Multi-registry analysis of patients with multiple sclerosis and neuromyelitis optica to improve capture of demographic data and compare visual outcomes.

IMPORTANCE: The American Academy of Neurology Axon Registry® provides real-world data for patients with multiple sclerosis and neuro-myelitis optica. However, some data are incomplete (e.g. demographics) and some relevant outcomes are not systematically captured in neurology documentation (e.g. visual acuity). The American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) contains demographic and visual function data that may complement Axon Registry-derived data to enhance understanding of real-world visual outcomes in neurological disease. OBJECTIVE: To combine Axon Registry and IRIS Registry data to reduce missingness of demographic information and characterize visual outcomes in patients with multiple sclerosis and neuro-myelitis optica. DESIGN: Cross-sectional study. SETTING: Outpatient neurology and ophthalmology clinical practices. PARTICIPANTS: Patients participating in both registries between January 1, 2014 through December 10, 2021 were included if they had repeat ICD-9/10 codes for with multiple sclerosis or neuro-myelitis optica in the Axon registry. EXPOSURE: Diagnosis (multiple sclerosis or neuro-myelitis optica). MAIN OUTCOME AND MEASURE: Age, sex, race and ethnicity were assessed in the individual registries and classified as conflicting, missing, or not missing in the combined data set. The IRIS Registry contributed visual acuity data. RESULTS: Among 60,316 patients with multiple sclerosis and 1,068 patients with neuro-myelitis optica in the Axon Registry, 14,085 and 252 had temporal overlap in the IRIS Registry. Combining data reduced missing or conflicting data for race and ethnicity by 15-19 % (absolute reduction, all p ≤ 0.0005), but not age (p = 1.0) or gender (p = 0.08). 10,907 patients with MS and 142 with NMO had visual acuity data in the IRIS Registry. Visual acuity averaged between eyes was worse in patients with NMO after adjusting for age and gender (0.17 logMAR, 95 %CI 0.12,0.21, p < 0.0005). CONCLUSION AND RELEVANCE: Using data from two registries reduced missing data for race and ethnicity and enabled examination of outcomes captured in the IRIS Registry for conditions that are diagnosed more frequently in the Axon Registry, demonstrating the utility of a multi-registry analysis.

Real-world evaluation of amblyopic patient characteristics, clinical outcomes, and treatment patterns using the IRIS Registry.

PURPOSE: To characterize the demographics, eye-related comorbidities, clinical characteristics, clinical outcomes, type of amblyopia tests used, and treatment patterns of a large cohort of pediatric, teenage, and adult amblyopic patients from the IRIS (Intelligent Research in Sight) Registry. METHODS: In this retrospective electronic health record analysis, we analyzed 456,818 patients, of whom 197,583 (43.3%) were pediatric patients; 65,308 (14.3%), teenagers; and 193,927 (42.5%), adults. Baseline best-corrected visual acuity examination in both eyes was conducted within 90 days prior to index date. Three age cohorts were analyzed based on age at the index date: pediatric (3-12 years), teen (13-17 years), and adult (18-50 years). RESULTS: At index date, unilateral amblyopia was more common than bilateral amblyopia in all age cohorts (pediatric, 55% vs 45%; teen, 61% vs 39%; adult, 63% vs 37%). In unilateral amblyopic patients, severe amblyopia was more frequent in adults (21%) than in pediatric patients (12%) and teenagers (13%); in bilateral amblyopic patients, severity was comparable in pediatric patients and adults (4% severe in both). The greatest level of visual acuity improvement was demonstrated in pediatric patients with severe unilateral amblyopia at baseline. Pediatric patients showed significant improvement in stereopsis over time at years 1 (P = 0.000033) and 2 (P = 0.000039) at the population level (per χ2 test vs baseline). CONCLUSIONS: Our findings highlight the need for more efficacious amblyopia therapies in older, more severe patients with refractory disease.

Sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan.

Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild-caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species' lifespan.