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ABSTRACT: Retinal vascular diseases are a leading cause of blindness and visual disability. The advent of adaptive optics retinal imaging has enabled us to image the retinal vascular at cellular resolutions, but imaging of the vasculature can be difficult due to the complex nature of the images, including features of many other retinal structures, such as the nerve fiber layer, glial and other cells. In this paper we show that varying the size and centration of the confocal aperture of an adaptive optics scanning laser ophthalmoscope (AOSLO) can increase sensitivity to multiply scattered light, especially light forward scattered from the vasculature and erythrocytes. The resulting technique was tested by imaging regions with different retinal tissue reflectivities as well as within the optic nerve head.
Biomedical Optics Express 10/2012; 3(10):2537-49. · 2.33 Impact Factor
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ABSTRACT: We evaluated the relationship between cone photoreceptor packing density and outer nuclear layer (ONL) thickness within the central 15 degrees.
Individual differences for healthy subjects in cone packing density and ONL thickness were examined in 8 younger and 8 older subjects, mean age 27.2 versus 56.2 years. Cone packing density was obtained using an adaptive optics scanning laser ophthalmoscope (AOSLO). The ONL thickness measurements included the ONL and the Henle fiber layer (ONL + HFL), and were obtained using spectral domain optical coherence tomography (SDOCT) and custom segmentation software.
There were sizeable individual differences in cone packing density and ONL + HFL thickness. Older subjects had on average lower cone packing densities, but thicker ONL + HFL measurements. Cone packing density and ONL + HFL thickness decreased with increasing retinal eccentricity. The ratio of the cone packing density-to-ONL2 was larger for the younger subjects group, and decreased with retinal eccentricity.
The individual differences in cone packing density and ONL + HFL thickness are consistent with aging changes, indicating that normative aging data are necessary for fine comparisons in the early stages of disease or response to treatment. Our finding of ONL + HFL thickness increasing with aging is inconsistent with the hypothesis that ONL measurements with SDOCT depend only on the number of functioning cones, since in our older group cones were fewer, but thickness was greater.
Investigative ophthalmology & visual science 05/2012; 53(7):3545-53. · 3.43 Impact Factor
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ABSTRACT: To compare retinal measurements obtained by time domain optical coherence tomography (OCT) devices before and after myopic laser in situ keratomileusis (Lasik) and to assess the interaction of Lasik and retinal structures as measured by time domain OCT.
Fifty-three patients randomly selected participated in the study. Only the right eye of each subject was included in the study. Comprehensive ophthalmic examinations including refraction examination, slit lamp examination, dilated fundus examination, corneal topography, corneal thickness, intraocular pressure, and retinal Stratus OCT scans were acquired for each patient before myopic Lasik and 3months after surgery.
Total macular volume (TMV) changed significantly between preoperative and postoperative measurements (p=0.003). No statistical differences were found between preoperative and postoperative disc area, rim area, cup/disk vert. ratio, or average foveal thickness (p>0.05). The variation in TMV correlated significantly with the change in spherical refraction equivalent, maximal corneal curvature, minimal corneal curvature, and corneal ablation depth.
Most retinal OCT measurements undergo no obvious changes after myopic Lasik. The increased TMV measurements we measured after Lasik seem to be correlated with the alteration in corneal shape. The exact mechanism for this change is not clear, while we examined several possibilities including subclinical macular oedema, magnification changes, errors in OCT analysis and IOP, none of these seem to be a likely cause.
Ophthalmic and Physiological Optics 05/2012; 32(3):222-7. · 1.58 Impact Factor
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ABSTRACT: To develop a clinical planning module (CPM) to improve the efficiency of imaging subjects with a steerable wide-field adaptive optics scanning laser ophthalmoscope (AOSLO) and to evaluate the performance of this module by imaging the retina in healthy and diseased eyes.
We developed a software-based CPM with two submodules: a navigation module and a montage acquisition module. The navigation module guides the AOSLO to image identified retinal regions from a clinical imaging platform using a matrix-based mapping between the two. The montage acquisition module systematically moves the AOSLO steering mirrors across the retina in predefined patterns. The CPM was calibrated using a model eye and tested on five normal subjects and one patient with a retinal nerve fiber layer defect.
