Correct the setting, lubricate, control inflammation & proteolysis
Treatment first aims to identify and remove the factors delaying healing, then to stimulate re-epithelialization and to block stromal proteolysis. The approach is stepwise and regularly reassessed.
1. Correct the setting and remove iatrogenic factors
Stop (temporarily or permanently) any potentially toxic eye drop; a drug holiday often helps unmask the causative agent. Prefer preservative-free formulations. Prolonged use of topical antibiotics in non-infectious ulcers promotes delayed healing and resistance: favor antiseptics and drug holidays. Treat mechanical and exposure factors (lid surgery, epilation/electrolysis of trichiatic lashes, correction of lagophthalmos).
2. Lubrication and surface protection
Preservative-free tear substitutes (hyaluronic acid, with healing properties), gels and ointments at night, punctal plugs where the etiology allows. The bandage contact lens worn continuously protects the healing epithelium, under antiseptic cover and close monitoring.
3. Control inflammation and proteolysis
Anti-inflammatory drugs (steroidal or not) must be handled with caution: they inhibit healing and can worsen melting. In burns, corticosteroids are useful for the first 7–10 days then become harmful.
Useful antiproteases: systemic tetracyclines (doxycycline 50–100 mg/day, anti-MMP effect), topical N-acetylcysteine. Topical ciclosporin is a suitable maintenance treatment for severe dry eye (Sjögren, rosacea). High-dose oral ascorbic acid and topical vitamin A retain an empirical place, especially in burns and deficiencies.
Trophic factors: blood derivatives, cenegermin (NGF), RGTA, insulin
Blood derivatives
Autologous serum (usually 20%) remains a mainstay: rich in EGF, TGF-β, fibronectin, vitamin A, substance P, IGF-1, NGF and protease inhibitors, it improves epithelial healing and limits melting, with documented benefit in neurotrophic keratopathy and corneal nerve regeneration [9]. Later developments include umbilical cord blood serum (even richer in growth factors), platelet-rich plasma (PRP) and plasma rich in growth factors (PRGF/E-PRP), useful when repeated autologous sampling is not possible.
Cenegermin is a recombinant human nerve growth factor (rhNGF), the first topical biologic to obtain marketing authorization in ophthalmology (European MA 2017, FDA 2018; assessed by the HAS). Indication: moderate to severe neurotrophic keratitis (Mackie stages 2 and 3) in adults. It acts on the TrkA/p75 receptors. Regimen: eye drops at 20 µg/mL, 1 drop 6 times a day (every 2 hours) for 8 weeks. In the pivotal trials (REPARO in Europe, the US trial), about 70% of patients achieve complete corneal healing at 8 weeks, versus ~29% under vehicle, with healing maintained at one year in most responders [7,8].
RGTA (poly-carboxymethylglucose sulfate; Cacicol®) are biopolymers that mimic the heparan sulfate of the extracellular matrix; they protect growth factors from degradation and rebuild the scaffold needed for cell migration. Used as a medical device (typically 1 drop every 1–2 days), they have shown value in refractory neurotrophic ulcers and PEDs, with good tolerability [10].
Insulin eye drops (hospital preparation, low dilution, off-label) are attracting growing interest: several series and recent systematic reviews report re-epithelialization of refractory PEDs, including of neurotrophic or diabetic origin, insulin acting as an epithelial growth factor (IGF-1/insulin pathway). An inexpensive, well-tolerated option, under evaluation in controlled trials [11].