Jason Porter

Monochromatic aberrations of the human eye in a large population

From both a fundamental and a clinical point of view, it is necessary to know the distribution of the eyes aberrations in the normal population and to be able to describe them as efficiently as possible. We used a modified Hartmann-Shack wave-front sensor to measure the monochromatic wave aberration of both eyes for 109 normal human subjects across a 5.7-mm pupil. We analyzed the distribution of the eyes aberrations in the population and found that most Zernike modes are relatively uncorrelated with each other across the population. A principal components analysis was applied to our wave-aberration measurements with the resulting principal components providing only a slightly more compact description of the population data than Zernike modes. This indicates that Zernike modes are efficient basis functions for describing the eyes wave aberration. Even though there appears to be a random variation in the eyes aberrations from subject to subject, many aberrations in the left eye were found to be significantly correlated with their counterparts in the right eye.

In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells

The ability to resolve single cells noninvasively in the living retina has important applications for the study of normal retina, diseased retina, and the efficacy of therapies for retinal disease. We describe a new instrument for high-resolution, in vivo imaging of the mammalian retina that combines the benefits of confocal detection, adaptive optics, multispectral, and fluorescence imaging. The instrument is capable of imaging single ganglion cells and their axons through retrograde transport in ganglion cells of fluorescent dyes injected into the monkey lateral geniculate nucleus (LGN). In addition, we demonstrate a method involving simultaneous imaging in two spectral bands that allows the integration of very weak signals across many frames despite inter-frame movement of the eye. With this method, we are also able to resolve the smallest retinal capillaries in fluorescein angiography and the mosaic of retinal pigment epithelium (RPE) cells with lipofuscin autofluorescence.

Calculated impact of higher-order monochromatic aberrations on retinal image quality in a population of human eyes

We calculated the impact of higher-order aberrations on retinal image quality and the magnitude of the visual benefit expected from their correction in a large population of human eyes. Wave aberrations for both eyes of 109 normal subjects and 4 keratoconic patients were measured for 3-, 4-, and 5.7-mm pupils with a Shack-Hartmann sensor. Retinal image quality was estimated by means of the modulation transfer function (MTF) in white light. The visual benefit was calculated as the ratio of the MTF when the monochromatic higher-order aberrations are corrected to the MTF corresponding to the best correction of defocus and astigmatism. On average, the impact of the higher-order aberrations for a 5.7-mm pupil in normal eyes is similar to an equivalent defocus of approximately 0.3 D. The average visual benefit for normal eyes at 16 c/deg is approximately 2.5 for a 5.7-mm pupil and is negligible for small pupils (1.25 for a 3-mm pupil). The benefit varies greatly among eyes, with some normal eyes showing almost no benefit and others a benefit higher than 4 at 16 c/deg across a 5.7-mm pupil. The benefit for keratoconic eyes is much larger. The benefit at 16 c/deg is 12 and 3 for 5.7- and 3-mm pupils, respectively, averaged across four keratoconics. These theoretical benefits could be realized in normal viewing conditions but only under specific conditions.

Visual Benefit of Correcting Higher Order Aberrations of the Eye

There is currently considerable debate concerning the visual impact of correcting the higher order aberrations of the eye. We describe new measurements of a large population of human eyes and compute the visual benefit of correcting higher order aberrations. We also describe the increase in contrast sensitivity when higher order aberrations are corrected with an adaptive optics system. All these results suggest that many, though not all, observers with normal vision would receive worthwhile improvements in spatial vision from customized vision correction, at least over a range of viewing distances and particularly when the pupils are large. Keratoconic patients or patients suffering from spherical aberration as a result of laser refractive surgery as it is presently performed would especially benefit. These results encourage the development of methods to correct higher order aberrations.

Aberrations induced in wavefront-guided laser refractive surgery due to shifts between natural and dilated pupil center locations

PURPOSE: To determine the aberrations induced in wavefront‐guided laser refractive surgery due to shifts in pupil center location from when aberrations are measured preoperatively (over a dilated pupil) to when they are corrected surgically (over a natural pupil). SETTING: Center for Visual Science and Department of Ophthalmology, University of Rochester, Rochester, New York, USA. METHODS: Shifts in pupil center were measured between dilated phenylephrine hydrochloride (Neo‐Synephrine [2.5%]) and nonpharmacological mesopic conditions in 65 myopic eyes treated with wavefront‐guided laser in situ keratomileusis (Technolas 217z, Bausch & Lomb). Each patients preoperative and 6‐month postoperative wave aberrations were measured over the dilated pupil. Aberrations theoretically induced by decentration of a wavefront‐guided ablation were calculated and compared with those measured 6 months postoperatively (6.0 mm pupil). RESULTS: The mean magnitude of pupil center shift was 0.29 mm ± 0.141 (SD) and usually occurred in the inferonasal direction as the pupil dilated. Depending on the magnitude of shift, the fraction of the higher‐order postoperative root‐mean‐square wavefront error that could be due theoretically to pupil center decentrations was highly variable (mean 0.26 ± 0.20 mm). There was little correlation between the calculated and 6‐month postoperative wavefronts, most likely because pupil center decentrations are only 1 of several potential sources of postoperative aberrations. CONCLUSIONS: Measuring aberrations over a Neo‐Synephrine‐dilated pupil and treating them over an undilated pupil typically resulted in a shift of the wavefront‐guided ablation in the superotemporal direction and an induction of higher‐order aberrations. Methods referencing the aberration measurement and treatment with respect to a fixed feature on the eye will reduce the potential for inducing aberrations due to shifts in pupil center.

