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Central Corneal Thickness and Its Association with Ocular and General Parameters in Indians: The Central India Eye and Medical Study
Central Corneal Thickness and Its Association with Ocular and General Parameters in Indians: The Central India Eye and Medical Study Vinay Nangia, FRCS, MD,1* Jost B. Jonas, MD,2* Ajit Sinha, DO, MD,1 Arshia Matin, MS, MD,1 Maithili Kulkarni, DO, MD1 Purpose: To evaluate the distribution of central corneal thickness (CCT) and its associations in an adult Indian population. Design: Population-based study. Participants: The Central India Eye and Medical Study is a population-based study performed in a rural region close to Nagpur in Central India; it included 4711 subjects (ages 30⫹ years) of 5885 eligible subjects (response rate, 80.1%). Methods: The participants underwent a detailed ophthalmic and medical examination, including 200 standardized questions on socioeconomic background, lifestyle, social relations, and psychiatric depression. This study was focused on CCT as measured by sonography and its associations. Intraocular pressure was measured by applanation tonometry. Main Outcome Measures: Central corneal thickness and intraocular pressure. Results: Central corneal thickness measurement data were available on 9370 (99.4%) eyes. Mean CCT was 514⫾33 m (median, 517 m; range, 290 – 696 m). By multiple regression analysis, CCT was associated significantly with younger age (P⬍0.001), male gender (P⬍0.001), higher body mass index (P ⫽ 0.006), lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.02), and shorter axial length (P ⫽ 0.006). Central corneal thickness was not associated significantly with refractive error (P ⫽ 0.54) or cylindrical refractive error (P ⫽ 0.20). If eyes with a corneal refractive power of 45 or more diopters were excluded, the relationship between CCT and axial length was no longer statistically significant (P⬎0.05), whereas all other relationships remained significant. Intraocular pressure readings increased significantly (P⬍0.001) with both higher CCT and higher corneal refractive power. Conclusions: Indians from rural Central India have markedly thinner corneas than do Caucasians or Chinese, and, as in other populations, CCT is greater in men. CCT was associated with younger age, higher body mass index, lower corneal refractive power, deeper anterior chamber, thicker lens, and shorter axial length. Intraocular pressure readings were associated with CCT, with high readings in those eyes that had thick corneas or steep corneas. Central corneal thickness and steepness of the anterior corneal surface may thus both have to be taken into account when applanation tonometry is performed. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010;117:705–710 © 2010 by the American Academy of Ophthalmology.
Central corneal thickness (CCT) has emerged as a clinically important parameter in the diagnosis of glaucoma, because errors in intraocular pressure measurement may result from either low or high CCT.1–16 If dependence of the intraocular pressure measurements on CCT is not taken into account, a thin cornea becomes a diagnostic risk factor for undetected glaucoma and causes underestimation of the true glaucoma risk. In addition, some studies have suggested that a thin cornea may be a structural risk factor for increased glaucoma susceptibility,3,11 which shows the importance that measurement of the CCT has gained. Previous population-based investigations and hospitalbased investigations, such as the Rotterdam Study, the Mon© 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
golian study, the Reykjavik Eye Study, the Barbados Eye Study, the Tajimi study, and the Singapore Malay Eye Study, have already assessed the CCT in various population groups, including Caucasians, Hispanics, Mongolians, Japanese, Chinese, and Malay.17–30 However, because studies focused on the CCT have not yet been carried out in India,31,32 the nation with the second largest population in the world, the present investigation was carried out to assess CCT in a population-based study in Central India. In addition, a purely rural region was chosen as the study site, a region that has a relatively low socioeconomic level. This particular rural region is associated with a lifestyle not yet markedly influenced by the products of modern civilization. ISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.09.003
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Ophthalmology Volume 117, Number 4, April 2010 In addition, mobility of the inhabitants is relatively low. This study site may therefore allow us to assess the CCT in a population group who is largely untouched by outside influences.
Materials and Methods The Central India Eye and Medical Study is a population-based cross-sectional study in Central India.33 It was carried out in 8 villages in the rural region of Central India in the Eastern Maharashtra region at a distance of approximately 40 km from Nagpur. The Medical Ethics Committee of the Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Germany, and the ethics committee of Suraj Eye Institute, India, approved the study; all participants gave informed consent, and all studies were in accordance with the Declaration of Helsinki. Inclusion criterion was an age of 30⫹ years. As the first step, social workers mapped the villages and went from house to house to list all inhabitants, and all villagers aged 30 years and older were invited to participate in the study. The subjects were taken by bus to the hospital, where they underwent a day-long examination. Of a total population of 13,606 villagers, 5885 subjects fulfilled the inclusion criterion of being at least 30 years of age and were thus eligible for the study. Of these 5885 subjects, 4711 participated, resulting in a response rate of 80.1% (Table 1). There were 2520 (53.5%) women and 2191 men; mean age was 49.5⫾13.4 years (median, 47 years; range, 30 –100 years). All examinations were carried out at the hospital. Trained social workers filled out a questionnaire, which included 200 questions on the socioeconomic background and living