Within the central ±7° from the fixation target, the CPM can direct the AOSLO beam to the desired regions with localization errors of <0.3°. The navigation error increases with eccentricity, and larger errors (up to 0.8°) were evident for regions beyond 7°. The repeatability of CPM navigation was tested on the same locations from two subjects. The localization errors between trials on different days did not differ significantly (p > 0.05). The region with a size of approximately 13° × 10° can be imaged in about 30 min. An approximately 12° × 4.5° montage of the diseased region from a patient was imaged in 18 min.
We have implemented a clinical planning module to accurately guide the AOSLO imaging beam to desired locations and to quickly acquire high-resolution AOSLO montages. The approach is not only friendly for patients and clinicians but also convenient to relate the imaging data between different imaging platforms.
Optometry and vision science: official publication of the American Academy of Optometry 04/2012; 89(5):593-601. · 1.53 Impact Factor
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ABSTRACT: A Lagrange multiplier-based damped least-squares control algorithm for woofer-tweeter (W-T) dual deformable-mirror (DM) adaptive optics (AO) is tested with a breadboard system. We show that the algorithm can complementarily command the two DMs to correct wavefront aberrations within a single optimization process: the woofer DM correcting the high-stroke, low-order aberrations, and the tweeter DM correcting the low-stroke, high-order aberrations. The optimal damping factor for a DM is found to be the median of the eigenvalue spectrum of the influence matrix of that DM. Wavefront control accuracy is maximized with the optimized control parameters. For the breadboard system, the residual wavefront error can be controlled to the precision of 0.03 μm in root mean square. The W-T dual-DM AO has applications in both ophthalmology and astronomy.
Applied Optics 03/2012; 51(9):1198-208. · 1.41 Impact Factor
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ABSTRACT: To investigate the retinal microvasculature at the fovea and peripheral retina in humans using an adaptive optics scanning laser ophthalmoscope (AOSLO) and to examine the association of foveal avascular zone (FAZ) and foveal pit morphology.
Retinal imaging of the foveal capillary network was performed on 11 subjects (15 eyes; age range 20 to 54 years) with an AOSLO. Standard deviation maps of the AOSLO images were generated from ∼10 to 30 frames, producing high-resolution maps delineating the complete capillary distribution of the retina. Foveal pit morphology was investigated in the same subjects by using a spectral domain optical coherence tomography. In an additional subject, only a relatively large retinal vasculature map was obtained using AOSLO.
A well-demarcated FAZ was seen in 11 subjects tested with foveal capillary imaging. There was considerable individual variation in the size and shape of the FAZ. The mean FAZ area and mean FAZ effective diameter were 0.33 mm(2) and 622 μm, respectively. Foveal thickness was found to be negatively correlated with the FAZ effective diameter.
The structure of the capillary network could be evaluated in the fovea and parafovea using our approach. We find that a smaller FAZ is associated with a narrower foveal pit opening and a thicker fovea.
Optometry and vision science: official publication of the American Academy of Optometry 03/2012; 89(5):602-10. · 1.53 Impact Factor
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ABSTRACT: We investigated the effect of localized visual stimulation on human retinal blood velocity using an adaptive optics scanning laser ophthalmoscope (AOSLO). To measure the blood velocity response, the AOSLO scanning raster was moved over the target arteries and red blood cell velocity was measured. Localized visual stimuli were delivered by projecting flicker patterns inside or outside the target artery's downstream region. The blood velocity increased in the presence of a flicker stimulus in the downstream region but not when outside the downstream region. The blood velocity increased more with larger area of stimulation. This increase was significant even when the stimulus was smaller than 600 μm × 600 μm. These findings suggest that when the retina regulates its blood flow to metabolic demands, it regulates blood velocity in the vascular system selectively, according to activity of neurons within its field of influence.
Journal of Vision 01/2012; 12(6):3. · 3.38 Impact Factor
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ABSTRACT: An ophthalmic adaptive optics (AO) imaging system is especially affected by pupil edge effects due to the higher noise and aberration level at the edge of the human pupil as well as the impact of head and eye motions on the pupil. In this paper, a two-step approach was proposed and implemented for reducing the edge effects and improving wavefront slope boundary condition. First, given an imaging pupil, a smaller size of sampling aperture can be adopted to avoid the noisy boundary slope data. To do this, we calibrated a set of influence matrices for different aperture sizes to accommodate pupil variations within the population. In step two, the slope data was extrapolated from the less noisy slope data inside the pupil towards the outside such that we had reasonable slope data over a larger aperture to stabilize the impact of eye pupil dynamics. This technique is applicable to any Neumann boundary-based active /adaptive modality but it is especially useful in the eye for improving AO retinal image quality where the boundary positions fluctuate.
