Reference Clinical Database for Fixation Stability Metrics in Normal Subjects Measured with the MAIA Microperimeter.

PURPOSE: The purpose of this study was to establish a normal reference database for fixation stability measured with the bivariate contour ellipse area (BCEA) in the Macular Integrity Assessment (MAIA) microperimeter. METHODS: Subjects were 358 healthy volunteers who had the MAIA examination. Fixation stability was assessed using two BCEA fixation indices (63% and 95% proportional values) and the percentage of fixation points within 1° and 2° from the fovea (P1 and P2). Statistical analysis was performed with linear regression and Pearson's product moment correlation coefficient. RESULTS: Average areas of 0.80 deg2 (min = 0.03, max = 3.90, SD = 0.68) for the index BCEA@63% and 2.40 deg2 (min = 0.20, max = 11.70, SD = 2.04) for the index BCEA@95% were found. The average values of P1 and P2 were 95% (min = 76, max = 100, SD = 5.31) and 99% (min = 91, max = 100, SD = 1.42), respectively. The Pearson's product moment test showed an almost perfect correlation index, r = 0.999, between BCEA@63% and BCEA@95%. Index P1 showed a very strong correlation with BCEA@63%, r = -0.924, as well as with BCEA@95%, r = -0.925. Index P2 demonstrated a slightly lower correlation with both BCEA@63% and BCEA@95%, r = -0.874 and -0.875, respectively. CONCLUSIONS: The single parameter of the BCEA@95% may be taken as accurately reporting fixation stability and serves as a reference database of normal subjects with a cutoff area of 2.40 ± 2.04 deg2 in MAIA microperimeter. TRANSLATIONAL RELEVANCE: Fixation stability can be measured with different indices. This study originates reference fixation values for the MAIA using a single fixation index.

Compass: clinical evaluation of a new instrument for the diagnosis of glaucoma.

AIMS: To evaluate Compass, a new instrument for glaucoma screening and diagnosis that combines scanning ophthalmoscopy, automated perimetry, and eye tracking. MATERIALS AND METHODS: A total of 320 human subjects (200 normal, 120 with glaucoma) underwent full ophthalmological evaluation and perimetric evaluation using the Humphrey SITA standard 24° test (HFA), and the Compass test that consisted of a full-threshold program on the central 24° with a photograph of the central 30° of the retina. A subgroup of normal subjects and glaucoma patients underwent a second Compass test during the same day in order to study test-retest variability. After exclusion of 30 patients due to protocol rules, a database was created to compare the Compass to the HFA, and to evaluate retinal image quality and fixation stability. RESULTS: The difference in mean sensitivity between Compass and HFA was -1.02 ± 1.55 dB in normal subjects (p<0.001) and -1.01 ± 2.81 dB in glaucoma (p<0.001). Repeatability SD for the average sensitivity was 1.53 for normal subjects and 1.84 for glaucoma. Test time with the Compass was 634±96 s (607±78 for normals, 678±108 for glaucoma). Compass analysis showed the percentage of fixation within the central 1° was 86.6% in normal subjects, and 79.3% in glaucoma patients. Color image quality was sufficient for diagnostic use in >65% of cases; Image-based diagnosis was in accordance with the initial diagnosis in 85% of the subjects. CONCLUSIONS: Based on preliminary results, Compass showed useful diagnostic characteristics for the study of glaucoma, and combined morphological information with functional data.

Variability of subjective classifications of corneal topography maps from LASIK candidates.

PURPOSE: To evaluate the variability of subjective corneal topography map classification between different experienced examiners and the impact of changing from an absolute to a normative scale on the classifications. METHODS: Preoperative axial curvature maps using Scheimpflug imaging obtained with the Pentacam HR (Oculus Optikgeräte, Wetzlar, Germany) and clinical parameters were sent to 11 corneal topography specialists for subjective classification according to the Ectasia Risk Scoring System. The study population included two groups: 11 eyes that developed ectasia after LASIK and 14 eyes that had successful and stable LASIK outcomes. Each case was first reviewed using the absolute scale masked to the patient group. After 3 months, the same cases were represented using a normative scale and reviewed again by the same examiners for new classifications masked to the patient group. RESULTS: Using the absolute scale, 17 of 25 (68%) cases had variations on the classifications from 0 to 4 for the same eye across examiners, and the overall agreement with the mode was 60%. Using the normative scale, the classifications from 11 of 25 (44%) cases varied from 0 to 4 for the same eye across examiners, and the overall agreement with the mode was 61%. Eight examiners (73%) reported statistically higher scores (P < .05) when using the normative scale. Considering all 550 topographic analyses (25 cases, 11 examiners, and two scales), the same classification from the two scales was reported for 121 case pairs (44%). CONCLUSION: There was significant inter-observer variability in the subjective classifications using the same scale, and significant intra-observer variability between scales. Changing from an absolute to a normative scale increased the scores on the classifications by the same examiner, but significant inter-observer variability in the subjective interpretation of the maps still persisted.

