Fisher Jennifer B, Jacobs Dina A, Markowitz Clyde E, Galetta Steven L, Volpe Nicholas J, Nano-Schiavi M Ligia, Baier Monika L, Frohman Elliot M, Winslow Heather, Frohman Teresa C, Calabresi Peter A, Maguire Maureen G, Cutter Gary R, Balcer Laura J
Division of Neuro-ophthalmology, Departments of Neurology, Ophthalmology, and Biostatistics, University of Pennsylvania School of Medicine, Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
Ophthalmology. 2006 Feb;113(2):324-32. doi: 10.1016/j.ophtha.2005.10.040. Epub 2006 Jan 10.
To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes.
Cross-sectional study.
Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes).
Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed.
Retinal nerve fiber layer thickness measured by OCT, and visual function test results.
Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum.
Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.
研究视功能与视网膜神经纤维层（RNFL）厚度之间的关系，将其作为多发性硬化症（MS）轴突损失的一种结构生物标志物，并比较有急性视神经炎病史的MS患者眼（MS ON眼）、无视神经炎病史的MS患者眼（MS非ON眼）和无病对照眼之间的RNFL厚度。
横断面研究。
MS患者（n = 90；180只眼）和无病对照者（n = 36；72只眼）。
使用光学相干断层扫描（OCT；快速RNFL厚度软件协议）测量视网膜神经纤维层厚度。在OCT扫描前，对每只眼及双眼进行视力测试，采用先前已证明可检测MS患者功能障碍的指标：（1）低对比度字母视力（Sloan视力表，2米处对比度为2.5%和1.25%）和（2）对比敏感度（1米处Pelli-Robson视力表）。还测量了视力（3.2米处视网膜反光早期治疗糖尿病性视网膜病变视力表），并进行了验光。
通过OCT测量的视网膜神经纤维层厚度和视功能测试结果。
尽管两组的Snellen视力等效值中位数均优于20/20，但MS患者眼（92μm）的RNFL厚度明显低于对照组（105μm）（P<0.001），尤其是MS ON眼（85μm；P<0.001；考虑年龄并对患者眼内相关性进行校正）。较低的视功能评分与MS患者眼中平均总体RNFL厚度降低相关；低对比度字母视力或对比敏感度评分每降低1行，平均RNFL厚度降低4μm。
低对比度字母视力和对比敏感度评分与作为结构生物标志物的RNFL厚度密切相关，支持这些视功能测试作为MS试验次要临床结局指标的有效性。这些结果还表明，在研究神经保护和其他疾病修饰疗法的试验中，OCT等眼部成像技术具有一定作用。尽管有急性视神经炎病史的眼RNFL厚度降低最为明显，但MS非ON眼的RNFL厚度低于对照组，这表明MS患者中存在与急性发作无关的慢性轴突损失。
