Retinal Nerve Fiber Layer Thickness in Patients With Alzheimer Disease

Kırbaş, Serkan; Türkyılmaz, Kemal; Anlar, Ömer; Tüfekçi, Ahmet; Durmuş, Mustafa

doi:10.1097/wno.0b013e318267fd5f

Cited by 189 publications

(173 citation statements)

References 13 publications

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“…This is consistent with previous OCT findings 13, 15, 16, 17, 18, 20. The preferential loss of fibers in the superior quadrant is also compatible with the predominant inferior visual field defect documented in AD patients 56.…”

Section: Discussionsupporting

confidence: 92%

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Melanopsin retinal ganglion cell loss in Alzheimer disease

Morgia

Ross‐Cisneros

Koronyo

et al. 2015

Annals of Neurology

321

397

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ObjectiveMelanopsin retinal ganglion cells (mRGCs) are photoreceptors driving circadian photoentrainment, and circadian dysfunction characterizes Alzheimer disease (AD). We investigated mRGCs in AD, hypothesizing that they contribute to circadian dysfunction.MethodsWe assessed retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in 21 mild‐moderate AD patients, and in a subgroup of 16 we evaluated rest–activity circadian rhythm by actigraphy. We studied postmortem mRGCs by immunohistochemistry in retinas, and axons in optic nerve cross‐sections of 14 neuropathologically confirmed AD patients. We coimmunostained for retinal amyloid β (Aβ) deposition and melanopsin to locate mRGCs. All AD cohorts were compared with age‐matched controls.ResultsWe demonstrated an age‐related optic neuropathy in AD by OCT, with a significant reduction of RNFL thickness (p = 0.038), more evident in the superior quadrant (p = 0.006). Axonal loss was confirmed in postmortem AD optic nerves. Abnormal circadian function characterized only a subgroup of AD patients. Sleep efficiency was significantly reduced in AD patients (p = 0.001). We also found a significant loss of mRGCs in postmortem AD retinal specimens (p = 0.003) across all ages and abnormal mRGC dendritic morphology and size (p = 0.003). In flat‐mounted AD retinas, Aβ accumulation was remarkably evident inside and around mRGCs.InterpretationWe show variable degrees of rest–activity circadian dysfunction in AD patients. We also demonstrate age‐related loss of optic nerve axons and specifically mRGC loss and pathology in postmortem AD retinal specimens, associated with Aβ deposition. These results all support the concept that mRGC degeneration is a contributor to circadian rhythm dysfunction in AD. ANN NEUROL 2016;79:90–109

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Section: Discussionsupporting

confidence: 92%

“…In vivo studies with optical coherence tomography (OCT) corroborated these findings, showing a reduction of the retinal nerve fiber layer (RNFL) thickness in AD patients 12, 13, 14, 15, 16, 17, 18, 19, 20. Accumulation of Aβ in the retina of AD patients has also been reported in a few studies.…”

mentioning

confidence: 60%

Melanopsin retinal ganglion cell loss in Alzheimer disease

Morgia

Ross‐Cisneros

Koronyo

et al. 2015

Annals of Neurology

321

397

View full text Add to dashboard Cite

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“…No statistically significant differences in GC-IPL thickness between AD and MCI most affected. While some studies report preferential superior quadrant RNFL thinning in AD, which would explain the predominantly inferior visual field defects previously described in AD [40,45,47,54,[70][71][72], other authors have reported different findings; these results are presented in Table 1. A meta-analysis of TD-OCT studies in AD demonstrated that peripapillary RNFL thinning occurred in all retinal quadrants [73].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 91%

“…A meta-analysis of TD-OCT studies in AD demonstrated that peripapillary RNFL thinning occurred in all retinal quadrants [73]. However, more recent SD-OCT studies have reported different findings, with most SD-OCT studies suggesting selective superior RNFL thinning [39,54,70]. Two more recent meta-analyses, which used both TD-OCT and SD-OCT studies, aimed to determine the diagnostic utility of OCT measurements of RNFL thickness in AD [74,75].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Cunha

Moura-Coelho

Proença

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on invivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.

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“…Recent studies have revealed degenerative changes in optic nerve fibers, causing thinning of the retinal nerve fiber layer (RNFL) in patients with AD (Berisha et al 2007; Kirbas et al 2013). The RNFL comprises axons originating in retinal ganglion cells and can be measured using ocular imaging technologies such as optical coherence tomography (OCT), which provides non-invasive, rapid, objective and reproducible measurements.…”

mentioning

confidence: 99%