Probing the causes of visual acuity loss in patients diagnosed with functional amblyopia.
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Amblyopia↗
Biomedical subjects
Arthur Bradley
Publications and source records attributed to Arthur Bradley.
Predicting subjective judgment of best focus with objective image quality metrics.
PURPOSE: To determine the impact of higher-order monochromatic aberrations on lower-order subjective sphero-cylindrical refractions. METHODS: Computationally-aberrated, monochromatic Sloan letters were presented on a high luminance display that was viewed by an observer through a 2.5mm pupil. Through-focus visual acuity (VA) was determined in the presence of spherical aberration (Z40) at three levels (0.10, 0.21 and 0.50D). Analogous through-astigmatism experiments measured visual acuity in the presence of secondary astigmatism (Z4+/-2) or coma (Z3-1). Measured visual acuity was correlated with 31 different metrics of image quality to determine which metric best predicts performance for degraded retinal images. The defocus and astigmatism levels that optimized each metric were compared with those that produced best visual acuity to determine which metric best predicts subjective refraction. RESULTS: Spherical aberration, coma and secondary astigmatism all reduced VA and increased depth of focus. The levels of defocus and primary astigmatism that produced the best performance varied with levels of spherical aberration and secondary astigmatism, respectively. The presence of coma, however, did not affect cylindrical refraction. Image plane metrics, especially those that take into account the neural contrast sensitivity threshold (e.g. the visual Strehl ratio, VSOTF), are good predictors of visual acuity in both the through-focus and through-astigmatism experiments (R = -0.822 for VSOTF). Subjective sphero-cylindrical refractions were accurately predicted by some image-quality metrics (e.g., pupil fraction, VSOTF and standard deviation of PSF light distribution). CONCLUSION: Subjective judgment of best focus does not minimize RMS wavefront error (Zernike defocus = 0), nor create paraxial focus (Seidel defocus = 0), but makes the retina conjugate to a plane between these two. It is possible to precisely predict subjective sphero-cylindrical refraction for monochromatic light using objective metrics.
Computer Simulation↗
Accuracy and precision of objective refraction from wavefront aberrations.
We determined the accuracy and precision of 33 objective methods for predicting the results of conventional, sphero-cylindrical refraction from wavefront aberrations in a large population of 200 eyes. Accuracy for predicting defocus (as specified by the population mean error of prediction) varied from -0.50 D to +0.25 D across methods. Precision of these estimates (as specified by 95% limits of agreement) ranged from 0.5 to 1.0 D. All methods except one accurately predicted astigmatism to within +/-1/8D. Precision of astigmatism predictions was typically better than precision for predicting defocus and many methods were better than 0.5D. Paraxial curvature matching of the wavefront aberration map was the most accurate method for determining the spherical equivalent error whereas least-squares fitting of the wavefront was one of the least accurate methods. We argue that this result was obtained because curvature matching is a biased method that successfully predicts the biased endpoint stipulated by conventional refractions. Five methods emerged as reasonably accurate and among the most precise. Three of these were based on pupil plane metrics and two were based on image plane metrics. We argue that the accuracy of all methods might be improved by correcting for the systematic bias reported in this study. However, caution is advised because some tasks, including conventional refraction of defocus, require a biased metric whereas other tasks, such as refraction of astigmatism, are unbiased. We conclude that objective methods of refraction based on wavefront aberration maps can accurately predict the results of subjective refraction and may be more precise. If objective refractions are more precise than subjective refractions, then wavefront methods may become the new gold standard for specifying conventional and/or optimal corrections of refractive errors.
Diagnostic Techniques, Ophthalmological↗
Test-retest reliability of clinical Shack-Hartmann measurements.
PURPOSE: To evaluate the stability of clinical monochromatic aberrometry measurements over a wide range of time scales. METHODS: Monochromatic aberrations in four normal eyes were measured with a clinical Shack-Hartmann aberrometer. A chin rest or a supplemental bite bar attachment was used to stabilize head and eye position. Five repeated measurements were taken within one test (5 frames, t < 1 second) without realignment. With realignment between each measurement, aberration measurements were repeated five times (t < 1 hour) on each day, at the same time of day on five consecutive days, and again on 5 days at monthly intervals. A control experiment studied the effect of systematically misaligning the eye to determine whether fixation errors can account for the variation in the repeated measurements. RESULTS: Variability of wavefront root mean square (RMS) error (excluding defocus and astigmatism) was tracked across repeated measurements. Variances for different time scales were: 8.10 x 10(-5) microm2 (t < 1 second), 3.24 x 10(-4) microm2 (t < 1 hour), 4.41 x 10(-4) microm2 (t < 1 week), 9.73 x 10(-4) microm2 (t < 1 year). Bite bar and chin rest data were almost identical. Rotational fixation error up to 3 degrees accounts for only part of the variability. CONCLUSIONS: Increased variability in aberration maps between days and months indicates biological fluctuations that are large enough to prevent achievement of "perfect vision," even in the unlikely event that spherical and astigmatic refractive errors are corrected perfectly. However, lack of stability does not justify withholding treatment. A lasting benefit of aberration correction is expected despite temporal variability.
Adolescent↗
Understanding the neural basis of amblyopia.
Amblyopia is the condition in which reduced visual function exists despite full optical correction and an absence of observable ocular pathology. Investigation of the underlying neurology of this condition began in earnest around 40 years ago with the pioneering studies conducted by Hubel and Wiesel. Their early work on the impact of monocular deprivation and strabismus initiated what is now a rapidly developing field of cortical plasticity research. Although the monocular deprivation paradigm originated by Hubel and Wiesel remains a key experimental manipulation in studies of cortical plasticity, somewhat ironically, the neurology underlying the human conditions of strabismus and amblyopia that motivated this early work remains elusive. In this review, the authors combine contemporary research on plasticity and development with data from human and animal investigations of amblyopic populations to assess what is known and to reexamine some of the key assumptions about human amblyopia.
Amblyopia↗
Validation of a combined corneal topographer and aberrometer based on Shack-Hartmann wave-front sensing.
A corneal aberrometer based on Shack-Hartmann wave-front sensing was developed and validated by using calibrated aspheric surfaces. The aberrometer was found to accurately measure corneal reflective aberrations, from which corneal topography and corneal refractive aberrations were derived. Measurements of reflective aberrations correlated well with theory (R2 = 0.964 to 0.994). The sag error root mean square (RMS) was small, ranging from 0.1 to 0.17 microm for four of the five calibrated surfaces with the fifth at 0.36 microm as a result of residual defocus. Measured refractive aberrations matched with theory and whole-eye aberrometry to within a small fraction of a wavelength. Measurements on three human corneas revealed very large refractive astigmatism (0.65-1.2 microm) and appreciable levels of trefoil (0.08-0.47 microm), coma (0.14-0.19 microm), and spherical aberration (0.18-0.25 microm). The mean values of these aberrations were significantly larger than the RMS in repeated measurements.
Algorithms↗
Comparison of monochromatic ocular aberrations measured with an objective cross-cylinder aberroscope and a Shack-Hartmann aberrometer.
Repeated measures of wavefront aberrations were taken along the line-of-sight of seven eyes using two instruments: an objective, cross-cylinder aberroscope (OA) and a Shack-Hartmann (SH) aberrometer. Both instruments were implemented on the same optical table to facilitate interleaved measurements on the same eyes under similar experimental conditions. Variability of repeated measures of individual coefficients tended to be much greater for OA data than for SH data. Although Zernike coefficients obtained from a single measurement were generally larger when measured with the OA than with the SH, the averages across five trials were often smaller for the OA. The Zernike coefficients obtained from the two instruments were not significantly correlated. Radial modulation-transfer functions and point-spread functions derived from the two sets of measurements were similar for some subjects, but not all. When average Zernike coefficients were used to determine optical quality, the OA indicated superior optics in some eyes, but the reverse trend was true if Zernike coefficients from individual trials were used. Possible reasons for discrepancies between the OA and SH measurements include difference in sampling density, quality of data images, alignment errors, and temporal fluctuations. Multivariate statistical analysis indicated that the SH aberrometer discriminated between subjects much better than did the objective aberroscope.
