S. Saidha
Johns Hopkins University School of Medicine NeurologyDr. Shiv Saidha specializes in the diagnosis, management, and treatment of multiple sclerosis (MS), as well as other neuroimmunological disorders of the central nervous system, including those afflicting the brain, spinal cord, and optic nerves.
Dr. Saidha received his medical degree, as well as his postgraduate Doctor of Medicine, from the National University of Ireland, Galway (NUIG), Ireland. He completed residency training in general internal medicine at Galway University Hospitals, Ireland. Subsequent to this he completed residency training in neurology at Galway, Cork, and Beaumont (located in Dublin) University Hospitals, Ireland. He then completed a further three years of specialized fellowship training in neuroimmunology & neuroinfectious diseases at Johns Hopkins University School of Medicine, Baltimore, Maryland. He is currently an Associate Professor of Neurology at Johns Hopkins University School of Medicine.
Dr. Saidha’s research interests to date have predominantly focused on the non-invasive interrogation of retinal structures using optical coherence tomography (OCT) and OCT angiography (OCTA) in multiple sclerosis (MS), in order to identify and investigate novel outcome strategies for assessing and monitoring neuroprotection and neurorestoration in MS, as well as to further our understanding of the pathobiology of MS, including how retinal pathology in MS may be related to more global central nervous system disturbances. He has been at the fore of discovering and demonstrating that inner and outer retinal layer pathology occur within the unmyelinated retina in MS (both quantitatively and qualitatively). He is committed to continuing to delineate and ascertain the mechanisms involved in the development of these findings, the clinical relevance of these changes (both locally in the retina, as well as more globally), and determine if this information may be used to guide the development of new, and potentially unique/novel effective MS therapies. His work to date has been primarily structurally focused (both within the retina using OCT and OCTA, as well as more globally within the central nervous system through the assessment of brain substructure volumes, diffusion tensor imaging & magnetization transfer ratio metrics within specific pathways in MS). He also has expertise in the functional assessment of the anterior visual pathway in MS through the application of multifocal electroretinography, pupillometry, and retinal function imaging techniques, amongst others, as well as of global and regional brain metabolism. He has published first author papers in Lancet, Lancet Neurology, Annals of Neurology, Brain, Neurology, JAMA neurology, and Multiple Sclerosis Journal amongst others.
Author Of 3 Presentations
PS15.01 - Disease Modifying Therapies and Retinal Atrophy
Abstract
Abstract
Background: Although the retina represents an unmyelinated central nervous system structure, almost all aspects of multiple sclerosis (MS) related pathology (except demyelination) may be observed in the retina. Moreover, the retina represents an opportune site to study neurodegeneration, since optic nerve affliction is virtually ubiquitous in MS. Optical coherence tomography (OCT) derived measures of retinal neurodegeneration have been shown to strongly reflect the global MS disease process, and may be ideal outcomes for assessing neuroprotection, and/or neurorestoration. Accordingly, OCT outcomes are being increasingly incorporated as primary or secondary outcomes in MS clinical trials.
Goals: To describe the effects of MS disease modifying therapies (DMTs) on OCT derived assessment of retinal atophy.
Methods: Discussion of the emerging role of OCT for monitoring MS, as well as the effects of high-potency (including natalizumab and rituximab), and low-potency (including interferons and glatiramer acetate) MS DMTs on rates of OCT derived measures of composite ganglion cell+inner plexiform layer (GCIPL), inner nuclear layer (INL), and outer nuclear layer (ONL) atrophy. Differences in the effects of DMTs on retinal atrophy according to MS subtype will be reviewed. Finally, the role of the international MS visual system (IMSVISUAL) consortium in large scale MS studies will be discussed.
