title: Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives.
abstract: OBJECTIVE
  To characterize contrast sensitivity (CS) across the visual field for two achromatic spatial-temporal frequencies in 21 families with Stargardt disease (STGD) and to correlate psychophysical impairment with patterns of change in multifocal electroretinography (mfERG).
  
  
  METHODS
  Twenty-seven eyes from patients with STGD, 16 eyes from asymptomatic relatives, and 44 age-matched control eyes were included. Chromatic CS function was assessed by comparing protan, deutan, and tritan (Cambridge Color Test; Cambridge Research Systems Ltd., Rochester, UK) and anomaloscope measures (IF-2; Roland Consult, Wiesbaden, Germany). Achromatic CS measures were obtained with custom-made software in nine locations by using randomly interleaved staircases. The first task-low spatial frequency (LSF)-matched the known frequency-doubling method that is believed to activate the magnocellular pathway preferentially. The second included an intermediate spatial frequency (ISF, 3.5 cyc/deg). mfERGs (RETIscan; Roland Consult) were also obtained. Relatives were screened for ABCA4 mutations by ABCR400 microarray and direct sequencing.
  
  
  RESULTS
  Central impairment of achromatic and chromatic CS (along the three isolation axes) was observed in STGD. LSF and ISF tasks revealed significant and widespread dysfunction in patients and their morphologically unaffected relatives, 80% of whom were found to be ABCA4 mutation carriers. Significant reduction of P1 amplitudes was also observed in both groups.
  
  
  CONCLUSIONS
  CS function is impaired in patients with STGD at distinct spatial-temporal frequencies, which, in addition to the color vision deficits, suggests dual impairment of the magno- parvocellular pathways. STGD morphologically unaffected carriers may show patterns of psychophysical dysfunction that are mirrored by abnormal mfERG responses.
authors.affiliation: Visual Neuroscience Laboratory, Centre for Ophthalmology, IBILI (Institute for Biomedical Research on Light and Image), Faculty of Medicine, Coimbra, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Maia-Lopes
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Silva
authors.forename: Maria Fátima
authors.initials: MF
authors.lastname: Silva
authors.forename: Aldina
authors.initials: A
authors.lastname: Reis
authors.forename: Pedro
authors.initials: P
authors.lastname: Faria
authors.forename: Miguel
authors.initials: M
authors.lastname: Castelo-Branco
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003119:Color Perception Tests; D003117:Color Vision Defects / Q000175:diagnosis* / Q000235:genetics; D015350:Contrast Sensitivity; D004596:Electroretinography; D005260:Female; D020869:Gene Expression Profiling; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011601:Psychophysics; D012160:Retina / Q000473:pathology*; D014794:Visual Fields
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters