title: Refined staging for chorioretinopathy in long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency.
abstract: OBJECTIVE
  Neonatal screening and earlier diagnosis have improved the prognosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency, which causes a need to refine the staging of the pigmentary chorioretinopathy and thus improve monitoring and comparability of patients under dietary therapy.
  
  
  METHODS
  Seven children with LCHAD deficiency caused by homozygous G1528C mutation attended sequential fundus photography for stage 2 chorioretinopathy in 1997–2006. After arranging 21 pairs of fund us photographs according to the severity of the fundus changes,the images best representing 3 different grades of pigmentary deposits (P1–P3) and retinal pigment epithelial(RPE) atrophy (A1–A3) were chosen as reference photographs.To evaluate the substaging, 29 pairs of photographs were graded according to the reference photographs.
  
  
  RESULTS
  In the assessment of pigmentary deposits, the 3 ophthalmologists agreed in 41% and differed by a single substage in 45% of instances (combined weighted ĸ statistic was 0.38, indicating moderate agreement). In pairwise comparisons,the weighted ĸ statistic ranged from 0.31 to 0.56 (agreement, 71–81%). In the assessment of RPE atrophy, all 3 raters agreed in 17% and 2 raters in 70% of instances (combined ĸ statistic 0.018, indicating poor agreement).
  
  
  CONCLUSIONS
  Despite variation in imaging techniques and limitations in the visual assessment of fundus photographs, the agreement obtained in grading the pigmentary deposits was comparable to that reported for photographic grading of retinopathy of prematurity. We recommend photographic documentation and substaging based on reference photographs in the follow-up of LCHAD retinopathy. The refined staging allows a more detailed assessment on the progression of the retinopathy and optimization of the therapeutic protocols in individual patients and between centres using different therapeutic protocols.
authors.affiliation: Department of Pediatric Neurology and Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Tyni
authors.forename: Tuuli
authors.initials: T
authors.lastname: Immonen
authors.forename: Päivi
authors.initials: P
authors.lastname: Lindahl
authors.forename: Anna
authors.initials: A
authors.lastname: Majander
authors.forename: Tero
authors.initials: T
authors.lastname: Kivelä
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D001284:Atrophy; D002675:Child, Preschool; D006801:Humans; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; D010781:Photography; D017354:Point Mutation; D012164:Retinal Diseases / Q000145:classification* / Q000201:enzymology* / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000473:pathology
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D063989:Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase