Summary
9 · Key references (selection)
Review — modulators of corneal healing › References
Growth factors / blood derivatives
Bonini S et al. REPARO, Ophthalmology 2018 · Pflugfelder SC et al. NGF0214, Ophthalmology 2020 ·
EMA — Oxervate EPAR (2017) · FDA — cenegermine approval (2018) ·
He et al. ASED dry-eye meta-analysis, Front Med 2024 · AAO Ophthalmic Technology Assessment (ASED), Ophthalmology 2020 ·
Vajpayee et al. cord serum, Br J Ophthalmol 2003 · Alió JL et al. (E-PRP) ·
Abdi et al. topical insulin for PED, Sci Rep 2024 · RGN-259 phase III (PMC9820614) & SEER-3 (2025) ·
Wilson SE et al. KGF/HGF/EGF after epithelial wounding, Exp Eye Res 1999; KGF accelerates healing in vivo, 1995.
Matrix agents & devices
Lee & Tseng, Am J Ophthalmol 1997 · Meller et al. burns, Ophthalmology 2000 ·
Cochrane (Clare et al. 2012, amniotic membrane/burns) · Aifa et al. RGTA, IOVS 2012 ·
Vejdani et al. hyaluronate/abrasion (RCT) 2015 · Willoughby et al. collagen shields, Surv Ophthalmol 2002 ·
RCT vitamin A post-PRK.
Anti-melt / MMP
Dursun et al. recurrent erosions/doxycycline, Am J Ophthalmol 2001 ·
Pfister & Paterson, ascorbate/alkali burns, IOVS 1976 ·
Berman/Slansky (collagenase inhibitors) · Gabison EE, Huet E, Baudouin C, Menashi S, EMMPRIN/CD147 & MMP induction in corneal wound healing, Prog Retin Eye Res 2009 · MMP review in infectious ulcers, Surv Ophthalmol 2023 ·
Dutra & Wilson, topical losartan / corneal fibrosis (dosage, efficacy, epithelial toxicity), J Ocul Pharmacol Ther 2025; HSV/VZV series, Case Rep Ophthalmol 2025.
Negative modulators
Gabison EE et al., diclofenac/perforation & MMP, Ophthalmology 2003 · Congdon/Flynn et al. NSAIDs — keratitis/perforation, Ophthalmology 2001 · FDA Acular (ketorolac) label ·
"Ocular benzalkonium chloride exposure", Eye 2021 · corticosteroids & scar resistance, Am J Ophthalmol ·
anesthetic-abuse keratopathy (Cornea; EyeWiki) · in vitro epithelial toxicity of aminoglycosides/FQ.
Future therapies
Rama et al. CLET, NEJM 2010 · EMA Holoclar EPAR (2015; standard MA 2024) ·
Jurkunas et al. CALEC, Nat Commun 2025 (NCT02592330) · NEXPEDE-1 (NCT05966493, Nexagon) ·
Grupcheva/Becker et al. Cx43 peptide, Exp Eye Res 2013 · MSC-exosome microneedles, ACS Nano 2024 ·
AAV6 endothelium, Cell Rep Med 2026 · Cortina/Bazan, PEDF+DHA, IOVS 2012.
Numbered bibliography (selection, with identifiers)
Verifiable references with clickable PMID/DOI (indexable and citable). Selective list; other works are cited inline within each fact sheet.
- Gabison EE, Chastang P, Menashi S, Mourah S, Doan S, Oster M, Mauviel A, Hoang-Xuan T. Late corneal perforation after photorefractive keratectomy associated with topical diclofenac: involvement of matrix metalloproteinases. Ophthalmology. 2003;110(8):1626-31. PMID 12917183.
- Gabison EE, Huet E, Baudouin C, Menashi S. Direct epithelial–stromal interaction in corneal wound healing: role of EMMPRIN/CD147 in MMPs induction and beyond. Prog Retin Eye Res. 2009;28(1):19-33. PMID 19056510.
- Bonini S, Lambiase A, Rama P, et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis (REPARO). Ophthalmology. 2018;125(9):1332-1343. PMID 29653858.
- Pflugfelder SC, Massaro-Giordano M, Perez VL, et al. Topical recombinant human nerve growth factor (cenegermin) for neurotrophic keratopathy: NGF0214. Ophthalmology. 2020;127(1):14-26. PMID 31585826.
- Rama P, Matuska S, Paganoni G, Spinelli A, De Luca M, Pellegrini G. Limbal stem-cell therapy and long-term corneal regeneration. N Engl J Med. 2010;363(2):147-155. PMID 20573916.
- Jurkunas UV, et al. Cultivated autologous limbal epithelial cell (CALEC) transplantation: phase I/II trial. Nat Commun. 2025. NCT02592330.
- Dutra BAL, Wilson SE. Topical losartan in the management of corneal scarring fibrosis: update on dosage, efficacy, and potential epithelial toxicity. J Ocul Pharmacol Ther. 2025. PMID 40238717.
- Topical losartan treatment of herpes simplex virus- or varicella-zoster virus-induced corneal scarring: a case series. Case Rep Ophthalmol. 2025. PMID 40248823.
- Congdon NG, Schein OD, von Kulajta P, Lubomski LH, Gilbert D, Katz J. Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs. J Cataract Refract Surg. 2001. PMID 11320025.
- Dursun D, Kim MC, Solomon A, Pflugfelder SC. Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids. Am J Ophthalmol. 2001;132(1):8-13. PMID 11438047.
- Wilson SE, Mohan RR, Ambrósio R, et al. Expression of HGF, KGF, EGF and receptor messenger RNAs following corneal epithelial wounding. Exp Eye Res. 1999. PMID 10192796.
- Chandrasekher G, et al. Keratinocyte growth factor accelerates corneal epithelial wound healing in vivo. Invest Ophthalmol Vis Sci. 1995. PMID 7601632.
- Abdi D, et al. Topical insulin for refractory persistent corneal epithelial defects. Sci Rep. 2024. PMID 38816428.
- Pfister RR, Paterson CA. Ascorbic acid in the treatment of alkali burns of the eye. Ophthalmology / Invest Ophthalmol Vis Sci. 1976–1980. PMID 992963.
- European Medicines Agency (EMA). Holoclar (ex vivo expanded autologous human corneal epithelial cells containing stem cells) — EPAR (conditional MA 2015; standard MA 2024). ema.europa.eu/…/holoclar.
- EMA. Oxervate (cenegermin) — EPAR (EU MA 2017). ema.europa.eu/…/oxervate.
- Amber Ophthalmics. NEXPEDE-1 — phase 2/3 trial of Nexagon (lufepirsen) in persistent PED. NCT05966493.
Identifiers (PMID/DOI/NCT) verified on PubMed / ClinicalTrials.gov at the time of compilation. A final check is recommended before any formal publication (exact volume/page numbers).