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1From the Maisonneuve-Rosemont Hospital, Montreal, QC, Canada; the 2Departments of Computer Science and Operations Research, 3Ophthalmology, and 4Mathematics and Statistic, University of Montreal, Montreal, Québec, Canada; and the 5INRS-EMT (Institut National de la Recherche Scientifique-Énergie, Matériaux et Télécommunications), Université du Québec, Varennes, Québec, Canada.
| Abstract |
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METHODS. Topographies (Orbscan II; Bausch & Lomb, Rochester, NY) of 516 normal subjects were used. Methodology for the construction of a corneal atlas consisted of (1) data acquisition from both anterior and posterior corneal surfaces in the format of a 101 x 101 grid of z elevations evenly spaced (every 0.1 mm) along the x and y axes; (2) spatial normalization of the topographies on a unique average best-fit sphere to reduce the large variability in size and spatial location between corneas; (3) generation of the average 3-D model; and (4) statistics maps including average, median, and SD for each point of the grid.
RESULTS. To demonstrate the informative potential of this methodology, examples of atlases were generated. Numerical corneal atlases allow (1) characterization of a population, (2) comparison of two or more populations, (3) comparison of an individual with a reference population, and (4) screening of a population for the detection of specific corneal shape abnormalities, such as keratoconus or previous refractive surgery.
CONCLUSIONS. The concept of a 3-D corneal atlas was developed. The proposed technique was meant to be simple, accurate, reliable, and robust and can be extended easily to any type of topographer capable of providing tridimensional corneal maps.
Videokeratographs are based on three acquisition principles: Most systems are based on the reflection of a Placido disc on the anterior corneal surface (EyeSys; EyeSys Vision, Houston, TX; Topographic Modeling System (TMS); Tomey Technology and Vision, Nagoya, Japan). The most recent generation of videokeratographs is based on slit scanning of the cornea, either alone (Pentacam; Oculus, Wetzlar, Germany) or in combination with a Placido disc (Orbscan; Bausch & Lomb, Rochester, NY). A video camera captures the slit of light projected on and through the cornea to calculate the shape of its anterior and posterior surfaces. Finally, in the fluorescein profilometry technique (Corneal Topography System; PAR Vision Systems Corp., New Hartford, NY), fluorescein is instilled to delineate the anterior corneal surface, and a stereo triangulation algorithm is used to calculate the shape of this surface.
Despite significant progress in the concept of corneal shape analysis, these systems are only able to study one topography at the time. At the most, two topographies from the same subject can be compared by using a difference map. Some groups have attempted to characterize sets of topographies. In 1994, Hayashi et al.1 2 generated average, standard deviation (SD) and count maps from the TMS-1 topographies of a group of 104 subjects. They also provided difference maps between average maps. Their goal was to compare superolateral versus superior phacoemulsification incisions. Buehren et al.3 facilitated the comparison between two populations by providing a Students t-test map. Fam et al.4 also generated SD maps to evaluate the repeatability of the Orbscan pachymetry maps that they used to generate an average corneal pachymetry model. The repeatability was greatest in the center and decreased toward the periphery. The notion of alignment of the topographies before their averaging was raised by Buehren et al.5 who were concerned about eye movement between successive topographies. In their technique, a regression plane was used to correct for the tilt between two topographies, the best-fit sphere (BFS) apex was used to adjust for x, y, z shifts, and a best-fit spherocylinder alignment was used to rectify the cyclodeviation error. In 2005, Grzybowski et al.6 addressed the usefulness of three different fitting zones (apex, global, and peripheral fit) for the alignment of pre- and post-LASIK topographies. They concluded that the choice of the fitting zone could influence the appearance of the central posterior elevation after LASIK. Dealing with right and left eyes also necessitates data conversion to account for the natural symmetry between both eyes with respect to the sagittal plane (enantiomorphism). The temporal cornea being steeper than the nasal cornea,7 simple averaging (without alignment of the corneas) results in an increased variability. Topuz et al.8 and Smolek and Klyce (Smolek MK et al. IOVS 2001;42:ARVO Abstract 2839) used the mirrored images of left eyes to convert them in right eyes before merging the data from both eyes.
