title: Inner and outer retinal changes in retinal degenerations associated with ABCA4 mutations.
abstract: OBJECTIVE
  To investigate in vivo inner and outer retinal microstructure and effects of structural abnormalities on visual function in patients with retinal degeneration caused by ABCA4 mutations (ABCA4-RD).
  
  
  METHODS
  Patients with ABCA4-RD (n = 45; age range, 9-71 years) were studied by spectral-domain optical coherence tomography (OCT) scans extending from the fovea to 30° eccentricity along horizontal and vertical meridians. Thicknesses of outer and inner retinal laminae were analyzed. Serial OCT measurements available over a mean period of 4 years (range, 2-8 years) allowed examination of the progression of outer and inner retinal changes. A subset of patients had dark-adapted chromatic static threshold perimetry.
  
  
  RESULTS
  There was a spectrum of photoreceptor layer thickness changes from localized central retinal abnormalities to extensive thinning across central and near midperipheral retina. The inner retina also showed changes. There was thickening of the inner nuclear layer (INL) that was mainly associated with regions of photoreceptor loss. Serial data documented only limited change in some patients while others showed an increase in outer nuclear layer (ONL) thinning accompanied by increased INL thickening in some regions imaged. Visual function in regions both with and without INL thickening was describable with a previously defined model based on photoreceptor quantum catch.
  
  
  CONCLUSIONS
  Inner retinal laminar abnormalities, as in other human photoreceptor diseases, can be a feature of ABCA4-RD. These changes are likely due to the retinal remodeling that accompanies photoreceptor loss. Rod photoreceptor-mediated visual loss in retinal regionswith inner laminopathy at the stages studied did not exceed the prediction from photoreceptor loss alone.
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Wei Chieh
authors.initials: WC
authors.lastname: Huang
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Roman
authors.forename: Alexander
authors.initials: A
authors.lastname: Sumaroka
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sheplock
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055211:Retinal Photoreceptor Cell Inner Segment / Q000473:pathology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000473:pathology*; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D004247:DNA
keywords: Stargardt disease; optical coherence tomography; retinal remodeling