1. Risk Factor Analysis of Topographic Progression in Keratoconus Seong Joon Ahn, MD 1,2, Mee Kum Kim MD, PhD 1,2, Won Ryang Wee, MD, PhD 1,2 1 Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea 2 Laboratory of corneal regenerative medicine and ocular immunology, Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea The authors have no financial interest in the subject matter of this poster.

2.  Keratoconus is a progressive noninflammatory disease of the cornea characterized by central stromal thinning that causes apical protrusion, irregular astigmatism, and decreased vision.  In previous studies on keratoconus progression, the criteria of progression had been diverse. From the clinical progression which needed penetrating keratoplasty To several topographic indices such as parameters of corneal apex, thinnest point, and central point Introduction

3. AuthorYear Number of patients Mean age Follow-up period (months) Indices used for progression Proportion of progressed case Sahin et al. 1 20087931.624 Radius, semimeridian, elevation, pachymetry, tangential curvature, mean spheric curvature at apex and thinnest/center point, SimK max, SimK min NS Kang et al. 2 20106822.317.5 SimK max, SimK min, Astigmatism, anterior/posterior elevation, corneal thinnest/central pachymetry, anterior/ posterior best fit sphere value NS Suzuki et al. 3 20093424.172 Regular astigmatism, asymmetry, and higher-order irregularity component in the central 3 mm zone. NS Hwang et al. 4 2010107 eyes24.522.6/20.5* Sim Kmax, Sim Kmin, apical power, astigmatic index, irregularity index, anterior elevation NS Weed et al. 5 2007364 eyes19/241004 daysProgression to corneal graft surgery4% Reeves et al. 6 2005131 eyes37.1NSProgression to penetrating keratoplasty45% Li et al. 7 200736932/39*4.0/3.8* yearsCentral K (CK), I-S, and KISA valuesNS McMahon et al. 8 2006103238.98 yearsFlat K24.1% (> or = 3.0D) Oshika et al. 9 20026428.3 ≥ 1 yearSpherical component, regular astigmatism, decentration component, and higher order irregularity NS Table. The criteria for keratoconus progression in previous studies * Follow-up periods and mean ages were denoted as those in lens-wearing or keratoconus group / those in control group.

4.  We intended to develop the criterion for topographic progression of keratoconus. By including many topographic parameters which were reported previously  Using the criterion, all patients were classified into progressed or non-progressed cases.  Subsequently, we performed risk factor analysis to explore associated factors with topographic progression. Purpose

5.  Retrospective study The patients who visited Seoul National University Hospital from May 2005 to July 2009 Inclusion criteria Patients who underwent follow-up examinations for more than 2 yrs. In patients who underwent surgical treatment, the preoperative follow-up examinations were performed for more than 2 years. Orbscan II topography were performed more than twice. Exclusion criteria Any surgical treatment before the first visit Corneal topography was performed using Orbscan II (Bausch & Lomb, Claremont, CA).  In total, 211 eyes of 128 patients were included. Methods

6.  Previously used 8 topographic indices suggesting progression in earlier studies Increase in Simulated K (SimK), astigmatism Irregularity index of 3 mm and 5 mm Anterior and posterior elevation Inferior minus superior (I-S value) asymmetry Decrease in Thinnest-point pachymetry  The criterion for topographic progression Patient showing ≥ 5 progressed parameters compared to baseline examination This criterion has the greatest value of kappa with gold standard (progression to keratoplasty)  Logistic analysis was performed to evaluate the risk factors associated with topographic progression. Age, sex, the age of diagnosis, the use and duration of contact lens, follow-up period, severity at initial visit, atopic disease, slit-lamp findings. Using Statistical Package for the Social Sciences (SPSS) Ver. 12.0 Methods

7. Clinical characteristicsProgression (n=94)No Progression (n=117)p value* Sex (M:F)58.5%:41.5%59.0%:41.0%0.946 Age of diagnosis 22.23  5.65 † 24.65  7.87 0.049 Follow-up period (months) 43.1  12.440.7  14.0 0.214 History of atopic disease12 (12.7%)15 (12.8%)0.991 Severity of keratoconus7:54:33 ‡ 6:59:420.764 Treatment Glasses prescription10 (10.6%)11 (9.4%)0.781 Contact lens use76 (80.9%)98 (83.8%)0.487 Keratoplasty21 (22.3%)16 (13.8%)0.098 Slit lamp findings Central PEE25 (26.6%)33 (28.2%)0.795 Corneal opacity15 (15.6%)29 (24.8%)0.126 Results Table. Comparision of clinical features and treatment methods between patients with and without progression * P value was obtained by Chi-square test for nominal or interval variables and Student’s t test for continuous variables. † Mean  standard deviation ‡ Mild (central K 52D)

8. Index With progressionWithout progression P value for change* BaselineFollow-upBaselineFollow-up SimK max 50.0  4.752.1  5.452.1  6.151.1  5.0 <0.001 Corneal astigmatism 3.9  2.65.1  2.85.2  3.44.2  2.6 <0.001 Irregularity at 3mm 5.5  2.76.2  2.56.3  2.95.1  2.7 <0.001 Irregularity at 5mm 6.2  3.26.5  2.67.1  3.26.0  2.8 <0.001 Thinnest-point pachymetry 443  73436  78.3432  85444  91.1 <0.001 Anterior elevation 29.4  18.534.9  20.137.0  22.230.3  21.2 0.045 Posterior elevation 63.7  38.877.6  44.986.0  41.571.2  45.6 <0.001 Inferior minus superior (I-S) index 6.0  3.67.0  4.27.1  3.84.5  3.3<0.001 Results Table. Comparison of topographic parameters at baseline and follow-up examinations between patients with and without progression *The change of a topographic parameter was calculated by subtraction of the value at baseline from that at the last follow-up. The value was compared between patients with and without progression using Student’s t test. Logistic analysis for risk factors of topographic progression Age of onset was the only risk factor for the progression OR = 0.948 (95% confidence interval = 0.907 - 0.991), p value = 0.010

9.  This study developed the criterion which determines whether keratoconic eye is topographically progressed or not. Despite its clinical usefulness, there has been no trial to develop the criterion. Keratoconic eye have diverse changes in several topographic indices. If some patients show progressive changes in only a few indices but these indices were used for the criterion for keratoconus progression, bias can come. We used various (8) parameters to evaluate topographic progression in keratoconus. Progression in equal to or more than 5 parameters indicates generalized progressive changes in corneal topography. We set gold standard as progression to keratoplasty and the most agreeable criterion with gold standard was chosen. Thus, patients with topographic progression under our criterion may have greater chance of keratoplasty. Discussion

10.  Under the criterion of topographic progression, younger age was discovered to be a risk factor of topographic progression. Age is a well-known risk factor of keratoconus progression. 3,6,8 Our study confirmed it, using a new criterion for topographic progression. Discussion

11.  Our study developed the criterion for topographic progression of keratoconus and suggests that younger age is a risk factor for the progression.  In clinical practice, Clinicians can envisage the course of keratoconus in individual patients with patients’ age The decision on the surgical treatment can be supported using the criterion. Summary

12. 1. Sahin, A., N. Yildirim, et al. (2008). "Two-year interval changes in Orbscan II topography in eyes with keratoconus." J Cataract Refract Surg 34(8): 1295-1299. 2. Kang, Y. S., Y. K. Park, et al. (2010). "The effect of the YK lens in keratoconus." Ophthalmic Physiol Opt 30(3): 267-273. 3. Shirayama-Suzuki, M., S. Amano, et al. (2009). "Longitudinal analysis of corneal topography in suspected keratoconus." Br J Ophthalmol 93(6): 815-819. 4. Hwang, J. S., J. H. Lee, et al. (2010). "Effects of multicurve RGP contact lens use on topographic changes in keratoconus." Korean J Ophthalmol 24(4): 201-206. 5. Weed, K. H., C. J. Macewen, et al. (2007). "The Dundee University Scottish Keratoconus Study II: a prospective study of optical and surgical correction." Ophthalmic Physiol Opt 27(6): 561-567. 6. Reeves, S. W., S. Stinnett, et al. (2005). "Risk factors for progression to penetrating keratoplasty in patients with keratoconus." Am J Ophthalmol 140(4): 607-611. 7. Li, X., H. Yang, et al. (2007). "Longitudinal study of keratoconus progression." Exp Eye Res 85(4): 502-507. 8. McMahon, T. T., T. B. Edrington, et al. (2006). "Longitudinal changes in corneal curvature in keratoconus." Cornea 25(3): 296-305. 9. Oshika, T., T. Tanabe, et al. (2002). "Progression of keratoconus assessed by fourier analysis of videokeratography data." Ophthalmology 109(2): 339-342. References