[Efficacy of a recombinant bovine basic fibroblast growth factor gel for the treatment of moderate dry eye: a multicenter randomized double-blind parallel controlled clinical trial].

Objective: To compare the clinical efficacy of a recombinant bovine basic fibroblast growth factor (rb-bFGF) gel and a gel matrix in the treatment of moderate dry eye. Methods: It was a prospective random double-blind controlled study. One hundred patients diagnosed as moderate dry eye in Eye Institute and Affiliated Xiamen Eye Center of Xiamen University, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Beijing Tongren Hospital, Capital Medical University, Eye & ENT Hospital of Fudan University and Zhongshan Ophthalmic Center from August 2015 to April 2019 were divided into two groups: experimental group and control group. Two groups of patients were allocated to receive either a rb-bFGF gel or a gel matrix 4 times per day for 4 weeks. Subjective symptoms, break-up time of the tear film (BUT), Schirmer Ⅰ test (SⅠt) and corneal fluorescein sodium staining were assessed at baseline, 2 and 4 weeks after treatment. Bulbar impression cytology was evaluated at baseline and 4 weeks after treatment. Irritation of the rb-bFGF gel and the gel matrix was estimated after treatment. T test, Wilcoxon signed-rank test or Mann-Whitney U test was used for quantitative data, and Chi-square test was used for enumerative data. Results: Eighty-four subjects were included for statistical analyses after the exclusion of 16 subjects who were lost for followup, with an age of 43±14 years. There were 42 cases in the experimental group and the control group, respectively. There was no statistically significant difference between the two groups in demographic baseline characteristics before treatment (P>0.05). The total score of subjective symptoms was 7.17±3.60 and 5.95±3.25 at 2 and 4 weeks after therapy in the experimental group, which were lower than 9.48±3.88 before treatment (t=6.226, 6.563; both P<0.05); in the control group, it was 7.01±3.25 and 6.32±3.85 at 2 and 4 weeks after treatment, with a significant reduction in comparison with that before treatment (9.15±3.58; t=4.693, 4.726; both P<0.05). The median (lower quartile, upper quartile) BUT was 4.00 (2.40, 5.00) s and 4.64 (3.00, 5.00) s at 2 and 4 weeks after therapy in the experimental group, which were longer than 3.72 (2.00, 4.39) s before treatment (Z=-2.485, -3.152; both P<0.05). The BUT was 4.41 (2.79, 5.12) s at 2 weeks after therapy in the control group, which was of no statistical difference compared with 3.89 (2.09, 4.25) s before treatment (Z=-1.953, P>0.05). The BUT was 5.21 (3.00, 5.02) s at 4 weeks after therapy in the control group, which was longer than that before treatment (Z=-2.485, P<0.05). The SⅠt score was 7.31 (3.75, 10.00) mm and 8.50 (4.00, 11.00) mm at 2 and 4 weeks after therapy in the experimental group, which were significantly higher than 6.69 (2.00, 8.13) mm before treatment (Z=-2.031, -2.236; both P<0.05); in the control group, it was 6.82 (2.00, 8.25) mm and 6.86 (3.00, 9.25) mm at 2 and 4 weeks after therapy, which were not significantly increased compared with 6.50 (2.00, 7.75) mm before treatment (Z=-0.179, -1.161; both P>0.05). The corneal fluorescein sodium staining points were 5.00 (2.00, 5.00) and 3.71 (0.00, 5.00) at 2 and 4 weeks after therapy in the experimental group, which were significantly lower than 7.10 (5.00, 7.00) before treatment (t=-2.895, -4.639; both P<0.05); those in the control group were 5.52 (0.00, 7.00) and 6.19 (0.75, 6.25) at 2 and 4 weeks after treatment, with a significant reduction in comparison with 8.90 (5.00, 10.50) before treatment (t=-2.776, -1.991; both P<0.05). The differences in the average total score of subjective symptoms, BUT, SIt, and corneal fluorescein sodium staining points between both groups were not statistically significant at each time point. The impression cytology grade was decreased from 1.72 (1.00, 2.00) before treatment to 0.94 (0.00, 2.00) at 4 weeks after therapy in the experimental group (Z=-2.803, P<0.05). The staining grade of conjunctival imprinted cells in the control group was 1.42 (1.00, 2.00) at 4 weeks, which showed no statistical significance compared with 1.56 (1.00, 2.00) before treatment (Z=1.195, P>0.05). The impression cytology grade was significantly reduced in the experimental group compared with the control group at 4 weeks after treatment (Z=-3.308, P<0.05). The number of goblet cells was 10.90 (5.00, 20.00) at 4 weeks after therapy in the experimental group, which was significantly higher than 6.30 (5.00, 8.00) before treatment (Z=-2.383, P<0.05); in the control group, it was 8.36 (4.00, 12.00) at 4 weeks after treatment, with no significant increase in comparison with that before treatment [7.55 (5.00, 11.00)] (Z=-0.095, P>0.05). The number of goblet cells was not significantly increased in the experimental group compared with the control group at 4 weeks after treatment (Z=-1.162, P>0.05). Most patients indicated that the drug was non-irritating, and no patient had intolerable irritation affecting daily lives at 4 weeks after therapy; there was no difference between the two groups (Z=-0.290, P>0.05). Conclusions: Both the rb-bFGF gel and the gel matrix can effectively improve the symptoms and signs of moderate dry eye. However, compared with the gel matrix, the rb-bFGF gel shows obvious advantages in promoting conjunctival epithelial cell repair and increasing the number of goblet cells. (Chin J Ophthalmol, 2021, 57: 930-938).目的： 比较重组牛碱性成纤维细胞生长因子（rb-bFGF）凝胶和凝胶基质治疗中度干眼的临床疗效。 方法： 随机、双盲、平行对照的临床试验研究。纳入2015年8月至2019年4月在厦门大学眼科研究所及厦门大学附属厦门眼科中心、华中科技大学同济医学院附属协和医院、首都医科大学附属北京同仁医院、复旦大学附属眼耳鼻喉科医院和中山大学中山眼科中心5个单位符合条件的中度干眼患者，采用动态随机化将患者分为试验组和对照组。试验组和对照组分别给予rb-bFGF凝胶和凝胶基质治疗4周。分别于治疗前和治疗后2、4周对患者的干眼症状进行评分，并进行泪膜破裂时间（BUT）、基础泪液分泌试验（SⅠt）和角膜荧光素钠染色等检查，在治疗前和治疗后第4周行结膜印迹细胞学检查，并观察用药后的药物刺激性。定量资料的比较采用t检验、威尔科克森符号秩检验或曼-惠特尼U检验；计数资料的比较采用χ²检验。 结果： 共100例患者纳入研究，84例患者完成随访，其中男性25例，女性59例；年龄（43±14）岁；试验组和对照组各42例。治疗后2、4周，试验组干眼症状总评分分别为（7.17±3.60）、（5.95±3.25）分，对照组分别为（7.01±3.25）、（6.32±3.85）分，均明显低于治疗前试验组的（9.48±3.88）分（t=6.226，6.563）和对照组的（9.15±3.58）分（t=4.693，4.726），差异有统计学意义（P<0.05）。治疗后2、4周，试验组BUT分别为4.00（2.40，5.00）、4.64（3.00，5.00）s，较治疗前的3.72（2.00，4.39）s均明显延长（Z=-2.485，-3.152；P<0.05）；治疗后2周，对照组BUT为4.41（2.79，5.12）s，较治疗前的3.89（2.09，4.25）s差异无统计学意义（Z=-1.953，P>0.05）；治疗后4周，对照组BUT为 5.21（3.00，5.02）s，较治疗前明显延长（Z=-2.485，P<0.05）。治疗后2、4周，试验组SⅠt结果分别为 7.31（3.75，10.00）、8.50（4.00，11.00）mm，较治疗前的6.69（2.00，8.13）mm均明显增多，差异有统计学意义（Z=-2.031，-2.236；P<0.05）；治疗后2、4周，对照组SIt结果分别为6.82（2.00，8.25）、6.86（3.00，9.25）mm，较治疗前的6.50（2.00，7.75）mm均无明显增加（Z=-0.179，-1.161；P>0.05）。治疗后2、4周，试验组和对照组角膜荧光素钠染色点数均较治疗前明显增多（均P<0.05）。治疗后各时间点2个组的干眼症状总评分、BUT、SⅠt结果及角膜荧光素钠染色点数差异均无统计学意义（均P>0.05）。治疗后4周，试验组结膜印迹细胞染色分级和杯状细胞数量均较治疗前差异有统计学意义（Z=-2.803，-3.308；P<0.05）；对照组则差异均无统计学意义（Z=1.195，-0.095；P>0.05）。治疗后4周，2个组结膜印迹细胞染色分级差异有统计学意义（Z=-2.383，P<0.05），而结膜杯状细胞数量差异无统计学意义（Z=-1.162，P>0.05）。治疗期间2个组大部分患者均认为药物无刺激性，仅有少部分患者出现眼部刺激症状，组间差异无统计学意义（Z=-0.290，P>0.05）。 结论： rb-bFGF凝胶和凝胶基质均能有效改善中度干眼的症状和体征，但rb-bFGF凝胶在促进结膜上皮细胞修复和增加杯状细胞数量方面较凝胶基质有明显优势。（中华眼科杂志，2021，57：930-938）.