Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial.

Purpose: Neurotrophic keratopathy is part of the leprosy sequelae and causes progressive deterioration of visual acuity. Although leprosy is bacteriologically curable, there is currently no efficient treatment. Eye drops containing tetrapeptides, phenylalanine-glycine-leucine-methionine-amide (FGLM-NH) and serine-serine-serine-arginine (SSSR), derived from substance P and insulin-like growth factor 1, are clinically efficacious in the treatment of corneal epithelial disorders caused by neurotrophic keratopathy. To further investigate the effect of this treatment on leprosy sequalae, we evaluated the clinical efficacy of FGLM-NH+SSSR eye drops for treating neurotrophic keratopathy.

Design: Clinical trial: interventional, multicenter, exploratory, single-arm, before and after comparison.

Participants: The eyes (12) of 11 patients, aged >60 years, were studied from 2 leprosy sanatoriums in Japan.

Methods: Patients with neurotrophic keratopathy in leprosy sanatorium, specifically those with corneal perception of <40 mm, assessed by the Cochet-Bonnet corneal esthesiometer, and persistent corneal epithelial defects (PEDs) or corneal stromal thinning, or both, were included in this study. Those treated for infection in the acute phase were excluded from the study. Eye drops containing FGLM-NH 0.05% and SSSR 5 × 10% were administered 4 times daily for up to 3 months. Fluorescein staining and optical corneal sections were photographed using a slit lamp microscope at protocol-set intervals. Where possible, anterior segment OCT was performed before and after the intervention.

Main Outcome Measures: The primary outcome measured was improvement in neurotrophic keratopathy. The patient was judged to have improved when ≥1 of the following criteria were met: (1) healing epithelial defects or (2) increased thickness in the thin area of the cornea. Secondary end points were visual acuity, subjective findings, and time to complete healing for a PED.

Results: Neurotrophic keratopathy on epithelial defects or stromal thickness improved in 83.3% of the patients (90% confidence interval 56.2%-97.0%,  < 0.00001). The mean value of corrected visual acuity increased -0.16 by logarithm of the minimum angle of resolution. There were no adverse events reported in association with the treatment.

Conclusions: We confirmed that FGLM-NH+SSSR eye drops are effective for neurotrophic keratopathy without any adverse reaction in leprosy. These results should be disseminated to any parties who could need this information.

Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.