Comparative Clinical And In Vivo Confocal Microscopy Outcomes Of Medical And Surgical Regenerative Strategies For Neurotrophic Keratopathy

Neurotrophic keratopathy (NK) is a rare degenerative corneal disease characterized by reduced corneal sensitivity, epithelial breakdown, and risk of ulceration due to trigeminal nerve impairment. Regenerative approaches have recently emerged to restore ocular surface homeostasis and corneal innervation. This study evaluates the clinical response to different medical and surgical regenerative strategies in moderate-to-advanced NK, focusing on corneal sensory recovery and structural nerve regeneration assessed through multimodal imaging.

University Eye Clinic, IRCCS Ospedale Policlinico San Martino, AOM, University of Genoa, Italy

Twenty-seven eyes with moderate-to-advanced NK were retrospectively analyzed. Patients were treated with different regenerative strategies including recombinant human nerve growth factor (cenegermin), thymosin β4, or minimally invasive indirect corneal neurotization. Clinical evaluation included corneal sensitivity measured with the Cochet-Bonnet esthesiometer, Schirmer I test, tear film break-up time (BUT), Ocular Surface Disease Index (OSDI), anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy to assess corneal nerve regeneration. Outcomes during the first six months after treatment were analyzed.

All treatment groups showed epithelial healing. Treatment with recombinant human nerve growth factor resulted in rapid improvement of corneal sensitivity, exceeding 10 mm on Cochet-Bonnet esthesiometry within two months, with a reduction of Ocular Surface Disease Index scores. Thymosin β4 produced gradual symptomatic improvement and stabilization of tear film parameters, although recurrence occurred in one eye after treatment discontinuation. In surgically treated eyes, recovery of corneal sensitivity exceeding 15 mm was observed within two months. In vivo confocal microscopy demonstrated subepithelial nerve regeneration, while AS-OCT confirmed epithelial restoration and surface stabilization.

Different regenerative strategies may effectively restore ocular surface integrity in neurotrophic keratopathy but show distinct response profiles depending on the severity of trigeminal nerve impairment. Medical therapies can promote epithelial healing and support corneal nerve recovery, particularly when some degree of innervation persists, whereas corneal neurotization may provide structural restoration in cases of severe trigeminal damage. Multimodal imaging with anterior segment optical coherence tomography and in vivo confocal microscopy may help document structural recovery and support personalized management of neurotrophic keratopathy.