Adaptive optics retinal imaging: emerging clinical applications

Abstract

The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy and spectral domain-optical coherence tomography provide clinicians with remarkably clear pictures of the living retina. Although the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, the same optics induce significant aberrations that obviate cellular-resolution imaging in most cases. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. When applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, retinal pigment epithelium cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here, we review some of the advances that were made possible with AO imaging of the human retina and discuss applications and future prospects for clinical imaging.

Figure 1

Schematic of an AO retinal imaging system. A beam of light is shined into the eye, and a small amount is reflected back out of the eye and into the optical system. Reflected light is split between a wavefront sensor, which measure the aberrations, and the image capturing device. Information about the aberrations of the wavefront, as measured by the wavefront sensor, is processed by a control system. The control system sends a signal to an active optical component, causing a shape change, which minimizes the wavefront aberration. Modified from Carroll et al. (2005), with permission. A color version of this figure is available online at www.opvissci.com.

Figure 2

Capillaries forming the edge of the FAZ in a normal eye. This image is generated by computing the motion contrast of a stabilized AOSLO video. Motion contrast images from several videos were stitched together to form this montage, showing the continuous rim of the FAZ as well as the surrounding capillary network. Scale bar is 1 degree.

Figure 3

Images of the cone mosaic from individuals with different cone opsin mutations. Images are from 1-degree temporal retina from a normal trichromat (A), a dichromat harboring a pigment with the LIAVA polymorphism (B), and a dichromat harboring a pigment with the C203R missense mutation (C). While both dichromats have approximately the same reduction in cone density (31,771 cones/mm² for the LIAVA retina; 27,799 cones/mm² for the C203R retina, compared with normal of 55,184 cones/mm²), the arrangement of the remaining cone photoreceptors is more regular for the C203R retina. Scale bar = 50 μm.

Figure 4

Imaging the cone mosaic in albinism. Shown are images of the cone mosaic centered at approximately 1 degree superior retina. The foveal center is located just off the bottom edge of each image. Images from a normal retina (A) and a subject with OCA1B (B) reveal a gradual decrease in cone packing density moving from bottom (inferior retina) to top (superior retina). Image from a subject with OA1 (C) reveals more uniform cone packing density. Cones vary individually in their reflectivity, and there are regional differences in image intensity, but this is in stark contrast to the pigment mottling seen in (D). Scale bar is 100 microns.

Figure 5

Image from a patient with autosomal dominant RP. The background is an infra-red SLO image from the Heidelberg Spectralis. The line indicates the location of the SD-OCT scan, which goes through fixation. The SD-OCT scan shows that photoreceptors are preserved in the central macula only with attenuation of outer retinal layers beginning about 6 degrees eccentric to fixation, and also reveals the presence of mild cystoid macular edema, or CME. A reduced-scale AOSLO montage is aligned and superimposed on the background image. The insets are full scale-sections of the AOSLO montage at two locations indicated by the black squares. The left inset is from the advancing front of degeneration, and RPE cells are clearly seen as a polygonal network of cells comprising the left half of the image. Some irregularly distributed cones are still visible on the right side of the image, albeit at a lower density than normal. The right inset is of the foveal region. Small white squares indicate the locus of fixation. Cones are resolved across most of the field, and are lower density than would be found in a normal eye. The dark lines and shadows in the inset do not indicate where cones are lost, but rather are formed by capillaries and the boundaries of the cystic spaces. It is presumed that preserved and functioning cones are likely to be present beneath these shadows, although cones are not clearly seen. Scale bar for the inset is 1 degree.

Figure 6

Two prototype clinical AO systems. (A, B) Picture of the Imagine Eyes system and corresponding image of the cone mosaic obtained with this system. (C, D) Picture of the Physical Sciences Incorporated system and corresponding image of the cone mosaic obtained with this system. Both systems provide qualitatively similar cone contrast and resolution to that obtained by research systems.