Cellular mode of serotonin action on Cl- transport in the rabbit corneal epithelium.

The present work examines serotonin-induced changes in cell potential difference and barrier resistances in the corneal epithelium in vitro using voltage-measuring microelectrodes and related techniques. Component resistances were determined using voltage and resistance profiles of the epithelium before and during the serotonin response. Serotonin, added to the stromal side of the cornea in the presence of nialamide, markedly reduced transcorneal and apical membrane resistances, while basal barrier resistance increased slightly and shunt resistance was unchanged. The marked drop in apical membrane resistance after serotonin treatment reflects an increase in apical membrane chloride permeability, inasmuch as the serotonin-stimulated short-circuit current is indistinguishable from the increase in net chloride flux. Prolonged (more than 1 h) exposure of corneas to serotonin markedly depolarized the epithelial cells and reduced the voltage divider ratio from 12.3 +/- 2.1 to 1.5 +/- 0.5, while not significantly affecting the stimulated short-circuit current. These later effects suggest changes in epithelial ion distribution during long periods of stimulation by serotonin.

Enhancing fluid secretion by the corneal epithelium.

Swollen rabbit corneas incubated in vitro with their posterior surfaces blocked with silicone oil maintained fairly constant thickness over an 11 hr. period. Increasing the simulated intraocular pressure from 10 to 30 mm. Hg did not produce stromal thinning. When theophylline was added to stimulate epithelial Cl secretion by increasing the Cl permeability of the tear-facing epithelial membrane, corneas thinned at the average of 1.3 micrometer/hr. over a 6 1/2 hr. period. When the epithelial perfusion solution was made Cl-free by SO4 substitution to favor the passive flow of Cl from the cells to the tear solution, thinning of 3.91 micrometer/hr. over a 7 hr. period was observed. When corneas were perfused with Cl-free medium plus theophylline, thinning at the average rate of 6.20 micrometer/hr. over an 8 hr. period was achieved. Therefore the corneal epithelium is capable of thinning a swollen stroma by transport of fluid coupled to its Cl secretion, which can be enhanced by simple substitutions in the tear-side bathing solution.

Computer-assisted corneal topography. High-resolution graphic presentation and analysis of keratoscopy.

Keratoscopy is a useful clinical tool for the evaluation of topographic abnormalities of the corneal surface. However, not all the detailed information presented by keratoscope photographs is assessed easily by visual inspection. A computer-based analysis system therefore was developed to assist in the clinical interpretation of keratoscope images. With this system, deviations from sphericity are displayed in graphic form to aid in the recognition of abnormalities, and surface powers are presented in tabular form. Human eyes that are emmetropic, and eyes with keratoconus and severe astigmatism were analyzed. This process provides a useful quantitative method with which to determine corneal shape, as well as a useful adjunct to the clinical evaluation and teaching of keratoscopy. In addition, such a quantitative analysis may provide the basis for the development of new techniques for the correction of visual distortion caused by corneal surface irregularities.

Current keratoconus detection methods compared with a neural network approach.

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.

Electrophysiologic and morphologic effects of ophthalmic preparations on rabbit cornea epithelium.

The effects of several components of ophthalmic preparations on isolated rabbit cornea were studied by continuous electrophysiologic monitoring followed by fixation for scanning electron microscopy (SEM). Benzalkonium chloride (0.001 percent), thimerosal (0.0004 percent), and amphotericin B (0.0025 percent) all briefly increased ion transport, then greatly decreased epithelial resistance. Severe disruption of surface cell layers occurred simultaneously with resistance decrease. Silver nitrate (0.00017 percent) stimulated transport with less accompanying morphologic damage. Tetracaine (0.05 percent) disrupted epithelial function and caused exfoliation of several cell layers. Chlorobutanol (0.1 percent) produced a nearly complete loss of the squamous cell layer. Chloramphenicol, epinephrine, and pilocarpine produced minor changes in structure and electrophysiology at full clinical concentration. It was concluded that low concentrations of preservatives in ophthalmic preparations disrupt the barrier and transport properties of the corneal epithelium.

Neural network classification of corneal topography. Preliminary demonstration.

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.

Keratoconus and contact lens-induced corneal warpage analysis using the keratomorphic diagram.

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.

Automated keratoconus screening with corneal topography analysis.

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.

Changes in corneal wavefront aberrations with aging.