conditions, daily food intake, smoking or other types of tobacco used, alcohol consumption, and amount and type of daily physical activity. A medical and family history of eye diseases and a history of psychiatric illness with respect to depression were recorded. The study participants underwent a detailed ophthalmologic examination, including measurement of uncorrected and bestcorrected visual acuity and perimetry (frequency-doubling perimetry; screening program C-20-1 [Zeiss-Humphrey, Dublin, CA]). Intraocular pressure was measured by a slit-lamp mounted Goldmann applanation tonometer. If the measurements were greater than 21 mmHg, tonometry was repeated and the mean of 3 measurements was recorded. Slit-lamp biomicroscopy was performed before and after medical mydriasis. Digital photographs of the lens were taken to assess the degree of cataract according to the Age Related Eye Disease Study.34 Digital monoscopic photographs of Table 1. Demographic Data of the Central India Eye and Medical Study Age
Male
Female
Total
30–34 yrs 35–39 yrs 40–44 yrs 45–49 yrs 50–54 yrs 55–59 yrs 60–64 yrs 65–69 yrs 70–74 yrs 75–79 yrs 80–85 yrs 85⫹ yrs Total
264 (12.0%) 226 (10.3%) 340 (15.5%) 292 (13.3%) 237 (10.8%) 160 (7.3%) 182 (8.3%) 172 (7.9%) 187 (8.5%) 74 (3.4%) 37 (1.7%) 20 (0.9%) 2191 (100%)
333 (13.2%) 297 (11.8%) 460 (18.3%) 282 (11.2%) 242 (9.6%) 164 (6.4%) 306 (12.1%) 237 (9.4%) 153 (6.1%) 29 (1.2%) 13 (0.5%) 4 (0.2%) 2520 (100%)
597 (12.7%) 523 (11.1%) 800 (17.0%) 574 (12.2%) 479 (10.2%) 324 (6.9%) 488 (10.4%) 409 (8.7%) 340 (7.2%) 103 (2.2%) 50 (1.1%) 24 (0.5%) 4711 (100%)
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the optic disc (20 degrees) and the disc and macula (50 degrees) were also obtained. The optic disc size was measured by confocal laser scanning tomography (Heidelberg Engineering Co., Heidelberg, Germany). With the subject in the supine position, ocular pachymetry and biometry were carried out by ultrasonography using the Pacscan (Sonomed; Bayamon, Puerto Rico). Central corneal thickness, anterior chamber depth, lens thickness, and axial length were measured for both eyes of all subjects. In all subjects, the pulse, arterial blood pressure, body height, and weight were measured, and a chest x-ray and electrocardiogram were taken. One and a half hours after a standardized lunch, blood and urine samples were obtained. Additional selection criterion for the present study, as part of the Central India Eye and Medical Study, was the availability of CCT measurements. There were no other exclusion criteria, such as the presence of corneal disorders. Statistical analysis was performed using a commercially available statistical software package (SPSS for Windows, version 16.0, SPSS Inc., Chicago, IL). In the analysis, we first calculated the mean values and the statistical distribution of the CCT in the study population. As a second step, we assessed the association between CCT and other ocular and general parameters in a univariate manner. As the third step of the statistical analysis, we performed a multivariate analysis with CCT as a dependent parameter and all other measurements as independent parameters; these independent assessments were those that had been associated significantly with CCT in the univariate analysis. The data are given as mean⫾standard deviation; confidence intervals are presented. All P values are 2-sided and considered statistically significant less than 0.05. Only 1 randomly selected eye per subject was used for statistical analysis.
Results Of the 4711 subjects (9422 eyes), CCT data were available on 9370 eyes (99.4%). Central corneal thickness measurements were not available because either the subject refused the measurement, for reasons such as marked blepharospasm, or the measurements could not be performed because of corneal reasons, such as dense scars. Because cataract surgery can lead to a secondary decompensation of the corneal endothelium, all pseudophakic eyes (n ⫽ 249 eyes) and aphakic eyes (n ⫽ 69 eyes) were excluded, so that the study eventually consisted of 4612 subjects with a mean age of 49.1⫾13.2 years (median, 46 years; range, 30 –100 years) and a mean refractive error of ⫺0.19⫾1.50 diopters (median, 0 diopters; range, ⫺20.0 to ⫹6.00 diopters). The mean CCT was 514⫾33 m (median, 517 m; range, 290 – 696 m) (Fig 1). By univariate analysis, CCT was significantly (P⬍0.001) thicker in men (518⫾34 m) than in women (511⫾33 m). Central corneal thickness increased significantly (P⬍0.001) with decreasing age, higher level of education, higher body height, higher body weight, and higher body mass index (Table 2). It also increased with increasing depth of the anterior chamber (P⬍0.001), lens thickness (P⫽0.04), axial length (P⬍0.001), and hyperopic refractive error (P⬍0.001), with decreasing horizontal and vertical corneal refractive power (diopters) (P⬍0.001), and with decreasing cylindrical refractive error (P⬍0.001) (Table 2). Central corneal thickness was not associated significantly with optic disc size (P ⫽ 0.35). Multiple regression analysis, with CCT as the dependent parameter and age, gender, and body weight as independent parameters, revealed that the associations between CCT and age (P⬍0.001), male gender (P⬍0.001), and body mass index (P⬍0.001) remained statistically significant. If body weight (P ⫽ 0.35), body height (P ⫽ 0.44), or level of education (P ⫽ 0.30) were added, all 3 parameters no longer were significantly associ-
Nangia et al 䡠 Central Corneal Thickness in Indians Table 3. Association between Central Corneal Thickness and Ocular and General Parameters in the Central India Eye and Medical Study (Multivariate Analysis) Parameter
P Value
Odds Ratio
95% CI of Odds Ratio
Age (yrs) Gender (male ⫽ 1; female ⫽ 2) Body mass index Corneal refractive power (D) Anterior chamber depth (mm) Lens thickness (mm) Axial length (mm) Refractive error (diopters) Cylindrical refractive error
⬍0.001 ⬍0.001 0.006 ⬍0.001 0.02 0.02 0.006 0.54 0.20
⫺0.31 ⫺6.52 0.39 ⫺3.07 3.94 2.36 ⫺1.95 (NS) (NS)
⫺0.38, ⫺0.24 ⫺8.53, ⫺4.51 0.11, 0.66 ⫺3.78, ⫺2.35 0.76, 7.13 0.32, 4.41 ⫺3.34, ⫺0.56
CI ⫽ confidence interval; D ⫽ diopter; NS ⫽ not significant.
Figure 1. Histogram showing distribution of the CCT in the entire population of the Central India Eye and Medical Study. CCT ⫽ central corneal thickness.
ated with CCT. For the multivariate analysis (including CCT, age, gender, and body mass index), we then added all the ocular parameters that were associated significantly with corneal thickness in the univariate analysis. This analysis revealed that CCT remained associated significantly with lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.02), and shorter axial length (P ⫽ 0.006) (Table 3). Refractive error (P ⫽ 0.54) and cylindrical refractive error (P ⫽ 0.20) were no longer associated significantly with CCT. To avoid Table 2. Association between Central Corneal Thickness and Ocular and General Parameters in the Central India Eye and Medical Study (Univariate Analysis)
Parameter Age Corneal refractive power: Horizontal Vertical Mean Anterior chamber depth Lens thickness Axial length Refractive error (spherical equivalent) Cylindrical refractive error Body height Body weight Body mass index Level of education Intraocular pressure Measurements Optic disc size
Steepness P Correlation Regression Value Coefficient Line
95% CI
⬍0.001
0.14
⫺0.35
⫺0.42, ⫺0.27
⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.17 0.15 0.16 0.07
⫺3.40 ⫺2.73 ⫺3.31 7.23
⫺3.90, 2.78 ⫺3.27, ⫺2.19 ⫺3.88, ⫺2.73 4.30, 10.2
0.04 ⬍0.001 ⬍0.001
0.03 0.08 0.07
2.09 2.85 1.46
⬍0.001
0.09
⫺3.30
⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.13 0.13 0.07 0.07 0.21
0.45 0.41 0.70 0.70 2.04
0.39
(NS)
CI ⫽ confidence interval; NS ⫽ not significant.
a potential bias by including in the analysis those eyes with keratoconus, we excluded all eyes with a corneal refractive power of 46⫹ diopters. We arrived at a similar result: Central corneal thickness was associated significantly with younger age (P⬍0.001), male gender (P⬍0.001), higher body mass index (P ⫽ 0.003), lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.04), and shorter axial length (P ⫽ 0.03). If eyes with a corneal refractive power of 45 or more diopters were excluded, the relationship between CCT and axial length was no longer statistically significant (P⬎0.05), whereas all other relationships remained significant. The relation between corneal thickness and intraocular pressure was examined in separate analyses. In the univariate analysis, intraocular pressure measurements were associated significantly with CCT (P⬍0.001; correlation coefficient, 0.21; equation of the regression line, intraocular pressure [mmHg] ⫽ 0.021⫻CCT [m]⫹2.78). According to the equation of the regression line, intraocular pressure measurements increased from 0.02 mm for each micrometer increase in CCT (Fig 2). A multivariate analysis included the intraocular pressure measurement as the dependent
0.07, 4.11 1.77, 3.93 0.82, 2.10 ⫺4.37, ⫺2.22 0.34, 0.55 0.32, 0.60 0.43, 0.98 0.43, 0.98 1.76, 2.32 Figure 2. Scattergram showing the relationship between intraocular pressure and CCT in the entire population of the Central India Eye and Medical Study (P⬍0.001; correlation coefficient, 0.21; equation of the regression line; intraocular pressure [mmHg] ⫽ 0.021⫻CCT [m]⫹2.78). CCT ⫽ central corneal thickness.
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Ophthalmology Volume 117, Number 4, April 2010 Table 4. Multivariate Analysis of the Association between Intraocular Pressure and Structural Parameters in the Central India Eye and Medical Study
Central corneal thickness (m) Corneal refractive power (D)
P Value
Coefficient
95% CI of the Coefficient
⬍0.001 ⬍0.001
0.118 0.022
0.060–0.177 0.019–0.025
CI ⫽ confidence interval; D ⫽ diopter.
variable and CCT and mean corneal refractive power as independent parameters. It showed that the intraocular pressure measurements were correlated significantly with increasing corneal thickness and with increasing corneal refractive power (or increasing steepness of the anterior corneal curvature) (Table 4). To avoid a potential bias by including in the analysis those eyes with keratoconus, we excluded all eyes with a corneal refractive power of 46⫹ diopters, but this led to the same result: The intraocular pressure readings were associated strongly (significantly) with thicker corneas (P⬍0.001; coefficient, 0.15) and higher corneal refractive power, that is, steeper corneas (P⬍0.001; coefficient, 0.022).
Discussion Previous studies by Goldmann and Schmidt,1 Ehlers and coworkers,2 the Ocular Hypertension Treatment Study group,3 and others4 –16 have shown the importance of CCT in the diagnosis of glaucoma. Accordingly, it was the purpose of this study to measure the CCT in adult Indians, particularly because population-based data on corneal thickness of subjects from Central or Northern India have not been reported. The results of our study show that the mean CCT in Indians from rural Central India is 514⫾33 m, and that corneal thickness is associated significantly with younger age (P⬍0.001), male gender (P⬍0.001), higher body mass index (P ⫽ 0.006), lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.02), and shorter axial length (P ⫽ 0.006) (Table 3). If eyes with a corneal refractive power of 45 or more diopters were excluded, the relationship between CCT and axial length was no longer statistically significant (P⬎0.05), whereas all other relationships remained significant. Intraocular pressure readings were associated significantly (P⬍0.001) with thicker corneas and higher corneal refractive power. These results indicate that Indians from rural Central India have markedly thinner corneas than do Caucasians or Chinese. The mean value of 514 m for CCT, found in the present study, is considerably less than the 537 m in the Rotterdam Study,17 the 527 m in the Icelandic Reykjavik Eye Study,19 the 556 m in the Beijing Eye Study,26 the 541 m in the Singapore Malay Eye Study,27 and the 521 m in the Japanese Tajimi study.24,30 The value found in our study (514 mm) is less than that reported for African Americans (530 mm) in the Barbados Eye Study20 and appears to be similar to the value found for indigenous Australians (512 mm) within Central Australia.23 The value
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found in our study (514 mm) is also rather similar to the value found in a rural South Indian population-based study by Vijaya et al32 (502.8⫾35.3 m in subjects with primary openangle glaucoma and 505.9⫾31.1 m in normal subjects), a study that was primarily focused on the prevalence of glaucoma.31 In a similar manner, the Chennai Glaucoma Study32 in South India reported a mean CCT of 520.7⫾33.4 m. The finding that CCT is not associated with refractive error confirms previous hospital-based studies and populationbased investigations.22,26 As an example, Fam et al22 investigated the association between CCT and the degree of myopia among 714 consecutive Chinese patients, and found no significant relationship. Correspondingly, CCT was not associated with axial length in our study if keratoconus eyes or eyes with a high corneal refractive error (ⱖ45 diopters) were excluded. Central corneal thickness was associated significantly with male gender (P⬍0.001) and higher body mass index (P ⫽ 0.028), which is in agreement with the recent Singapore Malay Eye Study, in which CCT, after controlling for age and gender, was greater in individuals with a higher body mass index (P ⫽ 0.038).27 As in our study, CCT was also associated with greater radius of corneal curvature (lower corneal refractive power), deeper anterior chamber, and greater lens thickness. Also as in the Singapore Malay Eye Study,27 CCT was associated with a longer axial length in univariate analysis in our study (Table 2). In the multivariate analysis after exclusion of eyes with a steep cornea, the association was no longer statistically significant in our study. In our study of villagers from Central India, CCT was not related to the size of the optic nerve head, which is in contrast with a finding from the Beijing Eye Study, in which corneal thickness was marginally significantly (P ⫽ 0.043) correlated with larger disc size.26 These studies do agree, however, that, in the multivariate analysis, corneal thickness was not associated significantly with body weight, body height, or refractive error. As expected, intraocular pressure readings were highly associated with CCT in our study, which is in agreement with the methodological study conducted by Goldmann and Schmidt1 and with hospital-based investigations and population-based studies.2,3,6 –10,16 –19,25,26 In addition to dependence of the intraocular pressure measurements on corneal thickness, our study revealed an association between intraocular pressure readings and corneal curvature: the less curved (i.e., the flatter) the cornea was, the lower were the intraocular pressure readings. This is in contrast with the Reykjavik Eye Study, in which corneal curvature was not associated significantly with the intraocular pressure readings.19 Our finding may be explained by geometry, because a relatively flat structure, compared with a steep structure, requires less external pressure to be further flattened, an observation that may well have clinical implications. After corneal refractive surgery, for example, the corneal surface is markedly flattened so that, in addition to the surgical thinning, the surgical flattening of the cornea may be a second factor for underestimation of the true intraocular pressure.
Nangia et al 䡠 Central Corneal Thickness in Indians The finding that CCT was lower in our study than in most previous population-based studies conducted on other ethnic groups is paralleled by the results of ocular tonometry in our study, in which a mean intraocular pressure of 13.6⫾3.4 mmHg was found (Nangia V, Jonas JB, unpublished data). This is slightly lower than the values found in other population-based studies, such as the Beaver Dam Study and the Blue Mountains Eye Study,35,36 and it is similar to that reported in rural South Indians by Vijaya and colleagues31 (14.29⫾3.32 mmHg), who in a parallel manner also found relatively thin CCT measurements in their study population.
Limitations There are limitations of the present study. A major concern in any prevalence study is nonparticipation. The Central India Eye and Medical Study had a reasonable response rate of 80.1%, but differences between participants and nonparticipants can lead to a selection bias. Another potential weakness of the study design is that subjects from only a rural region were included, a region that can be considered to be markedly rural according to the questionnaire on socioeconomic background and lifestyle. The study did not, however, include subjects from an urban region, so our study does not provide information on differences between rural and urban regions with respect to the examined parameters. Another limitation is that the CCT was measured by ultrasonic pachymetry, whereas other studies used optical coherence tomography. Ultrasonic pachymetry is known to lead to relatively lower corneal thickness measurements,37 but the difference in mean corneal thickness between Central Indians in the present study and the Caucasians and Chinese in previous studies is considerably larger than could be explained by differences in methodology. Therefore, one may assume that Central Indians, indeed, have thinner corneas than do Caucasians or Chinese. Another limitation of our study is that we used sonographic pachymetry for measurement of corneal thickness, so the equation of the regression line of the association between intraocular pressure and corneal thickness (and corneal curvature) may be compared only cautiously with the corneal thickness as measured by optical coherence tomography. In a similar manner, the intraocular pressure in our study was measured by applanation tonometry, so again, the equation of the regression line may only cautiously be extrapolated to situations in which the pressure is measured by a noncontact method. Independently of the techniques, it may be that the anterior corneal curvature should be taken into account for accurate measurement of intraocular pressure. In conclusion, Indians from rural Central India have markedly thinner corneas than do Caucasians or Chinese, but, as in other populations, the CCT is greater in men. Central corneal thickness was associated with younger age, higher body mass index, lower corneal refractive power, deeper anterior chamber, thicker lens, and shorter axial length. Intraocular pressure readings were associated with CCT, with high intraocular pressure readings in those eyes that had thick corneas and steep corneas. Central corneal
thickness and steepness of the anterior corneal surface should both, most likely, be taken into account when applanation tonometry is performed.
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Footnotes and Financial Disclosures Originally received: February 17, 2009. Final revision: August 2, 2009. Accepted: September 3, 2009. Available online: January 4, 2010. 1
Manuscript no. 2009-228.
Suraj Eye Institute, Nagpur, India.
2
Department of Ophthalmology, Medical Faculty Mannheim, of the Ruprecht-Karls-University of Heidelberg, Germany. ⴱ
The first 2 authors contributed equally to this work.
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Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Supported by an unrestricted grant from Heidelberg Engineering Co., Om Drishti Trust Nagpur, ORBIS, Rotary Sight Saver, and Carl Zeiss Meditec Co. Correspondence: Jost B. Jonas, MD, Universitäts-Augenklinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. E-mail: [email protected].
