Changes in visual function and retinal structure in the progression of Alzheimer's disease

Abstract

Background: Alzheimer's Disease (AD) can cause degeneration in the retina and optic nerve either directly, as a result of amyloid beta deposits, or secondarily, as a result of the degradation of the visual cortex. These effects raise the possibility that tracking ophthalmologic changes in the retina can be used to assess neurodegeneration in AD. This study aimed to detect retinal changes and associated functional changes in three groups of patients consisting of AD patients with mild disease, AD patients with moderate disease and healthy controls by using non-invasive psychophysical ophthalmological tests and optical coherence tomography (OCT).

Methods: We included 39 patients with mild AD, 21 patients with moderate AD and 40 age-matched healthy controls. Both patients and controls were ophthalmologically healthy. Visual acuity, contrast sensitivity, colour perception, visual integration, and choroidal thicknesses were measured. In addition, OCT and OCT angiography (OCTA) were applied.

Findings: Visual acuity, contrast sensitivity, colour perception, and visual integration were significantly lower in AD patients than in healthy controls. Compared to healthy controls, macular thinning in the central region was significant in the mild AD patients, while macular thickening in the central region was found in the moderate AD group. The analysis of macular layers revealed significant thinning of the retinal nerve fibre layer, the ganglion cell layer and the outer plexiform layer in AD patients relative to controls. Conversely, significant thickening was observed in the outer nuclear layer of the patients. However, mild AD was associated with significant thinning of the subfovea and the nasal and inferior sectors of the choroid. Significant superonasal and inferotemporal peripapillary thinning was observed in patients with moderate disease.

Conclusions: The first changes in the mild AD patients appear in the psychophysical tests and in the central macula with a decrease in the central retinal thickness. When there was a disease progression to moderate AD, psychophysical tests remained stable with respect to the decrease in mild AD, but significant thinning in the peripapillary retina and thickening in the central retina appeared. The presence of AD is best indicated based on contrast sensitivity.

Fig 1. Flow diagram patient's inclusion.

Fig 2. OCT report of retinal thickness analysis.

(A) Concentric macular rings and four peripapillary quadrants (B) Rectangular grid 6x6 macular sectors and peripapillary thickness for each 12-o’clock hour and (C) Macular thickness segmentation of 10 retinal layers.

Fig 3. Median data of the psychophysical tests.

(A) Visual acuity, (B) contrast sensitivity, (C) desaturated Rue 28-hue color test, and (D) perception digital test. Each bar represents the median ± interquartile range. * P < 0.05 versus control. ** P < 0.01 versus control. Mann-Whitney U test.

Fig 4. Colorimetric percentage differences of retinal thickness between groups.

(A) Macular OCT. Upper: OCT concentric circular rings. Bottom: 6x6 mm rectangular grid, (B) Peripapillary OCT. Upper: Four peripapillary quadrants. Bottom: 12-o’clock hour position segmentation. In red, thickness decrease; in green thickening. In bold: *P < 0.05. **P < 0.01. Mann-Whitney U test.

Fig 5. Colorimetric percentage differences of the all retinal layers between mild AD and control group.

In red, thickness decrease; in green thickening. *P < 0.05. **P < 0.01. Mann-Whitney U test.