ABSTRACT
Introduction: Corneal ulcers normally resolve spontaneously because of the proliferative ability of the corneal epithelium; however, sometimes, epithelial healing is diminished, even when standard treatments are administered. Hence, the treatment of refractory corneal ulcers is challenging and is the subject of ongoing efforts in preclinical and clinical development. Emerging treatment approaches include thymosine β4, CODA001, and topical insulin. Cenegermin eye drops, containing recombinant human nerve growth factor and ReGenerating Agent, a matrix therapy agent, have recently been commercialized for the treatment of moderate to severe neurotrophic keratitis in adults.
Areas covered: We describe emerging therapeutic approaches for the management of refractory corneal ulcers and treatments recently introduced to the market. Pubmed and Clinicaltrial.gov databases were first searched including the terms: “corneal ulcer” or “neurotrophic keratopathy” and “treatment.” Each treatment was searched in the same databases separately.
Expert opinion: Affections of the sensory corneal nerves are the main factor contributing to the pathophysiology of neurotrophic keratopathy; this explains the healing difficulties of this form of ulcer. Cenegermin is a promising therapy acting as a neurotrophic agent for corneal healing. ReGenerating Agent has led to rapid pain relief and corneal healing, but randomized clinical trials are still necessary for further assessment.
Article highlights
A refractory corneal ulcer is defined as a sterile corneal ulcer that has failed to respond to conventional therapy. Manifestations range from PED to stromal melting.
The treatment of refractory corneal ulcers is a challenge so efforts in preclinical and clinical development are necessary and ongoing.
Based on two randomized, double-blind, placebo-controlled, phase-II clinical studies, cenegermin eye drops, containing recombinant human nerve growth factor has recently been marked for the treatment of moderate to severe neurotrophic keratitis in adults.
Several observational, non-controlled studies suggested that instillation of ReGenerating Agent, a matrix therapy agent, promotes and expedites corneal healing.
Emerging treatment approaches for refractory corneal ulcers include Thymosine β4, CODA001, topical insulin, substance P and insulin-like growth factor 1, plasma enriched in growth factors eye drops and fingerprick autologous blood.
Declaration of interest
D Bremond-Gignac is a Consultant for Allergan, Alcon, Horus, Thea, Santen, and Novartis.
A. Daruich is a consultant for Novartis
F. Chiambaretta is a Consultant for Allergan, Alcon, Horus, Thea, Santen, and Novartis.
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose