Phenotypic marker for early disease detection in dominant late-onset retinal degeneration

PURPOSE. TO define early disease expression in autosomal dominant late-onse t retinal degeneration (L-ORD), a retinopathy that becomes symptomatic afte r age 50 and is characterized histopathologically by sub-RPE deposits. METHODS. Three families with L-ORD were included; two families had postmort em eye donors with retina-wide sub-RPE deposits. Six patients with severe v isual loss (ages 62-93) were examined clinically, and 17 available individu als (ages 35-60) at a 50:50 risk to inherit L-ORD were also studied with da rk adaptometry. A short-term trial of vitamin A at 50,000 IU/day was conduc ted 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 G of 1 2. 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 l esions and abnormal dark adaptation, whereas the others had normal fundi an d normal adaptometry. Vitamin A accelerated adaptation kinetics but not to normal rates. Three-year follow-up examinations demonstrated further slowin g of adaptation kinetics, whereas rod and cone thresholds remained unchange d. CONCLUSIONS. Dark-adaptation abnormalities can precede symptoms and fundusc opic signs of L-ORD by at least a decade. Short-term, high-dose vitamin A a ccelerates 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.