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Michael K Smolek,1 Neil F Notaroberto,1,2 Arley G Jaramillo,1,2 Lisa R Pradillo1,2 1CLEVER Eye Institute, 2EyeCare 20/20, Slidell, LA, USA 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 (R2 = 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. Keywords: diabetes, diabetic retinopathy, vitamin B, homocysteine, nitric oxide, microperimetry

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 deg 2 (min = 0.03, max = 3.90, SD = 0.68) for the index BCEA@63% and 2.40 deg 2 (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 deg 2 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.

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.

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., (Copyright 2013, SLACK Incorporated.)

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.

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., (Copyright © 2010 S. Karger AG, Basel.)

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.

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.

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.

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.

The air/tear interface contributes 70% of the vergence in the eye and, because of this, even minor variations in its shape can produce significant visual deficit. Placido disc-based corneal topographers measure the precise characteristics of the corneal surface, transforming shape into color-coded dioptric power maps and topography indexes related to optical quality and specific patterns associated with pathology. Artificial intelligence-based methods are used to classify corneal topography and these are used as screening tools. Coupling corneal topography measurements with aberrometry measurements permits the display of the internal aberrations of the eye. Together, these data provide the opportunity to extend refractive correction beyond sphere and cylinder to the higher order aberrations as well.

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.

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.

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.

Purpose: To demonstrate an objective method of screening for previous refractive surgery using corneal topography., Setting: Corneal topography research laboratories, LSU Eye Center, New Orleans, Louisiana, USA., Methods: Videokeratography (TMS-1, Tomey) examinations from the LSU Eye Center were randomly divided into training and test sets that each included 32 normal corneas and 106 corneas with previous radial keratotomy or photorefractive keratectomy from 1 month up to 10 years after surgery. A set of 1024 axial curvature values were extracted from mires 1 to 25 from each cornea to form a 1-dimensional waveform. Multiresolution wavelet decomposition was performed on this waveform using the s8 Symmlet wavelet. A portion of the resulting wavelet coefficients was input into a backpropagation neural network that was trained to 5% error. After training, the independent test set was passed though the neural net and scored., Results: The trained network correctly recognized 32 of 32 normal corneas and 105 of 106 refractive surgery corneas for a 99.3% accuracy, 99.1% sensitivity, and 100% specificity for previous myopic refractive surgery detection., Conclusions: The 1-dimensional wavelet-based neural network approach was an effective and accurate method of distinguishing eyes that had had myopic refractive surgery from normal eyes. The single error was a result of having too few examples of grossly decentered procedures in the training set.

Background: Keratoconus has long been considered to be an ectasia produced by stromal stretching. Although stretching should result in increased corneal surface area, previous observations of topography during progression of keratoconus have suggested that surface area may actually be conserved. A novel objective surface area measurement based on corneal topography was tested and applied to data from actual corneas under various conditions for comparative analysis., Setting: The LSU Eye Center clinic videokeratography archives., Methods: TMS-1 videokeratography files (Tomey Corp, Cambridge, Mass) were obtained from 6 groups of corneas: normal (n = 29), keratoconus from mild to severe states (n = 51), topographically judged keratoconus-suspect conditions (n = 10), postoperative photorefractive keratectomy for myopia (n = 39), with-the-rule corneal astigmatism (n = 17), and keratoglobus (n = 1). Additionally, 3 different spherical test surfaces were analyzed to verify the accuracy of the process. Only maps with no missing data out to ring 29 were used. The cumulative surface area from center to periphery was determined by calculating and summing the area of individual patches along consecutive annular rings. Mean surface area with respect to mean chord radius was plotted for each corneal condition, and curve fitting was used to extend each result to a 5. 85-mm limbus. Means, SEs, and 95% confidence intervals were calculated at intervals for statistical comparisons among all groups. Computer-generated surfaces helped to evaluate the relationship between shape and surface area., Results: When videokeratographic test targets were used, surface area error was less than 2%, which was deemed acceptable. Normal corneas had a mean +/- SE surface area of 120.3 +/- 2.2 mm(2), whereas all keratoconus corneas combined had a mean +/- SE surface area of 116.2 +/- 3.4 mm(2). The difference was not significant at any chord radius (analysis of variance, P<. 05). The keratoglobus cornea was found to have a surface area of 129. 9 mm(2), which was 7.98% greater than normal. An individual with progressive keratoconus exhibited no appreciable trend toward increasing surface area during a 76-month period. The corneas in the other groups resembled normal corneas in their total surface area., Conclusions: With the exception of the single case of keratoglobus, corneal surface area tended to be conserved near a value of 120 mm(2) for all groups in the study, including corneas with keratoconus. Surface area is remarkably insensitive to curvature change near the vertex. Flattening seen in the periphery of corneas with keratoconus suggests that biomechanical coupling compensates for any increase in curvature occurring in the region of the cone itself. Thus, it seems that keratoconus is not a true ectasia as is keratoglobus, but rather a specialized type of warpage, at least in mild to moderate forms of the disease. Arch Ophthalmol. 2000;118:1179-1186

