title: Spectral-domain optical coherence tomography staging and autofluorescence imaging in achromatopsia.
abstract: IMPORTANCE Evidence is mounting that achromatopsia is a progressive retinal degeneration, and treatments for this condition are on the horizon. OBJECTIVES To categorize achromatopsia into clinically identifiable stages using spectral-domain optical coherence tomography and to describe fundus autofluorescence imaging in this condition. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study was performed between 2010 and 2012 at the Edward S. Harkness Eye Institute, New York-Presbyterian Hospital. Participants included 17 patients (aged 10-62 years) with full-field electroretinography-confirmed achromatopsia. MAIN OUTCOMES AND MEASURES Spectral-domain optical coherence tomography features and staging system, fundus autofluorescence and near-infrared reflectance features and their correlation to optical coherence tomography, and genetic mutations served as the outcomes and measures. RESULTS Achromatopsia was categorized into 5 stages on spectral-domain optical coherence tomography: stage 1 (2 patients [12%]), intact outer retina; stage 2 (2 patients [12%]), inner segment ellipsoid line disruption; stage 3 (5 patients [29%]), presence of an optically empty space; stage 4 (5 patients [29%]), optically empty space with partial retinal pigment epithelium disruption; and stage 5 (3 patients [18%]), complete retinal pigment epithelium disruption and/or loss of the outer nuclear layer. Stage 1 patients showed isolated hyperreflectivity of the external limiting membrane in the fovea, and the external limiting membrane was hyperreflective above each optically empty space. On near infrared reflectance imaging, the fovea was normal, hyporeflective, or showed both hyporeflective and hyperreflective features. All patients demonstrated autofluorescence abnormalities in the fovea and/or parafovea: 9 participants (53%) had reduced or absent autofluorescence surrounded by increased autofluorescence, 4 individuals (24%) showed only reduced or absent autofluorescence, 3 patients (18%) displayed only increased autofluorescence, and 1 individual (6%) exhibited decreased macular pigment contrast. Inner segment ellipsoid line loss generally correlated with the area of reduced autofluorescence, but hyperautofluorescence extended into this region in 2 patients (12%). Bilateral coloboma-like atrophic macular lesions were observed in 1 patient (6%). Five novel mutations were identified (4 in the CNGA3 gene and 1 in the CNGB3 gene). CONCLUSIONS AND RELEVANCE Achromatopsia often demonstrates hyperautofluorescence suggestive of progressive retinal degeneration. The proposed staging system facilitates classification of the disease into different phases of progression and may have therapeutic implications.
authors: Department of Ophthalmology, Columbia University, New York, New York.
authors: Jonathan P
authors: JP
authors: Greenberg
authors: Department of Clinical Sciences, State University of New York College of Optometry, New York, New York.
authors: Jerome
authors: J
authors: Sherman
authors: The Vitreous, Retina, Macula Consultants of New York, New York4The LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York.
authors: Sandrine A
authors: SA
authors: Zweifel
authors: Department of Ophthalmology, Columbia University, New York, New York.
authors: Royce W S
authors: RW
authors: Chen
authors: Department of Ophthalmology, Columbia University, New York, New York.
authors: Tobias
authors: T
authors: Duncker
authors: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Susanne
authors: S
authors: Kohl
authors: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Britta
authors: B
authors: Baumann
authors: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors: Bernd
authors: B
authors: Wissinger
authors: The Vitreous, Retina, Macula Consultants of New York, New York4The LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York.
authors: Lawrence A
authors: LA
authors: Yannuzzi
authors: Department of Ophthalmology, Columbia University, New York, New York6Bernard and Shirlee Brown Glaucoma Laboratory, Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York 7Department of Pathology and Cell Biology, Columbia Un.
authors: Stephen H
authors: SH
authors: Tsang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003117:Color Vision Defects / Q000145:classification* / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D004596:Electroretinography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D061848:Optical Imaging; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C518238:CNGA3 protein, human; C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels