Ganglion Cell Layer Thinning in Alzheimer’s Disease

Abstract

The main advantages of optical retinal imaging may allow researchers to achieve deeper analysis of retinal ganglion cells (GC) in vivo using optical coherence tomography (OCT). Using this device to elucidate the impact of Alzheimer’s disease (AD) on retinal health with the aim to identify a new AD biomarker, a large amount of studies has analyzed GC in different stages of the disease. Our review highlights recent knowledge into measuring retinal morphology in AD making distinctive between whether those studies included patients with clinical dementia stage or also mild cognitive impairment (MCI), which selection criteria were applied to diagnosed patients included, and which device of OCT was employed. Despite several differences, previous works found a significant thinning of GC layer in patients with AD and MCI. In the long term, an important future direction is to achieve a specific ocular biomarker with enough sensitivity to reveal preclinical AD disorder and to monitor progression.

Ocular Biomarkers for Alzheimer Disease Dementia

“…After duplicates were manually removed, the search retrieved 591 references, of which 32 systematic reviews were obtained in full text. Eighteen of these were excluded for 1 or more of the following reasons: published before 2016 (7 reviews); used surrogates of dementia as a target condition (1 review); used ocular conditions as biomarker, rather than test technique results (2 reviews); and absence of meta-analyses (10 reviews). Five reviews published before 2016 reported on OCT and 2 on retinal microvascular changes .…”

“…Alber et al and Mahajan et al were broad-spectrum but primarily narrative reviews and quantitative data were not considered for meta-analysis. A number of reviews were systematic reviews of OCT data in several neurologic conditions with no meta-analysis. Wu et al provided quantitative data with OCT and OCTA and reported differences between AD and MCI but did not conduct a meta-analysis.…”

“…However, the field is still developing and there are potential risks of bias and small sample size that could hamper efforts, so it remains unclear which methods are most promising. The most widely studied parameters from ophthalmic techniques are RNFL thickness, ganglion cells–inner plexiform layer complex, foveal avascular zone (FAZ) area, vessel density, and perfusion density that are altered in dementia …”

Myopia Alters the Structural Organization of the Retinal Vasculature, GFAP-Positive Glia, and Ganglion Cell Layer Thickness

“…Ocular pathologies exhibiting GCL and RNFL thinning with disease progression include glaucoma [ 70 ], macular degeneration [ 71 ], optic neuritis [ 72 ], and Alzheimer’s disease [ 73 ]. In this study, the RNFL was significantly thinner in myopic marmoset eyes and remained significant after correcting for the effects of magnification secondary to myopic stretch, suggesting that myopia affects ganglion cell axon distribution, which has been described by others in human eyes [ 71 , 74 , 75 , 76 , 77 ].…”

Myopia alters the structural organization of the retinal astrocyte template, associated vasculature and ganglion layer thickness

“…Ocular pathologies exhibiting GCL and RNFL thinning with disease progression include glaucoma(Wang et al, 2009), macular degeneration(Lee and Yu, 2015), optic neuritis(Kupersmith et al, 2016), and Alzheimer’s disease(Lopez-de-Eguileta et al, 2020). In this study, the RNFL was significantly thinner in myopic marmoset eyes and remained significant after correcting for the effects of magnification secondary to myopic stretch, suggesting that myopia affects ganglion cell axon distribution, which has been described by others in human eyes(Grytz et al, 2020, Lee and Yu, 2015, Seo et al, 2017, Chen et al, 2020, Jonas et al, 2020).…”