title: Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front.
abstract: OBJECTIVE
  To evaluate the progression of the earliest stage of disease in ABCA4-associated retinal degenerations (RDs).
  
  
  METHODS
  Near-infrared excited reduced-illuminance autofluorescence imaging was acquired across the retina up to 80 degrees eccentricity in 44 patients with two ABCA4 alleles. The eccentricity of the leading disease front (LDF) corresponding to the earliest stage of disease was measured along the four meridians. A mathematical model describing the expansion of the LDF was developed based on 6 years of longitudinal follow-up.
  
  
  RESULTS
  The extent of LDF along the superior, inferior, and temporal meridians showed a wide spectrum from 3.5 to 70 degrees. In patients with longitudinal data, the average centrifugal expansion rate was 2 degrees per year. The nasal extent of LDF between the fovea and ONH ranged from 4.3 to 16.5 degrees and expanded at 0.35 degrees per year. The extent of LDF beyond ONH ranged from 19 to 75 degrees and expanded on average at 2 degrees per year. A mathematical model fit well to the longitudinal data describing the expansion of the LDF.
  
  
  CONCLUSIONS
  The eccentricity of the LDF in ABCA4-RD shows a continuum from parafovea to far periphery along all four meridians consistent with a wide spectrum of severity observed clinically. The model of progression may provide a quantitative prediction of the LDF expansion based on the age and eccentricity of the LDF at a baseline visit, and thus contribute significantly to the enrollment of candidates appropriate for clinical trials planning specific interventions, efficacy outcomes, and durations.
authors.affiliation: Scheie Eye Institute Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.affiliation: Scheie Eye Institute Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Swider
authors.affiliation: Scheie Eye Institute Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.affiliation: Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States 3Howard Hughes Medical Institute, Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa, United Sta.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.affiliation: Scheie Eye Institute Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D061848:Optical Imaging / Q000379:methods; D011237:Predictive Value of Tests; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters