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    Spectral-Domain OCT Measurements in Alzheimer's Disease: A Systematic Review and Meta-analysis. Chan Victor T T,Sun Zihan,Tang Shumin,Chen Li Jia,Wong Adrian,Tham Clement C,Wong Tien Y,Chen Christopher,Ikram M Kamran,Whitson Heather E,Lad Eleonora M,Mok Vincent C T,Cheung Carol Y Ophthalmology TOPIC:OCT is a noninvasive tool to measure specific retinal layers in the eye. The relationship of retinal spectral-domain (SD) OCT measurements with Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains unclear. Hence, we conducted a systematic review and meta-analysis to examine the SD OCT measurements in AD and MCI. CLINICAL RELEVANCE:Current methods of diagnosing early AD are expensive and invasive. Retinal measurements of SD OCT, which are noninvasive, technically simple, and inexpensive, are potential biomarkers of AD. METHODS:We conducted a literature search in PubMed and Excerpta Medica Database to identify studies published before December 31, 2017, that assessed the associations between AD, MCI, and measurements of SD OCT: ganglion cell-inner plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular thickness. We used a random-effects model to examine these relationships. We also conducted meta-regression and assessed heterogeneity, publication bias, and study quality. RESULTS:We identified 30 eligible studies, involving 1257 AD patients, 305 MCI patients, and 1460 controls, all of which were cross-sectional studies. In terms of the macular structure, AD patients showed significant differences in GC-IPL thickness (standardized mean difference [SMD], -0.46; 95% confidence interval [CI], -0.80 to -0.11; I = 71%), GCC thickness (SMD, -0.84; 95% CI, -1.10 to -0.57; I = 0%), macular volume (SMD, -0.58; 95% CI, -1.03 to -0.14; I = 80%), and macular thickness of all inner and outer sectors (SMD range, -0.52 to -0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness (SMD, -0.67; 95% CI, -0.95 to -0.38; I = 89%) and choroidal thickness (SMD range, -0.88 to -1.03; all P < 0.001) also were thinner in AD patients. CONCLUSIONS:Our results confirmed the associations between retinal measurements of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as biomarkers of AD. 10.1016/j.ophtha.2018.08.009
    Visualization of Focal Thinning of the Ganglion Cell-Inner Plexiform Layer in Patients with Mild Cognitive Impairment and Alzheimer's Disease. Shao Yi,Jiang Hong,Wei Yantao,Shi Yingying,Shi Ce,Wright Clinton B,Sun Xiaoyan,Vanner Elizabeth A,Rodriguez Anny D,Lam Byron L,Rundek Tatjana,Baumel Barry S,Gameiro Giovana Rosa,Dong Chuanhui,Wang Jianhua Journal of Alzheimer's disease : JAD BACKGROUND:A detailed analysis of the tomographic thickness of intraretinal layers may provide more information on neurodegeneration in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). OBJECTIVE:The goal was to analyze tomographic thickness patterns of intraretinal layers in patients with AD andMCI. METHOD:Forty-nine patients (25 AD and 24 MCI) and 21 cognitively normal (CN) controls were imaged using ultra-high-resolution optical coherence tomography to obtain volumetric data centered on the fovea. The segmented intraretinal layers were retinal nerve fiber layer (RNFL), ganglion cell- inner plexiform layer (GCIPL), inner nuclear layer (INL), outer nuclear layer (ONL), outer plexiform layer (OPL), and retinal photoreceptor (PR), in addition to the total retinal thickness(TRT). RESULTS:The thickness differences were negative (thinning) mainly in TRT, RNFL, and GCIPL in both AD and MCI groups in comparison to CN, while the thickness differences were positive (thickening) mainly in ONL and PR in AD. GCIPL of AD and MCI was thinner in superior, nasal superior, and temporal superior quadrants, compared to CN (p < 0.05). GCIPL of the inner superior, inner nasal superior, inner temporal superior, and outer nasal superior sectors was significantly thinner in AD than CN (p < 0.05). GCIPL of the outer superior, inner temporal superior, outer nasal, and temporal superior sectors was significantly thinner in MCI than CN (p < 0.05). CONCLUSION:Focal thinning of the GCIPL was visualized and quantified by detailed partitions in AD and MCI, which provides specific information about neurodegeneration in MCI and AD. 10.3233/JAD-180070
    Outer Retinal Assessment Using Spectral-Domain Optical Coherence Tomography in Patients With Alzheimer's and Parkinson's Disease. Uchida Atsuro,Pillai Jagan A,Bermel Robert,Bonner-Jackson Aaron,Rae-Grant Alexander,Fernandez Hubert,Bena James,Jones Stephen E,Leverenz James B,Srivastava Sunil K,Ehlers Justis P Investigative ophthalmology & visual science Purpose:To investigate outer retinal parameters among patients with various chronic neurodegenerative disorders by using spectral-domain coherence tomography (OCT) in a prospective cross-sectional cohort study. Methods:A total of 132 participants were enrolled following a comprehensive diagnostic evaluation with neurologic, neuropsychology, and magnetic resonance imaging volumetric evaluations. Participants were 50 years or older, either diagnosed with Alzheimer's disease (AD) dementia, amnestic mild cognitive impairment (MCI), non-AD dementia, Parkinson's disease (PD), or age- and sex-matched controls. All participants underwent a macular cube scan for both eyes by using the Cirrus 4000 HD-OCT (Zeiss, Oberkochen, Germany). The OCT image with the best quality was selected for further analysis. Outer retinal parameters including ellipsoid zone mapping and outer nuclear layer metrics were evaluated with a novel software platform. Results:One hundred twenty-four eyes of 124 participants with AD dementia (24 eyes), amnestic MCI (22 eyes), non-AD dementia (20 eyes), PD (22 eyes), and age- and sex-matched controls (36 eyes) were included in the analysis. Eight eyes were excluded either due to the presence of macular disease or poor quality of the OCT image. The mean ages of participants were 65.9 ± 8.9 years. The outer retinal thickness measures did not show any statistical significance between the groups. However, ellipsoid zone to retinal pigment epithelium volume correlated with cognitive testing scores in all study participants. Conclusions:There were no identifiable differences in the outer retinal metrics across neurodegenerative disease groups and controls. The relationship between the degree of cognitive impairment and ellipsoid zone to retinal pigment epithelium volume warrants further study. 10.1167/iovs.17-23240
    Retinal nerve fiber layer thickness in patients with Alzheimer disease. Kirbas Serkan,Turkyilmaz Kemal,Anlar Omer,Tufekci Ahmet,Durmus Mustafa Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society The aim of this study was to investigate retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer disease (AD) without visual impairment using spectral domain optical coherence tomography (SD-OCT) and to compare the results with healthy controls. A total of 80 subjects, including 40 patients with early untreated AD (mean age, 69.3 ± 4.9 years) and 40 healthy controls (mean age, 68.9 ± 5.1 years) were enrolled. Both eyes of patients with AD and controls were imaged using SD-OCT. The average RNFL thickness was significantly less in the AD patients than in controls (65 ± 6.2 μm vs 75 ± 3.8μm; P = 0.001). There was selective thinning of the RNFL in the superior quadrant, the mean superior quadrant RNFL thickness being 76 ± 6.7 μm in AD patients and 105 ± 4.8 μm in controls (P = 0.001). In our study, the thickness of RNFL in patient with AD was lower than that of controls. This suggests that SD- OCT has the potential to be used in the early diagnosis of AD as well as in the study of therapeutic agents. Further studies are needed to validate this technology as a viable ocular biomarker over time in AD. 10.1097/WNO.0b013e318267fd5f
    OCT in Alzheimer's disease: thinning of the RNFL and superior hemiretina. Cunha João Paulo,Proença Rita,Dias-Santos Arnaldo,Almeida Rita,Águas Helena,Alves Marta,Papoila Ana Luísa,Louro Carlota,Castanheira-Dinis António Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie BACKGROUND:Peripapillary retinal nerve fiber layer (pRNFL) and internal macular layer thinning have been demonstrated in Alzheimer's disease (AD) with optical coherence tomography (OCT) studies. The purpose of this study is to compare the pRNFL thickness and overall retinal thickness (RT) in AD patients with non-AD patients, using spectral domain optical coherence tomography (SD-OCT) and determine the sectors most characteristically affected in AD. METHODS:A cross-sectional study was performed to determine the pRNFL and overall macular RT thicknesses in AD and non-AD patients, attending a tertiary hospital center. For pRNFL, the global and six peripapillary quadrants were calculated, and for overall RT values, the nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas were used. A multiple regression analysis was applied to assess the effects of disease, age, gender, spherical equivalent, visual acuity, intraocular pressure, axial length and blood pressure on pRNFL and overall macular RT. RESULTS:A total of 202 subjects, including 50 eyes of 50 patients with mild AD (mean age 73.10; SD = 5.36 years) and 152 eyes of 152 patients without AD (mean age 71.03; SD = 4.62 years). After Bonferroni correction, the pRNFL was significantly thinner for the AD group globally and in the temporal superior quadrant (10.76 μm and 20.09 μm mean decrease, respectively). The RT thickness was also decreased in superior sectors S3 and S6 (mean thinning of 9.92 μm and 11.65 μm, respectively). Spearman's correlation coefficient showed a direct association between pRNFL in the temporal superior quadrant and RT in superior S6 and S3 sectors (r = 0.41; p < 0.001 and r = 0.28; p < 0.001, respectively). CONCLUSIONS:Patients with AD showed a significant thickness reduction in global and temporal superior quadrants in pRNFL and in superior pericentral and peripheral sectors of RT. These findings may reflect a peripapillary and retinal changes characteristic of AD, suggesting the importance of SD-OCT as a potential adjuvant in early diagnosis of AD. Further studies are needed to understand which retinal layers and macular sectors are more useful as potential ocular biomarker over time in AD. 10.1007/s00417-017-3715-9
