Monocular and binocular low-contrast visual acuity and optical coherence tomography in pediatric multiple sclerosis

Abstract

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 to 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 vi...

Pediatric multiple sclerosis

“…32 The anterior visual pathway has been interrogated in pediatric MS using functional scales (such as low-contrast letter acuity) and structural imaging (with OCT). While decreased lowcontrast letter acuity scores and retinal nerve fiber layer (RNFL) thinning have been demonstrated in pediatric patients with MS with a history of ON, 33 there are conflicting data regarding the relationship between deficits in low-contrast visual function and retinal pathology in the eyes of children with MS unaffected by a clinical attack of ON (MS non-ON eyes). 34,35 One study has shown preserved RNFL in MS non-ON eyes, 33 suggesting that OCT may capture only local thinning after ON.…”

“…While decreased lowcontrast letter acuity scores and retinal nerve fiber layer (RNFL) thinning have been demonstrated in pediatric patients with MS with a history of ON, 33 there are conflicting data regarding the relationship between deficits in low-contrast visual function and retinal pathology in the eyes of children with MS unaffected by a clinical attack of ON (MS non-ON eyes). 34,35 One study has shown preserved RNFL in MS non-ON eyes, 33 suggesting that OCT may capture only local thinning after ON. However, 2 other studies have shown decreased RNFL in pediatric MS non-ON eyes, suggesting that OCT might capture a more global degenerative component of MS. 34,35 Further validation of OCT as an outcome in pediatric MS is needed.…”

MRI in the evaluation of pediatric multiple sclerosis

“…It is important to perform paraclinical testing to evaluate for subclinical disease or for evidence of a prior attack that was not identified-a key issue in young children who may not have reported mild symptoms. Visualevoked responses 22 or optical coherence tomography features 23,24 consistent with prior optic neuritis can be used to support a prior demyelinating event, which in combination with MRI evidence of DIT and DIS can confirm the diagnosis of MS. Further research on the implications of RIS in the pediatric population and consensus regarding management of both children and adults with accrual of new MRI lesions is required.…”

Pediatric optic neuritis

“…22 In contrast, another study demonstrated that LCVA was not associated with RNFL thinning after adjusting for age and intereye correlations. 25 Decreases in other functional testing, including color vision and VF, correlate with decreases in RNFL. Replication of these results in other cohorts is needed.…”

“…14,23,24 Three pediatric studies have demonstrated decreased low-contrast visual acuity (LCVA) after ON. 21,22,25 One study showed a correlation between RNFL thickness and LCVA (using 2.5% Sloan letter charts) for all demyelinating disease eyes (R 5 0.42, p 5 0.002). 22 In contrast, another study demonstrated that LCVA was not associated with RNFL thinning after adjusting for age and intereye correlations.…”