CLINICAL SCIENCE

Keratoconus Clinical Findings According to Different Classifications

Mohammad Naderan, MD,* Saeed Shoar, MD,* Mohammad A. Kamaleddin, PhD,† Mohammad T. Rajabi, MD,‡ Morteza Naderan, MD,* and Marjan Khodadadi, MD*

Key Words: , topographic findings, keratometry read- fi Purpose: To demonstrate the topographic and keratometric nd- ing, sex, age, severity, Amsler–Krumeich, keratoconus severity ings in patients with keratoconus (KC), according to age, sex, and score, validity KC severity groups. ( 2015;34:1005–1011) Methods: A total of 2073 of 1081 patients with KC were consecutively diagnosed and enrolled in this prospective cross- sectional study. All patients underwent ophthalmic examination eratoconus (KC) is a progressive ectatic disease of the and Pentacam (Oculus Optikgerate GmbH) measurements. The Kcornea with a usual onset at puberty.1,2 Although it may be patients were divided into different groups according to their age, asymptomatic in the early stages, KC usually progresses until sex, Amsler–Krumeich classification, and keratoconus severity the fourth decade of life when irregular and visual score classification. Keratometric (K) values (flattest, steepest, impairment emerges because of corneal steepening and and mean), central and thinnest corneal thickness, and manifest scarring.1–4 There are reported differences in the incidence rate, refraction were recorded for each patient with KC and they were presenting scenarios, clinical findings, and progression course of then compared according to the patient’s age, sex, and KC severity KC across different geographic regions.1–4 This may be due to groups. the different stages of corneal changes before the presentation of Results: The age (mean 6 SD) of the population was 24 6 7 patients to clinics. Meanwhile, differences in clinical and ophthalmologic findings in patients with KC may arise from years. The average central corneal thickness and mean K of all 5,6 patients were 462 6 45 mmand48.86 4.8 diopters, respectively. different diagnostic criteria and keratometric indices. Female patients with KC were significantly younger and had Topographic and biomechanical properties of the fi cornea have been proposed to be indispensable tools for the signi cantly higher K values and lower anterior chamber depth 7–10 than those of men. All parameters except for the pupil diameter and diagnosis and treatment of corneal diseases such as KC. astigmatism were significantly associated with KC severity grades. Previous studies have extensively pointed out age-related and sex-related variations in the distribution of KC character- The thinnest corneal thickness was the most important and also the 3,4 most sensitive and specific parameter for distinguishing all stages istics. Moreover, there are other studies regarding topo- fi – graphic findings of keratoconic eyes with respect to the age of KC severity in all KC severity classi cations. The Amsler 5,6,11,12 fi and sex groups. Hence, we sought to demonstrate Krumeich classi cation had the most correlation with other fi severity classifications. topographic and keratometric ndings of keratoconic eyes in a large Iranian population. Conclusions: The results of this study enable clinicians and researchers to understand better the differences between clinical characteristics between sex, age groups, and the changes in clinical MATERIALS AND METHODS characteristics during disease progression, which may lead to further advancement in KC management. Patients and Study Design This study is a part of the Farabi keratoconus study. We conducted this prospective observational study in the Zarrin- Received for publication March 9, 2015; revision received May 22, 2015; accepted May 25, 2015. Published online ahead of print July 23, 2015. bakhsh Clinic, a tertiary eye care center in Tehran, Iran, From the *School of Medicine, Tehran University of Medical Sciences, from 2012 to 2014. A total of 2073 eyes of 1081 patients with Tehran, Iran; †Department of Biotechnology, College of Science, Univer- the diagnosis of KC were enrolled in this study. The diagnosis sity of Tehran, Tehran, Iran; and ‡Eye Research Center, Farabi Eye of KC was made by expert attending ophthalmologists based Hospital, Tehran University of Medical Sciences, Tehran, Iran. on the presence of one or more of the clinical signs found by The authors have no funding or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL slit-lamp examination, including Fleischer rings, corneal citations appear in the printed text and are provided in the HTML and tilting, Vogt striae, corneal stromal thinning, or scissoring PDF versions of this article on the journal’s Web site (www. reflex on , and also the pattern corneajrnl.com). (asymmetric bow tie with a skewed radial axis) and anterior Reprints: Mohammad Naderan, MD, School of Medicine, Tehran University of Medical Sciences, Tehran 1336616351, Iran (e-mail: moh@naderan. or posterior elevation map by the Pentacam (OCULUS com). Optikgerate GmbH, Wetzlar, Germany). Those with a history Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. of eye or trauma, corneal scar, or any concomitant

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ophthalmic conditions other than KC were excluded. This population comprises whites. Male and female patients study is in concordance with the guidelines of the Declaration counted to 667 (62%) and 408 (38%), respectively. Of the of Helsinki, and the institutional review board of the hospital total 2073 eyes, 1287 (62%) were those of male and 786 approved the study protocol. All patients signed an informed (38%) were of female patients. Mean 6 SD age of the consent form to enter this study. Data were gathered by patients was 24 6 7 years (range, 10–68 years). Moreover, a trained nurse and recorded in the study database. the average CCT, TCT, and mean K were 462 6 45 mm, 444 6 50 mm, and 48.8 6 4.8 diopters (D), respectively. Outcome Measures Figure 1 shows the total eyes’ frequency distribution of The following characteristics of KC were evaluated: mean K. keratometry reading values [steep, flat, mean, and maximum (max)], central corneal thickness (CCT), thinnest corneal Comparison of Ophthalmic Parameters thickness (TCT), anterior chamber depth (ACD), and corneal volume (CV) were measured using the Pentacam; pupil According to the Age and Sex Groups diameter (PD) with a measuring caliper; and spherical equiv- Ophthalmic parameters were compared between age groups and sex in Table 1. The PD, ACD, and CV had alent (SE), uncorrected distance (UDVA), and fi corrected distance visual acuity (CDVA) were evaluated. asignicant association with the age groups (univariate analysis). It is perceived from the table that the PD and Patients were divided into even quartiles based on the mean fi , K value in an attempt to find a different classification system for ACD decrease signi cantly with increasing age (P 0.001). Other variables, including sphere, cylinder, SE, grading KC severity. However, KC severity was measured fi – fi 13 CCT, and the average K values did not reveal signi cant according to the Amsler Krumeich classi cation and kerato- . conus severity score (KSS).14 Measurement of KC character- changes between the age groups (P 0.05). Multivariate 5 analysis revealed that when controlling for sex, only the PD istics and other eye parameters have been previously explained. fi The UDVA and CDVA were measured using the Snellen chart. andACDhadasigni cant association with the age groups In noncontact lens wearers, the CDVA was determined only by (P = 0.004 and 0.006, respectively). Figure 2 shows the box manifest refraction, and in contact lens wearers, by both plot for SE values according to different age groups and sex. overrefraction (refraction over their contact lenses) and manifest fi refraction. The better vision was recorded as the CDVA. Female patients with KC were signi cantly older than male patients and also had significantly higher steep, flat, and mean keratometry values (P , 0.001). The average ACD had Statistical Analysis a significantly higher mean among male patients (3.5 6 0.3 Data analysis was performed using SPSS for Windows mm vs. 3.4 6 0.4 mm, P , 0.001). Moreover, male patients (version 21; Chicago, IL). All variables were compared revealed more severe astigmatism than did female patients according to the age groups (,20, 20 to ,30, 30 to ,40, (1.54 6 4.23 D vs. 1.16 6 4.23 D, P = 0.051). Multivariate and $40 years) and sex. Moreover, a cross-tabulation was analysis revealed that when controlling for age groups, ACD, performed between severity of KC and patients’ age and sex. sphere, steep K, and SE had a significant association with sex Comparison of the continuous variables was performed (P , 0.05). using the 1-way analysis of variance and Student t test, whereas the x2 test has been used for cross-tabulation of categorical variables. Multivariate analysis was performed to determine the differences when controlling for age or sex. The Pearson correlation coefficient has also been calculated to evaluate the relationship between age and CCT, TCT, mean values and max K, SE, and corneal astigmatism as well as for comparing different severity classifications. Post hoc analysis was performed using the Tukey test to evaluate the differences between severity stages. In an attempt to determine the predictive accuracy of CCT and TCT with maximum sensitivity and specificity, the receiver-operating curve (ROC) was used. The area under the ROC curve of 1 indicates that the test perfectly discriminates between the groups. Data are presented as mean 6 SD and number (%). P , 0.05 was considered statistically significant.

