Background Microcystic macular edema (MME) of the retinal inner nuclear layer (INL) has recently been identified in multiple sclerosis (MS) patients with optical coherence tomography (OCT). We aimed to determine if MME of the INL, and/or higher thickness of the INL, are associated with disease activity, or disability progression. Methods This retrospective study was performed at Johns Hopkins Hospital (between 09/2008 and 03/2012). 164 MS patients and 60 healthy-controls underwent serial OCT scans and clinical evaluation (including visual function). OCT scanning, including automated intra-retinal layer segmentation, yielded thicknesses of the retinal nerve fiber layer, ganglion cell layer (plus inner plexiform layer), INL (plus outer plexiform layer), and outer nuclear layer. MS patients also underwent annual brain MRI scans. Disability scores were compared with the Wilcoxon rank-sum test. Mixed-effects linear regression was used to compare OCT measures and letter-acuity scores. Logistic regression was used to examine the relationships of baseline OCT thicknesses with clinico-radiological parameters. Findings Mean follow-up (standard deviation) for MS patients and healthy-controls was 25·8-months (9·1-months) and 22·4-months (11·4-months) respectively. 10 MS patients (6·1% of the cohort) demonstrated MME during at least one study visit, but MME was not visible at baseline in 6 of these patients. MS patients with vs. without MME (151 MS patients) at any time during the study had higher baseline multiple sclerosis severity scores (p=0·032), although expanded disability status scale (EDSS) scores were not significantly different (p=0·097). MS eyes with MME (12 eyes) vs. without MME (302 eyes) had lower letter-acuity scores (100%-contrast: p=0·017; 2·5%-contrast: p=0·031; 1·25%-contrast: p=0·014), and higher INL thicknesses (p=0·003) at baseline. Higher baseline INL thickness in MS predicted the development of contrast-enhancing lesions (p=0·007), new T2 lesions (p=0·015), EDSS progression (p=0·034), and relapses (in relapsing-remitting MS; p=0·008) during the study. MME was not associated with disease activity during follow-up. Healthy-controls did not demonstrate MME. Interpretation Increased INL thickness on OCT, potentially representing inflammation of the unmyelinated retina, is associated with disease activity in MS. If this finding is confirmed, INL thickness may be a useful predictor of disease progression in MS. Funding National Multiple Sclerosis Society (TR3760-A-3, RG4212-A-4), National Eye Institute (R01-EY014993, R01-EY019473), Braxton Debbie Angela Dillon and Skip Donor Fund.

Optical coherence tomography (OCT) has proven to be an essential imaging modality for ophthalmology and is proving to be very important in neurology. OCT enables high resolution imaging of the retina, both at the optic nerve head and the macula. Macular retinal layer thicknesses provide useful diagnostic information and have been shown to correlate well with measures of disease severity in several diseases. Since manual segmentation of these layers is time consuming and prone to bias, automatic segmentation methods are critical for full utilization of this technology. In this work, we build a random forest classifier to segment eight retinal layers in macular cube images acquired by OCT. The random forest classifier learns the boundary pixels between layers, producing an accurate probability map for each boundary, which is then processed to finalize the boundaries. Using this algorithm, we can accurately segment the entire retina contained in the macular cube to an accuracy of at least 4.3 microns for any of the nine boundaries. Experiments were carried out on both healthy and multiple sclerosis subjects, with no difference in the accuracy of our algorithm found between the groups.

Objective: To determine the effect of clinical and radiologic disease activity on the rate of thinning of the ganglion cell/inner plexiform (GCIP) layer and the retinal nerve fiber layer in patients with multiple sclerosis (MS) using optical coherence tomography (OCT).Methods: One hundred sixty-four patients with MS and 59 healthy controls underwent spectraldomain OCT scans every 6 months for a mean follow-up period of 21.1 months. Baseline and annual contrast-enhanced brain MRIs were performed. Patients who developed optic neuritis during follow-up were excluded from analysis.Results: Patients with the following features of disease activity during follow-up had faster rates of annualized GCIP thinning: relapses (42% faster, p 5 0.007), new gadolinium-enhancing lesions (54% faster, p , 0.001), and new T2 lesions (36% faster, p 5 0.02). Annual GCIP thinning was 37% faster in those with disability progression during follow-up, and 43% faster in those with disease duration ,5 years vs .5 years (p 5 0.003). Annual rates of GCIP thinning were highest in patients exhibiting combinations of new gadolinium-enhancing lesions, new T2 lesions, and disease duration ,5 years (70% faster in patients with vs without all 3 characteristics, p , 0.001).Conclusions: MS patients with clinical and/or radiologic nonocular disease activity, particularly early in the disease course, exhibit accelerated GCIP thinning. Our findings suggest that retinal changes in MS reflect global CNS processes, and that OCT-derived GCIP thickness measures may have utility as an outcome measure for assessing neuroprotective agents, particularly in early, active MS. The anterior visual pathway is frequently affected in multiple sclerosis (MS), with 94% to 99% of patients with MS demonstrating optic nerve lesions postmortem.