Browsing by Author "Beaulieu, Wesley T."

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    Defining “Strong” versus “Weak” Response to Anti-VEGF Treatment for Center-Involved Diabetic Macular Edema
    (Wolters Kluwer, 2023) Sun, Jennifer K.; Beaulieu, Wesley T.; Melia, Michele; Ferris, Frederick L., III; Maturi, Raj K.; Nielsen, Jared S.; Solomon, Sharon D.; Jampol, Lee M.; DRCR Retina Network; Ophthalmology, School of Medicine
    Background/purpose: To define "strong" versus "weak" antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME). Methods: Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25-20/32, 20/40-20/63, or 20/80-20/320, respectively. Thresholds of 50, 100, or 200- µ m reduction defined strong anatomical response when baseline central subfield thickness (CST) was <75, ≥75 to <175, or ≥175- µ m above standard thresholds. Additional thresholds from regression equations were calculated. Results: At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50%) for VA and 505 eyes (53%) for CST. At 104 weeks among the 32% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69%) maintained strong VA and CST response, whereas 20 (7%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations. Conclusion: These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.
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    Locomotor analysis identifies early compensatory changes during disease progression and subgroup classification in a mouse model of amyotrophic lateral sclerosis
    (Medknow Publications, 2017-10) Haulcomb, Melissa M.; Meadows, Rena M.; Miller, Whitney M.; McMillan, Kathryn P.; Hilsmeyer, MeKenzie J.; Wang, Xuefu; Beaulieu, Wesley T.; Dickinson, Stephanie L.; Brown, Todd J.; Sanders, Virginia M.; Jones, Kathryn J.; Anatomy and Cell Biology, School of Medicine
    Amyotrophic lateral sclerosis is a motoneuron degenerative disease that is challenging to diagnose and presents with considerable variability in survival. Early identification and enhanced understanding of symptomatic patterns could aid in diagnosis and provide an avenue for monitoring disease progression. Use of the mSOD1G93A mouse model provides control of the confounding environmental factors and genetic heterogeneity seen in amyotrophic lateral sclerosis patients, while investigating underlying disease-induced changes. In the present study, we performed a longitudinal behavioral assessment paradigm and identified an early hindlimb symptom, resembling the common gait abnormality foot drop, along with an accompanying forelimb compensatory mechanism in the mSOD1G93A mouse. Following these initial changes, mSOD1 mice displayed a temporary hindlimb compensatory mechanism resembling an exaggerated steppage gait. As the disease progressed, these compensatory mechanisms were not sufficient to sustain fundamental locomotor parameters and more severe deficits appeared. We next applied these initial findings to investigate the inherent variability in B6SJL mSOD1G93A survival. We identified four behavioral variables that, when combined in a cluster analysis, identified two subpopulations with different disease progression rates: a fast progression group and a slow progression group. This behavioral assessment paradigm, with its analytical approaches, provides a method for monitoring disease progression and detecting mSOD1 subgroups with different disease severities. This affords researchers an opportunity to search for genetic modifiers or other factors that likely enhance or slow disease progression. Such factors are possible therapeutic targets with the potential to slow disease progression and provide insight into the underlying pathology and disease mechanisms.