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Corneal Refractive Power and Its Associations with Ocular and General Parameters: The Central India Eye and Medical Study
Corneal Refractive Power and Its Associations with Ocular and General Parameters: The Central India Eye and Medical Study Jost B. Jonas, MD,1,2 Vinay Nangia, MD,1 Ajit Sinha, MD,1 Rajesh Gupta, MD1 Purpose: To investigate the normal distribution of corneal refractive power (CRP) and its associations with other ocular and systemic parameters in the Central Indian population. Design: Population-based study. Participants: The Central India Eye and Medical Study is a population-based study performed in a rural region of Central India. The study comprised 4711 subjects aged 30⫹ years. Methods: A detailed ophthalmic and medical examination was performed. Horizontal and vertical CRP were measured using a non-automatic keratometer. Main Outcome Measures: Corneal refractive power. Results: After excluding pseudophakic or aphakic eyes, keratometric measurements were available on 9024 eyes of 4617 study participants (98.0%) with a mean age of 49.1⫾13.2 years (range, 30 –100 years) and a mean refractive error of ⫺0.20⫾1.52 diopters (D). Mean horizontal CRP was 44.60⫾1.68 D (mean ⫾ standard deviation; range, 36.5–52.0 D), and vertical CRP was 44.62⫾1.74 D (range, 37.75–52.0 D) with no significant difference between both parameters (P⫽0.27). In multivariate analysis, CRP was significantly (P ⬍ 0.001) associated with the systemic parameters of increasing age (P ⬍ 0.001), lower level of education (P⫽0.02), and lower body height (P ⬍ 0.001), and with the ocular parameters of thinner central corneal thickness (P ⬍ 0.001), deeper anterior chamber (P ⬍ 0.001), shorter axial length (P ⬍ 0.001), and myopic refractive error (P ⬍ 0.001). The results remained unchanged if eyes with CRP ⱖ48 D were excluded. Conclusions: Horizontal CRP increased with higher age, lower level of education, lower body height, thinner central cornea, deeper anterior chamber, shorter axial length, and myopic refractive error. The association with age may be of importance for refractive surgery. The association of a steeper cornea with a shorter body stature and a shorter axial length parallels an association between shorter body length and shorter axial length without association with refractive error. The association among steeper cornea, shorter body length, and lower educational level complements the association between shorter body length and lower educational level. The correlation between steeper cornea and deeper anterior chamber may be explained geometrically. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:1805–1811 © 2011 by the American Academy of Ophthalmology.
The refractive power of the cornea is a basic parameter in ophthalmology. Its physiologic importance is derived from its close association with the optical system of the eye; its clinical importance is related to the dependence of intraocular pressure readings on the anterior corneal curvature radius1 and to the association between the corneal refractive power (CRP) and corneal shape abnormalities, such as keratoglobus and keratoconus, to mention only a few. In acknowledgment of the importance of CRP, recent population-based studies partially explored the normal distribution of the CRP and some of its associations with ocular and general parameters in populations from Iceland, Japan, Singapore, Australia, California, Myanmar, and North America.2–17 Except for a relatively small group of subjects from South India, there is no major information available on the distribution of CRP and its associations in India, the world’s © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
second largest nation. We therefore conducted this study to examine the normative data of CRP and its associations with other ophthalmic parameters (e.g., axial length) and systemic parameters (e.g., age, general anthropomorphic measurements, and socioeconomic data) in a populationbased investigation in Central India. The findings may provide information on the normal anatomy of the eye, be helpful for issues of corneal refractive surgery, and provide hints for diseases such as primary angle closure glaucoma, the prevalence of which is associated with the dimensions of the anterior ocular segment.
Materials and Methods The Central India Eye and Medical Study is a population-based cross-sectional study in Central India. As described recently in ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2011.02.001
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Ophthalmology Volume 118, Number 9, September 2011 detail,17,18 the study was performed in 8 villages in Kalmeshwar Tehsil, a rural region of Eastern Maharashtra ⬃40 km from Nagpur. The Medical Ethics Committee of the Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg and a similar committee of the Suraj Eye Institute/Nagpur approved the study; all participants gave informed consent, according to the Declaration of Helsinki. The villages were chosen as locations for the study because they were located in a typical rural region of Central India and a relatively long distance from the nearest city (Nagpur). Of a total population of 13 606 villagers, 5885 met the inclusion criterion of an age of 30⫹ years. There was no exclusion criterion. Of the 5885 eligible subjects, 4711 (2191 men [46.5%]) participated, resulting in a response rate of 80.1%. The mean age was 49.5⫾13.4 years (median: 47 years; range: 30 –100 years), and the mean reported monthly income was 1584⫾1233 rupees (1 US dollar ⫽ ⬃50 rupees); the rate of illiteracy was 35%. Among the 1174 nonparticipants, 685 (58.3%) were men; the mean age was 48.6⫾14.1 years (median, 45 years; range: 30 –95 years). The group of study participants and the group of nonparticipants did not differ significantly in age (P⫽0.06), whereas the proportion of men was significantly (P ⬍ 0.001) higher in the group of nonparticipants. All examinations were carried out at the hospital. Trained social workers filled out a questionnaire for the participants, which included questions regarding socioeconomic background and living conditions, tobacco use and alcohol consumption, and any known diagnosis of major systemic diseases. In all subjects, the pulse, arterial blood pressure, body height, weight, and results of a chest x-ray and an electrocardiogram were recorded. Blood and urine samples were obtained and biochemically analyzed 1.5 hours after a standardized lunch. The study participants underwent a detailed ophthalmologic examination, including testing of visual acuity by ophthalmologists or optometrists. Uncorrected visual acuity and visual acuity with the subjects’ glasses and after refractive correction were measured using modified Early Treatment of Diabetic Retinopathy Study charts (Light House Low Vision Products, New York, NY) at a distance of 4 m. Automated refractometry and subjective refraction were performed on all subjects independently of visual acuity. Keratometry was performed using a nonautomatic keratometer (Appassawamy Ass., Chennai, India). We measured the CRP in the horizontal and vertical meridians. With the use of calibration devices supplied by the company, the calibration of the keratometer was tested at the beginning of the study and in regular intervals during the study period, with no major deviation found at any of the calibration examinations. In addition, the measurements made by the keratometer were compared with measurements made by an automated ocular biometric device (IOL Master; Zeiss Co, Oberkochen, Germany). Visual field examinations were performed with frequency-doubling perimetry using the 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 ⬎21 mmHg, tonometry was repeated. Slit-lamp biomicroscopy was carried out by a fellowshiptrained ophthalmologist, and any abnormality of the anterior segment was noted. By using the slit lamp, photographs of the limbal region were taken to assess the limbal anterior chamber depth at the most peripheral part of the cornea, as described by Van Herick et al.19 With the slit-lamp beam set at an angle of 60 degrees to the sagittal axis, the chamber depth was expressed as a percentage of the corneal thickness at that location. A similar concept as proposed by Foster et al20 was applied to assess the peripheral chamber depth in 6 grades, ranging from 1 for “1% to 5% of limbal chamber depth,” 2 for “6% to 10% of limbal chamber depth, 3 for “11% to 25% of limbal chamber depth,” 4 for “26% to 50% of limbal
