活动期甲状腺相关眼病泪液中神经生长因子与泪膜稳定性的相关性研究

The relationship between the nerve growth factor level in tears in active thyroid-associated ophthalmopathy and tear film stability

背景神经生长因子（NGF）在维持泪膜稳定性方面起着重要作用，甲状腺相关眼病（TAO）患者眼表功能紊乱，干眼症状明显，但NGF是否能够维护TAO患者泪膜的稳定性尚不清楚。目的检测活动期TAO患者在糖皮质激素治疗前后泪液中NGF的质量浓度及泪膜稳定性的变化，探讨活动期TAO患者泪液NGF与泪膜稳定性的相关性。方法采用前瞻性队列研究设计。纳入TAO临床活动期患者38例38眼和年龄、性别相匹配的无系统性疾病及眼表疾病者30人30眼。TAO患者以逐渐减量的方式口服醋酸泼尼松龙共4周，分别于用药前及用药后4周收集患者及对照组泪液，采用ELSIA法检查泪液中NGF质量浓度的变化，并同时进行TAO临床活动性评分（CAS）、基础泪液分泌试验及泪膜破裂时间（BUT）的测定。结果用药前TAO患者泪液总NGF质量浓度明显高于对照组，差异有统计学意义（u=-5．026，P〈0．01）；用药后，TAO患者泪液NGF质量浓度由用药前的46．23（42．34，51．42）ng／L降低到27．45（19．38，29．12）ng／L，差异有统计学意义（Z=-6．172，P〈0．05）；TAO患者的CAS分值由用药前的6（5，7）分降低到4（2，5）分，差异有统计学意义（Z=-2．496，P〈0．01）；基础泪液分泌试验结果显示泪液分泌量由用药前的6（4，11）mm增加到11（7，16）mm，差异有统计学意义（Z=-4．286，P〈0．05），而BUT由用药前的5（3，9）S延长到11（6，14）s，差异有统计学意义（z=-3．160，P〈0．05）。NGF表达量与CAS呈正相关（r=0．645，P〈0．01），与基础泪液分泌试验及BUT均呈负相关（r=-0．530，P〈0．01；r=-0．430，P〈0．01）。结论泪液中的NGF在活动期TAO患者眼表炎症中起保护作用。抗炎治疗可以显著降低泪液中NGF的质量浓度，增加泪液的分泌和泪膜的稳定性。

Background Nerve growth factor （NGF） plays an important role in the maintenance of the tear film stability. It is well known that the damage of ocular surface causes dry eye in the patients with thyroid-associated ophthalmopathy （TAO）. However,if NGF is helpful for the stability of tear film is unclear. Objective This study was to investigate the relationship of NGF concentration in tear with tear film stability in TAO patient before and after glucocorticoid treatment. Methods Prospective observational cohort study was designed. This study was approved by the Ethic Committee of Binzhou Medical College, and written informed consent was obtained from each subject before entering this trial. Thirty-eight patients with active TAO and thirty age- and gender-matched controls were enrolled in the study. Prednisolone acetate tablets were administered in TAO patients for 4 weeks at a back-titration regimen. The tear fluid was collected and NGF level was detected by ELISA. Clinical activity score （CAS） was evaluated under the slit lamp lamp. Schirmer I test （S I t） was performed and breakup time of tear film （BUT） was obtained in controls and patients with active TAO before and 4 weeks after steroid treatment. Results Baseline NGF levels in tear was higher in the patients with active TAO than in the controls （ U= -5. 026, P〈0. 01 ）. NGF level decreased from 46.23 （42. 34, 51.42） ng/L to 27.45 （ 19.38, 29. 12 ） ng/L 4 weeks after steroid treatment （Z=-6.172,P〈0.05）,andCASdecreased significantly from 6 （5,7） to4 （2,5） （Z=-2.496,P〈O. 01）.SIt value increased from 6 （4,11）ram to 11 （7,16）mm 4 weeks after steroid treatment （Z=-4. 286,P〈0.05） ,and the BUT prolonged from 5 （3,9） seconds to 11 （6,14） seconds（Z=-3.160,P〈0.05）.NGF levels in active TAO was significantly correlated with CAS （ r= 0. 645 ,P〈0. 01 ）, S I t value （ r= -0. 530, P〈0. 01 ） and BUT （ r = -0. 430, P〈0. 01 ）. Conehtsions Tear NGF may stabilized the tear film. The application of steroid anti-inflammation drug can reduce the tear NGF level,increase the tear secretion and improve the tear film stability in patients with active TAO.