112-degree field of view high-resolution single-shot retinal imaging of rodents enabled by swept-source OCT angiography

Introduction:: Retinopathy, a major cause of visual impairment and blindness worldwide, involves vascular complications in the peripheral region of the retina. The development of an ultra-wide field (UWF) optical coherence tomography angiography (OCTA) system tailored for rodent retinal imaging presents a significant breakthrough in the study of retinopathy. In this study we introduce a novel UWF OCTA system capable of achieving a 112-degree field of view with 8.9-micrometer lateral resolution in rodent retinas, overcoming limitations of conventional imaging modalities for rodent retinal vascular imaging.

The UWF OCTA system is based on an asymmetrical relay system that differs from the traditional 4-f relay system, which also incorporates a contact lens originally designed for pediatric patients, addressing the unique challenges associated with rodent retinal imaging. The performance of the system is demonstrated through a longitudinal study involving Brown Norway rats, including healthy adult rats, oxygen-induced retinopathy (OIR) models, and age-matched controls. High-resolution images of single capillaries and nerve fibers throughout the retina are showcased, highlighting the potential of the UWF OCTA system for detailed retinal imaging in rodents.

This study also discusses the use of the UWF OCTA system for studying OIR models, revealing non-perfusion areas, tortuous vessels, and reduced vessel density in affected rats, with similarities to human retinopathy of prematurity. The UWF OCTA system holds great promise for advancing our understanding of retinopathy pathophysiology, providing a valuable tool for the exploration of novel therapeutic approaches and the optimization of existing treatments in rodent models.


Materials and Methods:: The system uses a vertical-cavity surface-emitting laser (VCSEL) (Thorlabs, Inc., USA) with an A-scan rate of 400 kHz. This swept-source laser has a 1060 nm central wavelength and a 100-nm bandwidth, which corresponds to an axial resolution of 3.7-µm in tissue. Three groups of lens including a contact lens is used in the scan lens creating an asymmetrical relay system to increase FOV and reduce eye movement. It can realize 8.9-µm lateral resolution with a 112˚ FOV in rats. OIR model was induced by placing the newborn rats in an oxygen-controlled chamber cycling between 50% and 10% oxygen concentration every 24 hours for 20 days. Subjects were anesthetized with inhaled 2.5% isoflurane during imaging and were kept in a warm blanket circulated with 37°C water to prevent body temperature loss and discomfort. The acquired raw spectrum data was converted to k-space, and compensated dispersion was applied to the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm to produce OCT and OCTA volumetric data. Volumes were segmented along anatomic boundaries by an artificial intelligence algorithm to generate en face projections of specific layers.

Results, Conclusions, and Discussions:: The ultra-wide field (UWF) optical coherence tomography angiography (OCTA) system was successfully implemented for rodent retinal imaging, achieving a 112-degree field of view and 8.9-µm lateral resolution. We imaged healthy adult rats, oxygen-induced retinopathy (OIR) models, and age-matched controls in a longitudinal study. High-resolution images of single capillaries and nerve fibers throughout the retina were obtained, and vascular disparities were found between OIR rats and age-matched specimens, emphasizing the system's capability for longitudinal detailed retinal imaging in rodents.
The novel UWF OCTA system overcomes the limitations of conventional imaging modalities, enabling the study of retinopathy in rodent models with unprecedented detail. The system's performance demonstrates its potential for advancing our understanding of retinopathy pathophysiology and investigating the effects of various treatments in animal models. Additionally, the UWF OCTA system could enable further exploration of retinal vascular changes in both macular and peripheral regions, contributing to the development of more effective therapeutic interventions for retinal disorders.

The UWF OCTA system revealed non-perfusion areas, tortuous vessels, and reduced vessel density in OIR models, which share similarities to human retinopathy of prematurity. As the OIR models were relocated to normal housing conditions, the non-perfusion areas and tortuous vessels decreased, indicating the potential for retinal recovery. These findings highlight the importance of conducting longitudinal studies to assess disease progression and the time-dependent effects of various therapeutic interventions.

Future studies could investigate the application of UWF OCTA for monitoring the effects of treatments such as Aflibercept, Ranibizumab, and Bevacizumab at different time points in OIR models. The UWF OCTA system's ability to provide high-resolution, large field of view imaging paves the way for a more comprehensive analysis of retinal vascular changes, ultimately contributing to improved patient outcomes in the management of retinal disorders.


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