Diagnostic Techniques, Ophthalmological↗
Relationship between refractive error and monochromatic aberrations of the eye.
PURPOSE: To examine the relationship between ametropia and optical aberrations in a population of 200 normal human eyes with refractive errors spanning the range from +5.00 to -10.00 D. METHODS: Using a reduced-eye model of ametropia, we tested the hypothesis that the optical system of the eye is uncorrelated with the degree of ametropia. These predictions were evaluated experimentally with a Shack-Hartmann aberrometer that measured the monochromatic aberrations across the central 6 mm of the dilated pupil in well-corrected, cyclopleged eyes. RESULTS: Optical theory predicted, and control experiments on a model eye verified, that Shack-Hartmann measurements of spherical aberration will vary with axial elongation of the eye even if the dioptric components of the eye are fixed. Contrary to these predictions, spherical aberration was not significantly different from emmetropic eyes. Root mean square of third-order aberrations, fourth-order aberrations, and total higher aberrations (third to 10th) in myopic and hyperopic eyes were also uncorrelated with refractive error. Astigmatic eyes tended to have larger total higher-order aberrations than nonastigmatic eyes. CONCLUSIONS: We conclude that a reduced-eye model of myopia assuming fixed optical parameters and variable axial length is not tenable.
Accommodation, Ocular↗
Use of retroillumination to visualize optical aberrations caused by tear film break-up.
PURPOSE: The aim of the current study was to develop quantitative methods to assess optical aberrations caused by tear film disruption. METHODS: We used standard fluorescein imaging (FL) and a novel retroillumination (RI) method to image tear film disruption in 12 eyes. Using a clinical slit lamp biomicroscope, we alternated between widefield blue and narrow-beam white light to obtain an interleaved series of FL and RI images of the time course and pattern of tear film break-up. We developed an optical analysis that indicates that the RI image should be proportional to the spatial derivative of the FL image. Intensity fluctuations in the RI images are due to thickness changes in the tear film, whereas intensity fluctuations in FL images are directly determined by tear film thickness. RESULTS: As predicted by optical analysis of RI, the spatial distribution of gaps in the tear film seen with fluorescein appeared as pairs of light and dark contours in the RI images, and a precise correspondence between the spatial derivative of the FL image (slope) and the RI image was found. Both methods showed a gradual spreading of the tear disruption during blink suppression that varied tremendously among eyes in both time and spatial pattern. Resumption of normal blinking did not produce an immediate reconstitution of the normal tear film, and areas of tear break-up created during blink suppression remained abnormal for up to several minutes of normal blinking. CONCLUSIONS: Our analysis indicates that both FL and RI have the potential to quantify optical changes occurring during tear break-up. These results support an interpretation of RI as an intensity-based method for mapping the highly irregular optical aberrations of the eye produced by tear film disruption.
Adult↗
Validation of a clinical Shack-Hartmann aberrometer.
PURPOSE: To validate the accuracy, tolerance, and repeatability of the complete ophthalmic analysis system aberrometer (COAS, Wavefront Sciences Inc.) with model eyes and normal human eyes. METHOD: Model eyes were constructed from six polymethyl methacrylate, single-surface lenses with known characteristics. Accuracy of second-order aberrations was verified by measuring defocus and astigmatism induced by series of spherical and cylindrical trial lenses. Accuracy of higher-order aberrations was evaluated by comparing ray-tracing predictions with measured spherical aberration and coma of the aspheric model eyes. Tolerance to axial and lateral misalignment was measured by controlled displacements of the model eye relative to the aberrometer. Repeatability was tested on the same model eyes with repeated measurements taken within 1 s or within half an hour with realignment between each trial. Analyses were based on a 5-mm pupil diameter. RESULTS: Defocus and astigmatism were accurately measured within the working range of the instrument automatic focus adjustment (e.g., measured defocus was within +/-0.25 diopters over a -6.50 to +3.00 D range of refractive error). Accuracy of spherical aberration and coma agreed closely with theoretical predictions (e.g., for all six aspheric models, the mean absolute difference between predicted and measured Z(4)0 was 0.007 microm). Axial displacements over the range +/-2.5 mm had little effect on measurements for myopic and emmetropic model eyes. Also, lateral displacements over the range +/-1.5 mm did not produce significant coma. The standard deviations of repeated measurements of higher-order root mean square on model eyes were <1% of the mean with repeated measures within 1 s and 10% of the mean for five individual measurements with realignment in between each. Tolerance to small lateral displacements was also observed for human eyes. CONCLUSION: The complete ophthalmic analysis system aberrometer can measure second-, third-, and fourth-order aberrations accurately and repeatedly on model eyes.