Results: Congruent with the effects of DMTs on rates of brain atrophy, high potency DMTs are associated with slower rates of retinal atophy in relapsing remitting MS (RRMS), as compared to low potency DMTs. Therepeutic optimization of the effect of rituximab on retinal atrophy in MS may take up to 6-12 months in RRMS. INL and ONL atrophy appear to be relatively speficic to progressive MS (PMS; both primary and secondary PMS), as compared to RRMS, and in PMS, INL and ONL atrophy are accelerated, independent of age. Rates of GCIPL, INL and ONL atrophy do not differ significantly between untreated PMS patients, and PMS patients treated with either low or high potency DMTs. Large scale MS studies utilizing visual system outcomes are facilitated by IMSVISUAL.
Conclusions: Rates of GCIPL atrophy are slower in RRMS patients treated with high potency, as compared to low potency DMTs. INL and ONL atrophy measures appear to be relatively specific to PMS, and may be novel outcomes for assessing neuroprotection and/or neurorestoration in PMS. Current, conventional, and primarily anti-inflammatory DMTs (whether high or low potency) have not been shown to significantly reduce retinal atophy in PMS, unlike RRMS.
PS15.04 - The presence of epiretinal membranes in multiple sclerosis may be associated with increased disability
Abstract
Background
Neuroglial cells are implicated in the pathobiology of Multiple sclerosis (MS). Müller glia, specialized radial glial cells of the retina responsible for helping maintain retinal neuronal integrity, are postulated to be activated in MS. Müller glia activation is also implicated in epiretinal membrane (ERM) formation, an aberrant healing response to retinal damage.
Objectives
To examine ERM prevalence in MS, and differences in expanded disability status scale (EDSS) and optical coherence tomography (OCT) measured retinal layer thicknesses, between MS patients with (ERM-MS) and without ERMs (non-ERM-MS).
Methods
In this cross-sectional study, 1463 MS patients (2926 eyes) underwent Cirrus spectral-domain OCT (with automated macular layer segmentation). All scans underwent qualitative and quantitative quality control (QC), and ERM presence was recorded. Excluding patients with optic neuritis history, ERM-MS (n=48) were matched 1:1 to non-ERM-MS based on age, body mass index (BMI) and sex. Fellow eye layer thicknesses of ERM-MS were compared to the average binocular layer thicknesses of non-ERM-MS patients, to investigate the possibility of a phenotype effect. Mixed effects linear regression models were used in analyses.
Results
ERM prevalence in this MS cohort was 4.9%. Post-matching mean age and BMI were respectively 60.7 years (SD 6.3) and 28.2 kg/m2 (SD 9.6) in ERM-MS, and 60.4 years (SD 5.7) and 27.5 kg/m2 (SD 8.9) in non-ERM-MS (p=0.7 for both). Both groups had 77.1% females. Median EDSS was 4 (IQR 2.5-6.5) in ERM-MS and 3 (IQR 1.5-6) in non-ERM-MS (difference: 1.1, CI: 0.2 – 1.9, p=0.021). Mean ganglion cell-inner plexiform layer (GCIPL) thickness was 67.1 um (SD 6.5) in ERM-MS and 70.2 um (SD 6.2) in non-ERM-MS (difference: -3.1, CI: -6.3 – -0.1, p=0.049). Moreover, mean retinal pigment epithelium (RPE) thickness was 31.6 um (SD 1.3) in ERM-MS and 32.4 um (SD 0.9) in non-ERM-MS (difference: -0.7 um, CI: -1.3 - -0.1, p=0.017).
Conclusions
Our findings suggest ERM-MS patients phenotypically have higher EDSS scores, and lower GCIPL and RPE thicknesses, as compared to non-ERM-MS patients. Blood-retinal barrier disruption due to retinal inflammation, among other reasons, may activate Müller glia in MS. This may help explain our finding that ERM presence in MS may be associated with disability. Moreover, RPE cells may be recruited in the ERM formation process, similarly explaining our finding of reduced RPE thickness among ERM-MS patients.
