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局部用环孢素联合泪小点栓子治疗干眼症和炎症的疗效

Efficacy of Topical Cyclosporine Combined with Punctal Plugs in Treating Dry Eye Disease and Inflammation.

作者信息

Feng Changming, Wang Wushuang, Gong Lan, Lin Tong

机构信息

Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.

出版信息

Curr Eye Res. 2025 Feb;50(2):148-161. doi: 10.1080/02713683.2024.2411699. Epub 2024 Oct 7.

Abstract

PURPOSE

To evaluate the effect of punctal plugs combined with cyclosporine eye drops on dry eye disease (DED) and ocular surface inflammation.

METHODS

In a clinical trial, 73 patients were randomly allocated into three groups: punctal plug group, combination therapy group, and cyclosporine group. At the baseline and four weeks after treatment, the Schirmer I test score, fluorescein tear film break-up time (FBUT), ocular surface staining score and dry eye symptoms were assessed. Tear samples were collected to detect the level of inflammatory factors (interleukins, matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor alpha (TNF-α)). In an animal experiment, a New Zealand rabbit dry eye model was induced. The rabbits were randomly divided into control group, punctal plug group, and combination therapy group ( = 6). Conjunctival goblet cell density, protein level of MMP-9 in conjunctiva and mRNA levels of inflammatory factors in conjunctiva and cornea were measured before and after treatment.

RESULTS

In combination therapy group of the clinical trial, the following results were observed: significant improvement in Schirmer I test scores and FBUT compared to the cyclosporine group and punctal plug group, respectively; a decrease in the tear levels of IL-6, IL-1, and MMP-9 compared to the punctal plug group; and a decrease in the tear levels of IL-1α, IL-6, and IL-17 compared to the baseline (all  < 0.05). In the animal experiment, rabbits in combination therapy group had a higher goblet cell density ( < 0.01) and lower mRNA levels of IL-16 ( < 0.05), IL-17 ( < 0.05), and MMP-9 ( < 0.01) in conjunctiva and that of MMP-9 ( < 0.01) in cornea compared to punctal plug group.

CONCLUSION

Cyclosporine eye drops combined with degradable punctal plugs is a more optimized clinical treatment strategy for DED compared with degradable punctal plugs or cyclosporine eye drops alone, considering the influence of comprehensive clinical efficacy and ocular surface inflammation.

摘要

目的

评估泪点塞联合环孢素滴眼液对干眼症(DED)及眼表炎症的影响。

方法

在一项临床试验中,73例患者被随机分为三组:泪点塞组、联合治疗组和环孢素组。在基线期及治疗4周后,评估泪液分泌试验I(Schirmer I)评分、荧光素泪膜破裂时间(FBUT)、眼表染色评分及干眼症状。采集泪液样本检测炎症因子(白细胞介素、基质金属蛋白酶9(MMP-9)和肿瘤坏死因子α(TNF-α))水平。在一项动物实验中,诱导建立新西兰兔干眼模型。将兔随机分为对照组、泪点塞组和联合治疗组(每组 = 6只)。测量治疗前后结膜杯状细胞密度、结膜中MMP-9蛋白水平以及结膜和角膜中炎症因子的mRNA水平。

结果

在临床试验的联合治疗组中,观察到以下结果:与环孢素组和泪点塞组相比,Schirmer I试验评分和FBUT分别有显著改善;与泪点塞组相比,泪液中IL-6、IL-1和MMP-9水平降低;与基线相比,泪液中IL-1α、IL-6和IL-17水平降低(均P < 0.05)。在动物实验中,与泪点塞组相比,联合治疗组兔结膜杯状细胞密度更高(P < 0.01),结膜中IL-16(P < 0.05)、IL-17(P < 0.05)和MMP-9(P < 0.01)的mRNA水平以及角膜中MMP-9的mRNA水平更低(P < 0.01)。

结论

考虑到综合临床疗效和眼表炎症的影响,与单独使用可降解泪点塞或环孢素滴眼液相比,环孢素滴眼液联合可降解泪点塞是一种更优化的DED临床治疗策略。

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