背景:Cenegermin(Oxervate,DompèFarmaceutici,米兰,IT),重组人NGF,是治疗神经营养性角膜病变(NK)的潜在新药,一种罕见但具有挑战性的影响角膜的疾病。迄今为止,缺乏评估其对角膜神经和敏感性的中期影响的研究。
目的:评估Cenegermin治疗NK的患者基底下角膜神经的恢复和形态,并评估其与角膜敏感性的相关性。
方法:这种前瞻性,观察性病例系列研究于2018年5月至2020年8月在维罗纳大学眼科诊所进行.临床评价,灵敏度,和体内共聚焦显微镜(IVCM)在中央和所有四个角膜部分在基线进行,治疗结束(8周),治疗后2、4和8个月。连续NK患者(2-3期),用Cenegermin治疗(每天1滴6次,共8周),已注册。每次访问期间,角膜神经纤维长度(CNFL),角膜神经纤维总支密度(CTBD),测量角膜神经纤维分形维数(CNFraD)和Cochet-Bonnet美学(CBE)。
结果:我们招募了18名患者。治疗8周后,14/18(78%)患者的NK完全愈合;然后在14(78%),15(83%),13名(72%)患者在2-,4-,8个月,分别。从8周开始,经过4个月的随访,所有角膜部位的CBE均逐渐改善(p≤0.01),此后继续。有显著的角膜神经再生,尤其是在周围角膜:向心进展开始于8周(CNFL和CNFrad)和显著分支开始于2个月(CTBD),一直持续到后续行动结束。部门耦合IVCM和CBE结果在所有评估中都相关(从2个月开始,所有r≥0.62,外围部门的价值最高)。
结论:在Cenegermin后,我们观察到基底角膜下神经再生,敏感性的恢复和持久的上皮愈合,这表明NK患者在停药后几个月其作用持续存在。
BACKGROUND: Cenegermin (Oxervate, Dompè Farmaceutici, Milan, IT), a recombinant human NGF, is a potentially healing new drug for neurotrophic keratopathy (NK), a rare but challenging disease affecting the cornea. To date, studies that evaluate its mid-term effect on corneal nerves and sensitivity are lacking.
OBJECTIVE: To evaluate the recovery and morphology of subbasal corneal nerves in patients treated with Cenegermin for NK and assess their correlation with corneal sensitivity.
METHODS: This prospective, observational case series study was carried out between May 2018 and August 2020 at the Ophthalmic Clinic of the University of Verona. Clinical evaluation, sensitivity, and in vivo confocal microscopy (IVCM) were performed in the central and all four corneal sectors at baseline, the end of therapy (8 weeks), and 2, 4, and 8 months after therapy. Consecutive patients with NK (stage 2-3), treated with Cenegermin (1 drop 6 times daily for 8 weeks), were enrolled. During each visit, Corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber fractal dimension (CNFraD) and Cochet-Bonnet esthesiometry (CBE) were measured.
RESULTS: We enrolled 18 patients. Complete NK healing was noted in 14/18(78%) patients after 8 weeks of treatment; then in 14(78%), 15(83%), and 13(72%) patients at 2-, 4-, and 8-months, respectively. Starting at 8 weeks through 4-month follow-up there was progressive improvement in CBE in all corneal sectors (p ≤ 0.01), which continued thereafter. There was significant corneal nerve regrowth especially in the peripheral cornea: centripetal progression starting at 8 weeks (CNFL and CNFrad) and significant branching starting at 2 months (CTBD), which continued through to the end of follow up. Sector-coupled IVCM and CBE findings correlated at all evaluations (all r ≥ 0.62 starting at 2 months, with highest values in the peripheral sectors).
CONCLUSIONS: After Cenegermin we observed a subbasal corneal nerve regeneration, a recovery of sensitivity and a lasting epithelial healing, suggesting that the effect of its action persists several months after discontinuation in patients with NK.