YI02.01 - Optic Neuritis-Independent Retinal Atrophy In Neuromyelitis Optica Spectrum Disorders
Abstract
Background
Prior studies have suggested that retinal neuro-axonal loss may occur in aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) in the absence of optic neuritis (ON), but data are conflicting.
Objectives
To examine whether patients with AQP4-IgG seropositive NMOSD exhibit progressive retinal neuro-axonal loss, independently of optic neuritis (ON) attacks.
Methods
In this single-center, longitudinal study, 32 AQP4-IgG+ NMOSD patients and 48 healthy controls (HC) were followed with serial spectral-domain optical coherence tomography (OCT). NMOSD patients with ON less than 6 months prior to baseline were excluded, while data from patients with ON during follow-up were censored at the last visit prior to ON. Rates of peri-papillary retinal nerve fiber layer (pRNFL) and macular ganglion cell+inner plexiform layer (GCIPL) thinning were compared between groups utilizing mixed-effects linear regression models adjusted for age, race and sex.
Results
Median follow-up duration was 4.3 years (IQR: 2.6 -7.5) for the NMOSD cohort and 4.0 years (IQR: 1.8 – 7.5) for the HC. We observed faster pRNFL (β=-0.25µm/year, 95%CI: -0.45 to -0.05, p=0.014) and GCIPL thinning (β=-0.09µm/year, 95%CI: -0.17 to 0, p=0.05) in NMOSD compared to HC eyes. This difference appeared to be driven by faster pRNFL and GCIPL thinning in NMOSD eyes without a history of ON compared to HC (GCIPL: β=-0.15µm/year, 95%CI: -0.25 to -0.05, p=0.005; pRNFL: β=-0.43µm/year, 95%CI: -0.67 to -0.19, p<0.001), while rates of pRNFL (β=-0.07µm/year , 95%CI: -0.31 to 0.16, p=0.53) and GCIPL (β=-0.01µm/year, 95%CI: -0.11 to 0.10, p=0.90) thinning did not differ between NMOSD-ON and HC eyes .
Furthermore, we explored the effects of non-ON relapses during follow-up on rates of pRNFL and GCIPL thinning. Ten patients had relapses during follow-up (9 transverse myelitis, 1 area postrema syndrome). Patients with relapses did not exhibit differences in rates of GCIPL (β=0.05µm/year, 95%CI:-0.10 to 0.20, p=0.51) or pRNFL thinning (pRNFL: β=0.08µm/year, 95%CI: -0.28 to 0.43, p=0.67), compared to those who were clinically stable.
Conclusions
In this longitudinal study, we observed progressive pRNFL and GCIPL atrophy in AQP4-IgG+ NMOSD eyes unaffected by ON. These results support that subclinical involvement of the anterior visual pathway may occur in AQP4-IgG+ NMOSD.
Presenter Of 1 Presentation
PS15.01 - Disease Modifying Therapies and Retinal Atrophy
Abstract
Abstract
Background: Although the retina represents an unmyelinated central nervous system structure, almost all aspects of multiple sclerosis (MS) related pathology (except demyelination) may be observed in the retina. Moreover, the retina represents an opportune site to study neurodegeneration, since optic nerve affliction is virtually ubiquitous in MS. Optical coherence tomography (OCT) derived measures of retinal neurodegeneration have been shown to strongly reflect the global MS disease process, and may be ideal outcomes for assessing neuroprotection, and/or neurorestoration. Accordingly, OCT outcomes are being increasingly incorporated as primary or secondary outcomes in MS clinical trials.
Goals: To describe the effects of MS disease modifying therapies (DMTs) on OCT derived assessment of retinal atophy.
Methods: Discussion of the emerging role of OCT for monitoring MS, as well as the effects of high-potency (including natalizumab and rituximab), and low-potency (including interferons and glatiramer acetate) MS DMTs on rates of OCT derived measures of composite ganglion cell+inner plexiform layer (GCIPL), inner nuclear layer (INL), and outer nuclear layer (ONL) atrophy. Differences in the effects of DMTs on retinal atrophy according to MS subtype will be reviewed. Finally, the role of the international MS visual system (IMSVISUAL) consortium in large scale MS studies will be discussed.
