IUSO PUBMED listings for Larry Thibos June 27, 2012

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1 1. Amigo A, Bonaque S, López-Gil N, Thibos L. Simulated effect of corneal asphericity increase (q-factor) as a refractive therapy for presbyopia. J Refract Surg Jun;28(6): doi: / X PMID: [PubMed - in process] PURPOSE: To determine the theoretical effect of an increase in the negative Q-factor (hyperprolateness) on the refractive state and its effect on presbyopia treatment. METHODS: Ray tracing software was used to simulate the Navarro eye model. To simulate refractive therapy, corneal Q-factor ranged from 0 to Refractive state of the model eye was defined as the target vergence required to maximize retinal image quality according to several image quality metrics. The change of refractive state produced by pupil constriction from 6 to 2 mm was estimated. RESULTS: For 0 Q -0.6, spherical aberration of the model eye is positive, therefore, pupil miosis causes a hypermetropic shift in refractive state. Over the range -0.6 Q - 1.5, spherical aberration becomes negative and pupil constriction causes the eye's far point to approach the eye, inducing a myopic shift. A maximum 0.60-diopter myopic shift in refractive state due to pupil constriction occurred for Q= CONCLUSIONS: Optical modeling predicts that surgically induced negative corneal Q- value will produce a change in the refractive state of the eye after pupillary miosis. Copyright 2012, SLACK Incorporated. 2. López-Gil N, Peixoto-de-Matos SC, Thibos LN, González-Méijome JM. Shedding light on night myopia. J Vis Jan 1;12(5). pii: 4. doi: / Print PMID: [PubMed - in process] Free Article First described during the 18th century, the cause of night myopia remains a controversial topic. Whereas several explanations have been suggested in the literature, particularly related with accommodation or chromatic shift in scotopic light conditions, no definitive explanation for its aetiology has been provided. We describe an experiment in which ocular refractive state was objectively and subjectively measured while viewing two kind of stimulus: letters on a bright background and a punctual source of light in a dark background. We found that under photopic conditions the optimum refractive state of the accommodating eye is significantly more myopic when maximizing perceived quality of a point source on a dark background compared to a conventional letter chart with black letters on a white background. Optical modeling suggested this difference in refractive state is due to spherical aberration. Since isolated point sources are more likely encountered at night, whereas extended objects are more likely encountered in the daytime, our results suggest that a significant part of the night myopia phenomenon is determined by the nature of the visual stimulus and the visual task used to assess ocular refractive state. 3. Demirel S, Anderson RS, Dakin SC, Thibos LN. Detection and resolution of vanishing optotype letters in central and peripheral vision. Vision Res Apr 15;59:9-16. Epub 2012 Mar 3. PMID: [PubMed - indexed for MEDLINE] 1

2 Previous studies of peripheral vision have shown that detection acuity is superior to resolution acuity for gratings over a range of contrasts, which is attributed to different limiting mechanisms (contrast insufficiency and neural undersampling) for the two tasks. To extend the analysis to letters in a way that avoided luminance cues, we used "vanishing optotype" characters, conveying second-order information, and constructed from tripole strokes having the same mean luminance as the surround. We measured the minimum letter size for detection and identification tasks for two different pairs of vanishing optotype characters (O vs. + and orthogonally oriented Landolt-C's) as a function of contrast in central and peripheral vision. Foveally there was no significant difference between detection acuity and resolution acuity for either pair of letters over a range of stimulus contrasts from 20% to 100%, indicating performance is contrastlimited for both tasks. The same result was obtained at 30 eccentricity in the peripheral field for the O vs. + letters, again indicating performance is contrast-limited for both tasks. However, resolution acuity for the Landolt-C letters was significantly worse than detection acuity in the periphery over the same range of contrasts, which suggests performance is limited by neural undersampling for these letters. All of our experimental results are explained by a model of neural sampling in which detection acuity is determined by the size of neural receptive fields relative to the dimensions of the tripole responsible for spatial contrast, whereas resolution acuity is determined by the spacing of receptive fields relative to the spacing between strokes responsible for letter form. Copyright 2012 Elsevier Ltd. All rights reserved. 4. Autrusseau F, Thibos L, Shevell SK. Chromatic and wavefront aberrations: L-, M- and S-cone stimulation with typical and extreme retinal image quality. Vision Res Nov;51(21-22): Epub 2011 Aug 31. PMID: [PubMed - indexed for MEDLINE] PMCID: PMC [Available on 2012/11/1] The first physiological process influencing visual perception is the optics of the eye. The retinal image is affected by diffraction at the pupil and several kinds of optical imperfections. A model of the eye (Thibos & Bradley, 1999), which takes account of pupil aperture, chromatic aberration and wavefront aberrations, was used to determine wavelength-dependent point-spread functions, which can be convolved with any stimulus specified by its spectral distribution of light at each point. The resulting retinal spectral distribution of light was used to determine the spatial distribution of stimulation for each cone type (S, M and L). In addition, individual differences in retinal-image quality were assessed using a statistical model (Thibos, Bradley, & Hong, 2002) for population values of Zernike coefficients, which characterize imperfections of the eye's optics. The median and relatively extreme (5th and 95th percentile) modulation transfer functions (MTFs) for the S, M and L cones were determined for equal-energy-spectrum (EES) 'white' light. The typical MTF for S cones was more similar to the MTF for L and M cones after taking wavefront aberrations into account but even with aberrations the S- cone MTF typically was below the M- or L-cone MTF by a factor of at least 10 (one log unit). More generally, the model presented here provides a technique for estimating retinal image quality for the S, M and L cones for any stimulus presented to the eye. The model is applied to some informative examples. Copyright 2011 Elsevier Ltd. All rights reserved. 2

