@article {809, title = {In vivo identification of morphologic retinal abnormalities in neuromyelitis optica.}, journal = {Neurology}, volume = {80}, year = {2013}, month = {2013 Apr 9}, pages = {1406-14}, abstract = {

OBJECTIVE: To assess eyes with neuromyelitis optica (NMO) for morphologic retinal abnormalities utilizing high-definition optical coherence tomography (OCT) imaging.

METHODS: In this cross-sectional study, 39 patients with NMO spectrum disorders and 39 age- and sex-matched healthy controls underwent spectral-domain OCT and visual function testing.

RESULTS: Microcystic macular edema (MME) of the inner nuclear layer (INL) was identified in 10 of 39 patients (26\%) and was exclusively found in eyes with a history of optic neuritis (ON). MME eyes had lower high- and low-contrast letter-acuity scores (100\%: p = 0.002; 2.5\%: p = 0.002; 1.25\%: p = 0.004), lower peripapillary retinal nerve fiber layer (RNFL) thickness (p = 0.04), lower macular RNFL thickness (p = 0.004), lower ganglion cell layer + inner plexiform layer (GCIP) thickness (p = 0.007), higher INL thickness (p < 0.001), and a greater number of ON episodes (p = 0.008) relative to non-MME eyes with a history of ON. After adjusting for history of multiple ON episodes, these findings remained significant for macular-RNFL thickness (p = 0.03), INL thickness (p < 0.001), and 100\% and 2.5\% contrast letter-acuity scores (p = 0.008 and p = 0.03, respectively). NMO spectrum eyes without ON history had lower macular RNFL thickness (p = 0.003), GCIP thickness (p = 0.002), outer nuclear layer thickness (p = 0.02), and low-contrast letter-acuity scores (2.5\%: p = 0.03; 1.25\%: p = 0.002) compared to healthy controls.

CONCLUSIONS: We have identified a pattern of retinal morphologic abnormalities in NMO that is associated with severe retinal axonal and neuronal loss and corresponding visual disability. MME may contribute to poor visual outcomes following NMO-associated ON or alternatively represent a marker of ON severity. Additionally, our results support that subclinical involvement of the anterior visual pathway may occur in NMO spectrum disorders.

}, keywords = {Adolescent, Adult, Aged, Aquaporin 4, Autoantibodies, Case-Control Studies, Chi-Square Distribution, Female, Humans, Macular Edema, Male, Middle Aged, Nerve Fibers, Neuromyelitis Optica, Retina, Tomography, Optical Coherence, Vision Tests, Visual Acuity, Young Adult}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31828c2f7a}, author = {Sotirchos, Elias S and Saidha, Shiv and Byraiah, Gita and Mealy, Maureen A and Ibrahim, Mohamed A and Sepah, Yasir Jamal and Newsome, Scott D and Ratchford, John N and Frohman, Elliot M and Balcer, Laura J and Crainiceanu, Ciprian M and Nguyen, Quan Dong and Levy, Michael and Calabresi, Peter A} } @article {812, title = {Likelihood-based population independent component analysis.}, journal = {Biostatistics}, volume = {14}, year = {2013}, month = {2013 Jul}, pages = {514-27}, abstract = {

Independent component analysis (ICA) is a widely used technique for blind source separation, used heavily in several scientific research areas including acoustics, electrophysiology, and functional neuroimaging. We propose a scalable two-stage iterative true group ICA methodology for analyzing population level functional magnetic resonance imaging (fMRI) data where the number of subjects is very large. The method is based on likelihood estimators of the underlying source densities and the mixing matrix. As opposed to many commonly used group ICA algorithms, the proposed method does not require significant data reduction by a 2-fold singular value decomposition. In addition, the method can be applied to a large group of subjects since the memory requirements are not restrictive. The performance of our approach is compared with a commonly used group ICA algorithm via simulation studies. Furthermore, the proposed method is applied to a large collection of resting state fMRI datasets. The results show that established brain networks are well recovered by the proposed algorithm.

}, keywords = {Adult, Algorithms, Attention Deficit Disorder with Hyperactivity, Biostatistics, Brain, Child, Computer Simulation, Databases, Factual, Humans, Imaging, Three-Dimensional, Likelihood Functions, Magnetic Resonance Imaging, Principal Component Analysis, Statistics, Nonparametric}, issn = {1468-4357}, doi = {10.1093/biostatistics/kxs055}, author = {Eloyan, Ani and Crainiceanu, Ciprian M and Caffo, Brian S} } @article {811, title = {Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis.}, journal = {JAMA Neurol}, volume = {70}, year = {2013}, month = {2013 Jan}, pages = {34-43}, abstract = {

OBJECTIVE: To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS).

DESIGN: Cross-sectional study.

SETTING: Johns Hopkins University, Baltimore, Maryland.

PARTICIPANTS: A total of 84 patients with MS and 24 healthy control subjects.

MAIN OUTCOME MEASURES: High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes.

