High-resolution retinal imaging using adaptive optics
Retinal imaging is limited due to optical aberrations caused by imperfections in the optical media of the eye. Consequently, diffraction limited retinal imaging can only be achieved if optical aberrations in the eye are measured and corrected. Information about retinal pathology and structure on a cellular level is thus not available in a clinical setting but only from histological studies of excised retinal tissue. In addition to limitations such as tissue shrinkage and distortion, the main limitation of histological preparations is that longitudinal studies of disease progression and/or results of medical treatment are not possible. (click on image to enlarge)
Adaptive optics (AO) is the science, technology and art of capturing diffraction-limited images in adverse circumstances that would normally lead to strongly degraded image quality and loss of resolution. In non-military applications, it was first proposed and implemented in astronomy. AO technology has since been applied in many disciplines, including vision science, where retinal features down to a few microns can be resolved by correcting the aberrations of ocular optics.
The general principle of AO is to measure the aberrations introduced by the media between an object of interest and its image with a wavefront sensor, analyze the measurements, and calculate a correction with a control computer. The corrections are applied to a corrective element, e.g. a deformable mirror (DM), positioned in the optical path between the object and its image, thereby enabling high-resolution imaging of the object.
Modern telescopes with integrated AO systems employ the laser guide star technique to create an artificial reference object above the earth's atmosphere. Analogously, the vast majority of present-day vision research AO systems employ a single point source on the retina as a reference object for aberration measurements, consequently termed guide star (GS). AO correction is accomplished with a single DM in a plane conjugated to the pupil plane. An AO system with one GS and one DM will henceforth be referred to as single-conjugate AO (SCAO) system. Aberrations in such a system are measured for a single field angle and correction is uniformly applied over the entire field of view (FOV). Since the eye's optical aberrations are dependent on the field angle this will result in a small corrected FOV of approximately 2 degrees. The property of non-uniformity is shared by most optical aberrations such as e.g. the well known primary aberrations of coma, astigmatism, field curvature and distortion.
A method to deal with this limitation of SCAO is known as multiconjugate AO (MCAO) and uses multiple DMs conjugated to separate turbulent layers of the atmosphere and several GS to increase the corrected FOV. In theory, correcting (in reverse order) for each turbulent layer could yield diffraction limited performance over the entire FOV. However, as is the case for both the atmosphere and the eye, aberrations do not originate solely from a discrete set of thin layers but from a distributed volume. By measuring aberrations in different angular directions using several GSs and correcting aberrations in several layers of the eye using multiple DMs (at least two), it is possible to correct aberrations over a larger FOV than compared to SCAO.
The concept of MCAO for astronomy has been studied extensively. However, MCAO for the eye is just emerging, with only a few published theoretical papers. Our group has published the first experimental studies and practical applications of this technique in the eye, implementing a laboratory demonstrator comprising multiple GSs and two DMs, consequently termed dual-conjugate adaptive optics (DCAO). It enables imaging of retinal features down to a few microns, such as retinal cone photoreceptors and capillaries, the smallest blood vessels in the retina, over an imaging area of approximately 7 deg x 7 deg. It is unique in its ability to acquire single images over a retinal area that is up to 50 times larger than most other flood illumination AO instruments, thus potentially allowing for clinical use.
A second-generation Proof-of-Concept (PoC) prototype based on the DCAO laboratory demonstrator is currently under evaluation.
Structural consequences of arrested foveal development in preterms
There is no detailed topographic description of external retinal layers in OCT images. Therefore, there is a need for a structural model to be able to evaluate deviations from normal structure. A loss of outer and inner photoreceptor segments may be followed by cell or axon loss in peripherally displaced retinal layers. Consequently, lesions or changes in the outer and inner retina must be analyzed separately.
A fundamental problem in evaluating high resolution images of the central retina with optical coherence tomography (OCT) is the fact that internal retinal structures are peripherally displaced from photoreceptors in the fovea and that it is difficult to delineate the layers representing photoreceptors or internal retinal structures in of the central retina.
The overall aim is to characterize the topography of external and internal retinal layers in normal individuals and individuals with a history of premature birth (prematurity) and establish a structural model of fovea with the possibility of diagnosing abnormalities.
The specific objective is to develop and evaluate two methods for quantitative analysis of the retinal layer structure in OCT images. Both the manual and the densitometric method offer advantages since positions and thicknesses of individual retinal layers can be determined and compared in vertical sections perpendicular to the pigment epithelial layer (RPE).
A model of the retina describing the profile of each layer or anatomical structure with relevant landmarks and positions is useful to increase future clinicians' ability to detect and evaluate pathological changes in the central retina. Previous methods have been more time-consuming, boundaries between layers difficult to define and no critical selection of relevant measurement positions has taken place.