RESULTS Demographics and Primary Characteristics of the Patients A total of 2073 eyes of 1081 patients were enrolled in FIGURE 1. The frequency distribution of mean keratometry this study with no patient being excluded. Most of the Iranian readings (D).

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TABLE 1. Ocular Parameters in the Keratoconic Eyes According to the Age and Sex Groups Group 2 Group 3 Group 1 (20 to ,30 (30 to ,40 Group 4 (,20 Years) Years) Years) (‡40 Years) P* P† Male Female P* P‡ Number, % 443 (21.4) 1280 (61.7) 249 (12.0) 101 (4.8) ——1287 (62) 786 (38) —— Age, yr 16.9 6 2.2 23.8 6 2.6 32.5 6 2.3 46.3 6 6.8 ——23.9 6 6.6 25.5 6 7.9 0.001 0.086 CCT, mm 463 6 48 461 6 42 463 6 54 462 6 48 0.924 0.659 462 6 45 462 6 45 0.678 0.662 TCT, mm 447 6 51 444 6 48 444 6 58 440 6 49 0.481 0.108 445 6 49 444 6 52 0.669 0.266 PD, mm 4.0 6 1.2 3.9 6 1.2 3.6 6 1.0 3.6 6 1.2 ,0.001 0.004 3.9 6 1.2 4.0 6 1.2 0.101 0.494 ACD, mm 3.5 6 0.3 3.5 6 0.3 3.4 6 0.4 3.3 6 0.5 ,0.001 0.006 3.5 6 0.3 3.4 6 0.4 ,0.001 0.001 CV, mm3 56.6 6 3.9 56.0 6 3.7 56.5 6 3.5 56.2 6 4.1 0.021 0.098 56.2 6 3.7 56.2 6 3.9 0.826 0.720 Sphere, D 21.86 6 3.63 22.01 6 3.63 21.80 6 3.45 22.07 6 4.82 0.79 0.553 21.85 6 3.61 22.12 6 3.76 0.105 0.036 Cylinder, D 23.47 6 2.85 23.49 6 2.73 23.31 6 2.59 23.59 6 2.73 0.770 0.592 23.51 6 2.86 23.41 6 2.53 0.450 0.209 Steep K, D 51.2 6 5.2 50.8 6 5.2 50.4 6 6.4 50.7 6 5.5 0.287 0.881 50.6 6 5.4 51.2 6 5.2 0.014 0.044 Flat K, D 47.1 6 4.3 47.0 6 4.4 46.9 6 6.0 46.7 6 5.1 0.839 0.766 46.8 6 4.6 47.4 6 4.7 0.008 0.073 Mean K, D 49.0 6 4.6 48.8 6 4.6 48.6 6 6.1 48.6 6 5.2 0.623 0.938 48.6 6 4.8 49.2 6 4.8 0.007 0.065 Max K, D 55.8 6 7.1 55.4 6 7.3 55.4 6 7.6 56.0 6 7.9 0.698 0.26 55.5 6 7.4 55.6 6 7.2 0.659 0.895 SE, D 23.60 6 4.00 23.75 6 3.96 23.46 6 3.67 23.87 6 5.00 0.668 0.511 23.61 6 4.00 23.83 6 3.99 0.217 0.015 Astigmatism, D 1.70 6 4.38 1.30 6 4.21 1.26 6 4.08 1.64 6 4.25 0.319 0.611 1.54 6 4.23 1.16 6 4.23 0.051 0.084 UDVA, logMAR 0.50 6 0.36 0.53 6 0.38 0.52 6 0.36 0.59 6 0.39 0.324 0.647 0.51 6 0.37 0.55 6 0.37 0.077 0.066 CDVA, logMAR 0.25 6 0.23 0.24 6 0.024 0.24 6 0.24 0.30 6 0.29 0.171 0.35 0.24 6 0.25 0.24 6 0.23 0.964 0.194

Data are given as mean 6 SD. Bold values are statistically significant. *Univariate analysis. †Multivariate analysis after adjusting for sex. ‡Multivariate analysis after adjusting for age. logMAR, logarithm of the minimum angle of resolution.

Distribution of KC Severity According to the Table 2. All parameters were significantly associated with Age Groups and Sex disease severity except for the PD and astigmatism. CCT and Patients of age group 2 (20 to ,30 years) constituted TCT were significantly decreased with severity, whereas the most cases, followed by group 1 (patients younger than 20 keratometry values (flat, steep, min, and max), ACD, years), group 3 (30 to ,40 years), and group 4 (patients older cylinder, sphere, and SE, significantly increased with disease than 40 years). Noticeably, stages 1 and 2 were more severity. prevalent among all age groups. However, no significant Table 3 demonstrates the comparison of ophthalmic difference was observed in cross-tabulation of KC severity parameters according to the KSS. CCT, TCT, ACD, and K and age groups (P = 0.149). Similar to the age groups, stages values were significantly different between all severity 1 and 2 were the most common KC classification with no subgroups. Sphere, cylinder, SE, UDVA, and CDVA were significant difference between men and women for KC significantly different between mild-to-moderate and mild-to- severity (P = 0.072) (see Table, Supplemental Digital severe stages but not between moderate-to-severe stages. Content 1, http://links.lww.com/ICO/A289). ROC Curve Sensitivity, specificity, and area under the ROC curve Comparison of Ophthalmic Parameters of the corneal thickness values for distinguishing the different According to the Different severity stages of keratoconus were evaluated. It was found Severity Classifications that TCT is the most important and also the most sensitive The comparison of ophthalmic parameters according to and specific parameter for distinguishing all stages of KC the quartile classification and intergroup comparison is demon- severity in all KC severity classifications. Sensitivity of TCT strated in Supplemental Digital Content 2 (see Table, http://links. was 0.806, 0.792, and 0.851, and specificity was 0.767, lww.com/ICO/A290). Statistical analysis revealed that quartile 0.745, and 0.811 for Amsler–Krumeich, quartile, and KSS groups had a significant difference in terms of age, CCT, TCT, classifications, respectively (P , 0.001). ACD, sphere, cylinder, K values, SE, astigmatism, UDVA, and CDVA. This difference was seen between each severity grade of CCT, TCT, ACD, and K values. CCT and TCT significantly Correlation Between Different decreased and ACD, K values, sphere, cylinder, and SE Severity Classifications significantly increased with increasing severity grades. To assess the correlation between different severity Comparison of ophthalmic parameters with KC severity classifications, the Pearson correlation coefficient (R) was according to the Amsler–Krumeich classification is shown in used. The results revealed that all classifications were

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Some authors propose that KC arrests in the fifth decade,15 whereas others believe that the progression rate only slows down with age.5 Another study of Asian Indian patients with KC reported that most patients had demon- strated their most severe KC by the second decade.3 Our study found only the PD and ACD to decrease significantly with increasing age. It was previously reported that reduction in ACD is associated with aging.16 ACD gets smaller because the lens gets bigger and the PD decreases with age physiologically. By the way, ACD can vary with the and cataract and is therefore a non- specific finding for keratoconus. However, no correlation was observed between age and CCT, mean K, SE, and corneal astigmatism. Despite various postulations for age- related alterations such as horizontal steepening of the cornea and neovascularization and stiffening of the cornea due to cross-linking of the collagen fibrils,17,18 our knowl- edge of the underlying age-related corneal changes is preliminary.

Sex and KC Several studies have declared a male preponderance in their KC population with slightly younger age of onset.4,5,19,20 FIGURE 2. Box plot of the values of SE (D) in different age and In accordance with previous studies, men constituted 62% of sex groups, bold lines in the boxes shows the median (Q2 or our patients and were younger than women. Owens and 50% percentile), the upper and lower limits of the box show Gamble19 also reported a preponderance of men for their KC the first quartile (Q1 or 25% percentile) and third quartile (Q3 cases in New Zealand revealing an earlier onset and more or 75% percentile), and the bars represent the minimum and rapid disease progression. In contrast, our study and the maximum values. Asterisks and circles show outliers. results of some other researches do not show any differences in KC severity between the sex groups.5,20 In contrast to Ramdas et al21 who showed that women 22 fi , had larger K values and Abu Ameerh et al who found that signi cantly correlated with each other (P 0.001). Among fi fl them, the Amsler–Krumeich classification had the most corre- women had only signi cantly higher at K, we found that fi flat, steep, and mean K were significantly higher in women lation with quartile and KSS classi cations, respectively (r = 22 0.849 and 0.815, respectively), and KSS and quartile classi- (univariate analysis). Similar to Abu Ameerh et al, we fications had the least correlation (r = 0.667) with each other. found that the ACD has higher values among men than women. After adjusting for age, steep K, ACD, and SE had asignificant difference between men and women. These Correlation of Age With Some findings are both similar to and in contrast with the study of 22 fl Ophthalmic Parameters AbuAmeerhetal who found that after age adjustment, at K, anterior chamber depth, and volume, and the basement Correlation of age with CCT, mean K, SE, and corneal fi astigmatism is shown in Figure 3. As the scattergrams show, membrane thickness had signi cant differences between no significant correlation was observed between age and any men and women. Physiological differences between men of these ophthalmic parameters. and women (such as sex hormones) have been suggested as a possible explanation for sex-related KC variations. However, one study has postulated that sex-related differ- DISCUSSION ences in KC originate from the patient history, vision, and ocular symptoms, each having a predisposing role for KC Age and KC and its progression in relation to the sex groups.23 However, Our study revealed no significant relationship between there is a significant sex bias in this study. This could be KC severity and age or sex. Conversely, in a similar cross- explained by the greater attendance of male patients at the sectional study, Ertan and Muftuoglu5 studied 482 eyes of eye clinics because of the functional disability caused by 248 patients with KC and found a clear inverse correlation visual impairment; because in our country, men are the main between age and severity of keratoconus. However, although workforce. This results in a greater predominance of men not statistically significant in our population, group 3 patients presenting at the eye clinic. The older age and steeper (aged 30 to ,40 years) presented with more severe disease cornea in women in this study suggest that they present later followed by group 1 (,20 years), group 2 (20 to ,30 years), in the course of disease rather than that sex affects the and group 4 ($40 years old). disease severity.

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TABLE 2. Comparison of the Ophthalmic Parameters Between the Different Keratoconus Severity According to the Amsler– Krumeich Classification Post Hoc Analysis Stage 1 Stage 2 Stage 3 Stage 4 P S1-S2 S1-S3 S1-S4 S2-S3 S2-S4 S3-S4 Number, % 981 (47.3) 739 (35.6) 227 (11.0) 126 (6.1) ——————— Age, yr 24.7 6 7.3 24.1 6 6.6 24.8 6 8.3 24.2 6 7.3 0.401 0.432 0.994 0.919 0.549 0.697 0.803 CCT, mm 482 6 39 455 6 38 437 6 39 393 6 36 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 TCT, mm 468 6 44 437 6 38 415 6 33 358 6 44 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 PD, mm 3.9 6 1.2 3.9 6 1.2 3.8 6 1.2 3.9 6 1.1 0.411 0.928 0.555 0.991 0.341 0.931 0.927 ACD, mm 3.4 6 0.3 3.5 6 0.3 3.6 6 0.3 3.7 6 0.4 ,0.001 ,0.001 ,0.001 ,0.001 0.016 ,0.001 0.239 CV, mm3 56.2 6 3.7 56.3 6 3.6 56.9 6 4.1 54.7 6 3.9 ,0.001 0.929 0.074 ,0.001 0.206 ,0.001 ,0.001 Sphere, D 21.40 6 2.97 21.96 6 3.86 23.46 6 4.39 23.55 6 4.7 ,0.001 0.008 ,0.001 ,0.001 ,0.001 ,0.001 0.996 Cylinder, D 22.87 6 2.56 23.97 6 2.72 24.11 6 3.06 24.09 6 2.61 ,0.001 ,0.001 ,0.001 ,0.001 0.897 0.964 1 Steep K, D 46.6 6 2.5 52.5 6 1.9 57.6 6 2.7 61.7 6 5.7 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 Flat K, D 43.5 6 2.1 48.3 6 1.5 52.7 6 2.3 57.1 6 5.5 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 Mean K, D 44.9 6 2.0 50.3 6 1.3 55.0 6 2.1 59.4 6 5.3 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 Max K, D 50.3 6 4.6 57.5 6 3.7 64.3 6 4.8 69.5 6 6.2 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 SE, D 22.83 6 3.26 23.94 6 4.10 25.52 6 4.73 25.60 6 5.05 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 0.998 Astigmatism, D 1.44 6 3.50 1.54 6 4.46 0.81 6 5.69 1.24 6 5.02 0.138 0.969 0.173 0.955 0.105 0.883 0.798 UDVA, logMAR 0.42 6 0.35 0.62 6 0.35 0.66 6 0.37 0.65 6 0.40 ,0.001 ,0.001 ,0.001 ,0.001 0.587 0.887 0.997 CDVA, logMAR 0.16 6 0.19 0.31 6 0.24 0.32 6 0.29 0.37 6 0.31 ,0.001 ,0.001 ,0.001 ,0.001 0.954 0.094 0.329

