Alzheimer's disease: screening biomarkers using frequency doubling technology visual field (original) (raw)
Related papers
Valenti 2013 Alzheimer's disease and Frequency Doubling Technology Visual Field
This study was to investigate the feasibility of frequency doubling technology (FDT) visual field testing in Alzheimer's disease (AD) in order to identify early biomarkers of AD in patients already diagnosed with AD and compare the findings to participants not having Alzheimer's disease. This biomarker would be useful in a battery of tests for the early identification of those with AD. It was not the intent to correlate the visual system biomarker with severity of disease, but to determine if the biomarker was present in pass or fail screening criteria. The study showed with very strong significance that the FDT can identify biomarkers of those with AD compared to an age-matched population that does not have AD. FDT is a simple test to take and administer and has been used to screen for eye and retinal diseases such as glaucoma, retinal macular degeneration, and diabetic retinopathy. The results obtained in the FDT readout are analyzed and compared to the age normative database within the system. The FDT ability to screen for AD biomarker in the visual system was significant in those with AD compared to the controls, and the deficits were not related to any ocular pathology.
Changes in Ocular Biomarkers from Normal Cognitive Aging to Alzheimer’s Disease: A Pilot Study
Eye and Brain
To identify ophthalmic findings in Alzheimer's type dementia (ATD) compared to normal subjects. Patients and Methods: This comparative descriptive study included participants from the institution's cognitive fitness center. Complete ophthalmic examinations were performed. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to analyze retinal thickness and vascular density. The Ocular Surface Disease Index (OSDI) score and tear breakup time (TBUT) were used to assess dry eye. The blink rate was counted by a well-trained observer. Cognitive function was evaluated using the Thai Mental State Examination (TMSE) score. Correlation analysis was performed to compare OCT, OCTA parameters, and TMSE. Results: We included 24 ATD patients and 39 normal participants as a control group by age and sex-matched. The prevalence of dry eye using the Asia Dry Eye Society criteria was 15% and 13% in normal and ATD patients, respectively. The differences in OSDI scores, TBUT, and blink rate between the two groups were not statistically significant. The parafoveal and perifoveal macular thickness of the ATD group were significantly lower than that of the control group (p<0.01). All parameters of the vessel density of the ATD group were significantly lower than in the control group, including the whole macular vessel density (p<0.01), optic disc vessel density at the nerve head level (p<0.01), and optic disc vessel density at the radial peripapillary capillary level (p<0.05). After age adjustment, there were no statistically significant differences in all the OCT and OCTA parameters. There was a positive correlation between retinal thickness and vessel density in the macular and optic disc region and TMSE scores. Conclusion: Perifoveal and parafoveal retinal thickness might be more sensitive than peripapillary RNFL thickness to detect neurodegenerative changes in patients with ATD. Macular thickness and vessel density reduction were also positively correlated with cognitive decline.
Frontiers in Neuroscience, 2015
To assess the frequency of glaucoma-like alterations in Alzheimer's disease (AD) patients using Heidelberg Retinal Tomograph III (HRT-3) and Frequency Doubling Technology (FDT) perimetry. Methods: The study included 51 eyes of 51 AD subjects and 67 eyes of 67 age-and sex-matched controls. Subjects underwent an ophthalmological examination including measurements of intraocular pressure (IOP), Matrix FDT visual field testing, optic nerve head morphology and retinal nerve fiber layer thickness (RNFLt) assessment by slit-lamp biomicroscopy and HRT-3. Results: The frequency of alterations was significantly higher in the AD group (27.5 vs. 7.5%; p = 0.003; OR = 4.69). AD patients showed lower IOP (p = 0.000) despite not significantly different values of central corneal thickness (CCT) between the groups (p = 0.336). Of all the stereometric parameters measured by HRT-3, RNFLt was significantly lower in AD patients (p = 0.013). This group also had significantly worse results in terms of Moorfields Regression Analysis (p = 0.027). Matrix showed significantly worse Mean Deviation (MD) (p = 0.000) and Pattern Standard Deviation (PSD) (p = 0.000) values and more altered Glaucoma Hemifield Test (p = 0.006) in AD patients. Pearson's R correlation test showed that Mini Mental State Examination is directly correlated with MD (R = 0.349; p = 0.034) and inversely correlated with PSD (R = −0.357; p = 0.030). Conclusion: Patients with AD have a higher frequency of glaucoma-like alterations, as detected by the use of HRT-3. These alterations were not associated with elevated IOP or abnormal CCT values.
Frontiers in neurology, 2016
Alzheimer's disease (AD) is the most common form of dementia affecting the growing aging population today, with prevalence expected to rise over the next 35 years. Clinically, patients exhibit a progressive decline in cognition, memory, and social functioning due to deposition of amyloid β (Aβ) protein and intracellular hyperphosphorylated tau protein. These pathological hallmarks of AD are measured either through neuroimaging, cerebrospinal fluid analysis, or diagnosed post-mortem. Importantly, neuropathological progression occurs in the eye as well as the brain, and multiple visual changes have been noted in both human and animal models of AD. The eye offers itself as a transparent medium to cerebral pathology and has thus potentiated the development of ocular biomarkers for AD. The use of non-invasive screening, such as retinal imaging and visual testing, may enable earlier diagnosis in the clinical setting, minimizing invasive and expensive investigations. It also potentiall...
Peripheral Retinal Imaging Biomarkers for Alzheimer's Disease: A Pilot Study
Ophthalmic research, 2018
To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer's disease (AD) and its progression. Images were taken using a UWF scanning laser ophthalmoscope (Optos P200C AF) to determine phenotypic variations in 59 patients with AD and 48 healthy controls at baseline (BL). All living participants were invited for a follow-up (FU) after 2 years and imaged again (if still able to participate). All participants had blood taken for genotyping at BL. Images were graded for the prevalence of age-related macular degeneration-like pathologies and retinal vascular parameters. Comparison between AD patients and controls was made using the Student t test and the χ2 test. Analysis at BL revealed a significantly higher prevalence of a hard drusen phenotype in the periphery of AD patients (14/55; 25.4%) compared to controls (2/48; 4.2%) [χ2 = 9.9, df = 4, p = 0.04]. A markedly increased drusen number was observed at the 2-year FU in patients with AD compared ...
Macular Thickness as a Potential Biomarker of Mild Alzheimer's Disease
Ophthalmology, 2014
Although several postmortem findings in the retina of patients with Alzheimer's disease (AD) are available, 1 new biomarkers for early diagnosis and follow-up of AD are still lacking. It has been postulated that the defects in the retinal nerve fiber layer (RNFL) may be the earliest sign of AD, even before damage to the hippocampal region that affects memory. 2 This fact may reflect retinal neuronal-ganglion cell death and axonal loss in the optic nerve in addition to aging. 1 Changes in longitudinal optical coherence tomography (OCT) measurements of RNFL can act as a surrogate marker of axonal health, making OCT an invaluable tool for measuring axonal loss as a biomarker. 2 The goal of this study was to examine the thickness of the macular and peripapillary RNFL with OCT to determine the most predictive area affected in patients with mild AD, Geriatric Depression Scale-4, Reisberg scale, and make comparisons using normal subjects. Twenty patients with mild AD and 28 age-matched control subjects from the Geriatric Unit in the Hospital Clínico San Carlos, Madrid, Spain, were studied. The AD patients met the criteria for AD according to the National Institute of Neurological and Communicative Disorders and StrokeeAlzheimer's Disease and Related Disorders Association and the Diagnostic and Statistical Manual of Mental Disorders IV, having mild cognitive impairment according to the Clinical Dementia Rating scale. Informed consent was obtained from both groups. The research followed the tenets of the Declaration of Helsinki, and the protocol was approved by the local ethics committee. The inclusion criteria for patients were: being free of ocular disease and systemic disorders affecting vision; best-corrected visual acuity (BCVA) of 20/40; AE5 spherocylindrical refractive error; and intraocular pressure of <20 mmHg. All the subjects underwent a complete ophthalmologic examination, including visual acuity, refraction, anterior and posterior segment biomicroscopy, intraocular pressure measurement, dilated fundus examination, and OCT. The RNFL thickness and macular thickness were measured by OCT Model 3D OCT-1000 (Topcon, Japan) after pupil dilatation. The analysis area was centered manually and the absence of segmentation errors was confirmed for each scan. One eye of each patient assigned at random was analyzed. In the peripapillary area the average thickness (360) and the temporal (316 e45), superior (46 e135), nasal (136 e225), and inferior (226 e315) quadrant thicknesses were evaluated. Macular RNFL thickness data were displayed in 3 concentric rings centered in the foveola, distributed as follows: A central macular ring, 1 mm from the fovea; an inner macular ring, 3 mm from the fovea; and an outer macular ring, 6 mm from the fovea. The inner and outer rings were each divided into 4 quadrants (superior, inferior, nasal, and temporal (Fig 1). The data are reported as mean values AE standard deviations. The differences between groups were analyzed using the Manne Whitney U test. Sensitivity at 90% specificity and receiver operating characteristics (ROCs) analysis for discriminating between healthy and mild AD patients were calculated for the RNFL thickness in all the areas studied. Data were processed in a SPSS 19.0. P < 0.05 was considered statistically significant.
The Eye As a Biomarker for Alzheimer's Disease
Frontiers in Neuroscience, 2016
Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in dementia and eventual death. It is the leading cause of dementia and the number of cases are projected to rise in the next few decades. Pathological hallmarks of AD include the presence of hyperphosphorylated tau and amyloid protein deposition. Currently, these pathological biomarkers are detected either through cerebrospinal fluid analysis, brain imaging or post-mortem. Though effective, these methods are not widely available due to issues such as the difficulty in acquiring samples, lack of infrastructure or high cost. Given that the eye possesses clear optics and shares many neural and vascular similarities to the brain, it offers a direct window to cerebral pathology. These unique characteristics lend itself to being a relatively inexpensive biomarker for AD which carries the potential for wide implementation. The development of ocular biomarkers can have far implications in the discovery of treatments which can improve the quality of lives of patients. In this review, we consider the current evidence for ocular biomarkers in AD and explore potential future avenues of research in this area.
Retinal Examination for the Diagnosis of Alzheimer’s Disease
International Journal of Ophthalmic & Pathology, 2014
Objective: To demonstrate AD plaques in retina. Methods: We examined 30 patients with Mild Cognitive İmpairment (MCI). In the patients in whom we found hyper or hypo fluorescent lesions on Fundus Auto Fluorescence (FAF), Optical Scanning Tomography (OCT) was performed through these regions to reveal depositions in the retina. Drusen like spots-dots were noticed in different parts of the retina. 20 randomly chosen patients and 20 age-matched healthy controls were given curcumin to check for the changes in FAF and OCT. Results: In 26 patiens, we were able to find abnormal deposits in different layers. We believe that these plaque-like lesions are related to neuro-degenerative disease. Curcumin caused patchyhypofluorescent FAF to occur and spots seemed brighter on OCT. Conclusion: We stress that all the middle-aged patients who have family history of Alzheimer'sDisease (AD) and/or cognitive defects should have thorough medical examinations including retina exam.
PloS one, 2016
To evaluate the ability of frequency domain optical coherence tomography (fd-OCT) to estimate retinal neural loss in eyes with Alzheimer's disease (AD). We also verified the existence of a correlation between AD-related cognitive impairment and macular and peripapillary retinal nerve fiber layer (RNFL) thickness measurements. fd-OCT scans were obtained from 45 eyes of 24 patients with AD and 48 control eyes. Peripapillary RNFL, macular full-thickness and segmented inner macular thickness parameters were calculated. The inner macular parameters included macular retinal nerve fiber layer (mRNFL) thickness, ganglion cell layer (GCL) plus inner plexiform layer thickness (GCL+), and RNFL plus GCL+ thickness (GCL++). The Mini-Mental State Examination (MMSE) was used to assess cognition in all subjects. The two groups were compared and the relationship between MMSE scores and fd-OCT measurements was verified. Average, superior and inferior quadrant RNFL thickness parameters and all but...
Optometry and Vision Science, 2011
Purpose. To determine the agreement between the Humphrey Matrix perimeter 10-2 test and the 10-2 Humphrey Field Analyzer (HFA) test when assessing visual function in patients with age-related macular degeneration (AMD). Methods. Forty-two eyes of 42 subjects with AMD (average 75.0 years, SD ϭ 6.2: median visual acuity in logarithm of the minimum angle of resolution of 0.26, range, Ϫ0.12 to 1.04) were evaluated with the Matrix and HFA 10-2 visual field tests. Mean deviation (MD), pattern standard deviation, and test time were recorded. We calculated spatial concordance of individual test locations, being the proportion of spatially agreeing locations with identical classification (normal vs. abnormal, p Ͻ 5%) on the pattern deviation plot. As multiple HFA stimuli overlapped with some Matrix locations, several criteria for grouping HFA data into locations were investigated. Results. Both MD and pattern standard deviation were significantly correlated for the two devices (r 2 ϭ 0.79 and r 2 ϭ 0.80, respectively, p Ͻ 0.0001). Using our standard criterion for abnormal HFA locations (Ն50% stimuli abnormal), the median spatial concordance was 0.76, with 95% of tests giving a concordance of Ն0.59. A small, but significant, increase in concordance occurred when a stricter criterion (all stimuli abnormal at a location) was applied. Median fixation loss percentages were 7 and 0% for the HFA and Matrix, respectively. Visual acuity in logarithm of the minimum angle of resolution showed modest correlations with both defect depth (HFA MD: r 2 ϭ 0.39, p Ͻ 0.0001) and size of defect (number of abnormal points on the HFA: r 2 ϭ 0.24, p Ͻ 0.0001). Conclusions. Using a simple metric to calculate spatial concordance, the Matrix 10-2 test quantifies the spatial extent of significant depression of the central visual fields in AMD in a manner similar to the HFA 10-2. The spatial extent and depth of central visual field loss in AMD are only modestly predicted by visual acuity measurements.