title: Histopathology of the Retina from a Three Year-Old Suspected to Have Joubert Syndrome.
abstract: OBJECTIVE
  To define the retinal pathology in a 3 year-old eye donor who died from complications of an undiagnosed genetic syndrome.
  
  
  METHODS
  Eyes were fixed and analyzed using macroscopic fundus photography (MF), confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT). Small areas from the perifovea and periphery were processed for histology and indirect immunofluorescence, using antibodies specific to retinal proteins such as rhodopsin, cone arrestin, RPE65 and others. Available medical records were also reviewed.
  
  
  RESULTS
  With all three imaging modalities, the affected donor's eyes lacked the distinct morphological detail typically observed with these techniques in postmortem control eyes. MF images showed a "photonegative effect" due to a hypopigmented macula relative to a hyperpigmented retinal background. cSLO imaging demonstrated a weak autofuorescence signal that was largely devoid of the usual retinal structures compared to the control. SD-OCT suggested disorganization of the affected retina, absence of a photoreceptor layer, and degeneration of the choroid in the macular area. Histologic findings indicated a highly disorganized photoreceptor layer in the macula and periphery. The RPE layer displayed thinning in some regions of the periphery and decreased pigmentation in most areas. Rods and cones were significantly reduced in the affected retina but a few cones were detected in the perifovea. Centrin-2 labeling was mostly absent from the connecting cilium of the photoreceptor cells. Medical record review pointed to a possible clinical diagnosis of Joubert syndrome.
  
  
  CONCLUSIONS
  The retinal degenerative findings, and absence of centrin-2 labeling are compatible with the expected retinal phenotype in patients with Joubert syndrome.
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, USA.
authors.forename: V L
authors.initials: VL
authors.lastname: Bonilha
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Rayborn
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Bell
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Marino
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA.
authors.forename: E I
authors.initials: EI
authors.lastname: Traboulsi
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Hagstrom
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Cleveland, USA; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Hollyfield
keywords: Disorganized photoreceptors; Genetic abnormalities; Histology; Immunohistochemistry; Retina