Home › Review — modulators of corneal healing › Matrix agents, regenerating agents and protective devices for the cornea
Matrix agents, regenerating agents and protective devices for the cornea
This family does not aim to stimulate the cell but to give it back a support. In a chronic ulcer the extracellular matrix has been degraded: the heparan sulfates that sequester and protect growth factors are gone, the basement membrane is altered, the epithelium has nothing to migrate on. Delivering a growth factor into such an environment is sowing on washed-away soil.
Three strategies coexist. Matrix substitution — RGTA, hyaluronate — replaces or mimics the lost components. Biological matrix grafting — amniotic membrane — provides a true basement membrane, with its collagens IV and VII, laminins and protease inhibitors. Mechanical protection — bandage lens, collagen shield — shields the migrating epithelium from lid shear, which alone can undo each night what the day achieved.
Overview
| Agent | Mechanism | Level of evidence |
|---|---|---|
| Human amniotic membrane (graft / PROKERA®) | Collagen IV/V/VII-, laminin-, and fibronectin-rich basement membrane that serves as a scaffold for epithelial adhesion/m… | Oxford II–IV Moderate Present · established |
| RGTA | "Matrix therapy": a biodegradable polysaccharide mimicking heparan sulfate, resistant to mammalian glycanases/heparanase… | Oxford III–IV Weak–Moderate Human: withdrawn |
| Bandage / therapeutic contact lenses (BCL, scleral lenses) | Mechanical protection (splinting) of the regenerating epithelium against eyelid shear → uninterrupted migration/adhesion… | Oxford II–IV Moderate–Strong Present · mainstay |
| Sodium hyaluronate (hyaluronic acid) | A pro-migratory effect mediated by the CD44 receptor (and RHAMM): adhesion, spreading, and directed migration of epithel… | Oxford I–II Moderate Present · universal |
| Vitamin A (retinol / retinoic acid) | Nuclear RAR/RXR receptors → epithelial differentiation, goblet (mucus) cell density, prevention of squamous metaplasia/k… | Oxford I (systemic) · II (topical) Strong (deficiency) Present · classic |
| Collagen shields | Dual function: mechanical bandage plus a dissolving collagen scaffold (migration support), and a drug-eluting reservoir… | Oxford IV–V Weak / Investigational Past |
Human amniotic membrane (graft / PROKERA®)
Cryopreserved (AmnioGraft, PROKERA — self-retaining ring) or dehydrated (AmbioDisk) · graft, patch, or filler
Collagen IV/V/VII-, laminin-, and fibronectin-rich basement membrane that serves as a scaffold for epithelial adhesion/migration; anti-inflammatory (exclusion and apoptosis of inflammatory cells, IL-1RA, IL-10), anti-fibrotic (TGF-β suppression), anti-angiogenic, and anti-protease. The HC-HA/PTX3 complex (preserved by cryopreservation, degraded by dehydration) accounts for most of the effect.
IndicationsRefractory neurotrophic PEDs, acute chemical/thermal burns, sterile ulcers and melts, partial limbal deficiency, bullous keratopathy (for pain relief), post-infectious surface reconstruction.
Route & dosingSurgical application (suture or fibrin glue) or self-retaining PROKERA for ~3–5 days (inserted like a large contact lens, sutureless, at the slit lamp). Can be repeated.
Level of evidenceOxford II–IV (a few RCTs, numerous cohorts; Cochrane review with limited certainty for burns) · Scale: Moderate.
Detailed sheet →RGTA — CACICOL® (poly-carboxymethylglucose sulfate, OTR4120)
Matrix-regenerating agent · heparan-sulfate mimetic · OTR3 (D. Barritault). Cacicol (human eye drops) — discontinued. The molecule remains available in veterinary medicine under the name Clerapliq®.
"Matrix therapy": a biodegradable polysaccharide mimicking heparan sulfate, resistant to mammalian glycanases/heparanases. Replaces destroyed HS, binds structural proteins (collagens, fibronectin, laminin), and re-protects heparin-binding growth factors (FGF, TGF-β, VEGF) in their native conformation → restoration of the matrix microenvironment. It is not a growth factor and has no intrinsic pharmacological/antibiotic activity.
IndicationsNeurotrophic corneal ulcers and refractory PEDs, delayed epithelial healing after cross-linking (CXL)/refractive surgery, dystrophic/recurrent ulcers.
Route & dosingSingle-dose eye drops. Distinctive feature: very low dosing frequency — 1 drop every 2 days (sometimes 1–2×/week), as the product is non-degradable and long-acting. Applied in the evening, for several weeks until closure.
