Analysis of optic disk color changes in Alzheimer's disease: A potential new biomarker

Bambo, M; García‐Martín, Elena; Gutierrez-Ruiz, Fernando; Pinilla, Juan; Pérez‐Oliván, Susana; Larrosa, José M.; Polo, Vicente; Júlvez, Luis Pablo

doi:10.1016/j.clineuro.2015.02.016

Cited by 39 publications

(41 citation statements)

References 20 publications

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“…Further studies of the AD eye have followed, reporting NFL and macular thinning, as well as optic nerve degeneration. Findings of NFL thinning have indicated a significant reduction of thickness among quadrants of this tissue layer [10, 13, 19, 34, 62, 87, 104, 106, 113, 114, 124, 135, 145–147, 167], although some findings did not reach statistical significance [1, 50, 79, 91, 110, 111, 167]. A small number of studies have provided evidence against NFL thinning.…”

Section: Non-specific Ocular Abnormalities In Ad Patientsmentioning

confidence: 99%

“…Conversely, two recent studies that examined the risk of glaucoma patients developing AD found no relationship [12, 105]. Recently, optic disc color pallor, indicative of axon loss, has been investigated as a potential biomarker, given that the optic discs of AD patients show a significant paleness compared with those of controls [13]. In light of overlap between AD and glaucoma, some researchers have even termed glaucoma “Ocular AD” [16, 129].…”

Section: Non-specific Ocular Abnormalities In Ad Patientsmentioning

confidence: 99%

“…As AMD progresses, patients show central visual field loss [2, 141], which differs from the inferior visual field loss described in some AD patients [175]. The primary degeneration noted in AMD typically takes place in the photoreceptors of the macula and in the underlying RPE, while AD retinas primarily show degeneration in the GCL and NFL [10, 13, 19, 21, 22, 34, 62, 81, 87, 104, 106, 113, 114, 124, 135, 145–147, 167]. Interestingly, Aβ has been detected in the eyes of both AMD and AD patients, within drusen deposits in AMD [42, 122] and as the primary constituent of extracellular fibrillar plaques in AD retinas [107, 113].…”

Section: Ocular Findings Shared By Ad and Amdmentioning

confidence: 99%

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Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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Although historically perceived as a disorder confined to the brain, our understanding of Alzheimer’s disease (AD) has expanded to include extra-cerebral manifestation, with mounting evidence of abnormalities in the eye. Among ocular tissues, the retina, a developmental outgrowth of the brain, is marked by an array of pathologies in patients suffering from AD, including nerve fiber layer thinning, degeneration of retinal ganglion cells, and changes to vascular parameters. While the hallmark pathological signs of AD, amyloid β-protein (Aβ) plaques and neurofibrillary tangles (NFT) comprising hyperphosphorylated tau (pTau) protein, have long been described in the brain, identification of these characteristic biomarkers in the retina has only recently been reported. In particular, Aβ deposits were discovered in post-mortem retinas of advanced and early stage cases of AD, in stark contrast to non-AD controls. Subsequent studies have reported elevated Aβ42/40 peptides, morphologically diverse Aβ plaques, and pTau in the retina. In line with the above findings, animal model studies have reported retinal Aβ deposits and tauopathy, often correlated with local inflammation, retinal ganglion cell degeneration, and functional deficits. This review highlights the converging evidence that AD manifests in the eye, especially in the retina, which can be imaged directly and non-invasively. Visual dysfunction in AD patients, traditionally attributed to well-documented cerebral pathology, can now be reexamined as a direct outcome of retinal abnormalities. As we continue to study the disease in the brain, the emerging field of ocular AD warrants further investigation of how the retina may faithfully reflect the neurological disease. Indeed, detection of retinal AD pathology, particularly the early presenting amyloid biomarkers, using advanced high-resolution imaging techniques may allow large-scale screening and monitoring of at-risk populations.

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Section: Non-specific Ocular Abnormalities In Ad Patientsmentioning

confidence: 99%

Section: Non-specific Ocular Abnormalities In Ad Patientsmentioning

confidence: 99%

Section: Ocular Findings Shared By Ad and Amdmentioning

confidence: 99%

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Ocular indicators of Alzheimer’s: exploring disease in the retina

et al. 2016

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“… This table shows a summary of key studies documenting ocular manifestations in Alzheimer's disease .a Prettyman et al (1997), Fotiou et al (2000), Fotiou et al (2007), Frost et al (2013a), Bittner et al (2014) .b Kerbage et al (2013, 2015) .c Koronyo-Hamaoui et al (2011), Campbell et al (2015), More and Vince (2015) .d Parisi et al (2001), Iseri et al (2006), Berisha et al (2007), Paquet et al (2007), Lu et al (2010), Kesler et al (2011), Kirbas et al (2013), Moreno-Ramos et al (2013), Ascaso et al (2014), Larrosa et al (2014), Cheung et al (2015) .e Berisha et al (2007), de Jong et al (2011), Cheung et al (2014), Frost et al (2013b), Feke et al (2015), Williams et al (2015) .fParisi et al (2001) Krasodomska et al (2010), Sartucci et al (2010), Moschos et al (2012), Stothart et al (2015)g Tsai et al (1991), Bambo et al (2015) .…”

Section: Non-retinal Biomarkersmentioning

confidence: 99%

The Eye As a Biomarker for Alzheimer's Disease

et al. 2016

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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.

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“…Therefore, examination of macular images was suggested as a monitoring tool for the changes in the brain [9, 10]. Changes in retinal morphology such as optic disc changes [11-14], retinal nerve fiber layer thinning [14-16], and loss of retinal ganglion cells [17-20] might be associated with AD. A possible relationship between drusen formation in the macula and the severity of AD [21-24] has also been shown.…”

Section: Introductionmentioning

confidence: 99%

Peripheral Retinal Imaging Biomarkers for Alzheimer’s Disease: A Pilot Study

et al. 2018

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Purpose: To examine whether ultra-widefield (UWF) retinal imaging can identify biomarkers for Alzheimer’s disease (AD) and its progression. Methods: 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. Results: 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 to controls. There was a significant increase in venular width gradient at BL (zone C: 8.425 × 10^–3 ± 2.865 × 10^–3 vs. 6.375 × 10^–3 ± 1.532 × 10^–3, p = 0.008; entire image: 8.235 × 10^–3 ± 2.839 × 10^–3 vs. 6.050 × 10^–3 ± 1.414 × 10^–3, p = 0.004) and a significant decrease in arterial fractal dimension in AD at BL (entire image: 1.250 ± 0.086 vs. 1.304 ± 0.089, p = 0.049) with a trend for both at FU. Conclusions: UWF retinal imaging revealed a significant association between AD and peripheral hard drusen formation and changes to the vasculature beyond the posterior pole, at BL and after clinical progression over 2 years, suggesting that monitoring pathological changes in the peripheral retina might become a valuable tool in AD monitoring.

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Analysis of optic disk color changes in Alzheimer's disease: A potential new biomarker

Cited by 39 publications

References 20 publications

Ocular indicators of Alzheimer’s: exploring disease in the retina

Ocular indicators of Alzheimer’s: exploring disease in the retina

The Eye As a Biomarker for Alzheimer's Disease

Peripheral Retinal Imaging Biomarkers for Alzheimer’s Disease: A Pilot Study

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