RESULTS: Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer+inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P=.01 and P=.04, respectively) and caudate (P=.04 and P=.03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P=.007) and inversely associated with normal-appearing white matter volume (P=.005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. CONCLUSIONS Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes.

}, keywords = {Adult, Axons, Caudate Nucleus, Central Nervous System, Cerebral Cortex, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Retina, Retinal Neurons, Tomography, Optical Coherence}, issn = {2168-6157}, doi = {10.1001/jamaneurol.2013.573}, author = {Saidha, Shiv and Sotirchos, Elias S and Oh, Jiwon and Syc, Stephanie B and Seigo, Michaela A and Shiee, Navid and Eckstein, Chistopher and Durbin, Mary K and Oakley, Jonathan D and Meyer, Scott A and Frohman, Teresa C and Newsome, Scott and Ratchford, John N and Balcer, Laura J and Pham, Dzung L and Crainiceanu, Ciprian M and Frohman, Elliot M and Reich, Daniel S and Calabresi, Peter A} } @article {709, title = {Microcystic macular oedema, thickness of the inner nuclear layer of the retina, and disease characteristics in multiple sclerosis: a retrospective study.}, journal = {Lancet Neurol}, volume = {11}, year = {2012}, month = {2012 Nov}, pages = {963-72}, abstract = {

BACKGROUND: Microcystic macular oedema (MMO) of the retinal inner nuclear layer (INL) has been identified in patients with multiple sclerosis (MS) by use of optical coherence tomography (OCT). We aimed to determine whether MMO of the INL, and increased thickness of the INL are associated with disease activity or disability progression.

METHODS: This retrospective study was done at the Johns Hopkins Hospital (Baltimore, MD, USA), between September, 2008, and March, 2012. Patients with MS and healthy controls underwent serial OCT scans and clinical assessments including visual function. OCT scanning, including automated intraretinal layer segmentation, yielded thicknesses of the retinal nerve fibre layer, the ganglion cell layer plus inner plexiform layer, the INL plus outer plexiform layer (the combined thickness of these layers was used as a surrogate measure of INL thickness), and the outer nuclear layer. Patients with MS 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 relations of baseline OCT thicknesses with clinical and radiological parameters.

FINDINGS: 164 patients with MS and 60 healthy controls were assessed. Mean follow-up was 25{\textperiodcentered}8 months (SD 9{\textperiodcentered}1) for patients with MS and 22{\textperiodcentered}4 months (11{\textperiodcentered}4) for healthy controls. Ten (6\%) patients with MS had MMO during at least one study visit; MMO was visible at baseline in four of these patients. Healthy controls did not have MMO. Patients with MS and MMO had higher baseline MS severity scores (median 5{\textperiodcentered}93 [range 2{\textperiodcentered}44-8{\textperiodcentered}91]) than those who did not have MMO at any time during the study (151 patients; 3{\textperiodcentered}81 [0{\textperiodcentered}13-9{\textperiodcentered}47]; p=0{\textperiodcentered}032), although expanded disability status scale (EDSS) scores were not significantly different (5{\textperiodcentered}2 [1{\textperiodcentered}0-6{\textperiodcentered}5] for patients with MS and MMO vs 2{\textperiodcentered}5 [0{\textperiodcentered}0-8{\textperiodcentered}0] for those without MMO; p=0{\textperiodcentered}097). The eyes of patients with MS and MMO (12 eyes) versus those without MMO (302 eyes) had lower letter-acuity scores (100\% contrast, p=0{\textperiodcentered}017; 2{\textperiodcentered}5\% contrast, p=0{\textperiodcentered}031; 1{\textperiodcentered}25\% contrast, p=0{\textperiodcentered}014), and increased INL thicknesses (p=0{\textperiodcentered}003) at baseline. Increased baseline INL thickness in patients with MS was associated with the development of contrast-enhancing lesions (p=0{\textperiodcentered}007), new T2 lesions (p=0{\textperiodcentered}015), EDSS progression (p=0{\textperiodcentered}034), and relapses in patients with relapsing-remitting MS (p=0{\textperiodcentered}008) during the study. MMO was not associated with disease activity during follow-up.

INTERPRETATION: Increased INL thickness on OCT is associated with disease activity in MS. If this finding is confirmed, INL thickness could be a useful predictor of disease progression in patients with MS.

FUNDING: National Multiple Sclerosis Society, National Eye Institute, Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.

}, keywords = {Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Macular Edema, Male, Middle Aged, Multiple Sclerosis, Retina, Retinal Ganglion Cells, Retrospective Studies, Tomography, Optical Coherence}, issn = {1474-4465}, doi = {10.1016/S1474-4422(12)70213-2}, author = {Saidha, Shiv and Sotirchos, Elias S and Ibrahim, Mohamed A and Crainiceanu, Ciprian M and Gelfand, Jeffrey M and Sepah, Yasir J and Ratchford, John N and Oh, Jiwon and Seigo, Michaela A and Newsome, Scott D and Balcer, Laura J and Frohman, Elliot M and Green, Ari J and Nguyen, Quan D and Calabresi, Peter A} }