Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis

Grazioli, Erica; Zivadinov, Robert; Weinstock‐Guttman, Bianca; Lincoff, Norah S.; Baier, Monika; Wong, Jan Rang; Hussein, Sara; Cox, Jennifer L.; Hojnacki, David; Ramanathan, Murali

doi:10.1016/j.jns.2007.10.020

Cited by 153 publications

(126 citation statements)

References 28 publications

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“…121 These findings may be explained by the reported correlations between RNFL thickness and brain atrophy. 122,123 Not all studies have found the same, however, others have reported an association between cognitive impairment in MS patients and performance in visual function tests such as low contrast sensitivity testing. 124 Early detection of cognitive dysfunction is important, as cognitive symptoms significantly impact the quality of life in MS patients.…”

Section: Cognitive Impairment In Msmentioning

confidence: 97%

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Jones-Odeh

Hammond

2015

Eye

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Glaucoma is a neurodegenerative disorder with established relationships with ocular structures such as the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL). Ocular imaging techniques such as optical coherence tomography (OCT) allow for quantitative measurement of these structures. OCT has been used in the monitoring of glaucoma, as well as investigating other neurodegenerative conditions such as Alzheimer's disease (AD) and multiple sclerosis (MS). In this review, we highlight the association between these disorders and ocular structures (RNFL and GCL), examining their usefulness as biomarkers of neurodegeneration. The average RNFL thickness loss in patients with AD is 11 μm, and 7 μm in MS patients. Most of the studies investigating these changes are cross-sectional. Further longitudinal studies are required to assess sensitivity and specificity of these potential ocular biomarkers to neurodegenerative disease progression. Eye (2015Eye ( ) 29, 1270Eye ( -1284 doi:10.1038/eye.2015; published online 4 September 2015 IntroductionGlaucoma is a neurodegenerative optic neuropathy manifesting with progressive retinal ganglion cell (RGC) and axonal loss, which can result in visual field defects and blindness because of permanent cellular and neuronal damage. Subjective clinical examination of the optic nerve head (ONH) allows for assessment and monitoring of the structural changes associated with glaucoma. However, objective detection of defects in the peripapillary retinal nerve fibre layer (RNFL) by ophthalmoscopy is difficult. The relationship between glaucoma progression and the structural changes observed at the ONH, RGC layer, and RNFL in glaucoma is well established. [1][2][3][4] Early diagnosis and treatment of glaucoma is vital to maintain visual field, as loss of RGCs is irreversible, 5 and even before any detectable visual field defects, there is a substantial loss of RGCs. Morphological abnormalities can develop 3-5 years before any functional loss is detected. 6 Since the introduction of ocular imaging techniques such as optical coherence tomography (OCT), peripapillary RNFL thickness measurements have been used for the detection and monitoring of glaucoma. 7,8 However, the use of OCT has extended beyond RNFL measurements for glaucoma, and has also been used in the investigation of other neurodegenerative disorders such as Alzheimer's disease (AD) 9-11 and multiple sclerosis (MS). [12][13][14] In addition, given the similarities of brain and retinal foetal angiogenesis, 15,16 retinal microvasculature has also been investigated as a biomarker of changes in cerebral vasculature and cognitive decline. [17][18][19] In this review, we examine the relationships between glaucoma, neurodegenerative disease, and cognitive impairment, and the use of RNFL thickness and RGC loss as potential ocular biomarkers for neurodegenerative disorders such as AD and MS. We review the strength of associations between RNFL and RGC and Eye (2015Eye ( ) 29, 1270Eye ( -1284Eye ( © 2015 Macmillan Publis...

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Section: Cognitive Impairment In Msmentioning

confidence: 97%

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Jones-Odeh

Hammond

2015

Eye

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“…Correlation of RNFL thickness with brain atrophy in MS has also been reported. [41][42][43] OCT measures of RNFL thickness could also have prognostic value. 44 Baseline temporal quadrant RNFL atrophy was found to be associated with new relapses and changes in the Expanded Disability Status Scale.…”

Section: Neurodegenerative Diseasementioning

confidence: 99%

Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions

MacGillivray¹,

Trucco²,

Cameron³

et al. 2014

BJR

121

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imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions. Br J Radiol 2014;87:20130832. REVIEW ARTICLERetinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions 1,2 T J MACGILLIVRAY, MSc ABSTRACTThe black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions.Currently about 20 million people in the UK suffer from at least 1 long-term condition (a health problem that cannot be cured but can be controlled by medication or other therapies), and this is set to increase 3-fold over the next decade placing an enormous economic and humanresource strain on the National Health Service.1-3 The retina is unique in the body in allowing easy observation of blood vessels with simple, non-invasive instruments. It is also the only accessible site for studying the central nervous system (CNS) in vivo.4 This makes it a ripe environment for the study of systemic and neurological disease, in a patient-acceptable way. Changes to the retina can occur in some chronic diseases years before other signs become apparent. [5][6][7][8][9] Thus, studying the retina may provide an additional means for clinicians to stratify risk and help identify people who would benefit from early lifestyle changes and preventative therapies, as well as assessing the efficacy of new treatments. In addition, there is some early evidence that certain retinal measures may correlate with disease characterization and also prognosis, which not only provides clinicians with a useful assessment tool but also offers research scientists new avenues to explore in the understanding of the p...

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“…In particular, patients with greater brain atrophy, as measured by validated metrics (such as the brain parenchymal fraction), have a more substantial retinal involvement, as measured by RNFL loss [14,64]. Thus, the eye would seem to be able to accurately model the mechanisms of neurodegeneration and could even be used to detect and monitor neuroprotection in MS.…”

Section: Role For Oct In Modeling Axonal and Neuronal Loss In Msmentioning

confidence: 99%

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

et al. 2011

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Summary: Axonal and neuronal degeneration are important features of multiple sclerosis (MS) and other neurologic disorders that affect the anterior visual pathway. Optical coherence tomography (OCT) is a non-invasive technique that allows imaging of the retinal nerve fiber layer (RNFL), a structure which is principally composed of ganglion cell axons that form the optic nerves, chiasm, and optic tracts. Since retinal axons are nonmyelinated until they penetrate the lamina cribrosa, the RNFL is an ideal structure (no other central nervous system tract has this unique arrangement) for visualizing the processes of neurodegeneration, neuroprotection and, potentially, even neuro-repair. OCT is capable of providing high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and permits objective analysis of the RNFL (axons) as well as ganglion cells and other neurons in the macula. In a systematic OCT examination of multiple sclerosis (MS) patients, RNFL thickness and macular volumes are reduced when compared to disease-free controls.Conspicuously, these changes, which signify disorganization of retinal structural architecture, occur over time even in the absence of a history of acute demyelinating optic neuritis. RNFL axonal loss in MS is most severe in those eyes with a corresponding reduction in low-contrast letter acuity (a sensitive vision test involving the perception of gray letters on a white background) and in those patients who exhibit the greatest magnitude of brain atrophy, as measured by validated magnetic resonance imaging techniques. These unique structure-function correlations make the anterior visual pathway an ideal model for investigating the effects of standard and novel therapies that target axonal and neuronal degeneration. We provide an overview of the physics of OCT, its unique properties as a non-invasive imaging technique, and its potential applications toward understanding mechanisms of brain tissue injury in MS, other optic neuropathies, and neurologic disorders.

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Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis

Cited by 153 publications

References 28 publications

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

How strong is the relationship between glaucoma, the retinal nerve fibre layer, and neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis?

Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

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