Abstract

Adaptive optics (AO), when coupled to different imaging modalities, has enabled resolution of various cell types across the entire retinal depth in the living human eye. Extraction of information from retinal cells is optimal when their optical properties, structure, and physiology are matched to the unique capabilities of each imaging modality. Despite the earlier success of multimodal AO (mAO) approaches, the full capabilities of the individual imaging modalities were often diminished rather than enhanced when integrated into multimodal platforms. Furthermore, many mAO designs added unnecessary complexity, making clinical translation difficult. In this study, we present a novel mAO system that combines two complementary approaches, scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT), in one instrument using a simplified optical design, flexible alternation of scanning modes, and independent focus control. The mAO system imaging performance was demonstrated by visualization of cells in their mosaic arrangement across the full depth of the retina in three human subjects, including microglia, nerve fiber bundles, retinal ganglion cells and axons, and capillaries in the inner retina and foveal cones, peripheral rods, and retinal pigment epithelial cells in the outer retina. Multimodal AO is a powerful tool to capture the most complete picture of retinal health.

Highlights

  • High-resolution retinal imaging has gained increased use for disease diagnosis and treatment outcome assessment owing to tremendous technological advances over the last two decades

  • Since its first demonstration for ophthalmic imaging [1], adaptive optics (AO) has been successfully integrated into many imaging modalities, including non-confocal fundus photography, confocal scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and one- and two-photon fluorescence imaging, enabling microscopic views of single retinal cells in the living eye [2,3,4]

  • Various researchers have resolved for the first time in the live human eye, rod photoreceptor cells [10,11,12], cone photoreceptor inner segments [14], the retinal pigment epithelial cell mosaic [5,6,7,8, 13, 49], nerve fiber bundles (NFB) [23, 24], retinal capillaries, vascular mural cells and wall structure [20, 50], and most recently, microglia [22], retinal ganglion cells [35], and the RGC mosaic [22]

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Summary

Introduction

High-resolution retinal imaging has gained increased use for disease diagnosis and treatment outcome assessment owing to tremendous technological advances over the last two decades. Many cells and cellular structures across the entire retinal depth have been resolved using different imaging modalities, including retinal pigment epithelium (RPE) [5,6,7,8,9], cones and rods [10,11,12,13], cone inner segments [14], Henle’s fiber bundles [15, 16], retinal capillaries [17, 18] and vessel walls [19, 20], retinal ganglion cells (RGC) [21, 22], nerve fiber bundles (NFB) [23,24,25], and microglia [22] Each of these AO imaging modalities has unique advantages for resolving particular cell types or retinal features [18], and there has been increased interest in the use of multimodal AO (mAO) systems for a more complete picture of retinal health. Those solutions diminished the full capability of the two imaging modalities, and often added unnecessary system complexity with implementation

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