TY - JOUR
T1 - Monocular and binocular low-contrast visual acuity and optical coherence tomography in pediatric multiple sclerosis
AU - Waldman, Amy T.
AU - Hiremath, Girish
AU - Avery, Robert A.
AU - Conger, Amy
AU - Pineles, Stacy L.
AU - Loguidice, Michael J.
AU - Talman, Lauren S.
AU - Galetta, Kristin M.
AU - Shumski, Michael J.
AU - Wilson, James
AU - Ford, E'Tona
AU - Lavery, Amy M.
AU - Conger, Darrel
AU - Greenberg, Benjamin
AU - Ellenberg, Jonas H.
AU - Frohman, Elliot
AU - Balcer, Laura J.
AU - Calabresi, Peter A.
N1 - Funding Information:
Supported by the National Multiple Sclerosis Society-American Academy of Neurology Foundation Clinician Scientist Development Award (FAN 1750-A-1) and National Institute for Neurologic Disorders and Stroke, National Institutes of Health (1K23NS069806-01A1). The sponsors did not have any role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit for publication.
Funding Information:
Dr. A. Waldman has received honoraria from TEVA and funding from the National Multiple Sclerosis Society and National Institutes of Health (National Institute of Neurological Disorders and Stroke) and serves on the Clinical Advisory Committee for the Greater Delaware Valley Chapter of the National Multiple Sclerosis Society.
Funding Information:
Dr. P. Calabresi has consulted, served on the scientific advisory board, or received research grant support from Novartis, Genzyme, Vertex, Abbott, Biogen-Idec, Vaccinex, and Bayer.
PY - 2014/5
Y1 - 2014/5
N2 - Background: Low-contrast letter acuity and optical coherence tomography (OCT) capture visual dysfunction and axonal loss in adult-onset multiple sclerosis (MS), and have been proposed as secondary outcome metrics for therapeutic trials. Clinical trials will soon be launched in pediatric MS, but such outcome metrics have not been well-validated in this population. Objectives: To determine whether MS onset during childhood and adolescence is associated with measurable loss of visual acuity and thinning of the retinal nerve fiber layer (RNFL), whether such features are noted only in the context of clinical optic nerve inflammation (optic neuritis, ON) or are a feature of MS even in the absence of optic nerve relapses, and to define the optimal methods for such detection. Study design: Cross-sectional study. Methods: Monocular and binocular high- and low-contrast letter acuity and contrast sensitivity were assessed in a cross-sectional cohort of children (ages 5-17 years) with MS (N=22 patients, 44 eyes; 8 patients with a history of ON) and disease-free controls (N=29 patients; 58 eyes) from three academic centers. Binocular summation was determined by calculating the number of letters correctly identified using the binocular score minus the better eye score for each visual test. RNFL thickness was measured using OCT (Stratus OCT-3). Results were analyzed in terms of "eyes" as: MS ON+, MS ON-, and control eyes. Generalized estimating equation (GEE) regression models were used to compare patients to controls. Results: Traditional high-contrast visual acuity scores did not differ between MS ON+, MS ON-, and controls eyes. MS ON+ eyes had decreased monocular (p<0.001) and decreased binocular (p=0.007) low-contrast letter acuity (Sloan 1.25% contrast charts) scores. Monocular visual acuity did not differ when comparing MS ON- and control eyes. The magnitude of binocular summation using low-contrast charts was similar for pediatric MS participants and controls and was not diminished in children with a history of ON. While the mean RNFL thickness for all MS eyes (103±17 μm) trended lower when compared to corresponding measures in control eyes (109±9 μm, p=0.085), we confirmed a highly significant reduction in mean RNFL thickness in MS eyes with a history of ON (86±22 μm, p<0.001). RNFL thickness of MS ON- eyes in pediatric MS patients (109±11 μm) did not differ from controls (p=0.994). Conclusions: Low-contrast letter acuity detects subtle visual loss in MS patients with prior ON, consistent with incomplete recovery, a finding further supported by RNFL loss in ON affected eyes. In MS patients with prior unilateral ON, binocular acuity is decreased; however, the magnitude of binocular summation is preserved, unlike adult-onset MS who exhibit a reduced capacity for visual compensation in the context of unilateral injury. Also unlike findings in adult-onset MS, we did not demonstrate RNFL thinning in ON- eyes of children and adolescents with MS. Further validation is required to confirm whether neurodegeneration of visual pathways occurs in the absence of relapse, and thus whether OCT will serve as a sensitive metric for such pathology in the pediatric and adolescent MS context.
AB - Background: Low-contrast letter acuity and optical coherence tomography (OCT) capture visual dysfunction and axonal loss in adult-onset multiple sclerosis (MS), and have been proposed as secondary outcome metrics for therapeutic trials. Clinical trials will soon be launched in pediatric MS, but such outcome metrics have not been well-validated in this population. Objectives: To determine whether MS onset during childhood and adolescence is associated with measurable loss of visual acuity and thinning of the retinal nerve fiber layer (RNFL), whether such features are noted only in the context of clinical optic nerve inflammation (optic neuritis, ON) or are a feature of MS even in the absence of optic nerve relapses, and to define the optimal methods for such detection. Study design: Cross-sectional study. Methods: Monocular and binocular high- and low-contrast letter acuity and contrast sensitivity were assessed in a cross-sectional cohort of children (ages 5-17 years) with MS (N=22 patients, 44 eyes; 8 patients with a history of ON) and disease-free controls (N=29 patients; 58 eyes) from three academic centers. Binocular summation was determined by calculating the number of letters correctly identified using the binocular score minus the better eye score for each visual test. RNFL thickness was measured using OCT (Stratus OCT-3). Results were analyzed in terms of "eyes" as: MS ON+, MS ON-, and control eyes. Generalized estimating equation (GEE) regression models were used to compare patients to controls. Results: Traditional high-contrast visual acuity scores did not differ between MS ON+, MS ON-, and controls eyes. MS ON+ eyes had decreased monocular (p<0.001) and decreased binocular (p=0.007) low-contrast letter acuity (Sloan 1.25% contrast charts) scores. Monocular visual acuity did not differ when comparing MS ON- and control eyes. The magnitude of binocular summation using low-contrast charts was similar for pediatric MS participants and controls and was not diminished in children with a history of ON. While the mean RNFL thickness for all MS eyes (103±17 μm) trended lower when compared to corresponding measures in control eyes (109±9 μm, p=0.085), we confirmed a highly significant reduction in mean RNFL thickness in MS eyes with a history of ON (86±22 μm, p<0.001). RNFL thickness of MS ON- eyes in pediatric MS patients (109±11 μm) did not differ from controls (p=0.994). Conclusions: Low-contrast letter acuity detects subtle visual loss in MS patients with prior ON, consistent with incomplete recovery, a finding further supported by RNFL loss in ON affected eyes. In MS patients with prior unilateral ON, binocular acuity is decreased; however, the magnitude of binocular summation is preserved, unlike adult-onset MS who exhibit a reduced capacity for visual compensation in the context of unilateral injury. Also unlike findings in adult-onset MS, we did not demonstrate RNFL thinning in ON- eyes of children and adolescents with MS. Further validation is required to confirm whether neurodegeneration of visual pathways occurs in the absence of relapse, and thus whether OCT will serve as a sensitive metric for such pathology in the pediatric and adolescent MS context.
KW - Demyelinating disease
KW - Multiple sclerosis
KW - Optic neuritis
KW - Optical coherence tomography
KW - Pediatric
KW - Retinal nerve fiber layer
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U2 - 10.1016/j.msard.2013.10.008
DO - 10.1016/j.msard.2013.10.008
M3 - Article
C2 - 24683535
AN - SCOPUS:84896546939
SN - 2211-0348
VL - 3
SP - 326
EP - 334
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
IS - 3
ER -