    Interplay Between Macular Retinal Changes and White Matter Integrity in Early Alzheimer's Disease. Alves Carolina,Jorge Lília,Canário Nádia,Santiago Beatriz,Santana Isabel,Castelhano João,Ambrósio António Francisco,Bernardes Rui,Castelo-Branco Miguel Journal of Alzheimer's disease : JAD This study aims to investigate the relationship between structural changes in the retina and white matter in the brain, in early Alzheimer's disease (AD). Twenty-three healthy controls (mean age = 63.4±7.5 years) and seventeen AD patients (mean age = 66.5±6.6 years) were recruited for this study. By combining two imaging techniques-optical coherence tomography and diffusion tensor imaging (DTI)-the association between changes in the thickness of individual retinal layers and white matter dysfunction in early AD was assessed. Retinal layers were segmented, and thickness measurements were obtained for each layer. DTI images were analyzed with a quantitative data-driven approach to evaluating whole-brain diffusion metrics, using tract-based spatial statistics. Diffusion metrics, such as fractional anisotropy, are markers for white matter integrity. Multivariate and partial correlation analyses evaluating the association between individual retinal layers thickness and diffusion metrics were performed. We found that axial diffusivity, indexing axonal integrity, was significantly reduced in AD (p = 0.016, Cohen's d = 1.004) while in the retina, only a marginal trend for significance was found for the outer plexiform layer (p = 0.084, Cohen's d = 0.688). Furthermore, a positive association was found in the AD group between fractional anisotropy and the inner nuclear layer thickness (p < 0.05, r = 0.419, corrected for multiple comparisons by controlling family-wise error rate). Our findings suggest that axonal damage in the brain dominates early on in this condition and shows an association with retinal structural integrity already at initial stages of AD. These findings are consistent with an early axonal degeneration mechanism in AD. 10.3233/JAD-190152
    Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer's disease. Jentsch Susanne,Schweitzer Dietrich,Schmidtke Kai-Uwe,Peters Sven,Dawczynski Jens,Bär Karl-Jürgen,Hammer Martin Acta ophthalmologica PURPOSE:To determine alterations in the retina of patients with Alzheimer's disease (AD) by the newly developed technique of fluorescence lifetime imaging ophthalmoscopy (FLIO) in a pilot study. METHODS:FLIO set-up uses a scanning laser ophthalmoscope (HRA2, Heidelberg Engineering, Germany), which was modified by the use of an excitation pulse laser BLD440 (Becker&Hickl, Berlin, Germany) and detection of fluorescence lifetime by time-correlated single photon counting (TCSPC; Becker&Hickl) in two spectral channels (channel 1: 490-560 nm, channel 2: 560-700 nm). Least square fit of three exponential functions was used for fluorescence decay analysis. That resulted in three fluorescent components with lifetimes τi , amplitudes αi and relative contributions Qi . 16 patients with AD (mean age 77.2 ± 7.0 years) were investigated. After regular ophthalmic investigation, FLIO examination and OCT examination were performed. Alzheimer-specific clinical data were collected (MMSE, cerebrospinal fluid (CSF) concentration of amyloid-β (1-42), total-tau and phosphorylated tau181 (p-tau181) protein). RESULTS:The FLIO parameters of the second fluorescent component α2 and Q2 (channel 2) correlated significantly with MMSE score (Q2 , R = -0.757, p = 0.007; α2 , R = -0.618, p = 0.043) as well as p-tau181-protein concentration in CSF (Q2 , R = 0.919, p = 0.009; α2 , R = 0.881, p = 0.020) in patients with AD. OCT measurements of retinal nerve fibre layer thickness, optic disc excavation and macular thickness neither correlated with Alzheimer-specific CSF data nor MMSE score. CONCLUSIONS:Unlike conventional techniques, such as OCT, the new technique of FLIO revealed changes in the retina of patients with AD in relation to Alzheimer-specific markers in this pilot study. 10.1111/aos.12609
    Retinal nerve fiber layer thinning in dementia associated with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease. Moreno-Ramos Teresa,Benito-León Julián,Villarejo Alberto,Bermejo-Pareja Félix Journal of Alzheimer's disease : JAD Optical coherence tomography is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL). Previous studies have shown that degenerative changes occur in optic nerve fibers and are manifested as thinning of RNLF in patients with Alzheimer's disease (AD). However, there are no studies on the thickness of the RNLF in other types of dementia, such as dementia with Lewy bodies and dementia associated with Parkinson's disease. In this study, patients fulfilling diagnostic for AD (n = 10), dementia with Lewy bodies (n = 10), dementia associated with Parkinson's disease (n = 10), and cognitively normal age-matched controls (n = 10) underwent optical coherence tomography examinations to measure RNLF thickness. There was a significant decrease in RNLF thickness in each type of dementia compared to the control group (Mann-Whitney test, all p < 0.001). Although patients with dementia with Lewy bodies may have a greater thinning than both patients with AD and dementia associated with Parkinson's disease, the differences were statistically nonsignificant (Kruskal-Wallis test, p = 0.525). The thickness of the RNLF correlated significantly (p < 0.001) with both the Mini-Mental State Examination and the Mattis Dementia Rating Scale scores in all types of dementia; that is to say, the greater the cognitive deterioration, the greater the reduction of thickness of the RNLF. The findings from this study show that retinal involvement measured by optical coherence tomography may also be present in non-AD dementias. 10.3233/JAD-121975
    Visual function and retinal nerve fibre layer degeneration in patients with Alzheimer disease: correlations with severity of dementia. Bambo Maria P,Garcia-Martin Elena,Otin Sofia,Pinilla Juan,Larrosa José M,Polo Vicente,Pablo Luis E Acta ophthalmologica 10.1111/aos.12635
