目的: 探讨0.05%环孢素A(CsA)滴眼液预防飞秒激光制瓣准分子激光原位角膜磨镶(FS-LASIK)术后干眼的效果。
方法: 采用前瞻性随机对照研究设计。选取2025年1月至2025年9月在徐州医科大学附属医院接受FS-LASIK手术的患者80例80眼(仅纳入右眼数据分析),采用计算机生成的随机序列,按1:1比例随机分为对照组和试验组。所有患者术后1 d开始均接受常规治疗,即0.5%左氧氟沙星滴眼液,0.1%氟米龙滴眼液,0.1%玻璃酸钠滴眼液(每日4次,持续3 mo); 试验组在对照组基础上加用0.05%环孢素A滴眼液。比较术前,术后1、3 mo两组患者眼表疾病指数(OSDI)评分、数字评分量表(NRS)眼表评分、泪膜脂质层厚度(LLT)、睑板腺缺失评分、泪膜分泌试验(SⅠt)、角膜荧光素染色(CFS)评分、非侵入性泪膜破裂时间(NIBUT)及泪河高度(TMH)。采用共聚焦显微镜观察角膜神经参数,包括角膜神经纤维密度(CNFD)、神经分支密度(CNBD)、神经纤维长度(CNFL)和总分支密度(CTBD),并计数朗格汉斯细胞密度(DCD); 同时,利用液相芯片技术检测泪液中干扰素-γ(IFN-γ)、白细胞介素(IL)-1β、IL-6、IL-10及基质金属蛋白酶-9(MMP-9)的浓度。
结果: 最终共有72例患者完成随访(试验组37例中男15例,女22例,平均年龄24.05±4.00岁; 对照组35例中男16例,女19例,平均年龄23.77±3.71岁)。术后1、3 mo试验组OSDI评分、NRS眼痛评分、CFS评分均显著低于对照组(均P < 0.01),NIBUT、TMH显著高于对照组(均P<0.01)。共聚焦显微镜检查结果显示,试验组术后1、3 mo的DCD均显著低于对照组,而术后3 mo试验组CNFD、CNBD、CNFL、CTBD均显著高于对照组(均P<0.01)。术后1、3 mo泪液炎性因子分析表明,试验组患者泪液中IFN-γ、IL-1β、IL-6及MMP-9水平均显著低于对照组(均P<0.01)。Spearman相关性结果显示,OSDI评分、NRS评分与NIBUT、角膜神经参数(CNFD、CNBD、CNFL、CTBD)、角膜敏感性呈负相关(均P<0.01),与CFS评分、泪液中炎性因子(IFN-γ、IL-10、IL-1β、IL-6和MMP-9)水平、DCD呈正相关(均P<0.01); 泪液中炎性因子水平与角膜神经参数、NIBUT、角膜敏感性呈负相关,与CFS评分、DCD呈正相关(均P<0.01),其余参数之间无相关性(P>0.05)。
结论: 预防性使用0.05%环孢素A滴眼液,能显著改善FS-LASIK术后患者的干眼症状和体征,抑制眼表炎症反应,促进泪膜稳定性恢复。环孢素A通过抗炎与促神经修复的双重作用,是促进屈光术后眼表微环境稳态重建的有效辅助疗法。
AIM: To explore the efficacy of 0.05% cyclosporine A(CsA)eye drops for preventing dry eye after femtosecond laser-assisted laser
in situ keratomileusis(FS-LASIK).
METHODS: In this prospective randomized controlled study, a total of 80 patients(80 eyes)who underwent FS-LASIK surgery at the Affiliated Hospital of Xuzhou Medical University from January 2025 to September 2025 were enrolled, and only the data from the right eye were included for analysis. Before surgery, these patients were randomly assigned in a 1:1 ratio using a computer-generated sequence to a control group or an experimental group. All patients received standard postoperative treatment starting from postoperative day 1, including 0.5% levofloxacin eye drops, 0.1% fluorometholone eye drops, and 0.1% sodium hyaluronate eye drops(four times daily for 3 mo). The experimental group additionally received 0.05% cyclosporine A eye drops in addition to the standard treatment. The following parameters were compared between the two groups preoperatively and at 1 and 3 mo postoperatively: ocular surface disease index(OSDI)score, numerical rating scale(NRS)for ocular symptoms, lipid layer thickness(LLT), meibomian gland dropout score, Schirmer's Ⅰ test(SⅠt), corneal fluorescein staining(CFS)score, non-invasive tear breakup time(NIBUT), and tear meniscus height(TMH). Confocal microscopy was employed to evaluate corneal nerve parameters, including corneal nerve fiber density(CNFD), corneal nerve branch density(CNBD), corneal nerve fiber length(CNFL), and corneal total branch density(CTBD), and to count Langerhans cell density(DCD). In addition, levels of interferon-gamma(IFN-γ), interleukin(IL)-1β, IL-6, IL-10, and matrix metalloproteinase-9(MMP-9)in the tear were measured using liquid chip technology.
RESULTS: A total of 72 patients completed the final follow-up, including 37 patients(15 males, 22 females, mean age 24.05±4.00 y)in the experimental group, 35 patients(16 males, 19 females, mean age 23.77±3.71 y)in the control group. At 1 and 3 mo postoperatively, the experimental group showed significantly lower OSDI scores, NRS eye pain scores, and CFS scores(all P<0.01), and significantly higher NIBUT and TMH values, compared with the control group. Confocal microscopy revealed that DCD was significantly lower in the experimental group at 1 and 3 mo postoperatively, whereas CNFD, CNBD, CNFL, and CTBD were significantly higher at 3 mo postoperatively(all P<0.01). Analysis of tear inflammatory cytokines showed that the levels of IFN-γ, IL-1β, IL-6, and MMP-9 were significantly lower in the experimental group at 1 and 3 mo postoperatively compared with the control group(all P<0.01). Spearman correlation analysis revealed that OSDI and NRS scores were negatively correlated with NIBUT, corneal nerve parameters(CNFD, CNBD, CNFL, CTBD), and corneal sensitivity(all P<0.01), and positively correlated with CFS scores, tear inflammatory cytokines(IFN-γ, IL-10, IL-1β, IL-6, and MMP-9), and DCD(all P<0.01). Tear inflammatory cytokines were negatively correlated with corneal nerve parameters, NIBUT, and corneal sensitivity(all P<0.01), and positively correlated with CFS scores and DCD(all P<0.01). No significant correlations were observed among the remaining parameters(P>0.05).
CONCLUSION: Prophylactic use of 0.05% cyclosporine A eye drops significantly improves dry eye symptoms and signs, suppresses ocular surface inflammation, and promotes the restoration of tear film stability in patients after FS-LASIK. Through its dual anti-inflammatory and neuroregenerative effects, cyclosporine A constitutes an effective adjuvant therapy for reestablishing ocular surface microenvironment homeostasis after refractive surgery.