方法：收集局部应用抗青光眼药物3mo以上的患者35例49眼和健康志愿者作为正常对照组45例45眼，药物治疗组分为A亚组(单独应用一种药物)和B亚组(联合应用两种及以上药物)。对所有患者及健康志愿者行泪膜破裂时间(BUT)、泪液分泌试验(SⅠt)、角膜上皮荧光素染色(FL)、结膜上皮虎红染色(RB)及结膜印迹细胞学检查(CIC)、黏蛋白MUC5AC检测。

结果：正常对照SⅠt(11.54±5.47)mm/5min，BUT(11.86±3.13)s，FL和RB评分为(0.42±0.61)分、(0.37±0.98)分，药物治疗组SⅠt(8.11±4.30)mm/5min，BUT(7.49±2.62)s，FL和RB评分为(1.15±0.87)分、(1.28±1.08)分，两组相比差异具有统计学意义(t=3.395，P=0.001； t=7.363，P=0.001， t=-4.266，P=0.001； t=7.363，P=0.000)； A亚组SⅠt(9.51±4.76)mm/5min，BUT(8.46±1.24)s，FL和RB评分为(0.91±1.03)分、(0.85±1.07)分； B亚组SⅠt(6.34±4.05)mm/5min，BUT(6.38±1.25)s，FL和RB评分为(1.84±1.14)分、(1.56±1.31)分，A亚组与B亚组相比差异具有统计学意义(t=2.514，P=0.012； t=5.844，P=0.000，t=-2.992，P=0.003； t=-2.072，P=0.043)。与正常对照组相比，药物治疗组的结膜上皮细胞体积变大，浆核比变小，细胞受损明显，药物治疗组的结膜印记细胞学检查评分明显增高，两组之间差异有统计学意义(u=6.354，P=0.000)，A亚组与B亚组的结膜印记细胞学检查评分无统计学差异(u=0.69，P=0.48)。正常对照组及药物治疗组的杯状细胞密度分别为(68.37±12.82)个/mm²及(32.83±10.68)个/mm²，差异显著(t=14.610，P=0.000)。抗青光眼药物治疗后，A亚组和B亚组的杯状细胞密度分别为(39.12±9.35)个/mm²及(27.58±8.47)个/mm²， 两者的差异具有统计学意义(t=4.530，P=0.001)。正常对照组的泪液MUC5AC含量为(32.61±8.65)ng/mL，药物治疗组的泪液MUC5AC明显减少(13.84±6.72)ng/mL，差异具有统计学意义(t=11.804，P=0.000)。抗青光眼药物治疗后，B亚组的泪液MUC5AC含量(10.67±4.58)ng/mL较A亚组(20.17±5.84)ng/mL明显减少，两者差异显著(t=6.349，P=0.000)。

结论：局部应用抗青光眼药物会导致患者泪液分泌减少、泪膜稳定性下降，眼表结构受损，增加用药种类会加重这种损害。

METHODS: Forty-nine eyes from 35 patients treated with topical antiglaucoma medication over 3mo and 45 eyes from 45 normal subjects were collected. The antiglaucoma medication group was divided to subgroup A(single antiglaucoma medication treated group)and subgroup B(combined antiglaucoma medication treated group). The ocular surface structures were performed in all subjects, including Schirmer I test(S I t), tear film break-up time(BUT), fluorescein staining(FL), rose bengal staining(RB), conjunctival impression cytology(CIC), goblet cells density(GCD), content of tear MUC5AC.

RESULTS:The results of S I t was 11.54±5.47mm, and BUT was 11.86±3.13s, and FL and RB score was0.42±0.61 and 0.37±0.98 in normal control group, which was 8.11±4.30mm and 7.49±2.62s, and 1.15±0.87, 1.28±1.08 respectively in antiglaucoma medication group. The differences were significant between normal group and antiglaucoma medication group(t=3.395, P=0.001; t=7.363, P=0.001, t=-4.266, P=0.001; t=7.363, P=0.000); The results of S I t was 9.51±4.76mm, BUT was 8.46±1.24s, and FL and RB score was 0.91±1.03 and 0.85±1.07 in subgroup A, which was 6.34±4.05mm and 6.38±1.25s, and FL and RB score was 1.84±1.14 and 1.56±1.31 in subgroup B. The differences were significant between subgroup A and subgroup B(t=2.514, P=0.012; t=5.844, P=0.000; t=-2.992, P=0.003; t=-2.072, P=0.043). Compared with normal control group, conjunctival epithelium cells damage was observed in antiglaucoma medication group that cell volume enlarged, and cytoplasm/nucleus decreased. The score of CIC of antiglaucoma medication group was significantly increased compared with normal control group(u=6.354, P=0.000), while there was no difference between subgroup A and subgroup B(u=0.69, P=0.48). GCD of normal group and antiglaucoma medication group was(68.37±12.82)/mm² and(32.83±10.68)/mm² respectively. The difference was dramatically(t=14.610, P=0.000); GCD of subgroup A and subgroup B was(39.12±9.35)/mm² and(27.58±8.47)/mm², which was statistically different(t=4.530, P=0.001). The content of tear MUC5AC was significantly decreased in antiglaucoma medication group(13.84±6.72ng/mL)compared with normal control group(32.61±8.65ng/mL)(t=11.804, P=0.000), while the content of tear MUC5AC was also significantly decreased in subgroup B(10.67±4.58ng/mL)compared with subgroup A(20.17±5.84ng/mL)(t=6.349, P=0.000).

CONCLUSION: Topical antiglaucoma medication can decrease tear secretionand tear film stability and damage ocular surface. Combined antiglaucoma medication caused severe damage on ocular surface structures.