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Sarah-Jane Martin,1,2 Melanie Guenette,1 Jiwon Oh1 1Division of Neurology, Department of Medicine, St Michael’s Hospital, Toronto, Canada; 2University of Glasgow, Glasgow, UKCorrespondence: Jiwon Oh, Email jiwon.oh@unityhealth.toAbstract: B cells are critical to the pathogenesis of multiple sclerosis (MS), an autoimmune disease of the central nervous system. B cell depletion using anti-CD20 monoclonal antibodies (mAbs) has proven to be an extremely successful treatment strategy, with profound suppression of both clinical and radiological evidence of focal inflammatory disease. Several anti-CD20 mAbs are now licensed for use in MS, with ublituximab being the latest to gain regulatory approval. The unique properties of each of the anti-CD20 mAb may result in nuanced differences in timing, duration and depth of B cell depletion, with the potential for such differences to have a clinical relevance to both drug efficacy and adverse effects. In this review, we summarize the design, development, and current place in MS therapy for ublituximab.Keywords: multiple sclerosis, ublituximab, B-cell therapy, anti-CD20 monoclonal antibody

Lucas E Hepler,1 Samuel J Martin,2 Kennedy Fuglseth,1 Laney Cuddihee,3 Peter Giannulis,3 Robert W Arnold3 1College of Osteopathic Medicine, Pacific Northwest University, Yakima, WA, USA; 2School of Medicine, Loma Linda University, Loma Linda, CA, USA; 3Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, USACorrespondence: Robert W Arnold, Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, 3500 Latouche &num;280, Anchorage, AK, 99508, USA, Tel +1907561-1917, Fax +1907563-5373, Email eyedoc@alaska.netPurpose: Existing and emerging visual acuity methods like dynamic and dichoptic presentation, preferential looking and eye tracking promise to afford better and earlier assessment in children with and without amblyopia so we propose methods needed to easily evaluate and compare their metrics.Subjects and Methods: Patients older than 8 years with treated amblyopia and superb vision (logMAR − 0.1 to − 0.3) normals performed timed, patched eETDRS with Sloan matching card at 3.00 m and PDI Check dichoptic near rivalry dynamic test to demonstrate test re-Test and compared disparate acuity with intraclass correlation (ICC) and Bland Altman 95% limits of agreement (LOA) to generate a simple method of qualifying acuity test matching.Results: 26 amblyopic patients and 11 superb-vision normals performed eETDRS retest, PDI Check retest and combined ICC of 0.98, 0.60 and 0.27, respectively, and Bland Altman LOA of 0.24, 2.06 and 2.28 logMAR. The time to test one eye with eETDRS had median (interquartile range; IQR) duration of 280 (205 to 346) seconds, while the PDI Check autostereoscopic dichoptic for both eyes only took 39 (30 to 47) seconds. Optimum ICC and LOA for visual acuity comparison should be > 0.95 and < 0.3 logMAR, whereas “good” ICC and should be 0.75– 0.89 ICC and 1.0– 1.49 logMAR LOA.Conclusion: Superb vision subjects (logMAR < − 0.1) and treated amblyopic patients confirmed optimum comparable eETDRS, and fair test re-Test PDI Check but suppression on near dichoptic testing confirmed disparity compared to optimized eETDRS distance acuity.Keywords: visual acuity, Bland Altman, amblyopia, suppression, superior, optimum, correlation, dichoptic

Robert W Arnold,1 Samuel J Martin,2 Joshua R Beveridge,3 Andrew W Arnold,4 Stephanie L Arnold,4 Nathanael R Beveridge,5 Kyle A Smith1,6 1Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, 99508, USA; 2Loma Linda Medical School, Loma Linda, CA, USA; 3Idaho College of Osteopathic Medicine, Boise, ID, USA; 4Ascension Genesys Residency Program, Grand Blanc, MI, USA; 5US Airforce Academy, Colorado Springs, CO, USA; 6Accurate Vision, Anchorage, AK, USACorrespondence: Robert W ArnoldAlaska Children’s EYE & Strabismus, 3500 Latouche Street #280, Anchorage, AK, 99508, USATel +1(907)561-1917Fax +1 9075635373Email eyedoc@alaska.netBackground: Handheld devices can automatically give an estimate of refraction. The established method for refraction comparison using spherical equivalent (M) and J0, J45 vector transformations by Bland–Altman analysis is too complex for non-eye doctors involved with vision screening and remote vision clinics. Therefore, a simpler comparison technique was developed.Methods: Based on the spectacle limit to resolve grade A 1 logMAR, B 3 logMAR and C 6 logMAR blur, J0, J45, and M are combined into the Alaska Blind Child Discovery (ABCD) composite ellipsoid GRADE system. Pediatric eye patients had confirmatory examination after dry refraction with three portable autorefractors: Plusoptix, 2WIN and Retinomax. The refractions were then compared using both Bland–Altman and ABCD composite. Performance to detect AAPOS amblyopia risk factors was also assessed.Results: A total of 202 children, mean age seven years, 28% high spectacle need and 43% AAPOS 2013 amblyopia risk factors showed high correlation with cycloplegic refraction (intraclass correlation 0.49 to 0.90) for sphere, J0 and J45 spectacle components. Plusoptix had more (10%) inconclusives due to patients out-of-range. The Retinomax was unable to screen some younger children and was less reliable for sphere but gave more precise astigmatism estimates. The proportion of autorefractions expected to give GRADE A/B high-need patients acuity improvement to 20/40 would be 41% for Plusoptix, 39% for 2WIN and 65% for Retinomax. Sensitivity/specificity for amblyopia risk factor detection was 80%/83% for Plusoptix, 72%/88% for 2WIN and 84%/73% for Retinomax.Conclusion: The simplified spectacle comparison resembled Bland–Altman and could assist lay vision screeners and non-eye doctors attempting remote spectacle donation worldwide.Keywords: spectacles, remote dispensing, autorefractors, validation

Robert W Arnold,1 Joshua S Beveridge,1 Samuel J Martin,1 Nathanael R Beveridge,1 Elise J Metzger,2 Kyle A Smith3 1The Alaska Blind Child Discovery, Anchorage, AK 99508, USA; 2Grace Christian School, Anchorage, AK, USA; 3Kyle Smith, Accurate Vision, Anchorage, AK, USACorrespondence: Robert W ArnoldThe Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, 3500 Latouche #280, Anchorage, AK 99508, USATel +1 907 561-1917Fax +1 907 563-5373Email eyedoc@alaska.netBackground: Portable autorefractors can estimate refractive error in remote locations, but sphero-cylinder comparison and donated-spectacle dispensing are not yet simple.Methods: Normal astigmats determined best corrected acuity, then degraded 1 logMAR (Grade A), 3 logMAR (Grade B), and 6 logMAR (Grade C) to determine limits of astigmatism axis and power at these levels. The cylindrical refraction was vector transformed with J0 on the abscissa and J45 on the ordinate.Results: Ten subjects produced multiple refractions at the interfaces of Grades A, B, and C representing ovals on the J0 and J45 coordinates. When rotated, the vertical axis represented 45° or 135°, the horizontal long axis was 1.6× the short axis. The size of the ovals positively correlated with cylinder power. Given a target refraction, the comparability of a candidate lens was demonstrated on our interactive database yielding a simple A, B, C, or worse grade for cylinder, spherical equivalent, and pupillary diameter.Conclusion(s)/Relevance: Inputting a remote autorefraction, pupillary diameter and age as target and a donated spectacle as the candidate with a “B” grade similarity would be expected to attain 20/40 acuity (3 logMAR degrade) if best corrected visual acuity was 20/20. This practical Excel database could facilitate widespread remote lay dispensing of the cylinder as well as spherical spectacles. The grade similarity can also compare refracting tools such as photoscreeners and hand-held autorefractors.Clinical Trials Registry: NCT04297969.Keywords: donated recyled spectacles, remote dispensing, portable autorefraction, vision screen validation, forensic optometry

