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Alice Laughlin, John Ringman, Bright Senyo Ashimatey, Anoush Shahidzadeh, Amir H. Kashani; Retinal changes in early-onset Alzheimer disease. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4563.
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Retinal findings are being investigated as indices of neurodegenerative disease. A cross-sectional, observational pilot study was conducted to investigate retinal changes in individuals with a mutation causing early-onset autosomal dominant Alzheimer disease (AD).
Retinal images were examined in 14 subjects, each of whom had at least one first-degree relative with the A431E mutation in PSEN1. Not all subjects had all imaging modalities available. Mutation status and Clinical Dementia Rating Sum of Boxes (CDR-SOB) score, representing overall severity of dementia, were determined. Non-mutation-carrying subjects (NCs) and healthy age-matched subjects (HCs) served as controls. Color fundus photographs (CFP), ultra-widefield photographs (UWF), and autofluorescence images (AF) were inspected for fundus lesions. Retinal layer thicknesses were measured using optical coherence tomography (OCT). Retinal microvasculature was assessed using previously described vessel skeleton density (VSD) and vessel diameter index (VDI) metrics from OCT-angiograms (OCTA). Generalized estimating equations and Pearson correlations were used to assess group differences.
Eight subjects were mutation carriers (MCs; 1 homozygote, 7 heterozygotes); six were NCs. In MCs, CDR scores ranged from normal to severe dementia (0-3), with the most severely affected MC being a homozygote. Hypopigmented and/or refractile lesions were identified in CFP images of 3 MCs (Fig 1). Nothing notable was observed on AF images. Mean temporal peripapillary RNFL thickness was greater in MCs compared with NCs (75 vs 64µm, P=0.006). No differences were observed in mean thickness for other retinal layers. Mean VDI was greater in MCs compared with HCs (2.84 vs. 2.80, P=0.008; Fig 2). No difference was observed in VSD between any groups. Among MCs, there was a significant negative correlation between CDR-SOB score and VSD (R=-0.93, P=0.002).
Retinal biomarkers of AD may include the presence of hypopigmentary lesions as well as alterations in RNFL thickness and capillary density. Further studies are needed to elucidate these changes.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Fig 1. Hypopigmented lesion is observed in the superior nasal aspect.
Fig 2. Mean VDI is increased in MCs compared to HCs. **P<0.01
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