Central corneal thickness (CCT) has emerged as a clinically important parameter in the diagnosis of glaucoma, because errors in intraocular pressure measurement may result from either low or high CCT.1–16 If dependence of the intraocular pressure measurements on CCT is not taken into account, a thin cornea becomes a diagnostic risk factor for undetected glaucoma and causes underestimation of the true glaucoma risk. In addition, some studies have suggested that a thin cornea may be a structural risk factor for increased glaucoma susceptibility,3,11 which shows the importance that measurement of the CCT has gained. Previous population-based investigations and hospitalbased investigations, such as the Rotterdam Study, the Mon© 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
golian study, the Reykjavik Eye Study, the Barbados Eye Study, the Tajimi study, and the Singapore Malay Eye Study, have already assessed the CCT in various population groups, including Caucasians, Hispanics, Mongolians, Japanese, Chinese, and Malay.17–30 However, because studies focused on the CCT have not yet been carried out in India,31,32 the nation with the second largest population in the world, the present investigation was carried out to assess CCT in a population-based study in Central India. In addition, a purely rural region was chosen as the study site, a region that has a relatively low socioeconomic level. This particular rural region is associated with a lifestyle not yet markedly influenced by the products of modern civilization. ISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.09.003
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Ophthalmology Volume 117, Number 4, April 2010 In addition, mobility of the inhabitants is relatively low. This study site may therefore allow us to assess the CCT in a population group who is largely untouched by outside influences.
Materials and Methods The Central India Eye and Medical Study is a population-based cross-sectional study in Central India.33 It was carried out in 8 villages in the rural region of Central India in the Eastern Maharashtra region at a distance of approximately 40 km from Nagpur. The Medical Ethics Committee of the Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Germany, and the ethics committee of Suraj Eye Institute, India, approved the study; all participants gave informed consent, and all studies were in accordance with the Declaration of Helsinki. Inclusion criterion was an age of 30⫹ years. As the first step, social workers mapped the villages and went from house to house to list all inhabitants, and all villagers aged 30 years and older were invited to participate in the study. The subjects were taken by bus to the hospital, where they underwent a day-long examination. Of a total population of 13,606 villagers, 5885 subjects fulfilled the inclusion criterion of being at least 30 years of age and were thus eligible for the study. Of these 5885 subjects, 4711 participated, resulting in a response rate of 80.1% (Table 1). There were 2520 (53.5%) women and 2191 men; mean age was 49.5⫾13.4 years (median, 47 years; range, 30 –100 years). All examinations were carried out at the hospital. Trained social workers filled out a questionnaire, which included 200 questions on the socioeconomic background and living conditions, daily food intake, smoking or other types of tobacco used, alcohol consumption, and amount and type of daily physical activity. A medical and family history of eye diseases and a history of psychiatric illness with respect to depression were recorded. The study participants underwent a detailed ophthalmologic examination, including measurement of uncorrected and bestcorrected visual acuity and perimetry (frequency-doubling perimetry; screening program C-20-1 [Zeiss-Humphrey, Dublin, CA]). Intraocular pressure was measured by a slit-lamp mounted Goldmann applanation tonometer. If the measurements were greater than 21 mmHg, tonometry was repeated and the mean of 3 measurements was recorded. Slit-lamp biomicroscopy was performed before and after medical mydriasis. Digital photographs of the lens were taken to assess the degree of cataract according to the Age Related Eye Disease Study.34 Digital monoscopic photographs of Table 1. Demographic Data of the Central India Eye and Medical Study Age
Male
Female
Total
30–34 yrs 35–39 yrs 40–44 yrs 45–49 yrs 50–54 yrs 55–59 yrs 60–64 yrs 65–69 yrs 70–74 yrs 75–79 yrs 80–85 yrs 85⫹ yrs Total
264 (12.0%) 226 (10.3%) 340 (15.5%) 292 (13.3%) 237 (10.8%) 160 (7.3%) 182 (8.3%) 172 (7.9%) 187 (8.5%) 74 (3.4%) 37 (1.7%) 20 (0.9%) 2191 (100%)
333 (13.2%) 297 (11.8%) 460 (18.3%) 282 (11.2%) 242 (9.6%) 164 (6.4%) 306 (12.1%) 237 (9.4%) 153 (6.1%) 29 (1.2%) 13 (0.5%) 4 (0.2%) 2520 (100%)
597 (12.7%) 523 (11.1%) 800 (17.0%) 574 (12.2%) 479 (10.2%) 324 (6.9%) 488 (10.4%) 409 (8.7%) 340 (7.2%) 103 (2.2%) 50 (1.1%) 24 (0.5%) 4711 (100%)
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the optic disc (20 degrees) and the disc and macula (50 degrees) were also obtained. The optic disc size was measured by confocal laser scanning tomography (Heidelberg Engineering Co., Heidelberg, Germany). With the subject in the supine position, ocular pachymetry and biometry were carried out by ultrasonography using the Pacscan (Sonomed; Bayamon, Puerto Rico). Central corneal thickness, anterior chamber depth, lens thickness, and axial length were measured for both eyes of all subjects. In all subjects, the pulse, arterial blood pressure, body height, and weight were measured, and a chest x-ray and electrocardiogram were taken. One and a half hours after a standardized lunch, blood and urine samples were obtained. Additional selection criterion for the present study, as part of the Central India Eye and Medical Study, was the availability of CCT measurements. There were no other exclusion criteria, such as the presence of corneal disorders. Statistical analysis was performed using a commercially available statistical software package (SPSS for Windows, version 16.0, SPSS Inc., Chicago, IL). In the analysis, we first calculated the mean values and the statistical distribution of the CCT in the study population. As a second step, we assessed the association between CCT and other ocular and general parameters in a univariate manner. As the third step of the statistical analysis, we performed a multivariate analysis with CCT as a dependent parameter and all other measurements as independent parameters; these independent assessments were those that had been associated significantly with CCT in the univariate analysis. The data are given as mean⫾standard deviation; confidence intervals are presented. All P values are 2-sided and considered statistically significant less than 0.05. Only 1 randomly selected eye per subject was used for statistical analysis.
