Phenotypic marker for early disease detection in dominant late-onset retinal degeneration.
OBJECTIVE
To define early disease expression in autosomal dominant late-onset retinal degeneration (L-ORD), a retinopathy that becomes symptomatic after age 50 and is characterized histopathologically by sub-RPE deposits.


METHODS
Three families with L-ORD were included; two families had postmortem eye donors with retina-wide sub-RPE deposits. Six patients with severe visual loss (ages 62-93) were examined clinically, and 17 available individuals (ages 35-60) at a 50:50 risk to inherit L-ORD were also studied with dark adaptometry. A short-term trial of vitamin A at 50,000 IU/day was conducted in three members. Three-year follow-up examinations were performed in a subset of members.


RESULTS
Family 1 had 12 available members at risk. On initial examination, only one member had fundus abnormalities: yellow-white punctate lesions in the midperipheral fundus. Dark-adaptation kinetics were abnormal in 6 of 12. The youngest age with an abnormality was 35. Family 2 had two available members at risk, both of whom had punctate fundus lesions and abnormal dark adaptation. Family 3 had three available members at risk. One had fundus lesions and abnormal dark adaptation, whereas the others had normal fundi and normal adaptometry. Vitamin A accelerated adaptation kinetics but not to normal rates. Three-year follow-up examinations demonstrated further slowing of adaptation kinetics, whereas rod and cone thresholds remained unchanged.


CONCLUSIONS
Dark-adaptation abnormalities can precede symptoms and funduscopic signs of L-ORD by at least a decade. Short-term, high-dose vitamin A accelerates the kinetics of dark adaptation to a limited degree. The results contribute clues about early pathophysiology of this retinal degeneration and provide additional power for genetic mapping of the L-ORD locus.
Jacobson
S G
SG
Department of Ophthalmology, Scheie Eye Institute, 51 N. 39th Street, University of Pennsylvania, Philadelphia, PA 19104, USA. jacobsos@mail.med.upenn.edu
Cideciyan
A V
AV
Wright
E
E
Wright
A F
AF
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D003623:Dark Adaptation / Q000187:drug effects / Q000502:physiology; D004596:Electroretinography; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D012307:Risk Factors; D014792:Visual Acuity; D014801:Vitamin A / Q000008:administration & dosage
D015415:Biomarkers; D014801:Vitamin A