Transscleral optical phase imaging of the human retina

Abstract

The in vivo observation of the human retina at the cellular level is crucial to detect lesions before irreversible visual loss occurs, to follow the time course of retinal diseases and to evaluate and monitor the early effects of treatments. Despite the phenomenal advances in optical coherence tomography (OCT) and adaptive optics systems, in vivo imaging of several retinal cells is still elusive. Here we propose a radically different method compared to OCT, called transscleral optical phase imaging (TOPI), which allows to image retinal cells with high contrast, high resolution, and within an acquisition time suitable for clinical use. TOPI relies on high-angle oblique illumination of the retina, combined with adaptive optics, to enhance the phase contrast of transparent cells. We first present in-vivo images of retinal cells, from the retinal pigment epithelium (RPE) to the nerve and vascular layers of the retina, in eleven healthy volunteers without pupil dilation. The morphology of the cells in vivo is then compared to that of images obtained with the same technique applied on ex vivo human RPE and pig retinas. Finally, we demonstrate the ability of high resolution phase microscopy to image pericytes and microglia around rat retinal capillaries. Our results show the ability of TOPI to image and quantify retinal cells up to the RPE depth within a maximum time of 9 seconds over a field of view of 4.4 x 4.4°, opening new avenue in the in vivo exploration of the deepest layer of the retina in healthy and diseased eyes.

Histologic Cell Shape Descriptors for the Retinal Pigment Epithelium in Age-Related Macular Degeneration: A Comparison to Unaffected Eyes

“…This knowledge could then support clinical diagnostics, as these cell alterations would be visible early on without the requirement of large affected areas to be visualized. Since RPE cells are now trackable in vivo using adaptive optics scanning laser ophthalmoscopy (AOSLO) 16 , 17 or transscleral optical phase imaging (TOPI), 18 cell shape descriptors and AF measures that reliably characterize individual AMD-affected RPE cells are of particular importance.…”

Inverse scattering for reflection intensity phase microscopy

“…Consequently, OBM also relies on the dominant forward-scattering signal from the object, similar to our model. The volumetric scattering medium effectively suppresses the backscattering contribution from the object, making it possible to establish a similar, yet less stringent linear model for quantitative phase recovery [42][43][44].…”

“…In addition, QPI requires accurate scattering models for recovery, which vary significantly in reflection with the imaging modality design [22,41,51,79,91] and desired application [2,22,29,33,41,64]. Specifically, the presence of boundaries or structures near the object can generate additional scattering requiring complex models [2,29,55,67,89] or can result in transmission-like imaging conditions [24,[42][43][44]. These constraints suggest that QPI in reflection with standard microscope designs and computationally efficient, easily implementable inverse scattering models would be highly advantageous for biological research.…”

Anomalous Angiogenesis in Retina

“…These blood vessels and their leaking may form scars, leading to permanent loss of central vision. Diagnosis of wet AMD [ 4 ] has improved with important non-invasive techniques such as optical coherence tomography [ 5 , 6 ] or, quite recently, transscleral optical phase imaging [ 7 ]. The retina contains many membranes and tissue layers that make imaging cells and understanding pathologies difficult.…”