目的：探究不同浓度ZKY001滴眼液治疗原发性翼状胬肉切除术后角膜上皮缺损的有效性和安全性。

方法：本研究为多中心、随机、双盲、安慰剂对照的Ⅱ期临床研究。选取2022-03-15/11-14全国12家三甲医院原发性翼状胬肉术后患者，采用区组随机化的方法按照1：1：1比例将患者178例178眼随机分为三组：安慰剂组(给予ZKY001模拟滴眼液治疗)60例60眼，0.002% ZKY001滴眼液组59例59眼，0.004% ZKY001滴眼液组59例59眼。各组患者接受研究药物每次1滴，每天4次，使用4 d。观察各组患者在不同时间点的角膜上皮缺损面积较基线改善百分比，角膜上皮缺损区首次完全愈合时间，角膜上皮缺损首次愈合人数，眼部不适(眼痛、异物感、畏光、流泪)等视觉模拟量表评分变化。

结果：三组患者角膜上皮缺损首次愈合时间、在不同的随访点三组角膜上皮缺损面积较基线改善百分比、首次愈合人数百分比均无差异(均P>0.05)。但从数值上看，0.002% ZKY001组(67.87±21.688 h)、0.004% ZKY001组(61.48 ±22.091 h)角膜上皮缺损首次愈合时间较安慰剂组短(68.85±20.851 h)。在 D1上午，0.004% ZKY001滴眼液组的角膜缺损面积较基线改善的百分比与安慰剂组的数值差值达到最大，且在后续的随访点保持着数值差值的优势。试验组在不同随访点的角膜上皮缺损区首次愈合人数较安慰剂组多。眼部不适改善方面：试验组较安慰剂组的VAS评分总分值降低多，以异物感评分、疼痛感评分降低为主，在D3时0.004% ZKY001滴眼液组对异物感的改善明显优于其他两组(P<0.017)。安全性方面：总体不良事件发生率低(9.0%)，且三组间相似。

结论：原发性翼状胬肉术后使用ZKY001滴眼液可改善角膜上皮缺损修复，改善术后因角膜上皮缺损引起的不适症状且安全性良好。

METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.

RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.

CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.