关键词: cenegermin corneal nerves neurotrophic keratitis neurotrophic keratopathy recombinant human nerve growth factor

来  源:   DOI:10.3389/fnins.2023.1210179   PDF(Pubmed)

Abstract:
UNASSIGNED: Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using in vivo confocal microscopy (IVCM) and on corneal sensitivity in NK patients.
UNASSIGNED: This is a retrospective, longitudinal, case-control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison.
UNASSIGNED: The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30-93 years). Total, main, and branch nerve densities [median (range) in mm/mm2] were lower in the NK group pre-treatment [2.3 (0.0-21.1); 1.7 (0.0-13.0); 0.5 (0.0-10.2); respectively] vs. controls [22.3 (14.9-29.0); 10.1 (3.2-15.4); and 12.1 (6.2-18.4), (p < 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0-19.4, p = 0.0083) for total, 3.5 (0.0-13.2, p = 0.0059) for main, and 2.0 (0.0-10.4, p = 0.0251) for branch nerves, but remained lower than controls (p < 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (p = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0-1.6) to 0.12 (-0.1 to 1.6) (p = 0.007).
UNASSIGNED: Patients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.
摘要:
神经营养性角膜病(NK)是一种导致角膜感觉减弱的神经退行性角膜疾病。先前的研究发现Cenegermin0.002%,重组人神经生长因子(rhNGF),改善2期和3期NK患者的角膜上皮愈合。然而,rhNGF对角膜感觉和神经再生的影响尚未得到很好的证实。因此,本研究旨在使用体内共聚焦显微镜(IVCM)分析rhNGF对NK患者角膜神经再生的影响以及对角膜敏感性的影响。
这是一个回顾,纵向,包括NK患者的病例对照研究,用rhNGF治疗至少4周,治疗前和治疗后的IVCM图像可用于分析。进行了图表审查,记录了先前的医疗和手术史,临床症状和体征,和角膜感觉使用Cochet-Bonnet美学测量法。通过IVCM评估角膜神经参数。从健康受试者的数据库中选择性别和年龄匹配的参考对照用于比较。
该研究包括25名患者,22例(88%)1期,2例(8%)2期和1例(4%)3期NK患者,年龄中位数为64岁(范围:30-93岁)。总计,主要,NK组治疗前[2.3(0.0-21.1);1.7(0.0-13.0);0.5(0.0-10.2);控制[22.3(14.9-29.0);10.1(3.2-15.4);和12.1(6.2-18.4),(所有p<0.0001),分别]。与治疗前相比,治疗后的神经密度增加至5.3(0.0-19.4,p=0.0083),3.5(0.0-13.2,p=0.0059),分支神经为2.0(0.0-10.4,p=0.0251),但仍低于对照组(全部p<0.0001)。角膜感觉从治疗前的2.3±1.1cm增加到治疗后的4.1±1.4cm(p=0.001)。rhNGF治疗后,最佳矫正视力中位数从0.4(0.0-1.6)显着增加到0.12(-0.1至1.6)(p=0.007)。
接受至少4周rhNGF治疗的NK患者,显示治疗后角膜神经密度显着增加。角膜感觉显著增加,以及最佳矫正视力,治疗后观察到。
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