Review · Ophthalmology / Ocular surface

Factors modulating corneal wound healing

Past, present and future — one fact sheet per agent: mechanism of action, route of administration, dosage, level of evidence (Oxford CEBM + simplified scale) and regulatory status (FDA, EU marketing authorisation, availability in France / Asia / United States).

Author: Pr Éric E. Gabison (MD, PhD — ophthalmology, cornea & ocular surface) · Reference document intended for an MD-PhD readership · Compiled 6 August 2026, sourced 7 August 2026 · Sources: PubMed/PMC, FDA, EMA, ANSM, ClinicalTrials.gov, specialty journals — every key study is linked to its PMID/DOI/NCT where one exists.
Disclaimer: informative and scientific document — does not replace current prescribing information/marketing authorisations or clinical judgment. Many corneal uses are off-label or hospital-compounded preparations.

Where this review comes from. It expands on chapter 21 of the SFO 2023 Report, “Corneal wound-healing agents” (Médicaments et biothérapies en ophtalmologie), written by Pr Éric E. Gabison for the French Society of Ophthalmology. The chapter sets the frame and gathers the main clinical studies for each agent; the sheets that follow extend it, agent by agent, with regulatory status and data published since. Read the chapter — open access (in French).

Methodology & levels of evidence

Two grading systems are given for each agent, as requested: a formal level and a simplified scale, always accompanied by key studies.

Grading system used

Formal level — Oxford CEBM (2011) I = systematic review / meta-analysis of randomised trials or high-powered RCT · II = individual RCT or prospective cohort study · III = non-randomised controlled study / cohort · IV = case series, case-control study · V = mechanistic, preclinical data or expert opinion. (GRADE mentioned where relevant.)

Simplified scale

Strong — robust evidence (RCT / MA) Moderate — consistent, limited data Weak — case series / heterogeneous Investigational — preclinical / investigational Negative — delays/impairs healing

Reading tip: each fact sheet carries badges (Oxford level, simplified scale, temporal category) and a 5-column regulatory table (FDA · EU MA · France · USA · Asia). The document is self-contained (no connection required) and optimised for printing (one section per page).

Physiopathological overview

Corneal healing unfolds in intertwined phases that constitute the targets of the agents described below.

1 · Epithelial phaseMigration (lamellipodia, α5/α6 integrins, fibronectin), proliferation from limbal stem cells (p63-bright), then differentiation and restoration of adhesion complexes (hemidesmosomes, basement membrane). Targets: EGF, HGF, serum, hyaluronate, insulin, NGF.

2 · Stromal phaseEarly keratocyte apoptosis followed by activation into fibroblasts/myofibroblasts (α-SMA, TGF-β) → collagen synthesis and remodelling. Excess = fibrosis/haze; protease/anti-protease imbalance (MMP-2/-9, collagenases) = stromal melting. Targets: MMC, TGF-β, MMP inhibitors, vitamin C.

3 · Innervation & trophic supportTrigeminal (V1) nerves release NGF, substance P, CGRP, IGF-1, essential for epithelial renewal. Their loss → neurotrophic keratopathy (Mackie classification, stages 1–3). Targets: cenegermine (rhNGF), substance P + IGF-1, PEDF+DHA, neurotisation.

4 · InflammationNecessary but deleterious when excessive (neutrophil proteases, cytokines). Modulated by corticosteroids, amniotic membrane, tetracyclines, ciclosporin.

The six families, in summary

Growth factors and blood-derived products in corneal wound healingMatrix agents, regenerating agents and protective devices for the corneaAnti-collagenolytics and prevention of corneal meltingMechanical adjuncts and modulation of corneal fibrosisWhat delays corneal healing: eye drops and toxic agentsEmerging therapies in corneal wound healing: cells, genes, exosomes

Directory of fact sheets, by category

36 agents, one dedicated page each. Click a name to open its full fact sheet.

1 · Growth factors & blood derivatives

Delivery of epitheliotrophic factors (EGF, TGF-β, NGF, IGF-1, PDGF, fibronectin). Most blood derivatives are not registered medicines: they fall under hospital preparation (French Blood Establishment, EFS) or compounding pharmacy, used off-label.

2 · Matrix, regenerative agents & supportive devices

Restoration of the extracellular matrix, mechanical protection and a scaffold for re-epithelialisation.

3 · Anticollagenolytics & anti-melt agents

Corneal melting results from an excess of zinc-dependent matrix metalloproteinases (MMP-1/-8/-13 collagenases, MMP-2/-9 gelatinases). Strategy: zinc chelation, transcriptional repression and supply of endogenous inhibitors.

4 · Mechanical, surgical adjuncts & fibrosis modulators

Non-pharmacological interventions protecting the ocular surface, plus mitomycin C as a deliberate anti-fibrotic modulator.

5 · Factors delaying or impairing healing

As the brief covers every modulating factor, this section brings together the clinically decisive negative modulators — often iatrogenic. The four most important: BAK, corticosteroids on a defect/melting cornea, topical NSAIDs, topical anaesthetic abuse.

6 · Emerging therapies — cellular, gene & innovative

Research frontier. Only Holoclar is an approved product (EMA); everything else is investigational or preclinical.