Results: Congruent with the effects of DMTs on rates of brain atrophy, high potency DMTs are associated with slower rates of retinal atophy in relapsing remitting MS (RRMS), as compared to low potency DMTs. Therepeutic optimization of the effect of rituximab on retinal atrophy in MS may take up to 6-12 months in RRMS. INL and ONL atrophy appear to be relatively speficic to progressive MS (PMS; both primary and secondary PMS), as compared to RRMS, and in PMS, INL and ONL atrophy are accelerated, independent of age. Rates of GCIPL, INL and ONL atrophy do not differ significantly between untreated PMS patients, and PMS patients treated with either low or high potency DMTs. Large scale MS studies utilizing visual system outcomes are facilitated by IMSVISUAL.
Conclusions: Rates of GCIPL atrophy are slower in RRMS patients treated with high potency, as compared to low potency DMTs. INL and ONL atrophy measures appear to be relatively specific to PMS, and may be novel outcomes for assessing neuroprotection and/or neurorestoration in PMS. Current, conventional, and primarily anti-inflammatory DMTs (whether high or low potency) have not been shown to significantly reduce retinal atophy in PMS, unlike RRMS.
Invited Speaker Of 1 Presentation
PS15.01 - Disease Modifying Therapies and Retinal Atrophy
Abstract
Abstract
Background: Although the retina represents an unmyelinated central nervous system structure, almost all aspects of multiple sclerosis (MS) related pathology (except demyelination) may be observed in the retina. Moreover, the retina represents an opportune site to study neurodegeneration, since optic nerve affliction is virtually ubiquitous in MS. Optical coherence tomography (OCT) derived measures of retinal neurodegeneration have been shown to strongly reflect the global MS disease process, and may be ideal outcomes for assessing neuroprotection, and/or neurorestoration. Accordingly, OCT outcomes are being increasingly incorporated as primary or secondary outcomes in MS clinical trials.
Goals: To describe the effects of MS disease modifying therapies (DMTs) on OCT derived assessment of retinal atophy.
Methods: Discussion of the emerging role of OCT for monitoring MS, as well as the effects of high-potency (including natalizumab and rituximab), and low-potency (including interferons and glatiramer acetate) MS DMTs on rates of OCT derived measures of composite ganglion cell+inner plexiform layer (GCIPL), inner nuclear layer (INL), and outer nuclear layer (ONL) atrophy. Differences in the effects of DMTs on retinal atrophy according to MS subtype will be reviewed. Finally, the role of the international MS visual system (IMSVISUAL) consortium in large scale MS studies will be discussed.
Results: Congruent with the effects of DMTs on rates of brain atrophy, high potency DMTs are associated with slower rates of retinal atophy in relapsing remitting MS (RRMS), as compared to low potency DMTs. Therepeutic optimization of the effect of rituximab on retinal atrophy in MS may take up to 6-12 months in RRMS. INL and ONL atrophy appear to be relatively speficic to progressive MS (PMS; both primary and secondary PMS), as compared to RRMS, and in PMS, INL and ONL atrophy are accelerated, independent of age. Rates of GCIPL, INL and ONL atrophy do not differ significantly between untreated PMS patients, and PMS patients treated with either low or high potency DMTs. Large scale MS studies utilizing visual system outcomes are facilitated by IMSVISUAL.
Conclusions: Rates of GCIPL atrophy are slower in RRMS patients treated with high potency, as compared to low potency DMTs. INL and ONL atrophy measures appear to be relatively specific to PMS, and may be novel outcomes for assessing neuroprotection and/or neurorestoration in PMS. Current, conventional, and primarily anti-inflammatory DMTs (whether high or low potency) have not been shown to significantly reduce retinal atophy in PMS, unlike RRMS.