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chamber depth,” 5 for “51% to 75% of limbal chamber depth,” and 6 for “75% to 100% of limbal chamber depth.” Gonioscopy was performed for all study participants in dim illumination using the magna view single mirror gonio lens (Ocular Instruments, Bellevue, WA). The slit beam was brought to its narrowest and least height on a Haag Streit-type slit lamp to reduce the effect of light on the anatomy of the anterior chamber angle. According to Foster et al,21 the chamber angle was estimated as open if in primary position the posterior pigmented part of the trabecular meshwork was visible without indentation. The angles were considered to be occludable if in primary position 270 degrees of the posterior trabecular meshwork were not visible without indentation. There was appositional closure of the angle if, independently of the direction of gaze, the posterior trabecular meshwork could be seen only on indentation. There was synechial closure of the anterior chamber angle if even on indentation gonioscopy the posterior trabecular meshwork could not be seen. In subjects with any extent of occludable angles, indentation gonioscopy was performed with the Sussman 4 mirror goniolens (Ocular Instruments). The pupil was dilated using tropicamide 0.8% and phenylephrine 5% three times at 15-minute intervals so that all subjects attained maximal pupillary dilation. A second slit-lamp examination was performed to assess the presence of pseudoexfoliation of the lens. Digital photographs of the lens were taken, and nuclear sclerosis was graded according to the AgeRelated Eye Disease Study.22 Retro-illuminated photographs of the lens for assessment of cortical opacities were obtained using the Zeiss FF450 telecentric fundus camera (Zeiss Meditec Co., Oberkochen, Germany). Digital monoscopic photographs of the optic disc (20 degrees) and the disc and macula (50 degrees) were also taken. Magnification by optic media was corrected for by a built-in algorithm. 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. Only those subjects with horizontal and vertical CRP measurements were included in the study described. Statistical analysis was performed using a commercially available statistical software package (SPSS for Windows, version 17.0, SPSS, Chicago, IL). In the analysis, we first calculated the mean values and statistical distribution of the CRP in the study population. In the second step, we assessed the association between CRP and other ocular and general parameters in a univariate manner. In the third step, we performed a stepwise multivariate analysis with CRP as the dependent parameter and all other variables as independent parameters for which the P value in the univariate analysis was ⱕ0.20. In a first part of that multivariate analysis, we assessed the relationship between CRP and the systemic parameters age, gender, body height, weight and body mass index, and level of education. In a second part of the multivariate analysis, we adjusted CRP for the systemic parameters that remained significantly associated with CRP and assessed the relationship with ocular parameters, such as central corneal thickness and axial length. Only 1 randomly selected eye from each subject was used for statistical analysis. The data were given as mean ⫾ standard deviation, and 95% confidence intervals (CIs) were presented. All P values were 2 sided and considered statistically significant when less than 0.05.
Jonas et al 䡠 Corneal Refractive Power and Its Associations
Figure 1. Histogram showing the horizontal CRP in the Central India Eye and Medical Study.
Results Of the 4711 subjects (9422 eyes), data on CRP were available on 9334 eyes (99.1%) of 4705 subjects (99.9%). Keratometric measurements were not available for reasons such as marked blepharospasm and dense corneal scars. Because cataract surgery can lead to a change in CRP, all eyes that had undergone cataract surgery (n⫽310 eyes, 3.3%) were excluded, so the study eventually consisted of 9024 eyes of 4617 subjects with a mean age of 49.1⫾13.2 years (median, 46 years; range, 30 –100 years) and a mean refractive error of ⫺0.20⫾1.52 diopters (D) (median, 0 D; range, ⫺20.0 to ⫹7.25 D). The mean CRP was 44.60⫾1.68 D (median, 44.5 D; range, 36.5–52.0 D) horizontally and 44.62⫾1.74 D (median, 44.5 D; range, 37.75–52.0 D) vertically with no significant difference between both parameters (P⫽0.27) (Fig 1). The horizontal CRP and vertical CRP were significantly (P ⬍ 0.001) correlated with each other. The CRP was significantly (P ⬍ 0.001) higher in women than in men (horizontal CRP: 44.90⫾1.60 D vs. 44.27⫾1.71 D; vertical CRP: 45.02⫾1.67 D vs. 44.18⫾1.72 D). In univariate analysis, the horizontal CRP increased significantly with age (P ⬍ 0.001). For each year increase in age, the horizontal CRP increased by 0.03 D. By starting at an age of 30 years, the horizontal CRP increased by approximately 1 D over the next 35 years. The vertical CRP was not significantly associated with age (P⫽0.51).
In univariate analysis, the horizontal CRP and vertical CRP decreased significantly with the level of education (P ⬍ 0.001), body height (P ⬍ 0.001), weight (P ⬍ 0.001) and body mass index (P ⬍ 0.001), central corneal thickness (P ⬍ 0.001), anterior chamber depth (P⫽0.002), and axial length (P ⬍ 0.001). The horizontal CRP (P ⬍ 0.001) was significantly associated with refractive error (spherical equivalent) (Tables 1 and 2, available at http://aaojournal. org). In a similar manner, the horizontal CRP (P ⬍ 0.001) was significantly associated with intraocular pressure measurements (Tables 1 and 2, available at http://aaojournal.org). Horizontal and vertical CRP did not vary significantly between right and left eyes (P⫽0.56 and P⫽0.28). In univariate analysis, they were not significantly associated with lens thickness (P⫽0.90 and P⫽0.65). This also held true if age was added to the analysis (horizontal CRP: P⫽0.21; vertical CRP: P⫽0.61). Both CRPs were not associated with the presence of diabetes mellitus (P⫽0.88 and P⫽0.87) or arterial hypertension (P⫽0.88 and P⫽0.87). In the third step of the statistical analysis, we performed a multiple regression analysis, with the horizontal CRP as the dependent parameter and the systemic parameters age, gender, level of education, body height and weight, and body mass index as independent parameters. The analysis revealed that the horizontal CRP was still significantly associated with increasing age (P ⬍ 0.001; ⫽0.02; 95% CI, 0.01– 0.03), lower level of education (P ⬍ 0.001; ⫽⫺0.13; 95% CI, ⫺0.19 to ⫺0.07), and lower body height (P⫽0.02; ⫽⫺0.05; 95% CI, ⫺0.08 to ⫺0.01), whereas the associations with gender (P⫽0.31), body weight (P⫽0.73), and body mass index (P⫽0.96) were no longer statistically significant. In the next step, we adjusted the horizontal CRP for age, level of education, and body height, and added the ocular parameters of central corneal thickness, anterior chamber depth, axial length and refractive error as independent parameters to the multivariate analysis. This revealed that the horizontal CRP was significantly (P ⬍ 0.001) associated with thinner central corneal thickness, deeper anterior chamber, shorter axial length, and myopic refractive error, in addition to increasing age, lower educational level, and lower body height (Table 3). If eyes with a horizontal CRP of ⱖ48 D were excluded (in an attempt to exclude eyes with keratoconus; n⫽212 eyes, 2.3%) or eyes with an axial length ⬎27 mm were excluded (in an attempt to exclude highly myopic eyes; n⫽34 eyes, 0.4%), the results of the multivariate analysis remained unchanged. If intraocular pressure measurements were added to the model, they were significantly associated with CRP (P ⬍ 0.001; regression coefficient 0.03; 95% CI, 0.02– 0.05), in addition to thinner central corneal thickness, deeper anterior chamber, shorter axial length, myopic refractive error, higher age, lower educational level, and lower body height. If the vertical CRP was taken as the dependent parameter in the multivariate analysis, the vertical CRP was significantly associated
Table 3. Association between Horizontal Corneal Refractive Power (Diopters) and Ocular and General Parameters in the Central India Eye and Medical Study (Multivariate Analysis) Parameter
P Value
Regression Coefficient
95% Confidence Interval of Regression Coefficient
Age (yrs) Level of education (0–4) Body height (cm) Central corneal thickness (m) Anterior chamber depth (mm) Axial length (mm) Refractive error (D)
⬍0.001 0.03 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.02 ⫺0.05 ⫺0.02 ⫺0.003 1.01 ⫺1.16 ⫺0.25
0.02–0.03 ⫺0.10 to ⫺0.01 ⫺0.02 to ⫺0.01 ⫺0.005 to ⫺0.002 0.82–1.19 ⫺1.28 to ⫺1.09 ⫺0.28 to ⫺0.22
The level of education was graded into 5 categories: illiterate; school visit up to 5th standard; school visit up to 6th to 8th standard; school attendance up to 9th and 12th standard; graduation or higher.
