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Evaluation of retinal fiber layer by Optical Coherence Tomography (OCT): A new biomarker in AD?

Alzheimer’s disease (AD) is the major primary cause of dementia, affecting 60%-80% of demented people. According to the World Alzheimer Report, in 2009 35.6 million people worldwide suffered from dementia and the burden is expected to increase to 115.4 million in 2050 (1). Current therapies for AD focus on alleviating the symptoms or slowing the progression of the disease. Treatment strategy is often based on patients who have already been diagnosed with AD, but the pathological process can start one or two decades before the first dementia symptoms occur (2). Therefore, it is crucial to treat asymptomatic individuals in whom degeneration is not yet severe. There is a serious need for biomarkers for the purposes of early diagnosis in the preclinical stages.

There are many methods to biomarker discovery and identification, however new biomarkers for early diagnosis and follow-up of AD are still controversial. Multiple different candidate biomarkers for disease progression have been investigated in AD, but the majority of studies examined some form of brain imaging and measurement of tau protein in the CSF, which mostly have been recommended by the European Federation of Neurological Societies (3,4). Though it has not been recommended as a biomarker by any of these authorities yet, demonstrating retinal nerve fiber loss in the early stage of AD through Optical Coherence Tomography (OCT), can be a non-invasive, quick, simple and repeatable test. OCT is a relatively new non-invasive, non-contact, transpupillary imaging technology that provides high-resolution cross-sectional images of the retinal nerve fiber layer (RNFL) and macular volume. It has been extensively applied to ocular pathologies and is now being studied as a biomarker in various neurodegenerative disorders including MCI, AD, and Parkinson’s disease.

It has been suggested that neuronal loss in RNFL may be the earliest sign of AD, even preceding neurodegeneration in the hippocampus and areas related to memory. Recent studies have shown not only retinal fiber loss in AD, but also in MCI, which is recognized to be a risk factor to AD and lies between normal aging and AD (5). Several studies have examined the loss of retinal ganglion cells (RGCs) and macular thickness by using OCT in patients with AD and correlated it with the severity of the disease. Studies with this approach reported a reduction in the average measurements in the superior and the nasal quadrants (6,7). Some, but not all, observational studies have suggested RNFL loss in different quadrants. One recent study showed significant differences in the superior quadrant thickness of RNFL between the groups, and another study has showed an RNFL thickness reduction in each quadrant. In contrast, a study indicated no relationship between them (6,8,9). A meta-analysis by Xue-Fei He et al., showed that the RNFL thickness reduced in dementia patients compared with normal age-matched control in all the quadrants (10).
These studies indicate the need for further research to draw the frame of the retinal findings related to the severity of the disease, to develop the acceptance of OCT retinal examination as a biomarker in the early stages of AD, and to use an indicator to evaluate the progress. The routine evaluation of retinal nerve fiber layer loss in the elderly population would help to follow the progress of cognitive decline and the response of the illness to the treatment strategies.

References

1. Alzheimer’s Disease International. World Alzheimer Report 2009. Available from: http://www.alz.co.uk/research/files/World%20Alzheimer%20Report.pdf Accessed: June 27, 2014.
2. Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol. 1999;45:358–68.
3. Hort J, O’Brien JT, Gainotti G, Pirttila T, Popescu BO, Rektorova I, et al. EFNS guidelines for the diagnosis and management of Alzheimer’s disease. Eur J Neurol. 2010;17:1236–48.
4. Simić G, Kostović I, Winblad B, Bogdanović N. Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer’s disease. J Comp Neurol. 1997;379:482–94.
5. Petersen RC. Mild cognitive impairment. 2006;367(9527):1979
6. Parisi V, Restuccia R, Fattapposta F, Mina C, Bucci MG, Pierelli F. Morphological and functional retinal impairment in Alzheimer’s disease patients. 2001;112(10):1860-1867
7.Iseri PK, Altinas O, Tokay T, Yuksel N. Relationship between cognitive impairment and retinal morphological and visual functional abnormalities in Alzheimer disease. 2006;26(1):18-24
8. Chi Y, Wang YH, Yang L. The investigation of retinal nerve fiber loss
in Alzheimer’s disease. 2010;46(2):134-139
9. Kergoat H, Kergoat MJ, Justino L, Chertkow H, Robillard A, Bergman H. An evaluation of the retinal nerve fiber layer thickness by scanning laser polarimetry in individuals with dementia of the Alzheimer type. 2001;79(2):187-191
10. Optical coherence tomography assessed retinal nerve fiber layer thickness in patients with Alzheimer’s disease: a meta-analysis. He XF, Liu YT, Peng C, Zhang F, Zhuang S, Zhang JS. Int J Ophthalmol. 2012;5(3):401-5.

Pervin Iseri, MD, Director and Professor, Department of Neurology, Kocaeli University, School of Medicine, Kocaeli, Turkey

Excerpted article as reprint from IPA’s newsletter, the IPA Bulletin, Volume 32, Number 1

Acknowledgements

Acadia Pharmaceuticals Otsuka Pharmaceuticals Cambridge University Press Avanir Pharmaceuticals
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