Contributions
Abstract: P835
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - OCT
Introduction: Radiologically isolated syndrome (RIS) is a term introduced to describe asymptomatic individuals with incidentally identified brain lesions suggestive of multiple sclerosis (MS). RIS often represents a pre-symptomatic stage of MS, with approximately one-third of RIS subjects developing a clinical demyelinating event within 5-years of initial imaging. Various risk factors for conversion to MS have been proposed including younger age, male sex, presence of spinal cord (SC) lesions and cerebrospinal fluid (CSF) abnormalities. The anterior visual pathway is a frequent site of subclinical involvement in MS, however the role of retinal imaging with optical coherence tomography (OCT) in the assessment of RIS remains largely unexplored.
Objectives: To assess retinal layer thicknesses in RIS subjects and examine their associations with clinical features suggestive of increased risk for conversion to MS.
Methods: Thirty RIS subjects, fulfilling 2009 Okuda diagnostic criteria, and 60 age- and sex-matched healthy controls (HC) underwent retinal imaging with high-definition spectral-domain OCT. Retinal layer thicknesses were derived automatically, utilizing a validated segmentation algorithm. Statistical analyses were performed with generalized estimating equations (GEE), accounting for within-subject inter-eye correlation.
Results: Overall, retinal layer thicknesses did not differ between the RIS and HC cohorts. However, RIS subjects with presence of SC lesions (n=12) had reduced ganglion cell + inner plexiform layer (GCIP) thickness as compared to HC (-4.41µm, p=0.007) and RIS subjects without SC lesions (-3.54µm, p=0.04). Other proposed high-risk features, including younger age, male sex, abnormal CSF (oligoclonal bands and/or elevated IgG index), and presence of gadolinium-enhancing lesions, were not associated with differences in retinal layer thicknesses.
Conclusions: In this cross-sectional study, the presence of SC lesions was associated with reduced GCIP thickness in RIS. Our findings suggest that retinal neuro-axonal loss may be present in RIS, especially in subjects with higher risk for development of clinical demyelinating events. Longitudinal studies of larger cohorts of RIS subjects are necessary to confirm these findings and to evaluate the potential prognostic value of decreased GCIP thickness for conversion to MS.
Disclosure: Funding: This study was funded by the NIH (5R01NS082347 to P.C.) and National MS Society (FP-1607-24999 to E.S.; RG-1606-08768 to S.S).
Disclosures: Angeliki Filippatou has nothing to disclose.
Thomas Shoemaker is funded by a Sylvia Lawry physician fellowship award from the National Multiple Sclerosis Society (NMSS) and has received consulting honorariums from Genentech.
Megan Esch has received postdoctoral fellowship funding from the National Multiple Sclerosis Society (NMSS).
Madiha Qutab has nothing to disclose.
Natalia Gonzalez-Caldito has nothing to disclose.
Jerry Prince is a founder of Sonovex, Inc. and serves on its Board of Directors.
Ellen M. Mowry has grants from Biogen and Genzyme, is site PI for studies sponsored by Biogen and Sun Pharma, has received free medication for a clinical trial from Teva and receives royalties for editorial duties from UpToDate.
Peter A. Calabresi has received personal honorariums for consulting from Disarm Therapeutics. He is PI on research grants to Johns Hopkins from MedImmune, Annexon, and Genzyme.
Shiv Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation, EMD Serono & Novartis. He is the PI of investigator-initiated studies funded by Genentech Corporation and Biogen Idec, and received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He is also the site investigator of a trial sponsored by MedDay Pharmaceuticals.
Elias S. Sotirchos is funded by a Sylvia Lawry physician fellowship award from the National Multiple Sclerosis Society (NMSS).
Abstract: P835
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - OCT
Introduction: Radiologically isolated syndrome (RIS) is a term introduced to describe asymptomatic individuals with incidentally identified brain lesions suggestive of multiple sclerosis (MS). RIS often represents a pre-symptomatic stage of MS, with approximately one-third of RIS subjects developing a clinical demyelinating event within 5-years of initial imaging. Various risk factors for conversion to MS have been proposed including younger age, male sex, presence of spinal cord (SC) lesions and cerebrospinal fluid (CSF) abnormalities. The anterior visual pathway is a frequent site of subclinical involvement in MS, however the role of retinal imaging with optical coherence tomography (OCT) in the assessment of RIS remains largely unexplored.
Objectives: To assess retinal layer thicknesses in RIS subjects and examine their associations with clinical features suggestive of increased risk for conversion to MS.
Methods: Thirty RIS subjects, fulfilling 2009 Okuda diagnostic criteria, and 60 age- and sex-matched healthy controls (HC) underwent retinal imaging with high-definition spectral-domain OCT. Retinal layer thicknesses were derived automatically, utilizing a validated segmentation algorithm. Statistical analyses were performed with generalized estimating equations (GEE), accounting for within-subject inter-eye correlation.
Results: Overall, retinal layer thicknesses did not differ between the RIS and HC cohorts. However, RIS subjects with presence of SC lesions (n=12) had reduced ganglion cell + inner plexiform layer (GCIP) thickness as compared to HC (-4.41µm, p=0.007) and RIS subjects without SC lesions (-3.54µm, p=0.04). Other proposed high-risk features, including younger age, male sex, abnormal CSF (oligoclonal bands and/or elevated IgG index), and presence of gadolinium-enhancing lesions, were not associated with differences in retinal layer thicknesses.
Conclusions: In this cross-sectional study, the presence of SC lesions was associated with reduced GCIP thickness in RIS. Our findings suggest that retinal neuro-axonal loss may be present in RIS, especially in subjects with higher risk for development of clinical demyelinating events. Longitudinal studies of larger cohorts of RIS subjects are necessary to confirm these findings and to evaluate the potential prognostic value of decreased GCIP thickness for conversion to MS.
Disclosure: Funding: This study was funded by the NIH (5R01NS082347 to P.C.) and National MS Society (FP-1607-24999 to E.S.; RG-1606-08768 to S.S).
Disclosures: Angeliki Filippatou has nothing to disclose.
Thomas Shoemaker is funded by a Sylvia Lawry physician fellowship award from the National Multiple Sclerosis Society (NMSS) and has received consulting honorariums from Genentech.
Megan Esch has received postdoctoral fellowship funding from the National Multiple Sclerosis Society (NMSS).
Madiha Qutab has nothing to disclose.
Natalia Gonzalez-Caldito has nothing to disclose.
Jerry Prince is a founder of Sonovex, Inc. and serves on its Board of Directors.
Ellen M. Mowry has grants from Biogen and Genzyme, is site PI for studies sponsored by Biogen and Sun Pharma, has received free medication for a clinical trial from Teva and receives royalties for editorial duties from UpToDate.
Peter A. Calabresi has received personal honorariums for consulting from Disarm Therapeutics. He is PI on research grants to Johns Hopkins from MedImmune, Annexon, and Genzyme.
Shiv Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology and has served on scientific advisory boards for Biogen-Idec, Genzyme, Genentech Corporation, EMD Serono & Novartis. He is the PI of investigator-initiated studies funded by Genentech Corporation and Biogen Idec, and received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. He is also the site investigator of a trial sponsored by MedDay Pharmaceuticals.
Elias S. Sotirchos is funded by a Sylvia Lawry physician fellowship award from the National Multiple Sclerosis Society (NMSS).