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中华眼科医学杂志(电子版) ›› 2021, Vol. 11 ›› Issue (04) : 205 -210. doi: 10.3877/cma.j.issn.2095-2007.2021.04.003

论著

角膜神经分布情况与睑板腺功能障碍患者眼表炎症相关性的临床研究
韦振宇1, 郑攀攀1, 陈前坤1, 梁庆丰1,†()   
  1. 1. 100730　首都医科大学附属北京同仁医院　北京同仁眼科中心　北京市眼科研究所　北京市眼科学与视觉科学重点实验室
  • 收稿日期:2021-04-29 出版日期:2021-08-28
  • 通信作者: 梁庆丰
  • 基金资助:
    国家自然科学基金项目(81470607); 北京航空航天大学与首都医科大学北京大数据精准医疗高精尖创新中心开放基金项目(BHTR-KFJJ-202003); 北京市科委医药协同重点专项项目(Z181100001918031)

Correlation of corneal nerve innervation and ocular surface inflammationin in meibomain gland dysfunction

Zhenyu Wei1, Panpan Zheng1, Qiankun Chen1, Qingfeng Liang1,†()   

  1. 1. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab., Beijing 100730, China
  • Received:2021-04-29 Published:2021-08-28
  • Corresponding author: Qingfeng Liang
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韦振宇, 郑攀攀, 陈前坤, 梁庆丰. 角膜神经分布情况与睑板腺功能障碍患者眼表炎症相关性的临床研究[J]. 中华眼科医学杂志(电子版), 2021, 11(04): 205-210.

Zhenyu Wei, Panpan Zheng, Qiankun Chen, Qingfeng Liang. Correlation of corneal nerve innervation and ocular surface inflammationin in meibomain gland dysfunction[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2021, 11(04): 205-210.

目的

探讨睑板腺功能障碍(MGD)患者眼表炎症与角膜神经分布情况相关性。

方法

收集2017年8月至2018年11月于首都医科大学附属北京同仁医院眼科中心就诊的MGD患者38例(76只眼)，健康者25例(50只眼)。其中，男性22例(44只眼)，女性41例(82只眼)；年龄18~54岁，平均年龄(41.7±10.4)岁。为全部患者行角结膜荧光素染色、泪膜破裂时间(TBUT)、泪膜脂质层厚度(LLT)及泪液分泌试验(SchirmerⅠ试验)检测，以问卷调查患者的眼表疾病评分指数(OSDI)，以裂隙灯显微镜的检查结果对睑缘的健康状态进行评分，以睑板腺红外线照相计数睑板腺的缺失率，并行活体共聚焦显微镜检查以获取角膜上皮下神经分布的密度、数量、最大长度、最短长度及平均长度，同时计数角膜树突状细胞(DC)的数量和密度。MGD组与正常对照组的OSDI评分、LLT、TBUT、Schirmer Ⅰ试验、活体共聚焦显微镜图像及睑板腺红外线照相符合正态分布，以±s表示，组间比较采用t检验；睑缘评分和角结膜荧光素染色，以中位数和上下四分位数表示，组间比较采用Wilcoxon秩和检验。相关分析采用Pearson相关性检验。

结果

MGD组患者OSDI平均分、TBUT平均值、角结膜荧光素染色评分、SchirmerⅠ试验、睑板腺缺失率、LLT及睑缘异常评分分别为(41.16±21.17)分、(3.13±2.35)s、0.5(0，1)分、(7.00±5.49)mm、(24.73±11.65)%、(56.77±23.64)nm及3.0(2.25，3.50)分。两组患者LLT比较的差异无统计学意义(t＝-1.171，P>0.05)，其他指标比较的差异均有统计学意义(t＝10.321，-17.362，-5.801，2.417；P<0.05)；经Wilcoxon秩和检验，角结膜荧光素染色评分和睑缘异常评分比较的差异均有统计学意义(T＝11.810，11.532；P<0.05)。活体共聚焦显微镜检查显示MGD组患者DC密度、神经数量、神经密度、平均神经长度、最大神经长度及最小神经长度分别为(30.52±16.81)个/mm2、(15.50±6.75)条/图、(16 767±6418)μm/mm2、(184.77±34.61)μm、(412.83±60.47)μm及(43.30±24.67)μm。两组患者DC密度、神经密度、最大及最小神经长度比较的差异有统计学意义(t＝2.129，-2.143，-3.529，2.188；P<0.05)；神经数量和平均神经长度比较的差异无统计学意义(t＝-1.541，1.481；P>0.05)。MGD患者神经密度与OSDI、角结膜荧光素染色及最小神经长度均呈负相关；神经密度与神经数量和最大神经长度均呈正相关，有统计学意义(r＝-0.365，-0.506，-0.536，0.888，0.698；P<0.05)。DC密度与睑缘异常评分和最小神经长度均呈正相关；DC密度与神经密度、神经数量及最大神经长度均呈负相关，有统计学意义(r＝0.446，0. 545，-0.440，-0.459，-0.418；P<0.05)。

结论

MGD患者OSDI评分、角结膜荧光素染色评分、睑缘异常评分及睑板腺缺失率均提高，TBUT和Schirmer Ⅰ值下降。活体共聚焦显微镜检查发现MGD患者角膜上皮及浅基质层DC浸润与基底膜下神经损伤相关，提示MGD患者的眼表炎症可造成基底膜下神经损伤。

关键词: 睑板腺功能障碍, 眼表炎症, 角膜基底膜下神经, 活体共聚焦显微镜
Objective

The aim of this study was to investigate the relationship between ocular surface inflammation and corneal sub-basal nerve in meibomain gland dysfunction (MGD) patients.

Methods

From August 2017 to November 2018, 38 MGD patients (76 eyes) and 25 healthy controls (50 eyes) in Beijing Tongren Eye Center, Beijing Tongren Hospital affiliated to Capital Medical University were collected. Among of them, there were 22 male (44 eyes) and 41 female (82 eyes) with an average age of (41.7±10.4) years-old (ranged from 18 to 54 years-old). All subjects were checked corneal fluorescein staining, tear film break-up time (TBUT), lipid layer thickness measurement (LLT), Schirmer Ⅰ test, and conducted ocular surface disease index (OSDI) by questionare, lid margin score using slit-lamp microscope, and DC density, rate of meibomian gland loss using infrared photography for meibomian gland, the dendritic cell (DC) density, nerve number, nerve density, average nerve length, maximum nerve length, minimum nerve length using in vivo confocal microscopy (IVCM). The ocular surface indicators were expressed as ±s, and the comparison of those between MGD group and control group was performed using the independent sample t test. Corneal fluorescein staining, lid margin score were expressed as median and quartile, and compared by rank-sum test. Pearson correlation was used for correlation analysis.

Results

The OSDI score, TBUT, score of corneal fluorescein staining, Schirmer Ⅰ value, rate of meibomian gland loss, lid margin score of MGD patients were (41.16±21.17), (3.13±2.35) s, 0.5 (0, 1) scores, (7.00±5.49) mm, (24.73±11.65)%, (56.77±23.64) nm, 3.0(2.25, 3.50) scores, respectively. There were non-significant difference in LLT between them (t=-1.171, P>0.05), significant difference in other indices between them expect LLT (t=10.321, -17.362, -5.801, 2.417; P<0.05); significant difference in corneal fluorescein staining and lid margin score using rank-sum test (T=11.810, 11.532; P<0.05). After IVCM examination, DC density, nerve number, nerve density, average nerve length, maximum nerve length, minimum nerve length of MGD patients were (30.52±16.81)/mm2, (15.50±6.75)/p, (16 767±6418)μm/mm2, (184.77±34.61)μm, (412.83±60.47)μm, (43.30±24.67)μm, respectively with significant difference from controls (t=2.129, -2.143, -3.529, 2.188; P<0.05) expect nerve number and average nerve length (t=-1.541, 1.481; P>0.05). Using ocular surface indicators of MGD patients, nerve density was negatively associated with OSDI, score of corneal fluorescein staining, the minimum nerve length. The nerve density was positive correlated with nerve number and the maximum nerve length with significant difference (r=-0.365, -0.506, -0.536, 0.888, 0.698; P<0.05). DC density was positively correlated with score of lid margin and minimum nerve length. The nerve density, nerve number and maximum nerve length all were showed negative correlations with DC density. After Pearson correlation analysis, there was significant difference (r=0.446, 0.545, -0.440, -0.459, -0.418; P<0.05).

Conclusions

OSDI, score of corneal fluorescein staining, rate of meibomian gland loss, lid margin score was increased in MGD patients, while TBUT and Schirmer I value decreased. The result of IVCM suggested that there was a correlation between DC density and sub-basal corneal nerve, indicating that ocular surface inflammation may induce the sub-basal corneal nerve injury.

Key words: Meibomain gland dysfunction, Ocular surface inflammation, Subbasal corneal nerve, In vivo confocal microscopy
表1 两组患者眼表情况的比较
组别 眼数(只) 性别[男性(%)] 年龄(±s，岁) 眼表疾病评分指数(±s，分) 泪膜破裂时间(±s，s) Schirmer Ⅰ (±s，mm)
MGD组 76 13(34.2) 42.61±15.15 41.16±21.17 3.13±2.35 7.00±5.49
对照组 50 9(36.0) 41.00±10.36 4.87± 3.77 14.08±2.13 16.40±6.53
χ2/t值   0.021* 0.499 10.321 -17.362 -5.801
P值   >0.05 >0.05 <0.05 <0.05 <0.05
组别 角结膜荧光素染色[M(Q1，Q3)，分] 睑板腺缺失率(±s，%) 泪膜脂质层厚度(±s，nm) 睑缘异常评分(±s，分)
MGD组 0.5(0，1) 24.73±11.65 56.77±23.64 3.0(2.25，3.50)
对照组 0(0，0) 18.88± 5.80 64.28±23.74 1.5(0.50，1.75)
T/t值 11.810# 2.417 -1.171 11.532#
P值 <0.05 <0.05 >0.05 <0.05
表2 两组患者树突状细胞和角膜神经分布情况的比较(±s)
组别 眼数(只) 树突状细胞密度(个/mm2) 神经数量(条/图) 神经密度(μm/mm2) 平均神经长度(μm) 最大神经长度(μm) 最小神经长度(μm)
MGD组 76 30.52±16.81 15.50±6.75 16 767±6418 184.77±34.61 412.83±60.47 43.30±24.67
对照组 50 26.83±11.81 19.38±4.07 21 903±4002 170.92±19.51 455.97±14.83 30.71±10.13
t值   2.129 -1.541 -2.143 1.481 -3.529 2.188
P值   <0.05 >0.05 <0.05 >0.05 <0.05 <0.05
图1 睑板腺功能障碍患者角膜树突状细胞密度和角膜上皮下神经分布参数相关性的散点图　图A示神经密度与树突状细胞密度的相关性；图B示神经数量与树突状细胞密度的相关性；图C示最大神经长度与树突状细胞密度的相关性；图D示最小神经长度与树突细胞密度的相关性
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