Contributions
Abstract: P1037
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Introduction: We currently lack reliable, rapid, and sensitive methods for prognosis and disease monitoring in multiple sclerosis (MS). Fixational eye movements are one of the finest motor movements the human body is capable of making and provide a non-invasive window into motor function at the micron-level. Objectively measuring MS motor deficits allows for highly quantitative and reliable functional assessments.
Methods: We recruited 111 people with MS (diagnosed by 2010 International Panel criteria) from the UCSF MS Center as test and validation cohorts of 51 and 60 subjects and 100 controls as test/validation cohorts of 50 subjects each. Retinal eye-tracking was performed using a custom built, tabletop device - the tracking scanning laser ophthalmoscope (TSLO). Three, 10-second recordings of fixation per eye were acquired using 840nm light to raster scan the retina over a 5 x 5° field of view. Patients were instructed to fixate on the upper right-hand corner of the raster. Strip-based, offline analysis was used to extract eye motion at 480 Hz. Microsaccadic metrics of velocity, amplitude, and quantity were compared between MS patients and controls.
Results: For MS cohort 1 (C1) mean EDSS was 3.45 (range 1-8), with MS cohort 2 (C2) having a mean EDSS of 3.28 (range 0-7). Patients diagnosed with MS had a higher average (avg) number of microsaccades (micsacs) (14.29 +/- 8.20) vs. controls (11.92 +/- 6.11); with a statistically significant increase of 2.37 micsacs p = 0.020. Additionally, MS patients had a higher avg micsac peak velocity and standard deviation (53.15°/s +/- 49.16°/s) compared to controls (36.91°/s +/- 19.10°/s); with a statistically significant increase of 16.24°/s, p=0.011. In a multivariable linear regression the avg number of micsacs increased with increasing EDSS score (C1: p< 0.001, C2 p=0.045).
Conclusions: MS patients had a greater avg number and velocity of micsacs compared to controls as recorded by the TSLO during 10s of fixation. The number of micsacs also correlated with disability even in patients with a low average level of disability. TSLO fixation abnormalities are detectable early in the course of disease and show promise as a highly sensitive, quantitative biomarker to predict disease progression and provide prognosis for MS patients. It also has potential to serve as an outcome measure for early phase clinical trials assessing motor function in MS. Longitudinal studies are needed to further evaluate its potential.
Disclosure: Christy K. Sheehy: Commercial and financial interests in C. Light Technologies and holds patents with this company and with UC Berkeley. Ethan S. Bensinger: Paid consultant for C. Light Technologies. Andrew Romeo: nothing to disclose. Lakshmisahithi Rani: nothing to disclose. Bingyan Shi: nothing to disclose. Jeffrey M. Gelfand: Research support from Genentech and MedDay. Consulting for Biogen. Personal compensation for medical legal consulting. Scott B. Stevenson: Scientific advisor for C. Light Technologies (Nonremunerative). Ari J. Green: Nonremunerative commercial relationships with Bionure, Biogen, and Medimmune. Consultant for Mylan Pharmaceuticals, Inception Sciences, and Amneal Pharmaceuticals. Financial support from Mylan Pharmaceurticals, Amneal Pharmaceuticals, Novartis, and Inception Sciences.
Abstract: P1037
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Neuro-ophthalmology
Introduction: We currently lack reliable, rapid, and sensitive methods for prognosis and disease monitoring in multiple sclerosis (MS). Fixational eye movements are one of the finest motor movements the human body is capable of making and provide a non-invasive window into motor function at the micron-level. Objectively measuring MS motor deficits allows for highly quantitative and reliable functional assessments.
Methods: We recruited 111 people with MS (diagnosed by 2010 International Panel criteria) from the UCSF MS Center as test and validation cohorts of 51 and 60 subjects and 100 controls as test/validation cohorts of 50 subjects each. Retinal eye-tracking was performed using a custom built, tabletop device - the tracking scanning laser ophthalmoscope (TSLO). Three, 10-second recordings of fixation per eye were acquired using 840nm light to raster scan the retina over a 5 x 5° field of view. Patients were instructed to fixate on the upper right-hand corner of the raster. Strip-based, offline analysis was used to extract eye motion at 480 Hz. Microsaccadic metrics of velocity, amplitude, and quantity were compared between MS patients and controls.
Results: For MS cohort 1 (C1) mean EDSS was 3.45 (range 1-8), with MS cohort 2 (C2) having a mean EDSS of 3.28 (range 0-7). Patients diagnosed with MS had a higher average (avg) number of microsaccades (micsacs) (14.29 +/- 8.20) vs. controls (11.92 +/- 6.11); with a statistically significant increase of 2.37 micsacs p = 0.020. Additionally, MS patients had a higher avg micsac peak velocity and standard deviation (53.15°/s +/- 49.16°/s) compared to controls (36.91°/s +/- 19.10°/s); with a statistically significant increase of 16.24°/s, p=0.011. In a multivariable linear regression the avg number of micsacs increased with increasing EDSS score (C1: p< 0.001, C2 p=0.045).
Conclusions: MS patients had a greater avg number and velocity of micsacs compared to controls as recorded by the TSLO during 10s of fixation. The number of micsacs also correlated with disability even in patients with a low average level of disability. TSLO fixation abnormalities are detectable early in the course of disease and show promise as a highly sensitive, quantitative biomarker to predict disease progression and provide prognosis for MS patients. It also has potential to serve as an outcome measure for early phase clinical trials assessing motor function in MS. Longitudinal studies are needed to further evaluate its potential.
Disclosure: Christy K. Sheehy: Commercial and financial interests in C. Light Technologies and holds patents with this company and with UC Berkeley. Ethan S. Bensinger: Paid consultant for C. Light Technologies. Andrew Romeo: nothing to disclose. Lakshmisahithi Rani: nothing to disclose. Bingyan Shi: nothing to disclose. Jeffrey M. Gelfand: Research support from Genentech and MedDay. Consulting for Biogen. Personal compensation for medical legal consulting. Scott B. Stevenson: Scientific advisor for C. Light Technologies (Nonremunerative). Ari J. Green: Nonremunerative commercial relationships with Bionure, Biogen, and Medimmune. Consultant for Mylan Pharmaceuticals, Inception Sciences, and Amneal Pharmaceuticals. Financial support from Mylan Pharmaceurticals, Amneal Pharmaceuticals, Novartis, and Inception Sciences.