Emerging imaging developments in experimental vision sciences and ophthalmology

With delicate anterior and posterior structures, the eye works as a robust optical imager to capture visual information, which is essential for sensing the beauty of the world and effective communication. The anterior segment of the eye, particularly the cornea and the crystalline lens, functions as an optical lens to project the target image into the fundus. Located at the posterior of the eye, the retina is a complex neural network responsible for capturing light photons, converting light energy to bioelectronic activities, and initiating the visual information processing. Because different diseases can target different parts of the eye, clinical examination of both anterior and posterior segments is important for eye disease detection and treatment assessment. As one part of the central nerve system (CNS), retinal neurovascular system is also frequently affected by neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In order to provide intuitive information for identifying ocular pathologies or neurodegenerations through the eye, different imaging approaches have been established for ophthalmic examination. Developments of quantitative imaging are also important for advancing the study of the nature of visual system. Optical imaging methods, such as slit lamp biomicroscopy and fundus photography, have played an indispensable role for the eye examination. In traditional fundus cameras, a white light source is typically used for color fundus imaging. It is known that the short wavelength, such as blue or green, light is predominantly sensitive to the retinal morphology, while long wavelength, such as red and near infrared (NIR), light provides enhanced penetration through the retina to reveal choroidal structure. Therefore, multiple-spectral imaging can be used to selectively evaluate the retinal and choroidal layers. With the confocal configuration to reject out-of-focus light, scanning laser ophthalmoscopy (SLO) provides a feasible strategy to enhance the resolution and contrast of chorioretinal imaging. Adaptive optics (AO) can be incorporated to compensate for optical aberrations of the eye to further enhance the fundus image resolution and contrast. Super-resolution ophthalmoscopy has been recently explored through virtually structured detection and optically reassigned SLO. By coherent gating of the light from different depths, optical coherence tomography (OCT) enables three-dimensional (3D) imaging of ocular structures at micrometer level resolution. While most of the ophthalmic imaging modalities are based on the recording of backward scattered light from the ocular tissues, photoacoustic imaging has been demonstrated to map absorption properties of the anterior and posterior segments of animal eyes. Moreover, ultrasound biomicroscopy have been also developed for evaluating the anterior and posterior segments. In addition to morphological imaging assessment, there are active efforts to expand the imaging capabilities for functional assessment of physiological condition of the eye. For example, as a special OCT modality, OCT angiography (OCTA) can provide high-contrast imaging of the vasculatures with active blood flow at capillary-level resolution. In coordination with visible stimulation, functional OCT has been demonstrated for objective optoretinography of stimulus evoked intrinsic optical signal changes in animal and human retinas. Functional OCT has been also validated for depthresolved rhodopsin molecular contrast imaging in retinal photoreceptors. OCT and ultrasound elastography have been explored for imaging biomechanical property of ocular tissues. Moreover, quantitative feature analysis and disease classification are being explored on fundus photos, OCT, and OCTA using computer-aidedmethods. Recently, extensive efforts have been made on implementing artificial