Page 48 - GTM-3-3

Global Translational Medicine Ocular changes in Alzheimer’s disease

the sclera and the retina. 70-72 One of the main functions of observed in brain tissue. Vascular impairment in the
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the choroid is to provide nutrients to the retina and there retina discussed previously such as reduced blood flow,
are therefore fewer pericytes in this region compared to and sparser and narrower vessels may also impair Aβ
the capillaries supplying blood to the inner retina. 29,70 The clearance from the outer retina. Accumulated Aβ may
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choroid is also responsible for the clearance of metabolic trigger an inflammatory response, and ultimately cause cell
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waste from the retinal pigment epithelium. Due to the death and choroidal thinning. Choroidal thinning is also
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important functions of this region, structural changes in a common feature in age-related macular degeneration,
the choroid are likely to cause ocular diseases. 25 which involves Aβ accumulation in the form of drusen
along the basal surface of the retinal pigment epithelium.
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A thinner choroid in AD patients compared to healthy
controls has been described. 25,26,74,75 A 2016 study was the Therefore, Aβ toxicity may be responsible for choroidal
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first to observe choroidal thinning in individuals with thinning in both pathologies. Due to the common feature
MCI and AD, revealing that choroidal thinning may be an of choroidal thinning in AMD and AD, choroidal thinning
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early biomarker of AD. Choroidal thinning was further as a diagnostic tool for AD should be limited to non-AMD
correlated with MMSE scores, indicating the potential patients.
use of monitoring the choroid as an indicator of AD 3.6. Visual changes
progression. Moreover, a study using a rat transgenic
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model of AD is consistent with other evidence of a reduced AD is associated with significant structural changes to
thickness of the choroid, but this study also noted that the the retina, retinal vasculature, and choroid, which are
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peripheral choroid is thinner than the central choroid. hypothesized to be caused by Aβ accumulation. These
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There has also been conflicting evidence with one study structures are vital to vision function. Therefore, AD is
reporting no significant correlation between choroidal associated with significant visual alterations as well. It
was reported that individuals with AD are less likely to
thinning and AD; however, the conclusions of this study report their visual impairments compared to healthy
may be limited due to the small sample size. 76
aged-matched controls, potentially leading to undetected
In addition, choroidal thinning was identified as a visual problems. Salobrar-Garcia et al. evaluated the
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part of the normal aging process with an average 16 μm visual changes associated with AD and found significantly
decrease in choroidal thickness occurring each decade. lower visual acuity, contrast sensitivity, color perception,
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A histological study on human retinas revealed that sub- and visual integration in AD patients compared to healthy
foveal choroid thickness is approximately 194 μm at birth age-matched controls. The sample groups in this study
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and decreases to approximately 80 μm around 90 years excluded participants with other eye diseases that could
of age. Cunha et al. were the first to examine choroidal mask the effects of AD. The sample groups were also
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thickness in cognitively normal older subjects using an matched according to age, stage of disease, ethnicity, and
SD-OCT imaging device. The purpose of the study was education level. However, this study did not examine
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to assess choroidal thinning in AD, independent of aging. participants with advanced dementia; only mild and
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Seventy-year-old subjects with mild AD symptoms were moderate AD were considered because participants
compared to two groups of individuals without AD, an age- needed to have sufficient cognitive ability to understand
matched group and an 80-year-old group. Compared to instructions to perform the test. The visual alterations
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the younger control group choroidal thinning was present observed by Salobrar-Garcia et al. are consistent with other
in the older non-diseased age group; however, AD patients studies. 72,81-83 Polo et al. also observed reduced contrast
from the younger cohort showed the most significant sensitivity and color vision in AD patients. Furthermore,
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thinning, revealing that vascular pathology associated with a correlation was identified between visual function and
AD has more of an impact on choroid thickness than the structural changes observed using SD-OCT. Contrast
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normal aging process. 26 sensitivity was the most impacted by AD and had the
The mechanism behind choroidal thinning in AD is still strongest correlation to structural changes compared to
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unclear. However, similar to the thinning of the RNFL, it visual acuity and color vision and changes in macular
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is possibly due to the accumulation of Aβ deposits in the volume and thickness had the strongest correlation to
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choroid. Post-mortem analysis of transgenic mouse models visual impairments.
of AD has revealed Aβ accumulation in the choroid; A possible reason for these visual impairments is due
however, in vivo examinations have not been conducted. to a loss of RGCs. The RGC layer contains parvocellular
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Aβ deposits may trigger inflammatory responses and and magnocellular ganglion cells. The parvocellular
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complement activation resulting in damage to choroidal ganglion cells are smaller and more numerous than the
vasculature, similar to the pathological mechanism magnocellular ganglion cells. They are responsible for
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Volume 3 Issue 3 (2024) 9 doi: 10.36922/gtm.4094