Purpose: To investigate the nature and cause of an acute, anomalous stromal edema after epithelial debridement in the rabbit cornea., Methods: Series I: Adult New Zealand White rabbit corneas were mounted in perfusion chambers. The endothelium was bathed with Ringer's fluid, and the outer surface was covered with silicone oil. The epithelium of one eye was débrided with a scalpel before mounting, and the cornea of the fellow eye was débrided with a rotating brush after stabilization in the perfusion chamber. Using specular microscope tracking software, it was possible to measure total swelling and local swelling within the cornea. Series II: Diclofenac sodium ophthalmic solution 0.1% or a placebo was applied topically, 1 drop per 45 minutes for 3 hours before animals were euthanatized., Results: Series I: Corneas with their epithelium scraped with a scalpel before mounting were 37.5 +/- 17.5 microm (n = 6; P < 0.001) thicker in vitro than the stromas of perfused, intact fellow corneas. Epithelial débridement with a rotating brush after mounting resulted in an immediate (within 8 minutes) stromal swelling that plateaued in 1 hour at 31.0 +/- 5.3 microm (n = 6; P < 0.001). Curiously, in six of six corneas, the anterior stroma swelled more than the posterior stroma. In four of six corneas, the posterior stroma thinned. Analysis showed this pattern to be consistent with a sudden increase in anterior swelling pressure or osmotic pressure and to be inconsistent with a change in endothelial transport properties. Series II: Placebo-treated corneas swelled 30.6 +/- 7.7 microm (n = 5) 1 hour after débridement, whereas corneas pretreated with diclofenac sodium swelled only 19.2 +/- 3.1 microm (n = 6; P < 0.008)., Conclusions: The anterior stromal swelling occurs rapidly and near the site of epithelial injury suggesting messenger and/or enzymatic involvement with an effect parallel to apoptosis. Reduction of the swelling response with nonsteroidal anti-inflammatory drugs (NSAIDs) implicates the cyclooxygenase pathway. The swelling is similar to the unexplained acute edema that occurs during inflammation in the rat paw edema model, and may represent a general mechanism for mobilization of inflammatory cells.

Purpose: To determine whether uneven corneal surface hydration during excimer laser photorefractive keratectomy (PRK) is related to postoperative occurrence of central islands., Setting: LSU Eye Center, New Orleans, Louisiana, USA., Methods: A retrospective study reviewed intraoperative videotapes and postoperative videokeratography of 49 eyes of 49 patients who had excimer laser PRK for myopia. The uniformity of corneal hydration within the photoablation zone, particularly the frosty appearance of the ablated zone, was characterized. The presence or absence of a topographic central island (steepening of at least 3.0 diopters and 1.5 mm in diameter) was determined from the 1 month postoperative videokeratographs., Results: Twelve eyes (24.5%) developed central islands postoperatively. A statistically significant association was observed between the uneven surface hydration (central accumulation of fluid) within the ablation zone intraoperatively and the formation of central islands postoperatively (P < .001, Kruskal-Wallis test; Kendall tau rank correlation = 0.534; P < .001)., Conclusion: Nonuniform fluid distribution during photoablation was a risk factor for central island formation after PRK. Intraoperatively, the presence of excess fluid in the central cornea appeared as a shiny area. This mirror-like surface layer may reduce the rate of central ablation by reflecting and absorbing a significant amount of the incident excimer laser light.