Astigmatism↗
Design principles and limitations of wave-front guided contact lenses.
The concept of the wave-front guided design of contact lenses is presented from three vantage points: ray optics, wave front aberrations, and optical path-length errors. We argue that the goal of contact lenses is to make all of the optical paths from a distant object to the retina equal in length, regardless of where the path intersects the plane of the eye's pupil. The aberration map of an eye is a prescription for such a lens. Unfortunately, variability of measured aberration maps is a fundamental limit to our knowledge of the true aberration structure of an eye. Variability arises because the eye is a biologic system that changes over time for normal, physiologic reasons. Furthermore, uncertainty in our measurement of the aberration map because of such variable factors, such as alignment of the aberrometer to the eye by the clinician or small fixation errors committed by the patient, will make it difficult to achieve a full measure of success with aberration-correcting contact lenses. The clinical implication of these findings is that multiple measurements of the aberration map should be collected using a protocol that includes realignment of the instrument and then averaging the aberration maps to reduce the level of uncertainty associated with any single measurement.
Contact Lenses↗
Nonveridical visual perception in human amblyopia.
PURPOSE: Amblyopia is a developmental disorder of spatial vision. There is evidence to suggest that some amblyopes misperceive spatial structure when viewing with the affected eye. However, there are few examples of these perceptual errors in the literature. This study was an investigation of the prevalence and nature of misperceptions in human amblyopia. METHODS: Thirty amblyopes with strabismus and/or anisometropia participated in the study. Subjects viewed sinusoidal gratings of various spatial frequencies, orientations, and contrasts. After interocular comparison, subjects sketched the subjective appearance of those stimuli that had nonveridical appearances. RESULTS: Nonveridical visual perception was revealed in 20 amblyopes ( approximately 67%). In some subjects, misperceptions were present despite the absence of a deficit in contrast sensitivity. The presence of distortions was not simply linked to the depth of amblyopia, and anisometropes were affected as well as those with strabismus. In most cases, these spatial distortions arose at spatial frequencies far below the contrast detection acuity cutoff. Errors in perception became more severe at higher spatial frequencies, with low spatial frequencies being mostly perceived veridically. The prevalence and severity of misperceptions were frequently found to depend on the orientation of the grating used in the test, with horizontal orientations typically less affected than other orientations. Contrast had a much smaller effect on misperceptions, although there were cases in which severity was greater at higher contrasts. CONCLUSIONS: Many types of misperceptions documented in the present study have appeared in previous investigations. This suggests that the wide range of distortions previously reported reflect genuine intersubject differences. It is proposed that nonveridical perception in human amblyopia has its origins in errors in the neural coding of orientation in primary visual cortex.
Adolescent↗
Predicting optical effects of tear film break up on retinal image quality using the Shack-Hartmann aberrometer and computational optical modeling.
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Adult↗
Isolation of stimulus characteristics contributing to Weber's law for position.
To examine the independent contribution of various stimulus characteristics to positional judgements, we measured vernier alignment performance for three types of Gabor stimuli. In one, only the contrast envelope of the upper and lower stimulus elements was offset, with the luminance-modulated carrier grating remaining in alignment. In the second, only the carrier grating was offset. In the third, both carrier and envelope were offset together. Performance was examined over a range of element separations. When both cues are available, thresholds for small separations are dominated by carrier offset information and are inversely proportional to carrier frequency. At large separations, thresholds are governed by the spatial scale characteristics of the envelope. For broad-band stimuli such as lines, bars or dots typically used for vernier acuity, their higher frequency content can be used when separations are small, but as separation increases a smooth transition between the scales that determine threshold results in the continuum known as Weber's law for position. That is, with increasing separation, larger scales must be used, and thresholds increase in direct proportion to 1/frequency.
