G. Kalaitzidis
Johns Hopkins University School of Medicine Division of Neuroimmunology and Neurological Infections, Department of NeurologyAuthor Of 3 Presentations
LB1217 - Macular pigment concentration and distribution in multiple sclerosis (ID 2084)
Abstract
Background
Oxidative stress is implicated in inflammation and neurodegeneration in multiple sclerosis (MS). Similar to the brain, the retina is susceptible to reactive oxygen species (ROS). Macular pigment (MP), consisting primarily of the carotenoids lutein (L) and zeaxanthin (Z) blocks deleterious blue light, and provides anti-oxidant protection. To date, there has been a paucity of study of MP in MS.
Objectives
To examine MP concentration and distribution in MS eyes relative to healthy control (HC) eyes using macular pigment optical density (MPOD) imaging.
Methods
In this cross-sectional study, 27 MS patients (47 eyes) and 19 HCs (37 eyes) underwent MPOD imaging on a Spectralis (Heidelberg) device. MP absorbs blue light, but allows the free passage of green light. MPOD imaging involves the subtraction of blue from green wavelength auto-fluorescence macular scans, providing the optical density (OD) of MP. Radii of interest for MPOD were 0°, 0.23°, 0.51°, 0.98° and 1.99° degrees of eccentricity from the fovea, as well as peak, and half-peak MPOD locations. Study participants completed dietary L & Z screening questionnaires. Mixed effects linear regression models were used in analyses.
Results
Mean MPOD at 0° was 0.52 density units (d.u.) (SD 0.14) in MS and 0.63 d.u. (SD 0.18) in HC eyes (difference: -0.10 d.u., CI: -0.18 - -0.01, p=0.027). The median MPOD peak location eccentricity was 0.08° (IQR: 0 - 0.12) in MS and 0.04° (IQR: 0 - 0.08) in HC eyes (difference: 0.10°, CI: 0.01 - 0.20, p=0.031). Mean MPOD at the peak location was -0.09 d.u. lower in MS eyes relative to HC eyes (CI: -0.18 - -0.01, p=0.04). In addition, the half-peak MPOD location, similar to the MPOD peak location, was situated further from the fovea in MS eyes relative to HC eyes (difference: 0.28°, CI: 0.10 - 0.47, p=0.002). Analyses adjusted for age, body mass index, sex, and L & Z dietary scores, showed similar differences for MPOD at 0° eccentricity, and at the peak MPOD location, between MS and HC eyes.
Conclusions
Our findings suggest MP concentrations are reduced in MS eyes, with peak and half-peak MPOD locations shifted further from the fovea than in HC eyes. Increases in ROS consuming antioxidant MPs, and/or dysfunction in proteins transferring carotenoids to the fovea, among other reasons, may help explain reductions in MPOD in MS eyes. Our preliminary finding warrant further study, in larger, prospective MS cohorts, including determination of their clinical relevance.
P0036 - Cerebral hypometabolism is a marker of disease severity in multiple sclerosis: a non-invasive imaging study using T2-Relaxation-Under-Spin-Tagging MRI (ID 1856)
Abstract
Background
Metabolic dysfunction at a cellular level is a crucial element of progressive neuronal dysfunction, and ultimately neurodegeneration in multiple sclerosis (MS). Changes in retinal superficial vascular plexus (SVP) density, which is known to be reduced in MS, may in part reflect metabolic demand in the neuronal layers of the retina, and could accordingly provide insight regarding concurrent metabolic alterations in the brain.
Objectives
To compare cerebral metabolism in people with MS (PwMS) to healthy controls (HCs) using T2-Relaxation-Under-Spin-Tagging (TRUST) and phase-contrast (PC) MRI, and assess whether cerebral hypometabolism is related to reduced SVP density measured using optical coherence tomography angiography (OCTA).
Methods
In this cross-sectional study, PwMS and HC underwent TRUST and PC MRI to derive the oxygen extraction fraction (OEF; a measure of the efficiency of cerebral tissue in extracting oxygen from circulating blood) and cerebral metabolic rate of oxygen consumption (CMRO2; a volume-adjusted measure of cerebral tissue metabolism). A subset of PwMS underwent OCTA, with quantification of retinal SVP density using a deep neural network based-algorithm. Statistical analyses were adjusted for age and intra-subject inter-eye correlations, where relevant.
Results
We included 49 PwMS and 80 HCs. Overall, OEF was lower, and CMRO2 trended towards being lower, in PwMS as compared to HCs (OEF: 35.9% [SD 5.1] vs. 40.9%, [SD 5.1], p=0.04; CMRO2: 156.3 umol/mL/min [SD 23.9] vs. 158.7 umol/mL/min [SD 19.9], p=0.08). Lower CMRO2 was associated with longer MS disease duration (p=0.02), higher expanded disability status scale score (p=0.01) and lower subcortical gray matter volume fraction (p=0.04). Additionally, lower CMRO2 was associated with higher age in PwMS (p=0.02), but not in HCs (p=0.19), in whom effective neurovascular coupling is expected to maintain a fairly constant rate with aging. Lower OEF correlated with lower retinal SVP density in PwMS (r=0.32, p=0.02).
Conclusions
Cerebral hypometabolism is evident in PwMS compared to HCs, and is associated with longer disease duration and greater disability. Furthermore, alterations in cerebral metabolism are mirrored by alterations in retinal SVP density, supporting the utility of these non-invasive imaging techniques to measure inter-linked pathobiological processes. The ability to detect metabolic dysfunction in-vivo in PwMS may help facilitate the identification of new therapeutic targets and outcome measures for clinical trials.