Intervention with vitamins in patients with nonproliferative diabetic retinopathy: a pilot study.

BACKGROUND: The purpose of this study was to determine whether a combination of vitamins B6, B9, and B12 is an effective intervention for reducing the signs and symptoms of nonproliferative diabetic retinopathy. METHODS: Ten subjects with type 2 diabetes mellitus (n = 20 eyes) with clinically diagnosed mild to moderate nonproliferative diabetic retinopathy were recruited from a private practice ophthalmology clinic for this open-label, uncontrolled, prospective six-month study. Metanx® vitamin tablets (containing 3 mg L-methylfolate calcium, 35 mg pyridoxal-5'-phosphate, and 2 mg methylcobalamin) were administered at a dosage of two tablets daily. Primary outcome indicators were the percent change in mean retinal sensitivity threshold measured by macular microperimetry and the percent change in mean central retinal thickness measured by spectral-domain optical coherence tomography. RESULTS: Three subjects were lost to follow-up. In the remaining seven subjects, two of 14 eyes had foveal edema that prevented microperimetry measurements due to poor fixation. The remaining 12 eyes showed a nonlinear improvement in mean threshold retinal sensitivity (P < 0.001). Overall change in mean central retinal thickness in 14 eyes was linear (R(2) = 0.625; P = 0.034), with a significant reduction between one and six months (P = 0.012). CONCLUSION: In this pilot study, the Metanx intervention appeared to have some beneficial effects with respect to reducing retinal edema and increasing light sensitivity in subjects with nonproliferative diabetic retinopathy.

Method for expressing clinical and statistical significance of ocular and corneal wave front error aberrations.

PURPOSE: The significance of ocular or corneal aberrations may be subject to misinterpretation whenever eyes with different pupil sizes or the application of different Zernike expansion orders are compared. A method is shown that uses simple mathematical interpolation techniques based on normal data to rapidly determine the clinical significance of aberrations, without concern for pupil and expansion order. METHODS: Corneal topography maps (TOMEY, Inc, Nagoya, Japan) from 30 normal corneas were collected, and the corneal wave front error was analyzed by Zernike polynomial decomposition into specific aberration types for pupil diameters of 3, 5, 7, and 10 mm and Zernike expansion orders of 6, 8, 10, and 12. Using this 4 × 4 matrix of pupil sizes and fitting orders, the best-fitting 3-dimensional functions were determined for the mean and standard deviation of the root-mean-square error for specific aberrations. The functions were encoded into a software application to determine the significance of data acquired from nonnormal cases. RESULTS: The best-fitting functions for 6 types of aberrations were determined: defocus, astigmatism, prism, coma, spherical aberration, and all higher-order aberrations. A clinical screening method of color coding the significance of aberrations in normal, postoperative laser in situ keratomileusis, and keratoconus cases having different pupil sizes and different expansion orders is demonstrated. CONCLUSIONS: A method to calibrate wave front aberrometry devices using a standard sample of normal cases was devised. This method could be potentially useful in clinical studies involving patients with uncontrolled pupil sizes or in studies that compare data from aberrometers that use different Zernike fitting-order algorithms.

Detection of macular function changes in early (AREDS 2) and intermediate (AREDS 3) age-related macular degeneration.

BACKGROUND/AIM: To evaluate if retinal sensitivity values obtained with a dedicated (screening) device can be used to functionally identify early and intermediate age-related macular degeneration (ARMD). METHODS: A fully automatic fundus perimeter combined with an image-stabilized scanning laser ophthalmoscope was used in 200 ARMD patients (319 eyes) in 5 study sites. The age-matched control group consisted of 200 normals. Sensitivity point values (S values), mean retinal sensitivity, number of points below 24 dB (K value, cutoff for normal values) and fixation stability were recorded. RESULTS: Of 319 eyes, 164 were classified as early (AREDS 2) and 155 as intermediate (AREDS 3) ARMD. Mean retinal sensitivity was significantly reduced in ARMD patients versus normals (p < 0.001). K values were different between normals and ARMD patients (p < 0.001). Fixation stability did not differ between early and intermediate ARMD patients. CONCLUSIONS: Macular sensitivity is reduced in patients with early and intermediate ARMD when compared to age-matched normals. These changes may be detected with a screening device.

