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.

Keywords: Alzheimer’s disease; amyotrophic lateral sclerosis; biomarker; multiple sclerosis; neurodegeneration; optical coherence tomography; parkinson’s disease; prion disease; retina.

Figure 1.

A spectral domain OCT cross-sectional macula scan of the retinal layers. BM, Bruch’s membrane; GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; OCT, optical coherence tomography; ONL, outer nuclear layer; OPL, outer plexiform layer; PR IS/OS, photoreceptor inner segment/outer segment; RNFL, retinal nerve fibre layer; RPE, retinal pigment epithelium.

Figure 2.

An SD-OCT pRNFL scan of the right eye of a patient who has had ON, demonstrating temporal pRNFL thinning. Red sectors indicate those outside normal limits. pRNFL, peripapillary retinal nerve fibre layer; ON, optic neuritis; SD-OCT, spectral domain optical coherence tomography.

Figure 3.

Ganglion cell layer thickness maps from a segmented SD-OCT scan of the macula from the right eye of a healthy (left) and ON (right) patient. The segmented GCL is selected in this example, demonstrating superior loss of ganglion cells and corresponding thinning. GCL, ganglion cell layer; ON, optic neuritis; SD-OCT, spectral domain optical coherence tomography.