Browsing by Author "Fahim, Abigail T"
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Item Open Access Advancing Clinical Trials for Inherited Retinal Diseases: Recommendations from the Second Monaciano Symposium.(Translational vision science & technology, 2020-06-03) Thompson, Debra A; Iannaccone, Alessandro; Ali, Robin R; Arshavsky, Vadim Y; Audo, Isabelle; Bainbridge, James WB; Besirli, Cagri G; Birch, David G; Branham, Kari E; Cideciyan, Artur V; Daiger, Steven P; Dalkara, Deniz; Duncan, Jacque L; Fahim, Abigail T; Flannery, John G; Gattegna, Roberto; Heckenlively, John R; Heon, Elise; Jayasundera, K Thiran; Khan, Naheed W; Klassen, Henry; Leroy, Bart P; Molday, Robert S; Musch, David C; Pennesi, Mark E; Petersen-Jones, Simon M; Pierce, Eric A; Rao, Rajesh C; Reh, Thomas A; Sahel, Jose A; Sharon, Dror; Sieving, Paul A; Strettoi, Enrica; Yang, Paul; Zacks, David N; Monaciano ConsortiumMajor advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations. This position paper reviews recent accomplishments and existing challenges in clinical trials for IRDs and presents a set of recommendations aimed at rapidly advancing future progress. The goal is to stimulate discussions among researchers, funding agencies, industry, and policy makers that will further the design, conduct, and analysis of clinical trials needed to accelerate the approval of effective treatments for IRDs, while promoting advocacy and ensuring patient safety.Item Open Access Characterization of the Spectrum of Ophthalmic Changes in Patients With Alagille Syndrome.(Investigative ophthalmology & visual science, 2021-06) da Palma, Mariana Matioli; Igelman, Austin D; Ku, Cristy; Burr, Amanda; You, Jia Yue; Place, Emily M; Wang, Nan-Kai; Oh, Jin Kyun; Branham, Kari E; Zhang, Xinxin; Ahn, Jeeyun; Gorin, Michael B; Lam, Byron L; Ronquillo, Cecinio C; Bernstein, Paul S; Nagiel, Aaron; Huckfeldt, Rachel; Cabrera, Michelle T; Kelly, John P; Bakall, Benjamin; Iannaccone, Alessandro; Hufnagel, Robert B; Zein, Wadih M; Koenekoop, Robert K; Birch, David G; Yang, Paul; Fahim, Abigail T; Pennesi, Mark EPurpose
The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome.Methods
We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings.Results
Cardiovascular abnormalities were found in 83% of all cases (of those, 74% had cardiac murmur), whereas 61% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel.Conclusions
This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.Item Open Access The RUSH2A Study: Best-Corrected Visual Acuity, Full-Field Electroretinography Amplitudes, and Full-Field Stimulus Thresholds at Baseline.(Translational vision science & technology, 2020-10-08) Birch, David G; Cheng, Peiyao; Duncan, Jacque L; Ayala, Allison R; Maguire, Maureen G; Audo, Isabelle; Cheetham, Janet K; Durham, Todd A; Fahim, Abigail T; Ferris, Frederick L; Heon, Elise; Huckfeldt, Rachel M; Iannaccone, Alessandro; Khan, Naheed W; Lad, Eleonora M; Michaelides, Michel; Pennesi, Mark E; Stingl, Katarina; Vincent, Ajoy; Weng, Christina Y; Foundation Fighting Blindness Consortium Investigator GroupPurpose
The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), full-field stimulus thresholds (FST), and their relationship with baseline demographic and clinical characteristics in the Rate of Progression in Usher syndrome type 2 (USH2A)-related Retinal Degeneration (RUSH2A) multicenter study.Methods
Participants had Usher syndrome type 2 (USH2, N = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, N = 47) associated with biallelic variants in the USH2A gene. Associations of demographic and clinical characteristics with BCVA, ERG, and FST were assessed with regression models.Results
In comparison to ARRP, USH2 had worse BCVA (median 79 vs. 82 letters; P < 0.001 adjusted for age), lower rod-mediated ERG b-wave amplitudes (median 0.0 vs. 6.6 µV; P < 0.001) and 30 Hz flicker cone-mediated ERG amplitudes (median 1.5 vs. 3.1 µV; P = 0.001), and higher (white, blue, and red) FST thresholds (means [-26, -31, -23 dB] vs. [-39, -45, -28 dB]; P < 0.001 for all stimuli). After adjusting for age, gender, and duration of vision loss, the difference in BCVA between diagnosis groups was attenuated (P = 0.09). Only diagnosis was associated with rod- and cone-mediated ERG parameters, whereas both genders (P = 0.04) and duration of visual loss (P < 0.001) also were associated with FST white stimulus.Conclusions
USH2 participants had worse BCVA, ERG, and FST than ARRP participants. FST was strongly associated with duration of disease; it remains to be determined whether it will be a sensitive measure of progression.Translational relevance
Using standardized research protocols in RUSH2A, measures have been identified to monitor disease progression and treatment response and differentiate features of prognostic relevance between USH2 and ARRP participants with USH2A mutations.