Level of evidenceOxford III–IV (case series, no large corneal RCT) · Scale: Weak–Moderate (consistent positive series, without randomized confirmation).
Detailed sheet →Bandage / therapeutic contact lenses (BCL, scleral lenses)
High-Dk silicone hydrogel; scleral lenses / PROSE · purely mechanical action
Mechanical protection (splinting) of the regenerating epithelium against eyelid shear → uninterrupted migration/adhesion; covers exposed sub-basal nerves (pain relief); maintains hydration and a tear reservoir (scleral vaulting); tamponades micro-perforations. Can also serve as a drug reservoir.
IndicationsPED/recurrent erosions, post-surgery (PRK/CXL/PKP), bullous keratopathy (pain relief), filamentary keratitis, micro-perforations (with glue), retention of amniotic membrane. Caution in active infectious keratitis.
Route & dosingContinuous/extended wear from a few days to weeks, with topical antibiotic prophylaxis + preservative-free lubricants; scleral lenses worn during the day.
Level of evidenceOxford II–IV · Scale: Moderate–Strong (pain and closure after surgery), Moderate as an adjunct for PEDs.
Detailed sheet →Sodium hyaluronate (hyaluronic acid) — eye drops
0.1% to 0.3% · with or without preservative (Hylo, Vismed, Hyabak…)
A pro-migratory effect mediated by the CD44 receptor (and RHAMM): adhesion, spreading, and directed migration of epithelial cells; viscoelastic mucoadhesive rheological effect (hydration, prolonged tear break-up time, protection); mild free-radical scavenging effect.
IndicationsAdjunct to healing: superficial abrasions, post-PRK/cataract surgery, PEDs, dry-eye/diabetic epitheliopathy, surface protection.
Route & dosingTopical, 4–6×/day (up to hourly); 0.3% for severe involvement; preservative-free formulations preferred with frequent dosing.
Level of evidenceOxford I–II (RCTs, meta-analysis for abrasion/post-PRK) · Scale: Moderate (real but modest effect, adjunctive role).
Detailed sheet →Vitamin A (retinol / retinoic acid) — topical / systemic
Retinyl palmitate ointment (VitA-POS); systemic retinol (for deficiency)
Nuclear RAR/RXR receptors → epithelial differentiation, goblet (mucus) cell density, prevention of squamous metaplasia/keratinization. Deficiency → xerophthalmia, keratomalacia. Topically: accelerates re-epithelialization and supports the mucin layer.
IndicationsVitamin A deficiency / xerophthalmia / keratomalacia (systemic, sight-saving); severe dry eye, cicatricial conjunctivitis, burns with keratinization, post-PRK (adjunct).
Route & dosingSystemic (WHO xerophthalmia protocol): retinol 200,000 IU on days 1, 2, and 14 (adjusted in children). Topical: retinyl palmitate ointment 1–4×/day.
Level of evidenceOxford I (systemic, deficiency — RCT/WHO); II (topical, ocular surface) · Scale: Strong (deficiency) / Moderate–Weak (topical, outside deficiency).
Detailed sheet →Collagen shields
Cross-linked porcine/bovine collagen disc, dissolving in 12/24/72 h · largely obsolete
Dual function: mechanical bandage plus a dissolving collagen scaffold (migration support), and a drug-eluting reservoir (antibiotics/corticosteroids) that increases corneal contact time. Biodegradable (no removal required).
IndicationsPost-surgical healing (post-keratoplasty, RK/PRK era), post-abrasion, prolonged drug-delivery vehicle.
Route & dosingPlaced on the cornea (rehydrated), left in place until dissolution (12/24/72 h); can be pre-soaked in medication.
Level of evidenceOxford IV–V · Scale: Weak / Investigational — never demonstrated superiority over soft lenses; blurred vision, discomfort. Superseded.
Detailed sheet →Key points
The bandage lens is the simplest and most underrated measure: on its own it resolves a share of epithelial delays, provided it is placed early and monitored — the infectious risk on an ulcerated cornea is not negligible.
Amniotic membrane remains the reference in severe situations: deepening ulcer, early melting, chemical burn. Its effect combines support, anti-inflammatory and anti-protease action, and it is the only member of this family to provide all three at once.
RGTA illustrates a recurring difficulty of the field: an elegant mechanism, consistent positive series, no sizeable randomised trial — and withdrawal of the human eye drop, leaving the molecule available in veterinary medicine. Hyaluronate and vitamin A belong to supportive care rather than to the treatment of the ulcer itself.
The other families in this review
Updated 26 August 2026