Functional Imaging of the Outer Retinal Complex using High Fidelity Imaging Retinal Densitometry

Tom H Margrain,Stephen Todd,Chris Jones,Trevor D Lamb,James Fergusson,Allannah Gaffney,David Atkinson,Alison M Binns,David Henry,Chris Miller,Ashley Wood,Dave Melotte

doi:10.1038/s41598-020-60660-9

Abstract

We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min−1 and v = 0.119 SD 0.046 min−1, respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min−1 for rods and v = 0.206 SD 0.069 min−1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD.

Highlights

Continuous photoreceptor function is dependent on the constant renewal of visual pigment molecules by a physiological process known as the visual cycle[1]
One of the major challenges associated with imaging retinal densitometry (IRD) has been maintaining precise optical alignment with the eye over a period of several minutes, during visual pigment synthesis
The optical density maps produced by IRD correspond to the known distributions of rod and cone photoreceptors

Summary

Introduction

Continuous photoreceptor function is dependent on the constant renewal of visual pigment molecules by a physiological process known as the visual cycle[1]. By measuring rod photoreceptor visual pigment synthesis rates we can probe a key aspect of RPE physiology. By measuring visual pigment synthesis rates we obtain information about the status of a vital physiological process, the visual cycle, and information about the functional integrity of the outer retinal complex i.e. the photoreceptors, RPE, Müller Cells, Bruch’s membrane and the choriocapillaris. Visual pigment synthesis rates can be measured by recording the subtle changes in retinal reflectance associated with the visual cycle using a technique called densitometry[6,7]. One of the major challenges associated with imaging retinal densitometry (IRD) has been maintaining precise optical alignment with the eye over a period of several minutes, during visual pigment synthesis. We reasoned that a similar approach could be used to maintain precise alignment with the pupil of the eye in three dimensions without the need for a dental impression

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