Alexa H Levitt,1 Samuel J Martin,2 Robert W Arnold3 1Human and Organizational Development, Vanderbilt University, Nashville, TN, USA; 2Research Department, Alaska Blind Child Discovery, Anchorage, AK, USA; 3Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, USACorrespondence: Robert W ArnoldAlaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, USAEmail eyedoc@alaska.netBackground: A low-detail, glowing fixation device was added to GoCheck Kids (GCK) photoscreener in the hope of unmasking hyperopia and amblyopia risk factors (ARF).Methods: Pediatric eye patients were screened by GCK and 2WIN photoscreeners, and Retinomax autorefractor before being compared to AAPOS ARFs.Results: Screening was attempted by 131 children who then had school bus accommodation-relaxing skiascopy (SBA-RS) before cycloplegic examination. By 2013 AAPOS uniform guidelines, sensitivity/specificity for GCK was 87%/68%, for 2WIN 87%/71% and for Retinomax 79%/68%. Detection of amblyopia had sensitivity/specificity by GCK of 78%/63%, for 2WIN 79%/65% and for Retinomax 77%/68%. Inconclusive screens were seven for GCK, six for 2WIN and 13 for Retinomax. Mean hyperopia for GCK (+2.49± 0.74 D) was similar to cycloplegic refraction (+2.93± 0.72 D) and SBA-RS (+2.80± 0.82 D) while GCK was slightly more than Retinomax (+1.59± 0.93 D, p=0.13) but significantly more than 2WIN (+1.02± 0.49 D, p< 0.01).Conclusion: GCK, 2WIN and Retinomax had similar validity detecting uniform amblyopia risk factors and amblyopia itself. The nondetailed glow fixation device allowed GCK to uncover substantial hyperopia while the detailed flashing fixation devices on 2WIN and Retinomax seemed to stimulate accommodation in some hyperopic children.Clinical Trials Registry: NCT04297969. Data Access: http://www.abcd-vision.org/references/GCK%20glow%202WIN%20deidentify.pdf.Précis: A glow fixation device on a smart phone photoscreener allowed robust detection of hyperopia.Keywords: amblyopia risk factor, vision screening, photoscreener, hyperopia

Samuel Joseph Martin,1 Hser Eh Htoo,2 Nay Hser,2 Robert W Arnold1 1Alaska Blind Child Discovery, Anchorage, AK, USA; 2Jungle School of Medicine Kawthoolei, Karen State, Burma (Myanmar)Correspondence: Robert W ArnoldAlaska Blind Child Discovery, Anchorage, AK, USATel +1 907561-1917Email eyedoc@alaska.netBackground: Photoscreeners provide valid, cost-effective early detection of amblyopia risk factors; however, they require proper illumination, flash intensity, pupil dilation and patient cooperation. The Kaleidos case for the 2WIN infrared photoscreener fixes focal distance, decreases luminance and provides electric power. GoCheck Kids (GCK) has developed a flash-concentrating case for the Apple iPhone 7 Plus smartphone to reduce exposure time.Methods: In remote Burmese and urban Alaskan clinics, Kaleidos and GCK were used before a confirmatory eye examination using 2013 AAPOS uniform guidelines validation, including some older patients. 2WIN refraction was compared to a cycloplegic examination using J0 and J45 vector transformation.Results: In total, 48 Burmese patients and 114 Alaskan patients aged 8± 6 years were evaluated utilizing 2013 amblyopia risk factor guidelines. Kaleidos, with 13 Burmese inconclusives, had a sensitivity of 84%, specificity of 65% and positive predictive value (PPV) of 63%. GCK, with only six inconclusives, had a sensitivity of 63%, specificity of 83% and PPV of 73%, with sensitivity improving to 74% with central expert interpretation. Kaleidos closely matched cycloplegic refraction, with intraclass correlations of 0.47 for J0 vector and 0.57 for J45 vector. The protective cases provided clearer images and better pupil dilation than similar devices without cases.Conclusion: Both devices detected amblyopia risk factors well. GCK gave fewer inconclusive results even with the Asian eyelid configuration, while Kaleidos matched sphere and cylinder refraction. The specialized housing enhanced the performance of the 2WIN and GCK photoscreeners, improving the speed and reliability of amblyopia screening and refraction, even in populous and luminous locations.Clinical Trials Registry: NCT04068129.Keywords: pediatric vision screening, amblyopia, instrument-based screening, validation