Results Of the 4711 subjects (9422 eyes), CCT data were available on 9370 eyes (99.4%). Central corneal thickness measurements were not available because either the subject refused the measurement, for reasons such as marked blepharospasm, or the measurements could not be performed because of corneal reasons, such as dense scars. Because cataract surgery can lead to a secondary decompensation of the corneal endothelium, all pseudophakic eyes (n ⫽ 249 eyes) and aphakic eyes (n ⫽ 69 eyes) were excluded, so that the study eventually consisted of 4612 subjects with a mean age of 49.1⫾13.2 years (median, 46 years; range, 30 –100 years) and a mean refractive error of ⫺0.19⫾1.50 diopters (median, 0 diopters; range, ⫺20.0 to ⫹6.00 diopters). The mean CCT was 514⫾33 m (median, 517 m; range, 290 – 696 m) (Fig 1). By univariate analysis, CCT was significantly (P⬍0.001) thicker in men (518⫾34 m) than in women (511⫾33 m). Central corneal thickness increased significantly (P⬍0.001) with decreasing age, higher level of education, higher body height, higher body weight, and higher body mass index (Table 2). It also increased with increasing depth of the anterior chamber (P⬍0.001), lens thickness (P⫽0.04), axial length (P⬍0.001), and hyperopic refractive error (P⬍0.001), with decreasing horizontal and vertical corneal refractive power (diopters) (P⬍0.001), and with decreasing cylindrical refractive error (P⬍0.001) (Table 2). Central corneal thickness was not associated significantly with optic disc size (P ⫽ 0.35). Multiple regression analysis, with CCT as the dependent parameter and age, gender, and body weight as independent parameters, revealed that the associations between CCT and age (P⬍0.001), male gender (P⬍0.001), and body mass index (P⬍0.001) remained statistically significant. If body weight (P ⫽ 0.35), body height (P ⫽ 0.44), or level of education (P ⫽ 0.30) were added, all 3 parameters no longer were significantly associ-
Nangia et al 䡠 Central Corneal Thickness in Indians Table 3. Association between Central Corneal Thickness and Ocular and General Parameters in the Central India Eye and Medical Study (Multivariate Analysis) Parameter
P Value
Odds Ratio
95% CI of Odds Ratio
Age (yrs) Gender (male ⫽ 1; female ⫽ 2) Body mass index Corneal refractive power (D) Anterior chamber depth (mm) Lens thickness (mm) Axial length (mm) Refractive error (diopters) Cylindrical refractive error
⬍0.001 ⬍0.001 0.006 ⬍0.001 0.02 0.02 0.006 0.54 0.20
⫺0.31 ⫺6.52 0.39 ⫺3.07 3.94 2.36 ⫺1.95 (NS) (NS)
⫺0.38, ⫺0.24 ⫺8.53, ⫺4.51 0.11, 0.66 ⫺3.78, ⫺2.35 0.76, 7.13 0.32, 4.41 ⫺3.34, ⫺0.56
CI ⫽ confidence interval; D ⫽ diopter; NS ⫽ not significant.
Figure 1. Histogram showing distribution of the CCT in the entire population of the Central India Eye and Medical Study. CCT ⫽ central corneal thickness.
ated with CCT. For the multivariate analysis (including CCT, age, gender, and body mass index), we then added all the ocular parameters that were associated significantly with corneal thickness in the univariate analysis. This analysis revealed that CCT remained associated significantly with lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.02), and shorter axial length (P ⫽ 0.006) (Table 3). Refractive error (P ⫽ 0.54) and cylindrical refractive error (P ⫽ 0.20) were no longer associated significantly with CCT. To avoid Table 2. Association between Central Corneal Thickness and Ocular and General Parameters in the Central India Eye and Medical Study (Univariate Analysis)
Parameter Age Corneal refractive power: Horizontal Vertical Mean Anterior chamber depth Lens thickness Axial length Refractive error (spherical equivalent) Cylindrical refractive error Body height Body weight Body mass index Level of education Intraocular pressure Measurements Optic disc size
Steepness P Correlation Regression Value Coefficient Line
95% CI
⬍0.001
0.14
⫺0.35
⫺0.42, ⫺0.27
⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.17 0.15 0.16 0.07
⫺3.40 ⫺2.73 ⫺3.31 7.23
⫺3.90, 2.78 ⫺3.27, ⫺2.19 ⫺3.88, ⫺2.73 4.30, 10.2
0.04 ⬍0.001 ⬍0.001
0.03 0.08 0.07
2.09 2.85 1.46
⬍0.001
0.09
⫺3.30
⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.13 0.13 0.07 0.07 0.21
0.45 0.41 0.70 0.70 2.04
0.39
(NS)
CI ⫽ confidence interval; NS ⫽ not significant.
a potential bias by including in the analysis those eyes with keratoconus, we excluded all eyes with a corneal refractive power of 46⫹ diopters. We arrived at a similar result: Central corneal thickness was associated significantly with younger age (P⬍0.001), male gender (P⬍0.001), higher body mass index (P ⫽ 0.003), lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.04), and shorter axial length (P ⫽ 0.03). If eyes with a corneal refractive power of 45 or more diopters were excluded, the relationship between CCT and axial length was no longer statistically significant (P⬎0.05), whereas all other relationships remained significant. The relation between corneal thickness and intraocular pressure was examined in separate analyses. In the univariate analysis, intraocular pressure measurements were associated significantly with CCT (P⬍0.001; correlation coefficient, 0.21; equation of the regression line, intraocular pressure [mmHg] ⫽ 0.021⫻CCT [m]⫹2.78). According to the equation of the regression line, intraocular pressure measurements increased from 0.02 mm for each micrometer increase in CCT (Fig 2). A multivariate analysis included the intraocular pressure measurement as the dependent
0.07, 4.11 1.77, 3.93 0.82, 2.10 ⫺4.37, ⫺2.22 0.34, 0.55 0.32, 0.60 0.43, 0.98 0.43, 0.98 1.76, 2.32 Figure 2. Scattergram showing the relationship between intraocular pressure and CCT in the entire population of the Central India Eye and Medical Study (P⬍0.001; correlation coefficient, 0.21; equation of the regression line; intraocular pressure [mmHg] ⫽ 0.021⫻CCT [m]⫹2.78). CCT ⫽ central corneal thickness.