    Altered Macular Microvasculature in Mild Cognitive Impairment and Alzheimer Disease. Jiang Hong,Wei Yantao,Shi Yingying,Wright Clinton B,Sun Xiaoyan,Gregori Giovanni,Zheng Fang,Vanner Elizabeth A,Lam Byron L,Rundek Tatjana,Wang Jianhua Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society BACKGROUND:The goal of the present study was to analyze the macular microvacular network in mild cognitive impirment (MCI) and Alzheimer disease (AD). METHODS:Twelve patients with AD and 19 patients with MCI were recruited together with 21 cognitively normal controls with a similar range of ages. Optical coherence tomography angiography was used to image the retinal microvascular network at the macular region, including retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP). Fractal analysis (box counting, Dbox) representing the microvascular density was performed in different annular zones and quadrantal sectors. The macular ganglion cell-inner plexiform layer (GC-IPL) thickness was measured using Zeiss OCT. The relationship between the retinal microvasculature and clinical manifestations was analyzed. RESULTS:Patients with AD had lower densities of RVN, SVP, and DVP in the annulus, from 0.6 to 2.5 mm in diameter (P < 0.05) in comparison with controls. Patients with MCI had lower density of DVP in the superior nasal quadrant (P < 0.05) than that of the controls. There were no significant differences of GC-IPL thickness among groups (P > 0.05). There was a trend of vascular density loss from control to MCI then AD (P < 0.05). Retinal microvascular density of DVP was correlated with GC-IPL thickness (P < 0.05) in patients with AD, but not in patients with MCI and controls. CONCLUSIONS:Patients with AD had less density of retinal microvascular networks than controls. Our findings suggest the presence of retinal microvascular dysfunction in AD. 10.1097/WNO.0000000000000580
    Thinner changes of the retinal nerve fiber layer in patients with mild cognitive impairment and Alzheimer's disease. Liu Dachuan,Zhang Lina,Li Zhen,Zhang Xuxiang,Wu Yue,Yang Huiqing,Min Baoquan,Zhang Xinqing,Ma Daqing,Lu Yan BMC neurology BACKGROUND:Alzheimer's disease (AD) is the most common form of dementia and patients often have visual disorders. Mild cognitive impairment (MCI) is characterized by a memory deficit when compared with those of a similar age and education level which could indicate an earlier onset of AD. The aim of this study is to measure the changes of the retinal nerve fiber layer (RNFL) thickness of AD and MCI patients in comparison with the normal age controls. METHODS:The RNFL thickness was assessed using optical coherence tomography (OCT) in patients with MCI, AD (mild, moderate and severe) and the age matched controls. RESULTS:The thickness of RNFL in the superior quadrant and total mean values are gradually and significantly decreased from MCI to severe AD when compared to that in the controls. There is also a significant reduction of the retinal nerve fiber layer in the inferior quadrant in severe AD patients. CONCLUSIONS:Our data indicate that the retinal nerve fiber layer degeneration is paralleled with dementia progression. Owing to its non-invasive and cost effective nature, monitoring RNFL thickness may have a value in assessing disease progression and the efficacy of any treatments. 10.1186/s12883-015-0268-6
    Retinal texture biomarkers may help to discriminate between Alzheimer's, Parkinson's, and healthy controls. Nunes Ana,Silva Gilberto,Duque Cristina,Januário Cristina,Santana Isabel,Ambrósio António Francisco,Castelo-Branco Miguel,Bernardes Rui PloS one A top priority in biomarker development for Alzheimer's disease (AD) and Parkinson's disease (PD) is the focus on early diagnosis, where the use of the retina is a promising avenue of research. We computed fundus images from optical coherence tomography (OCT) data and analysed the structural arrangement of the retinal tissue using texture metrics. We built clinical class classification models to distinguish between healthy controls (HC), AD, and PD, using machine learning (support vector machines). Median sensitivity is 88.7%, 79.5% and 77.8%, for HC, AD, and PD eyes, respectively. When the same subject has the same classification for both eyes, 94.4% (median) of the classifications are correct. A significant amount of information discriminating between multiple neurodegenerative states is conveyed by OCT imaging of the human retina, even when differences in thickness are not yet present. This technique may allow for simultaneously diagnosing Alzheimer's and Parkinson's diseases. 10.1371/journal.pone.0218826
    Greater attenuation of retinal nerve fiber layer thickness in Alzheimer's disease patients. Shi Zhongyong,Wu Yujie,Wang Meijuan,Cao Jing,Feng Wei,Cheng Yan,Li Chunbo,Shen Yuan Journal of Alzheimer's disease : JAD Thinning of retinal nerve fiber layer (RNFL) may reflect neurodegeneration of the central nervous system, which has been reported as part of the neuropathogenesis of Alzheimer's disease (AD). Specifically, AD patients have thinner RNFL as compared to age-matched normal controls. However, whether reduction of RNFL over time can predict those at higher risk to develop cognitive deterioration remains unknown. We therefore set out a prospective clinical investigation to determine both the reduction of RNFL thickness and the deterioration of cognitive function over a period of 25 months in 78 participants (mean age 72.31 ± 3.98 years, 52% men). The participants were categorized as stable participants whose cognitive status remained unchanged (n = 60) and converted participants whose cognitive status deteriorated, which was diagnosed by DSM-VI (for AD) and Petersen's definition (for mild cognitive impairment) (n = 18). Here we show for the first time that the converted participants had greater reduction of RNFL thickness than the stable participants. Specifically, the reduction in the thickness of the inferior quadrant RNFL in the converted participants was greater than that in stable participants [-11.0 ± 12.8 (mean ± standard deviation) μm versus 0.4 ± 15.7 μm, p = 0.009]. These data showed that greater reduction in the inferior quadrant of RNFL thickness might indicate a higher risk for the old adults to develop cognitive deterioration. These findings have established a system to embark on a larger scale study to further test whether changes in RNFL thickness can serve as a biomarker of AD. 10.3233/JAD-131898
    Comparison of Retinal Microvasculature in Patients With Alzheimer's Disease and Primary Open-Angle Glaucoma by Optical Coherence Tomography Angiography. Zabel Przemyslaw,Kaluzny Jakub J,Wilkosc-Debczynska Monika,Gebska-Toloczko Martyna,Suwala Karolina,Zabel Katarzyna,Zaron Agata,Kucharski Robert,Araszkiewicz Aleksander Investigative ophthalmology & visual science Purpose:Comparison of retinal microvasculature within the macula and the optic nerve head in the eyes of patients with Alzheimer's disease (AD), primary open-angle glaucoma (POAG), and in a healthy control (HC) group, using optical coherence tomography angiography (OCTA). Methods:In this cross-sectional study, 27 patients with AD, 27 with POAG, and 27 healthy controls were enrolled. The Mini-Mental State Examination test was used to assess cognitive function. Ophthalmic examination included OCTA, which was used for the imaging of vascular flow within the layer of radial peripapillary capillaries (RPCs), and also in the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the retina. Results:In the AD group, the density of vessels in DVP was significantly reduced and the foveal avascular zone was increased when compared to POAG and HC groups (P < 0.001). Patients with POAG had a significantly reduced vessel density in RPCs and SVP as compared to AD and HC groups (P < 0.001). The average thickness of peripapillary retinal nerve fiber layer was correlated with the vessel density in SVP in patients with POAG (Pearson's r = 0.66; P = 0.0002) and was significantly lower in POAG and AD groups than in the HC group (P < 0.001). Conclusions:AD and POAG are neurodegenerative diseases associated with apoptosis of nerve cells and impairment of microvasculature. Despite the fact that in both diseases there are abnormalities of the entire retinal vascular system, significant microcirculatory impairment in POAG patients affects superficial vessels, whereas in AD patients it affects vessels located in the deeper retinal layers. 10.1167/iovs.19-27028
    Detection of structural and electrical disturbances in macula and optic nerve in Alzheimer's patients and their correlation with disease severity. Sen Sagnik,Saxena Rohit,Vibha Deepti,Tripathi Manjari,Sharma Pradeep,Phuljhele Swati,Tandon Radhika,Kumar Pawan Seminars in ophthalmology : To evaluate and compare structural and functional changes in macula and optic nerve in Alzheimer disease (AD) patients and healthy subjects.: Both eyes of 20 AD patients and 40 age-matched healthy controls were evaluated. All subjects were evaluated by cognitive testing and comprehensive ophthalmological examination, including visual acuity, visual fields, color vision, contrast sensitivity, anterior, and posterior segment examination, optical coherence tomography, multifocal electroretinography (mfERG), and pattern-reversal visual evoked potential (pVEP).: AD patients showed significantly reduced contrast sensitivity, thinner nerve fiber layer, ganglion cell layer andmacular volume. Multifocal ERG wave amplitudes were significantly reduced with delayed implicit times, which correlated significantly with the inner retinal layer thinning and poorer disease severity scores. The correlation with structural changes and disease severity was highest for pVEP, which showed significant derangement in AD patients.: Subclinical visual dysfunction may be present in AD patients, which may be detected as inner retinal thinning. A probable photoreceptor abnormality may also form a part of the AD disease process. 10.1080/08820538.2020.1748203
    Abnormal retinal nerve fiber layer thickness and macula lutea in patients with mild cognitive impairment and Alzheimer's disease. Gao LiYan,Liu Ying,Li XiaoHong,Bai QuanHao,Liu Ping Archives of gerontology and geriatrics OBJECTIVE:We investigated possible abnormalities in the retinal nerve fiber layer (RNFL) and macula lutea of patients diagnosed with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and tested for any correlation with the severity of dementia. METHODS:A total of 72 subjects, comprising 25 AD patients, 26 MCI patients and 21 healthy individuals (controls) were enrolled in this study. The thickness of the RNFL and volume of the macula lutea was determined using optical coherence tomography (OCT). RESULTS:When compared with controls, we found statistically significant thinning of the RNFL in AD patients at all clock-hour positions except 12:00, and nasal quadrant, 2:00, 3:00 and 4:00. After adjusting several risk factors, the average thickness of the RNFL was reduced in MCI patients compared to AD patients, with specific reductions at inferior quadrant, 5:00 and 6:00. Compared to controls, MCI patients showed a significant decrease in RNFL thickness only in the temporal quadrant, 8:00, 9:00 and 10:00. We found significant reduction in the volume of the macula lutea both in AD and MCI patients. Finally, we could not establish any correlation between patient Mini-Mental State Examination (MMSE) scores (an estimation of the severity of cognitive impairment) and any OCT parameter. CONCLUSION:Retinal degeneration in AD and MCI patients results in decreased thickness of the RNFL, and reduced macular volume in AD and MCI patients. However, there seems to be no correlation between these changes and the severity of dementia. 10.1016/j.archger.2014.10.011
    Retinal Microvascular and Neurodegenerative Changes in Alzheimer's Disease and Mild Cognitive Impairment Compared with Control Participants. Yoon Stephen P,Grewal Dilraj S,Thompson Atalie C,Polascik Bryce W,Dunn Cynthia,Burke James R,Fekrat Sharon Ophthalmology. Retina PURPOSE:Evaluate and compare the retinal microvasculature in the superficial capillary plexus (SCP) in Alzheimer's disease (AD), mild cognitive impairment (MCI), and cognitively intact controls using OCT angiography. OCT parameters were also compared. DESIGN:Cross-sectional study. PARTICIPANTS:Seventy eyes from 39 AD participants, 72 eyes from 37 MCI participants, and 254 eyes from 133 control participants were enrolled. METHODS:Participants were imaged using Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Dublin, CA) and underwent cognitive evaluation with Mini-Mental State Examination. MAIN OUTCOME MEASURES:Vessel density (VD) and perfusion density (PD) in the SCP within the Early Treatment Diabetic Retinopathy Study 6-mm circle, 3-mm circle, and 3-mm ring were compared between groups. Foveal avascular zone (FAZ) area, central subfield thickness (CST), macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness were also compared. RESULTS:Alzheimer's participants showed significantly decreased SCP VD and PD in the 3-mm ring (P = 0.001 and P = 0.002, respectively) and 3-mm circle (P = 0.003 and P = 0.004, respectively) and decreased SCP VD in the 6-mm circle (P = 0.047) compared with MCI and significantly decreased SCP VD and PD in the 3-mm ring (P = 0.008 and P = 0.004, respectively) and 3-mm circle (P = 0.015 and P = 0.009, respectively) and SCP PD in the 6-mm circle (P = 0.033) when compared with cognitively intact controls. There was no difference in SCP VD or PD between MCI and controls (P > 0.05). FAZ area and CST did not differ significantly between groups (P > 0.05). Alzheimer's participants showed significantly decreased GC-IPL thickness over the inferior (P = 0.032) and inferonasal (P = 0.025) sectors compared with MCI and significantly decreased GC-IPL thickness over the entire (P = 0.012), superonasal (P = 0.041), inferior (P = 0.004), and inferonasal (P = 0.006) sectors compared to controls. MCI participants showed significantly decreased temporal RNFL thickness (P = 0.04) compared with controls. CONCLUSIONS:Alzheimer's participants showed significantly reduced macular VD, PD, and GC-IPL thickness compared with MCI and controls. Changes in the retinal microvasculature may mirror small vessel cerebrovascular changes in AD. 10.1016/j.oret.2019.02.002
    [The relationship between cognitive impairment and changes in retinal neuroarchitectonics]. Bogolepova A N,Makhnovich E V,Jyravleva A N Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova OBJECTIVE:To study the relationship between cognitive deficits and retinal neuroarchitectonics in Alzheimer's disease, vascular dementia, and glaucoma based on optical coherence tomography. MATERIAL AND METHODS:A comprehensive examination of 90 patients with Alzheimer's disease, vascular dementia and glaucoma was conducted. The patients were divided into three groups of 30 people each. The groups were comparable by gender and age and initial socio-economic status. All patients underwent a comprehensive neurological and neuropsychological study as well as optical coherence tomography. RESULTS AND CONCLUSION:The results of optical coherence tomography in Alzheimer's disease and glaucoma reveal retinal changes in the perifocal region in the upper and lower quadrants. In patients with vascular dementia, the process is observed in the foveal (central) region of the retina, which can be considered as a potential biomarker of the neurodegenerative damage. The severity of cognitive deficit in the Alzheimer's disease group correlates with the degree of degeneration in the layers of the peripapillary layer of the nerve fibers of the retina of the temporal region, the perifocal region of the lower quadrant of the retina, ganglion cells, and the inner plexiform layers of the retina. In the vascular dementia group, the severity of cognitive deficit positively correlates with the degree of cell degeneration in the foveal region of the inner plexiform retinal layer. 10.17116/jnevro20201200917
    The Retina in Alzheimer's Disease: Histomorphometric Analysis of an Ophthalmologic Biomarker. Asanad Samuel,Ross-Cisneros Fred N,Nassisi Marco,Barron Ernesto,Karanjia Rustum,Sadun Alfredo A Investigative ophthalmology & 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 ± 12.7 years) and from 11 age-matched controls (mean age: 78 ± 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. 10.1167/iovs.18-25966
    Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline. Asanad Samuel,Fantini Michele,Sultan William,Nassisi Marco,Felix Christian M,Wu Jessica,Karanjia Rustum,Ross-Cisneros Fred N,Sagare Abhay P,Zlokovic Berislav V,Chui Helena C,Pogoda Janice M,Arakaki Xianghong,Fonteh Alfred N,Sadun Alfredo A,Harrington Michael G PloS one BACKGROUND:Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. METHODS:As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. RESULTS:Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) μm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS:Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology. 10.1371/journal.pone.0232785
    Evaluation of retinal nerve fiber layer thickness in Alzheimer disease using spectral-domain optical coherence tomography. Güneş Alime,Demirci Seden,Tök Levent,Tök Özlem,Demirci Serpil Turkish journal of medical sciences BACKGROUND/AIM:To evaluate the retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer disease (AD) and to compare the results with those of healthy controls. MATERIALS AND METHODS:Forty patients (mean age: 75.02 ± 6.34 years; 23 women) with untreated AD and 40 age-, sex-, and education-matched healthy patients were examined in this case-control prospective study. All patients underwent detailed ophthalmic and neurological examination. The Mini Mental State Examination (MMSE) was performed and RNFL thickness was measured using spectral-domain optical coherence tomography. The association between RNFL and MMSE score was also assessed. RESULTS:The average RNFL thickness was 84 ± 7.0 µm in AD patients and 107 ± 6.3 µm in healthy subjects (P < 0.001). The mean MMSE score was 21.9 ± 2.13 in AD patients. There was no significant correlation between the RNFL thickness and MMSE score. CONCLUSION:Patients with AD had reduced RNFL thickness in all quadrants compared with the control group. This finding suggests that RNFL thickness analysis may be useful in the early diagnosis of AD.
    Retinal nerve fibre layer thickness changes in Alzheimer's disease: Results from a 12-month prospective case series. Trebbastoni Alessandro,D'Antonio Fabrizia,Bruscolini Alice,Marcelli Michela,Cecere Michela,Campanelli Alessandra,Imbriano Letizia,de Lena Carlo,Gharbiya Magda Neuroscience letters PURPOSE:To compare the 12-month peripapillary retinal nerve fibre layer (pRNFL) thickness change between AD patients and normal subjects. METHODS:In this prospective case series, thirty-six patients with a diagnosis of mild to moderate AD and 36 age-matched control subjects were included. All the subjects underwent neuropsychological (MMSE, ADAS-Cog and CDR) and ophthalmological evaluation, including spectral domain optical coherence tomography (SD-OCT), at baseline and after 12 months. RESULTS:Compared with controls, AD patients had a significant reduction of the total pRNFL thickness, as well as the pRNFL thickness of the inferior and superior quadrants (p=0.04, p=0.001, and p=0.01, respectively, adjusted for baseline pRNFL measurement, age, gender, and axial length). Correlation analysis showed a significant relationship between inferior pRNFL thickness change and ADAS-Cog scores change (r=-0.35, p=0.02) as well as CDR scores at 12 months (r=-0.39, p=0.008). CONCLUSIONS:Compared with controls, AD patients had a significant reduction in pRNFL thickness over a period of 12 months. The pRNFL reduction was more prominent in the inferior quadrant and paralleled patient's cognitive decline. 10.1016/j.neulet.2016.07.006
    Peripapillary Retinal Nerve Fiber Layer Thickness in Patients with Alzheimer's Disease: A Comparison of Eyes of Patients with Alzheimer's Disease, Primary Open-Angle Glaucoma, and Preperimetric Glaucoma and Healthy Controls. Zabel Przemysław,Kałużny Jakub J,Wiłkość-Dębczyńska Monika,Gębska-Tołoczko Martyna,Suwała Karolina,Kucharski Robert,Araszkiewicz Aleksander Medical science monitor : international medical journal of experimental and clinical research BACKGROUND The aim of this study was to assess and compare peripapillary retinal nerve fiber layer (RNFL) thickness in patients with Alzheimer's disease (AD), primary open-angle glaucoma (POAG), preperimetric glaucoma (PPG), and healthy controls with the use of Spectral Domain Optical Coherence Tomography (SD-OCT). MATERIAL AND METHODS Thirty patients with AD, 30 patients with POAG, 30 patients with PPG, and 30 healthy controls were enrolled in this cross-sectional study. Only 1 randomly selected eye of each patient was analyzed. Every subject underwent a thorough ophthalmological examination and OCT of the optic disc. The peripapillary RNFL thickness in each of the 6 sectors and globally was analyzed. RESULTS The RNFL was thinnest in patients with POAG. The mean RNFL thickness value was 60.97±12.97 µm and it was significantly lower than in healthy controls (106.30±8.95 µm), patients with PPG (93.20±12.04 µm), and AD patients (95.73±13.52 µm). Mean RNFL thickness in patients with AD was significantly lower when compared to healthy controls, and was higher compared to eyes with POAG, while there were no significant differences compared to patients with PPG. CONCLUSIONS Neuronal damage in the central nervous system (CNS) also affects to retinal axons. A major problem is to distinguish the cause for a moderate decrease in the RNFL thickness. This is particularly true for patients with glaucoma who have not been diagnosed with changes in the visual field. It is not possible to distinguish the cause of a mild decrease in the RNFL thickness based on the SD-OCT. This may result in misdiagnosis of glaucoma, unnecessary use of anti-glaucoma eye drops, and a delayed diagnosis of AD. 10.12659/MSM.914889
    Retinal Nerve Fiber Layer Thinning in Alzheimer's Disease: A Case-Control Study in Comparison to Normal Aging, Parkinson's Disease, and Non-Alzheimer's Dementia. Pillai Jagan A,Bermel Robert,Bonner-Jackson Aaron,Rae-Grant Alexander,Fernandez Hubert,Bena James,Jones Stephen E,Ehlers Justis P,Leverenz James B American journal of Alzheimer's disease and other dementias Retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and macular volume (MV) utilizing spectral domain optical coherence tomography (SD-OCT) were compared among patients with Alzheimer's disease (AD) dementia, non-Alzheimer's disease (non-AD) dementia, amnestic mild cognitive impairment (aMCI), Parkinson's disease (PD), and age- and sex-matched controls in a cross-sectional cohort study. A total of 116 participants were diagnosed and evaluated (21 AD, 20 aMCI, 20 non-AD, 20 PD, and 34 controls) after comprehensive neurological, neuropsychology, and magnetic resonance imaging (MRI) volumetric evaluations. Retinal nerve fiber layer thickness, GCL thickness, and MV were measured. Analysis of variance models were used to compare groups on MRI volumetric measures, cognitive test results, and SD-OCT measures. Associations between SD-OCT measures and other measures were performed using mixed-effect models. Spectral domain optical coherence tomography analysis of retinal markers, including RNFL thickness, GCL thickness, and MV, did not differ between amnestic MCI, AD dementia, PD, non-AD, dementia, and age- and sex-matched controls in a well-characterized patient cohort. 10.1177/1533317515628053
    Analysis of the Retinal Nerve Fiber Layer Thickness in Alzheimer Disease and Mild Cognitive Impairment. Kwon Jin Young,Yang Ji Ho,Han Ji Sang,Kim Do Gyun Korean journal of ophthalmology : KJO PURPOSE:To compare the retinal nerve fiber layer (RNFL) as well as the macula volume and thickness in the eyes of age-matched healthy controls with no cognitive disabilities with those of elderly people with mild cognitive impairment (MCI) or Alzheimer disease (AD). We used optical coherence tomography (OCT) to determine the effectiveness of the above quantities for early diagnosis of MCI or AD. METHODS:Ninety eyes were considered in this study, split between 30 normal eyes, 30 eyes from patients with MCI, and 30eyes from patients with AD. All subjects underwent ophthalmologic and cognitive examinations, and measurements of the RNFL thickness as well as macular volume and thickness were taken for all patients using OCT. RESULTS:The mean RNFL thickness upon OCT was significantly thinner in the AD group than in the MCI group (p = 0.01). The RNFL was thinner in the superior quadrant in patients with AD when compared to the healthy controls (p = 0.03). The RNFL thicknesses in the inferior, nasal, and temporal quadrants did not differ significantly between the groups. Measurements in the 12 clock-hour zones revealed that zone 11 had a significantly thinner RNFL in the AD group as compared with the healthy control group (p = 0.02). In zone 2, the MCI group had a significantly thinner RNFL than the AD group (p = 0.03). CONCLUSIONS:Our OCT findings revealed a neuroanatomic difference in the RNFL thickness among the three groups, i.e., the AD, MCI, and healthy control groups. This suggests that a change in average RNFL thickness could be a meaningful index for diagnosing early AD. 10.3341/kjo.2016.0118
    [Assessment of changes in the retina of patients with Alzheimer's disease]. Guliyeva R N Vestnik oftalmologii PURPOSE:To assess the thickness of the retinal nerve fiber layer and its morphometric parameters using optical coherent tomography in Alzheimer's disease (AD). MATERIAL AND METHODS:The study included 105 patients, among which 45 were with AD and 60 patients without AD (control group). Visual acuity of each eye was measured using Snellen chart, intraocular pressure according to Goldman, and cognitive state on the MMSE scale. All patients underwent optical coherence tomography. RESULTS:The average thickness of the nerve fibers of the retina in patients with AD was lower by 27.0%, in the temporal, upper and lower quadrants - by 24.0, 17.9 and 24.9%, respectively. The thickness in the nasal quadrant with AD was reduced by 15.4%. Excavation to diameter ratio, as well as vertical and horizontal excavation to diameter ratios on average exceeded the benchmark by 12.5%, 23.4% and 30.8% (<0.05), respectively. There was a decrease in the size of the area of the neuroretinal belt and the area of the disk by an average of 28.5% (<0.05) and 8.8%, respectively. The average thickness, the thickness in the upper and lower segments of the ganglion cell complex is reduced, the indices of focal and global loss of the volume of retinal ganglion cells complex are increased respectively by 1.7 (<0.05) and 2.8 times (<0.01). CONCLUSION:In patients with moderate AD, the thickness of retinal nerve fibers (RNFL) in the temporal, upper, and lower segments decreases significantly (<0.001); a statistically significant (<0.05) increase in the excavation to diameter ratio of the optic nerve head and a decrease in the area of the neuroretinal belt is observed; the increase in the indices of focal and global loss of the volume of ganglion cells complex is statistically significant (<0.01). 10.17116/oftalma202013603174