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-...

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Main Authors: Shoko Kondo, MD, Yoshiko Okano, MD, PhD, Satoshi Iraha, MD, PhD, Shoji Tokunaga, PhD
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Ophthalmology Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666914524001702
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author Shoko Kondo, MD
Yoshiko Okano, MD, PhD
Satoshi Iraha, MD, PhD
Shoji Tokunaga, PhD
author_facet Shoko Kondo, MD
Yoshiko Okano, MD, PhD
Satoshi Iraha, MD, PhD
Shoji Tokunaga, PhD
author_sort Shoko Kondo, MD
collection DOAJ
description 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-NH2) 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-NH2+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-NH2 0.05% and SSSR 5 × 10-6% 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%, P < 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-NH2+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 Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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spelling doaj-art-1cba7e56d07142d18b208be0208368e82025-08-20T02:21:03ZengElsevierOphthalmology Science2666-91452025-03-015210063410.1016/j.xops.2024.100634Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical TrialShoko Kondo, MD0Yoshiko Okano, MD, PhD1Satoshi Iraha, MD, PhD2Shoji Tokunaga, PhD3Department of Ophthalmology, National Sanatorium Kikuchi Keifuen, Koshi, Japan; Correspondence: Shoko Kondo, MD, National Sanatorium Kikuchi Keifuen, 3796 Sakae, Koshi-shi, Kumamoto 861-1113, Japan.Department of Ophthalmology, National Sanatorium Oshima Seishoen, Takamatsu, JapanDepartment of Ophthalmology, National Sanatorium Kikuchi Keifuen, Koshi, Japan; Department of Ophthalmology, Kumamoto University School of Medicine, Kumamoto, JapanMedical Information Center, Kyushu University Hospital, Fukuoka, JapanPurpose: 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-NH2) 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-NH2+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-NH2 0.05% and SSSR 5 × 10-6% 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%, P < 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-NH2+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 Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914524001702Insulin-like growth factor 1LeprosyNeurotrophic keratopathySubstance PTetrapeptides
spellingShingle Shoko Kondo, MD
Yoshiko Okano, MD, PhD
Satoshi Iraha, MD, PhD
Shoji Tokunaga, PhD
Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial
Ophthalmology Science
Insulin-like growth factor 1
Leprosy
Neurotrophic keratopathy
Substance P
Tetrapeptides
title Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial
title_full Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial
title_fullStr Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial
title_full_unstemmed Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial
title_short Substance P- and Insulin-like Growth Factor 1-derived Tetrapeptides for Neurotrophic Keratopathy Related to Leprosy: A Clinical Trial
title_sort substance p and insulin like growth factor 1 derived tetrapeptides for neurotrophic keratopathy related to leprosy a clinical trial
topic Insulin-like growth factor 1
Leprosy
Neurotrophic keratopathy
Substance P
Tetrapeptides
url http://www.sciencedirect.com/science/article/pii/S2666914524001702
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