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Ophthalmology Volume 117, Number 4, April 2010 Table 4. Multivariate Analysis of the Association between Intraocular Pressure and Structural Parameters in the Central India Eye and Medical Study
Central corneal thickness (m) Corneal refractive power (D)
P Value
Coefficient
95% CI of the Coefficient
⬍0.001 ⬍0.001
0.118 0.022
0.060–0.177 0.019–0.025
CI ⫽ confidence interval; D ⫽ diopter.
variable and CCT and mean corneal refractive power as independent parameters. It showed that the intraocular pressure measurements were correlated significantly with increasing corneal thickness and with increasing corneal refractive power (or increasing steepness of the anterior corneal curvature) (Table 4). To avoid a potential bias by including in the analysis those eyes with keratoconus, we excluded all eyes with a corneal refractive power of 46⫹ diopters, but this led to the same result: The intraocular pressure readings were associated strongly (significantly) with thicker corneas (P⬍0.001; coefficient, 0.15) and higher corneal refractive power, that is, steeper corneas (P⬍0.001; coefficient, 0.022).
Discussion Previous studies by Goldmann and Schmidt,1 Ehlers and coworkers,2 the Ocular Hypertension Treatment Study group,3 and others4 –16 have shown the importance of CCT in the diagnosis of glaucoma. Accordingly, it was the purpose of this study to measure the CCT in adult Indians, particularly because population-based data on corneal thickness of subjects from Central or Northern India have not been reported. The results of our study show that the mean CCT in Indians from rural Central India is 514⫾33 m, and that corneal thickness is associated significantly with younger age (P⬍0.001), male gender (P⬍0.001), higher body mass index (P ⫽ 0.006), lower corneal refractive power (P⬍0.001), deeper anterior chamber (P ⫽ 0.02), thicker lens (P ⫽ 0.02), and shorter axial length (P ⫽ 0.006) (Table 3). If eyes with a corneal refractive power of 45 or more diopters were excluded, the relationship between CCT and axial length was no longer statistically significant (P⬎0.05), whereas all other relationships remained significant. Intraocular pressure readings were associated significantly (P⬍0.001) with thicker corneas and higher corneal refractive power. These results indicate that Indians from rural Central India have markedly thinner corneas than do Caucasians or Chinese. The mean value of 514 m for CCT, found in the present study, is considerably less than the 537 m in the Rotterdam Study,17 the 527 m in the Icelandic Reykjavik Eye Study,19 the 556 m in the Beijing Eye Study,26 the 541 m in the Singapore Malay Eye Study,27 and the 521 m in the Japanese Tajimi study.24,30 The value found in our study (514 mm) is less than that reported for African Americans (530 mm) in the Barbados Eye Study20 and appears to be similar to the value found for indigenous Australians (512 mm) within Central Australia.23 The value
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found in our study (514 mm) is also rather similar to the value found in a rural South Indian population-based study by Vijaya et al32 (502.8⫾35.3 m in subjects with primary openangle glaucoma and 505.9⫾31.1 m in normal subjects), a study that was primarily focused on the prevalence of glaucoma.31 In a similar manner, the Chennai Glaucoma Study32 in South India reported a mean CCT of 520.7⫾33.4 m. The finding that CCT is not associated with refractive error confirms previous hospital-based studies and populationbased investigations.22,26 As an example, Fam et al22 investigated the association between CCT and the degree of myopia among 714 consecutive Chinese patients, and found no significant relationship. Correspondingly, CCT was not associated with axial length in our study if keratoconus eyes or eyes with a high corneal refractive error (ⱖ45 diopters) were excluded. Central corneal thickness was associated significantly with male gender (P⬍0.001) and higher body mass index (P ⫽ 0.028), which is in agreement with the recent Singapore Malay Eye Study, in which CCT, after controlling for age and gender, was greater in individuals with a higher body mass index (P ⫽ 0.038).27 As in our study, CCT was also associated with greater radius of corneal curvature (lower corneal refractive power), deeper anterior chamber, and greater lens thickness. Also as in the Singapore Malay Eye Study,27 CCT was associated with a longer axial length in univariate analysis in our study (Table 2). In the multivariate analysis after exclusion of eyes with a steep cornea, the association was no longer statistically significant in our study. In our study of villagers from Central India, CCT was not related to the size of the optic nerve head, which is in contrast with a finding from the Beijing Eye Study, in which corneal thickness was marginally significantly (P ⫽ 0.043) correlated with larger disc size.26 These studies do agree, however, that, in the multivariate analysis, corneal thickness was not associated significantly with body weight, body height, or refractive error. As expected, intraocular pressure readings were highly associated with CCT in our study, which is in agreement with the methodological study conducted by Goldmann and Schmidt1 and with hospital-based investigations and population-based studies.2,3,6 –10,16 –19,25,26 In addition to dependence of the intraocular pressure measurements on corneal thickness, our study revealed an association between intraocular pressure readings and corneal curvature: the less curved (i.e., the flatter) the cornea was, the lower were the intraocular pressure readings. This is in contrast with the Reykjavik Eye Study, in which corneal curvature was not associated significantly with the intraocular pressure readings.19 Our finding may be explained by geometry, because a relatively flat structure, compared with a steep structure, requires less external pressure to be further flattened, an observation that may well have clinical implications. After corneal refractive surgery, for example, the corneal surface is markedly flattened so that, in addition to the surgical thinning, the surgical flattening of the cornea may be a second factor for underestimation of the true intraocular pressure.
Nangia et al 䡠 Central Corneal Thickness in Indians The finding that CCT was lower in our study than in most previous population-based studies conducted on other ethnic groups is paralleled by the results of ocular tonometry in our study, in which a mean intraocular pressure of 13.6⫾3.4 mmHg was found (Nangia V, Jonas JB, unpublished data). This is slightly lower than the values found in other population-based studies, such as the Beaver Dam Study and the Blue Mountains Eye Study,35,36 and it is similar to that reported in rural South Indians by Vijaya and colleagues31 (14.29⫾3.32 mmHg), who in a parallel manner also found relatively thin CCT measurements in their study population.
Limitations There are limitations of the present study. A major concern in any prevalence study is nonparticipation. The Central India Eye and Medical Study had a reasonable response rate of 80.1%, but differences between participants and nonparticipants can lead to a selection bias. Another potential weakness of the study design is that subjects from only a rural region were included, a region that can be considered to be markedly rural according to the questionnaire on socioeconomic background and lifestyle. The study did not, however, include subjects from an urban region, so our study does not provide information on differences between rural and urban regions with respect to the examined parameters. Another limitation is that the CCT was measured by ultrasonic pachymetry, whereas other studies used optical coherence tomography. Ultrasonic pachymetry is known to lead to relatively lower corneal thickness measurements,37 but the difference in mean corneal thickness between Central Indians in the present study and the Caucasians and Chinese in previous studies is considerably larger than could be explained by differences in methodology. Therefore, one may assume that Central Indians, indeed, have thinner corneas than do Caucasians or Chinese. Another limitation of our study is that we used sonographic pachymetry for measurement of corneal thickness, so the equation of the regression line of the association between intraocular pressure and corneal thickness (and corneal curvature) may be compared only cautiously with the corneal thickness as measured by optical coherence tomography. In a similar manner, the intraocular pressure in our study was measured by applanation tonometry, so again, the equation of the regression line may only cautiously be extrapolated to situations in which the pressure is measured by a noncontact method. Independently of the techniques, it may be that the anterior corneal curvature should be taken into account for accurate measurement of intraocular pressure. In conclusion, Indians from rural Central India have markedly thinner corneas than do Caucasians or Chinese, but, as in other populations, the CCT is greater in men. Central corneal thickness was associated with younger age, higher body mass index, lower corneal refractive power, deeper anterior chamber, thicker lens, and shorter axial length. Intraocular pressure readings were associated with CCT, with high intraocular pressure readings in those eyes that had thick corneas and steep corneas. Central corneal
thickness and steepness of the anterior corneal surface should both, most likely, be taken into account when applanation tonometry is performed.
References 1. Goldmann H, Schmidt T. Applanation tonometry [in German]. Ophthalmologica 1957;134:221– 42. 2. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh) 1975; 53:34 – 43. 3. Gordon MO, Beiser JA, Brandt JD, et al, Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary openangle glaucoma. Arch Ophthalmol 2002;120:714 –20. 4. Herndon LW, Weizer JS, Stinnett SS. Central corneal thickness as a risk factor for advanced glaucoma damage. Arch Ophthalmol 2004;122:17–21. 5. Copt RP, Thomas R, Mermoud A. Corneal thickness in ocular hypertension, primary open-angle glaucoma, and normal tension glaucoma. Arch Ophthalmol 1999;117:14 – 6. 6. Hansen FK, Ehlers N. Elevated tonometer readings caused by a thick cornea. Acta Ophthalmol (Copenh) 1971;49:775– 8. 7. Ehlers N, Hansen FK. Central corneal thickness in low-tension glaucoma. Acta Ophthalmol (Copenh) 1974;52:740 – 6. 8. Argus WA. Ocular hypertension and central corneal thickness. Ophthalmology 1995;102:1810 –2. 9. Stodtmeister R. Applanation tonometry and correction according to corneal thickness. Acta Ophthalmol Scand 1998;76: 319 –24. 10. Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and metaanalysis approach. Surv Ophthalmol 2000;44:367– 408. 11. Leske MC, Heijl A, Hyman L, et al, EMGT Group. Predictors of long-term progression in the Early Manifest Glaucoma Trial. Ophthalmology 2007;114:1965–72. 12. Medeiros FA, Sample PA, Weinreb RN. Corneal thickness measurements and frequency doubling technology perimetry abnormalities in ocular hypertensive eyes. Ophthalmology 2003;110:1903– 8. 13. Henderson PA, Medeiros FA, Zangwill LM, Weinreb RN. Relationship between central corneal thickness and retinal nerve fiber layer thickness in ocular hypertensive patients. Ophthalmology 2005;112:251– 6. 14. Kim JW, Chen PP. Central corneal pachymetry and visual field progression in patients with open-angle glaucoma. Ophthalmology 2004;111:2126 –32. 15. Brandt JD, Beiser JA, Kass MA, Gordon MO, Ocular Hypertension Treatment Study (OHTS) Group. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology 2001;108:1779 – 88. 16. Shah S, Chatterjee A, Mathai M, et al. Relationship between corneal thickness and measured intraocular pressure in a general ophthalmology clinic. Ophthalmology 1999;106:2154 – 60. 17. Wolfs RC, Klaver CC, Vingerling JR, et al. Distribution of central corneal thickness and its association with intraocular pressure: the Rotterdam Study. Am J Ophthalmol 1997;123: 767–72. 18. Foster P, Baasanhu J, Alsbirk PH, et al. Central corneal thickness and intraocular pressure in a Mongolian population. Ophthalmology 1998;105:969 –73. 19. Eysteinsson T, Jonasson F, Sasaki H, et al, Reykjavik Eye Study Group. Central corneal thickness, radius of the corneal curvature and intraocular pressure in normal subjects using non-contact
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Footnotes and Financial Disclosures Originally received: February 17, 2009. Final revision: August 2, 2009. Accepted: September 3, 2009. Available online: January 4, 2010. 1
Manuscript no. 2009-228.
Suraj Eye Institute, Nagpur, India.
2
Department of Ophthalmology, Medical Faculty Mannheim, of the Ruprecht-Karls-University of Heidelberg, Germany. ⴱ
The first 2 authors contributed equally to this work.
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Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Supported by an unrestricted grant from Heidelberg Engineering Co., Om Drishti Trust Nagpur, ORBIS, Rotary Sight Saver, and Carl Zeiss Meditec Co. Correspondence: Jost B. Jonas, MD, Universitäts-Augenklinik, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. E-mail: [email protected].