Biomedical Optics Express 12/2011; 2(12):3309-20. · 2.33 Impact Factor
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ABSTRACT: Adaptive optics (AO) has greatly improved retinal image resolution. However, even with AO, temporal and spatial variations in image quality still occur due to wavefront fluctuations, intraframe focus shifts, and other factors. As a result, aligning and averaging images can produce a mean image that has lower resolution or contrast than the best images within a sequence. To address this, we propose an image postprocessing scheme called "lucky averaging," analogous to lucky imaging [J. Opt. Soc. Am. 68, 1651 (1978)] based on computing the best local contrast over time. Results from eye data demonstrate improvements in image quality.
Optics Letters 10/2011; 36(19):3786-8. · 3.40 Impact Factor
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ABSTRACT: This study quantified normal age-related changes to the photoreceptor axons in the central macula using the birefringent properties of the Henle fiber layer. A scanning laser polarimeter was used to acquire 15° × 15° macular images in 120 clinically normal subjects, ranging in age from the third decade to the eighth. Raw image data of the macular cross were used to compute phase retardation maps associated with Henle fiber layer. Annular regions of interest ranging from 0.25° to 3° eccentricity and centered on the fovea were used to generate intensity profiles from the phase retardation data, which were then analyzed using sine curve fitting and Fast Fourier Transform (FFT). The amplitude of a 2f sine curve was used as a measure of macular phase retardation magnitude. For FFT analysis, the 2f amplitude, as well as the 4f, were normalized by the remaining FFT components. The amplitude component of the 2f curve fit and the normalized 2f FFT component decreased as a function of age, while the eccentricity of the maximum value for the normalized 2f FFT component increased. The phase retardation changes in the central macula indicate structural alterations in the cone photoreceptor axons near the fovea as a function of age. These changes result in either fewer cone photoreceptors in the central macula, or a change in the orientation of their axons. This large sample size demonstrates systematic changes to the central cone photoreceptor morphology using scanning laser polarimetry.
Vision research 08/2011; 51(21-22):2263-72. · 2.29 Impact Factor
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ABSTRACT: We evaluated the relationship between the size of the peripapillary crescent and the axial length (AL) of the eye as well as the fine structure of the peripapillary crescent in selected eyes. Infrared fundus imaging and spectral domain optical coherence tomography (SDOCT) (Spectralis HRA+OCT, Heidelberg Engineering, Germany) centered at the fovea were performed on 72 healthy adults. On the infrared fundus images, we measured (a) the distance between the foveola and the temporal edge of the optic disc (FOD) and (b) the distance between the foveola and the temporal edge of the peripapillary crescent (FOC) (if present). A peripapillary crescent presented at the nasal margin of the disc in 64% of the subjects. The FOD and FOC were 4.22mm±0.46 and 3.97mm±0.25, respectively. Only the FOD was significantly correlated with axial length. As AL increased by 10%, the FOD increased by 13%, the outer neural retina only expanded by 4% (as indicated by the FOC). This result emphasizes that retinal stretching may not mirror scleral growth, and the existence in some eyes of a difference between the photoreceptor margin and retinal pigment epithelium (RPE) margin suggests that within the retina there could be slippage during eye growth.
Vision research 08/2011; 51(19):2132-8. · 2.29 Impact Factor
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ABSTRACT: To study the variation of cone photoreceptor packing density across the retina in healthy subjects of different ages.
High-resolution adaptive optics scanning laser ophthalmoscope (AOSLO) systems were used to systematically image the retinas of two groups of subjects of different ages. Ten younger subjects (age range, 22-35 years) and 10 older subjects (age range, 50-65 years) were tested. Strips of cone photoreceptors, approximately 12° × 1.8° long were imaged for each of the four primary retinal meridians: superior, inferior, nasal, and temporal. Cone photoreceptors within the strips were counted, and cone photoreceptor packing density was calculated. Statistical analysis (three-way ANOVA) was used to calculate the interaction for cone photoreceptor packing density between age, meridian, and eccentricity.
As expected, cone photoreceptor packing density was higher close to the fovea and decreased with increasing retinal eccentricity from 0.18 to 3.5 mm (∼0.6-12°). Older subjects had approximately 75% of the cone density at 0.18 mm (∼0.6°), and this difference decreased rapidly with eccentricity, with the two groups having similar cone photoreceptor packing densities beyond 0.5 mm retinal eccentricity on average.
Cone packing density in the living human retina decreases as a function of age within the foveal center with the largest difference being found at our most central measurement site. At all ages, the retina showed meridional difference in cone densities, with cone photoreceptor packing density decreasing faster with increasing eccentricity in the vertical dimensions than in the horizontal dimensions.
Investigative ophthalmology & visual science 07/2011; 52(10):7376-84. · 3.43 Impact Factor
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ABSTRACT: We implemented a Lagrange-multiplier (LM)-based damped least-squares (DLS) control algorithm in a woofer-tweeter dual deformable-mirror (DM) adaptive optics scanning laser ophthalmoscope (AOSLO). The algorithm uses data from a single Shack-Hartmann wavefront sensor to simultaneously correct large-amplitude low-order aberrations by a woofer DM and small-amplitude higher-order aberrations by a tweeter DM. We measured the in vivo performance of high resolution retinal imaging with the dual DM AOSLO. We compared the simultaneous LM-based DLS dual DM controller with both single DM controller, and a successive dual DM controller. We evaluated performance using both wavefront (RMS) and image quality metrics including brightness and power spectrum. The simultaneous LM-based dual DM AO can consistently provide near diffraction-limited in vivo routine imaging of human retina.
Biomedical Optics Express 07/2011; 2(7):1986-2004. · 2.33 Impact Factor
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ABSTRACT: To quantitatively model the changes in blood velocity profiles for different cardiac phases in human retinal vessels.
An adaptive optics scanning laser ophthalmoscope (AOSLO) was used to measure blood velocity profiles in three healthy subjects. Blood velocity was measured by tracking erythrocytes moving across a scanning line. From the radial position of the cells within the lumen, the blood velocity profile was computed. The cardiac pulsatility was recorded with a cardiac signal monitor.
The shape of the blood velocity profile in retinal arteries changed systematically during the cardiac cycle, with the flattest profile occurring during the diastolic phase. The measured blood velocity profiles were typically flatter than the commonly assumed parabolic shape. The flatness increased with decreasing vessel size. For the large veins (>80 μm), the ratio of the centerline velocity to the cross-sectional average velocity was between 1.50 and 1.65. This ratio decreased to 1.36 in the smallest vein studied (32 μm). Velocity profiles downstream from a venous confluence showed two peaks at 120 μm from the confluence, but a single velocity peak 500 μm downstream from the confluence.
The cardiac cycle influences the blood flow velocity profiles systematically in retinal arteries but not in veins. Parabolic flow was not found in even the largest vessels studied, and deviations from parabolic flow increased in smaller vessels. The measurements are sensitive enough to measure the dual-humped blood velocity profile at a vein confluence.
Investigative ophthalmology & visual science 04/2011; 52(7):4151-7. · 3.43 Impact Factor
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ABSTRACT: We have developed a new, unified implementation of the adaptive optics scanning laser ophthalmoscope (AOSLO) incorporating a wide-field line-scanning ophthalmoscope (LSO) and a closed-loop optical retinal tracker. AOSLO raster scans are deflected by the integrated tracking mirrors so that direct AOSLO stabilization is automatic during tracking. The wide-field imager and large-spherical-mirror optical interface design, as well as a large-stroke deformable mirror (DM), enable the AOSLO image field to be corrected at any retinal coordinates of interest in a field of >25 deg. AO performance was assessed by imaging individuals with a range of refractive errors. In most subjects, image contrast was measurable at spatial frequencies close to the diffraction limit. Closed-loop optical (hardware) tracking performance was assessed by comparing sequential image series with and without stabilization. Though usually better than 10 μm rms, or 0.03 deg, tracking does not yet stabilize to single cone precision but significantly improves average image quality and increases the number of frames that can be successfully aligned by software-based post-processing methods. The new optical interface allows the high-resolution imaging field to be placed anywhere within the wide field without requiring the subject to re-fixate, enabling easier retinal navigation and faster, more efficient AOSLO montage capture and stitching.
Journal of the Optical Society of America A 11/2010; 27(11):A265-77. · 1.56 Impact Factor
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ABSTRACT: We constructed a high speed and high-resolution Stokes vector retinal imaging polarimeter with dual electro-optical modulators based on adaptive optics scanning laser ophthalmoscope. By varying the voltages on the EO crystals line by line, we were able to measure over 500,000 Stokes vectors per second. We used this system in three human subjects demonstrating the capability of the system to be employed in vivo. The high speed effectively decreases the adverse impact of eye motion induced errors in polarization calculations, improving the contrast of retinal structures based on their polarization properties.