3 5. Shen J, Thibos LN. Peripheral aberrations and image quality for contact lens correction. Optom Vis Sci Oct;88(10): PMID: PMCID: PMC [Available on 2012/10/1] PURPOSE: Contact lenses (CLs) reduced the degree of hyperopic field curvature present in myopic eyes and rigid CLs reduced spherocylindrical image blur on the peripheral retina, but their effect on higher order aberrations and overall optical quality of the eye in the peripheral visual field is still unknown. The purpose of our study was to evaluate peripheral wavefront aberrations and image quality across the visual field before and after CL correction. METHODS: A commercial Hartmann-Shack aberrometer was used to measure ocular wavefront errors in 5 steps out to 30 of eccentricity along the horizontal meridian in uncorrected eyes and when the same eyes are corrected with soft or rigid CLs. Wavefront aberrations and image quality were determined for the full elliptical pupil encountered in off-axis measurements. RESULTS: Ocular higher order aberrations (HOA) increase away from fovea in the uncorrected eye. Third-order aberrations are larger and increase faster with eccentricity compared with the other HOA. CLs increase all HOA except third-order Zernike terms. Nevertheless, a net increase in image quality across the horizontal visual field for objects located at the foveal far point is achieved with rigid lenses, whereas soft CLs reduce image quality. CONCLUSIONS: Second-order aberrations limit image quality more than HOA in the periphery. Although second-order aberrations are reduced by CLs, the resulting gain in image quality is partially offset by increased amounts of HOA. To fully realize the benefits of correcting HOA in the peripheral field requires improved correction of second-order aberrations as well. 6. Martin J, Vasudevan B, Himebaugh N, Bradley A, Thibos L. Unbiased estimation of refractive state of aberrated eyes. Vision Res Jul 14. [Epub ahead of print] PMID: [PubMed - indexed for MEDLINE] PMCID: PMC [Available on 2012/9/1] We seek unbiased methods for estimating the target vergence required to maximize visual acuity based on wavefront aberration measurements. Experiments were designed to minimize the impact of confounding factors that have hampered previous research. Objective wavefront refractions and subjective acuity refractions were obtained for the same monochromatic wavelength. Accommodation and pupil fluctuations were eliminated by cycloplegia. Unbiased subjective refractions that maximize visual acuity for high contrast letters were performed with a computer controlled forced choice staircase procedure, using diopter steps of defocus. All experiments were performed for two pupil diameters (3mm and 6mm). As reported in the literature, subjective refractive error does not change appreciably when the pupil dilates. For 3mm pupils most metrics yielded objective refractions that were about 0.1D more hyperopic than subjective acuity refractions. When pupil diameter increased to 6mm, this bias changed in the myopic direction and the variability between metrics also increased. These inaccuracies were small compared to the precision of the measurements, which implies that most metrics provided unbiased estimates of 3

4 refractive state for medium and large pupils. Thus a variety of image quality metrics may be used to determine ocular refractive state for monochromatic (635nm) light, thereby achieving accurate results without the need for empirical correction factors.copyright 2011 Elsevier Ltd. All rights reserved. 7. Nam J, Thibos LN, Bradley A, Himebaugh N, Liu H. Forward light scatter analysis of the eye in a spatially-resolved double-pass optical system. Opt. Express Apr 11; 19(8): doi: /OE PubMed PMID: An optical analysis is developed to separate forward light scatter of the human eye from the conventional wavefront aberrations in a double pass optical system. To quantify the separate contributions made by these micro- and macro-aberrations, respectively, to the spot image blur in the Shark-Hartmann aberrometer, we develop a metric called radial variance for spot blur. We prove an additivity property for radial variance that allows us to distinguish between spot blurs from macro-aberrations and micro-aberrations. When the method is applied to tear break-up in the human eye, we find that micro-aberrations in the second pass accounts for about 87% of the double pass image blur in the Shack- Hartmann wavefront aberrometer under our experimental conditions Optical Society of America 8. Ravikumar S, Bradley A, Thibos L. Phase changes induced by optical aberrations degrade letter and face acuity. J Vis Dec 16; 10(14):18. doi: / Print PMID: Optical aberrations of the eye reduce image contrast and induce spatial phase shifts in the retinal image. The resulting degradation of retinal image quality hampers recognition of complex objects such as letters and faces. To study the effects of spatial phase shifts on object recognition, we simulated image blur computationally for 4 types of aberrations (defocus, astigmatism, coma, and spherical aberration) present individually or in combinations. Phase errors in the computed images were corrected (by setting phase to zero), or avoided, by removing the affected frequency components (by setting modulation to zero). The resulting images served as visual stimuli to determine the effects of phase errors on visual acuity for single letters, letter clusters, and faces. The results show that 180 phase reversals induced by optical aberrations reduce visual acuity, when there is sufficient contrast in the affected frequency components. In the presence of positive spherical aberration, acuity loss due to phase errors was more for hyperopic defocus than for myopic defocus, because the contrast of phase-reversed components was much higher for hyperopic defocus. Phase shifts introduced by coma are less than 180 and consequently have a smaller impact on acuity. Although visual acuity improved the most when all frequency components were phase-corrected, phase-reversed components were nevertheless found to aid visual acuity, demonstrating phase-reversed resolution. 9. Sawides L, Marcos S, Ravikumar S, Thibos L, Bradley A, Webster M. Adaptation to astigmatic blur. J Vis Oct 18; 10(12):22. Print PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article 4

5 Adapting to blurred or sharpened images alters the perceived focus of subsequently viewed images. We examined whether these adaptation effects could arise from actual sphero-cylindrical refractive errors, by testing aftereffects in images simulating secondorder astigmatism. Image blur was varied from negative (vertical) through isotropic to positive (horizontal) astigmatism while maintaining constant blur strength. A 2AFC staircase was used to estimate the stimulus that appeared isotropically blurred before or after adapting to images with astigmatism. Adaptation to horizontal blur caused isotropically blurred images to appear vertically biased and vice versa, shifting the perceived isotropic point toward the adapting level. Aftereffects were similar for different types of images and showed partial selectivity so that strongest effects generally occurred when testing and adapting images were the same. Further experiments explored whether the adaptation depended more strongly on the blurring or "fuzziness" in the images vs. the apparent "figural" changes introduced by the blur, by comparing how the aftereffects transfer across changes in size or orientation. Our results suggest that strong selective adaptation can occur for different lower order aberrations of the eye and that these may be at least partly driven by the apparent figural changes that blurring introduces into the retinal image. 10. Wei X, Thibos LN. Modal estimation of wavefront phase from slopes over elliptical pupils. Optom Vis Sci Oct; 87(10):E PMID: [PubMed - indexed for MEDLINE] PURPOSE: Measuring the off-axis optical quality of the eye with a Shack-Hartmann wavefront sensor requires methods for reconstructing wavefront from the gradient data defined within an elliptical pupil. Such methods for modal estimation of wavefront aberrations are sensitive to pupil shape. METHODS: We develop a conceptual framework that reconciles two published, but apparently dissimilar, methods for reconstruction over an elliptical pupil based on Zernike analysis. Our unified treatment shows that the two methods have different interpretations but the vectors of Zernike coefficients they produce are related linearly. Two novel methods based on Fourier series are also introduced for a model of gradient sensors based on Southwell geometry. RESULTS: All four methods were evaluated numerically with three test-cases: a defocus wavefront (1), a spherocylindrical wavefront (2), and a random-generated wavefront (3). Under noise-free conditions, all four methods reconstructed the tested wavefronts accurately. The reconstruction error is negligible at the level of numerical computation. Furthermore, the Monte-Carlo simulation with test case 2 revealed small differences in sensitivity to noise between the two Zernike methods but no difference between the two Fourier methods. Because of the smoothing effects, the two Zernikebased methods are more robust to noise than are the two Fourier methods. However, Fourier methods are computationally faster. CONCLUSIONS: All four modal methods are validated methods to reconstruct wavefronts from the gradients over the elliptical pupil. The choice of these methods is application dependent. 11. Aaron MT, Applegate RA, Porter J, Thibos LN, Schallhorn SC, Brunstetter TJ, Tanzer DJ. Why preoperative acuity predicts postoperative acuity in 5

