Abstract：
This study aims to investigate the role of in vivo corneal confocal microscopy (IVCCM) in the detection of corneal inflammatory activity and subbasal nerve alterations in patients with multiple sclerosis (MS) and to further determine whether IVCCM can be used to detect (acute) disease relapse.
Prospective cross-sectional study, with a subgroup follow-up.
This single-center study included 58 patients with MS (MS-Relapse group [n = 27] and MS-Remission group [n = 31]), and 30 age- and sex-matched healthy control subjects. Patients with a history of optic neuritis or trigeminal symptoms were excluded. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and dendritic cell (DC) density were evaluated in all patients with MS and control subjects by IVCCM. Patients in the MS-Relapse group who were in remission for ≥6 months after the MS incident underwent a repeat IVCCM.
No statistical difference was observed between the MS-Relapse and MS-Remission groups regarding age, sex, MS duration, and the number of relapses (P > .05). Compared with healthy control subjects, all subbasal nerve parameters were significantly lower (CNFD: P < .001, CNFL: P < .001, CNBD: P < .001), and the DC density was significantly higher (P = .023) in patients with MS. However, no significant difference was observed between MS-Relapse and MS-Remission groups in terms of CNFD (mean [SE] difference -2.05 [1.69] fibers/mm2 [95% confidence interval {CI} -1.32 to 5.43]; P < .227), CNFL (mean [SE] difference -1.10 [0.83] mm/mm2 [95% CI -0.56 to 2.75]; P < .190), CNBD (mean [SE] difference -3.91 [2.48] branches/mm2 [95% CI -1.05 to 8.87]; P < .120), and DC density (median [IQR], 59.38 [43.75-85.0] vs 75.0 [31.25-128.75]; P = .596). The repeat IVCCM in relapse patients (n = 16 [59.3%]) showed a significant increase in CNFD (P = .036) and CNBD (P = .018), but no change was observed in CNFL (P = .075) and DC density (P = .469).
Although increased inflammation and neurodegeneration can be demonstrated in patients with MS compared with healthy control subjects, a single time point evaluation of IVCCM does not seem to be sufficient to confirm the occurrence of relapse in patients with MS. However, IVCCM holds promise for demonstrating early neuroregeneration in patients with MS.
Prospective cross-sectional study, with a subgroup follow-up.
This single-center study included 58 patients with MS (MS-Relapse group [n = 27] and MS-Remission group [n = 31]), and 30 age- and sex-matched healthy control subjects. Patients with a history of optic neuritis or trigeminal symptoms were excluded. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and dendritic cell (DC) density were evaluated in all patients with MS and control subjects by IVCCM. Patients in the MS-Relapse group who were in remission for ≥6 months after the MS incident underwent a repeat IVCCM.
No statistical difference was observed between the MS-Relapse and MS-Remission groups regarding age, sex, MS duration, and the number of relapses (P > .05). Compared with healthy control subjects, all subbasal nerve parameters were significantly lower (CNFD: P < .001, CNFL: P < .001, CNBD: P < .001), and the DC density was significantly higher (P = .023) in patients with MS. However, no significant difference was observed between MS-Relapse and MS-Remission groups in terms of CNFD (mean [SE] difference -2.05 [1.69] fibers/mm2 [95% confidence interval {CI} -1.32 to 5.43]; P < .227), CNFL (mean [SE] difference -1.10 [0.83] mm/mm2 [95% CI -0.56 to 2.75]; P < .190), CNBD (mean [SE] difference -3.91 [2.48] branches/mm2 [95% CI -1.05 to 8.87]; P < .120), and DC density (median [IQR], 59.38 [43.75-85.0] vs 75.0 [31.25-128.75]; P = .596). The repeat IVCCM in relapse patients (n = 16 [59.3%]) showed a significant increase in CNFD (P = .036) and CNBD (P = .018), but no change was observed in CNFL (P = .075) and DC density (P = .469).
Although increased inflammation and neurodegeneration can be demonstrated in patients with MS compared with healthy control subjects, a single time point evaluation of IVCCM does not seem to be sufficient to confirm the occurrence of relapse in patients with MS. However, IVCCM holds promise for demonstrating early neuroregeneration in patients with MS.
摘要：
目的：本研究旨在探讨体内角膜共聚焦显微镜（IVCCM）在多发性硬化（MS）患者角膜炎症活动和基底下神经改变检测中的作用，并进一步确定IVCCM是否可用于检测（急性）疾病复发。
方法：前瞻性横断面研究，方法：这项单中心研究包括58例MS患者（MS复发组[n=27]和MS缓解组[n=31]），和年龄性别匹配的30名健康对照。排除有视神经炎或三叉神经症状的患者。角膜神经纤维密度（CNFD），角膜神经分支密度（CNBD），角膜神经纤维长度（CNFL），通过IVCCM评估所有MS患者和对照组的树突状细胞（DC）密度。MS复发组的患者，在MS发作后至少6个月内缓解，进行了重复IVCCM。
结果：MS复发组和MS缓解组之间在年龄方面没有观察到统计学差异，性别,MS持续时间,和复发次数(p>0.05)。与健康对照相比，所有基底下神经参数均显着降低（CNFD：p<0.001，CNFL：p<0.001，CNBD：p<0.001），MS患者DC密度显著增高(p=0.023)。然而,在CNFD方面，MS复发和MS缓解组之间没有观察到显著差异(平均[SE]差异，-2.05[1.69]纤维/mm2；%95CI，-1.32至5.43；p<0.227），CNFL(平均[SE]差异，-1.10[0.83]mm/mm2;%95CI,-0.56至2.75;p<0.190),CNBD(平均[SE]差异，-3.91[2.48]个分支/mm2；%95CI，-1.05至8.87；p<0.120），和DC密度(中位数[IQR]，59.38[43.75-85.0]vs.75.0[31.25-128.75],p=0.596)。复发患者（n=16[59.3％]）的重复IVCCM显示CNFD（p=0.036）和CNBD（p=0.018）显着增加，但未观察到CNFL(p=0.075)和DC密度(p=0.469)的变化。
结论：尽管与健康对照组相比，MS患者的炎症和神经变性增加，对IVCCM进行单一时间点评估似乎不足以确认MS患者是否发生复发.然而,IVCCM有望证明MS患者的早期神经再生。
方法：前瞻性横断面研究，方法：这项单中心研究包括58例MS患者（MS复发组[n=27]和MS缓解组[n=31]），和年龄性别匹配的30名健康对照。排除有视神经炎或三叉神经症状的患者。角膜神经纤维密度（CNFD），角膜神经分支密度（CNBD），角膜神经纤维长度（CNFL），通过IVCCM评估所有MS患者和对照组的树突状细胞（DC）密度。MS复发组的患者，在MS发作后至少6个月内缓解，进行了重复IVCCM。
结果：MS复发组和MS缓解组之间在年龄方面没有观察到统计学差异，性别,MS持续时间,和复发次数(p>0.05)。与健康对照相比，所有基底下神经参数均显着降低（CNFD：p<0.001，CNFL：p<0.001，CNBD：p<0.001），MS患者DC密度显著增高(p=0.023)。然而,在CNFD方面，MS复发和MS缓解组之间没有观察到显著差异(平均[SE]差异，-2.05[1.69]纤维/mm2；%95CI，-1.32至5.43；p<0.227），CNFL(平均[SE]差异，-1.10[0.83]mm/mm2;%95CI,-0.56至2.75;p<0.190),CNBD(平均[SE]差异，-3.91[2.48]个分支/mm2；%95CI，-1.05至8.87；p<0.120），和DC密度(中位数[IQR]，59.38[43.75-85.0]vs.75.0[31.25-128.75],p=0.596)。复发患者（n=16[59.3％]）的重复IVCCM显示CNFD（p=0.036）和CNBD（p=0.018）显着增加，但未观察到CNFL(p=0.075)和DC密度(p=0.469)的变化。
结论：尽管与健康对照组相比，MS患者的炎症和神经变性增加，对IVCCM进行单一时间点评估似乎不足以确认MS患者是否发生复发.然而,IVCCM有望证明MS患者的早期神经再生。
