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

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2024-10-21 DOI:10.1016/j.xops.2024.100634

Shoko Kondo MD , Yoshiko Okano MD, PhD , Satoshi Iraha MD, PhD , Shoji Tokunaga PhD

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Abstract

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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P物质和胰岛素样生长因子1衍生的四肽治疗与麻风病相关的神经营养性角膜病变：一项临床试验

目的：神经营养性角膜病变是麻风病后遗症的一部分，导致视力进行性恶化。虽然麻风病在细菌学上是可以治愈的，但目前还没有有效的治疗方法。含有P物质衍生的苯丙氨酸-甘氨酸-亮氨酸-蛋氨酸-酰胺（FGLM-NH2）和丝氨酸-丝氨酸-丝氨酸-精氨酸（SSSR）四肽滴眼液和胰岛素样生长因子1在临床上治疗神经营养性角膜病变引起的角膜上皮疾病是有效的。为了进一步探讨这种治疗对麻风后遗症的影响，我们评估了FGLM-NH2+SSSR滴眼液治疗神经营养性角膜病变的临床疗效。设计：临床试验：介入性、多中心、探索性、单臂、前后比较。研究对象：来自日本两家麻风病疗养院的11名患者的眼睛（12），年龄在50 ~ 60岁之间。方法：麻风疗养院神经营养性角膜病变患者，特别是角膜感知为2 0.05%，SSSR为5 × 10-6%的患者，每天给药4次，持续3个月。荧光素染色和光学角膜切片在协议设定的间隔使用裂隙灯显微镜拍摄。在可能的情况下，在干预前后进行前段OCT检查。主要观察指标：主要观察指标为神经营养性角膜病变的改善。当满足以下标准≥1项时，判断患者改善：(1)上皮缺损愈合或(2)角膜薄区厚度增加。次要终点是视力、主观表现和PED的完全愈合时间。结果：83.3%的神经营养性角膜病变患者上皮缺损或间质厚度改善（90%可信区间56.2% ~ 97.0%，P）。结论：我们证实FGLM-NH2+SSSR滴眼液对麻风病神经营养性角膜病变有效，无不良反应。这些结果应散发给任何可能需要这些资料的各方。财务披露：专有或商业披露可在本文末尾的脚注和披露中找到。

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