Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer's disease

Jentsch, Susanne; Schweitzer, Dietrich; Schmidtke, Kai Uwe; Peters, Sven; Dawczynski, J.; Bär, Karl Jürgen; Hammer, Martin

doi:10.1111/aos.12609

Cited by 80 publications

(66 citation statements)

References 40 publications

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“…Nearly a century following the first description of these signs in the brain, documentation of their manifestation in ocular tissues has begun to emerge [1, 69, 91, 100, 107, 113, 163, 178]. Table 1 presents key findings from research on hallmark AD pathology in the ocular tissues of human patients.…”

Section: Hallmark Pathology In Ocular Tissues Of Ad Patientsmentioning

confidence: 99%

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: Hallmark Pathology In Ocular Tissues Of Ad Patientsmentioning

confidence: 99%

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

et al. 2016

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“…Another new technique called fluorescence lifetime imaging ophthalmoscopy (FLIO) has been developed which demonstrates changes in the retina of patients of AD. It uses a scanning laser ophthalmoscope coupled to an excitation pulse laser BLD 440 and detects fluorescence lifetime (Jentsch et al 2015). It measures fluorescence lifetime by measuring time correlated single photon counting in two spectral channels.…”

Section: Fluorescent Ligand Eye Scanning System (Fles)mentioning

confidence: 99%

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Mahajan

Votruba

2017

Acta Ophthalmologica

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Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of senile dementia. It impairs the quality of life of a person and their family, posing a serious economic and social threat in developed countries. The fact that the diagnosis can only be definitively made post‐mortem, or when the disease is fairly advanced, presents a serious problem if novel therapeutic interventions are to be devised and used early in the course of the disease. There is therefore a pressing need for more sensitive and specific diagnostic tests with which we can detect AD in the preclinical stage. The tau proteins and beta‐amyloid proteins start to accumulate 20 years before the symptoms begin to manifest. Detecting them in the preclinical stage would be a potential breakthrough in the management of AD. A high degree of clinical suspicion is needed to correlate problems in cognition with the changes in the eye, particularly the retina, pupil and ocular movements, so that the disease can be detected early and managed in the prodromal phase. In this systematic review, we ask the question whether the retina can be used to make a specific and early diagnosis of AD.

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“…There were reports demonstrating a decrease in the thickness of RNFL in AD patients [5,70,71,72,73,74,75,76], while other studies found no differences in the RNFL thickness of AD patients [77,78]. These inconsistent results might be due to the distinct evaluation techniques, as well as the evaluation criteria, such as the retinal region [73].…”

Section: Retinal Alterations In Admentioning

confidence: 99%

“…A recent study showed that changes in RNFL might be dependent on the progression of the pathology [79]. With the evaluation of RNFL being performed with spectral OCT, a noninvasive and cost-effective technique that allows the quantification of retinal layer thickness, it is reasonable to hypothesize that a reduction in RNFL thickness may be used as an early biomarker for AD [65,74,75]. …”

Section: Retinal Alterations In Admentioning

confidence: 99%

Glia-Mediated Retinal Neuroinflammation as a Biomarker in Alzheimer's Disease

Madeira

Ambrósio²,

Santiago³

2015

Ophthalmic Res

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Alzheimer's disease (AD) is the most common type of dementia worldwide; it is characterized by a progressive decline in cognitive functions and memory, resulting from synaptic and cell loss, and accompanied by a strong neuroinflammatory response. Besides the vast progress in the understanding of the pathophysiology of AD in the past decades, there is still no effective treatment. Moreover, the diagnosis occurs usually at an advanced stage of the disease, where the neurological damage has already occurred. The identification of biomarkers that would allow an early diagnosis of this disease is a major goal that would also help managing AD progression. Due to its cellular and physiological resemblances with the brain, the retina has long been regarded as a window to the brain. Several brain manifestations have been associated with retinal alterations. In AD patients, some structural and functional alterations in the retina can be associated with disease onset. However, only a few studies have focused on the alterations in retinal glial cells associated with AD. This review aims at giving an overview of the AD-associated retinal alterations, particularly in glial cells. The documented alterations in retinal glia will be discussed concerning their potential to predict the brain alterations occurring in AD.

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Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer's disease

Cited by 80 publications

References 40 publications

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

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

Can the retina be used to diagnose and plot the progression of Alzheimer's disease?

Glia-Mediated Retinal Neuroinflammation as a Biomarker in Alzheimer's Disease

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