title: Natural History of the Central Structural Abnormalities in Choroideremia: A Prospective Cross-Sectional Study.
abstract: To describe in detail the central retinal structure of a large group of patients with choroideremia (CHM).
  
  
  
  A prospective, cross-sectional, descriptive study.
  
  
  
  Patients (n = 97, age 6-71 years) with CHM and subjects with normal vision (n = 44; ages 10-50 years) were included.
  
  
  
  Subjects were examined with spectral-domain optical coherence tomography (SD OCT) and near-infrared reflectance imaging. Visual acuity (VA) was measured during their encounter or obtained from recent ophthalmic examinations. Visual thresholds were measured in a subset of patients (n = 24) with automated static perimetry within the central regions (±15°) examined with SD OCT.
  
  
  
  Visual acuity and visual thresholds; total nuclear layer, inner nuclear layer (INL), and outer nuclear layer (ONL) thicknesses; and horizontal extent of the ONL and the photoreceptor outer segment (POS) interdigitation zone (IZ).
  
  
  
  Earliest abnormalities in regions with normally appearing retinal pigment epithelium (RPE) were the loss of the POS and ellipsoid zone associated with rod dysfunction. Transition zones (TZs) from relatively preserved retina to severe ONL thinning and inner retinal thickening moved centripetally with age. Most patients (88%) retained VAs better than 20/40 until their fifth decade of life. The VA decline coincided with migration of the TZ near the foveal center. There were outer retinal tubulations in degenerated, nonatrophic retina in the majority (69%) of patients. In general, RPE abnormalities paralleled photoreceptor degeneration, although there were regions with detectable but abnormally thin ONL co-localizing with severe RPE depigmentation and choroidal thinning.
  
  
  
  Abnormalities of the POS and rod dysfunction are the earliest central abnormalities observed in CHM. Foveal function is relatively preserved until the fifth decade of life. Migration of the TZs to the foveal center with foveal thinning and structural disorganization heralded central VA loss. The relationships established may help outline the eligibility criteria and outcome measures for clinical trials for CHM.
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: aleman@mail.med.upenn.edu.
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Grace
authors.initials: G
authors.lastname: Han
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Leona W
authors.initials: LW
authors.lastname: Serrano
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Fuerst
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Charlson
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Pearson
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chung
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Traband
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Maguire
authors.affiliation: Scheie Eye Institute, Perelman School of Medicine, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jessica I W
authors.initials: JI
authors.lastname: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015794:Choroideremia / Q000175:diagnosis* / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D055351:Retinal Neurons / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000000981:diagnostic imaging / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology