Analysis of optic disk color changes in Alzheimer's disease: A potential new biomarker (original) (raw)
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Clinical Ophthalmology
Objective: To evaluate the feasibility of using optical coherence tomography (OCT) for the detection of Alzheimer's disease (AD), by measuring the thickness of the retinal nerve fiber layer (RNFL) and the ganglion cell layer and inner plexiform layer (GCL-IPL). Material and Methods: This was a single-center, cross-sectional study. The study included 29 patients with AD (mean age ± standard deviation: 75.61 ± 6.24 years) and 29 healthy age-and sex-matched controls. All participants underwent cognitive evaluations using the Montreal Cognitive Assessment test. Measurements of the RNFL thickness, as well as GCL-IPL thickness, were obtained for all participants using OCT. Both RNFL and GCL-IPL parameters were adjusted for best-corrected visual acuity, hypertension, diabetes and dyslipidemia. Results: The mean RNFL thickness was significantly thinner in the AD group than in the control group (85.24 and 90.68 µm, respectively, adjusted P=0.014). The superior quadrant was thinner in the AD group (adjusted P=0.033). The thicknesses did not differ significantly between groups for the other quadrants. The mean GCL-IPL thickness in the AD (68.81 µm) was significantly thinner than that in the controls (76.42 µm) (adjusted P=0.014). Overall, there was a negative correlation between age and mean RNFL; and between age and GCL-IPL thickness (r=−0.338, P=0.010 and r=−0.346, P=0.008, respectively). Conclusion: The mean RNFL and GCL-IPL thicknesses were thinner in the AD group than in the control group. These findings suggest that RNFL and GCL-IPL thickness may be biological markers for AD.
Changes in visual function and retinal structure in the progression of Alzheimer's disease
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 PLOS ONE |
Colour vision deficiencies in Alzheimer's disease
Age and Ageing, 2003
Objective: visual disorders are among the earliest symptoms of Alzheimer's disease. It is, however, still controversial as to whether Alzheimer's disease impairs colour vision. In this study, colour vision of Alzheimer's disease patients was tested using the Ishihara test and the PV-16 choice test. The latter test, primarily designed for children, was chosen in order to avoid problems due to cognitive decline. Methods: 26 patients with mild to severe Alzheimer's disease (M:F=5:21; mean age: 80"9 years, range: 53-95 years) and 25 controls (M:F=5:20; mean age 80"10 years, range: 56-100 years) were rated after undergoing complete neuro-ophthalmologic examination. Results: the Alzheimer's disease patients made significantly more unspecific errors in the Ishihara test (P=0.02) and in the PV-16 choice test (P=0.0008) than the controls. No relation between test performance and severity of Alzheimer's disease was found. Conclusions: Alzheimer's disease patients have an unspecific colour vision deficiency independent of the severity of the disease.
Acta Ophthalmologica, 2012
the retina is an attractive source of biomarkers since it shares many features with the brain. thickness differences in 10 retinal layers between 19 patients with mild Alzheimer's disease (AD) and a control group of 24 volunteers were investigated. Retinal layers were automatically segmented and their thickness at each scanned point was measured, corrected for tilt and spatially normalized. When the mean thickness of entire layers was compared between patients and controls, only the outer segment layer of patients showed statistically significant thinning. However, when the layers were compared point-by point, patients showed statistically significant thinning in irregular regions of total retina and nerve fiber, ganglion cell, inner plexiform, inner nuclear and outer segment layers. Our method, based on random field theory, provides a precise delimitation of regions where total retina and each of its layers show a statistically significant thinning in AD patients. All layers, except inner nuclear and outer segments, showed thickened regions. new analytic methods have shown that thinned regions are interspersed with thickened ones in all layers, except inner nuclear and outer segments. Across different layers we found a statistically significant trend of the thinned regions to overlap and of the thickened ones to avoid overlapping. Alzheimer's disease (AD) is an increasing health issue for elderly people and healthcare services in developed countries. There is wide agreement about the relevance of its early detection, leading to interest in early, convenient and affordable biomarkers. The brain is the main tissue affected in AD, and the retina is the only neuronal tissue that can be analyzed non-invasively in AD. Increasing evidence suggests that retinal analysis can provide insights into brain pathology. In a sample of 2,124 patients with mild AD, Mutlu et al. found that a thinner ganglion cell layer (GCL), nerve fiber layer (NFL) and inner plexiform layer (IPL) are associated with smaller grey matter, white matter and hippocampal volume 1. Ong et al. found that thinner total retinal thickness is associated with smaller grey matter volume only in the temporal lobe, whereas thinner GC-IPL complex is associated with smaller grey matter and white matter volumes in the temporal lobe, as well as smaller grey matter volume in the occipital lobe 2. Casaletto et al. found thinner retinal thickness and GCL to be related to medial temporal lobe atrophy 3. In a homogeneous sample of patients with early-stage AD, Salobrar-Garcia et al. 4 found that peripapillary total retinal thinning accompanies AD development. More recently, our group has found that retinal thinning in the macular area appears at a very early stage of AD 5 , together with a 40% decrease in contrast sensitivity 6. All these findings converge to demonstrate that the volume of brain structures involved in AD is related to retinal thickness and visual function. This suggests that AD-associated neuronal damage and deposits may occur in the retina before they occur in the brain, implying that retinal analyses could allow AD detection during the asymptomatic preclinical period 7,8. Ten retinal layers were segmented and studied: nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), inner
