothelial growth factor (VEGF) therapy. To assess experimental evidence of associations of other angiogenic growth factors and endothelial glycolytic pathways with the diseases and to propose the underlying mechanisms. Methods: Review of published clinical studies and experimental investigations. Results: Intravitreal injection of anti-VEGF biologic drugs (e.g. bevacizumab, ranibizumab, and aflibercept) is the front-line treatment for neovascular AMD and DME, and acts by halting the progression of excess blood vessel growth and leakage. Despite favorable clinical results, exudation returns in a number of patients after repeated administrations over time. Patients suffering from disease recurrence may have developed an acquired resistance to anti-VEGF therapy. We have analyzed clinical and preclinical findings on changes to angiogenic signaling pathways following VEGF-targeted treatment and hypothesize that switching to alternative pathways could potentially bypass VEGF blockade, accounting for development of resistance to anti-VEGF therapy. We have also discussed potential reprogramming of ocular endothelial glycolysis in response to VEGF antagonism and proposed that metabolic adaptations could impair blood-retinal barrier function, counteracting the clinical efficacy of VEGF-targeted therapies and contributing to a decline of response to them. Conclusions: Future studies of the mechanisms proposed in this review may shed some light on how these adaptations result in the development of acquired resistance to anti-VEGF therapy, which should help discover new therapeutic strategies for overcoming anti-VEGF resistance and improving clinical efficacy.
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Registered trials
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.