title: Microscopic inner retinal hyper-reflective phenotypes in retinal and neurologic disease.
abstract: OBJECTIVE
  We surveyed inner retinal microscopic features in retinal and neurologic disease using a reflectance confocal adaptive optics scanning light ophthalmoscope (AOSLO).
  
  
  METHODS
  Inner retinal images from 101 subjects affected by one of 38 retinal or neurologic conditions and 11 subjects with no known eye disease were examined for the presence of hyper-reflective features other than vasculature, retinal nerve fiber layer, and foveal pit reflex. The hyper-reflective features in the AOSLO images were grouped based on size, location, and subjective texture. Clinical imaging, including optical coherence tomography (OCT), scanning laser ophthalmoscopy, and fundus photography was analyzed for comparison.
  
  
  RESULTS
  Seven categories of hyper-reflective inner retinal structures were identified, namely punctate reflectivity, nummular (disc-shaped) reflectivity, granular membrane, waxy membrane, vessel-associated membrane, microcysts, and striate reflectivity. Punctate and nummular reflectivity also was found commonly in normal volunteers, but the features in the remaining five categories were found only in subjects with retinal or neurologic disease. Some of the features were found to change substantially between follow up imaging months apart.
  
  
  CONCLUSIONS
  Confocal reflectance AOSLO imaging revealed a diverse spectrum of normal and pathologic hyper-reflective inner and epiretinal features, some of which were previously unreported. Notably, these features were not disease-specific, suggesting that they might correspond to common mechanisms of degeneration or repair in pathologic states. Although prospective studies with larger and better characterized populations, along with imaging of more extensive retinal areas are needed, the hyper-reflective structures reported here could be used as disease biomarkers, provided their specificity is studied further.
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: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Higgins
authors.affiliation: Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Cooper
authors.affiliation: Moorfields Eye Hospital, London, United Kingdom Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Dubis
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Summerfelt
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: David V
authors.initials: DV
authors.lastname: Weinberg
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Judy E
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Stepien
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States Department of Biophysics, 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 Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Dubra
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods*; D009887:Ophthalmoscopy / Q000379:methods*; D009901:Optic Nerve Diseases / Q000473:pathology*; D010641:Phenotype; D015203:Reproducibility of Results; D012160:Retina / Q000473:pathology*; D012164:Retinal Diseases / Q000473:pathology*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence / Q000379:methods*
keywords: adaptive optics; inner retina; neuro-ophthalmology; ophthalmoscopy; retinal disease