Optics Express 10/2010; 18(21):21892-904. · 3.59 Impact Factor
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ABSTRACT: We present an iterative technique for improving adaptive optics (AO) wavefront correction for retinal imaging, called the Adaptive-Influence-Matrix (AIM) method. This method is based on the fact that the deflection-to-voltage relation of common deformable mirrors used in AO are nonlinear, and the fact that in general the wavefront errors of the eye can be considered to be composed of a static, non-zero wavefront error (such as the defocus and astigmatism), and a time-varying wavefront error. The aberrated wavefront is first corrected with a generic influence matrix, providing a mirror compensation figure for the static wavefront error. Then a new influence matrix that is more accurate for the specific static wavefront error is calibrated based on the mirror compensation figure. Experimental results show that with the AIM method the AO wavefront correction accuracy can be improved significantly in comparison to the generic AO correction. The AIM method is most useful in AO modalities where there are large static contributions to the wavefront aberrations.
Optics Express 10/2009; 17(22):20167-77. · 3.59 Impact Factor
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ABSTRACT: We characterized the perceptual, functional, and structural abnormalities associated with retinal ischemia during a cotton wool spot episode and its sequelae. The border of the visually salient field anomaly mirrored the quantitatively measured relative scotoma. Results of resolution perimetry and high resolution imaging indicated that there was a substantial loss of retinal ganglion cells within the affected region. A disruption in retinal nerve fiber arrangement was found at the cotton wool spot and within the arcuate relative scotoma. The presence of the arcuate relative scotoma is consistent with the hypothesis of failed signal transmission along the axons that pass through the cotton wool spot. The different levels of loss associated with the arcuate and focal scotomas indicate different underlying pathologies.
Vision research 09/2009; 49(23):2826-34. · 2.29 Impact Factor
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ABSTRACT: Laser ray tracing, a technique originally developed to measure ocular aberrations from the deviations of the local ray aberrations as a function of entry pupil, was used to assess cone directionality in 29 normal eyes (seven of which underwent LASIK surgery) and seven eyes after LASIK corneal refractive surgery for myopia. The total intensity of the retinal aerial images was computed as a function of the entry location of the illuminated beam. The measured intensity distribution was fit to a two-dimensional Gaussian function plus a constant background. The maximum of the distribution represents the pupillary location toward which the cone photoreceptors are oriented (peak of the optical Stiles–Crawford, SCE, function). We found the average SCE peak location was located 0:43 AE 0:96 mm nasally and 0:60 AE 0:87 mm inferiorly to the center of the pupil. In general, there was not a relation between the pupillary area of best quality and SCE peak location, either pre-operatively or post-operatively. The cone directionality shape factor was also unchanged by surgery. However, in two eyes, pre-and post-operative SCE peak location changed significantly. LASIK refractive surgery decreased the MTF in all eyes, even when the actual SCE directionality of the subject is considered. In the two eyes that showed significantly different SCE peak location, the apodized post-operative MTF with the post-operative SCE peak exceeded the simulated post-operative MTF assuming no shift in the SCE peak. However, the statistical power of these two cases is low, and the general findings are consistent with the hypothesis that differences in optical quality are not a major driving mechanism for cone orientation.
Journal of Modern Optics 01/2009; · 1.17 Impact Factor
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ABSTRACT: We have used an adaptive-optics scanning laser ophthalmoscope to image the cone photoreceptor mosaic throughout the central 10 degrees -12 degrees of the retina for four normal subjects. We then constructed montages of the images and processed the montages to determine cone locations. Cone densities range from approximately 10,000 cones/mm2 at 7 degrees to 40,000 cones/mm2 at 1 degrees . The smallest cones were not resolved in the center of the fovea. From the locations of the cones we also analyzed the packing properties of the cone mosaic, finding that all four subjects had a slight cone streak of increased cone density and that, in agreement with previous studies using different approaches, the packing geometry decreased in regularity from the fovea toward the periphery. We also found variations in packing density between subjects and in local anisotropy across retinal locations. The complete montages are presented for download, as well as the estimated cone locations.
Journal of the Optical Society of America A 01/2009; 25(12):3021-9. · 1.56 Impact Factor
