[Efficacy evaluation of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in the treatment of severe dry eye associated with chronic graft-versus-host disease].

Objective: To evaluate the effectiveness and safety of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in treating severe dry eye associated with chronic graft-versus-host disease (cGVHD). Methods: This non-randomized concurrent control trial enrolled 83 eyes from 83 patients with cGVHD-associated severe dry eye. The treatment had two phases. During the initial shock treatment period (0-3 months), 44 patients received 0.05% cyclosporine A eye drops (4 times/day; group A) and 39 patients received 0.1% tacrolimus eye drops (twice/day; group B) alongside basic treatment. In the maintenance treatment period (3-6 months), both groups used 0.05% cyclosporine A eye drops (twice/day) and sodium hyaluronate. Examinations were conducted at 1, 3, and 6 months after treatment initiation, assessing the Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS) score, and fluorescein tear break-up time (BUT) for efficacy. visual acuity and intraocular pressure (IOP) were evaluated for safety, and patients' post-medication irritation symptoms were recorded. Results: The study included 52 males and 31 females, aged (28.57±15.67) years. After 1 month of treatment, the CFS score in group A significantly decreased from 10.0 (6.0, 14.0) to 5.0 (3.0, 8.5) (P<0.001). in group B, the CFS score also significantly decreased from 10.0 (6.0, 15.0) to 6.0 (2.0, 10.0), and the BUT increased from 2.0 (1.0, 2.0) s to 2.0 (1.8, 3.3) s (P<0.001). No significant OSDI decrease was observed in either group. No significant differences were found in OSDI, CFS score, and BUT between the two groups. After 3 months, group A showed significant improvement in OSDI, CFS score, and BUT (P<0.05), while group B only demonstrated significant CFS score decrease (P<0.05). OSDI was significantly lower in group A than group B (P<0.05). No significant differences were noted in CFS score and BUT between groups. After 6 months, OSDI, CFS score, and BUT were 18.9 (9.3, 34.2), 7.0 (3.0, 8.5), and 2.0 (1.0, 3.0) s in group A, and 10.9 (3.6, 35.4), 5.5 (2.8, 10.0), and 2.0 (1.0, 10.0) s in group B. In both groups, CFS scores significantly decreased and BUT increased (P<0.05). Visual acuity improved significantly in group A at 1, 3, and 6 months (P<0.05), while no significant changes were seen in group B. Irritation symptoms were transient and self-resolving in both groups. Conclusions: Both 0.05% cyclosporine A and 0.1% tacrolimus eye drops, when combined with local glucocorticoids, exhibited significant anti-inflammatory effects, effectively and safely treating severe dry eye in cGVHD patients. Although the onset of 0.05% cyclosporine A was slower than 0.1% tacrolimus, it offered more stable long-term effects and better symptom improvement.目的： 评估0.05%环孢素A及0.1%他克莫司滴眼液治疗眼部慢性移植物抗宿主病（cGVHD）相关重度干眼的有效性和安全性。 方法： 前瞻性非随机同期对照试验。连续纳入2020年4至2021年6月于北京大学第三医院眼科门诊被诊断为cGVHD相关重度干眼的患者，纳入单眼进行研究。将纳入的患者分为A、B两组：前3个月A组局部给予0.05%环孢素A+0.1%氟米龙+玻璃酸钠+小牛血去蛋白提取物，B组在此基础上增加0.1%他克莫司；后3个月两组均只使用0.05%环孢素A和玻璃酸钠。观察两组患者治疗前和治疗后1、3、6个月的眼表疾病指数（OSDI）评分、角膜荧光素染色（CFS）评分和泪膜破裂时间（BUT），以及视力和眼压，并统计患者用药后的刺激症状。 结果： 共纳入83例（83只眼）眼部cGVHD患者，其中男性52例，女性31例，年龄为（28.57±15.67）岁；其中A组44例，B组39例。治疗后1个月，A组CFS由10.0（6.0，14.0）分降低至5.0（3.0，8.5）分（P<0.001）；B组CFS由10.0（6.0，15.0）分降低至6.0（2.0，10.0）分（P<0.001），BUT由2.0（1.0，2.0）s增加至2.0（1.8，3.3）s（P<0.001）；两组OSDI均无明显降低（均P>0.05），两组间OSDI、CFS、BUT的差异亦均无统计学意义（均P>0.05）。治疗3个月时，A组OSDI由治疗前的32.5（10.7，51.1）分降低至15.9（7.5，33.7）分（P<0.05），CFS降低至6.0（2.0，9.5）分（P<0.05），BUT增加至2.0 s（1.0，3.5）（P<0.05）；B组CFS降低至5.0（3.0，12.0）分（P<0.05），BUT增加至2.0（2.0，3.0）s（P<0.05），OSDI无明显降低（P>0.05）；A组OSDI低于B组（P<0.05）；两组间CFS、BUT比较差异无统计学意义（均P>0.05）。治疗6个月，A组OSDI评分、CFS评分和BUT分别为18.9（9.3，34.2）分、7.0（3.0，8.5）分和2.0（1.0，3.0）s，B组分别为10.9（3.6，35.4）分、5.5（2.8，10.0）和2.0（1.0，2.0）s。与治疗前相比，A组CFS降低、BUT增加，B组OSDI降低，差异均有统计学意义（P<0.05）；CFS、BUT较治疗前无明显改善。安全性：治疗1个月时B组眼压由13.2（11.0，19.0）mmHg（1 mmHg=0.133 kPa）升高至14.8（12.8，18.8）mmHg（P<0.05），但治疗期间两组眼压波动均在正常范围；治疗后A组视力有明显改善（P<0.05），B组视力较治疗前的差异无统计学意义（P>0.05）。用药后刺激症状：A组50%的患者报告使用0.05%环孢素A滴眼液后出现刺激症状，B组80%的患者报告使用0.1%他克莫司滴眼液后出现刺激症状，症状在用药后缓解。 结论： 0.05%环孢素A滴眼液或0.1%他克莫司滴眼液与局部糖皮质激素联用，均能发挥较好的抗炎效果，是治疗眼部cGVHD相关重度干眼安全、有效的手段。0.1%他克莫司滴眼液起效较快；0.05%环孢素A的远期效果更为稳定，改善症状较为明显。.