Contrast Sensitivity↗
A statistical model of the aberration structure of normal, well-corrected eyes.
A statistical model of the wavefront aberration function of the normal, well-corrected eye was constructed based on normative data from 200 eyes which show that, apart from spherical aberration, the higher-order aberrations of the human eye tend to be randomly distributed about a mean value of zero. The vector of Zernike aberration coefficients describing the aberration function for any individual eye was modelled as a multivariate, Gaussian, random variable with known mean, variance and covariance. The model was verified by analysing the statistical properties of 1000 virtual eyes generated by the model. Potential applications of the model include computer simulation of individual variation in aberration structure, retinal image quality, visual performance, benefit of novel designs of ophthalmic lenses, or outcome of refractive surgery.
Adult↗
Statistical variation of aberration structure and image quality in a normal population of healthy eyes.
A Shack-Hartmann aberrometer was used to measure the monochromatic aberration structure along the primary line of sight of 200 cyclopleged, normal, healthy eyes from 100 individuals. Sphero-cylindrical refractive errors were corrected with ophthalmic spectacle lenses based on the results of a subjective refraction performed immediately prior to experimentation. Zernike expansions of the experimental wave-front aberration functions were used to determine aberration coefficients for a series of pupil diameters. The residual Zernike coefficients for defocus were not zero but varied systematically with pupil diameter and with the Zernike coefficient for spherical aberration in a way that maximizes visual acuity. We infer from these results that subjective best focus occurs when the area of the central, aberration-free region of the pupil is maximized. We found that the population averages of Zernike coefficients were nearly zero for all of the higher-order modes except spherical aberration. This result indicates that a hypothetical average eye representing the central tendency of the population is nearly free of aberrations, suggesting the possible influence of an emmetropization process or evolutionary pressure. However, for any individual eye the aberration coefficients were rarely zero for any Zernike mode. To first approximation, wave-front error fell exponentially with Zernike order and increased linearly with pupil area. On average, the total wave-front variance produced by higher-order aberrations was less than the wave-front variance of residual defocus and astigmatism. For example, the average amount of higher-order aberrations present for a 7.5-mm pupil was equivalent to the wave-front error produced by less than 1/4 diopter (D) of defocus. The largest pupil for which an eye may be considered diffraction-limited was 1.22 mm on average. Correlation of aberrations from the left and right eyes indicated the presence of significant bilateral symmetry. No evidence was found of a universal anatomical feature responsible for third-order optical aberrations. Using the Marechal criterion, we conclude that correction of the 12 largest principal components, or 14 largest Zernike modes, would be required to achieve diffraction-limited performance on average for a 6-mm pupil. Different methods of computing population averages provided upper and lower limits to the mean optical transfer function and mean point-spread function for our population of eyes.
Adult↗
Estimating visual quality from wavefront aberration measurements.
PURPOSE: Root mean square (RMS) wavefront error may not be the best metric for predicting a patient's visual function; other metrics should be considered. We describe the most important metrics of optical quality, which are being investigated to predict vision quality and visual performance. METHODS: Optical quality can be described in two different ways. Pupil plane metrics describe variability of the wavefront error at the pupillary plane (eg, RMS wavefront error). Image plane metrics describe the retinal image and do so for either a point source of light (eg, point-spread function [PSF]) or sinusoidal gratings (optical transfer function [OTF]). Visual quality metrics, however, must also consider neural processing and subjective perception. RESULTS: Since vision is more sensitive to rays coming from the center of the pupil, "pupil fraction" appears to be a better predictor of visual acuity (r2 = 0.50) than RMS error (r2 = 0.13). However, image plane metrics, such as the visual Strehl ratio (r2 = 0.62) and the volume between the optical transfer function and neural contrast sensitivity function (r2 = 0.80) appear to be even better. CONCLUSION: Visual perception is highly subjective and involves many aspects of image quality. A single metric to describe all aspects of image quality may be unrealistic. Nevertheless, improved visual quality metrics need further investigation and will likely involve preferential weighing of light passing through the central area of the pupil and/or incorporating neural factors into image quality computation.
Contrast Sensitivity↗