Abstract Details

It is critical to understand if neuroaxonal loss in MS is continuously linear or declines with time.

To assess and compare rates of neurodegeneration in retina and brain throughout the MS disease course in a well-phenotyped longitudinal cohort.

We analyzed 598 MS patients (mean age 45.3±11 yrs; dz duration 11.6±9.7 yrs), who underwent longitudinal OCT imaging annually for a period of 4.5±2.4 years. Longitudinal MRI scans (study period of 10±3.4 yrs) were available from 434 patients (mean age 41.8±9.6 yrs; dz duration 8±8.3 yrs). Primary outcome parameters were macular ganglion cell–inner plexiform layer (GCIPL) volume and cortical gray matter (CGM) volume.

To evaluate the rate of loss, linear mixed-effects modeling with subject-specific intercepts and slopes were fitted using restricted maximum likelihood estimation. The association between the slope of decline in the anatomical structure and the age of entry in the cohort (categorized by the MRI cohort’s age quartiles) was assessed by linear regression models

The rate of CGM volume loss declined minimally with increasing age of study entry (ASE):1.3%/yr ASE<35yrs; 1.1%/yr ASE=35-41yrs;0.97%/yr ASE=41-49; and 0.9%/yr ASE>49 years. The rate of GCIPL thinning was highest in patients in the youngest ASE quartile, fell by nearly 50% in the following ASE quartile and then stabilized across ASE:0.7%/yr for ASE<35yrs; 0.29% for ASE=35-41yrs ; 0.34% for ASE=41-49yrs; 0.33% for ASE>49yrs.

An age-dependent reduction in rates of retinal and cortical volume loss during RRMS suggests deceleration in neurodegeneration in the earlier period of disease and further suggests that the period of greatest inflammatory activity is also the period with the greatest neuroaxonal loss. The observed difference in neurodegeneration between the CGM and retina could be due to differences in the architecture of the tissues, varying susceptibility to degenerative injury or differences in the sensitivity and specificity of OCT and MRI in detecting tissue atrophy.