6 wavefront-guided LASIK. Optom Vis Sci Nov; 87(11): PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article PURPOSE: To critically evaluate the following clinical wisdom regarding custom (wavefront-guided) laser in situ keratomileusis (LASIK) that subjects with better-thanaverage best-corrected visual acuity (BCVA) before surgery have a greater risk of losing BCVA postoperatively than do subjects with worse-than-average BCVA before surgery. METHODS: High contrast BCVA was measured once before and 3 months after custom LASIK in one eye of 79 subjects. Preoperative spherical equivalent refractive error ranged between and D. The sample was divided into one of two subsamples: eyes that had better-than-average preoperative BCVA (<-0.11 logmar) and eyes that had average or worse-than-average preoperative BCVA ( logmar). Controls were implemented for retinal magnification and for the statistical phenomenon of regression to the mean of the preoperative acuity measurement. RESULTS: On average, for the entire sample, moving the correction from the spectacle plane to the corneal plane increased letter acuity 4.7% (1 letter, 0.02 logmar). For each subsample, the percentage regression to the mean was 57.24%. After correcting for magnification effects and regression to the mean, eyes with better-than-average preoperative acuity had a small but significant gain in acuity ( 1 letter, p = 0.040) that was nearly identical to the gain for eyes with worse-than-average preoperative acuity ( 1.5 letters, p = 0.002). CONCLUSIONS: Custom LASIK produced a statistically significant gain in visual acuity after correction for magnification effects. Dividing the sample into two subsamples based on preoperative acuity confirmed the common clinical observation that eyes with better-than-average acuity tend to remain the same or lose acuity, whereas eyes with worse-than-average acuity tend to gain acuity. However, when only one acuity measurement is taken at a single time point and the sample is subsampled nonrandomly, this clinical observation is due to a statistical artifact (regression to the mean) and is not attributable to the surgery. 12. Shen J, Clark CA, Soni PS, Thibos LN. Peripheral refraction with and without contact lens correction. Optom Vis Sci Sep; 87(9): PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article PURPOSE: Peripheral refractive error degrades the quality of retinal images and has been hypothesized to be a stimulus for the development of refractive error. The purpose of this study was to investigate the changes in refractive error across the horizontal visual field produced by contact lenses (CLs) and to quantify the effect of CLs on peripheral image blur. METHODS: A commercial Shack-Hartmann aberrometer measured ocular wavefront aberrations in 5 degrees steps across the central 60 degrees of visual field along the horizontal meridian before and after CLs correction. Wavefront refractions for peripheral lines-of-sight were based on the full elliptical pupil encountered in peripheral measurements. Curvature of field is the change in peripheral spherical equivalent relative to the eye's optical axis. 6

7 RESULTS: Hyperopic curvature of field in the naked eye increases with increasing amounts central myopic refractive error as predicted by Atchison (2006). For an eccentricity of E degrees, field curvature is approximately E percent of foveal refractive error. Rigid gas permeable (RGP) lenses changed field curvature in the myopic direction twice as much as soft CLs (SCLs). Both of these effects varied with CLs power. For all lens powers, SCL cut the degree of hyperopic field curvature in half whereas RGP lenses nearly eliminated field curvature. The benefit of reduced field curvature was partly offset by increased oblique astigmatism. The net reduction of retinal blur because of CLs is approximately constant across the visual field. CONCLUSIONS: Both SCL and RGP lenses reduced the degree of hyperopic field curvature present in myopic eyes, with RGP lenses having greater effect. The tradeoff between field curvature and off-axis astigmatism with RGP lenses may limit their effectiveness for control of myopia progression. These results suggest that axial growth mechanisms that depend on retinal image quality will be affected more by RGP than by SCL lenses. 13. Nam J, Rubinstein J, Thibos L. Wavelength adjustment using an eye model from aberrometry data. J Opt Soc Am A Opt Image Sci Vis Jul 1; 27(7): doi: /JOSAA PMID: [PubMed - indexed for MEDLINE] We developed a method to convert aberrometry data obtained in one wavelength to the corresponding data in another wavelength using an eye model. A single map of aberrometry data is used to construct a free-form one-surface eye model. A general algorithm for the surface construction is described and implemented for real aberrometry data. Our method can handle varying conjugate distances of the measurement plane of the aberrometer and can also manage the chief ray prism that may be present. The algorithm is validated with the aid of an artificial plastic eye. The wavefronts in different wavelengths are compared through the Zernike analysis not only for lower-order aberrations, but also for higher-order aberrations. The results show that the changes of the Zernike aberration coefficients due to wavelengths are non-uniform. The defocus term has the highest effect from wavelength changes, which is consistent with the previous literature. Our method is compared with two approximate semianalytical algorithms. The wavelength adjustments from a multi-surface eye model are contrasted with our method. We prove analytically that the conventional method of wavelength adjustment is based on paraxial analysis. In addition, we provide a method of finding the chief ray using back-projection in some cases and discuss different meanings of prism. 14. Cheng X, Bradley A, Ravikumar S, Thibos LN. Visual impact of Zernike and Seidel forms of monochromatic aberrations. Optom Vis Sci May; 87(5): PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article PURPOSE: The aim of this study was to examine the impact of different aberrations modes (e.g., coma, astigmatism, spherical aberration [SA]) and different aberration basis functions (Zernike or Seidel) on visual acuity (VA). 7