PURPOSE: To investigate whether corneal wavefront aberrations vary with aging. METHODS: One hundred two eyes of 102 normal subjects were evaluated with videokeratography. The data were decomposed using Taylor and Zernike polynomials to calculate the monochromatic aberrations of the cornea for both small (3-mm) and large (7-mm) pupils. RESULTS: For a 3-mm pupil, the amount of total aberrations (Spearman rank correlation coefficient r(s) = 0.145; P = 0.103) and spherical-like aberrations (r(s) = -0.068; P = 0.448) did not change with aging, whereas comalike aberrations exhibited a weak but statistically significant correlation with age (r(s) = 0.256; P = 0.004). For a 7-mm pupil, total aberrations (r(s) = 0.552; P < 0.001) and comalike aberrations (r(s) = 0.561; P < 0.001) significantly increased with aging, but spherical-like aberrations showed no age-related changes (r(s) = 0.124; P = 0.166). Simulated pupillary dilation from 3 mm to 7 mm caused a 38.0+/-28.5-fold increase in the total aberrations, and the extent of increases significantly correlated with age (r(s) = 0.354; P < 0.001). Pupillary dilation influenced the comalike aberrations more in the older subjects than in the younger subjects (r(s) = 0.243; P = 0.006), but such age dependence was not found for spherical-like aberrations (r(s) = 0.141; P = 0.115). CONCLUSIONS: Comalike aberrations of the cornea correlate with age, implying that the corneas become less symmetrical along with aging. Spherical-like aberrations do not vary significantly with aging. Pupillary dilation markedly increases wavefront aberrations, and those effects are more prominent in older subjects than in younger subjects.

Alteration of corneal epithelial ion transport by sympathectomy.

The cornea is dually innervated, receiving afferent nerves from the trigeminal ganglion and efferent nerves from the superior cervical ganglion. This study examines the specific effects of superior cervical ganglionectomy (SCGX) on the in vitro ion transport characteristics of the rabbit corneal epithelium. Two weeks after SCGX, epithelial Cl--dependent transport and total ionic conductance were increased in comparison to values obtained in paired control eyes. This increased transport level appeared to be independent of membrane receptor activity as demonstrated by lack of responsiveness to alpha-adrenergic, beta-adrenergic, serotonergic, dopaminergic, nicotinic cholinergic, or muscarinic cholinergic blockade. Nevertheless, SCGX produced a supersensitivity to epinephrine-stimulated transport as measured by the responsiveness of the ion transport current. Furthermore, SCGX abolished the responsiveness of the epithelium to serotonin. On the basis of these and earlier findings, the authors conclude that corneal sympathetic innervation influences membrane and receptor properties. Autonomic neurotrophic effects in the corneal epithelium include suppression of apical membrane Cl- permeability and of beta-adrenoreceptor sensitivity to biogenic amines. It is proposed that the corneal serotonergic receptors that activate Cl- transport lie on the sympathetic nerve terminals and stimulate this transport process by causing the neural release of a catecholamine.

Epithelial wound closure in the rabbit cornea. A biphasic process.

The rapid and complete repair of the corneal epithelium following ocular surgery or trauma is essential for the maintenance of normal visual acuity. In this study the authors examined epithelial wound healing in the rabbit after cells were mechanically removed leaving the basal lamina intact. The decrease in wound area (mm2/hr) was neither linear nor amenable to simple kinetic analysis. However, analysis of the data in terms of the decrease in wound radius (mm/hr) revealed a biphasic process consisting of an initial latent phase with no epithelial movement (5.5 +/- .3 hr), followed by a linear healing phase. The rate of epithelial movement in the linear healing phase was 64 +/- 2 microns/hr. Neither the latent phase nor the rate of epithelial migration during the healing phase was affected by variations in initial wound size. Ultrastructural studies demonstrated that during the latent phase there was an increased desquamation of surface cells as well as cellular and subcellular reorganization of the basal cells. At the end of the latent phase, the leading edge of the wound was composed of a single cell layer. The onset of epithelial migration coincided with the first ultrastructural observation of typical ruffled membranes and filopodia. This work demonstrates that the analysis of the decrease in wound radius provides a straightforward and accurate means to assess the kinetics and therapeutic modulation of epithelial wound healing.

Dopamine modulation of active ion transport in rabbit corneal epithelium.

The addition of micromolar quantities of dopamine stimulated ion transport in the isolated rabbit corneal epithelium. This response was blocked by pretreatment with the dopamine antagonist, haloperidol, and by the elimination of Cl- from the bathing solutions. The beta-adrenergic antagonist, timolol, was also a potent inhibitor of the epithelial response to dopamine. The presence of the serotonin antagonist, methysergide, or the dopamine beta-hydroxylase inhibitor, FLA-63, did not significantly alter the corneal response to dopamine. Following superior cervical ganglionectomy, the epithelial response to dopamine was abolished. These findings are consistent with the idea that Cl- secretion in the rabbit corneal epithelium can be modulated by preterminal dopamine receptors located on the sympathetic nerve fibers; therefore, dopamine stimulation appears to be a serial process mediated by the release of norepinephrine from sympathetic nerve terminals in the epithelium.

Serotonin-stimulated cyclic AMP synthesis in the rabbit corneal epithelium.

Serotonin increases the level of cyclic AMP in incubated rabbit corneas; the concentration of agonist producing half-maximal stimulation is approximately 1.5 microM. Nialamide, an inhibitor of monoamine oxidase, potentiates the response to serotonin but not to epinephrine. Amitriptyline, an inhibitor of neuronal uptake of serotonin, does not potentiate the stimulation of cyclic AMP synthesis. Lysergic acid diethylamide, but not timolol, antagonizes the response to serotonin; the half-maximal inhibitory concentration is approximately 6 nM lysergic acid diethylamide. A comparison of the time course of the increase in cyclic AMP synthesis after addition of serotonin or epinephrine to the incubation media indicates that serotonin, but not epinephrine, must penetrate a barrier to its free diffusion. We conclude that the corneal epithelium contains specific serotonergic receptors that, upon activation, cause the synthesis of cyclic AMP, which mediates the stimulation of chloride transport (c.f. companion article, Klyce et al.). The serotonergic receptors must be at a location posterior to the beta-adrenergic receptors, which are on the anterior-surface of the apical cells.

Anomalous acute inflammatory response in rabbit corneal stroma.

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.

Neural serotonin stimulates chloride transport in the rabbit corneal epithelium.

Evidence is presented that serotonin acts as a neurotransmitter in the cornea of the adult rabbit. Serotonin was localized to granules in a sparse population of subepithelial corneal nerves by an electron microscopic histochemical procedure. Significant endogenous levels of serotonin and its principal metabolite, 5-hydroxyindoleacetic acid, were detected in the central cornea by a fluorometric assay. Exogenous serotonin stimulated ion transport by corneal epithelium. This effect was potentiated by monoamine oxidase inhibition and was unaffected by an alpha-adrenergic receptor antagonist. Serotonin-stimulated ion transport was inhibited by the specific antagonist, methysergide, and by the replacement of Cl- with an impermeable anion. In tracer experiments, the serotonin-stimulated ion transport was shown to be caused by increased epithelial Cl- secretion. The serotonin response was partially inhibited by the beta-adrenergic antagonist, timolol. In a companion article, assay of corneal cyclic AMP showed stimulation of cyclic AMP synthesis by serotonin, inhibition by the specific antagonist, lysergic acid diethylamide, and potentiation by monoamine oxidase inhibition. We postulate that specific serotonergic receptors are present in the corneal epithelium and that activation of these receptors by serotonin released from serotonergic neurons increases the level of cyclic AMP, which stimulates active Cl- secretion by the corneal epithelium.

Quantitative descriptors of corneal topography. A clinical study.

Quantitative descriptors of corneal topography determined by computerized algorithm and designed to augment the information derived from topographic maps were evaluated in a clinical study. The surface regularity index, a measure of central corneal optical quality, was highly correlated with best spectacle-corrected visual acuity (rho = 0.80, P less than .001). The relatively low correlation between the surface asymmetry index, a measure of central corneal asymmetry, and best spectacle-corrected visual acuity (rho = 0.62, P less than .005) suggests that corneal symmetry is a lesser but still important determinant of the optical performance of the anterior corneal surface. There was also a high correlation between factors determined from computer-generated orthogonal simulated keratometer values and clinical keratometry values (mean corneal power, total corneal cylinder, and the location of the steepest corneal meridian). The information derived from these algorithms has both clinical and research applications and can be incorporated into computer-assisted topographic analysis systems.

The topography of normal corneas.

Previously we have analyzed photokeratographs to determine the topography of congenital, acquired, and surgically induced deformations of corneal shape. In this article, we survey the variety of corneal shapes found in both eyes of 22 individuals with normal corneas. The degree of correlation of the distribution of corneal power around the visual axis was striking for both eyes of 18 of the 22 individuals, as was the variability of the corneal topography of different individuals. The average centrally weighted corneal power determined from the photokeratographs correlated well with the average keratometric corneal power (r = .96). By defining the topographic features characteristic of normal corneas, we will be better able to diagnose corneal shape anomalies and understand the role such anomalies play in the degradation of vision.

Is keratoconus a true ectasia? An evaluation of corneal surface area.

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

Comparison of methods for detecting keratoconus using videokeratography.

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.

Graphic presentation of computer-analyzed keratoscope photographs.

We describe a corneal topography analysis system that creates accurate high-resolution graphics of corneal surface power from computer analysis of keratoscope photographs, and we present several examples of corneal shape analyses. The major improvement in the updated version presented here is the development of a contour map of corneal surface power. Improvements in computer algorithms used to analyze the raw data obtained from the keratoscope photographs have also been made, resulting in increased accuracy. This system allows the ophthalmologist to see the patterns of power distribution on the corneal surface more easily than is possible by visual inspection of keratoscope photographs. Improved corneal topography analysis should find wide clinical application in the study of refractive corneal surgery techniques and in the study of corneal disorders that cause irregular astigmatism.