Retinal Axonal Loss Begins Early in the Course of Multiple Sclerosis and Is Similar between Progressive Phenotypes

University of California, San Francisco Department of Neurology, Multiple Sclerosis Center, University of California San Francisco, San Francisco, California, United States of America.
PLoS ONE (Impact Factor: 3.23). 05/2012; 7(5):e36847. DOI: 10.1371/journal.pone.0036847
Source: PubMed


To determine whether retinal axonal loss is detectable in patients with a clinically isolated syndrome (CIS), a first clinical demyelinating attack suggestive of multiple sclerosis (MS), and examine patterns of retinal axonal loss across MS disease subtypes.
Spectral-domain Optical Coherence Tomography was performed in 541 patients with MS, including 45 with high-risk CIS, 403 with relapsing-remitting (RR)MS, 60 with secondary-progressive (SP)MS and 33 with primary-progressive (PP)MS, and 53 unaffected controls. Differences in retinal nerve fiber layer (RNFL) thickness and macular volume were analyzed using multiple linear regression and associations with age and disease duration were examined in a cross-sectional analysis. In eyes without a clinical history of optic neuritis (designated as "eyes without optic neuritis"), the total and temporal peripapillary RNFL was thinner in CIS patients compared to controls (temporal RNFL by -5.4 µm [95% CI -0.9 to--9.9 µm, p = 0.02] adjusting for age and sex). The total (p = 0.01) and temporal (p = 0.03) RNFL was also thinner in CIS patients with clinical disease for less than 1 year compared to controls. In eyes without optic neuritis, total and temporal RNFL thickness was nearly identical between primary and secondary progressive MS, but total macular volume was slightly lower in the primary progressive group (p<0.05).
Retinal axonal loss is increasingly prominent in more advanced stages of disease--progressive MS>RRMS>CIS--with proportionally greater thinning in eyes previously affected by clinically evident optic neuritis. Retinal axonal loss begins early in the course of MS. In the absence of clinically evident optic neuritis, RNFL thinning is nearly identical between progressive MS subtypes.

Download full-text


Available from: John Boscardin, Feb 17, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Retinal nerve fibre layer (RNFL) thinning is associated with brain atrophy in multiple sclerosis (MS). An influence of optic neuritis is well documented but sparsely investigated. Recently, the retinal ganglion cell layer (GCL) has been shown to provide superior information regarding visual function and retinal neurodegeneration as compared with RNFL. OBJECTIVE: To investigate the association of white and grey matter brain volume with peripapillary RNFL and macular GCL in MS patients with and without a history of optic neuritis. METHODS: 63 patients with relapsing-remitting MS were included in a two-centre cross-sectional prospective study. All patients underwent retinal examination with spectral domain optical coherence tomography and 1.5 T MRI for determination of normalized brain volume (NBV), white matter volume (NWMV) and grey matter volume (NGMV). RESULTS: Both RNFL and GCL were associated with NBV, NWMV and NGMV in eyes without previous optic neuritis. This association is disrupted in the case of NGMV following optic neuritis. CONCLUSIONS: Both RNFL and GCL as parameters of neuro-axonal damage are comparably linked to whole brain as well as white and grey matter atrophy. An event of optic neuritis interferes with this relation, adding further damage to the optic nerve and disrupting especially an association with grey matter.
    No preview · Article · Aug 2012 · Multiple Sclerosis
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In addition to cirrhosis of the liver, Wilson's disease leads to copper accumulation and widespread degeneration of the nervous system. Delayed visual evoked potentials (VEPs) suggest changes to the visual system and potential structural changes of the retina. We used the latest generation of spectral domain optical coherence tomography to assess the retinal morphology of 42 patients with Wilson's disease and 76 age- and sex-matched controls. We measured peripapillary retinal nerve fiber layer (RNFL) thickness and total macular thickness and manually segmented all retinal layers in foveal scans of 42 patients with Wilson's disease and 76 age- and sex-matched controls. The results were compared with VEPs and clinical parameters. The mean thickness of the RNFL, paramacular region, retinal ganglion cell/inner plexiform layer and inner nuclear layer was reduced in Wilson's disease. VEPs were altered with delayed N75 and P100 latencies, but the N140 latency and amplitude was unchanged. An analysis of the laboratory parameters indicated that the serum concentrations of copper and caeruloplasmin positively correlated with the thickness of the outer plexiform layer and with N75 and P100 VEP latencies. Neuronal degeneration in Wilson's disease involves the retina and changes can be quantified by optical coherence tomography. While the VEPs and the thickness of the outer plexiform layer appear to reflect the current copper metabolism, the thicknesses of the RNFL, ganglion cell/inner plexiform layer, inner nuclear layer and the total paramacular thickness may be the best indicators of chronic neuronal degeneration.
    Full-text · Article · Nov 2012 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To determine whether fingolimod, an oral sphingosine-1-phosphate receptor modulator approved for treatment of multiple sclerosis (MS), generally leads to increased retinal tissue volume. Methods: In this longitudinal observational study, we compared changes in macular volume on spectral-domain optical coherence tomography (OCT) between consecutive patients with MS who initiated fingolimod and a matched reference cohort of patients with MS never exposed to the drug. The primary reference cohort was matched based on time interval between OCT examinations. A secondary reference cohort was matched based on age and disease duration. Change in macular volume within each group was analyzed using the paired t test. Change in macular volume between groups was examined using multiple linear regression. Results: Macular volume increased by a mean of 0.025 mm3 (95% confidence interval [CI] +0.017 to +0.033, p < 0.001) in the 30 patients with MS who initiated fingolimod over a mean follow-up time of 5 months (SD 3). Macular volume did not significantly change over a mean follow-up time of 6 months (SD 4) in a comparison group of 30 patients with MS never treated with fingolimod (mean change of -0.003 mm3, 95% CI -0.009 to +0.004, p = 0.47). Overall, 74% of eyes in the fingolimod-treated group exhibited an increase in macular volume vs. 37% of eyes in the comparison group. Conclusion: Initiation of fingolimod in MS is associated with a modest, relatively rapid increase in macular volume.
    No preview · Article · Dec 2012 · Neurology
Show more