Objective: To correlate new quantitative topographic indexes of corneal irregular astigmatism to best spectacle-corrected visual acuity (BSCVA) following excimer laser photorefractive keratectomy (PRK)., Setting: Department of Ophthalmology, LSU Eye Center, and Refractive Surgery Center of the South, Ear, Nose & Throat Hospital, New Orleans, Louisiana; Manhattan Eye, Ear and Throat Hospital, New York, New York, USA., Methods: Videokeratography data (TMS-1) were obtained preoperatively and 1, 3, 6, 12, 18, and 24 months postoperatively from 100 eyes having PRK for low to mild myopia. Algorithms measured fine local irregularity with the surface regularity index (SRIp), varifocality with the coefficient of variation of corneal power (CVPp), and central islands with the elevation/depression magnitude (EDM)., Results: The SRIp and CVPp increased after surgery and remained significantly higher than the preoperative levels throughout the 24 month follow-up (P < .05). The increase in EDM was significant from 1 to 6 months (P < .05) but not thereafter. Multiple regression analysis revealed that variables having a statistically significant relationship with postoperative BSCVA were CVPp and EDM at 1 month, CVPp at 3 months, and CVPp, haze, and age at 6 months. No statistically significant correlation between any measures of irregular astigmatism and BSCVA was found after 1 year of follow-up., Conclusion: The quantitative measures used in this study are sensitive methods by which irregular astigmatism after keratorefractive procedures can be classified, evaluated, and compared.

Purpose: TMS-1 videokeratography (Tomey Technologies, Inc.) was animated using computer morphing to visualize corneal shape change over time., Methods: Morphing was performed using keratoconus (8 examinations/76 months) and postoperative photorefractive keratectomy (PRK) corneas (8 examinations/37 months; LSU PRK Phase IIa)., Results: In the keratoconus animation, the inferior cone increased curvature, but not equally in all directions, nor at a constant rate. The cone apex did not drift over time. Periodic flattening and steepening was observed superiorly, as well as cone regression at month 76. The Keratoconus Prediction Index (KPI) at month 0 was 0.18, plateaued at 0.36 at month 46, and dropped to 0.33 at month 76. In the post-PRK animation there was continuous corneal remodeling out to 30 months. Fluctuating steep and flat regions of the ablation zone correlated with the Surface Regularity Index (SRI)., Conclusion: Cinemakeratography (Cinema-K) enhanced our appreciation of subtle changes in corneal topography.

Purpose: Four videokeratographic methods for keratoconus detection were compared with a neural network approach., Methods: A classification neural network for keratoconus screening was designed to detect the presence of keratoconus (KC) or keratoconus suspects (KCS); a separate cone severity network graded the severity of conelike topography patterns consistent with KC or KCS. Three hundred TMS-1 examinations (Tomey) were randomly divided into training and test sets. Ten topographic indexes were network inputs. Nine categories were used: normal, astigmatism, KC, KCS, contact lens-induced warpage, pellucid marginal degeneration, photorefractive keratectomy, radial keratotomy, and penetrating keratoplasty. KC was subdivided into KC1 (mild), KC2 (moderate), and KC3 (advanced). There were three outputs for the classification network (KC, KCS, and OTHER); target output values of 0 = OTHER, 0.25 = KCS, 0.5 = KC1, 0.75 = KC2, and 1.0 = KC3 were used for the severity network., Results: The best-trained classification network had 100% accuracy, specificity, and sensitivity for the test set. The severity network had mean outputs (+/-standard deviation) of OTHER = 0.02+/-0.02, KCS = 0.21+/-0.05, KC1 = 0.52+/-0.17, KC2 = 0.74+/-0.12, and KC3 = 0.91+/-0.15. The severity network output for all categories was well correlated to the keratoconus prediction index (R = 0.892, P < 0.0001). The classification network had an overall accuracy and specificity significantly better (P < or = 0.005) than the Klyce/Maeda keratoconus index (KCI) test, the Rabinowitz test (K & I-S), and simulated keratometry (average Sim K). However, there were no significant differences in keratoconus sensitivity between the classification network, KCI, and K & I-S. The sensitivity and specificity of average Sim K were significantly worse than those of the other tests. The classification network had significantly better sensitivity (P < 0.001) and specificity (P = 0.025) for KCS detection than the K & I-S., Conclusions: The neural networks completely distinguished KC from KCS and from topographies that resembled KC. The network approach equaled the sensitivity of currently used tests for keratoconus detection and outperformed them in terms of accuracy and specificity.

