Background: Visual acuity has been a significant outcome measure in clinical trials for patients suffering from neuro-ophthalmological diseases and multiple sclerosis; however, there are limited data on the comparison of various testing strategies in pediatric patients with these disorders. Clinical trials using vision as an outcome could include a variety of tools to assess the acuity, including 2-m and 4-m standardized retroilluminated charts., Methods: We investigated the difference in Early Treatment Diabetic Retinopathy Study (ETDRS) scores obtained using 2-m and 4-m charts, as well as the impact of optic neuritis, use of vision correction, age, and gender on visual acuity data from 71 patients with pediatric neuroimmunological conditions in a cross-sectional study., Results: We determine that the ETDRS letter scores obtained using 4-m charts are on average 3.43 points less (P = 0.0034) when testing monocular ETDRS letter scores and on average 4.14 points less (P = 0.0008) when testing binocular ETDRS letter scores, relative to that obtained using the 2-m charts. However, we find that when performing monocular testing, optic neuritis in the eye being tested did not result in a statistically significant difference between 2-m and 4-m ETDRS letter scores., Conclusions: Although visual acuity charts are formatted by the distance, there are significant differences in the number of letters correctly identified between 2-m and 4-m charts. Although the differences may not impact the clinical acuity, research protocols should consider these differences before collapsing data across disparate studies., Competing Interests: P. V. Sguigna has received grant support from the NMSS and PSTP. Morgan McCreary has nothing to declare. A. T. Waldman has received grant support from the NIH (K23NS069806), NMSS, and the United Leukodystrophy Foundation. She has received additional support for investigator-initiated research from Biogen Idec and Ionis Pharmaceuticals. She has received honoraria from UpToDate and consulting fees from Optum Inc. B. M. Greenberg has received grant support from the NIH, NMSS, Transverse Myelitis Association, PCORI, Guthy-Jackson Charitable Foundation, Chugai, MedImmune, MedDay, and Genentech. He has received consulting fees from Alexion, Novartis, EMD Serono, and Celgene. He is an unpaid board member of the Transverse Myelitis Association. The remaining authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.) more...