title: Retinal morphology of patients with achromatopsia during early childhood: implications for gene therapy.
abstract: OBJECTIVE
  While older children and adults with achromatopsia have been studied, less is known of young children with achromatopsia.
  
  
  OBJECTIVE
  To characterize the macular and foveal architecture of patients with achromatopsia during early childhood with handheld spectral-domain optical coherence tomographic imaging and to make phenotype-genotype correlations.
  
  
  METHODS
  Comparative case series of 9 patients with achromatopsia and 9 age-matched control participants at a tertiary ophthalmology referral center.
  
  
  METHODS
  Patients underwent complete ocular examination, full-field electroretinography, handheld spectral-domain optical coherence tomographic imaging, and screening for genetic mutations.
  
  
  RESULTS
  The mean (SD) age of the patients with achromatopsia was 4.2 (2.4) years, and the mean (SD) age of the control participants was 4.0 (2.1) years. Cone-driven responses to photopic single-flash or 30-Hz stimuli were nonrecordable in 7 patients and severely attenuated in 2. Rod-driven responses to dim scotopic single-flash stimuli were normal in 7 patients and mildly subnormal in 2. Six patients (67%) had foveal ellipsoid zone disruption, of which 1 had a hyporeflective zone. Four patients (44%) had foveal hypoplasia. The average total retinal thicknesses of the macula and fovea in the patients with achromatopsia were 14% and 17% thinner than in the control participants (P < .001 and P = .001), which was mostly due to the outer retina that was 18% and 26% thinner than in control participants (both P < .001), respectively. Genetic testing revealed a common homozygous mutation in CNGB3 in 5 patients with complete achromatopsia and heterozygous mutations in CNGA3 in 2 patients with incomplete achromatopsia. The youngest and worst-affected patient harbored compound heterozygous mutations in CNGB3 and a single mutation in CNGA3.
  
  
  CONCLUSIONS
  In early childhood, there is a spectrum of foveal pathology that is milder than reported in older individuals with achromatopsia, which suggests the need for early therapeutic intervention. Neither age alone nor genotype alone predicts the degree of photoreceptor loss or preservation. Thus, in anticipation of future gene therapy trials in humans, we propose that handheld spectral-domain optical coherence tomography is an important tool for the early assessment and stratification of macular architecture in young children with achromatopsia.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Paul
authors.initials: P
authors.lastname: Yang
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Keith V
authors.initials: KV
authors.lastname: Michaels
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Courtney
authors.affiliation: Baylor Visual Function Center, Baylor University Medical Center, Dallas, Texas.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Greninger
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Leah
authors.initials: L
authors.lastname: Reznick
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Karr
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Lorri B
authors.initials: LB
authors.lastname: Wilson
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Weleber
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Pennesi
mesh_terms: D002648:Child; D002675:Child, Preschool; D003117:Color Vision Defects / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D016368:Frameshift Mutation; D056726:Genetic Association Studies; D015316:Genetic Therapy; D006801:Humans; D007223:Infant; D008297:Male; D009759:Nystagmus, Pathologic / Q000175:diagnosis; D020795:Photophobia / Q000175:diagnosis; D012030:Refractive Errors / Q000175:diagnosis; D012160:Retina / Q000473:pathology*; D012164:Retinal Diseases / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: C518238:CNGA3 protein, human; C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels