Association of Retinal and Macular Damage with Brain Atrophy in Multiple Sclerosis

Abstract

Neuroaxonal degeneration in the central nervous system contributes substantially to the long term disability in multiple sclerosis (MS) patients. However, in vivo determination and monitoring of neurodegeneration remain difficult. As the widely used MRI-based approaches, including the brain parenchymal fraction (BPF) have some limitations, complementary in vivo measures for neurodegeneration are necessary. Optical coherence tomography (OCT) is a potent tool for the detection of MS-related retinal neurodegeneration. However, crucial aspects including the association between OCT- and MRI-based atrophy measures or the impact of MS-related parameters on OCT parameters are still unclear. In this large prospective cross-sectional study on 104 relapsing remitting multiple sclerosis (RRMS) patients we evaluated the associations of retinal nerve fiber layer thickness (RNFLT) and total macular volume (TMV) with BPF and addressed the impact of disease-determining parameters on RNFLT, TMV or BPF. BPF, normalized for subject head size, was estimated with SIENAX. Relations were analyzed primarily by Generalized Estimating Equation (GEE) models considering within-patient inter-eye relations. We found that both RNFLT (p = 0.019, GEE) and TMV (p = 0.004, GEE) associate with BPF. RNFLT was furthermore linked to the disease duration (p<0.001, GEE) but neither to disease severity nor patients' age. Contrarily, BPF was rather associated with severity (p<0.001, GEE) than disease duration and was confounded by age (p<0.001, GEE). TMV was not associated with any of these parameters. Thus, we conclude that in RRMS patients with relatively short disease duration and rather mild disability RNFLT and TMV reflect brain atrophy and are thus promising parameters to evaluate neurodegeneration in MS. Furthermore, our data suggest that RNFLT and BPF reflect different aspects of MS. Whereas BPF best reflects disease severity, RNFLT might be the better parameter for monitoring axonal damage longitudinally. Longitudinal studies are necessary for validation of data and to further clarify the relevance of TMV.

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

“…121 These findings may be explained by the reported correlations between RNFL thickness and brain atrophy. 122,123 Not all studies have found the same, however, others have reported an association between cognitive impairment in MS patients and performance in visual function tests such as low contrast sensitivity testing. 124 Early detection of cognitive dysfunction is important, as cognitive symptoms significantly impact the quality of life in MS patients.…”

Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

“…We are familiar with the notion that optic neuritis is more than a demyelination state and that substantial neuroaxonal damage may also occur in the patients, as revealed by recent optical coherence tomography (OCT) studies [15][16][17][18][19] . However, while the functional consequence of this neuroaxonal damage was previously established [20][21][22] , demonstrating reduced visual acuity, contrast acuity and visual quality of life, the functional consequence of demyelination was rarely addressed.…”

Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis

“…Based on these data, the RNFL thickness (RNFLT) and TMV have been proposed as potential surrogate outcome measures of neuro-axonal degeneration in MS [14]. Recent studies suggest that OCT measures of retinal degeneration correlate with MRI measures of brain tissue loss [17][18][19][20][21]. As a limitation of all these studies, time domain OCT (TD-OCT) has been used as opposed to the more advanced and more accurate spectral domain OCT technique (SD-OCT), with faster data acquisition, greater reliability and higher resolution [17,22].…”