These studies represent the first steps toward a population-based average corneal model. Average representations of topographies from more than one individual were given by Hayashi et al.,1 Topuz et al.,8 Fam et al.,4 and Smolek and Klyce groups (Smolek MK et al. IOVS 2001;42:ARVO Abstract 2839). However, alignment of the topographies before averaging was only used for topographies belonging to the same subject, and in none of the cases was the methodology for the development and optimization of these average models reported.
The present study was a logical extension of past studies. The goal was to describe and assess a methodology for the construction of a population-based 3-D atlas of the cornea and to provide useful tools to characterize this population. The particularities of this work include the 3-D combination of both anterior and posterior surfaces data, the detailed description of the alignment technique used before averaging, and the definition of the indications and contraindications for such alignment. The methodology described herein was meant to be simple, accurate, reliable, and robust, and it was conceived for easy and universal implementation with any type of topographer capable of providing tridimensional corneal surface maps.
| Materials and Methods |
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Definitions
We propose a method for the construction of an atlas from any set of corneal topographies, using any topographer available on the market. The quality of the atlas will depend on the quality of individual topographies. The greater the precision and accuracy of individual topographies and the greater the number of points available for computation, the greater the value of the resultant atlas.
In the present study, the topographies were obtained with the Orbscan II (Bausch & Lomb, Rochester, NY). This apparatus acquires approximately 10,000 data points (40 slits x 240 points/slit) from the anterior and posterior corneal surfaces within 1.5 seconds. The Orbscan software includes an optional recording utility that saves the data into text files with numerical arrays of 101 x 101 points uniformly spaced and centered on the visual axis. The horizontal and vertical distance between two points is 0.1 mm.
We used as raw data the 3-D coordinates of the anterior and posterior surfaces of the cornea provided by Orbscan. For each point (x, y) of the 101 x 101 grid, the z coordinate indicates the distance from the corneal surface to a reference plane perpendicular to the line of sight. Since the reference plane may vary from one topography to another, we made use of the anterior (or posterior) best-fit sphere (BFS) (i.e., the sphere that best adjusts to the anterior, or posterior, surface of the cornea in the sense of the least mean squares in a central adjustment zone of 10.0 mm in diameter). The BFS is characterized by its radius and center. Once the BFS was calculated from the elevation with respect to the reference plane, we used the elevation with respect to the BFS itself. We will explain in the next section how to compare two topographies using the BFS. The BFS also facilitates visualization of the corneal shapenamely, the highlighting of small elevation changes. Note that Orbscan provides its own BFS, but we preferred to compute the BFS ourselves, based on the raw elevation maps.
Orbscan computes corneal thickness as the distance between a point on the anterior surface and its corresponding (interpolated) point on the posterior surface along the anterior BFS radius. The manufacturer has added a correction factor (called the acoustic factor) to these calculations so that Orbscan and ultrasound central pachymetry values match more closelyultrasound still being recognized as the gold standard for pachymetry.9 10 This acoustic factor reduces all pachymetry values by 8% (Orbscan default acoustic factor of 0.92). In this study, we computed pachymetry according to the same method, using the acoustic correction factor.
To facilitate interpretation, and unless otherwise specified, the color scales used for the atlases were the same as those used by Orbscan (5-µm color steps for the elevation maps, green representing a point on the BFS, and 20-µm color steps for pachymetry maps). Color steps of 1 µm were used for the SD maps.
Spatial Normalization
Spatial normalization of the surfaces before their averaging is a fundamental step for the construction of a 3-D corneal atlas. It consists of an overall resizing of the corneas to a standard (average) size and a translation to a common reference point to minimize variation between corneas. The scaling process is isotropic for the entire corneal surface, which means that local variations and individual features remain.
For a given sample set of anterior surfaces, the reference BFS is generated by first identifying the BFS radius and center of each anterior surface in the sample set. The average radius rant/avg of all radii obtained and the average coordinates (xant/avg, yant/avg, zant/avg) of all corresponding centers are then computed.
Next, each anterior surface is normalized on the average BFSant/avg, as follows:
Step 1.
Translation of the anterior surface, to align its BFS center to coordinate (0, 0, 0). This step is essential to get an equal scaling on each axis.
Step 2.
Isotropic scaling (equal scaling on x, y, and z axes) of the surface points, to normalize the BFS radius to rant/avg.
Step 3.
Translation of the BFS center from (0, 0, 0) to the average BFS center (xant/avg, yant/avg, zant/avg).
Step 4.
Resampling of the new (transformed) surface points on the original 101 x 101 discrete grid with a cubic spline interpolation algorithm.11 This technique calculates a smooth surface passing by all realigned points and retrieves the surface elevation for the predefined grid points position.
The adjustment of the posterior surface follows these same steps. For the calculation of the pachymetry maps, the same transformation (translations and scaling) is applied to both anterior and posterior surfaces, to preserve the relative position between the two. The pachymetry is then computed along the radius emerging from the reference center (xant/avg, yant/avg, zant/avg) and the acoustic factor is taken into account, as just discussed.
Construction of the Numerical Atlas
After spatial normalization of the surfaces of the topography set, we are ready to build an atlas for the population under investigation. For each point (x, y) of the 101 x 101 grid, the average elevation and SD are calculated. As some of the points can be missing on the topographies, usually in the periphery (lashes, lid borders, and surface irregularities are usually responsible for this loss of information), statistics are computed only for the points for which at least 25% of the data are available.
We have decided to generate an average model paired with an SD map, because average and SD are commonly used in statistics and easily understood by the scientific community. Average and SD are interesting choices if the data are not (or are slightly) corrupted by artifacts. However, one could choose to generate a median model paired with percentile maps. For small data sets, median maps are less affected by outliers or artifacts caused by the limitations of the acquisition system.12 Large tear meniscus, surface irregularities, poor fixation by the subject, and/or incorrect alignment by the technician during acquisition are several possible causes of artifacts.
In the next sections, we mention some of the applications of corneal atlases.
Characterization of a Population
Corneal atlases allow population-based qualitative and quantitative description of the 3-D corneal shape. This could not be done with traditional single surface topography analysis. The methodology that we have described can be applied to all kinds of normal, pathologic, or postoperative eye populations.
Comparison of Two Populations
Atlases also represent a powerful tool for the numerical comparison between two or more populations. The typical process for comparing two atlases consists of the following:
Comparison of an Individual with a Reference Population
A third significant advantage of atlases is the objective numerical comparison between one individual and a reference population, another process that was not possible with individual topographies. The typical methodology to test a topography against a standard consists of the following:
![]() | (1) |
![]() | (2) |
Screening and Classification
Screening of a population for a specific disease requires a clear definition of the absence of the disease, which can be given by a normal cornea reference atlas. The methodology used is then the same as that described for testing a topography against a reference atlas. One could also use several atlases from different populations for classification purposes. Advanced classification algorithms could be used, including neural networks15 based on shape indices derived from differences between the reference atlas and the tested subject, to automate the screening process.
| Results |
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The normal eye topography (Fig. 4A ; left column) was very similar to that of the reference population. The elevation difference map showed no difference greater than 5 µm in the central zone and the entirely green ±3-SD map confirmed that all elevation points were within the ±3-SD range. The normal range of the percentile map illustrates that the tested eye is within the normal range, since the map appears completely green.
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The third case represents a clinically diagnosed keratoconus (Fig. 4C , right column). The inferotemporal protrusion is easily delineated in all difference and percentile maps as a reddish region. The annular area surrounding the cone appears blue rather than green, due in part to the forward shift of the BFS resulting from the keratoconus protrusion.
| Discussion |
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The methodology described in this article is not limited to the Orbscan topography system and could be used with any other type of instrument capable of providing corneal 3-D surface points (e.g., Pentacam, Oculus, Wetzlar, Germany; Artemis 2, Ultralink, St. Petersburg, FL; Visante OCT, Carl Zeiss Meditec, Dublin, CA). The choice of the parameter used to build the average model is also optional (e.g., elevation with respect to the BFS, true elevation, axial curvature, tangential curvature). We chose to use the raw elevation because it basically localizes the corneal shape in a specified volume, while several definitions have been proposed for corneal curvature depending on the method of calculation (axial, tangential, or Gaussian curvature), the index of refraction (corneal values or keratometric equivalents), and the definition of the corneal center. The choice of the statistic is also determined according to the needs (e.g., average and SD maps, median and percentile maps, difference map, Students t-test map, or mid-rank Wilcoxon test with the percentile information, with or without Benjaminis correction, ANOVA).
Spatial normalization of the surfaces before their averaging (described herein as steps 14) represents an important part of the average corneal model construction. Spatial normalization is a well-recognized technique in the field of medical imaging.19 When subjects are compared, it has been shown that the major problem is excessive shape variability and that without alignment, the usefulness of the atlas is limited.19 20 21 Spatial normalization (e.g., translation, rotation, and scaling) was used and validated in brain imaging for shape analysis of brain tissues19 20 22 23 and for the construction of population-based lung shape average models.24
The four-step spatial normalization proposed herein allows analysis of the corneal shape independently of corneal size and location. As it implies that all corneas have the same size and location, this model cannot be used for the analysis of corneal size or location. The model is used for the analysis of proportions and relative variations, not for the analysis of absolute (real) dimensions. If pachymetry or keratometry values are to be studied, isotropic scaling before averaging should be omitted. Similarly, when corneal topography is used to calculate optical aberrations,25 26 spatial normalization should be avoided, as the corneal refractive power would be altered proportionally to the stretching factor (scaling).
In the literature, spatial normalization is often underestimated, and more naive methodologies are usually adopted. For instance, the easiest way to compute a topographic average is to use the elevation raw data directly, without prior normalization, as illustrated on Figure 1B (left): Although the average elevation map remains adequate, the SD map shows much higher variability than that obtained with the 4-step normalization technique described herein (Fig. 1A , left). Such a variability makes it difficult to detect statistically significant differences between populations. The topographies could also be aligned with respect to a specified region, such as: the apex (e.g., central 1.0-mm-diameter zone; Fig. 1B , center), the entire surface (e.g., central 10.0-mm-diameter region; Fig. 1B , right),6 or the periphery (e.g., 8.8- to 9.0-mm-diameter annulus). Again, this yields SD maps with low variations near the registration locus but much higher variations anywhere else.
We used the BFS as a reference surface because it is routinely used with Orbscan topographies and because spheres are easy to calculate and align. Elevation maps, however, could also be treated without the BFS concept. In fact, it could be interesting to replace the BFS by the best-fit average surface of a normal reference population. The deviation maps generated from this more natural nonspherical standard could be more informative than the current Orbscan maps derived from a sphere, because they are more sensitive to smaller deviations from the normal shape.
| Conclusion |
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| Acknowledgements |
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| Footnotes |
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Supported by Canadian Institutes of Health Research (CIHR), Ottawa, Ontario, Canada; Fonds de la Recherche en Santé Québec (FRSQ), Research in Vision Network, Montreal, QC, Canada; Fonds de recherche en Ophtalmologie de lUniversité de Montréal (FROUM), University of Montreal, Montreal, QC, Canada; and the Quebec Eye Bank Foundation, Inc., Montreal, QC, Canada.
Submitted for publication June 20, 2006; revised November 6, 2006; accepted January 16, 2007.
Disclosure: J.-F. Laliberté, None; J. Meunier, None; M. Chagnon, None; J.-C. Kieffer, None; I. Brunette, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C.
1734 solely to indicate this fact.
Corresponding author: Isabelle Brunette, FRCSC, Ophthalmology Research Unit, Maisonneuve-Rosemont Hospital, 5415, de LAssomption Boulevard, Montreal, QC, H1T 2M4 Canada; i.brunett{at}videotron.ca.
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