Purpose: Because keratometry readings may no accurately reflect the refractive changes after keratorefractive surgery for myopia, better methods for the assessment of corneal curvature in the postsurgical cornea are needed., Methods: We developed a procedure to calculate the average central power (ACP) of the cornea within the entrance pupil from videokeratography. Videokeratograph-derived keratometry-style readings (average K; K) and calculated ACPs, as well as the differences between the two values, were compared in four groups: normal corneas (n = 30), corneas with regular astigmatism (n = 30); post-radial keratotomy corneas (RK, n = 85), and post-excimer laser photorefractive keratectomy corneas (PRK, n = 63). Intraocular lens (IOL) powers calculated by using K or ACP in the Sanders-Retzlaff-Kraff formula were compared., Results: In the groups with normal corneas or regular astigmatism, none of the eyes showed a difference between K and ACP > 0.25 D. However, six (7%) of the RK eyes and 16 (25%) of the PRK eyes had differences > 0.55 D; in these eyes, the disparity between IOL powers calculated by using K and IOL powers calculated by using ACP was > 0.5 D., Conclusion: These results suggest that basing the calculation of IOL powers on keratometry readings in patients who have undergone RK. PRK, or possibly other refractive procedures may result in a residual refractive error in some eyes. In particular, patients undergoing surgery involving a small optical zone or large attempted correction or both, as well as those with low postoperative keratometry readings, may be at risk for this problem if IOL placement becomes necessary in later years.

The greater utilization of soft contact lenses calls for the development of new and objective methods of evaluating the optical performance of the different lens types, in situ. We used videokeratography to examine the surface topography of soft contact lenses that had been worn for more than 1 year on 27 eyes of 23 patients, and compared the resulting color-coded maps and topographic indices as well as contact lens-corrected visual acuities, with those obtained with new replacement lenses on the same eyes. Visual inspection of the color-coded maps revealed differences in the surface characteristics of the used and new lenses. Comparison of quantitative indices including the SAI (Surface Asymmetry Index), IAI (Irregular Astigmatism Index), SRI (Surface Regularity Index), and SDP (Standard Deviation of Powers) showed that asymmetry, surface irregularity, potential visual acuity (derived from the SRI), and corneal power distribution were significantly poorer with the used lenses than with the new (P = 0.0001). The videokeratoscope is useful for evaluating the soft contact lens surface in situ, as an indicator of optical quality; it also permits the objective evaluation of lens cleaning techniques.

Background: The detection of keratoconus patterns on videokeratography is important for screening candidates for refractive surgery and for studying the genetic basis of keratoconus., Objective: We compared three quantitative approaches to identifying keratoconus from videokeratographic information to examine the limitations and capabilities of each test and to determine their suitability for use in the clinical setting., Methods: Videokeratographs typical of clinically diagnosed keratoconus (n = 44) and of various non-keratoconus conditions (n = 132, including normal, with-the-rule astigmatism, contact lens-induced corneal warpage, photorefractive keratectomy, keratoplasty, and pellucid marginal degeneration) were selected. Three methods for detecting keratoconus were used: keratometry (average Simulated Keratometry [SimK] readings > 45.7 diopters [D]); the modified Rabinowitz-McDonnell test (central corneal power > 47.2 D and/or Inferosuperior Asymmetry [I-S] value > 1.4 D); and an expert system classifier (classification based on discriminant analysis and classification tree with eight topographic indexes). Sensitivity and specificity were calculated for each test., Results: Sensitivities were 84% for keratometry, 96% for the modified Rabinowitz-McDonnell test, and 98% for the expert system classifier. Specificities for the three methods were 86%, 85%, and 99%, respectively. In terms of sensitivity, the expert system classifier was significantly better than keratometry (P = .04). In terms of specificity, the expert system classifier was significantly better than either of the other methods (P = .001)., Conclusions: For screening candidates for refractive surgery, where high sensitivity is needed, either the modified Rabinowitz-McDonnell test or the expert system classifier is suitable. For diagnosing keratoconus, where high specificity is more useful, the expert system classifier is more appropriate than the other two methods.

