Visual Features in Alzheimer’s Disease: From Basic Mechanisms to Clinical Overview

Table 1

AD ocular findings in human studies.

Ocular histopathological hallmarks in human studies
Ref.	Population (mean age, range years)	Tissue analyzed	AD stage (early vs. late-onset)	Findings
Williams et al. 2017 [198]	AD (77); Controls (77)	Retina, lens, and optic nerve	Late	No presence of tau, Aβ, ubiquitin, TDP-43, or a-synuclein.
Tsai et al. 2014 [67]	AD (63–95); Control (63–95)	Nasal and temporal regions of the retina	NS	Aβ plaques in retina and reduced choroidal thickness.
Ho et al. 2014 [204]	AD (82/61–92); Controls (74/66–86)	Peripheral nasal retina, posterior retina including the macular region and optic nerve head, and peripheral temporal retina	Late; Definite AD (); Probable AD ()	Cytoplasmic α-synuclein positivity, but not Aβ deposits and abnormal tau accumulation.
Schön et al. 2012 [77]	AD (37–79); Controls (53–60)	Retina	Early and late	Hyperphosphorylated tau but no Aβ plaques or fibrillar tau aggregates.
Koronyo-Hamaoui et al. 2011 [66]	AD (80/48–94); (79/65–92); Controls (76/66–85)	Retina	Late (); Early ()	Aβ40 plaques.
Syed et al. 2005 [205]	AD (81.9 ± 6.54/69–84); Controls (78.5 ± 8.57/66–82)	Optic nerve	Late	The density of axons was reduced in both the center and peripheral portions of the optic nerve with preferential loss of the smaller-sized axons.
Blanks et al. 1996 [68]	(GFAP-ir) AD (64–88); Controls (63–89); Neuronal and cell numbers (GCL); AD (16 retinas 45–92 years); Control (11 retinas 60–89 years)	Retina	Late	Extensive neuronal loss in the entire retina (36.4%), most pronounced in the superior and inferior quadrants, throughout the midperipheral regions (40–49%), and in the far peripheral inferior retina (50–59%). Increase in the astrocyte : neuron ratio. Also, more extensive labeling of glial fibrillary acidic protein immunoreactivity (GFAP-ir) in astrocytes in the GCL, in the Müller cells, and in radial processes.
Curcio and Drucker [206]	AD (67–86); Controls (66–86)	Retina	Late	No evidence of GCL loss between AD and controls.
Blanks et al. 1991 [207]	AD (13 retinas 83/69–93 years); Controls (14 retinas 78/60–98 years)	Retina	Late	The fovea shows a loss of neurons within the GCL, mainly in large and small ganglion cells.
Sadun and Bassi 1990 [129]	AD (10 optic nerves, 3 retinas 76–89 years); Controls (8 optic nerves, 2 retinas 70–79 years)	Optic nerve and retina	Late	Predominant loss of the largest class of retinal ganglion cells (M cells). Retina of 1/3 AD patients also showed degeneration of GCL and their axons in the NFL.
Blanks et al. 1989 [208]	AD (76–93); Controls (60–91)	Optic nerve and retina	Late	Degeneration in the GCL is characterized by a vacuolated appearance of the cytoplasm. Absence of neurofibrillary tangles, neuritic plaques, or amyloid angiopathy.
Hinton et al. 1986 [128]	AD (10 optic nerves, 4 retinas 73–89 years); Controls (73–89)	Optic nerve and retina	Late	Widespread axonal degeneration in optic nerves, decreased in the number of cells in GCL, and reduction in the thickness of NFL. There was no retinal neurofibrillary degeneration or amyloid angiopathy.