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Ophthalmology Volume 118, Number 9, September 2011 with decreasing age (P⫽0.048; ⫽⫺0.006; 95% CI, ⫺0.012 to 0.000) and lower level of education (P⫽0.002; ⫽⫺0.10; 95% CI, ⫺0.17 to ⫺0.04), whereas body height (P⫽0.21), body weight (P⫽0.16), body mass index (P⫽0.22), and gender (P⫽0.45) were not significantly associated. Adjusting the vertical CRP for age and level of education and adding the ocular parameters of central corneal thickness, anterior chamber depth, axial length, and refractive error as independent parameters to the multivariate analysis revealed that the vertical CRP was significantly associated with thinner central corneal thickness (P ⬍ 0.001; ⫽⫺0.004; 95% CI, ⫺0.006 to ⫺0.003), deeper anterior chamber (P ⬍ 0.001; ⫽ 0.92; 95% CI, 0.73–1.11), shorter axial length (P ⬍ 0.001; ⫽⫺1.31; 95% CI, ⫺1.38 to ⫺1.24), and myopic refractive error (P ⬍ 0.001; ⫽⫺0.23; 95% CI, ⫺0.26 to ⫺0.19). The association with lower level of education remained significant (P⫽0.009), whereas age was no longer associated (P⫽0.46). If the mean CRP instead of the horizontal CRP was taken as the dependent parameter in the multivariate analysis, the mean CRP was significantly associated with increasing age (P⫽0.03; ⫽0.006; 95% CI, 0.001, 0.01), lower level of education (P ⬍ 0.001; ⫽⫺0.12; 95% CI, ⫺0.17 to ⫺0.06), and lower body height (P ⬍ 0.001; ⫽-0.05; 95% CI, ⫺0.06 to ⫺0.03) and weight (P⫽0.01; ⫽⫺0.009; 95% CI, ⫺0.016 to ⫺0.002), whereas body mass index (P⫽0.52) and gender (P⫽0.91) were not significantly associated. In the next step, we adjusted the mean CRP for age, level of education, and body height and weight, and added the ocular parameters of central corneal thickness, anterior chamber depth, axial length, and refractive error as independent parameters to the multivariate analysis. This showed that the mean CRP was significantly associated with thinner central corneal thickness (P ⬍ 0.001; ⫽⫺0.004; 95% CI, ⫺0.005 to ⫺0.002), deeper anterior chamber (P ⬍ 0.001; ⫽0.99; 95% CI, 0.82–1.17), shorter axial length (P ⬍ 0.001; ⫽⫺1.21; 95% CI, ⫺1.27 to ⫺1.14), and myopic refractive error (P ⬍ 0.001; ⫽⫺0.24; 95% CI, ⫺0.27 to ⫺0.21). The association with lower level of education (P⫽0.09) and body weight (P⫽0.50) was no longer statistically significant.
Discussion In the adult population of rural Central India, the mean horizontal CRP was 44.60⫾1.68 D (or, using the formula of millimeters of corneal curvature ⫽ 0.3315/D of corneal power, 7.43⫾0.20 mm)8,23 and the mean vertical CRP was 44.62⫾1.74 D (or 7.43⫾0.19 mm) with no significant difference between both parameters (P⫽0.27). In multivariate analysis of our cross-sectional study, CRP was significantly (P ⬍ 0.001) associated with the systemic parameters of increasing age (P ⬍ 0.001), lower level of education (P⫽0.02), and lower body height (P ⬍ 0.001), and with the ocular parameters of thinner central corneal thickness (P ⬍ 0.001), deeper anterior chamber (P ⬍ 0.001), shorter axial length (P ⬍ 0.001), and greater myopic refractive error (P ⬍ 0.001). These findings complement previous population-based and hospital-based studies. In the Kumejima Study from Japan,1 the mean corneal curvature (D) was 44.2⫾1.4 D, a value similar to the mean CRP of 44.6 D in our study. In the Singaporean Tanjong Pagar Study,2 the mean corneal curvature was 7.65⫾0.27 mm with no association with age, which was slightly higher than in our study. In another study on Chinese eyes, the corneal curvature was similar to that in
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our study (an average of 7.35⫾0.37 mm).14 In the Singapore Malay Study,15 corneal curvature was 7.65 mm. In the Reykjavik Eye Study,3 the mean radius of the corneal curvature was 7.78⫾0.60 mm for men and 7.62⫾0.58 mm for women, with a statistically significant difference between men and women. Corneal power was significantly (P ⬍ 0.0001) associated with refractive error.8 The Reykjavik Eye Study3 did not find a significant association between the radius of the corneal curvature and the intraocular pressure or a significant association between the corneal curvature radius and age. In the Blue Mountains Eye Study,16 mean CRP was 43.42 D. In the Meiktila Eye Study from Myanmar,10 corneal curvature radius was 7.71⫾0.42 mm in men, 7.56⫾0.54 mm in women, and 7.62⫾0.50 mm in the total study group, with a significant difference between men and women (P ⬍ 0.001). In addition, men had longer axial lengths, deeper anterior chambers, and longer vitreous chambers compared with women. In the Los Angeles Latino Eye Study,24 CRP was 43.72⫾1.62 D in men, 43.35⫾1.64 D in women, and 43.95⫾1.6 D in the total study group, with a significant difference (P ⬍ 0.0001) between men and women. In the same study,24 corneal curvature did not affect intraocular pressure measurements if an adjustment for central corneal thickness was performed. In the Beaver Dam Study,13 mean corneal curvature radius was 7.70 mm, with adjustment for height accounting for all sex differences. By reviewing the studies mentioned, one may infer that most of the studies found a similar CRP as in our study sample, so that marked inter-ethnic differences in the CRP may not exist. This is in contrast with central corneal thickness25–31 and optic nerve head size,32–39 which decrease and increase, respectively, the closer the population originates from countries close to the equator. The association of a steeper cornea with a lower educational level and shorter body stature parallels the association between shorter body length and lower educational level, as demonstrated in previous population-based studies.40 The correlation between steeper cornea and lower body height has been reported in other population-based studies from different countries. If a meta-analysis, in which heterogeneity between studies would be driven by race, confirms that finding, it may then be considered an inter-ethnic characteristic.40 – 47 The association between steeper cornea and lower central corneal thickness and deeper anterior chamber is paralleled by the extreme of this correlation, that is, keratoconus; however, the association between steeper cornea and lower central corneal thickness remained significant if eyes with a CRP of ⱖ48 D were excluded. The association between a higher CRP and deeper anterior chamber may be explained by the correlation between CRP and anterior corneal curvature: The higher the CRP, the more curved or prominent the cornea, secondarily leading to a deeper anterior chamber, under the assumption that the position of the anterior lens surface is independent of the correlation between CRP and anterior chamber depth. The anterior CRP influenced the intraocular pressure readings after adjustment for central corneal thickness. This also holds true if the eyes with an intraocular pressure of ⱖ21 mmHg were excluded. The higher the CRP was (i.e., the steeper the cornea), the higher the intraocular pressure read-
Jonas et al 䡠 Corneal Refractive Power and Its Associations ings were. A similar result was found in previous populationbased studies and other investigations.1,23 This is not in agreement with the Reykjavik Eye Study, in which corneal curvature was not significantly associated with the intraocular pressure readings.3 The finding of our study may be explained by geometry, because an already flat structure compared with a steep structure requires less external pressure to be further flattened up to a standardized applanation area. The observation may have clinical implications. Particularly in eyes after corneal refractive surgery, 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 an underestimation of the true intraocular pressure.