Purpose: Videokeratography is a powerful tool for the diagnosis of corneal shape abnormalities. However, interpretation of the topographic map is sometimes difficult, especially when pathologies with similar topographic patterns are suspected. The neural networks model, an artificial intelligence approach, was applied for automated pattern interpretation in corneal topography, and its usefulness was assessed., Methods: One hundred eighty-three topographic maps were selected and classified by human experts into seven categories: normal, with-the-rule astigmatism, keratoconus (mild, moderate, advanced), postphotorefractive keratectomy, and postkeratoplasty. The maps were divided into a training set (108 maps) and a test set (75 maps). For each map, 11 topography-characterizing indices calculated from the data provided by the TMS-1 videokeratoscope, plus the corresponding diagnosis category, were used to train a neural network., Results: The correct classification was achieved by a trained neural network for all 108 maps in the training set. In the test set, the neural network correctly classified 60 of 75 maps (80%). For every category, accuracy and specificity were greater than 90%, whereas sensitivity ranged from 44% to 100%., Conclusions: With further testing and refinement, the neural networks paradigm for computer-assisted interpretation or objective classification of videokeratography may become a useful tool to aid the clinician in the diagnosis of corneal topographic abnormalities.

Purpose: Videokeratography of early keratoconus may be difficult to distinguish from contact lens-induced corneal warpage, even by experienced examiners. Furthermore, topographic irregularity may be judged inconsistently if quantitative standards are not applied. Quantitative measures based on videokeratographic data were developed and evaluated to determine if improved corneal topographic classification can be achieved., Methods: The Corneal Irregularity Coefficient (CIC) and Corneal Power Coefficient (CPC) were derived from multiple measures of mean corneal power and its variance for 207 videokeratographs of normal, warped, keratoconus, and keratoconus-suspect corneas. CIC was plotted against CPC, creating a distribution of points representing all maps that tended to be grouped according to surface conditions (the Keratomorphic Diagram). Normal, steep, abnormal, and warped zones were defined by CIC and CPC cutoff values chosen to distinguish normal from keratoconus corneas graphically., Results: Seventy of 76 normal corneas were grouped in the normal zone and 6 in the steep zone; 84 of 84 keratoconus corneas were grouped in the abnormal zone; 35 of 35 contact lens-induced warpage cases were grouped in the warped zone; and 10 of 12 keratoconus-suspect corneas were grouped in the warped zone, with 2 in the abnormal zone. Serially plotted data of keratoconus progression and warpage regression demonstrated that the vector displacement of CIC and CPC values may provide a potentially useful means of distinguishing contact lens-induced warpage from keratoconus-suspect corneas., Conclusion: The Keratomorphic Diagram aids in classifying and comparing corneal shape by plotting indices along axes with easily recalled scales. The diagram may become a useful tool to assess presurgical corneal surface instability and postoperative progression of corneal shape change due to healing.

Purpose: Although visual inspection of corneal topography maps by trained experts can be powerful, this method is inherently subjective. Quantitative classification methods that can detect and classify abnormal topographic patterns would be useful. An automated system was developed to differentiate keratoconus patterns from other conditions using computer-assisted videokeratoscopy., Methods: This system combined a classification tree with a linear discriminant function derived from discriminant analysis of eight indices obtained from TMS-1 videokeratoscope data. One hundred corneas with a variety of diagnoses (keratoconus, normal, keratoplasty, epikeratophakia, excimer laser photorefractive keratectomy, radical keratotomy, contact lens-induced warpage, and others) were used for training, and a validation set of 100 additional corneas was used to evaluate the results., Results: In the training set, all 22 cases of clinically diagnosed keratoconus were detected with three-false-positive cases (sensitivity 100%, specificity 96%, and accuracy 97%). With the validation set, 25 out of 28 keratoconus cases were detected with one false-positive case, which was a transplanted cornea (sensitivity 89%, specificity 99%, and accuracy 96%)., Conclusions: This system can be used as a screening procedure to distinguish clinical keratoconus from other corneal topographies. This quantitative classification method may also aid in refining the clinical interpretation of topographic maps.

Many methods to measure corneal elasticity destroy the tissue and thereby produce erroneous results. Holographic interferometry, a highly precise nondestructive optical comparison technique, was used to evaluate corneal elasticity of intact eye-bank eyes. A double-pulse holographic interferometer operating at 632.8 nm was used to measure corneal deformation in 20 whole-globe eyes from donors 45 to 83 years of age for intraocular pressures from 16 mm Hg to 21 mm Hg. Stress was computed from LaPlace's law, and arc length strain was derived from z-axis distention of the central cornea. The stress-strain relationship in the normal physiological range of intraocular pressure was linear with a Young's elastic modulus of 1.03 gigapascals for the central cornea (r = 0.999). During interferometry of radial keratotomy of the cornea, interference fringe patterns developed in association with each incision as it was made. When four incisions were placed deep along each of the primary semimeridians, the fringe pattern developed as expected, based on current keratotomy models. When incisions were shallow (approximately 50% depth) and placed asymmetrically along the nasal, temporal, and superior semimeridians, the resulting surface strain was symmetrical about the central cornea, forming an annular pattern of interference fringes. These results indicate that when the cornea was stressed at physiological pressures as part of the intact whole globe, it was less elastic than excised corneal tissue tested by strip extensiometry. Radially incised corneas demonstrated strain patterns suggestive of inherent structural anisotropy with a possible inferior quadrant weakness.

Purpose: Previously, human corneal stromal interlamellar cohesive strength in the horizontal meridian was shown to be twice as strong peripherally as centrally (approximately 2.90 x 10(-1) versus 1.40 x 10(-1) N/mm). In the current study, stromal samples excised from the vertical meridian were studied to determine if meridional differences also exist. Precise knowledge about corneal stromal structure is warranted, because anisotropy can influence postoperative healing strength and corneal shape., Methods: Limbus-to-limbus stromal strips with a constant 2.2-mm width were obtained from the vertical meridians of 52 eyebank corneas (8 single, 22 pairs). Cohesive strength was recorded as samples were split at a constant 1.6 mm/s at 50% stromal depth., Results: The mean cohesive strength in the inferior periphery was found to be only two thirds the strength observed in the nasal or temporal periphery (1.96 x 10(-1) N/mm versus approximately 2.94 x 10(-1) N/mm @ 5 mm). The mean cohesive strength in the inferior periphery was also significantly less than the strength of the superior periphery (1.85 x 10(-1) N/mm +/- 8.83 x 10(-3) SEM versus 2.34 x 10(-1) +/- 1.37 x 10(-2) @ 4 mm from the central cornea; P = 0.0027). Unlike the samples from the horizontal meridian, which could be described by a profile symmetric about the central cornea, force profiles for the vertical data could be characterized with distinct, classifiable patterns that were generally asymmetric. Fellow corneas from a single donor tended to have strength profiles belonging to the same class (P = 0.035; chi-square), although some paired eyes exhibited profiles from distinctly different classes., Conclusions: These data strongly support the concept of an anisotropic collagen macrostructure that is more complex than previously believed. This inherent structural anisotropy may become a significant determinant of corneal shape during ectatic disease and some forms of keratorefractive surgery.

The application of the 193 nm excimer laser for keratorefractive surgery promises to deliver a higher degree of precision and predictability than traditional procedures such as radial keratotomy. The development and evaluation of keratorefractive surgery have benefited from the parallel advances made in the field of corneal topography analysis. We used the Computed Anatomy Topography Modeling System (TMS-1) to analyze a Louisiana State University (LSU) Eye Center series of patients who had photorefractive keratectomy for the treatment of myopia with the VISX Twenty/Twenty excimer laser system. The excimer ablations were characterized by a relatively uniform distribution of surface powers within the treated zone. In the few cases that exhibited marked refractive regression, corneal topography analysis showed correlative changes. With topographical analysis, centration of the ablations relative to the center of the pupil could be evaluated. Marked improvement in centration occurred in the patients of LSU Series IIB in which the procedure to locate the point on the cornea directly over the pupil's center during surgery was refined. Corneal topographical analysis provides objective measures of keratorefractive surgical results and is able to measure the precise tissue removal effect of excimer laser ablation without the uncertainties caused by measuring visual acuity alone. Our observations forecast the need for improved aids to center the laser ablations and for the development of a course of treatment to prevent post-ablation stromal remodeling.

We compared the average force required to separate normal corneas at a 50% stromal depth, with the force required to separate corneas stored for 2, 5, 7, 10, and 14 days in either McCarey-Kaufman or Dexsol corneal storage medium. The required interlamellar separation force was calculated by standardizing the width of the test strips. The average required force for 35 fresh rabbit corneas (no storage) was 9.1 +/- 1.5 g/mm. There was no significant change in the required separation force after storage in either medium for up to 14 days.

The interlamellar biomechanical properties of stromal collagen are relatively unknown, yet may be highly significant with respect to wound healing and the efficacy of certain keratorefractive surgical procedures. Interlamellar adhesive strength was measured as the tearing force required to separate corneal lamellae at a 50% stromal depth in 16 human eyebank corneas. The mean value for the central cornea was found to be 14.2 (+/- 0.5 SEM) g-wt/mm of tissue width. Histology showed a smooth separation between the lamellae along the tearing plane in the central cornea. We believe that the adhesive strength measured in the central cornea may be primarily the force needed to break interlamellar proteoglycan bonds between collagen lamellae, because no torn lamellae were found in this region. The mean adhesive strength and the SEM increased toward the periphery in a symmetrical fashion. The mean adhesive strength in the far periphery was 31.6 (+/- 3.7 SEM) g-wt/mm at 5 mm nasally, and 28.4 (+/- 3.2 SEM) g-wt/mm at 5 mm temporally, and was approximately twice the mean central value. The rising value of the mean adhesive strength with increasing distance from the central cornea was believed to be due to a more highly disorganized collagen network in which greater numbers of lamellae passed obliquely in depth through the tearing plane. These lamellae would contribute their tensile strength to the adhesive strength measurement along the tearing plane. Histology from the peripheral cornea confirmed the existence of depth-varying collagen lamellae and the torn ends of lamellae that passed across the tearing plane.

Nonius horopter measurements were made on three normal subjects using both physically displaced (real viewing) and stereogrammetrically displaced (projected viewing) test objects. Three subjects with ocular anomalies were tested using the projected viewing arrangement with and without 5% overall magnifier before the right eye, and seven complete measurements of the projected viewing horopter were made on a fourth subject with an ocular anomaly over the period of 1 month. These latter individual plots showed large irregularities that changed location from day to day. Plotting the mean and standard error of the means of these seven sets of data produced a smoothing out of the horopter locus. Plotting each individual horopter setting in the sequence of measurement and monitoring eye position indicated that all of the irregularities and regional horopter changes found are most likely introduced by changes in fixation disparity (vergence eye movements).

Both the binocular nonius and classical nonius criteria were applied to a group of subjects in order to compare the resulting horopters. Results indicated that monocular visual directions shifted along with changing binocular disparities when using the binocular nonius technique. This method constitutes a modification of the frontal plane criterion, since binocular portions still can be set equidistant to the fixation object. Comparing equidistance (binocular nonius) with equidirection (nonius) indicated that the 2 loci were essentially the same. Shifts in the nonius horopter induced by a small overall magnifier could not be predicted for 2 out of 7 subjects; one of these with aniseikonia and the other with intermittent exotropia. Irregularities in all horopter data could be accounted for by shifts in the vergence angles during the experiment.