In vivo assessment of retinal neuronal layers in multiple sclerosis with manual and automated optical coherence tomography segmentation techniques
ABSTRACT Macular optical coherence tomography (OCT) segmentation, enabling quantification of retinal axonal and neuronal subpopulations, may help elucidate the neuroretinal pathobiology of multiple sclerosis (MS). This study aimed to determine the agreement, reproducibility, and visual correlations of retinal layer thicknesses measured by different OCT segmentation techniques, on two spectral-domain OCT devices. Macular scans of 52 MS patients and 30 healthy controls from Spectralis OCT and Cirrus HD-OCT were segmented using fully manual (Spectralis), computer-aided manual (Spectralis and Cirrus), and fully automated (Cirrus) segmentation techniques. Letter acuity was recorded. Bland-Altman analyses revealed low mean differences across OCT segmentation techniques on both devices for ganglion cell + inner plexiform layers (GCIP; 0.76-2.43 μm), inner nuclear + outer plexiform layers (INL + OPL; 0.36-1.04 μm), and outer nuclear layers including photoreceptor segment (ONL + PR; 1.29-3.52 μm) thicknesses. Limits of agreement for GCIP and ONL + PR thicknesses were narrow. Results of fully manual and computer-aided manual segmentation were comparable to those of fully automated segmentation. MS patients demonstrated macular RNFL, GCIP, and ONL + PR thinning compared to healthy controls across OCT segmentation techniques, irrespective of device (p < 0.03 for all). Low-contrast letter acuity in MS correlated significantly and more strongly with GCIP than peripapillary RNFL thicknesses, regardless of the segmentation method or device. GCIP and ONL + PR thicknesses, measured by different OCT devices and segmentation techniques, are reproducible and agree at the individual and cohort levels. GCIP thinning in MS correlates with visual dysfunction. Significant ONL + PR thinning, detectable across OCT segmentation techniques and devices, strongly supports ONL pathology in MS. Fully automated, fully manual and computer-assisted manual OCT segmentation techniques compare closely, highlighting the utility of accurate and time-efficient automated segmentation outcomes in MS clinical trials.
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ABSTRACT: Optical coherence tomography (OCT) is a biomedical imaging technique with high spatial-temporal resolution. With its minimally invasive approach OCT has been used extensively in ophthalmology, dermatology, and gastroenterology(1-3). Using a thinned-skull cortical window (TSCW), we employ spectral-domain OCT (SD-OCT) modality as a tool to image the cortex in vivo. Commonly, an opened-skull has been used for neuro-imaging as it provides more versatility, however, a TSCW approach is less invasive and is an effective mean for long term imaging in neuropathology studies. Here, we present a method of creating a TSCW in a mouse model for in vivo OCT imaging of the cerebral cortex.Journal of Visualized Experiments 01/2012; DOI:10.3791/50053
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ABSTRACT: Optical coherence tomography (OCT) is a non-invasive instrument, which can be used to estimate the thickness of the retinal nerve fibre layer (RNFL) and provides an indirect measurement of axonal destruction in multiple sclerosis (MS). The main aim of this study was to find out any correlations between P100 latency in visual evoked potential (VEP) and RNFL thickness. The patients with the definite history of optic neuritis regardless of the diagnosis of MS were included. The eyes with the history of blurred vision and increased VEP latency (> 115 milliseconds) were considered as cases and the eyes with normal latency were regarded as controls. RNFL thickness was compared between two groups of cases and controls. In addition, the correlation between VEP P100 latency and RNFL thickness in four quadrants of superior, nasal, inferior and temporal fields was estimated by spearman correlation coefficient. RNFL thickness between the patients with history of clinically isolated syndrome (CIS) was also compared to other two subgroups of RRMS and SPMS. There was significant negative correlation between VEP P100 latency and RNFL. In all four quadrants, with increasing VEP latency, RNFL thickness decreased. Furthermore, there was significant correlation between P100 latencies and mean RNFL thickness [Pearson correlation coefficient = -0.527, P < 0.001; RNFL (mean) = (-0.44 ± 0.087) × P100 + (153.6 ± 10.94)]. Comparing RNFL thickness between three groups of CIS, RRMS, and SPSM, no significant difference was detected in RNFL thickness (P > 0.05). Power analysis demonstrated that RNFL average had the highest area under curve. OCT does have good correlations with P100 latency, indicating retinal non-myelinated axonal involvement in early stages in addition to the myelinated axonal involvement. However, it cannot be used as the sole test in evaluating visual pathway in optic neuritis and complementary tests as VEPs are recommended.Iranian Journal of Neurology 03/2012; 11(1):12-5.
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ABSTRACT: 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. 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. 164 patients with MS and 60 healthy controls were assessed. Mean follow-up was 25·8 months (SD 9·1) for patients with MS and 22·4 months (11·4) 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 5·93 [range 2·44-8·91]) than those who did not have MMO at any time during the study (151 patients; 3·81 [0·13-9·47]; p=0·032), although expanded disability status scale (EDSS) scores were not significantly different (5·2 [1·0-6·5] for patients with MS and MMO vs 2·5 [0·0-8·0] for those without MMO; p=0·097). The eyes of patients with MS and MMO (12 eyes) versus those without MMO (302 eyes) had lower letter-acuity scores (100% contrast, p=0·017; 2·5% contrast, p=0·031; 1·25% contrast, p=0·014), and increased INL thicknesses (p=0·003) at baseline. Increased baseline INL thickness in patients with MS was associated with the development of contrast-enhancing lesions (p=0·007), new T2 lesions (p=0·015), EDSS progression (p=0·034), and relapses in patients with relapsing-remitting MS (p=0·008) during the study. MMO was not associated with disease activity during follow-up. 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. National Multiple Sclerosis Society, National Eye Institute, Braxton Debbie Angela Dillon and Skip Donor Advisor Fund.The Lancet Neurology 10/2012; 11(11):963-72. DOI:10.1016/S1474-4422(12)70213-2 · 21.82 Impact Factor