角膜神经痛的临床研究

发布时间：2018-02-07 12:05

  本文关键词： 角膜敏感性 角膜神经 朗格汉斯细胞 NSSDE 角膜触觉 角膜神经 朗格汉斯细胞 角膜神经痛 干眼症 角膜知觉 角膜神经 朗格汉斯细胞　出处：《复旦大学》2012年博士论文　论文类型：学位论文

【摘要】：第一部分 活体共焦显微镜下人角膜神经形态及其与角膜敏感性的相关性研究 目的：观察正常亚洲人角膜神经密度、中央区朗格汉斯细胞(Langerhans cell, LC)密度及角膜敏感性的范围,分析三者的年龄、性别特点及相关性。 方法：选取24位健康志愿者的24眼(10男14女,44.25±11.80岁),接受裂隙灯检查、非接触式眼压测量、泪液分泌功能(Schirmer I test, SIt)、泪膜破裂时间(Tear Breakup Time, TBUT)、角膜荧光染色(Fluorescein, FL)、接触式角膜知觉测量(Cochet-Bonnet角膜知觉计)和激光活体共聚焦显微镜(Laser In Vivo Confocal Microscopy, LSCM)检查。量表询问包括眼表疾病指数(Ocular Surface Disease Index, OSDI)和综合医院焦虑抑郁量表(Hospital Anxiety and Depression, HADS)评估。所有入组对象均详细记录相关病史和既往史。 结果：角膜触觉在中央、上方、下方、鼻侧、颞侧等方位的均值依次为：58.70±3.76mm,41.67±16.53mm,42.08±15.32mm,47.71±15.88mm,50.21±14.10mm;周边四个方位平均47.77±9.51mm；各方位平均49.96±8.16mm；两两比较显示中央与上方(p=0.000)、下方(p=0.000)及周边(p=0.012)均值的差异显著；各年龄层间或性别间无显著差异(p0.05)。LSCM下平均角膜神经密度(u m/幅)为2442.09±653.05,男、女分别为2598.62±642.14,2222.95±634.65,性别间无统计学差异(p=0.170)。平均LC密度(个/mm2)为10.24±19.38,其中未成熟型7.90±14.85,成熟型2.34±5.11；男、女平均LC密度分别为13.84±23.44,5.21±10.86,性别间差异不显著(p=0.292)。角膜触觉、角膜神经密度与角膜中央区LC密度三者间未见无明显相关。 结论：角膜机械觉阈值及神经密度水平与现有其他人种的报道结果相近,而中央区LC密度及其存在比例高于既往研究结果。三者均未发现年龄性别差异或相关性。 第二部分 非干燥综合征干眼症角膜神经变化及其与症状的相关性研究 目的：观察轻中度非干燥综合征型干眼症(non-Sjogren's syndrome dry eye, NSSDE)患者的症状、体征、角膜机械觉、角膜神经形态学改变,并分析其相关性。 方法：选取2010年10月至2011年11月于复旦大学附属眼耳鼻喉科医院眼表病专科诊断为NSSDE的24眼(7男17女,平均48.13±13.87岁),设年龄及性别匹配的健康对照组24眼(10男14女,44.25±11.80岁),均接受裂隙灯检查、非接触式眼压测量、泪液分泌功能(Schirmer Ⅰ test, SIt)、泪膜破裂时间(Tear Breakup Time, TBUT)、角膜荧光染色(Fluorescein, FL)、接触式角膜知觉测量(Cochet-Bonnet角膜知觉计)和激光活体共聚焦显微镜(Laser In Vivo Confocal Microscopy, LSCM)检查。患者的症状、疼痛程度及精神状态分别通过眼表疾病指数(Ocular Surface Disease Index, OSDI)、视觉模拟评分法(Visual Analogue Scale, VAS)和综合医院焦虑抑郁量表(Hospital Anxiety and Depression Scale, HADS)予以评估。所有入组对象均详细记录相关病史和既往史。 结果：NSSDE组SIt、TBUT均值分别为9.75±5.99mm,3.92±2.31Sec,显著低于正常组的14.26±8.18mm (p=0.036),11.89±6.43sec (p=0.000)。 NSSDE患者眼干及不适主诉明显,OSDI及VAS分别为15.83±3.23、1.79±0.38,均显著高于正常组的8.14±1.66和0.00(p值均0.001)。NSSDE患者HADS中焦虑(a)和抑郁(d)评价分别为4.84±3.00、4.21±3.55,与正常组(3.38±1.88；4.5±2.72)比均无统计学差异(p(a)=0.189, p(d)=0.988). NSSDE患者的各方位平均角膜机械觉阈值(48.91±7.42mm)与正常人(49.96±8.16mm)相当,组间比较p=0.622。NSSDE患者与正常组角膜神经密度分别为2826.28±291.24u m/幅、2442.09±653.05μm/幅(p=0.030),两组角膜中央区LC密度分别为33.43±39.80个/mm2、10.24±19.38个/mm2(p=0.014)。NSSDE患者中央区出现LC的比例为72.73%,高于正常组的41.67%。VAS与OSDI、角膜神经密度,角膜LC密度呈正相关,rho依次为0.722(p0.001)、0.322(p=0.032)、0.337(p=0.025)。TBUT与VAS、OSDI均呈负相关,rho分别为-0.613(p0.001)、-0.600(p0.001)。Sit与TBUT呈正相关,rho=0.342(p=0.019)。HADd与Sit呈负相关,rho=-0.330(p=0.033); HADd与角膜神经密度呈正相关,rho=0.348(p=0.026)。 结论：轻中度NSSDE患者角膜机械觉无明显变化,但其角膜神经密度及炎症细胞浸润多明显增加,且后两者与干眼症状严重程度一致。 第三部分 角膜神经痛的症状、体征及角膜神经的形态学观察 目的：观察角膜神经痛的临床特点,探讨该病有效的诊断方法。 方法：选取2010年10月至2011年11月于复旦大学附属眼耳鼻喉科医院眼表病专科诊断为角膜神经痛的25眼(9男16女,平均47.08±14.57岁),设年龄及性别匹配的干眼症对照组24眼(7男17女,平均48.13±13.87岁),健康对照组24眼(10男14女,44.25±11.80岁),三组均接受裂隙灯检查、非接触式眼压测量、泪液分泌功能(Schirmer I test, SIt)、泪膜破裂时间(Tear Breakup Time, TBUT)、角膜荧光染色(Fluorescein, FL)、接触式角膜知觉测量(Cochet-Bonnet角膜知觉计)和激光活体共聚焦显微镜(Laser In Vivo Confocal Microscopy, LSCM)检查。患者的症状、疼痛程度及精神状态分别通过眼表疾病指数(Ocular Surface Disease Index, OSDI)、视觉模拟评分法(Visual Analogue Scale, VAS)和综合医院焦虑抑郁量表(Hospital Anxiety and Depression Scale, HADS)予以评估。所有入组对象均详细记录相关病史和既往史。 结果：角膜神经痛组的平均SIt (12.79±7.29mm), TBUT (11.90±3.67sec)及FL(0.02±0.14分)与正常对照组(14.26±8.18mm;11.89±6.43sec;0.02±0.15分)比无显著差异(p0.1),而干眼症组SIt(9.75±5.99mm)、TBUT(3.92±2.31sec)、FL(0.42±0.97分)皆异常(p0.001)。三组眼压均正常,且HADS平均得分无统计学差别(p0.05)。神经痛患者的OSDI (38.67±19.51)及VAS(5.29±1.74)均与干眼组(29.80±15.83；4.77±1.79)相近(p0.05),明显高于正常组(7.84±8.26；0.00；p0.001),且OSDI与VAS正相关(rho=0.458,p0.01)。神经痛患者的角膜机械觉更敏感(56.43±4.51mm),高于干眼(48.91±7.42mm)和健康组(49.96±8.16mm)(p0.001)。三组平均角膜神经密度分别为(μm/幅)：神经痛组3094.35±887.09：干眼症组2668.36±534.59；正常组2476.08±600.23：差别显著(p=0.011)；研究组的朗格汉斯细胞(LC)密度(个/mm2)59.51±83.12,高于干眼对照组33.43±39.80(p0.10),显著高于正常组的10.24±19.38(p0.01)。LC密度与OSDI值间正相关(0.423,p=0.04)。 结论：角膜神经痛是一种有干眼类似症状却无“眼干”体征的疾病,常伴有角膜机械觉过度敏感、角膜神经密度及中央区LC密度明显增高,且与症状严重程度正相关；IVCM是该病确诊的关键。
[Abstract]:Part one
The correlation of corneal nerve morphology and corneal sensitivity in human confocal microscopy
Objective: To observe the normal corneal nerve density of Central Asians, Lange Hans (Langerhans cell, LC) cell density range and corneal sensitivity, analysis of the three age, gender characteristics and correlation.
