title: Multimodal imaging and multifocal electroretinography demonstrate autosomal recessive Stargardt disease may present like occult macular dystrophy.
abstract: OBJECTIVE
  To describe multimodal imaging and electrophysiologic characteristics of an unusual subset of patients with genetically confirmed autosomal recessive Stargardt disease (STGD1) who exhibited a central form of cone dysfunction resembling occult macular dystrophy that preceded the development of lipofuscin flecks, atrophy of retinal pigment epithelium (RPE), or full-field electroretinography abnormalities.
  
  
  METHODS
  Retrospective, observational descriptive case series.
  
  
  RESULTS
  Five patients with compound heterozygous ABCA4 mutations presented with bilateral visual acuity reduction, normal-appearing fundi, and blocked choroidal fluorescence on fluorescein angiography. One sibling each of two probands with identical genotypes was also included for analysis. Full-field electroretinography testing was normal in all patients, but multifocal electroretinography demonstrated centripetally depressed amplitudes exceeding areas of fundus autofluorescence, infrared imaging, and spectral domain optical coherence tomography abnormalities. Spectral domain optical coherence tomography initially revealed disruption of the inner segment ellipsoid band accompanying an ovoid hypofluorescent foveolar lesion. Progression to later stages was accompanied by the loss of the foveal photoreceptor outer segments, creating foveal cavitation with preservation of the RPE. Fundus autofluorescence and infrared imaging demonstrated corresponding bull's eye lesions. Over time, the foveal potential space on spectral domain optical coherence tomography collapsed, and three patients developed RPE atrophy and visible lipofuscin flecks. The flecks were detectable by fundus autofluorescence and infrared imaging earlier than by biomicroscopy. From these findings, a staging system for this subset of Stargardt disease presenting with central cone dysfunction was developed and presented herein.
  
  
  CONCLUSIONS
  Autosomal recessive Stargardt disease may present as a central cone dysfunction syndrome before the development of lipofuscin flecks, atrophy of RPE, or full-field electroretinography abnormalities. If emerging therapies for Stargardt disease succeed, early recognition and treatment of patients with preserved foveal photoreceptor and RPE cell bodies may yield a more favorable visual prognosis.
authors.affiliation: *Cincinnati Eye Institute, Cincinnati, Ohio; †Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; ‡Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio; and §Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sisk
authors.forename: Theodore
authors.initials: T
authors.lastname: Leng
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001284:Atrophy; D002648:Child; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005808:Genes, Recessive; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D064847:Multimodal Imaging; D009154:Mutation; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D012189:Retrospective Studies; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters