{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:47:17Z","timestamp":1792086437732,"version":"4.4.0"},"reference-count":335,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The cornea is an avascular, immune-privileged tissue critical to maintaining transparency, optimal light refraction, and protection from microbial and immunogenic insults. Corneal neovascularization (CoNV) is a pathological sequela of multiple anterior segment diseases and presents a major cause for reduced visual acuity and overall quality of life. Various aetiologies, including infection (e.g., herpes simplex), inflammation (e.g., infective keratitis), hypoxia (e.g., contact lens overuse), degeneration (e.g., chemical burns), and trauma, disrupt the homeostatic avascular microenvironment, triggering an overactive compensatory response. This response is governed by a complex interplay of pro- and anti-angiogenic factors. This review investigates the potential for these mediators to serve as therapeutic targets. Current therapeutic strategies for CoNV encompass topical corticosteroids, anti-VEGF injections, fine-needle diathermy, and laser modalities including argon, photodynamic therapy and Nd:YAG. Emerging therapies involve steroid-sparing immunosuppressants (including cyclosporine and rapamycin), anti-fibrotic agents and advanced drug delivery systems, including ocular nanosystems and viral vectors, to enhance drug bioavailability. Adjunctive therapy to attenuate the protective corneal epithelium prior to target neovascular plexi are further explored. Gene-based approaches, such as Aganirsen (antisense oligonucleotides) and CRISPR\/Cas9-mediated VEGF-A editing, have shown promise in preclinical studies for CoNV regression and remission. Given the multifactorial pathophysiology of CoNV, combination therapies targeting multiple molecular pathways may offer improved visual outcomes. Case studies of CoNV highlight the need for multifaceted approaches tailored to patient demographics and underlying ocular diseases. Future research and clinical trials are essential to elucidate optimal therapeutic strategies and explore combination therapies to ensure better management, improved treatment outcomes, and long-term remission of this visually disabling condition.<\/jats:p>","DOI":"10.3390\/biology15020136","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:52:57Z","timestamp":1768319577000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Corneal Neovascularization: Pathogenesis, Current Insights and Future Strategies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7973-3391","authenticated-orcid":false,"given":"Evita","family":"Muller","sequence":"first","affiliation":[{"name":"West of England Eye Unit, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Feinberg","sequence":"additional","affiliation":[{"name":"West of England Eye Unit, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK"},{"name":"Faculty of Health and Life Sciences, University of Exeter Medical School, Exeter EX1 2LU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-9764","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Woronkowicz","sequence":"additional","affiliation":[{"name":"North Devon District Hospital, Royal Devon University Healthcare NHS Foundation Trust, Barnstaple EX31 4JB, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"West of England Eye Unit, Royal Devon University Healthcare NHS Foundation Trust, Exeter EX2 5DW, UK"},{"name":"Faculty of Health and Life Sciences, University of Exeter Medical School, Exeter EX1 2LU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/bjophthalmol-2012-302137","article-title":"Subconjunctival bevacizumab induces regression of corneal neovascularisation: A pilot randomised placebo-controlled double-masked trial","volume":"97","author":"Petsoglou","year":"2013","journal-title":"Br. 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