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: keratoconus, 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. (Cornea 2015;34:1005–1011) Methods: A total of 2073 eyes 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 astigmatism 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 Eye 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 retinoscopy, and also the corneal topography 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 surgery or trauma, corneal scar, or any concomitant Cornea Volume 34, Number 9, September 2015 www.corneajrnl.com | 1005 Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Naderan et al Cornea Volume 34, Number 9, September 2015 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 visual acuity (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.