Comparison of 1% cyclosporine eye drops in olive oil and in linseed oil to treat experimentally-induced keratoconjunctivitis sicca in rabbits

ABSTRACTPurpose:To evaluate the effectiveness of topical 1% cyclosporine eye drops diluted in either of the two vehicles-olive and linseed oil-and that of the oils themselves in treating experimentally-induced keratoconjunctivitis sicca (KCS) in rabbits.Methods:KCS was induced in 25 New Zealand rabbits using 1% atropine sulfate eye drops for 7 days before treatment and throughout the treatment period (12 weeks). The rabbits were divided into five groups: one control (C) group without KCS induction and four treatment groups in which KCS was induced and treated topically with olive oil (O), linseed oil (L), cyclosporine in olive oil (CO), and cyclosporine in linseed oil (CL). The animals were evaluated using Schirmer tear test 1 (STT), the fluorescein test (FT), tear-film break-up time (TBUT), the rose bengal test (RBT), and histopathological analysis.Results:Values of STT and TBUT significantly decreased 1 week post-induction (p<0.05) and were similar to initial values after the 4th week of treatment, in all groups. After KCS induction, there was significantly less corneal damage in group L than in group CL, as assessed FT and RBT. Histopathology demonstrated that Groups L and CL presented less edema and corneal congestion. There was no significant difference in the goblet cell density (cells/mm2) between the groups (p=0.147).Conclusion:Cyclosporine diluted in olive oil or linseed oil was effective in the treatment of KCS, although it had better efficacy when diluted in linseed oil. Linseed oil presented better effectiveness, whether associated or not, than olive oil. These results may contribute to the creation of novel topical ophthalmic formulations for KCS treatment in future.

摘要
研究目的：评估分别以橄榄油、亚麻籽油作为赋形剂稀释的1%环孢素滴眼液，以及两种赋形剂本身，对实验性诱导的家兔角结膜干燥症（Keratoconjunctivitis sicca, KCS）的治疗效果。
实验方法：选取25只新西兰兔，在治疗前7天及整个12周治疗期间，持续给予1%硫酸阿托品滴眼液以诱导角结膜干燥症。将家兔分为5组：1组为未诱导KCS的空白对照组（C组），其余4组均诱导KCS后分别接受局部给药：橄榄油组（O组）、亚麻籽油组（L组）、橄榄油稀释环孢素组（CO组）、亚麻籽油稀释环孢素组（CL组）。采用泪液分泌试验1号（Schirmer tear test 1, STT）、荧光素染色试验（FT）、泪膜破裂时间（TBUT）、孟加拉红染色试验（RBT）及组织病理学分析对实验动物进行评估。
实验结果：所有组别在诱导KCS后1周时，STT与TBUT值均显著下降（p<0.05），并于治疗第4周后回升至接近初始水平。经FT与RBT评估发现，诱导KCS后L组的角膜损伤程度显著低于CL组。组织病理学结果显示，L组与CL组的角膜水肿及充血程度更轻微。各组间杯状细胞密度（cells/mm²）无显著统计学差异（p=0.147）。
研究结论：以橄榄油或亚麻籽油作为赋形剂稀释的环孢素滴眼液均可有效治疗KCS，其中以亚麻籽油作为赋形剂时疗效更优。无论是否联合环孢素，亚麻籽油的治疗效果均优于橄榄油。本研究结果可为未来开发用于KCS治疗的新型局部眼用制剂提供理论参考。