Home › Review — modulators of corneal healing › Growth factors and blood-derived products in corneal wound healing

Growth factors and blood-derived products in corneal wound healing

Overview

Autologous serum (eye drops) — ASED

Preparation derived from the patient's own blood (no INN or brand name) · diluted 20–100% in physiological saline

Biological tear substitute: provides EGF, TGF-β, PDGF, NGF, IGF-1, fibronectin, vitamin A, substance P + anti-proteases (α2-macroglobulin, TIMP) and antimicrobial factors (lysozyme, IgG) at near-physiological concentrations. Promotes epithelial migration/proliferation/differentiation and neurotrophic support.

Persistent epithelial defects (PED), severe/refractory dry eye (Sjögren, GVHD), neurotrophic keratopathy, recurrent erosions, burns, post-LASIK/PRK.

Topical. Usual concentrations 20% and 50% (100% for refractory PED); 4 to 8×/day, up to hourly in acute PED. Frozen aliquots (−20 °C, ~3–6 months); vial in use ~1 week at +4 °C.

Oxford II–III / GRADE weak–moderate · Scale: Moderate. Small RCTs + numerous case series; solid for dry eye symptoms, more pragmatic for PED (lack of large RCTs).

Umbilical cord blood serum (allogeneic)

Umbilical cord blood serum eye drops (UCBS) — allogeneic alternative to autologous serum

Identical to autologous serum but richer in NGF, EGF, TGF-β and vitamin A — particularly suited to neurotrophic disease and when the patient's own serum cannot be used (infants, compromised systemic status).

Neurotrophic PED, severe dry eye, chemical burns, pediatrics, neurotrophic keratopathy.

Topical, 20% dilution (up to 100%), 4–8×/day; frozen aliquots.

Oxford II–IV · Scale: Moderate. Comparative RCTs/cohorts (benefit ≥ autologous serum in several series).

PRP / platelet-rich growth factors (PRGF-Endoret)

Autologous platelet concentrate (2–5× baseline count) · liquid or fibrin membrane

Release, upon activation/lysis, of α-granule factors (PDGF, TGF-β, VEGF, EGF, IGF-1, bFGF, HGF) + fibrin scaffold and adhesion proteins — factor load higher than plain serum. PRGF is leukocyte-poor (less pro-inflammatory).

PED, dry eye, neurotrophic keratitis, recurrent erosions, post-surgery, burns; PRGF fibrin membrane as a surgical adjunct (ulcer/perforation).

Topical 4–6×/day for several weeks; concentration/preparation variable (diluted E-PRP, standardized PRGF-Endoret). Membranes applied intraoperatively.

Oxford II–IV / GRADE weak · Scale: Weak–Moderate. A few RCTs + numerous case series; high heterogeneity of protocols.

Cenegermine — recombinant human NGF · OXERVATE®

INN cenegermin (US: cenegermin-bkbj) · Dompé · first-in-class rhNGF

Recombinant human NGF (produced in E. coli) binding the high-affinity TrkA receptor and the low-affinity p75^NTR receptor (epithelium, keratocytes, sensory nerve endings). Restores neurotrophic support: epithelial proliferation/differentiation, corneal nerve regeneration and reinnervation.

Moderate to severe neurotrophic keratitis (stages 2–3: PED and ulcer). Only approved indication.

Eye drops 0.002% (20 µg/mL) · 1 drop 6×/day (~every 2 hours during waking hours) for 8 weeks. Cold chain, dedicated multidose delivery system.

Oxford I–II / GRADE moderate–high · Scale: Strong (for neurotrophic keratitis). Multicenter double-masked RCTs versus vehicle.

Recombinant human EGF (rhEGF) — eye drops

No single global brand · regional products (China; Cuba/CIGB; South Korea "Easyef"/nepidermin for skin)

Binding to the epithelial EGFR/ErbB1 receptor (tyrosine kinase) → RAS/MAPK and PI3K pathways → epithelial proliferation and migration, accelerated re-epithelialization. Overdosing may promote neovascularization (caution).

