Nathan Doble

The locus of fixation and the foveal cone mosaic.

High-resolution retinal imaging with adaptive optics was used to record the position of a light stimulus on the cone mosaic, with an error at least five times smaller than the diameter of the smallest foveal cones. We discuss the factors that limit the accuracy with which absolute retinal position can be determined. In five subjects, the standard deviation of fixation positions measured in discrete trials ranged from 2.1 to 6.3 arcmin, with an average of 3.4 arcmin (about 17 microm), in agreement with previous studies (R. W. Ditchburn, 1973; R. M. Steinman, G. M. Haddad, A. A. Skavenski, & D. Wyman, 1973). The center of fixation, based on the mean retinal position for each of three subjects, was displaced from the location of highest foveal cone density by an average of about 10 arcmin (about 50 microm), indicating that cone density alone does not drive the location on the retina selected for fixation. This method can be used in psychophysical studies or medical applications requiring submicron registration of stimuli with respect to the retina or in delivering light to retinal features as small as single cells.

Use of a microelectromechanical mirror for adaptive optics in the human eye

Ophthalmic instrumentation equipped with adaptive optics offers the possibility of rapid and automated correction of the eyes optics for improving vision and for improving images of the retina. One factor that limits the widespread implementation of adaptive optics is the cost of the wave-front corrector, such as a deformable mirror. In addition, the large apertures of these elements require high pupil magnification, and hence the systems tend to be physically large. We present what are believed to be the first closed-loop results when a compact, low-cost, surface micromachined, microelectromechanical mirror is used in a vision adaptive-optics system. The correction performance of the mirror is shown to be comparable to that of a Xinetics mirror for a 4.6-mm pupil size. Furthermore, for a pupil diameter of 6.0-mm, the residual rms error is reduced from 0.36 to 0.12 microm and individual photoreceptors are resolved at a pupil eccentricity of 1 degrees from the fovea.

Evidence of outer retinal changes in glaucoma patients as revealed by ultrahigh-resolution in vivo retinal imaging

Aims It is well established that glaucoma results in a thinning of the inner retina. To investigate whether the outer retina is also involved, ultrahigh-resolution retinal imaging techniques were utilised. Methods Eyes from 10 glaucoma patients (25–78 years old), were imaged using three research-grade instruments: (1) ultrahigh-resolution Fourier-domain optical coherence tomography (UHR-FD-OCT), (2) adaptive optics (AO) UHR-FD-OCT and (3) AO-flood illuminated fundus camera (AO-FC). UHR-FD-OCT and AO-UHR-FD-OCT B-scans were examined for any abnormalities in the retinal layers. On some patients, cone density measurements were made from the AO-FC en face images. Correlations between retinal structure and visual sensitivity were measured by Humphrey visual-field (VF) testing made at the corresponding retinal locations. Results All three in vivo imaging modalities revealed evidence of outer retinal changes along with the expected thinning of the inner retina in glaucomatous eyes with VF loss. AO-UHR-FD-OCT images identified the exact location of structural changes within the cone photoreceptor layer with the AO-FC en face images showing dark areas in the cone mosaic at the same retinal locations with reduced visual sensitivity. Conclusion Losses in cone density along with expected inner retinal changes were demonstrated in well-characterised glaucoma patients with VF loss.

Photoreceptor counting and montaging of en-face retinal images from an adaptive optics fundus camera

A fast and efficient method for quantifying photoreceptor density in images obtained with an en-face flood-illuminated adaptive optics (AO) imaging system is described. To improve accuracy of cone counting, en-face images are analyzed over extended areas. This is achieved with two separate semiautomated algorithms: (1) a montaging algorithm that joins retinal images with overlapping common features without edge effects and (2) a cone density measurement algorithm that counts the individual cones in the montaged image. The accuracy of the cone density measurement algorithm is high, with >97% agreement for a simulated retinal image (of known density, with low contrast) and for AO images from normal eyes when compared with previously reported histological data. Our algorithms do not require spatial regularity in cone packing and are, therefore, useful for counting cones in diseased retinas, as demonstrated for eyes with Stargardts macular dystrophy and retinitis pigmentosa.

The application of MEMS technology for adaptive optics in vision science

Recent years have seen remarkable results in high-resolution imaging and testing of the human visual system. The ability to obtain in vivo images of the human fundus on the micrometer scale will allow for much earlier diagnosis and treatment of a range of retina diseases. These advances have been made possible in part through the use of adaptive optics (AO). In order to utilize the full numerical aperture and, hence, maximize the resolution of the eye, it is necessary to provide a means of correcting all of the ocular aberrations. The concept of AO has been used successfully to overcome this difficulty. A key component of such a system is an optical element that can be deformed to provide high-order correction of these aberrations. Existing AO systems make use of deformable mirrors that were developed for large ground-based telescopes. In a drive to reduce their size and cost, fabrication of this element using microelectromechanical systems (MEMS) has been actively pursued. This paper explains the challenges in high-resolution imaging of the human eye and details how MEMS technology has been used to further research in this area.

In vivo imaging of the human rod photoreceptor mosaic

Although single cone receptors have been imaged in vivo, to our knowledge there has been no observation of rods in the living normal eye. Using an adaptive optics ophthalmoscope and post processing, evidence of a rod mosaic was observed at 5° and 10° eccentricities in the horizontal temporal retina. For four normal human subjects, small structures were observed between the larger cones and were observed repeatedly at the same locations on different days, and with varying wavelengths. Image analysis gave spacings that agree well with rod measurements from histological data.

Role of high-order aberrations in senescent changes in spatial vision

The contributions of optical and neural factors to age-related losses in spatial vision are not fully understood. We used closed-loop adaptive optics to test the visual benefit of correcting monochromatic high-order aberrations (HOAs) on spatial vision for observers ranging in age from 18 to 81 years. Contrast sensitivity was measured monocularly using a two-alternative forced-choice (2AFC) procedure for sinusoidal gratings over 6 mm and 3 mm pupil diameters. Visual acuity was measured using a spatial 4AFC procedure. Over a 6 mm pupil, young observers showed a large benefit of AO at high spatial frequencies, whereas older observers exhibited the greatest benefit at middle spatial frequencies, plus a significantly larger increase in visual acuity. When age-related miosis is controlled, young and old observers exhibited a similar benefit of AO for spatial vision. An increase in HOAs cannot account for the complete senescent decline in spatial vision. These results may indicate a larger role of additional optical factors when the impact of HOAs is removed, but also lend support for the importance of neural factors in age-related changes in spatial vision.

Requirements for discrete actuator and segmented wavefront correctors for aberration compensation in two large populations of human eyes

Numerous types of wavefront correctors have been employed in adaptive optics (AO) systems for correcting the ocular wavefront aberration. While all have improved image quality, none have yielded diffraction-limited imaging for large pupils (>/=6 mm), where the aberrations are most severe and the benefit of AO the greatest. To this end, we modeled the performance of discrete actuator, segmented piston-only, and segmented piston/tip/tilt wavefront correctors in conjunction with wavefront aberrations measured on normal human eyes in two large populations. The wavefront error was found to be as large as 53 microm, depending heavily on the pupil diameter (2-7.5 mm) and the particular refractive state. The required actuator number for diffraction-limited imaging was determined for three pupil sizes (4.5, 6, and 7.5 mm), three second-order aberration states, and four imaging wavelengths (0.4, 0.6, 0.8, and 1.0 microm). The number across the pupil varied from only a few actuators in the discrete case to greater than 100 for the piston-only corrector. The results presented will help guide the development of wavefront correctors for the next generation of ophthalmic instrumentation.

Effect of wavelength on in vivo images of the human cone mosaic

In images of the human fundus, the fraction of the total returning light that comes from the choroidal layers behind the retina increases with wavelength [Appl. Opt. 28, 1061 (1989); Vision Res. 36, 2229 (1996)]. There is also evidence that light originating behind the receptors is not coupled into the receptor waveguides en route to the pupil [S. A. Burns et al., Noninvasive Assessment of the Visual System, Vol. 11 of 1997 Trends in Optics and Photonics Series, D. Yager, ed. (Optical Society of America, 1997), p. al; Invest. Ophthalmol. Visual Sci. 38, 1657 (1997)]. These observations imply that the contrast of images of the cone mosaic should be greatly reduced with increasing wavelength. This hypothesis was tested by imaging the light distributions in both the planes of the photoreceptors and the pupil at three wavelengths, 550, 650, and 750 nm, with the Rochester adaptive optics ophthalmoscope. Surprisingly, the contrast of the retinal images varied only slightly with wavelength. Furthermore, the ratio of the receptorally guided component to the total reflected light measured in the pupil plane was found to be similar at each wavelength, suggesting that, throughout this wavelength range, the scattered light from the deeper layers in the retina is guided through the receptors on its return path to the pupil.

High-resolution, in vivo retinal imaging using adaptive optics and its future role in ophthalmology.

Until recently it was impossible to fully realize the optical resolution afforded by the human eye due to the inherent optical aberrations. These aberrations limit the ability to see fine structure in the retinal layers and visual perception of the outside world. A conventional spectacle or contact lens refraction only provides a static amelioration of the lowest order aberrations, namely defocus and astigmatism. In addition, all of these distortions are constantly evolving due to changes in accommodation and head/eye movements. The technique of adaptive optics not only corrects all of the static spatial modes but also measures and corrects any dynamic changes. Such systems have allowed for routine in vivo cellular imaging, the classification of individual photoreceptor cells and have enabled psychophysical testing of human visual function at the neural level. This review introduces the principle of adaptive optics and the key hardware required to implement such a scheme. The integration of adaptive optics into different imaging modalities is presented along with descriptions of current systems in use today and the experimental results obtained to date. Finally, the review concludes by discussing future technology and gives the author’s prediction of how the field will evolve over the coming years.