Burkholder Bryn M, Osborne Benjamin, Loguidice Michael J, Bisker Esther, Frohman Teresa C, Conger Amy, Ratchford John N, Warner Christina, Markowitz Clyde E, Jacobs Dina A, Galetta Steven L, Cutter Gary R, Maguire Maureen G, Calabresi Peter A, Balcer Laura J, Frohman Elliot M
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Arch Neurol. 2009 Nov;66(11):1366-72. doi: 10.1001/archneurol.2009.230.
Inner (area adjacent to the fovea) and outer regions of the macula differ with respect to relative thicknesses of the ganglion cell layer (neurons) vs retinal nerve fiber layer (RNFL; axons).
To determine how inner vs outer macular volumes relate to peripapillary RNFL thickness and visual function in multiple sclerosis (MS) and to examine how these patterns differ among eyes with vs without a history of acute optic neuritis (ON).
Study using cross-sectional optical coherence tomography.
Three academic tertiary care MS centers.
Patients with MS, diagnosed by standard criteria, and disease-free control participants.
Optical coherence tomography was used to measure macular volumes and RNFL thickness. Visual function was assessed using low-contrast letter acuity and high-contrast visual acuity (Early Treatment Diabetic Retinopathy Study charts).
Among eyes of patients with MS (n = 1058 eyes of 530 patients), reduced macular volumes were associated with peripapillary RNFL thinning; 10-microm differences in RNFL thickness (9.6% of thickness in control participants without disease) corresponded to 0.20-mm(3) reductions in total macular volume (2.9% of volume in control participants without disease, P < .001). This relation was similar for eyes of MS patients with and without a history of ON. Although peripapillary RNFL thinning was more strongly associated with decrements in outer compared with inner macular volumes, correlations with inner macular volume were significant (r = 0.58, P < .001) and of slightly greater magnitude for eyes of MS patients with a history of ON vs eyes of MS patients without a history of ON (r = 0.61 vs r = 0.50). Lower (worse) visual function scores were associated with reduced total, inner, and outer macular volumes. However, accounting for peripapillary RNFL thickness, the relation between vision and inner macular volume remained significant and unchanged in magnitude, suggesting that this region contains retinal structures separate from RNFL axons that are important to vision.
Analogous to studies of gray matter in MS, these data provide evidence that reductions of volume in the macula (approximately 34% neuronal cells by average thickness) accompany RNFL axonal loss. Peripapillary RNFL thinning and inner macular volume loss are less strongly linked in eyes of MS patients without a history of ON than in eyes of MS patients with a history of ON, suggesting alternative mechanisms for neuronal cell loss. Longitudinal studies with segmentation of retinal layers will further explore the relation and timing of ganglion cell degeneration and RNFL thinning in MS.
黄斑的内层（靠近中央凹的区域）和外层在神经节细胞层（神经元）与视网膜神经纤维层（RNFL；轴突）的相对厚度方面存在差异。
确定黄斑内层与外层体积如何与多发性硬化症（MS）患者的视乳头周围RNFL厚度及视觉功能相关，并研究这些模式在有与无急性视神经炎（ON）病史的眼睛之间有何不同。
采用横断面光学相干断层扫描的研究。
三个学术性三级医疗MS中心。
根据标准标准诊断的MS患者以及无疾病的对照参与者。
使用光学相干断层扫描测量黄斑体积和RNFL厚度。使用低对比度字母视力和高对比度视力（糖尿病视网膜病变早期治疗研究图表）评估视觉功能。
在MS患者的眼睛中（530例患者共1058只眼），黄斑体积减小与视乳头周围RNFL变薄相关；RNFL厚度相差10微米（在无疾病的对照参与者中占厚度的9.6%）对应于黄斑总体积减少0.20立方毫米（在无疾病的对照参与者中占体积的2.9%，P <.001）。对于有和无ON病史的MS患者的眼睛，这种关系相似。尽管与黄斑内层体积相比，视乳头周围RNFL变薄与外层体积减小的相关性更强，但与黄斑内层体积的相关性也很显著（r = 0.58，P <.001），并且有ON病史的MS患者的眼睛与无ON病史的MS患者的眼睛相比，相关性稍强（r = 0.61对r = 0.50）。较低（较差）的视觉功能评分与黄斑总体积、内层和外层体积减小相关。然而，在考虑视乳头周围RNFL厚度后，视力与黄斑内层体积之间的关系仍然显著且大小不变，这表明该区域包含与对视力重要的RNFL轴突分开的视网膜结构。
类似于MS中灰质的研究，这些数据提供了证据表明黄斑体积减小（按平均厚度约34%的神经元细胞）伴随着RNFL轴突丢失。与有ON病史的MS患者的眼睛相比，无ON病史的MS患者的眼睛中视乳头周围RNFL变薄与黄斑内层体积丢失的联系较弱，这表明神经元细胞丢失存在不同机制。对视网膜层进行分割的纵向研究将进一步探索MS中神经节细胞变性与RNFL变薄的关系及时间。
