1. Asymmetric Keratoconus Study: Novel Tomographic Parameters to enhance sensitivity to detect abnormalities in eyes with normal axial curvature maps from patients with obvious keratoconus in the fellow eye Marcella Q. Salomão, MD; José Salgado-Borges, MD; Eduardo Viteri, MD; Canrobert Oliveira, MD; Renato Ambrósio Jr.MD, PhD. Canrobert Oliveira, MD; Renato Ambrósio Jr.MD, PhD. No financial interest. Rio de Janeiro - Brazil

2. Purpose To introduce new tomographic diagnostic indices, beyond surface topography, to detect very early signs of ectasia. To calculate the sensitivity of these new parameters. San Francisco 2009

3. Justification Keratoconus is, by definition, a bilateral disease; however, a small percentage of cases present with a very asymmetric pattern. In some cases, the asymmetry can be so significant that the contra- lateral eye presents with normal anterior curvature maps. A bilateral presentation as in these “normal” eyes can occur and could even be the explanation for many cases of ectasia after LASIK with no identifiable pre-operative risk factors. Identifying asymptomatic cases with normal slit lamp exam, good spectacle corrected visual acuity, and normal corneal topography is critical; not only for screening of refractive surgery candidates, but to allow an enhanced treatment choice. San Francisco 2009

4. Patients and Methods 53 eyes showing normal anterior curvature maps (based on standard Rabinowitz criteria) from patients with advanced keratoconus in the fellow eye were evaluated in this multicenter study. All patients had tomographic exams using the Oculus Pentacam. Patient demographics 42 patients ♂ 11 patients ♀ Average age: 35.34 y (17 to 78) San Francisco 2009

5. New tomographic parameters Thickness Profiles 1 : Corneal Thickness Spatial Profile (CTSP) and Percentage Thickness Increase (PTI) Enhanced anterior and posterior elevation best fit sphere (BFS) 2 1- Ambrósio 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 Nov;32(11):1851-9. 1- Ambrósio 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 Nov;32(11):1851-9. 2- Belin MW, Khachikian SS, Ambrósio R Jr, Salomão MQ. Keratoconus / Ectasia detection with the Oculus Pentacam: Belin/Ambrosio enhanced ectasia display. Highlights of Ophthalmology. Volume 35- number 6. 2- Belin MW, Khachikian SS, Ambrósio R Jr, Salomão MQ. Keratoconus / Ectasia detection with the Oculus Pentacam: Belin/Ambrosio enhanced ectasia display. Highlights of Ophthalmology. Volume 35- number 6. San Francisco 2009

6. CTSP and PTI The The San Francisco 2009 The Corneal Thickness Spatial Profile (CTSP) represents the averages of thickness values of the points on 22 imaginary circles centered on the thinnest point with increased diameters at 0.4 mm steps. The Percentage of increase in thickness (PTI) starting from the thinnest point is also calculated. The calculated values are displayed in a progression graph, starting on the thinnest point, as the CTSP and PTI lines. Data from a 95% confidence interval of a normal population is also displayed, so that the clinician can compare the profile of each eye to a normal population. Abnormally thin corneas (ectatic) usually show abrupt and abnormal profiles, out of the 95% CI.

7. Enhanced BFS San Francisco 2009 The Standard BFS is basically an average of high and low elevations of the cornea. It is calculated considering the best reference sphere for the whole corneal surface. Thus, in an abnormal eye, data from an abnormal area might be used in the BFS calculation. The Enhanced BFS was calculated utilizing all the valid data from within the 9.0 mm central cornea with the exception of a 4mm area centered on the thinnest point. This would better approximate the normal cornea and accentuate the abnormal portion. Elevation maps using this new “reference shape” were calculated for both anterior and posterior corneal surfaces.

8. Methods Elevation maps considering the standard BFS were subtracted from the elevation maps with the enhanced BFS; and the highest difference between the maps in the central 4mm area was noted for anterior and posterior corneal surfaces. The differential map contains only 3 colors, each one corresponding to the amount of elevation change that occurs when moving between the standard and enhanced maps. Anterior - green is anything 12 Anterior - green is anything 12 Posterior: green is anything 20 Posterior: green is anything 20 Yellow and red maps were considered abnormal. San Francisco 2009

9. Results San Francisco 2009 ApproachKC eyesContra-lateral eyes Pachymmetric Profiles53 (100%)46 (87%) Enhanced Anterior Elevation 46 (87%)8 (15%) Enhanced Posterior Elevation 53 (100%)47 (89%) All eyes but 1 (52/53 = 98%) presented at least one abnormal finding in the new parameters described. The combination of Pachymetric Profiles and Enhanced Elevation add to each other in sensitivity and specificity. A new display (enhanced ectasia detection),combining the two indices, was developed.

10. Enhanced Ectasia Detection Display San Francisco 2009 On the left side of the display we can see anterior and posterior elevation maps. The bottom 2 maps are difference maps showing the relative change in elevation from the baseline elevation map to the exclusion map. On the right side of the display we’ll see the thickness profiles. In this clinical example, the enhanced display of the left eye showed an abnormal finding in the posterior elevation approach (yellow) along with abnormal thickness profiles, despite a normal anterior surface map.

11. Enhanced Ectasia Detection Display San Francisco 2009 In this clinical example, both thickness profiles were normal in the right eye; however, the posterior elevation approach demonstrated an abnormal finding (yellow).

12. Conclusion The combination of Pachymetric Profiles and Enhanced Elevation was capable of identifying abnormalities in the majority of eyes with normal anterior curvature maps of patients with very asymmetric keratoconus. The new parameters increase sensitivity and specificity for the screening of refractive surgery candidates. San Francisco 2009