title: Multimodal Imaging of Photoreceptor Structure in Choroideremia.
abstract: OBJECTIVE
  Choroideremia is a progressive X-linked recessive dystrophy, characterized by degeneration of the retinal pigment epithelium (RPE), choroid, choriocapillaris, and photoreceptors. We examined photoreceptor structure in a series of subjects with choroideremia with particular attention to areas bordering atrophic lesions.
  
  
  METHODS
  Twelve males with clinically-diagnosed choroideremia and confirmed hemizygous mutations in the CHM gene were examined. High-resolution images of the retina were obtained using spectral domain optical coherence tomography (SD-OCT) and both confocal and non-confocal split-detector adaptive optics scanning light ophthalmoscope (AOSLO) techniques.
  
  
  RESULTS
  Eleven CHM gene mutations (3 novel) were identified; three subjects had the same mutation and one subject had two mutations. SD-OCT findings included interdigitation zone (IZ) attenuation or loss in 10/12 subjects, often in areas with intact ellipsoid zones; RPE thinning in all subjects; interlaminar bridges in the imaged areas of 10/12 subjects; and outer retinal tubulations (ORTs) in 10/12 subjects. Only split-detector AOSLO could reliably resolve cones near lesion borders, and such cones were abnormally heterogeneous in morphology, diameter and density. On split-detector imaging, the cone mosaic terminated sharply at lesion borders in 5/5 cases examined. Split-detector imaging detected remnant cone inner segments within ORTs, which were generally contiguous with a central patch of preserved retina.
  
  
  CONCLUSIONS
  Early IZ dropout and RPE thinning on SD-OCT are consistent with previously published results. Evidence of remnant cone inner segments within ORTs and the continuity of the ORTs with preserved retina suggests that these may represent an intermediate state of retinal degeneration prior to complete atrophy. Taken together, these results supports a model of choroideremia in which the RPE degenerates before photoreceptors.
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Lynn W
authors.identifier: http://orcid.org/0000-0002-1080-1165
authors.initials: LW
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Johnson
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Vesper
authors.initials: V
authors.lastname: Williams
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Summerfelt
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States of America.|Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dubra
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: David V
authors.initials: DV
authors.lastname: Weinberg
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Stepien
authors.affiliation: Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States of America.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.affiliation: Department of Ophthalmology & Visual Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.|The Chicago Lighthouse, Chicago, Illinois, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D015794:Choroideremia / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009154:Mutation; D009887:Ophthalmoscopy / Q000379:methods; D015203:Reproducibility of Results; D012160:Retina / Q000000981:diagnostic imaging* / Q000473:pathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D012162:Retinal Degeneration / Q000000981:diagnostic imaging*; D055211:Retinal Photoreceptor Cell Inner Segment / Q000473:pathology; D012680:Sensitivity and Specificity; D041623:Tomography, Optical Coherence / Q000379:methods; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human