单纯疱疹病毒性角膜基质炎静止期泪膜改变的初步观察

Preliminary investigation on tear film alterations in latent herpes stromal keratitis

目的探讨单纯疱疹病毒性角膜基质炎（HSK）静止期患者泪膜稳定性变化。方法前瞻性对照研究。连续收集2007年12月至2009年3月在厦门大学附属厦门眼科中心定期就诊的24例单眼患病的HSK静止期患者，行双眼基础泪液分泌试验（SIT）测试和泪膜破裂时间（BUT）检查，并调查其干眼主观症状。同期取28名正常人作为对照组，行SIT与BUT检查。对正常对照者及BUT≤5s的患眼进行激光共焦角膜显微镜观察。应用SPSS16．0软件进行临床资料的分布和方差齐性检验及组间差异的非参数检验（Kruskal-Wallis检验及Mann-Whitney检验）。结果91．7％HSK静止期患者（22／24例）出现至少1项干眼相关症状。与正常对照组比较，HSK静止期患者双眼SIT均降低[正常组（16．2±3．2）mm／5min，患眼（10．4±7．8）mm／5min，对侧眼（11．2±8．8）mm／5min；对照与患病眼，U=135．0，P〈0．001；对照与对侧眼，U=155．0，P=0．001]，BUT缩短[正常组（12．1±0．7）s，患眼（4．3±3．3）s，对侧眼（9．2±4．4）s；对照与患病眼，U=28．0，P〈0．001；对照与对侧眼，U=114．0，P〈0．001]。HSK患眼与对侧眼SIT相比较，差异无统计学意义（U=273．0，P=0．757）；BUT明显缩短，差异有统计学意义（U=90．0，P〈0．001）。HSK患眼中58．3％（14／24例）SIT≤10mm／5min，95．8％（23／24例）BUT≤10s；而在对侧眼其比例分别为58．3％（14／24例）及70．8％（17／24例）。激光活体共焦显微镜检查显示12例泪膜异常的HSK静止期患眼的中央角膜表层上皮细胞明显增大伴细胞核高反光，角膜上皮下神经纤维密度降低，且出现明显的神经纤维串珠样改变等。结论HSK静止期患者多存在泪膜改变，活体共焦显微镜检查显示泪膜功能异常者出现与干眼类似的角膜上皮细胞及上皮下神经纤维的形态学改变。

Objective To investigate tear film alterations in patients with latent herpes stromal keratitis （HSK）. Methods Prospective comparative case series study. Twenty-four patients with latent HSK in one eye and 28 age and gender matched healthy individuals were recruited. All subjects were evaluated by subjective symptoms of dry eye, tear film break-up time（BUT） and Schirmer I test （S I T）. Laser in vivo confocal microscopic investigation was performed in 12 patients with severe tear film instability （BUT≤5 s）. Data distribution and homogeneity of variance was analyzed. Statistical comparisons of the mean values between different groups were performed using Kruskal-Wallis test, Mann-Whitney test or student t-test. Results Most of latent HSK patients （n = 22/24, 91.7% ） had symptoms as dryness, burning sensation, redness and foreign body sensation. Both eyes of patients with latent HSK had hyposeeretion （ S I T, control eyes （ 16. 2 ± 3.2） mm/5 rain; affected eyes （ 10. 4 ± 7. 8 ） mm/5 min; lateral eyes （ 11.2 ± 8. 8） mm/5 min; control and affected, U = 135. 0, P 〈 0. 001 ; control and lateral, U = 155. 0, P = 0. 001 ） and decreased tear film stability [ BUT, control eyes （ 12. 1± 0.7） s, affected eyes （4.3±3.3）s,lateral eyes （9.2±4.4）s; control and affected, U=28.0,P 〈0.001; control and lateral,U = 114.0, P 〈 0. 001 ] as compared to control group （Kruskal-Wallis nonparametric test）. The value of BUT showed significant difference between affected eyes and healthy eyes （U = 90. 0, P 〈 0. 001 ） , whereas no difference of the value of S IT was found （ U = 273.0 ,P = 0. 757 ）. Abnormal S I T （ ≤ 10 mm/min） and BUT （ ≤ 10 s） was presented in 14 （58. 3% ） and 23 （95. 8% ） affected eyes, as well as in lg （58. 3% ） and 17 （70. 8% ） lateral eyes, respectively. Laser in vivo confocal microscopy investigation in 12 affected corneas with abnormal tear film showed morphological alterations as corneal epithelial metaplasia with polymorphism and enlarged cells, reflective nuclei, and decreased nucleus/cytoplasm ratio; decreased nerve density in subepithelial plexus and obvious branching and beading, which is similar to those changes caused by dry eye. Conclusions Most of latent HSK patients had abnormal tear film. Dry eye related alterations could be found in affected corneas with abnormal tear film by in vivo confocal microscopy. （Chin J Ophthalmol , 2010, 46： 785-790）