title: Asymmetric Inter-Eye Progression in Stargardt Disease.
abstract: Asymmetry in disease progression between left and right eyes can occur in Stargardt disease (STGD1), and this needs to be considered in novel therapeutic trials with a fellow-eye paired controlled design. This study investigated the inter-eye discordance of best-corrected visual acuity (BCVA) and progression of RPE atrophy in STGD1.
  
  
  
  We performed a retrospective cohort study collecting 68 STGD1 patients (136 eyes) with ≥1 ABCA4 variants and ≥0.5-year follow-up on BCVA and fundus autofluorescence. We compared inter-eye correlations of RPE atrophy progression between early-onset (≤10 years), intermediate-onset (11-44), and late-onset (≥45) STGD1 and ABCA4 variant combinations by χ2 tests. We identified associations of discordant baseline BCVA and RPE atrophy with discordant RPE atrophy progression by odds ratios (OR). We defined discordance by differences >1.5 interquartile ranges ± first/third interquartiles.
  
  
  
  Progression of RPE atrophy correlated moderately between eyes (ρ = 0.766), which decreased with later onset (P = 9.8 × 10-7) and lower pathogenicity of ABCA4 combinations (P = 0.007). Twelve patients (17.6%) had discordant inter-eye RPE atrophy progression, associated with baseline discordance of RPE atrophy (OR, 6.50 [1.35-31.34]), but not BCVA (OR, 0.33 [0.04-2.85]).
  
  
  
  Lower inter-eye correlations are more likely found in late-onset STGD1 and patients carrying low pathogenic ABCA4 combinations. To achieve the highest power in a therapeutic trial, early-phase studies should minimize inter-eye discordance by selecting early-onset STGD1 patients carrying severe ABCA4 variants without evidence of asymmetry at baseline.
authors.affiliation: Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Stanley
authors.initials: S
authors.lastname: Lambertus
authors.affiliation: Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Bax
authors.affiliation: Department for Health Evidence, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joannes M M
authors.initials: JM
authors.lastname: Groenewoud
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.affiliation: Department for Health Evidence, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: van der Wilt
authors.affiliation: Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.affiliation: Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Theelen
authors.affiliation: Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D005654:Fundus Oculi; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D055213:Retinal Pigment Epithelium / Q000473:pathology* / Q000503:physiopathology; D012189:Retrospective Studies; D000080362:Stargardt Disease; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000379:methods; D014792:Visual Acuity; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters