Omar Al-Louzi

Optical Coherence Tomography Reflects Brain Atrophy in Multiple Sclerosis: A Four-Year Study

The aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS).

Automatic segmentation of microcystic macular edema in OCT

Microcystic macular edema (MME) manifests as small, hyporeflective cystic areas within the retina. For reasons that are still largely unknown, a small proportion of patients with multiple sclerosis (MS) develop MME-predominantly in the inner nuclear layer. These cystoid spaces, denoted pseudocysts, can be imaged using optical coherence tomography (OCT) where they appear as small, discrete, low intensity areas with high contrast to the surrounding tissue. The ability to automatically segment these pseudocysts would enable a more detailed study of MME than has been previously possible. Although larger pseudocysts often appear quite clearly in the OCT images, the multi-frame averaging performed by the Spectralis scanner adds a significant amount of variability to the appearance of smaller pseudocysts. Thus, simple segmentation methods only incorporating intensity information do not perform well. In this work, we propose to use a random forest classifier to classify the MME pixels. An assortment of both intensity and spatial features are used to aid the classification. Using a cross-validation evaluation strategy with manual delineation as ground truth, our method is able to correctly identify 79% of pseudocysts with a precision of 85%. Finally, we constructed a classifier from the output of our algorithm to distinguish clinically identified MME from non-MME subjects yielding an accuracy of 92%.

Outer retinal changes following acute optic neuritis

Background: Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined. Objectives: The objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON. Methods: Thirty-three AON patients underwent serial optical coherence tomography (OCT) and visual function testing (mean follow-up: 25 months). Longitudinal changes in retinal layer thickness were analyzed using mixed-effects linear regression. Results: Four months following AON, the mean decrease in GCIP thickness relative to baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in average ONL+PS thickness was observed (p < 0.001). The percentage decrease in GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = −0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12 months, was no longer significantly different from baseline (mean change: 0.5%; p = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed. Conclusions: Following AON, dynamic changes occur in the deep retinal layers, which are proportional to GCIP thinning. These novel findings help further our understanding of the biological and/or anatomical sequelae resulting from AON.

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis A retrospective study

Objective: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT). Methods: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression. Results: The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-β-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 μm/y (p < 0.001) and 0.14 μm/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 μm/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001). Conclusions: Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

Retinal damage and vision loss in African American multiple sclerosis patients

To determine whether African American (AA) multiple sclerosis (MS) patients exhibit more retinal damage and visual impairment compared to Caucasian American (CA) MS patients.

Optical coherence tomography reflects brain atrophy in MS: A four year study

The aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS).

Segmentation of microcystic macular edema in Cirrus OCT scans with an exploratory longitudinal study.

Microcystic macular edema (MME) is a term used to describe pseudocystic spaces in the inner nuclear layer (INL) of the human retina. It has been noted in multiple sclerosis (MS) as well as a variety of other diseases. The processes that lead to MME formation and their change over time have yet to be explained sufficiently. The low rate at which MME occurs within such diverse patient groups makes the identification and consistent quantification of this pathology important for developing patient-specific prognoses. MME is observed in optical coherence tomography (OCT) scans of the retina as changes in light reflectivity in a pattern suggestive of fluid accumulations called pseudocysts. Pseudocysts can be readily identified in higher signal-to-noise ratio (SNR) images, however pseudocysts can be indistinguishable from noise in lower SNR scans. In this work, we expand upon our earlier MME identification methods on Spectralis OCT scans to handle lower quality Cirrus OCT scans. Our approach uses a random forest classifier, trained on manual segmentation of ten subjects, to automatically detect MME. The algorithm has a true positive rate for MME identification of 0.95 and a Dice score of 0.79. We include a preliminary longitudinal study of three patients over four to five years to explore the longitudinal changes of MME. The patients with relapsing-remitting MS and neuromyelitis optica appear to have dynamic pseudocyst volumes, while the MME volume appears stable in the one patient with primary progressive MS.

Biopsy-negative PET-positive giant-cell arteritis

Giant-cell arteritis (GCA) is the most common systemic vasculitis of the elderly, with a lifetime risk of 1% in women and 0.5% in men.1 Failure to identify the early signs of GCA can result in treatment delay, predisposing patients to a number of potentially disabling and life-threatening complications, including anterior ischemic optic neuropathy, stroke, aortic aneurysm, and dissection.2 We present a case of biopsy-negative GCA in which PET-CT revealed evidence of extensive large-vessel vasculitis.

Longitudinal graph-based segmentation of macular OCT using fundus alignment

Segmentation of retinal layers in optical coherence tomography (OCT) has become an important diagnostic tool for a variety of ocular and neurological diseases. Currently all OCT segmentation algorithms analyze data independently, ignoring previous scans, which can lead to spurious measurements due to algorithm variability and failure to identify subtle changes in retinal layers. In this paper, we present a graph-based segmentation framework to provide consistent longitudinal segmentation results. Regularization over time is accomplished by adding weighted edges between corresponding voxels at each visit. We align the scans to a common subject space before connecting the graphs by registering the data using both the retinal vasculature and retinal thickness generated from a low resolution segmentation. This initial segmentation also allows the higher dimensional temporal problem to be solved more efficiently by reducing the graph size. Validation is performed on longitudinal data from 24 subjects, where we explore the variability between our longitudinal graph method and a cross-sectional graph approach. Our results demonstrate that the longitudinal component improves segmentation consistency, particularly in areas where the boundaries are difficult to visualize due to poor scan quality.

Voxel Based Morphometry in Optical Coherence Tomography: Validation & Core Findings

Optical coherence tomography (OCT) of the human retina is now becoming established as an important modality for the detection and tracking of various ocular diseases. Voxel based morphometry (VBM) is a long standing neuroimaging analysis technique that allows for the exploration of the regional differences in the brain. There has been limited work done in developing registration based methods for OCT, which has hampered the advancement of VBM analyses in OCT based population studies. Following on from our recent development of an OCT registration method, we explore the potential benefits of VBM analysis in cohorts of healthy controls (HCs) and multiple sclerosis (MS) patients. Specifically, we validate the stability of VBM analysis in two pools of HCs showing no significant difference between the two populations. Additionally, we also present a retrospective study of age and sex matched HCs and relapsing remitting MS patients, demonstrating results consistent with the reported literature while providing insight into the retinal changes associated with this MS subtype.