Absolute color scale for improved diagnostics with wavefront error mapping.

PURPOSE: Wavefront data are expressed in micrometers and referenced to the pupil plane, but current methods to map wavefront error lack standardization. Many use normalized or floating scales that may confuse the user by generating ambiguous, noisy, or varying information. An absolute scale that combines consistent clinical information with statistical relevance is needed for wavefront error mapping. The color contours should correspond better to current corneal topography standards to improve clinical interpretation. DESIGN: Retrospective analysis of wavefront error data. PARTICIPANTS: Historic ophthalmic medical records. METHODS: Topographic modeling system topographical examinations of 120 corneas across 12 categories were used. Corneal wavefront error data in micrometers from each topography map were extracted at 8 Zernike polynomial orders and for 3 pupil diameters expressed in millimeters (3, 5, and 7 mm). Both total aberrations (orders 2 through 8) and higher-order aberrations (orders 3 through 8) were expressed in the form of frequency histograms to determine the working range of the scale across all categories. The standard deviation of the mean error of normal corneas determined the map contour resolution. Map colors were based on corneal topography color standards and on the ability to distinguish adjacent color contours through contrast. MAIN OUTCOME MEASURES: Higher-order and total wavefront error contour maps for different corneal conditions. RESULTS: An absolute color scale was produced that encompassed a range of +/-6.5 microm and a contour interval of 0.5 microm. All aberrations in the categorical database were plotted with no loss of clinical information necessary for classification. In the few instances where mapped information was beyond the range of the scale, the type and severity of aberration remained legible. CONCLUSIONS: When wavefront data are expressed in micrometers, this absolute scale facilitates the determination of the severity of aberrations present compared with a floating scale, particularly for distinguishing normal from abnormal levels of wavefront error. The new color palette makes it easier to identify disorders. The corneal mapping method can be extended to mapping whole eye wavefront errors. When refraction data are expressed in diopters, the previously published corneal topography scale is suggested.

Screening patients with the corneal navigator.

PURPOSE: To present a corneal topography screening device for the detection of corneal ectasias and various refractive procedures based on corneal topography patterns. METHODS: A database of corneal topography patterns were analyzed and used to "train" a neural network on nine different corneal topography patterns using nineteen corneal topography indices of corneal shape and power. RESULTS: Sample normal and corneal topographies were recognized correctly. CONCLUSIONS: The use of the corneal navigator to screen various corneal topographies aids clinical diagnosis.

Goodness-of-prediction of Zernike polynomial fitting to corneal surfaces.

PURPOSE: To determine the goodness-of-prediction of the fitting routine by measuring the difference between topographic corneal surfaces and their Zernike reconstructions as a function of polynomial order and optical zone size for various corneal conditions. SETTING: Corneal research laboratory in a university eye center. METHODS: Corneal topography maps (N = 253) were obtained from the Louisiana State University Eye Center. A variety of corneal conditions were used: normals; astigmatism; laser in situ keratomileusis, photorefractive keratoplasty (PRK), and radial keratotomy (RK) postoperative cases (myopic spherical corrections); keratoconus suspect; mild, moderate, and severe keratoconus; pellucid marginal degeneration; contact lens-induced corneal warpage; and penetrating keratoplasty. The root-mean-square (RMS) error of the goodness-of-prediction of the Zernike representation of corneal surface elevation was extracted for 4, 6, and 10 mm optical zones, whereas Zernike radial orders were varied from 3 to 14 in 1-order steps. The mean +/- SEM of the RMS error was plotted as a function of Zernike order and compared with criteria for normal surface fits. RESULTS: Fitting accuracy improved as more Zernike terms were included, but some conditions showed significant errors (when compared with normal surfaces), even with many added terms. For a 6 mm optical zone, the normal cornea group had the lowest RMS error and did not require terms above the 4th order to achieve <0.25 microm RMS error. Astigmatism met the 0.25 microm threshold at the 5th order, whereas keratoconus suspect required 7 orders. Laser in situ keratomileusis and PRK met the 0.25 microm threshold at the 8th order, whereas RK required 10 orders. Contact lens-induced corneal warpage and mild keratoconus needed 12 orders to meet the 0.25 microm threshold, whereas pellucid marginal degeneration, moderate and severe keratoconus, and keratoplasty categories were not well fitted even at 14 orders. CONCLUSIONS: A 4th-order Zernike polynomial appeared reliable for modeling the normal cornea, but using a 4th-order fitting routine with an abnormal corneal surface caused a loss of fine-detail shape information. As more Zernike terms were added, the accuracy of the fit improved, and the result approached the minimum error found with normal corneas. Unless sufficient higher-order Zernike terms are included when analyzing irregular surfaces, some diagnostic applications of Zernike coefficients may not be rigorous. This conclusion also suggests that wavefront shape analysis is similarly dependent on the number of orders used. Current surgical corrections based on normal-eye wavefronts may fail to capture all visually relevant aberrations in abnormal eyes, such as those having laser retreatments or experiencing corneal warpage from contact lens wear. A clinical goodness-of-fit or goodness-of-prediction index would indicate whether the number of terms in use has fully accounted for all of the visually significant aberrations present in the eye.

Advantages and disadvantages of the Zernike expansion for representing wave aberration of the normal and aberrated eye.

PURPOSE: Zernike expansion has been selected for use in describing wavefront aberrations in the human eye. The advantages and limitations of this approach are assessed for eyes with varying degrees of aberration. METHODS: Corneal topography examinations were taken with the Nidek OPD-Scan topographer/aberrometer. These higher data density corneal topography examinations were converted to height data and subsequently to wavefront representations. System noise was evaluated with a 2D frequency analysis of 43-D test balls. Both Zernike polynomials and 2D Fourier transforms were used to evaluate fidelity in the presentation of the point spread function. A display format for potential clinical use was developed based upon Zernike decomposition. RESULTS: Systematic noise from the corneal topographer was found to be minimal and, when eliminated, produced small changes in the point spread function. Using Zernike decomposition up to the 30th order failed to preserve the higher frequency aberrations present in aberrated eyes. Use of a Zernike decomposition display with a fixed micron scale presented only clinically significant details of spherical aberration, coma, trefoil, irregular components above third order and total higher-order aberrations (above second order). CONCLUSIONS: Zernike polynomials excel in extracting the low-order optical characteristics of visual optics. Zernikes accurately represent both low- and high-order aberrations in normal eyes where high-order aberrations are clinically insignificant. For eyes after corneal surgery or eyes with corneal pathology such as keratoconus that have significant higher-order aberrations, the Zernike method fails to capture all clinically significant higher-order aberrations.

Zernike polynomial fitting fails to represent all visually significant corneal aberrations.

PURPOSE: It is assumed that wavefront error data arising from aberrometry are adequately described by a Zernike polynomial function, although this assumption has not been extensively tested. Inaccuracies in wavefront error may compromise clinical testing and refractive correction procedures. The current retrospective study correlates visual acuity with corneal wavefront error and with the residual surface elevation error after fitting with the Zernike method. METHODS: Corneal topography maps were obtained from 32 keratoconus cases, 27 postoperative penetrating keratoplasty cases, and 29 postoperative conductive keratoplasty cases (88 total). The best spectacle-corrected visual acuity (BSCVA) for each case ranged from -0.2 to 1.3 logarithm of the minimum angle of resolution (logMAR) units (20/12.5-20/400). Topography was analyzed to determine wavefront error and the elevation fit error for a 4-mm optical zone. The 4th and 10th expansion series were analyzed with the 0th-order (piston) and 1st order (tip and tilt) removed. Linear regression analysis was performed. The difference in root mean square (RMS) error between the 4th- and 10th-order analyses was assessed for both wavefront and elevation fit error. RESULTS: The correlation of BSCVA to wavefront error for 4th-order terms was moderately strong and significant (R2=0.581; P<0.001). The 10th-order correlation for wavefront error had a similar result (R2=0.565; P<0.001), but the regression was not significantly different from the 4th-order result. The correlation of BSCVA to the elevation fit error was strong and significant for the 4th order (R2=0.658; P<0.001). The 10th-order data had a similar result (R2=0.509; P<0.001), and there was no significant difference between the two regressions. Only 72% of the cases showed a shift toward increased wavefront error with the 10th-order series, whereas 18% lost wavefront error. All cases showed a shift toward improved elevation fit with the 10th-order expansion. CONCLUSIONS: The wavefront error correlation to acuity was moderately strong, but the corneal elevation fit error also strongly correlated with visual acuity, indicating that Zernike polynomials do not fully characterize the surface shape features that influence vision and that exist in postsurgical or pathologic eyes. In addition, the change in wavefront error when using a larger expansion series was found to increase or diminish somewhat unpredictably. The authors conclude that Zernike polynomials fail to model all the information that influences visual acuity, which may confound clinical diagnosis and treatment.

Inattention to nonsuperimposable midline symmetry causes wavefront analysis error.

BACKGROUND: The nonsuperimposable mirror-image symmetry of the body (enantiomorphism) is reflected in the wavefront error maps of eyes. Averaging the wavefront errors of right and left eyes has the potential to adversely affect correlations made between wavefront error and visual acuity or other factors. Not only are the results of past studies using Zernike terms suspected of being invalid, there is concern about possible errors in the algorithms used to create customized corneal ablations. OBJECTIVE: To compare the results of analysis with and without correction for enantiomorphism. METHODS: Fourteen TMS-1 corneal topographic maps from 7 patients having with-the-rule astigmatism in both corneas were selected for Zernike decomposition to 45 terms. The maps were distributed among 3 groups: 7 right eye maps, 7 left eye maps, and 7 left eye maps in which the topography was transposed about the vertical axial to correct for enantiomorphism (left eye-corrected). The wavefront error difference between the right and left eyes was compared with the difference between the right eyes and the left eyes in which enantiomorphism was corrected (right eye vs left eye-corrected). The left eye wavefront error was then compared with the left eye wavefront error after correction (left eye vs left eye-corrected). RESULTS: Correcting for enantiomorphism produced a statisticially significant difference in the first 5 radial orders of Zernike terms (P=.02). Of the 45 Zernike terms analyzed, 7 terms were significantly different at the P<.05 level in the right eye vs left eye category, compared with 4 terms in the right eye vs left eye-corrected category. Eleven terms were significantly different at the P<.05 level in the left eye vs left eye-corrected category. CONCLUSIONS: Correcting for enantiomorphism makes the Zernike terms in right and left eyes appear more similar. Failure to correct for enantiomorphism causes certain terms to cancel each other when averaged across right and left eyes. Wavefront error studies that do not consider enantiomorphism, including those used to adjust laser surgical nomograms, will introduce significant errors to certain Zernike terms.

The Universal Standard Scale: proposed improvements to the American National Standards Institute (ANSI) scale for corneal topography.

PURPOSE: To evaluate the American National Standards Institute (ANSI) corneal topography scale (ANSI Z-80.23-1999) and to develop a Universal Standard Scale (USS) based on scientific principles and clinical usefulness. DESIGN: Retrospective data analysis and computer modeling of frequency of corneal power distributions. METHODS: Four variations of corneal topography color scales were constructed using the ANSI standard description. The scales used 21 contour intervals with step sizes of 0.5, 1.0, or 1.5 diopters (D). In example 1, hue was varied, whereas saturation and brightness were held constant. In example 2, hue was varied systematically, whereas luminance was varied to compensate for spectral sensitivity. In example 3, hue was varied, whereas luminance was adjusted to improve color contrast at the center of the scale. In example 4, the palette was generated by varying the red, green, and blue color intensity levels. In the USS, colors were defined by hue, brightness, and saturation, and appearance was optimized by using contrast. The contour interval was determined from the standard deviation of keratometry for 27 normal corneas. The scale range was based on corneal powers found in 388 topography maps of 12 different corneal conditions. RESULTS: ANSI-derived maps were difficult to interpret because of poor color contrast and the inability to associate contours with specific colors in the scale. The 0.5 D interval slightly improved the appearance of some patterns but reduced the useful clinical range of the scale. ANSI colors did not match the user's expectations; abnormal patterns appeared in shades of green, which is associated with normality. The standard deviation of keratometry readings for the normal population was 1.59 D. Hence, the contour interval for the USS was set to 1.5 D. More than 99.9% of the corneal powers in 388 clinical maps were within the range of 30 to 67.5 D, which was chosen as the range for the USS. CONCLUSIONS: The ANSI scale for corneal topography is a series of scales that lead to clinical misinterpretations. The alternative USS would provide uniform presentation, unambiguous interpretation, and greater ease of comparison among maps produced by different topographers.