Fast Fourier Transform

The diffraction tomography theorem is adapted to one-dimensional length measurement. The resulting spectral interferometry technique is described and the first length measurements using this technique on a model eye and on a human eye in vivo are presented.

Measurement of intraocular distances by backscattering spectral interferometry

State-of-the-art retinal optical coherence tomography

The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.

Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye.

In the past two decades, optical coherence tomography (OCT) has been established as an adjunct diagnostic technique for noninvasive, high-resolution, cross-sectional imaging in a variety of medical fields. The rapid development of ultrabroad bandwidth light sources has recently enabled a significant improvement in OCT imaging resolution, demonstrating the potential of OCT to accomplish its original goal of performing noninvasive optical biopsies, i.e., the in vivo visualization of microstructural morphology in situ, which had previously only been possible with histopathology. In addition, these novel light sources might also enable the use of spectroscopic OCT, an extension of ultrahigh-resolution OCT, for enhancing image contrast as well as detecting spatially resolved functional, biochemical tissue information. State-of-the-art-light sources that now permit ultrahigh-resolution OCT covering the whole wavelength region from 500 to 1600 nm are reviewed and fundamental limitations of OCT image resolution are discussed. Ex vivo ultrahigh-resolution OCT tomograms are compared with histological results; first clinical in vivo ultrahigh-resolution OCT and preliminary spectroscopic OCT results are presented and their impact for future clinical and research applications is discussed.

Ultrahigh Resolution Optical Coherence Tomography

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 microm) and improved transverse resolution (5-10 microm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm x 300 mm) closed-loop AO system, based on a real-time Hartmann-Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 microm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.

Adaptive Optics Ultrahigh Resolution Optical Coherence Tomography

Merging of ultrahigh-resolution optical coherence tomography (UHR OCT) and adaptive optics (AO), resulting in high axial (3 µm) and improved transverse resolution (5–10 µm) is demonstrated for the first time to our knowledge in in vivo retinal imaging. A compact (300 mm×300 mm) closed-loop AO system, based on a real-time Hartmann–Shack wave-front sensor operating at 30 Hz and a 37-actuator membrane deformable mirror, is interfaced to an UHR OCT system, based on a commercial OCT instrument, employing a compact Ti:sapphire laser with 130-nm bandwidth. Closed-loop correction of both ocular and system aberrations results in a residual uncorrected wave-front rms of 0.1 µm for a 3.68-mm pupil diameter. When this level of correction is achieved, OCT images are obtained under a static mirror configuration. By use of AO, an improvement of the transverse resolution of two to three times, compared with UHR OCT systems used so far, is obtained. A significant signal-to-noise ratio improvement of up to 9 dB in corrected compared with uncorrected OCT tomograms is also achieved.

Adaptive-optics ultrahigh-resolution optical coherence tomography

A description of a Hartmann–Shack sensor to measure the aberrations of the human eye is presented We performed an analysis of the accuracy and limitations of the sensor using experimental results and computer simulations We compared the ocular modulation transfer function obtained from simultaneously recorded double-pass and Hartmann–Shack images The following factors affecting the sensor performance were evaluated: the statistical accuracy, the number of modes used to reconstruct the wave front, the size of the microlenses, and the exposure time

Analysis of the performance of the Hartmann–Shack sensor in the human eye

A wavefront aberration of an eye is determined, e.g., in real time. The eye is illuminated, and the light reflected from the retina is converted into spots with a device such as a Hartmann-Shack detector. The displacement of each spot from where it would be in the absence of aberration allows calculation of the aberration. Each spot is located by an iterative technique in which a corresponding centroid is located in a box drawn on the image data, a smaller box is defined around the centroid, the centroid is located in the smaller box, and so on. The wavefront aberration is calculated from the centroid locations by using a matrix in which unusable data can be eliminated simply by eliminating rows of the matrix. Aberrations for different pupil sizes are handled in data taken for a single pupil size by renormalization.

Rapid, automatic measurement of the eye's wave aberration

We evaluated the performance of a liquid-crystal spatial light modulator for static correction of the aberrations in the human eye. By applying phase-retrieval techniques to pairs of double-pass images we first estimated the wave aberration of the eye to be corrected. Then we introduced the opposite phase map in the modulator, which was placed in a plane conjugated with the eye’s pupil, and we recorded double-pass images of a point source before and after correction of the aberrations. In a slightly aberrated artificial eye a clear improvement was obtained after correction, and, although diffraction-limited performance was not achieved, the results were close to the theoretical predictions. In the two living eyes that we studied some benefit also appeared in the correction, but the performance was worse than that expected. We evaluated possible explanations for the relatively poor performance that was obtained in the human eye: an incorrect estimate of the ocular aberration, the limited spatial resolution of the modulator, and the dynamic changes in the ocular aberrations. Based on the results in the artificial eye, the first problem was not considered to be a major source of error. However, we showed that the spatial resolution of the liquid-crystal spatial light modulator limits the maximum correction to be attained. In addition, the changes in the ocular optics over time also impose a limit in the performance of static corrections.

Pedro M. Prieto

Papers

Adaptive Optics Ultrahigh Resolution Optical Coherence Tomography

Adaptive-optics ultrahigh-resolution optical coherence tomography

Analysis of the performance of the Hartmann–Shack sensor in the human eye

Rapid, automatic measurement of the eye's wave aberration

Correction of the aberrations in the human eye with a liquid-crystal spatial light modulator: limits to performance