Phenotyping the Living Human Retina in vivo With Cellular Resolution

Abstract

Purpose: : To visualise cellular structures in the human retina for non-invasive phenotyping of retinal abnormalities including colour-blindness, macular telangiectasis, retinitis pigmentosa and macular hole.

Methods: : A broadband (140 nm full-width-at-half-maximum) Ti:Sapphire laser centred at 800 nm is used for illumination and an achromatizing lens provides compensation of the resulting longitudinal chromatic aberration. Monochromatic aberrations are corrected with adaptive optics utilizing a single, high-stroke (±50 µm) deformable mirror. A high speed (160 k-A-lines/s) image acquisition allows to obtain a volume of 512x512x1536 pix³ in 1.6 s. This imaging modality was applied to normal and pathological retinas.

Results: : The combination of aberration correction and high-speed imaging enabled to achieve an isotropic resolution of 2-3 µm with little motion artefacts. This allowed to visualise and quantify cellular structures for non-invasive phenotyping of the human retina. The extent of cone loss in two colour-blind individuals was exposed and quantified at multiple depths within the retina. Extensive damage to several retinal layers in subjects with macular telangiectasis, retinitis pigmentosa and macular holes was revealed. The performance of the system was also demonstrated through visualisation of cellular structures that pose a great challenge for non-invasive retinal imaging including retinal pigment epithelial cells, choriocapillaris of the choroid, nerve fiber bundles and collagenous plates of the lamina cribrosa, and possibly retinal ganglion cells.

Conclusions: : The depth resolution and penetration of broadband OCT combined with high transverse and axial resolution from monochromatic and longitudinal chromatic aberration compensation provides a powerful tool for non-invasive retinal imaging. This imaging modality allowed for visualisation and quantification of several retinal abnormalities with extensive depth-probing capabilities, allowing to non-invasively phenotype the living human retina.

Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • retina • photoreceptors