Wide-Field Three-Dimensional Depth-Invariant Cellular-Resolution Imaging of the Human Retina.

Three-dimensional (3D) cellular-resolution imaging of the living human retina over a large field of view will bring a great impact in clinical ophthalmology, potentially finding new biomarkers for early diagnosis and improving the pathophysiological understanding of ocular diseases. While hardware-based and computational adaptive optics (AO) optical coherence tomography (OCT) have been developed to achieve cellular-resolution retinal imaging, these approaches support limited 3D imaging fields, and their high cost and intrinsic hardware complexity limit their practical utility. Here, this work demonstrates 3D depth-invariant cellular-resolution imaging of the living human retina over a 3 × 3 mm field of view using the first intrinsically phase-stable multi-MHz retinal swept-source OCT and novel computational defocus and aberration correction methods. Single-acquisition imaging of photoreceptor cells, retinal nerve fiber layer, and retinal capillaries is presented across unprecedented imaging fields. By providing wide-field 3D cellular-resolution imaging in the human retina using a standard point-scan architecture routinely used in the clinic, this platform proposes a strategy for expanded utilization of high-resolution retinal imaging in both research and clinical settings.

Multimodal evaluation of an interphotoreceptor retinoid-binding protein-induced mouse model of experimental autoimmune uveitis.

We aimed to characterize the vascular phenotypes of an experimental autoimmune retinal uveitis (EAU) model induced by interphotoreceptor retinoid-binding protein (IRBP) using multimodal imaging techniques. We systemically administered IRBP or vehicle to adult C57BL/6 mice. Fundus photography, optical coherence tomography (OCT), in vivo live confocal imaging using different tracers, OCT angiography (OCTA), and electroretinography (ERG) were performed after IRBP immunization. Hematoxylin and eosin and immunofluorescence staining were performed to characterize the immune response and vascular permeability. Mice with EAU exhibited perivascular inflammation, vitritis, and superficial retinal inflammation on fundus photography and OCT. H&E revealed immune cell infiltration in the perivascular area of the retina and choroid accompanied by a significant degree of perivasculitis that subsequently damaged photoreceptors 3 weeks postimmunization. Immunofluorescence staining showed subsequent transcytosis induction after local microglial activation followed by neutrophil recruitment in the perivascular area. Transcytosis in the superficial and deep vascular areas was improved by immune cell suppression. Intravital in vivo confocal imaging showed signs of neutrophil infiltration and obstructive vasculitis with perivascular leakage 3 weeks postimmunization. OCTA revealed a significant decrease in vascular flow in the deep capillary layer of the retina. Functional analysis showed that scotopic responses were intact at 2 weeks; however, normal photopic and scotopic responses were hardly detected in mice with EAU mice at 3 weeks postimmunization. Our data suggest that inflammatory cell activation and subsequent transcytosis induction in endothelial cells might be a major pathogenic factor for vascular leakage in uveitis, providing new insights into the pathophysiology of retinal vasculitis in noninfectious uveitis.