Biblio OPH
Clinicopathologic Correlation
Arch Ophthalmol. 2005;123:1588-1594.
Objective To provide the clinicopathologic findings of a patient who developed the clinical characteristics of Best disease (typically considered a juvenile macular degeneration) at the age of 75 years after being documented to be ophthalmoscopically normal at the age of 51 years. Design A member of a large family with Best disease, possessing a Y227N mutation in the VMD2 gene (the gene responsible for the disease, which encodes the bestrophin protein), developed small vitelliform lesions in both eyes at the age of 75 years and later developed yellow flecklike depositions at the level of the retinal pigment epithelium (RPE), which were aA Simplified Severity Scale for Age-Related Macular Degeneration AREDS Report No. 18 Age-Related Eye Disease Study Research Group* Arch Ophthalmol. 2005;123:1570-1574. Objective To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). Methods Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. Results The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large ( Conclusion This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study. Results Histopathologically, the retinal outer nuclear layer was attenuated, particularly in the macula. This attenuation was frequently associated with normal RPE. A large area of photoreceptor degeneration was present in the central macula, with loss of the underlying RPE cells. Outside of this region, the RPE density was within normal limits. The peripheral flecks were clusters of basal laminar deposits and drusen. Bestrophin immunohistochemistry revealed labeling along both the basolateral and apical membranes of the RPE. Conclusions Findings characteristic of Best disease may not manifest in a molecularly affected individual until late in life. Mutations in bestrophin appear to lead to extracellular deposit formation outside the macula in some families. The distribution of bestrophin in the RPE suggests that the protein may be mistargeted in those with Best disease who have the Y227N mutation, and that this may be a cause of the associated RPE and photoreceptor dysfunction.
125 µm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor.
*The Writing Team for the Age-Related Eye Disease Study (AREDS) Research Group consists of Frederick L. Ferris, MD; Matthew D. Davis, MD; Traci E. Clemons, PhD; Li-Yin Lee, MS; Emily Y. Chew, MD; Anne S. Lindblad, PhD; Roy C. Milton, PhD; Susan B. Bressler, MD; and Ronald Klein, MD.
Group Information: A complete list of the members of the AREDS Research Group appears in Arch Ophthalmol. 2004;122:723-724.
lso identified in fundus photographs of family members. The patient died at the age of 93 years, and the histological features of the macular lesion and peripheral flecks were examined.
Author Affiliations: Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City (Drs Mullins, Hageman, and Stone and Mr Heffron); Retina Eye Center, Augusta, Ga (Dr Oh); and Howard Hughes Medical Institute, Chevy Chase, Md (Dr Stone). Dr Oh is now with Retinal Consultants of Arizona, Phoenix.