Methods: 24 eyes of 24 healthy volunteers (10 male and 14 female, 44.25 + 11.80 years), underwent slit lamp examination, non-contact intraocular pressure measurement, tear secretion (Schirmer I test, SIt), break-up time (Tear Breakup, Time, TBUT), corneal fluorescein staining (Fluorescein, FL). Contact corneal measurement (Cochet-Bonnet corneal meter) and laser in vivo confocal microscopy (Laser In Vivo Confocal Microscopy, LSCM). Check the scale about including the ocular surface disease index (Ocular Surface Disease Index, OSDI) and comprehensive hospital anxiety and Depression Scale (Hospital Anxiety and Depression, HADS) in all evaluation. Group of objects were recorded the related history and past history.
Results: the corneal touch in the center, above, below the nose side, the mean temporal range is as follows: 58.70 + 3.76mm, 41.67 + 16.53mm, 42.08 + 15.32mm, 47.71 + 15.88mm, 50.21 + 14.10mm; around four range was 47.77 + 9.51mm; the average range of 49.96 + 8.16mm; 22 shows the central and above and below (p=0.000) (p=0.000) and peripheral (p=0.012) mean significant difference; there is no obvious difference between age or sex between (P0.05).LSCM average corneal nerve density (U m/) 2442.09 + 653.05, male, female were 2598.62 + 642.142222.95 + 634.65, there was no significant difference between the sexes (p=0.170). The average LC density (/mm2) was 10.24 + 19.38, 7.90 + 14.85 in immature and mature 2.34 + 5.11; male, female average LC density was 13.84 + 23.44,5.21 + 10.86, no gender difference (p= 0.292). Corneal touch, corneal nerve density and corneal No significant correlation between the three central LC density were not found.
Conclusion: corneal nerve density and mechanical threshold level and others existing reports similar results, while the central LC density and the proportion is higher than the previous research results. There are gender and age differences or correlation were not found in three.
The second part
The study of corneal nerve change and its correlation with symptoms in dry eye of non dry syndrome
Objective: To observe the symptoms, signs, corneal mechanical changes and morphological changes of corneal nerves in patients with mild to moderate non dry syndrome non-Sjogren's syndrome dry (eye), and analyze their correlation.
Methods: from October 2010 to November 2011 in Otolaryngological Hospital Affiliated to Fudan University of ocular surface disease specialist diagnosed NSSDE in 24 eyes (7 male and 17 female, with an average of 48.13 + 13.87 years), healthy control group 24 eyes with age - and sex matched (10 male and 14 female, 44.25 + 11.80 years), were connected by slit lamp examination, non-contact measurement of intraocular pressure, tear secretion (Schirmer I test, SIt), break-up time (Tear Breakup, Time, TBUT), corneal fluorescein staining (Fluorescein, FL), corneal contact measurement (Cochet-Bonnet corneal meter) and laser in vivo confocal microscopy (Laser In Vivo Confocal Microscopy, LSCM) were checked. The symptoms, pain and mental status were ocular surface disease index (Ocular Surface Disease Index, by OSDI), visual analogue scale (Visual Analogue Scale, VAS) and the hospital anxiety and Depression Scale (Hospital Anxie Ty and Depression Scale, HADS) was evaluated. All the entry objects were recorded in detailed history and previous history.
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