Data are given as mean 6 SD. Bold values are statistically significant. logMAR, logarithm of the minimum angle of resolution; S, stage.

Severity of KC 59.7 6 4.7 D in the severe groups, which confirms that the According to the KSS classification, the average results of both studies are very similar to each other. We corneal power in the study of McMahon et al14 was 47.1 6 proposed a different classification scale, which according to 2.7 D in the mild, 53.8 6 1.1 D in the moderate, and 62.8 6 the results of our study better demonstrated the intergroup 6.5 D in the severe groups, and mean K in our study was differences between severity stages in comparison with other 46.9 6 3.0 D in the mild, 53.6 6 1.1 D in the moderate, and classifications.

TABLE 3. Comparison of the Ophthalmic Parameters According to the KSS Classification Post Hoc Analysis Mild Moderate Severe P Mi-Mo Mi-Se Mo-Se Number, % 1610 (77.6) 310 (15.0) 153 (7.4) ———— Age, yr 24.5 6 7.3 24.6 6 7.7 23.7 6 7.2 0.38 0.971 0.376 0.714 Sex (male) 1005 (62.4) 191 (61.6) 91 (59.5) 0.76 ——— CCT, mm 472 6 40 734 6 43 410 6 44 ,0.001 ,0.001 ,0.001 ,0.001 TCT, mm 457 6 44 414 6 36 377 6 51 ,0.001 ,0.001 ,0.001 ,0.001 PD, mm 3.9 6 1.2 3.8 6 1.1 4.0 6 1.3 0.393 0.523 0.765 0.407 ACD, mm 3.4 6 0.3 3.6 6 0.3 3.7 6 0.4 ,0.001 ,0.001 ,0.001 0.042 CV, mm3 56.2 6 3.7 56.4 6 4.0 56.2 6 4.5 0.721 0.706 0.998 0.849 Sphere, D 21.56 6 3.34 23.09 6 4.14 23.80 6 4.77 ,0.001 ,0.001 ,0.001 0.117 Cylinder, D 23.27 6 2.63 24.26 6 3.04 23.99 6 3.85 ,0.001 ,0.001 0.005 0.568 Steep K, D 48.7 6 3.5 56.1 6 1.7 62.2 6 5.1 ,0.001 ,0.001 ,0.001 ,0.001 Flat K, D 45.2 6 2.8 51.4 6 1.7 57.1 6 5.0 ,0.001 ,0.001 ,0.001 ,0.001 Mean K, D 46.9 6 3.0 53.6 6 1.1 59.7 6 4.7 ,0.001 ,0.001 ,0.001 ,0.001 Max K, D 52.9 6 5.3 62.0 6 3.8 70.4 6 5.6 ,0.001 ,0.001 ,0.001 ,0.001 SE, D 23.20 6 3.62 25.23 6 4.45 25.79 6 5.16 ,0.001 ,0.001 ,0.001 0.301 Astigmatism, D 1.54 6 3.82 0.53 6 5.38 1.63 6 5.47 0.001 ,0.001 0.966 0.024 UDVA, logMAR 0.49 6 0.36 0.66 6 0.36 0.68 6 0.40 ,0.001 ,0.001 ,0.001 0.952 CDVA, logMAR 0.21 6 0.22 0.33 6 0.28 0.37 6 0.31 ,0.001 ,0.001 ,0.001 0.166

All data are mean 6 SD. Bold values are statistically significant. logMAR, logarithm of the minimum angle of resolution; Mi, mild; Mo, moderate; Se, severe.

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FIGURE 3. Correlation scattergrams between age and central corneal thickness (r = 20.004, P = 0.871) at top left, mean K (r = 20.042, P = 0.057) at top right, SE (r = 20.005, P = 0.805) at bottom left and corneal astigmatism (r = 20.013, P = 0.557) at bottom right.

Statistical evaluation revealed that the Amsler–Kru- significant, they may not have an impact. Consistent with meich classification has the highest correlation with other the literature,4,22,25,26 we found that the corneal thickness classifications. Although all classifications were nearly sim- measurements decrease with the progression of KC. These ilar in different values, especially for mild and severe stages, findings show that CCT, TCT, and mean, flat, and steep K are we propose that the Amsler–Krumeich classification can be important indicators of KC progression. It is well known that used as the choice scale for severity grading. Like previous progressive corneal thinning is a pathophysiological feature studies,4,22,24 our study findings revealed that keratometric of KC.27,28 and pachymetric values significantly differ between different In our study, there was a significant negative correlation KC stages. It should be noted that these classification systems between CCT, TCT, and severity levels of all severity use minimum corneal thickness, mean central K readings, classifications. Choi and Kim29 found that the CCT is reduced , and astigmatism for grouping severity; thus, the by KC severity according to the Amsler–Krumeich classifi- patients were grouped in the first place according to these cation. It was concluded by Sahebjada et al24 that central parameters and although these findings were statistically and apical corneal thickness are important parameters in

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distinguishing subclinical from clinical KC and also different 7. Arffa RC. Clinical uses of corneal topography analysis. Curr Opin disease severity levels. In our study, according to ROC curve Ophthalmol. 1992;3:71–77. 8. Kato N, Toda I, Kawakita T, et al. Topography-guided conductive results, TCT was the most important parameter for distin- keratoplasty: treatment for advanced keratoconus. Am J Ophthalmol. guishing different KC severity stages in all KC severity 2010;150:481–489 e1. classifications, which is in agreement with the findings of 9. Kanellopoulos AJ, Binder PS. Collagen cross-linking (CCL) with Demir et al.25 Based on these findings, it may be suggesting sequential topography-guided PRK: a temporizing alternative for kera- – that KC progression may begin with changes in corneal toconus to penetrating keratoplasty. Cornea. 2007;26:891 895. 10. Wilson SE, Klyce SD. Advances in the analysis of corneal topography. thickness. Therefore, progressive decrease in TCT and CCT Surv Ophthalmol. 1991;35:269–277. values are better markers of KC progression and can be used 11. Niederer RL, Perumal D, Sherwin T, et al. Age-related differences in the for monitoring and evaluating patients with KC30 and also in normal human cornea: a laser scanning in vivo confocal microscopy preoperative assessment of candidates to study. Br J Ophthalmol. 2007;91:1165–1169. 31,32 12. Atchison DA. Age-related paraxial schematic emmetropic eyes. Oph- diagnose KC or other ectatic corneal disorders. – 22,24,33 thalmic Physiol Opt. 2009;29:58 64. In contrast to previous studies, which did not find 13. Krumeich JH, Daniel J, Knulle A. Live- for keratoconus. a significant difference between CV and various KC stages, J Cataract Refract Surg. 1998;24:456–463. we observed a significant difference between CV and disease 14. McMahon TT, Szczotka-Flynn L, Barr JT, et al. A new method for severity only in the Amsler–Krumeich classification. 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