**2. Clinical manifestation of visual deficits in Alzheimer's patients**

Various visual deficits in AD have been reported since 1987 [42]. Cognitive visual changes have been reported in patients in the early stages of AD [43], including difficulties in reading and finding objects [44]-[46], depth perception [43] perceiving structure from motion [44], [46]- [48], color recognition [44], [49], and impairment in spatial contrast sensitivity [47], [50]. Previously, these changes have been attributed to neuronal damage to the visual pathways in the brain rather than the retina [51]. However, there are increasing lines of evidence showing that specific AD like pathology (amyloid plaques and NFT) in the brain can be found in the retina. In 2011, Koronyn-Hamaoui and co-workers [52] identified amyloid plaques in the retinas from AD patients as well as patients in mild cognitive impairment.

Cross-sectional imaging of the retina using optical coherence tomography (OCT) has demon‐ strated a significant reduction of thickness in peripapillary retinal fiber layer (RFL) of patients with early AD when compared with age-matched controls[53]-[57]. The thinning of RFL was observed predominantly in the inferior and superior quadrants, which was consistent with the inferior and superior visual field loss in AD patients[44], [54]. Reduction of the macular thickness has also been reported in AD; and the total volume of the macula is inversely correlated with the severity of the disease[55]. Changes in the optic nerve head have been observed using confocal scanning laser ophthalmoscopy (cSLO). The observed changes include reduced RFL thickness, neuroretinal rim volume and area, and increased cup-disc ratio; suggesting an overall reduction in the number of optic nerve fibers passing through the optic nerve head [58]. These *in vivo* findings are corroborated by the histopathological findings of axonal degeneration in optic nerves, reduced thickness of RFL and a significant reduction in the number of large diameter RGCs in the post-mortem AD retinas [59], [60].

According to the definitions of glaucoma published in 2002 by an international consensus panel [61], glaucoma is thought to be present when at least one eye has typical defects both in structural and functional aspects (optic disc damage and visual field loss, respectively) [62]. Characteristically, the damage indicates the death of RGC in the inner retina and loss of axons in the optic nerve. This structural loss of the axons can be recognized clinically by ophthal‐ moscope or can be detected by imaging devices such as OCT and scanning laser polarimetry. Besides NFL thinning, the similarities between the ocular effects of AD and glaucoma can be observed in pattern electroretinogram (PERG) responses [63], [64], the type of cell loss (large magnocellular RGC) and possibly the mechanisms for loss of RGC (apoptosis) [65], [66]. This may explain the high incidence of glaucoma in AD patients [7], [67]. The involvement of Aβ accumulation and hyperphosphorylated tau protein might be important causes of neurodegn‐ eration of RGCs in glaucoma.
