Bitirgen Gulfidan, Akpinar Zehra, Malik Rayaz A, Ozkagnici Ahmet
Department of Ophthalmology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey.
Department of Neurology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey.
JAMA Ophthalmol. 2017 Jul 1;135(7):777-782. doi: 10.1001/jamaophthalmol.2017.1590.
Multiple sclerosis (MS) is characterized by demyelination, axonal degeneration, and inflammation. Corneal confocal microscopy has been used to identify axonal degeneration in several peripheral neuropathies.
To assess corneal subbasal nerve plexus morphologic features, corneal dendritic cell (DC) density, and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with MS.
DESIGN, SETTING, AND PARTICIPANTS: This single-center, cross-sectional comparative study was conducted at a tertiary referral university hospital between May 27, 2016, and January 30, 2017. Fifty-seven consecutive patients with relapsing-remitting MS and 30 healthy, age-matched control participants were enrolled in the study. Corneal subbasal nerve plexus measures and DC density were quantified in images acquired with the laser scanning in vivo corneal confocal microscope, and peripapillary RNFL thickness was measured with spectral-domain optical coherence tomography.
Corneal nerve fiber density, nerve branch density, nerve fiber length, DC density, peripapillary RNFL thickness, and association with the severity of neurologic disability as assessed by the Kurtzke Expanded Disability Status Scale (score range, 0-10; higher scores indicate greater disability) and Multiple Sclerosis Severity Score (score range, 0.01-9.99; higher scores indicate greater severity).
Of the 57 participants with MS, 42 (74%) were female and the mean (SD) age was 35.4 (8.9) years; of the 30 healthy controls, 19 (63%) were female and the mean (SD) age was 34.8 (10.2) years. Corneal nerve fiber density (mean [SE] difference, -6.78 [2.14] fibers/mm2; 95% CI, -11.04 to -2.52; P = .002), nerve branch density (mean [SE] difference, -17.94 [5.45] branches/mm2; 95% CI, -28.77 to -7.10; P = .001), nerve fiber length (mean [SE] difference, -3.03 [0.89] mm/mm2; 95% CI, -4.81 to -1.25; P = .001), and the mean peripapillary RNFL thickness (mean [SE] difference, -17.06 [3.14] μm; 95% CI, -23.29 to -10.82; P < .001) were reduced in patients with MS compared with healthy controls. The DC density was increased (median [interquartile range], 27.7 [12.4-66.8] vs 17.3 [0-28.2] cells/mm2; P = .03), independent of a patient's history of optic neuritis. Nerve fiber density and RNFL thickness showed inverse associations with the Expanded Disability Status Scale (ρ = -0.295; P = .03 for nerve fiber density and ρ = -0.374; P = .004 for RNFL thickness) and the Multiple Sclerosis Severity Score (R = -0.354; P = .007 for nerve fiber density and R = -0.283; P = .03 for RNFL thickness), whereas other study measures did not.
These data suggest that corneal confocal microscopy demonstrates axonal loss and increased DC density in patients with MS. Additional longitudinal studies are needed to confirm the use of corneal confocal microscopy as an imaging biomarker in patients with MS.
多发性硬化症（MS）的特征是脱髓鞘、轴突退变和炎症。角膜共聚焦显微镜已被用于识别几种周围神经病变中的轴突退变。
评估MS患者的角膜基底神经丛形态学特征、角膜树突状细胞（DC）密度和视乳头周围视网膜神经纤维层（RNFL）厚度。
设计、设置和参与者：这项单中心横断面比较研究于2016年5月27日至2017年1月30日在一家三级转诊大学医院进行。连续纳入57例复发缓解型MS患者和30名年龄匹配的健康对照者。使用激光扫描体内角膜共聚焦显微镜采集的图像对角膜基底神经丛测量值和DC密度进行量化，并用谱域光学相干断层扫描测量视乳头周围RNFL厚度。
角膜神经纤维密度、神经分支密度、神经纤维长度、DC密度、视乳头周围RNFL厚度，以及与通过Kurtzke扩展残疾状态量表（评分范围0 - 10；分数越高表明残疾越严重）和多发性硬化症严重程度评分（评分范围0.01 - 9.99；分数越高表明病情越严重）评估的神经功能残疾严重程度的相关性。
57例MS参与者中，42例（74%）为女性，平均（标准差）年龄为35.4（8.9）岁；30名健康对照者中，19例（63%）为女性，平均（标准差）年龄为34.8（10.2）岁。与健康对照者相比，MS患者的角膜神经纤维密度（平均[标准误]差值， - 6.78[2.14]根/平方毫米；95%置信区间， - 11.04至 - 2.52；P = 0.002）、神经分支密度（平均[标准误]差值， - 17.94[5.45]支/平方毫米；95%置信区间， - 28.77至 - 7.10；P = 0.001）、神经纤维长度（平均[标准误]差值， - 3.03[0.89]毫米/平方毫米；95%置信区间， - 4.81至 - 1.25；P = 0.001）以及平均视乳头周围RNFL厚度（平均[标准误]差值， - 17.06[3.14]微米；95%置信区间， - 23.29至 - 10.82；P < 0.001）均降低。DC密度增加（中位数[四分位间距]，27.7[12.4 - 66.8]对17.3[0 - 28.2]个/平方毫米；P = 0.03），与患者的视神经炎病史无关。神经纤维密度和RNFL厚度与扩展残疾状态量表呈负相关（神经纤维密度ρ = - 0.295；P = 0.03，RNFL厚度ρ = - 0.374；P = 0.004）以及与多发性硬化症严重程度评分呈负相关（神经纤维密度R = - 0.354；P = 0.007，RNFL厚度R = - 0.283；P = 0.03），而其他研究测量指标则无此相关性。
这些数据表明角膜共聚焦显微镜显示MS患者存在轴突丢失和DC密度增加。需要更多的纵向研究来证实角膜共聚焦显微镜作为MS患者成像生物标志物的应用。
