Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Policlinico G.B. Rossi, P.Le L.A, Scuro 10, 37134, Verona, VR, Italy.
Ophthalmic Unit, San Bassiano Hospital, Via dei Lotti, 40, 36061, Bassano del Grappa, Italy.
Orphanet J Rare Dis. 2022 Feb 21;17(1):63. doi: 10.1186/s13023-022-02237-5.
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.
To evaluate the recovery and morphology of subbasal corneal nerves in patients treated with Cenegermin for NK and assess their correlation with corneal sensitivity.
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.
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).
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.
Cenegermin（Oxervate，Dompè Farmaceutici，米兰，意大利）是一种重组人神经生长因子，是一种有潜力的神经修复新药，可用于治疗神经营养性角膜病变（NK），这是一种罕见但具有挑战性的角膜疾病。迄今为止，缺乏评估其对角膜神经和敏感性的中期疗效的研究。
评估 Cenegermin 治疗 NK 患者的角膜基质下神经的恢复和形态，并评估其与角膜敏感性的相关性。
这是一项前瞻性、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。在基线、治疗结束时（8 周）以及治疗后 2、4 和 8 个月，进行临床评估、敏感性和活体共聚焦显微镜（IVCM）检查。纳入接受 Cenegermin（每天滴注 6 次，持续 8 周）治疗的 NK（2-3 期）连续患者。在每次就诊时，测量角膜神经纤维长度（CNFL）、角膜神经纤维总分支密度（CTBD）、角膜神经纤维分形维数（CNFraD）和 Cochet-Bonnet 触觉测定（CBE）。
我们共纳入 18 例患者。18 例患者中有 14 例（78%）在 8 周治疗后完全治愈 NK；然后在 14 例（78%）、15 例（83%）和 13 例（72%）患者在 2、4 和 8 个月时分别完全治愈 NK。从 8 周开始到 4 个月的随访期间，所有角膜区域的 CBE 均逐渐改善（p≤0.01），此后一直持续改善。角膜神经有明显的再生，特别是在周边角膜：8 周开始出现向心性进展（CNFL 和 CNFraD），2 个月开始出现明显分支（CTBD），这种情况一直持续到随访结束。节段性 IVCM 和 CBE 检查结果在所有评估中均相关（所有 r≥0.62，从 2 个月开始，在周边区域最高）。
使用 Cenegermin 后，我们观察到角膜基质下神经再生、敏感性恢复和持续的上皮愈合，提示 NK 患者停药后几个月内其作用仍持续。