Reproducibility of Measuring Lamina Cribrosa Pore Geometry in Human and Nonhuman Primates with In Vivo Adaptive Optics Imaging

PURPOSE The ability to consistently resolve lamina cribrosa pores in vivo has applications in the study of optic nerve head and retinal disease mechanisms. Repeatability was assessed in imaging laminar pores in normal living eyes with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). METHODS Reflectance images (840 nm) of the anterior lamina cribrosa were acquired using the AOSLO in four or more different sessions in two normal rhesus monkey eyes and three normal human eyes. Laminar pore areas, elongations (ratio of major to minor axes of the best-fit ellipse) and nearest neighbor distances were calculated for each session. Measurement repeatability was assessed across sessions. RESULTS Pore areas ranged from 90 to 4365 μm(2) in monkeys and 154 to 6637 μm(2) in humans. Mean variabilities in measuring pore area and elongation (i.e., mean of the standard deviation of measurements made across sessions for the same pores) were 50 μm(2) (6.1%) and 0.13 (6.7%), respectively, in monkeys and 113 μm(2) (8.3%) and 0.17 (7.7%), respectively, in humans. Mean variabilities in measuring nearest neighbor distances were 1.93 μm (5.2%) in monkeys and 2.79 μm (4.1%) in humans. There were no statistically significant differences in any pore parameters across sessions (ANOVA, P > 0.05). CONCLUSIONS The anterior lamina cribrosa was consistently imaged in vivo in normal monkey and human eyes. The small intersession variability in normal pore geometry suggests that AOSLO imaging could be used to measure and track changes in laminar pores in vivo during glaucomatous progression.

In Vivo Imaging of Microscopic Structures in the Rat Retina

PURPOSE The ability to resolve single retinal cells in rodents in vivo has applications in rodent models of the visual system and retinal disease. The authors have characterized the performance of a fluorescence adaptive optics scanning laser ophthalmoscope (fAOSLO) that provides cellular and subcellular imaging of rat retina in vivo. METHODS Enhanced green fluorescent protein (eGFP) was expressed in retinal ganglion cells of normal Sprague-Dawley rats via intravitreal injections of adeno-associated viral vectors. Simultaneous reflectance and fluorescence retinal images were acquired using the fAOSLO. fAOSLO resolution was characterized by comparing in vivo images with subsequent imaging of retinal sections from the same eyes using confocal microscopy. RESULTS Retinal capillaries and eGFP-labeled ganglion cell bodies, dendrites, and axons were clearly resolved in vivo with adaptive optics. Adaptive optics correction reduced the total root mean square wavefront error, on average, from 0.30 microm to 0.05 microm (measured at 904 nm, 1.7-mm pupil). The full width at half maximum (FWHM) of the average in vivo line-spread function (LSF) was approximately 1.84 microm, approximately 82% greater than the FWHM of the diffraction-limited LSF. CONCLUSIONS With perfect aberration compensation, the in vivo resolution in the rat eye could be approximately 2x greater than that in the human eye because of its large numerical aperture (approximately 0.43). Although the fAOSLO corrects a substantial fraction of the rat eyes aberrations, direct measurements of retinal image quality reveal some blur beyond that expected from diffraction. Nonetheless, subcellular features can be resolved, offering promise for using adaptive optics to investigate the rodent eye in vivo with high resolution.

Wavefront sensorless adaptive optics ophthalmoscopy in the human eye

Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor ‘beacon’ can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains.

Surgeon offsets and dynamic eye movements in laser refractive surgery

PURPOSE: To determine the amount of static and dynamic pupil decentrations that occur during laser refractive surgery. SETTING: The Center of Visual Science and the Department of Ophthalmology, University of Rochester, Rochester, New York, USA. METHODS: The surgeons accuracy in aligning the pupil center with the laser center axis was measured when engaging the eye‐tracker in 17 eyes receiving conventional laser in situ keratomileusis (LASIK) procedures (Technolas 217z; Bausch & Lomb). Eye movements were measured subsequently during the treatment in 10 eyes using a pupil camera operating at 50 Hz. Temporal power spectra were calculated from the eye movement measurements. RESULTS: The mean pupil misalignment by the surgeon at the beginning of the procedure was 206.1 μm ± 80.99 (SD) (with respect to the laser center). The laser center was typically misaligned below (inferiorly) and to the left (nasally and temporally in left and right eyes, respectively) of the laser center. Small amounts of cyclotorsion were observed during the ablation (<2 degrees). The mean magnitude of dynamic pupil decentration from the laser center during treatment was 227.0 ± 44.07 μm. The mean standard deviation of eye movements was 65.7 ± 25.64 μm. Temporal power spectra calculated from the horizontal and vertical changes in eye position during the ablation were similar. Ninety‐five percent of the total power of the eye movements was contained in temporal frequencies up to 1 Hz, on average, in both directions. CONCLUSIONS: Most eye movements during LASIK are slow drifts in fixation. An eye‐tracker with a 1.4 Hz closed‐loop bandwidth could compensate for most eye movements in conventional or customized ablations.

Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic

Blue cone monochromacy (BCM) is an X-linked condition in which long- (L) and middle- (M) wavelength-sensitive cone function is absent. Due to the X-linked nature of the condition, female carriers are spared from a full manifestation of the associated defects but can show visual symptoms, including abnormal cone electroretinograms. Here we imaged the cone mosaic in four females carrying an L/M array with deletion of the locus control region, resulting in an absence of L/M opsin gene expression (effectively acting as a cone opsin knockout). On average, they had cone mosaics with reduced density and disrupted organization compared to normal trichromats. This suggests that the absence of opsin in a subset of cones results in their early degeneration, with X-inactivation the likely mechanism underlying phenotypic variability in BCM carriers.