8 METHODS: Computational optics was used to generate retinal images degraded by either the Zernike or Seidel forms of second through fourth-order aberrations for an eye with a 5-mm pupil diameter. High contrast, photopic VA was measured using method of constant stimuli for letters displayed on a computer-controlled, linearized, quasimonochromatic (lambda = 556 nm) display. RESULTS: Minimum angle of resolution (MAR) varied linearly with the magnitude (root mean square error) of all modes of aberration. The impact of individual Zernike lowerand higher-order aberrations (HOAs) varied significantly with mode, e.g., arc minutes of MAR per micrometer of root mean square slopes varied from 7 (spherical defocus) to 0.5 (quadrafoil). Seidel forms of these aberrations always had a smaller visual impact. Notably, Seidel SA had 1/17th the impact of Zernike SA with the same wavefront variance, and about 1/4th the impact of Zernike SA with matching levels of r wavefront error. With lower-order components removed, HOAs near the center of the Zernike pyramid do not have a large visual impact. CONCLUSIONS: The majority of the visual impact of high levels of fourth-order Zernike aberrations can be attributed to the second-order terms within these polynomials. Therefore, the impact of SA can be minimized by balancing it with a defocus term that flattens the central wavefront (paraxial focus) or maximizes the area of the pupil with a flat wavefront. Over this wide range of aberration types and levels, image quality metrics based on the Point Spread Function (PSF) and Optical Transfer Function (OTF) can predict VA as reliably as VA measures can predict retests of VA, and, thus, such metrics may become valuable predictors of both VA and, via optimization, refractions. 15. Kirschen DG, Laby DM, Kirschen MP, Applegate R, Thibos LN. Optical aberrations in professional baseball players. J Cataract Refract Surg Mar; 36(3): PMID: [PubMed - indexed for MEDLINE] PURPOSE: To determine the presence, type, and size of optical higher-order aberrations (HOAs) in professional athletes with superior visual acuity and to compare them with those in an age-matched population of nonathletes. SETTING: Vero Beach and Fort Myers, Florida, USA. METHODS: Players from 2 professional baseball teams were studied. Each player's optical aberrations were measured with a naturally dilated 4.0 mm pupil using a Z-Wave aberrometer and a LADARWave aberrometer. RESULTS: One hundred sixty-two players (316 eyes) were evaluated. The HOAs were less than mum in all cases. Spherical aberration C(4,0) was the largest aberration with both aberrometers. There were small but statistically significant differences between the aberrometers in mean values for trefoil C(3,3) and C(3,-3) and secondary astigmatism C(4,2). Although statistically significant, the differences were clinically insignificant, being similar at approximately diopter (D) of spherical power. A statistically significant difference was found between the professional baseball players and the control population in trefoil C(3,-3). These differences were clinically insignificant, similar to D of spherical power. CONCLUSIONS: Professional baseball players have small higher-order optical aberrations when tested with naturally dilated pupils. No clinically significant differences were found between the 2 aberrometers. Statistically significant differences in trefoil were found between the players and the control population; however, the difference was 8

9 clinically insignificant. It seems as though the visual system of professional baseball players is limited by lower-order aberrations and that the smaller HOAs do not enhance visual function over that in a control population.copyright 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved. 16. Wei X, Thibos L. Design and validation of a scanning Shack Hartmann aberrometer for measurements of the eye over a wide field of view. Opt Express Jan 18; 18(2): doi: /OE PMID: [PubMed - indexed for MEDLINE] Peripheral vision and off-axis aberrations not only play an important role in daily visual tasks but may also influence eye growth and refractive development. Thus it is important to measure off-axis wavefront aberrations of human eyes objectively. To achieve efficient measurement, we incorporated a double-pass scanning system with a Shack Hartmann wavefront sensor (SHWS) to develop a scanning Shack Hartmann aberrometer (SSHA). The prototype SSHA successfully measured the off-axis wavefront aberrations over +/- 15 degree visual field within 7 seconds. In two validation experiments with a wide angle model eye, it measured change in defocus aberration accurately (<0.02microm, 4mm pupil) and precisely (<0.03microm, 4mm pupil). A preliminary experiment with a human subject suggests its feasibility in clinical applications. 17. Liu H, Thibos L, Begley CG, Bradley A. Measurement of the time course of optical quality and visual deterioration during tear break-up. Invest Ophthalmol Vis Sci Jun; 51(6): Epub 2010 Jan 27. PMID: [PubMed - indexed for MEDLINE] Free full text PURPOSE: To compare changes in optical quality and visual performance that accompany tear break-up (TBU) during blink suppression. METHODS: A three-channel optical system was developed that simultaneously measured refractive aberrations (Shack-Hartmann aberrometer), 20/40 letter contrast sensitivity (CS), and TBU (retroillumination, RI). Ten wearers of silicone hydrogel contact lenses were asked to keep one eye open for approximately 18 seconds, while CS, wavefront aberrations, and RI images were collected. The wavefront was reconstructed by zonal methods, and image quality was quantified with a series of metrics including RMS fit error. Novel metrics for quantifying TBU over the contact lens surface were developed by quantifying the contrast of the RI image and by using Fourier descriptors of the first Purkinje (PJ) image shape. RESULTS: There was a full range of TBU over the lens surface, with four subjects showing TBU across the corneal center and one subject with TBU in the inferior peripheral pupil. Among the four subjects with central corneal TBU, RMS fit error, RI contrast, and PJ Fourier descriptors showed high correlation with CS (r(2) range, , , and , respectively). Some of the general optical-quality metrics such as blur strength, neural sharpness, and area of modulation transfer function (MTF) also showed that change correlated with CS loss. CONCLUSIONS: Optical metrics of tear quality and retinal image quality are associated with the decline in vision that occurs with TBU. The evidence supports the hypothesis 9

10 that blurry vision symptoms reported by contact lens wearers are caused by poor quality of the retinal image due to TBU. 18. Evans DW, Wang Y, Haggerty KM, Thibos LN. Effect of sampling array irregularity and window size on the discrimination of sampled gratings. Vision Res Jan; 50(1): Epub. Erratum in: Vision Res May 12; 50(10):995. PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article The effect of sampling irregularity and window size on orientation discrimination was investigated using discretely sampled gratings as stimuli. For regular sampling arrays, visual performance could be accounted for by a theoretical analysis of aliasing produced by undersampling. For irregular arrays produced by adding noise to the location of individual samples, the incidence of perceived orientation reversal declined and the spatial frequency range of flawless performance expanded well beyond the nominal Nyquist frequency. These results provide a psychophysical method to estimate the spatial density and the degree of irregularity in the neural sampling arrays that limit human visual resolution. 19. Chui TY, Thibos LN, Bradley A, Burns SA. The mechanisms of vision loss associated with a cotton wool spot. Vision Res Nov; 49(23): Epub 2009 Aug 22. PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article 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. 20. Wei X, Van Heugten T, Thibos L. Validation of a Hartmann-Moiré wavefront sensor with large dynamic range. Opt Express Aug 3; 17(16): PMID: [PubMed - indexed for MEDLINE] Our goal was to validate the accuracy, repeatability, sensitivity, and dynamic range of a Hartmann-Moiré (HM) wavefront sensor (PixelOptics, Inc.) designed for ophthalmic applications. Methods: Testing apparatus injected a 4 mm diameter monochromatic (532 nm) beam of light into the wavefront sensor for measurement. Controlled amounts of defocus and astigmatism were introduced into the beam with calibrated spherical (- 20D to + 18D) and cylindrical (-8D to + 8D) lenses. Repeatability was assessed with three repeated measurements within a 2-minute period. Results: Correlation coefficients between mean wavefront measurements (n = 3) and expected wavefront vergence for both sphere and cylinder lenses were > For spherical lenses, the sensor was accurate to within 0.1D over the range from -20D to + 18D. For cylindrical lenses, the 10

11 sensor was accurate to within 0.1D over the range from -8D to + 8D. The primary limitation to demonstrating an even larger dynamic range was the increasingly critical requirements for optical alignment. Sensitivity to small changes of vergence was constant over the instrument's full dynamic range. Repeatability of measurements for fixed condition was within 0.01D. Conclusion: The Hartmann-Moiré wavefront sensor measures defocus and astigmatism accurately and repeatedly with good sensitivity over a large dynamic range required for ophthalmic applications. 21. Shen J, Thibos LN. Measuring ocular aberrations and image quality in peripheral vision with a clinical wavefront aberrometer. Clin Exp Optom May; 92(3): PMID: [PubMed - indexed for MEDLINE] BACKGROUND: Clinical aberrometers are accurate, robust instruments for measuring wavefront aberrations for foveal vision, but several practical concerns arise when performing aberrometry of the peripheral field. The purpose of this study was to evaluate these concerns experimentally using a physical eye model. METHODS: A physical model eye was constructed to provide a stable test case that resembled a human eye. Aberrations were measured with a commercial Shack- Hartmann aberrometer along lines-of-sight ranging from zero to 45 degrees of eccentricity. Commercial software for wavefront reconstruction and Zernike analysis was adapted for use with elliptical entrance pupils encountered off-axis. RESULTS: Pupil dimensions estimated from the array of Shack-Hartmann spots captured by the wavefront sensor followed geometrical optics predictions up to 30 degrees eccentricity. With careful attention to detail, aberration analysis over an elliptical pupil was verified with alternative software. Retinal image quality declined slowly as eccentricity increased due to the eye model's spherical aberration. The total RMS computed from Zernike coefficients overestimated the total RMS computed based on the wavefront error of the elliptical pupil.conclusion: Measurement of off-axis wavefront aberrations of a model eye over a restricted range of eccentricities is possible with the COAS clinical wavefront aberrometer and auxiliary lenses to correct astigmatism. When central image quality is good, the off-axis aberrations will have a powerful effect on peripheral image quality. When central image quality is poor, the additional effect of off-axis aberrations will be minor. 22. Iskander DR, Nam J, Thibos LN. The statistics of refractive error maps: managing wavefront aberration analysis without Zernike polynomials. Ophthalmic Physiol Opt May; 29(3): PMID: [PubMed - indexed for MEDLINE] The refractive error of a human eye varies across the pupil and therefore may be treated as a random variable. The probability distribution of this random variable provides a means for assessing the main refractive properties of the eye without the necessity of traditional functional representation of wavefront aberrations. To demonstrate this approach, the statistical properties of refractive error maps are investigated. Closed-form expressions are derived for the probability density function (PDF) and its statistical moments for the general case of rotationally-symmetric aberrations. A closed-form expression for a PDF for a general non-rotationally symmetric wavefront aberration is difficult to derive. However, for specific cases, such 11

12 as astigmatism, a closed-form expression of the PDF can be obtained. Further, interpretation of the distribution of the refractive error map as well as its moments is provided for a range of wavefront aberrations measured in real eyes. These are evaluated using a kernel density and sample moments estimators. It is concluded that the refractive error domain allows non-functional analysis of wavefront aberrations based on simple statistics in the form of its sample moments. Clinicians may find this approach to wavefront analysis easier to interpret due to the clinical familiarity and intuitive appeal of refractive error maps. 23. Thibos LN. Retinal image quality for virtual eyes generated by a statistical model of ocular wavefront aberrations. Ophthalmic Physiol Opt May; 29(3): PMID: [PubMed - indexed for MEDLINE] A statistical model of the aberration structure of normal, well-corrected eyes was developed previously (Opthal. Physiol. Opt22, , 2002.) from wavefront aberrations measured for 100 normal eyes (J. Opt. Soc. Am. A.19, , 2002.). The model is capable of generating an unlimited number of wavefront aberration functions for virtual eyes drawn randomly from a multivariate Gaussian distribution of Zernike aberration coefficients. This report provides evidence that monochromatic retinal image quality in virtual eyes, as quantified by 31 different image quality metrics (J. Vis.4, , 2004.), is representative of human eyes but slightly exaggerates the degradation of the retinal image caused by ocular aberrations. A demonstration program for producing virtual eyes is included as an Appendix to this paper. 24. Nam J, Thibos LN, Iskander DR. Zernike radial slope polynomials for wavefront reconstruction and refraction. J Opt Soc Am A Opt Image Sci Vis Apr; 26(4): PMID: [PubMed - indexed for MEDLINE] Ophthalmic wavefront sensors typically measure wavefront slope, from which wavefront phase is reconstructed. We show that ophthalmic prescriptions (in power-vector format) can be obtained directly from slope measurements without wavefront reconstruction. This is achieved by fitting the measurement data with a new set of orthonormal basis functions called Zernike radial slope polynomials. Coefficients of this expansion can be used to specify the ophthalmic power vector using explicit formulas derived by a variety of methods. Zernike coefficients for wavefront error can be recovered from the coefficients of radial slope polynomials, thereby offering an alternative way to perform wavefront reconstruction. 25. Nam J, Thibos LN, Iskander DR. Describing ocular aberrations with wavefront vergence maps. Clin Exp Optom May; 92(3): Epub 2009 Mar 19. PMID: [PubMed - indexed for MEDLINE] A common optometric problem is to specify the eye's ocular aberrations in terms of Zernike coefficients and to reduce that specification to a prescription for the optimum sphero-cylindrical correcting lens. The typical approach is first to reconstruct wavefront phase errors from measurements of wavefront slopes obtained by a wavefront aberrometer. This paper applies a new method to this clinical problem that does not require wavefront reconstruction. Instead, we base our analysis of axial wavefront 12