Epithelial defects, post-surgical healing (PRK/LASIK, pterygium), abrasions, diabetic keratopathy, burns — largely off-label / country-specific.

Topical, ~10–100 µg/mL (0.001–0.01%), generally 4×/day. No internationally harmonized regimen.

Oxford II–IV · Scale: Weak–Moderate. Solid biological rationale, few modern high-quality RCTs; neovascularization/dosing concerns.

Topical insulin (eye drops)

Regular human insulin diluted in artificial tears / physiological saline · repurposing of an old molecule

Binding to epithelial insulin and IGF-1 receptors → PI3K/Akt and MAPK pathways → epithelial proliferation, migration and metabolic support; support of nerve function. Strong rationale in the diabetic/neurotrophic cornea.

Refractory PED (diabetic, neurotrophic), post-surgery (post-vitrectomy), dry eye — often 2^nd line when serum and conventional measures fail.

Topical, ~1 IU/mL (protocols 1–100 IU/mL), generally ~4×/day until closure (days to weeks). Refrigerated; not standardized.

Oxford II–IV / GRADE very low–low but improving · Scale: Weak–Moderate (emerging). Consistent positive signals in refractory PED, low cost, good tolerability.

Thymosin β4 — RGN-259

Synthetic regenerative peptide (43 aa) · RegeneRx / ReGenTree / HLB Therapeutics · not marketed

Peptide that sequesters G-actin: promotes epithelial migration/adhesion, anti-inflammatory effect (↓NF-κB), anti-apoptotic, nerve regeneration and reduced fibrosis (multimodal action).

Neurotrophic keratopathy (PED) and dry eye disease.

0.1% eye drops, ~4–6×/day for several weeks (preservative-free).

Oxford II but mixed/negative pivotal results · Scale: Investigational (not approved). One positive phase III RCT in neurotrophic disease (2022), but the confirmatory phase III SEER-3 missed its primary endpoint (June 2025) — strong placebo response.

KGF (FGF-7) & HGF — epithelial–stromal crosstalk factors

Keratinocyte growth factor / hepatocyte growth factor · keratocyte→epithelium paracrine signals · mostly preclinical in the cornea

KGF (FGF-7) and HGF are produced by stromal keratocytes and act in paracrine fashion on the epithelial receptors KGFR (FGFR2-IIIb) and c-Met — a major support of the epithelial–stromal regulatory loop. They stimulate epithelial proliferation, migration and differentiation and modulate the wound-healing response (their expression is induced after injury, in parallel with EGF). HGF also has effects on motility and a potential anti-fibrotic role.

Epithelial defects, delayed re-epithelialization after PRK, keratopathies — no established clinical indication; interest remains conceptual/translational.

Topical in animal/in vitro models (recombinant KGF/KGF-2); no human corneal dosing regimen. Note: palifermin (recombinant KGF-1) is approved IV for oral mucositis, not for the eye; repifermin (KGF-2) remained experimental.

Oxford IV–V (solid preclinical data: HGF/KGF/EGF mRNA induction after injury, accelerated healing in vivo in animals) · Scale: Investigational — no corneal clinical trial.

Key points

In practice, autologous serum remains the mainstay for persistent epithelial defects on a diseased surface: accessible, well tolerated, with thirty years of clinical experience — but a demanding preparation, frozen storage and a composition that varies from patient to patient, which explains the absence of a large randomised trial.

Cenegermin occupies a distinct place: it is the only product in this family with a marketing authorisation, for a narrow indication — stage 2 or 3 neurotrophic keratitis — and with level I evidence. Its cost and supply route make it a second-line treatment.

The other agents — rhEGF, topical insulin, thymosin β4, KGF/HGF — share a sound rationale and encouraging series, but none has a simple route of access in France. Topical insulin, prepared by hospital pharmacies, is the one whose benefit-to-accessibility ratio is improving fastest.

The other families in this review

Updated 26 August 2026