Retinal correlates of neurological disorders

Abstract

Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.

Macular Thickness Decrease in Asymptomatic Subjects at High Genetic Risk of Developing Alzheimer’s Disease: An OCT Study

“…In patients with established AD, a reduction in mRNFL thickness has been demonstrated in different sectors [ 37 , 41 , 42 , 43 ]. The difference between the inclusion criteria of these patients, in relation to the MMSE, makes the classification of the different stages of AD not equivalent.…”

Association of retinal nerve fiber abnormalities with serum CNTF and cognitive functions in schizophrenia patients

“…This in turn provides the base for considering reduction in RNFL thickness as possible cost-effective and non-invasive biomarker alone or in combination with other markers for early stage identification of schizophrenia in patients. Retinal structure abnormalities have been extensively reported as biomarkers for various other neurological conditions such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis and prion diseases ( Yap et al, 2019 ). However, further follow-up research should be carried out in high-risk relatives to clarify if the retinal changes in schizophrenia occurred as a genetic endophenotype.…”

Early alterations of neurovascular unit in the retina in mouse models of tauopathy

“…The retina comprises several cell types including retinal neurons, vascular cells, microglia and glial cells. It is an extension of the neural network of the brain and shares many similar pathophysiological changes and underlying mechanisms with the brain during neurodegenerative diseases including AD [ 8 , 12 , 17 , 18 , 20 , 25 , 33 – 35 , 47 , 57 , 64 ]. Since the retina is not wrapped by the skull, it is much easier to observe the retina than the brain noninvasively.…”

“…Additionally, due to the anatomical and functional characters, the pathological changes in the retina may precede those in the brain. These features make the retina an appealing source of noninvasive biomarkers as well as an alternative platform to study neurovascular coupling in tauopathy [ 64 ]. Although previous studies have some exploration of retinal abnormality in different AD-related models [ 8 , 12 , 18 , 20 , 25 , 33 , 47 , 58 , 61 ], retinal vascular changes in this process are largely unknown; and quantitative and temporal analyses for the alterations of different retinal cell types are missing.…”