13 vergence as inferred directly from wavefront slopes. The result is a wavefront vergence map that is similar to the axial power maps in corneal topography and hence has a potential to be favoured by clinicians. We use our new set of orthogonal Zernike slope polynomials to systematically analyse details of the vergence map analogous to Zernike analysis of wavefront maps. The result is a vector of slope coefficients that describe fundamental aberration components. Three different methods for reducing slope coefficients to a spherocylindrical prescription in power vector forms are compared and contrasted. When the original wavefront contains only second order aberrations, the vergence map is a function of meridian only and the power vectors from all three methods are identical. The differences in the methods begin to appear as we include higher order aberrations, in which case the wavefront vergence map is more complicated. Finally, we discuss the advantages and limitations of vergence map representation of ocular aberrations. 26. Applegate RA, Thibos LN, Twa MD, Sarver EJ. Importance of fixation, pupil center, and reference axis in ocular wavefront sensing, videokeratography, and retinal image quality. J Cataract Refract Surg Jan; 35(1): PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article PURPOSE: To examine the impact of the location of the fixation target, pupil center, and reference axis of ophthalmic aberrometers and videokeratographers on the measurement of corneal aberrations relevant to vision. SETTING: Clinical Research, Visual Optics Institute, College of Optometry, University of Houston, Houston, Texas, USA. METHODS: The design features of a generic aberrometer and videokeratographer and their interaction with the eye were examined. The results provided a theoretical framework for experimental assessment of pupil translation errors on corneal aberrations relevant to vision and their correction in 129 eyes. RESULTS: Two key principles emerged. First, the aberrometer's measurement axis must coincide with the eye's line-of-sight (LoS). Second, the videokeratographer's measurement axis (the vertex normal) must be parallel with the eye's LoS. When these principles are satisfied, the eye will be in the same state of angular rotation and direct comparison of measurements is justified, provided any translation of the pupil from the vertex normal is taken into account. The error incurred by ignoring pupil displacement in videokeratography varies between eyes and depends on the type of aberration and amount of displacement, with the largest residual correction root-mean-square wavefront error being 1.26 mum over a 6.0 mm pupil, which markedly decreases retinal image quality. CONCLUSION: Translation of the pupil center with respect to the vertex normal in videokeratography should not be ignored in the calculation of the corneal first-surface, internal aberrations of the eye relevant to vision, or the design of refractive corrections based on videokeratography. 27. Wei X, Thibos L. Modeling the eye's optical system by ocular wavefront tomography. Opt Express Dec 8; 16(25): PMID: [PubMed - indexed for MEDLINE] 13

14 PURPOSE: Ocular wavefront tomography (OWT) is the process of using wavefront aberration maps obtained along multiple lines-of-sight (LoS) to determine the shape and position of the major refracting elements of an eye. One goal of OWT is to create a customized schematic model eye that is anatomically similar and functionally equivalent to the individual eye over a large field of view. METHODS: Wavefront aberration maps along multiple LoS were used as design goals for configuring a generic, multi-surface model eye with aberrations that match the measurements. The model was constrained by gross anatomical dimensions and optimized to mimic the measured eye. The method was evaluated with two test cases: (1) a physical model eye with a doublet lens measured with a clinical wavefront aberrometer along six LoS between -31 deg and +29 deg eccentricities, and (2) a mathematical model of the myopic eye for which wavefront aberrations were computed by ray tracing. RESULTS: In case 1, the OWT algorithm successfully predicted the structure of the doublet model eye from the experimental on- and off-axis aberration measurements. In case 2, the algorithm started with a symmetric five surface model eye and optimized it to generate the on- and off-axis aberrations of a GRIN myopia model eye. The adjusted model closely mimicked the physical parameters and optical behavior of the expected myopia model eye over a large field of view. The maximum discrepancy between aberrations of the OWT optimized model and measurements was 0.05 microns RMS for test case 1 and 0.2 microns RMS for test case 2. CONCLUSION: Our implementation of OWT is a valid, feasible, and robust method for constructing an optical model that is anatomically and functionally similar to the eye over a wide field of view. 28. Thibos LN. Where is the optimum far-point for a presbyopic eye? J Refract Surg Nov; 24(9): PMID: [PubMed - indexed for MEDLINE] PURPOSE: To resolve the presbyope's dilemma by determining the optimum location of the far-point that maximizes depth-of-field for reading printed text. METHODS: Geometrical optical analysis of defocused retinal images was used to compute the size of retinal blur circles relative to object size. Functional consequences of changes in viewing distance, pupil diameter, and far-point location were assessed using the blur ratio concept. Depth-of-field was specified by the ratio of the maximum distance to the minimum distance for which printed text of a given size is legible. RESULTS: For the emmetropic patient, text that is legible at one viewing distance remains legible at all shorter distances. Conversely, text that is illegible at one distance is illegible at all distances. For myopic (or undercorrected) patients, the location of the far-point determines the center of the depth-of-field, but not its size. The depth-of-field is shown numerically and analytically to be given by the approximate formula: log(far distance/near distance) = 0.174* blur ratio threshold* letter height/pupil diameter. CONCLUSIONS: Location of the far-point is a free parameter that can be adjusted to suit a patient's needs without affecting depth-of-field. This suggests a theoretically based clinical strategy for presbyopic refractive correction that takes account of reading needs, pupil size, text size, and habitual reading distance for the benefit of the presbyopic patient. 14

15 29. Ravikumar S, Thibos LN, Bradley A. Calculation of retinal image quality for polychromatic light. J Opt Soc Am A Opt Image Sci Vis Oct; 25(10): PMID: [PubMed - indexed for MEDLINE] Although the retinal image is typically polychromatic, few studies have examined polychromatic image quality in the human eye. We begin with a conceptual framework including the formulation of a psychophysical linking hypothesis that underlies the utility of image quality metrics based on the polychromatic point-spread function. We then outline strategies for computing polychromatic point-spread functions of the eye when monochromatic aberrations are known for only a single wavelength. Implementation problems and solutions for this strategy are described. Polychromatic image quality is largely unaffected by wavelength-dependent diffraction and higher-order chromatic aberration. However, accuracy is found to depend critically upon spectral sampling. Using typical aberrations from the Indiana Aberration Study, we assessed through-focus image quality for model eyes with and without chromatic aberrations using a polychromatic metric called the visual Strehl ratio. In the presence of typical levels of monochromatic aberrations, the effect of longitudinal chromatic aberration is greatly reduced. The effect of typical levels of transverse chromatic aberration is virtually eliminated in the presence of longitudinal chromatic aberration and monochromatic aberrations. Clinical value and limitations of the method are discussed. 30. Teel DF, Copland RJ, Jacobs RJ, Wells T, Neal DR, Thibos LN. Design and validation of an infrared Badal optometer for laser speckle. Optom Vis Sci Sep; 85(9): PMID: [PubMed - indexed for MEDLINE] PURPOSE: To validate the design of an infrared wavefront aberrometer with a Badal optometer employing the principle of laser speckle generated by a spinning disk and infrared light. The instrument was designed for subjective meridional refraction in infrared light by human patients. METHODS: Validation employed a model eye with known refractive error determined with an objective infrared wavefront aberrometer. The model eye was used to produce a speckle pattern on an artificial retina with controlled amounts of ametropia introduced with auxiliary ophthalmic lenses. A human observer performed the psychophysical task of observing the speckle pattern (with the aid of a video camera sensitive to infrared radiation) formed on the artificial retina. Refraction was performed by adjusting the vergence of incident light with the Badal optometer to nullify the motion of laser speckle. Validation of the method was performed for different levels of spherical ametropia and for various configurations of an astigmatic model eye. RESULTS: Subjective measurements of meridional refractive error over the range -4D to +4D agreed with astigmatic refractive errors predicted by the power of the model eye in the meridian of motion of the spinning disk. CONCLUSIONS: Use of a Badal optometer to control laser speckle is a valid method for determining subjective refractive error at infrared wavelengths. Such an instrument will be useful for comparing objective measures of refractive error obtained for the human eye with autorefractors and wavefront aberrometers that employ infrared radiation. 15