The Retina in Alzheimer's Disease: Histomorphometric Analysis of an Ophthalmologic Biomarker
Investigative Opthalmology & Visual Science
PURPOSE. To provide a histopathologic, morphometric analysis of the retina in Alzheimer's disease (AD). METHODS. Human postmortem retinas from eight patients with AD (mean age: 80 6 12.7 years) and from 11 age-matched controls (mean age: 78 6 16.57 years) were analyzed. The retinas were sampled from the superior quadrant on both the temporal and nasal sides with respect to the optic nerve. Thickness of the inner and outer layers involving the retinal nerve fiber layer (RNFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer (ONL) were measured and compared between controls and AD. A total of 16 measurements of retinal thickness were acquired for each layer. RESULTS. RNFL thinning supero-temporally was significant closest to the optic nerve (~35% thickness reduction; P < 0.001). Supero-nasally, RNFL was thinner throughout all points (~40% reduction; P < 0.001). Supero-temporally, RGCL thinning was pronounced toward the macula (~35% thickness reduction; P < 0.001). Supero-nasally, RGCL showed uniform thinning throughout (~35% reduction; P < 0.001). IPL thinning supero-temporally was statistically significant in the macula (~15% reduction; P < 0.01). Supero-nasal IPL featured uniform thinning throughout (~25% reduction; P < 0.001). Supero-temporally, INL and ONL thinning were pronounced toward the macula (~25% reduction; P < 0.01). Supero-nasally, INL and ONL were thinner throughout (~25% reduction; P < 0.01). CONCLUSIONS. Our study revealed marked thinning in both the inner and outer layers of the retina. These quantified histopathologic findings provide a more comprehensive understanding of the retina in AD than previously reported.
Scientific reports, 2018
The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer's Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer's disease's (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119...
Acta Ophthalmologica Scandinavica, 2001
The authors investigated the correlation between visual field defects detected by automated perimetry and the thickness of the retinal nerve fiber layer measured with optical coherence tomography, and examined whether there is a decrease in retinal nerve fiber layer thickness in the apparently normal hemifield of glaucomatous eyes. Patients and Methods: Forty-one patients with glaucoma and 41 normal control subjects were included in this study. Statistical correlations between the sum of the total deviation of 37 stimuli of each hemifield and the ratio of decrease in retinal nerve fiber layer thickness were evaluated. The statistical difference between the retinal nerve fiber layer thickness of the apparently normal hemifield in glaucomatous eyes and that of the corresponding hemifield in normal subjects was also evaluated. Results: There was a statistically significant correlation in the sum of the total deviation and retinal nerve fiber layer thickness decrease ratio (superior hemifield, P ס 0.001; inferior hemifield, P ס 0.003). There was no significant decrease in retinal nerve fiber layer thickness in the area that corresponded to the normal visual field in the hemifield defect with respect to the horizontal meridian in glaucomatous eyes (superior side, P ס 0.148; inferior side, P ס 0.341). Conclusions: Optical coherence tomography was capable of demonstrating and measuring retinal nerve fiber layer abnormalities. No changes in the retinal nerve fiber layer thickness of the apparently normal hemifield were observed in glaucomatous eyes.
PloS one, 2018
Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas o...
Basic and Clinical Neuroscience (BCN), 2022
Alzheimer disease (AD) is the most common form of dementia worldwide. The modalities to diagnose AD are generally expensive and limited. Both the central nervous system (CNS) and the retina are derived from the cranial neural crest; therefore, changes in retinal layers may reflect changes in the CNS tissue. Optical coherence tomography (OCT) machine can show delicate retinal layers and is widely used for retinal disorders. This study aims to find a new biomarker to help clinicians diagnose AD via retinal OCT examination. Methods: After considering the inclusion and exclusion criteria, 25 patients with mild and moderate AD and 25 healthy subjects were enrolled in the study. OCT was done for all eyes. The central macular thickness (CMT) and the ganglion cell complex (GCC) thickness were calculated. The groups were compared using the SPSS software, v. 22. Results: Both GCC thickness and CMT were significantly decreased in patients with AD when compared to healthy age-and sex-matched individuals. Conclusion: Retinal changes, specifically CMT and GCC thickness, may reflect the AD process in the brain. OCT can be considered a non-invasive and inexpensive method to help diagnose AD.