Neurotrophic keratopathy: a new therapeutic approach using a novel matrix regenerating agent

Abstract

Purpose: Neurotrophic keratopathy (NK) is a sight-threatening degenerative corneal disease, characterized by reduced corneal sensitivity, spontaneous epithelial breakdown and impairment of corneal healing. Treatment is usually of poor or transient efficacy and rehabilitation of the corneal healing response is rarely accomplished. Cacicol^® is a new regenerating agent (RGTA) designed to mimic heparan sulphates, protecting from proteolysis and enabling growth factors and cytokines to act on the injury. We performed a prospective, non-controlled, interventional study to evaluate the efficacy of Cacicol^® in the treatment of NK.

Methods: Patients with persistent corneal neurotrophic ulcers, not responding to other therapies, were treated with RGTA eye drops. All started with one instillation per week, increased to two instillations per week in the absence of ulcer area decrease. During follow-up, slit-lamp examination, anterior segment photography and best-corrected visual acuity were analysed. Ulcer evolution was evaluated using software image analysis of slit-lamp photographs. Ulcer area was calculated as proportion of total corneal area. Grading of images was made by an independent reader, blinded to patient’s identity and clinical status.

Results: We included 17 eyes of 17 patients. All patients except one (94.12%) had complete ulcer healing within an average of 3.53±2.17 weeks - ranging from 1 to 8.14 weeks. The healing rate after 7 days of treatment was 23.53% (n=4), followed by 41.18% (n=7) by day 14, 52.94% (n=9) after 21 days and 70.59% (n=12) within the first month. Mean ulcer area decreased significantly from 13.81±16.16% on the baseline to 4.52±7.59% on the 7^th day (n=13, p=0.004) and to 0.46±1.21% on the 14^th day (n=10, p=0.04). Mean ulcer area then stabilized - 0.79±1.32% on the 3^rd week (n=8, p=0.43) and 0.48±0.33 on the 1^st month (n=5, p=0.351). By the end of the 2^nd month all ulcers had healed except for one, occupying 2.10% of corneal area. The mean number of instillations until complete healing was 5.25±3.38. No neovascularization was observed but moderate corneal scarring was noticed. Despite successful reepithelization, improvement in visual acuity was not significant (p=0.157). One case of recurrence (5.88%) ocurred one month after healing. No systemic or local side effects were noticed.

Conclusions: RGTA (Cacicol^®) appears to be an effective and safe new alternative in the management of NK.