16 31. Validation of an off-eye contact lens Shack-Hartmann wavefront aberrometer. Kollbaum P, Jansen M, Thibos L, Bradley A. Optom Vis Sci Sep;85(9):E PMID: [PubMed - indexed for MEDLINE] Free PMC Article Free full text PMCID: PMC PURPOSE: To evaluate the ability of a commercially available single pass Shack- Hartmann aberrometer to evaluate contact lens aberrations. METHODS: Accuracy of second-order aberration measurements was verified by measuring a series of precision calibration lenses, spectacle lenses, and contact lenses. Power measurements were compared to those expected by an independent measurement or those provided by the lens manufacturer. Accuracy of third-order aberrations was verified by systematically decentering a lens with known amounts of spherical aberration and comparing the magnitude of induced coma to that of optical theory. Fourth-order aberration accuracy was verified by comparing measured longitudinal spherical aberration values to those expected by ray tracing based on the lens design. Accuracy of lower- and higher-order aberrations was verified for measurements of lenses taken in air and within a saline-filled wet cell. Repeatability was also assessed by comparing repeated measurements of the wet cell and lens in a wet cell, before and after manipulation of that cell. RESULTS: In all cases, measured values closely matched the expected values, generally exhibiting errors of <1%. CONCLUSIONS: The instrument demonstrates good accuracy and repeatability in measuring second-, third-, and fourth-order aberrations of contact lenses and provides the industry with an instrument for evaluating the ex vivo optical characteristics of contact lenses. 32. Applegate RA, Marsack JD, Thibos LN. Metrics of retinal image quality predict visual performance in eyes with 20/17 or better visual acuity. Optom Vis Sci Sep; 83(9): PMID: [PubMed - indexed for MEDLINE] PMCID: PMC Free PMC Article PURPOSE: The purpose of this study is to determine the ability of single-value metrics of retinal image quality of the eye to predict visual performance as measured by high (HC) and low (LC) -contrast acuity at photopic (P) and mesopic (M) light levels in eyes with 20/17 and better visual acuity. METHODS: Forty-nine normal subjects in good health ranging in age from 21.8 to 62.6 with 20/17 or better monocular high-contrast logarithm of the minimum angle of resolution (logmar) acuity served as subjects. Wavefront error through the 10th Zernike radial order over a 7-mm pupil was measured on each test eye using a custom-built Shack/Hartmann wavefront sensor. For each eye, 31 different single-value retinal image quality metrics were calculated. Visual acuity was measured using HC (95%) and LC (11%) logmar at photopic (270 cd/m) and mesopic (0.75 cd/m) light levels. To determine the ability of each metric of retinal image quality to predict each type of logmar acuity (P HC, P LC, M HC, and M LC), each acuity measure was regressed against each optical quality metric. RESULTS: The ability of the metrics of retinal image quality to predict logmar acuity improved as luminance and/or contrast is lowered. The best retinal image quality metric 16

17 (logpfsc) accounted for 2.6%, 15.1%, 27.6%, and 40.0% of the variance in P HC, P LC, M HC, and M LC logmar acuity, respectively. CONCLUSIONS: In eyes with 20/17 and better P HC acuity, P HC logmar acuity is insensitive to variations in retinal image quality compared with M LC logmar acuity. Retinal image quality becomes increasingly predictive of logmar acuity as contrast and/or luminance is decreased. Everyday life requires individuals to function over a large range of contrast and luminance levels. Clinically, the impact of retinal image quality as a function of luminance and contrast is readily measurable in a time-efficient manner with M LC logmar acuity charts. 33. Barbero S, Rubinstein J, Thibos LN. Wavefront sensing and reconstruction from gradient and Laplacian data measured with a Hartmann-Shack sensor. Opt Lett Jun 15; 31(12): PMID: [PubMed] PMCID: PMC Free PMC Article A new wavefront sensing and reconstruction technique is presented. It is possible to measure Laplacian and gradient information of a wavefront with a Hartmann-Shack setup. By simultaneously using the Laplacian and gradient data we reconstruct the wavefront by sequentially solving two partial differential equations. 34. Barbero S, Thibos LN. Error analysis and correction in wavefront reconstruction from the transport-of-intensity equation. Opt Eng. 2006; 45(9): PMID: [PubMed] PMCID: PMC Free PMC Article Wavefront reconstruction from the transport-of-intensity equation (TIE) is a well-posed inverse problem given smooth signals and appropriate boundary conditions. However, in practice experimental errors lead to an ill-condition problem. A quantitative analysis of the effects of experimental errors is presented in simulations and experimental tests. The relative importance of numerical, misalignment, quantization, and photodetection errors are shown. It is proved that reduction of photodetection noise by wavelet filtering significantly improves the accuracy of wavefront reconstruction from simulated and experimental data. 35. Miller D, Thibos L, Hong X. Requirements for segmented correctors for diffraction-limited performance in the human eye. Opt Express Jan 10; 13(1): PMID: [PubMed - in process] Wavefront correctors have yet to provide diffraction-limited imaging through the human eye's ocular media for large pupils (>/= 6 mm).to guide future improvements in corrector designs that might enable such imaging, we have modeled the performance of segmented piston correctors in conjunction with measured wave aberration data of normal human eyes (mean=34.2 yr; stdev= 10.6 yr). The model included the effects of pupil size and wavelength in addition to dispersion, phase wrapping, and number and arrangement of facets in the corrector. Results indicate that </= 100x100 facets are needed to reach diffraction-limited performance for pupils up to 8 mm (extrapolated) at 0.6 microm wavelength. Required facet density for the eye was found to be substantially higher at the pupil's edge than at its center, which is in stark contrast to the requirements for correcting atmospheric turbulence. Substantially more facets are 17

18 required at shorter wavelengths with performance highly sensitive to facet fill. In polychromatic light, the performance of segmented correctors based on liquid crystal technology was limited by the naturally occurring longitudinal chromatic aberration of the eye rather than phase wrapping and dispersion of the liquid crystal. Required facets to correct defocus alone was found highly sensitive to pupil size and decentration. 36. Chui TY, Yap MK, Chan HH, Thibos LN. Retinal stretching limits peripheral visual acuity in myopia. Vision Res Mar; 45(5): PMID: [PubMed - indexed for MEDLINE] Axial elongation of the myopic eye has the potential to stretch the retina, thereby reducing the sampling density of retinal neurons. Resolution acuity in the peripheral field of normal eyes is known to be sampling-limited, which suggests that retinal stretching in the myopic eye should have a direct effect on resolution acuity everywhere in the visual field except perhaps the fovea, which is usually optically limited. We tested this prediction that neural sampling density is reduced in myopic eyes by measuring resolution acuity for sinusoidal gratings in the fovea plus five peripheral locations in 60 myopic subjects exhibiting a wide range of refractive errors. Control experiments using a detection paradigm to provoke spatial aliasing verified that peripheral resolution was sampling limited. Retinal spatial frequencies of the grating stimulus were computed assuming Knapps' Law of visual optics, which ensures that retinal image size (in mm) is independent of refractive error when axial myopia is corrected by a spectacle lens located in the anterior focal plane of the eye. Results obtained at every retinal locus showed that resolution acuity declined linearly with magnitude of refractive error. Regression of the population data indicated that approximately 15 D of refractive error doubles the spacing between retinal neurons, thereby halving peripheral resolution acuity relative to the emmetropic eye. Several subjects also demonstrated samplinglimited performance in the fovea, which indicated that optical filtering by the eye's optical system failed to protect the fovea from aliasing artifacts of neural undersampling in these eyes. We conclude that stretching of the retina is a primary cause of reduced spatial resolution of the peripheral field, and occasionally of the fovea, in myopic eyes. Stretching appears to be locally uniform over the central +/-15 degrees of visual field but is globally non-uniform since the foveal region appears to stretch more than the globe itself. 37. Thibos LN. Unresolved issues in the prediction of subjective refraction from wavefront aberration maps. J Refract Surg Sep-Oct; 20(5):S Review. PMID: [PubMed - indexed for MEDLINE] Sources of uncertainty in the conversion of wavefront aberration maps to refractive prescriptions are described. These uncertainties highlight the nature of optimum corrections, the imprecise far point in human eyes, multiple strategies for locating an approximate far point, and unresolved aspects of the gold standard for judging success. The conclusion points to future experiments needed to resolve these uncertainties to achieve more accurate and precise methods of objective wavefront refraction. 38. Pesudovs K, Marsack JD, Donnelly WJ 3rd, Thibos LN, Applegate RA. Measuring visual acuity--mesopic or photopic conditions, and high or low 18

19 contrast letters? J Refract Surg Sep-Oct; 20(5):S PMID: [PubMed - indexed for MEDLINE] PURPOSE: To develop single-valued wavefront aberration metrics that correlate strongly with visual performance. The purpose of this study is to explore whether photopic high contrast visual acuity (VA) is an appropriate visual performance reference and whether mesopic and/or low contrast testing provides any advantage. METHODS: Subjects from the Texas Investigation of Cataract Optics study (N = 148) ranged in age from 21.6 to 83.8 years and from clear lens to dense nuclear cataract. Visual acuity was measured under four conditions: photopic high (VA(PHC)) and low (VA(PLC)) contrast, mesopic high (VA(MHC)) and low (VA(MLC)) contrast (photopic = 280 cd/m(2), mesopic = 0.75 cd/m(2)). Variables were tested for compliance with normality (-2.00 < skew and kurtosis < 2.00) and transformed if required. Linear regression and Bland-Altman 95% limits of agreement (+/-1.96 SD) were used to examine relationships between VA variables and between VA and wavefront aberration metrics. RESULTS: The two photopic measures VA(PHC) (skew = 2.57, kurtosis = 12.2) and VA(PLC) (1.67, 5.41) were poorly distributed, but the two mesopic measures VA(MHC) (0.88, 1.67) and VA(MLC) (0.29, -0.18) were normally distributed. Strong correlations existed between the (transformed) VA variables (R: 0.53 to 0.84). However, limits of agreement ranged over 0.30 to 0.42 logmar, whereas retest data suggested a range of All four were offered in stepwise multiple linear regression for 30 wavefront metrics: 20 included VA(MLC) alone, two included VA(PLC), two included VA(MHC) and six included both VA(MLC) and VA(MHC); R(2) averaged 25%. CONCLUSION: Although strongly correlated, low contrast and/or mesopic VA testing provides different information. Wave aberration metrics correlates better with VA(MLC) making this the visual performance test of choice. 39. Thibos LN. The optics of wavefront sensing. Ophthalmol Clin North Am Jun; 17(2):111-7, v. Review. PMID: [PubMed - indexed for MEDLINE] This article reviews the fundamental principles by which wavefront aberrometers measure ocular aberrations. Three different ways of interpreting aberration measurements are described in terms of wavefront phase, slope, and curvature. Although curvature is the more familiar concept from geometrical optics, the wave optics concept of wavefront phase is more useful for understanding the nature of aberrated retinal images and for prescribing treatments to correct high-order aberrations. 40. Zhou F, Hong X, Miller DT, Thibos LN, Bradley A. Validation of a combined corneal topographer and aberrometer based on Shack-Hartmann wavefront sensing. J Opt Soc Am A Opt Image Sci Vis May;21(5): PMID: [PubMed - indexed for MEDLINE] 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 = to 0.994). The sag error root mean square 19

20 (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 ( microm) and appreciable levels of trefoil ( microm), coma ( microm), and spherical aberration ( microm). The mean values of these aberrations were significantly larger than the RMS in repeated measurements. 41. Thibos LN, Hong X, Bradley A, Applegate RA. Accuracy and precision of objective refraction from wavefront aberrations. J Vis Apr 23; 4(4): PMID: [PubMed - indexed for MEDLINE] Free full text 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 D to 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. 42. Marsack JD, Thibos LN, Applegate RA. Metrics of optical quality derived from wave aberrations predict visual performance. J Vis Apr 23; 4(4): PMID: [PubMed - indexed for MEDLINE] Free full text Wavefront-guided refractive surgery and custom optical corrections have reduced the residual root mean squared (RMS) wavefront error in the eye to relatively low levels (typically on the order of 0.25 microm or less over a 6-mm pupil, a dioptric equivalent of 0.19 D). It has been shown that experimental variation of the distribution of 0.25 microm of wavefront error across the pupil can cause variation in visual acuity of two lines on a standard logmar acuity chart. This result demonstrates the need for single-value metrics other than RMS wavefront error to quantify the effects of low levels of aberration 20