P0713 - Evidence of subclinical quantitative retinal layer abnormalities in aquaporin-4-IgG seropositive NMOSD (ID 862)
Abstract
Background
Aquaporin-4-IgG (AQP4-IgG) seropositive Neuromyelitis Optica Spectrum Disorder (NMOSD) typically presents with discrete attacks of optic neuritis (ON) and transverse myelitis, and insidious subclinical disease activity is considered a rare occurrence. Prior optical coherence tomography (OCT) studies have suggested that subclinical retinal abnormalities, including lower foveal thickness and altered foveal morphology, may be present in AQP4-IgG+ NMOSD in the absence of a clinical history of ON; however, existing studies were relatively small.
Objectives
To compare retinal layer thicknesses at the fovea and surrounding macula between AQP4-IgG+ NMOSD eyes without a history of ON (AQP4-nonON) and healthy controls (HC).
Methods
In this single-center cross-sectional study, 83 AQP4-nonON and 153 HC eyes were studied with spectral-domain OCT. Statistical analyses were performed with generalized estimating equations (GEE) and were adjusted for age, sex and race.
Results
Total foveal thickness did not differ between AQP4-nonON and HC eyes (-3.55±3.79μm, p=0.35). AQP4-nonON eyes exhibited lower outer nuclear layer (ONL) and inner photoreceptor segment (IS) thickness at the fovea (ONL: -4.01±2.03μm, p=0.049; IS: -0.32±0.14μm, p=0.029) and surrounding macula (ONL: -1.98±0.95μm, p=0.037; IS: -0.16±0.07μm, p=0.023), compared to HC. Macular retinal nerve fiber layer (mRNFL: -1.34±0.51μm, p=0.009) and ganglion cell + inner plexiform layer (GCIPL: -2.44±0.93μm, p=0.009) thicknesses were also lower in AQP4-nonON compared to HC eyes. The magnitude of the estimated differences was similar in sensitivity analyses restricted to AQP4-IgG+ patients who had never experienced ON in either eye (n=33 patients; mRNFL: -1.33±0.60μm, p=0.026; GCIPL: -2.59±1.12μm, p=0.021; macular ONL: -2.01±1.04μm, p=0.052; macular IS: -0.16±0.08μm, p=0.031; foveal ONL: -3.78±2.28μm, p=0.10; foveal IS: -0.28±0.19μm, p=0.14).
Conclusions
AQP4-nonON eyes exhibited evidence of subclinical retinal ganglion cell neuronal and axonal loss, as well as structural evidence of photoreceptor layer involvement. These results remained largely unaltered in analyses limited to patients who had never experienced ON, suggesting that they are likely related to processes that are independent of clinically overt ON attacks. These findings support that subclinical anterior visual pathway involvement may occur in AQP4-IgG+ NMOSD, and may relate to a primary retinal process or subclinical optic neuropathy.
Presenter Of 1 Presentation
LB1217 - Macular pigment concentration and distribution in multiple sclerosis (ID 2084)
Abstract
Background
Oxidative stress is implicated in inflammation and neurodegeneration in multiple sclerosis (MS). Similar to the brain, the retina is susceptible to reactive oxygen species (ROS). Macular pigment (MP), consisting primarily of the carotenoids lutein (L) and zeaxanthin (Z) blocks deleterious blue light, and provides anti-oxidant protection. To date, there has been a paucity of study of MP in MS.
Objectives
To examine MP concentration and distribution in MS eyes relative to healthy control (HC) eyes using macular pigment optical density (MPOD) imaging.
Methods
In this cross-sectional study, 27 MS patients (47 eyes) and 19 HCs (37 eyes) underwent MPOD imaging on a Spectralis (Heidelberg) device. MP absorbs blue light, but allows the free passage of green light. MPOD imaging involves the subtraction of blue from green wavelength auto-fluorescence macular scans, providing the optical density (OD) of MP. Radii of interest for MPOD were 0°, 0.23°, 0.51°, 0.98° and 1.99° degrees of eccentricity from the fovea, as well as peak, and half-peak MPOD locations. Study participants completed dietary L & Z screening questionnaires. Mixed effects linear regression models were used in analyses.
Results
Mean MPOD at 0° was 0.52 density units (d.u.) (SD 0.14) in MS and 0.63 d.u. (SD 0.18) in HC eyes (difference: -0.10 d.u., CI: -0.18 - -0.01, p=0.027). The median MPOD peak location eccentricity was 0.08° (IQR: 0 - 0.12) in MS and 0.04° (IQR: 0 - 0.08) in HC eyes (difference: 0.10°, CI: 0.01 - 0.20, p=0.031). Mean MPOD at the peak location was -0.09 d.u. lower in MS eyes relative to HC eyes (CI: -0.18 - -0.01, p=0.04). In addition, the half-peak MPOD location, similar to the MPOD peak location, was situated further from the fovea in MS eyes relative to HC eyes (difference: 0.28°, CI: 0.10 - 0.47, p=0.002). Analyses adjusted for age, body mass index, sex, and L & Z dietary scores, showed similar differences for MPOD at 0° eccentricity, and at the peak MPOD location, between MS and HC eyes.
Conclusions
Our findings suggest MP concentrations are reduced in MS eyes, with peak and half-peak MPOD locations shifted further from the fovea than in HC eyes. Increases in ROS consuming antioxidant MPs, and/or dysfunction in proteins transferring carotenoids to the fovea, among other reasons, may help explain reductions in MPOD in MS eyes. Our preliminary finding warrant further study, in larger, prospective MS cohorts, including determination of their clinical relevance.