Abstract
Purpose :
To characterize retinal lesions in subjects at risk of Autosomal Dominant Alzheimer’s Disease (ADAD) and Late Onset Sporadic Alzheimer’s Disease (LOAD).
Methods :
This is a prospective study of Latino subjects with pathogenic ADAD mutations (F388S or A431E substitutions in PSEN1 or V717I substitution in APP). Elderly Latinos who may be at risk for LOAD were recruited as controls from the Los Angeles Latino Eye Study (LALES). All subjects underwent comprehensive neurological and ophthalmological evaluations as well as color fundus photographs. Lesions on fundus photographs were characterized by a trained grader and a retina specialist masked to subject genotype. Features of lesions including number, color, size, retinal quadrant and distance from the optic nerve head (ONH) were recorded (Figure 1). Wilcoxon rank sum test was used to compare differences in continuous variables between ADAD and LOAD groups.
Results :
A total of 41 subjects (80 eyes) were recruited (25 ADAD and 16 controls; median age (IQR) was 40 (19) and 67 (10) years, respectively (p<0.05). Twenty-two and 3 ADAD subjects had PSEN1 and APP mutations, respectively. Most lesions were perivascular, yellow, and appeared intraretinal. There were 385 lesions among all ADAD subjects and 185 lesions among all control subjects (median [IQR], 8[8]) and 4[8.5] respectively, p>0.05). Among subjects with ADAD causing mutations, there were 133[34%], 108[28%], 106 [28%], and 38 [10%] lesions in the superotemporal, inferotemporal, inferonasal and superonasal quadrants, respectively. Among controls, there were 72 [38.9%], 46 [24.8%], 41 [22.2%], and 26 [14.1%], lesions in similar regions, respectively. For ADAD and controls, 88% and 81% of lesions were 3 disc diameters (DD) or further from the ONH, respectively (p>0.05). In terms of size, 89% and 81% of lesions were between 1 to 30 microns in ADAD and controls, respectively (p<0.05). In a few cases from each group, lesions were irregularly shaped and were greater than 400 microns.
Conclusions :
Subjects with mutations for ADAD have perivascular, yellow, intraretinal lesions that appear to occur at higher frequency than similar lesions in elderly Latino subjects who may be at risk for LOAD. These lesions may be manifestations of underlying Alzheimer’s pathology.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.