Study Limitations First, a major concern in any prevalence study is nonparticipation. The Central India Eye and Medical Study had a reasonable response rate of 80.1%; however, differences between participants and nonparticipants can lead to a selection artifact. Second, our study included only those who resided in a purely rural region, a region that can be considered to be markedly rural according to responses to the questionnaire regarding socioeconomic background and lifestyle. The study did not include subjects from an urban region, so we can provide no information on any differences between rural and urban regions with respect to the examined parameters. The markedly rural character of our study site may also explain differences between our study and previous studies, most of which were performed in rather urbanized regions, such as the Tanjong Pagar Study. Third, our study as a cross-sectional investigation does not allow firm statements on a longitudinal association between CRP and age. As has been shown in previous population-based studies on urban regions at the Pacific rim,2,15 a myopization in younger generations can lead to a marked confounding effect on the association between refractive elements of the eye and age in a cross-sectional analysis. Fourth, although the described correlations with CRP were statistically highly significant, even if interdependencies between parameters were taken into account in the multivariate analysis, one has to discuss how clinically relevant they were. The relatively high number of patients included in the study might have allowed findings to be statistically significant without clinical relevance. The strengths of our study include the relatively large population size. In addition, the study population lived in rural villages in Central India, where modern civilization has not markedly influenced daily life and a marked myopization has not occurred. Finally, in contrast with some previous population-based studies, persons aged 30 to 40 years were included. In conclusion, in a rural population of Central India, mean CRP was 44.60⫾1.68 D horizontally and 44.62⫾1.74 D vertically. The CRP increased with higher age, lower level of education, shorter body height, thinner central corneal thickness, deeper anterior chamber, shorter axial length, and myopic refractive error. The association with age may be important for refractive surgery. The association
of a steeper cornea with a shorter body stature and a shorter axial length parallels an association between shorter body length and shorter axial length without association with refractive error. The association among steeper cornea, shorter body length, and lower educational level complements the association between shorter body length and lower educational level. The correlation between steeper cornea and deeper anterior chamber may be explained geometrically. The association between steeper cornea and lower corneal thickness suggests that steeper corneas also are thinner in eyes without keratoconus, which may be of interest in refractive surgery.
References 1. Tomoyose E, Higa A, Sakai H, et al. Intraocular pressure and related systemic and ocular biometric factors in a populationbased study in Japan: the Kumejima Study. Am J Ophthalmol 2010;150:279 – 86. 2. Wong TY, Foster PJ, Ng TP, et al. Variations in ocular biometry in an adult Chinese population in Singapore: the Tanjong Pagar Survey. Invest Ophthalmol Vis Sci 2001;42: 73– 80. 3. 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 techniques: Reykjavik Eye Study. Acta Ophthalmol Scand 2002;80:11–5. 4. George R, Paul PG, Baskaran M, et al. Ocular biometry in occludable angles and angle closure glaucoma: a population based survey. Br J Ophthalmol 2003;87:399 – 402. 5. Gudmundsdottir E, Arnarsson A, Jonasson F. Five-year refractive changes in an adult population: Reykjavik Eye Study. Ophthalmology 2005;112:672–7. 6. Ojaimi E, Rose KA, Morgan IG, et al. Distribution of ocular biometric parameters and refraction in a population-based study of Australian children. Invest Ophthalmol Vis Sci 2005; 46:2748 –54. 7. Shufelt C, Fraser-Bell S, Ying-Lai M, et al, Los Angeles Latino Eye Study Group. Refractive error, ocular biometry, and lens opalescence in an adult population: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci 2005;46: 4450 – 60. 8. Olsen T, Arnarsson A, Sasaki H, et al. On the ocular refractive components: the Reykjavik Eye Study. Acta Ophthalmol Scand 2007;85:361– 6. 9. Sawada A, Tomidokoro A, Araie M, et al, Tajimi Study Group. Refractive errors in an elderly Japanese population: the Tajimi study. Ophthalmology 2008;115:363–70. 10. Warrier S, Wu HM, Newland HS, et al. Ocular biometry and determinants of refractive error in rural Myanmar: the Meiktila Eye Study. Br J Ophthalmol 2008;92:1591– 4. 11. Ip JM, Huynh SC, Robaei D, et al. Ethnic differences in refraction and ocular biometry in a population-based sample of 11-15-year-old Australian children. Eye (Lond) 2008;22: 649 –56. 12. Trager MJ, Dirani M, Fan Q, et al. Testability of vision and refraction in preschoolers: the strabismus, amblyopia, and refractive error study in Singaporean children. Am J Ophthalmol 2009;148:235– 41. 13. Lee KE, Klein BE, Klein R, et al. Association of age, stature, and education with ocular dimensions in an older white population. Arch Ophthalmol 2009;127:88 –93.
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Ophthalmology Volume 118, Number 9, September 2011 14. Yuen LH, He M, Aung T, et al. Biometry of the cornea and anterior chamber in Chinese eyes: an anterior segment optical coherence tomography study. Invest Ophthalmol Vis Sci 2010;51:3433– 40. 15. Lim LS, Saw SM, Jeganathan VS, et al. Distribution and determinants of ocular biometric parameters in an Asian population: the Singapore Malay eye study. Invest Ophthalmol Vis Sci 2010;51:103–9. 16. Fotedar R, Wang JJ, Burlutsky G, et al. Distribution of axial length and ocular biometry measured using partial coherence laser interferometry (IOL Master) in an older white population. Ophthalmology 2010;117:417–23. 17. Nangia V, Jonas JB, Sinha A, et al. Ocular axial length and its associations in an adult population of central rural India: the Central India Eye and Medical Study. Ophthalmology 2010; 117:1360 – 6. 18. Jonas JB, Nangia V, Matin A, et al. Prevalence, awareness, control, and associations of arterial hypertension in a rural central India population: the Central India Eye and Medical Study. Am J Hypertens 2010;23:347–50. 19. Van Herick W, Shaffer RN, Schwartz A. Estimation of width of angle of anterior chamber: incidence and significance of the narrow angle. Am J Ophthalmol 1969;68:626 –9. 20. Foster PJ, Devereux JG, Alsbirk PH, et al. Detection of gonioscopically occludable angles and primary angle closure glaucoma by estimation of limbal chamber depth in Asians: modified grading scheme. Br J Ophthalmol 2000;84;186 –92. 21. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol 2002;86:238 – 42. 22. Age-Related Eye Disease Study Research Group. The AgeRelated Eye Disease Study (AREDS) system for classifying cataracts from photographs: AREDS report no. 4. Am J Ophthalmol 2001;131:167–75. 23. ULIB: User Group for Laser Interference Biometry. Haigis W. The keratometer index problem. Available at: http:// www.augenklinik.uni-wuerzburg.de/ulib/czm/texte/kprobl/kprobl. htm. Accessed January 7, 2011. 24. Francis BA, Hsieh A, Lai MY, et al, Los Angeles Latino Eye Study Group. Effects of corneal thickness, corneal curvature, and intraocular pressure level on Goldmann applanation tonometry and dynamic contour tonometry. Ophthalmology 2007;114:20 – 6. 25. Nemesure B, Wu SY, Hennis A, et al, Barbados Eye Study Group. Corneal thickness and intraocular pressure in the Barbados Eye Studies. Arch Ophthalmol 2003;121:240 – 4. 26. Tomidokoro A, Araie M, Iwase A, Tajimi Study Group. Corneal thickness and relating factors in a population-based study in Japan: the Tajimi Study. Am J Ophthalmol 2007;144:152–4. 27. Landers JA, Billing KJ, Mills RA, et al. Central corneal thickness of indigenous Australians within Central Australia. Am J Ophthalmol 2007;143:360 –2. 28. Zhang H, Xu L, Chen C, Jonas JB. Central corneal thickness in adult Chinese: association with ocular and general parameters. The Beijing Eye Study. Graefes Arch Clin Exp Ophthalmol 2008;246:587–92. 29. Su DH, Wong TY, Foster PJ, et al. Central corneal thickness and its associations with ocular and systemic factors: the Singapore Malay Eye Study. Am J Ophthalmol 2009;147:709–16.
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30. Vijaya L, George R, Baskaran M, et al. Prevalence of primary open-angle glaucoma in an urban south Indian population and comparison with a rural population: the Chennai Glaucoma Study. Ophthalmology 2008;115:648 –54. 31. Nangia V, Jonas JB, Sinha A, et al. Central corneal thickness and its association with ocular and general parameters in Indians: the Central India Eye and Medical Study. Ophthalmology 2010;117:705–10. 32. Jonas JB, Gusek GC, Guggenmoos-Holzmann I, Naumann GO. Size of the optic nerve scleral canal and comparison with intravital determination of optic disc dimensions. Graefes Arch Clin Exp Ophthalmol 1988;226:213–5. 33. Chi T, Ritch R, Stickler D, et al. Racial differences in optic nerve head parameters. Arch Ophthalmol 1989;107:836 –9. 34. Healey PR, Mitchell P. Optic disk size in open-angle glaucoma: the Blue Mountains Eye Study. Am J Ophthalmol 1999;128:515–7. 35. Ramrattan RS, Wolfs RC, Jonas JB, et al. Determinants of optic disc characteristics in a general population: the Rotterdam Study. Ophthalmology 1999;106:1588 –96. 36. Tsai CS, Zangwill L, Gonzalez C, et al. Ethnic differences in optic nerve head topography. J Glaucoma 1995;4:248 –57. 37. Wang Y, Xu L, Zhang L, et al. Optic disc size in a population based study in northern China: the Beijing Eye Study. Br J Ophthalmol 2006;90:353– 6. 38. Varma R, Tielsch JM, Quigley HA, et al. Race-, age-, gender-, and refractive error-related differences in the normal optic disc. Arch Ophthalmol 1994;112:1068 –76. 39. Nangia V, Matin A, Bhojwani K, et al. Optic disc size in a population-based study in central India: the Central India Eye and Medical Study (CIEMS). Acta Ophthalmol 2008;86:103–4. 40. Xu L, Wang YX, Jonas JB. Level of education associated with ophthalmic diseases: the Beijing Eye Study. Graefes Arch Clin Exp Ophthalmol 2010;248:49 –57. 41. Wong TY, Foster PJ, Johnson GJ, et al. The relationship between ocular dimensions and refraction with adult stature: the Tanjong Pagar Survey. Invest Ophthalmol Vis Sci 2001;42:1237– 42. 42. Wojciechowski R, Congdon N, Anninger W, Teo Broman A. Age, gender, biometry, refractive error, and the anterior chamber angle among Alaskan Eskimos. Ophthalmology 2003;110:365–75. 43. Wickremasinghe S, Foster PJ, Uranchimeg D, et al. Ocular biometry and refraction in Mongolian adults. Invest Ophthalmol Vis Sci 2004;45:776 – 83. 44. Eysteinsson T, Jonasson F, Arnarsson A, et al. Relationships between ocular dimensions and adult stature among participants in the Reykjavik Eye Study. Acta Ophthalmol Scand 2005;83:734 – 8. 45. Wu HM, Gupta A, Newland HS, et al. Association between stature, ocular biometry and refraction in an adult population in rural Myanmar: the Meiktila eye study. Clin Experiment Ophthalmol 2007;35:834 –9. 46. Xu L, Wang YX, Zhang HT, Jonas JB. Anthropomorphic measurements and general and ocular parameters in adult Chinese: the Beijing Eye Study. Acta Ophthalmol 2011;89: 442–7. 47. Xu L, Cao WF, Wang YX, et al. Anterior chamber depth and chamber angle and their associations with ocular and general parameters: the Beijing Eye Study. Am J Ophthalmol 2008; 145:929 –36.
Jonas et al 䡠 Corneal Refractive Power and Its Associations
Footnotes and Financial Disclosures Originally received: October 22, 2010. Final revision: December 31, 2010. Accepted: February 2, 2011. Available online: June 12, 2011. 1
Manuscript no. 2010-1468.
Suraj Eye Institute, Nagpur, India.
2
Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Germany. *J.B.J. and V.N. contributed equally to this work. 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 Om Drishti Trust, Nagpur, India; Heidelberg Engineering Co., Heidelberg, Germany; Rotary Sight Saver Netherlands; ORBIS International; and Carl Zeiss Meditec Co., Jena, Germany. This article contains online-only material. The following should appear online-only: Tables 1 and 2. Correspondence: Vinay Nangia, MD, Suraj Eye Institute, Plot No 559 New Colony, Necosabag Fly Over, Nagpur, 440001, India. E-mail: nagpursuraj@ gmail.com.
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The refractive power of the cornea is a basic parameter in ophthalmology. Its physiologic importance is derived from its close association with the optical system of the eye; its clinical importance is related to the dependence of intraocular pressure readings on the anterior corneal curvature radius1 and to the association between the corneal refractive power (CRP) and corneal shape abnormalities, such as keratoglobus and keratoconus, to mention only a few. In acknowledgment of the importance of CRP, recent population-based studies partially explored the normal distribution of the CRP and some of its associations with ocular and general parameters in populations from Iceland, Japan, Singapore, Australia, California, Myanmar, and North America.2–17 Except for a relatively small group of subjects from South India, there is no major information available on the distribution of CRP and its associations in India, the world’s © 2011 by the American Academy of Ophthalmology Published by Elsevier Inc.
second largest nation. We therefore conducted this study to examine the normative data of CRP and its associations with other ophthalmic parameters (e.g., axial length) and systemic parameters (e.g., age, general anthropomorphic measurements, and socioeconomic data) in a populationbased investigation in Central India. The findings may provide information on the normal anatomy of the eye, be helpful for issues of corneal refractive surgery, and provide hints for diseases such as primary angle closure glaucoma, the prevalence of which is associated with the dimensions of the anterior ocular segment.
Materials and Methods The Central India Eye and Medical Study is a population-based cross-sectional study in Central India. As described recently in ISSN 0161-6420/11/$–see front matter doi:10.1016/j.ophtha.2011.02.001
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Ophthalmology Volume 118, Number 9, September 2011 detail,17,18 the study was performed in 8 villages in Kalmeshwar Tehsil, a rural region of Eastern Maharashtra ⬃40 km from Nagpur. The Medical Ethics Committee of the Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg and a similar committee of the Suraj Eye Institute/Nagpur approved the study; all participants gave informed consent, according to the Declaration of Helsinki. The villages were chosen as locations for the study because they were located in a typical rural region of Central India and a relatively long distance from the nearest city (Nagpur). Of a total population of 13 606 villagers, 5885 met the inclusion criterion of an age of 30⫹ years. There was no exclusion criterion. Of the 5885 eligible subjects, 4711 (2191 men [46.5%]) participated, resulting in a response rate of 80.1%. The mean age was 49.5⫾13.4 years (median: 47 years; range: 30 –100 years), and the mean reported monthly income was 1584⫾1233 rupees (1 US dollar ⫽ ⬃50 rupees); the rate of illiteracy was 35%. Among the 1174 nonparticipants, 685 (58.3%) were men; the mean age was 48.6⫾14.1 years (median, 45 years; range: 30 –95 years). The group of study participants and the group of nonparticipants did not differ significantly in age (P⫽0.06), whereas the proportion of men was significantly (P ⬍ 0.001) higher in the group of nonparticipants. All examinations were carried out at the hospital. Trained social workers filled out a questionnaire for the participants, which included questions regarding socioeconomic background and living conditions, tobacco use and alcohol consumption, and any known diagnosis of major systemic diseases. In all subjects, the pulse, arterial blood pressure, body height, weight, and results of a chest x-ray and an electrocardiogram were recorded. Blood and urine samples were obtained and biochemically analyzed 1.5 hours after a standardized lunch. The study participants underwent a detailed ophthalmologic examination, including testing of visual acuity by ophthalmologists or optometrists. Uncorrected visual acuity and visual acuity with the subjects’ glasses and after refractive correction were measured using modified Early Treatment of Diabetic Retinopathy Study charts (Light House Low Vision Products, New York, NY) at a distance of 4 m. Automated refractometry and subjective refraction were performed on all subjects independently of visual acuity. Keratometry was performed using a nonautomatic keratometer (Appassawamy Ass., Chennai, India). We measured the CRP in the horizontal and vertical meridians. With the use of calibration devices supplied by the company, the calibration of the keratometer was tested at the beginning of the study and in regular intervals during the study period, with no major deviation found at any of the calibration examinations. In addition, the measurements made by the keratometer were compared with measurements made by an automated ocular biometric device (IOL Master; Zeiss Co, Oberkochen, Germany). Visual field examinations were performed with frequency-doubling perimetry using the 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 ⬎21 mmHg, tonometry was repeated. Slit-lamp biomicroscopy was carried out by a fellowshiptrained ophthalmologist, and any abnormality of the anterior segment was noted. By using the slit lamp, photographs of the limbal region were taken to assess the limbal anterior chamber depth at the most peripheral part of the cornea, as described by Van Herick et al.19 With the slit-lamp beam set at an angle of 60 degrees to the sagittal axis, the chamber depth was expressed as a percentage of the corneal thickness at that location. A similar concept as proposed by Foster et al20 was applied to assess the peripheral chamber depth in 6 grades, ranging from 1 for “1% to 5% of limbal chamber depth,” 2 for “6% to 10% of limbal chamber depth, 3 for “11% to 25% of limbal chamber depth,” 4 for “26% to 50% of limbal
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chamber depth,” 5 for “51% to 75% of limbal chamber depth,” and 6 for “75% to 100% of limbal chamber depth.” Gonioscopy was performed for all study participants in dim illumination using the magna view single mirror gonio lens (Ocular Instruments, Bellevue, WA). The slit beam was brought to its narrowest and least height on a Haag Streit-type slit lamp to reduce the effect of light on the anatomy of the anterior chamber angle. According to Foster et al,21 the chamber angle was estimated as open if in primary position the posterior pigmented part of the trabecular meshwork was visible without indentation. The angles were considered to be occludable if in primary position 270 degrees of the posterior trabecular meshwork were not visible without indentation. There was appositional closure of the angle if, independently of the direction of gaze, the posterior trabecular meshwork could be seen only on indentation. There was synechial closure of the anterior chamber angle if even on indentation gonioscopy the posterior trabecular meshwork could not be seen. In subjects with any extent of occludable angles, indentation gonioscopy was performed with the Sussman 4 mirror goniolens (Ocular Instruments). The pupil was dilated using tropicamide 0.8% and phenylephrine 5% three times at 15-minute intervals so that all subjects attained maximal pupillary dilation. A second slit-lamp examination was performed to assess the presence of pseudoexfoliation of the lens. Digital photographs of the lens were taken, and nuclear sclerosis was graded according to the AgeRelated Eye Disease Study.22 Retro-illuminated photographs of the lens for assessment of cortical opacities were obtained using the Zeiss FF450 telecentric fundus camera (Zeiss Meditec Co., Oberkochen, Germany). Digital monoscopic photographs of the optic disc (20 degrees) and the disc and macula (50 degrees) were also taken. Magnification by optic media was corrected for by a built-in algorithm. 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. Only those subjects with horizontal and vertical CRP measurements were included in the study described. Statistical analysis was performed using a commercially available statistical software package (SPSS for Windows, version 17.0, SPSS, Chicago, IL). In the analysis, we first calculated the mean values and statistical distribution of the CRP in the study population. In the second step, we assessed the association between CRP and other ocular and general parameters in a univariate manner. In the third step, we performed a stepwise multivariate analysis with CRP as the dependent parameter and all other variables as independent parameters for which the P value in the univariate analysis was ⱕ0.20. In a first part of that multivariate analysis, we assessed the relationship between CRP and the systemic parameters age, gender, body height, weight and body mass index, and level of education. In a second part of the multivariate analysis, we adjusted CRP for the systemic parameters that remained significantly associated with CRP and assessed the relationship with ocular parameters, such as central corneal thickness and axial length. Only 1 randomly selected eye from each subject was used for statistical analysis. The data were given as mean ⫾ standard deviation, and 95% confidence intervals (CIs) were presented. All P values were 2 sided and considered statistically significant when less than 0.05.
Jonas et al 䡠 Corneal Refractive Power and Its Associations
Figure 1. Histogram showing the horizontal CRP in the Central India Eye and Medical Study.
Results Of the 4711 subjects (9422 eyes), data on CRP were available on 9334 eyes (99.1%) of 4705 subjects (99.9%). Keratometric measurements were not available for reasons such as marked blepharospasm and dense corneal scars. Because cataract surgery can lead to a change in CRP, all eyes that had undergone cataract surgery (n⫽310 eyes, 3.3%) were excluded, so the study eventually consisted of 9024 eyes of 4617 subjects with a mean age of 49.1⫾13.2 years (median, 46 years; range, 30 –100 years) and a mean refractive error of ⫺0.20⫾1.52 diopters (D) (median, 0 D; range, ⫺20.0 to ⫹7.25 D). The mean CRP was 44.60⫾1.68 D (median, 44.5 D; range, 36.5–52.0 D) horizontally and 44.62⫾1.74 D (median, 44.5 D; range, 37.75–52.0 D) vertically with no significant difference between both parameters (P⫽0.27) (Fig 1). The horizontal CRP and vertical CRP were significantly (P ⬍ 0.001) correlated with each other. The CRP was significantly (P ⬍ 0.001) higher in women than in men (horizontal CRP: 44.90⫾1.60 D vs. 44.27⫾1.71 D; vertical CRP: 45.02⫾1.67 D vs. 44.18⫾1.72 D). In univariate analysis, the horizontal CRP increased significantly with age (P ⬍ 0.001). For each year increase in age, the horizontal CRP increased by 0.03 D. By starting at an age of 30 years, the horizontal CRP increased by approximately 1 D over the next 35 years. The vertical CRP was not significantly associated with age (P⫽0.51).
In univariate analysis, the horizontal CRP and vertical CRP decreased significantly with the level of education (P ⬍ 0.001), body height (P ⬍ 0.001), weight (P ⬍ 0.001) and body mass index (P ⬍ 0.001), central corneal thickness (P ⬍ 0.001), anterior chamber depth (P⫽0.002), and axial length (P ⬍ 0.001). The horizontal CRP (P ⬍ 0.001) was significantly associated with refractive error (spherical equivalent) (Tables 1 and 2, available at http://aaojournal. org). In a similar manner, the horizontal CRP (P ⬍ 0.001) was significantly associated with intraocular pressure measurements (Tables 1 and 2, available at http://aaojournal.org). Horizontal and vertical CRP did not vary significantly between right and left eyes (P⫽0.56 and P⫽0.28). In univariate analysis, they were not significantly associated with lens thickness (P⫽0.90 and P⫽0.65). This also held true if age was added to the analysis (horizontal CRP: P⫽0.21; vertical CRP: P⫽0.61). Both CRPs were not associated with the presence of diabetes mellitus (P⫽0.88 and P⫽0.87) or arterial hypertension (P⫽0.88 and P⫽0.87). In the third step of the statistical analysis, we performed a multiple regression analysis, with the horizontal CRP as the dependent parameter and the systemic parameters age, gender, level of education, body height and weight, and body mass index as independent parameters. The analysis revealed that the horizontal CRP was still significantly associated with increasing age (P ⬍ 0.001; ⫽0.02; 95% CI, 0.01– 0.03), lower level of education (P ⬍ 0.001; ⫽⫺0.13; 95% CI, ⫺0.19 to ⫺0.07), and lower body height (P⫽0.02; ⫽⫺0.05; 95% CI, ⫺0.08 to ⫺0.01), whereas the associations with gender (P⫽0.31), body weight (P⫽0.73), and body mass index (P⫽0.96) were no longer statistically significant. In the next step, we adjusted the horizontal CRP for age, level of education, and body height, and added the ocular parameters of central corneal thickness, anterior chamber depth, axial length and refractive error as independent parameters to the multivariate analysis. This revealed that the horizontal CRP was significantly (P ⬍ 0.001) associated with thinner central corneal thickness, deeper anterior chamber, shorter axial length, and myopic refractive error, in addition to increasing age, lower educational level, and lower body height (Table 3). If eyes with a horizontal CRP of ⱖ48 D were excluded (in an attempt to exclude eyes with keratoconus; n⫽212 eyes, 2.3%) or eyes with an axial length ⬎27 mm were excluded (in an attempt to exclude highly myopic eyes; n⫽34 eyes, 0.4%), the results of the multivariate analysis remained unchanged. If intraocular pressure measurements were added to the model, they were significantly associated with CRP (P ⬍ 0.001; regression coefficient 0.03; 95% CI, 0.02– 0.05), in addition to thinner central corneal thickness, deeper anterior chamber, shorter axial length, myopic refractive error, higher age, lower educational level, and lower body height. If the vertical CRP was taken as the dependent parameter in the multivariate analysis, the vertical CRP was significantly associated
Table 3. Association between Horizontal Corneal Refractive Power (Diopters) and Ocular and General Parameters in the Central India Eye and Medical Study (Multivariate Analysis) Parameter
P Value
Regression Coefficient
95% Confidence Interval of Regression Coefficient
Age (yrs) Level of education (0–4) Body height (cm) Central corneal thickness (m) Anterior chamber depth (mm) Axial length (mm) Refractive error (D)
⬍0.001 0.03 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001
0.02 ⫺0.05 ⫺0.02 ⫺0.003 1.01 ⫺1.16 ⫺0.25
0.02–0.03 ⫺0.10 to ⫺0.01 ⫺0.02 to ⫺0.01 ⫺0.005 to ⫺0.002 0.82–1.19 ⫺1.28 to ⫺1.09 ⫺0.28 to ⫺0.22
The level of education was graded into 5 categories: illiterate; school visit up to 5th standard; school visit up to 6th to 8th standard; school attendance up to 9th and 12th standard; graduation or higher.
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Ophthalmology Volume 118, Number 9, September 2011 with decreasing age (P⫽0.048; ⫽⫺0.006; 95% CI, ⫺0.012 to 0.000) and lower level of education (P⫽0.002; ⫽⫺0.10; 95% CI, ⫺0.17 to ⫺0.04), whereas body height (P⫽0.21), body weight (P⫽0.16), body mass index (P⫽0.22), and gender (P⫽0.45) were not significantly associated. Adjusting the vertical CRP for age and level of education and adding the ocular parameters of central corneal thickness, anterior chamber depth, axial length, and refractive error as independent parameters to the multivariate analysis revealed that the vertical CRP was significantly associated with thinner central corneal thickness (P ⬍ 0.001; ⫽⫺0.004; 95% CI, ⫺0.006 to ⫺0.003), deeper anterior chamber (P ⬍ 0.001; ⫽ 0.92; 95% CI, 0.73–1.11), shorter axial length (P ⬍ 0.001; ⫽⫺1.31; 95% CI, ⫺1.38 to ⫺1.24), and myopic refractive error (P ⬍ 0.001; ⫽⫺0.23; 95% CI, ⫺0.26 to ⫺0.19). The association with lower level of education remained significant (P⫽0.009), whereas age was no longer associated (P⫽0.46). If the mean CRP instead of the horizontal CRP was taken as the dependent parameter in the multivariate analysis, the mean CRP was significantly associated with increasing age (P⫽0.03; ⫽0.006; 95% CI, 0.001, 0.01), lower level of education (P ⬍ 0.001; ⫽⫺0.12; 95% CI, ⫺0.17 to ⫺0.06), and lower body height (P ⬍ 0.001; ⫽-0.05; 95% CI, ⫺0.06 to ⫺0.03) and weight (P⫽0.01; ⫽⫺0.009; 95% CI, ⫺0.016 to ⫺0.002), whereas body mass index (P⫽0.52) and gender (P⫽0.91) were not significantly associated. In the next step, we adjusted the mean CRP for age, level of education, and body height and weight, and added the ocular parameters of central corneal thickness, anterior chamber depth, axial length, and refractive error as independent parameters to the multivariate analysis. This showed that the mean CRP was significantly associated with thinner central corneal thickness (P ⬍ 0.001; ⫽⫺0.004; 95% CI, ⫺0.005 to ⫺0.002), deeper anterior chamber (P ⬍ 0.001; ⫽0.99; 95% CI, 0.82–1.17), shorter axial length (P ⬍ 0.001; ⫽⫺1.21; 95% CI, ⫺1.27 to ⫺1.14), and myopic refractive error (P ⬍ 0.001; ⫽⫺0.24; 95% CI, ⫺0.27 to ⫺0.21). The association with lower level of education (P⫽0.09) and body weight (P⫽0.50) was no longer statistically significant.
Discussion In the adult population of rural Central India, the mean horizontal CRP was 44.60⫾1.68 D (or, using the formula of millimeters of corneal curvature ⫽ 0.3315/D of corneal power, 7.43⫾0.20 mm)8,23 and the mean vertical CRP was 44.62⫾1.74 D (or 7.43⫾0.19 mm) with no significant difference between both parameters (P⫽0.27). In multivariate analysis of our cross-sectional study, CRP was significantly (P ⬍ 0.001) associated with the systemic parameters of increasing age (P ⬍ 0.001), lower level of education (P⫽0.02), and lower body height (P ⬍ 0.001), and with the ocular parameters of thinner central corneal thickness (P ⬍ 0.001), deeper anterior chamber (P ⬍ 0.001), shorter axial length (P ⬍ 0.001), and greater myopic refractive error (P ⬍ 0.001). These findings complement previous population-based and hospital-based studies. In the Kumejima Study from Japan,1 the mean corneal curvature (D) was 44.2⫾1.4 D, a value similar to the mean CRP of 44.6 D in our study. In the Singaporean Tanjong Pagar Study,2 the mean corneal curvature was 7.65⫾0.27 mm with no association with age, which was slightly higher than in our study. In another study on Chinese eyes, the corneal curvature was similar to that in
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our study (an average of 7.35⫾0.37 mm).14 In the Singapore Malay Study,15 corneal curvature was 7.65 mm. In the Reykjavik Eye Study,3 the mean radius of the corneal curvature was 7.78⫾0.60 mm for men and 7.62⫾0.58 mm for women, with a statistically significant difference between men and women. Corneal power was significantly (P ⬍ 0.0001) associated with refractive error.8 The Reykjavik Eye Study3 did not find a significant association between the radius of the corneal curvature and the intraocular pressure or a significant association between the corneal curvature radius and age. In the Blue Mountains Eye Study,16 mean CRP was 43.42 D. In the Meiktila Eye Study from Myanmar,10 corneal curvature radius was 7.71⫾0.42 mm in men, 7.56⫾0.54 mm in women, and 7.62⫾0.50 mm in the total study group, with a significant difference between men and women (P ⬍ 0.001). In addition, men had longer axial lengths, deeper anterior chambers, and longer vitreous chambers compared with women. In the Los Angeles Latino Eye Study,24 CRP was 43.72⫾1.62 D in men, 43.35⫾1.64 D in women, and 43.95⫾1.6 D in the total study group, with a significant difference (P ⬍ 0.0001) between men and women. In the same study,24 corneal curvature did not affect intraocular pressure measurements if an adjustment for central corneal thickness was performed. In the Beaver Dam Study,13 mean corneal curvature radius was 7.70 mm, with adjustment for height accounting for all sex differences. By reviewing the studies mentioned, one may infer that most of the studies found a similar CRP as in our study sample, so that marked inter-ethnic differences in the CRP may not exist. This is in contrast with central corneal thickness25–31 and optic nerve head size,32–39 which decrease and increase, respectively, the closer the population originates from countries close to the equator. The association of a steeper cornea with a lower educational level and shorter body stature parallels the association between shorter body length and lower educational level, as demonstrated in previous population-based studies.40 The correlation between steeper cornea and lower body height has been reported in other population-based studies from different countries. If a meta-analysis, in which heterogeneity between studies would be driven by race, confirms that finding, it may then be considered an inter-ethnic characteristic.40 – 47 The association between steeper cornea and lower central corneal thickness and deeper anterior chamber is paralleled by the extreme of this correlation, that is, keratoconus; however, the association between steeper cornea and lower central corneal thickness remained significant if eyes with a CRP of ⱖ48 D were excluded. The association between a higher CRP and deeper anterior chamber may be explained by the correlation between CRP and anterior corneal curvature: The higher the CRP, the more curved or prominent the cornea, secondarily leading to a deeper anterior chamber, under the assumption that the position of the anterior lens surface is independent of the correlation between CRP and anterior chamber depth. The anterior CRP influenced the intraocular pressure readings after adjustment for central corneal thickness. This also holds true if the eyes with an intraocular pressure of ⱖ21 mmHg were excluded. The higher the CRP was (i.e., the steeper the cornea), the higher the intraocular pressure read-
Jonas et al 䡠 Corneal Refractive Power and Its Associations ings were. A similar result was found in previous populationbased studies and other investigations.1,23 This is not in agreement with the Reykjavik Eye Study, in which corneal curvature was not significantly associated with the intraocular pressure readings.3 The finding of our study may be explained by geometry, because an already flat structure compared with a steep structure requires less external pressure to be further flattened up to a standardized applanation area. The observation may have clinical implications. Particularly in eyes after corneal refractive surgery, 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 an underestimation of the true intraocular pressure.
Study Limitations First, a major concern in any prevalence study is nonparticipation. The Central India Eye and Medical Study had a reasonable response rate of 80.1%; however, differences between participants and nonparticipants can lead to a selection artifact. Second, our study included only those who resided in a purely rural region, a region that can be considered to be markedly rural according to responses to the questionnaire regarding socioeconomic background and lifestyle. The study did not include subjects from an urban region, so we can provide no information on any differences between rural and urban regions with respect to the examined parameters. The markedly rural character of our study site may also explain differences between our study and previous studies, most of which were performed in rather urbanized regions, such as the Tanjong Pagar Study. Third, our study as a cross-sectional investigation does not allow firm statements on a longitudinal association between CRP and age. As has been shown in previous population-based studies on urban regions at the Pacific rim,2,15 a myopization in younger generations can lead to a marked confounding effect on the association between refractive elements of the eye and age in a cross-sectional analysis. Fourth, although the described correlations with CRP were statistically highly significant, even if interdependencies between parameters were taken into account in the multivariate analysis, one has to discuss how clinically relevant they were. The relatively high number of patients included in the study might have allowed findings to be statistically significant without clinical relevance. The strengths of our study include the relatively large population size. In addition, the study population lived in rural villages in Central India, where modern civilization has not markedly influenced daily life and a marked myopization has not occurred. Finally, in contrast with some previous population-based studies, persons aged 30 to 40 years were included. In conclusion, in a rural population of Central India, mean CRP was 44.60⫾1.68 D horizontally and 44.62⫾1.74 D vertically. The CRP increased with higher age, lower level of education, shorter body height, thinner central corneal thickness, deeper anterior chamber, shorter axial length, and myopic refractive error. The association with age may be important for refractive surgery. The association
of a steeper cornea with a shorter body stature and a shorter axial length parallels an association between shorter body length and shorter axial length without association with refractive error. The association among steeper cornea, shorter body length, and lower educational level complements the association between shorter body length and lower educational level. The correlation between steeper cornea and deeper anterior chamber may be explained geometrically. The association between steeper cornea and lower corneal thickness suggests that steeper corneas also are thinner in eyes without keratoconus, which may be of interest in refractive surgery.
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Jonas et al 䡠 Corneal Refractive Power and Its Associations
Footnotes and Financial Disclosures Originally received: October 22, 2010. Final revision: December 31, 2010. Accepted: February 2, 2011. Available online: June 12, 2011. 1
Manuscript no. 2010-1468.
Suraj Eye Institute, Nagpur, India.
2
Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Germany. *J.B.J. and V.N. contributed equally to this work. 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 Om Drishti Trust, Nagpur, India; Heidelberg Engineering Co., Heidelberg, Germany; Rotary Sight Saver Netherlands; ORBIS International; and Carl Zeiss Meditec Co., Jena, Germany. This article contains online-only material. The following should appear online-only: Tables 1 and 2. Correspondence: Vinay Nangia, MD, Suraj Eye Institute, Plot No 559 New Colony, Necosabag Fly Over, Nagpur, 440001, India. E-mail: nagpursuraj@ gmail.com.
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