title: In vivo imaging of human cone photoreceptor inner segments.
abstract: OBJECTIVE
  An often overlooked prerequisite to cone photoreceptor gene therapy development is residual photoreceptor structure that can be rescued. While advances in adaptive optics (AO) retinal imaging have recently enabled direct visualization of individual cone and rod photoreceptors in the living human retina, these techniques largely detect strongly directionally-backscattered (waveguided) light from normal intact photoreceptors. This represents a major limitation in using existing AO imaging to quantify structure of remnant cones in degenerating retina.
  
  
  METHODS
  Photoreceptor inner segment structure was assessed with a novel AO scanning light ophthalmoscopy (AOSLO) differential phase technique, that we termed nonconfocal split-detector, in two healthy subjects and four subjects with achromatopsia. Ex vivo preparations of five healthy donor eyes were analyzed for comparison of inner segment diameter to that measured in vivo with split-detector AOSLO.
  
  
  RESULTS
  Nonconfocal split-detector AOSLO reveals the photoreceptor inner segment with or without the presence of a waveguiding outer segment. The diameter of inner segments measured in vivo is in good agreement with histology. A substantial number of foveal and parafoveal cone photoreceptors with apparently intact inner segments were identified in patients with the inherited disease achromatopsia.
  
  
  CONCLUSIONS
  The application of nonconfocal split-detector to emerging human gene therapy trials will improve the potential of therapeutic success, by identifying patients with sufficient retained photoreceptor structure to benefit the most from intervention. Additionally, split-detector imaging may be useful for studies of other retinal degenerations such as AMD, retinitis pigmentosa, and choroideremia where the outer segment is lost before the remainder of the photoreceptor cell.
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States.
authors.forename: Drew
authors.initials: D
authors.lastname: Scoles
authors.affiliation: The Institute of Optics, University of Rochester, Rochester, New York, United States.
authors.forename: Yusufu N
authors.initials: YN
authors.lastname: Sulai
authors.affiliation: Departments of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Langlo
authors.affiliation: The Pangere Center for Inherited Retinal Diseases at the Chicago Lighthouse for People Who Are Blind or Visually Impaired, Chicago, Illinois, United States Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, Illinois, United States.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.affiliation: Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, Alabama, United States.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Curcio
authors.affiliation: Departments of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dubra
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003117:Color Vision Defects / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D009887:Ophthalmoscopy / Q000379:methods*; D015203:Reproducibility of Results; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics; D055211:Retinal Photoreceptor Cell Inner Segment / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics; D041623:Tomography, Optical Coherence / Q000379:methods*
keywords: AOSLO; gene therapy; photoreceptor