Tomographic Screening for Ectasia Susceptibility

Refractive surgeons routinely face the challenge of identifying cases at higher risk for progressive keratectasia, a rare but severe complication of keratorefractive procedures such as laser vision correction.¹ The lamellar cut and/or excimer laser ablation may cause or aggravate biomechanical failure of the corneal stroma, which, in the case of ectasia, is unable to support the continuous stresses of intraocular pressure, extraocular muscles, blinking, eye rubbing, and other forces.² Ectasia can occur after surface ablation procedures, but the biomechanical impact of this surgery is much less pronounced than the impact caused by LASIK. For example, a thick flap may cause biomechanical failure and ectasia progression.³

Prevention is the best approach for such severe complications. Thus, careful preoperative screening is crucial.^4,5 In the past, Placido disc-based corneal topography—the evaluation of corneal front surface curvature—and central corneal thickness (CCT) measurements were used as the standard methods for screening refractive surgery candidates for their risk of developing ectasia.^5-7

The ectasia risk scoring system (ERSS) was developed by Randleman and colleagues⁸ based on a retrospective case control study that evaluated anterior corneal topography, CCT, the degree of refractive correction, the depth of the residual stromal bed, and patient age. A second study by Randleman and coworkers⁹ confirmed abnormal preoperative topography as the most significant predictive variable. However, the ERSS had a false negative rate of 4% to 8% and a false positive rate of 6%.^8,9 Other studies have reported false positive rates as high as 35%.¹⁰ Additionally, a separate retrospective study of 36 cases with ectasia after LASIK identified nine eyes (25%) classified as low risk and seven eyes (19%) as moderate risk.¹¹ The relatively high incidence of false negatives of the ERSS along with other reported cases of ectasia after LASIK in the absence of apparent risk factors^{12- 15} supports the need for novel screening methods that enhance the ability to detect ectasia susceptibility or risk among refractive surgery candidates.¹⁶

Topography and Tomography

Corneal topography, or computerized videokeratography, has had an unquestionable role in the development of refractive surgery.¹⁷ The term topography is derived from the Greek words topos (place) and graphein (to write). Although topography has been classically related to the study of geographical elements, such as the Earth’s surface shape and features, corneal topography is a method of front or anterior corneal surface imaging. The term tomography is derived from the Greek words tomos (a cut or section) and graphein (to write). Tomography is a method for mathematically calculating a 3-D structure of a solid organ. Thus, the term corneal tomography should be used for the diagnostic characterization of the front and back surfaces of the cornea, along with thickness mapping. Several technologies for tomography, including horizontal slit scanning, rotational Scheimpflug imaging, arc scanning with high-frequency ultrasound, and anterior segment optical coherence tomography, are available in various commercial instruments.^18,19

To improve the sensitivity and specificity of screening protocols for refractive surgery candidates, corneal characterization should go beyond front surface curvature and single-point central thickness. A tomographic approach is essential.4 Tomography combines anterior and posterior corneal elevation with complete pachymetric data to reconstruct corneal architecture in three dimensions. Interpreting such an enormous amount of data is a complex task. Refractive surgeons should be aware that the goal of screening refractive surgery candidates for their risk of ectasia should not be limited to the detection of mild or subclinical forms of ectatic diseases (keratoconus and pellucid marginal degeneration); it should also include the assessment of a relatively normal cornea’s susceptibility to biomechanical failure.

Pentacam Corneal and Anterior Segment Tomography

The Pentacam (Oculus Optikgeräte GmbH) is a family of instruments that perform corneal tomography using a 360º rotating Scheimpflug camera. The WaveLight Oculyzer and Oculyzer II (Alcon Laboratories, Inc.) are built on the same platform as the Pentacam, with software capability for planning customized ablations based on corneal data. The Pentacam provides corneal and anterior segment reconstruction from limbus to limbus, up to the front surface of the iris and the crystalline lens. A wide range of maps and displays can be generated from the Pentacam exam using many color scales.

A standardized approach to the objective evaluation of tomographic data should be implemented to facilitate diagnosis of potential corneal ectasia. We recommend that the data be evaluated in an organized, stepwise fashion. The first crucial element is to assess the quality of the exam to determine the reliability of the data. The Oculus quality score comprises an objective set of indices that asses the analyzed area, eye movements, and any loss of segments due to eyelid blinking or other factors that may influence the data.

Scheimpflug images are of interest, as they allow the evaluation of stromal transparency and scattering caused by Descemet membrane, which is consistent with the presence of cornea guttata.²⁰ The most commonly used displays are the Quad (4 Maps) Refractive, the Belin- Ambrósio Enhanced Ectasia Display (BAD), the topometric display, and the Fourier display. All displays have several color-coded maps. The number of colors, the step values between each color, the hottest and coolest colors, and the values and grade changes between colors can significantly influence the presentation of the display. Table 1 summarizes the best scales according to our personal preferences. The Ambrósio 2 palette (Figure 1A) of colors was inspired based on the benefits and limitations of the Belin Intuitive Scale (Figure 1B), the Smolek-Klyce (Figure 1C), and the Wilson-Klyce classic scales.²¹

There has been long debate about the advantages of absolute fixed color bars and values versus a normative or relative scale with colors and powers adjustable according to the cornea being studied. The most commonly used scales have been the absolute Smolek-Klyce scale and the EyeSys normative scale, which is similar to the Holladay Primary palette on the Pentacam (relative 0.50 D or 0.25 D; 15 colors: blue to red scale [Figure 1D]). Although each scale has its advantages, we prefer to rely on absolute color scales, because this better facilitates comparison of different maps.

There is significant variability in the subjective interpretation of color-coded maps, which can lead to inaccuracy. Ramos et al²² conducted a study among 11 corneal topography specialists, showing significant subjective variation in their interpretation of topographic maps. Using the topographic classification of the ERSS, 17 of 25 cases had classification variation of 0 to 4 across examiners using an absolute scale (Smolek-Klyce) and 11 cases had a classification variation of 0 to 4 across examiners using a normative 0.50 D scale (Holladay Primary or classic EyeSys scale). The study also showed that color scale influences the interpretation of color-coded maps, with statistically significant differences for eight of the 10 examiners.

For accurate interpretation, it is helpful to understand the analysis involved in the construction of each map and display, along with the normative values for the most accurate parameters, including the best cut-off values for distinguishing normal from ectatic corneas. The best strategy, in our experience, is to rely on objective parameters.

Topometric indices derived from the curvature of the front surface of the cornea are available on the Pentacam (Figure 2). Although these indices may be used as objective parameters to detect ectasia, it is important for the clinician to understand that they may lead to relatively later identification of ectasia with lower sensitivity than tomographic indices based on posterior elevation and pachymetric distribution.²³ Additionally, previous studies found about 10% false positive and 10% false negatives for these front-surface–derived indices (Guerra, unpublished data 2010).

THE BELIN-AMBRÓSIO ENHANCED ECTASIA DISPLAY

The BAD is a comprehensive ectasia screening display designed to present, in a consistent and simplified way, anterior and posterior elevation data along with pachymetric distribution (Figures 3 and 4). Elevation maps of the front and back surfaces of the cornea are presented with their respective best-fit sphere for a fixed 8-mm zone. The Enhanced Ectasia Display, developed by Michael W. Belin, MD, calculates a new reference best-fit sphere for the 8-mm zone, excluding an area of 3.5 mm in diameter centered on the thinnest point. The differences between the standard and enhanced best-fit spheres of the front and back surfaces are calculated. Such analysis facilitates the identification of protruding areas on the front and back surfaces of the cornea. Normal, borderline, and abnormal values are presented in a green/yellow/red color-coded bar.

A pachymetric map enables the identification of the value and location of the true thinnest corneal point. Additionally, thickness progression indices are calculated based on the relative normal increment of thickness toward the periphery.^18,24 The thickness profile is based on the physiologic concept that the cornea is a meniscus (ie, a structure that is thinner in the center and thicker in the periphery). The corneal thickness spatial profile and percentage thickness increase are displayed in graphs that also show the mean and 95% confidence interval of a normal population. The software can detect the thinnest point and calculate the rate of increase in thickness from this point outward to the periphery. This approach enables the clinician to distinguish a normal thin cornea from one with mild ectatic changes, including predisposition or susceptibility to ectasia, even in corneas with relatively normal thickness.

Indices are generated from these maps, and the deviation from normal toward ectatic disease (ie, deviation value) is calculated. A final deviation value that combines the indices is calculated based on linear regression analysis to optimize the sensitivity and specificity to detect ectasia. It is important to note that this parameter was designed to detect mild abnormalities related to ectasia, such as in contralateral eyes, with apparently normal front surface topography, of a patient with keratoconus in one eye.

Case example

A 24-year-old woman presented for LASIK. Her manifest refraction was -3.25 -1.00 X 17° OD, yielding 20/15 BCVA, and -4.00 D of sphere OS, yielding 20/20 BCVA. CCT was 521 μm OD and 533 μm OS; corneal front surface curvature maps (Figure 2) were relatively normal in both eyes. The patient underwent uneventful LASIK with IntraLase-created (Abbott Medical Optics Inc.) planar flaps 120 μm thick in both eyes. The early postoperative period was uneventful, and the patient achieved 20/20 UCVA. At 6 months postoperative, however, the patient returned, complaining of reduced vision in both eyes. Regression of myopic astigmatism was observed in each eye. Further progression was observed, along with inferior steepening with mild reduction of BCVA. The patient was considered for corneal collagen crosslinking treatment.

The preoperative Pentacam data were retrieved, and a BAD display was generated (Figures 3 and 4). The Ambrósio Relational Thickness (ART) was calculated for the average and maximal progression indices (ARTAve and ART-Max, respectively). ART-Ave was 496 μm OD and 517 μm OS, and ARTMax was 404 μm OD and 419 μm OS. The ART concept combines the thinnest corneal point with the average pachymetric progression of all meridians and in the maximal meridian. For detecting keratoconus, ARTAve and ART-Max have areas under the receiver operating characteristic curves of 0.98 and 0.99, with cut-offs of approximately 430 μm and 340 μm, respectively.¹⁸ However, for the identification of ectasia susceptibility, we have elected not to perform LASIK if ART-Max is lower than 405 μm or ART-Ave is lower than 500 μm. The final deviation values were 1.93 OD and 2.09 OS. Interestingly, a deviation value of more than 1.45 represents the most accurate risk factor parameter for detecting mild cases of ectasia or susceptibility.

CONCLUSION

Enhanced screening should go beyond simple corneal curvature and central thickness analysis. There has been a tremendous evolution from manual keratometry to corneal topography to corneal tomography. Studies by the Rio de Janeiro Corneal Tomography and Biomechanics Study Group have focused on identifying criteria for ectasia susceptibility, including corneal tomography and biomechanical assessment.4,25 The Pentacam BAD provides a comprehensive refractive surgical screening tool to assist the refractive surgeon in identifying patients at risk for postoperative ectasia. Further improvements are expected with the integration of biomechanical assessment.

Renato Ambrósio Jr, MD, PhD, is the Director of Cornea and Refractive Surgery at the Instituto de Olhos Renato Ambrósio in Rio de Janeiro, Brazil. He is also Scientific Coordinator of the Rio de Janeiro Corneal Tomography and Biomechanics Study Group and an Associate Professor of Ophthalmology at Pontific Catholic University of Rio de Janeiro and Federal University of São Paulo. Dr. Ambrósio states that he is a consultant to Oculus, Inc. He may be reached at e-mail: dr.renatoambrosio@gmail.com.

Isaac Ramos, MD, is in practice at the Instituto de Olhos Renato Ambrósio and is a research associate with the Rio de Janeiro Corneal Tomography and Biomechanics Study Group. Dr. Ramos states that he has no financial interest in the products or companies mentioned.

Fernando Faria Correia, MD, is a research associate with the Rio de Janeiro Corneal Tomography and Biomechanics Study Group. Dr. Correia states that he has no financial interest in the products or companies mentioned

Michael Belin, MD, FACS, is a Professor of Ophthalmology and Vision Sciences at the University of Arizona in Tucson. Dr. Belin states that he is a consultant to Oculus, Inc. He may be reached at e-mail: mwbelin@aol.com.

1. Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK in a case of forme fruste keratoconus. J Cataract Refract Surg. 1998;24(7):1007-1009.
2. Dawson DG, Randleman JB, Grossniklaus HE, et al. Corneal ectasia after excimer laser keratorefractive surgery: histopathology, ultrastructure, and pathophysiology. Ophthalmology. 2008;115(12):2181-2191.e1
3. Giledi O, Daya SM. Unexpected flap thickness in laser in situ keratomileusis. J Cataract Refract Surg. 2003;29(9):1825-1826.
4. Ambrosio R Jr, Nogueira LP, Caldas DL, et al. Evaluation of corneal shape and biomechanics before LASIK. Int Ophthalmol Clin. 2011;51(2):11-38.
5. Ambrosio R Jr, Klyce SD, Wilson SE. Corneal topographic and pachymetric screening of keratorefractive patients. J Refract Surg. 2003;19(1):24-29.
6. Oshika T, Klyce SD. Corneal topography in LASIK. Semin Ophthalmol. 1998;13(2):64-70.
7. Ambrosio R Jr, Wilson SE. Complications of laser in situ keratomileusis: etiology, prevention, and treatment. J Refract Surg. 2001;17(3):350-379.
8. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology. 2008;115(1):37-50.
9. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia Risk Score System for preoperative laser in situ keratomileusis screening. Am J Ophthalmol. 2008;145(5):813-818.
10. Duffey RJ, Hardten DR, Lindstrom RL, et al. Ectasia after refractive surgery. Ophthalmology. 2008;115(10):1849; author reply 49-50.
11. Chan CC, Hodge C, Sutton G. External analysis of the Randleman Ectasia Risk Factor Score System: a review of 36 cases of post LASIK ectasia. Clin Experiment Ophthalmol. 2010;38(4):335-340.
12. Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal ectasia after laser in situ keratomileusis in patients without apparent preoperative risk factors. Cornea. 2006;25(4):388-403.
13. Amoils SP, Deist MB, Gous P, Amoils PM. Iatrogenic keratectasia after laser in situ keratomileusis for less than -4.0 to -7.0 diopters of myopia. J Cataract Refract Surg. 2000;26(7):967-977.
14. Ambrosio R Jr, Dawson DG, Salomao M, Guerra FP, Caiado AL, Belin MW. Corneal ectasia after LASIK despite low preoperative risk: tomographic and biomechanical findings in the unoperated, stable, fellow eye. J Refract Surg. 2010:1-6.
15. Tabbara KF, Kotb AA. Risk factors for corneal ectasia after LASIK. Ophthalmology. 2006;113(9):1618-1622.
16. Belin MW, Ambrosio R Jr. Corneal ectasia risk score: statistical validity and clinical relevance. J Refract Surg. 2010;26(4):238-240.
17. Wilson SE, Ambrosio R. Computerized corneal topography and its importance to wavefront technology. Cornea. 2001;20(5):441-454.
18. Ambrosio R Jr, Caiado AL, Guerra FP, et al. Novel pachymetric parameters based on corneal tomography for diagnosing keratoconus. J Refract Surg. 2011;27(10):753-738.
19. Ambrosio R Jr, Belin MW. Imaging of the cornea: topography vs tomography. J Refract Surg. 2010;26(11):847- 849.
20. Kwon RO, Price MO, Price FW, Jr., Ambrosio R Jr, Belin MW. Pentacam characterization of corneas with Fuchs dystrophy treated with Descemet membrane endothelial keratoplasty. J Refract Surg. 2010;26(12):972-979.
21. Wilson SE, Klyce SD, Husseini ZM. Standardized color-coded maps for corneal topography. Ophthalmology. 1993;100(11):1723-1727.
22. Ramos I, Ambrosio R Jr, Guerra FP, Belin MW, Trattler WB. Impact of the subjective variability of corneal topography classification on the ectasia risk score system. Paper presented at: the American Academy of Ophthalmology Annual Meeting; October 24, 2011; Orlando, FL.
23. Saad A, Gatinel D. Topographic and tomographic properties of forme fruste keratoconus corneas. Invest Ophthalmol Vis Sci. 2010;51(11):5546-5555.
24. Ambrosio R Jr, Alonso RS, Luz A, Coca Velarde LG. Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg. 2006;32(11):1851-1859.
25. Ambrosio R Jr, Dawson DG, Salomao M, Guerra FP, Caiado AL, Belin MW. Corneal ectasia after LASIK despite low preoperative risk: tomographic and biomechanical findings in the unoperated, stable, fellow eye. J Refract Surg. 2010;26(11):906-911.