Eye Clinic, Università degli Studi di Milano; ASST Santi Paolo e Carlo, San Paolo Hospital, Via di Rudini', 8, 20142, Milan, Italy.
ASST Rhodense, Garbagnate Milanese Hospital, Milan, Italy.
BMC Ophthalmol. 2020 Aug 1;20(1):315. doi: 10.1186/s12886-020-01584-w.
To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy.
This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups.
29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high.
Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect.
Trial registration NCT03906513 , retrospectively registered on 08 April 2019.
评估局部胞磷胆碱和维生素 B12（Cit-B12：OMK2，意大利 Omikron Italia srl）对糖尿病神经病变患者角膜神经支配的影响。
这是一项前瞻性、随机、双盲、安慰剂对照研究，纳入 30 名患者，按 2:1 的比例随机分为 Cit-B12 组或安慰剂组，每天 3 次，共 18 个月。在基线和第 4、8、12、18 个月，患者接受眼表面疾病指数问卷（OSDI）、泪膜破裂时间、角膜和结膜染色评估、Schirmer I 试验、Cochet-Bonnet 触诊测敏和角膜基质下神经丛（SBP）共焦生物显微镜检查。使用 NeuronJ 计算纤维长度密度（FLD），并以 mm/mm2 表示。对两组的原始数据和与基线的差值进行分析。
30 名患者中有 29 名完成了研究。两组在基线时的 FLD 相似；两组在整个研究期间至第 18 个月时均逐渐改善（Cit-B12，p<0.0001；对照组，<0.0001-0.03）；Cit-B12 组与安慰剂组相比，第 18 个月时的改善程度更高（33%比 15%，p=0.04）。Cit-B12 组患者的角膜敏感性（基线时为 28±18mm；第 18 个月时为 52±10mm，p<0.0001）、结膜染色（P=0.04）和 OSDI 问卷（P=0.05）均有逐渐改善。两种治疗方法均耐受良好，研究期间的依从性较高。
Cit-B12 改善了糖尿病患者角膜神经的形态和功能，提示其具有神经再生作用。
试验注册 NCT03906513，于 2019 年 4 月 8 日进行了回顾性注册。
