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Distribution of Axial Length and Ocular Biometry Measured Using Partial Coherence Laser Interferometry (IOL Master) in an Older White Population
Distribution of Axial Length and Ocular Biometry Measured Using Partial Coherence Laser Interferometry (IOL Master) in an Older White Population Reena Fotedar, MD,1 Jie Jin Wang, MMed, PhD,1,2 George Burlutsky, MAppStat,1 Ian G. Morgan, PhD,3 Kathryn Rose, PhD,4 Tien Y. Wong, MD, PhD,2 Paul Mitchell, MD, PhD1 Purpose: We aimed to describe norms for the distribution of axial length (AL) and other ocular biometric parameters in an older Caucasian population, measured using partial coherence laser interferometry (Zeiss IOL Master; Carl Zeiss AG, Oberkochen, Germany), a technique now routinely used in measuring AL before cataract surgery. We also aimed to assess age and gender relationships with these parameters and their correlations with spherical equivalent refraction (SER). Design: Cross-sectional analysis of the Blue Mountains Eye Study (BMES) cohort at the examinations (10-year follow-up examination). Participants: From 2002 to 2004, 1952 persons (76% of surviving baseline BMES participants) aged 59 years or older had ocular biometry measured at the 10-year examinations. Methods: Spherical equivalent refraction was calculated as the sum of sphere ⫹0.5 cylinder power, after protocol refraction. Measurements of AL, corneal curvature (K1), anterior chamber depth (ACD), and corneal diameter (WTW) were performed using the IOL Master. Only right phakic eyes (n ⫽ 1335) with biometry data were included. Main Outcome Measures: Axial length distribution. Results: Mean AL was 23.44 mm (95% confidence interval [CI], 23.38 –23.50) and was greater in men, 23.76 mm (CI, 23.68 –23.84), than in women, 23.19 mm (CI, 23.11–23.27). The mean K1, ACD, and WTW were 43.42 diopters (D), 3.10 mm, and 12.06 mm, respectively. The AL and ACD distributions were both positively skewed and peaked, whereas the WTW and K1 distributions were near normal. From age 59 years or older, a mean reduction in AL with age was observed (P for trend ⫽ 0.005), 0.12 mm per decade (P ⫽ 0.0176) in women but only 0.02 mm per decade (P ⫽ 0.6319) in men. Mean SER was 0.58 D, and the distribution was peaked with a negative skew. The SER was negatively correlated with both AL (beta coefficient – 0.688) and ACD (beta coefficient ⫺0.222), but not with K1 or WTW. Conclusions: These data provide normative values in the older general population for AL measured using the IOL Master. Axial length distribution was peaked and skewed, suggesting an active modulation process. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010;117:417– 423 © 2010 by the American Academy of Ophthalmology.
Cataract surgery is the most commonly performed surgical procedure in the United States and other developed countries. With advances in surgical techniques, intraocular lens (IOL) design, and instruments, there is now an increased expectation from surgeons and patients for precise postoperative refractive results. To meet these expectations, attention to accurate biometry measurements, particularly axial length (AL), is critical.1 However, the distribution and determinants of AL have been assessed in only a few population-based studies of older persons,2– 4 of which only one study has examined a predominantly European Caucasian (“white”) sample. Notably, no population studies to date have reported AL distribution measured using non-contact partial coherence laser interferometry (Zeiss IOL Master, Carl Zeiss AG, Oberkochen, Germany), now used routinely © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
by ophthalmologists worldwide to estimate IOL power before cataract surgery.5– 8 IOL Master measurements are considered more accurate and reproducible than applanation ultrasound, using contact techniques.9,10 Furthermore, the IOL Master also predicts postoperative refraction better than ultrasound biometry, particularly for close ranges.1 Increased accuracy of AL measurement using appropriate IOL power calculations (Holladay and SRK-T formulae for AL 22.0 –24.0 mm, and Hoffer for shorter AL) should lead to improved cataract surgical outcomes. The distribution of AL and other ocular biometric parameters, for example, the corneal radius of curvature or corneal power (K1) and anterior chamber depth (ACD), follow a common Gaussian curve, whereas spherical equivalent refraction (SER) in the general population has a nonISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.07.028
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Gaussian leptokurtic distribution. This type of distribution has a positive excess kurtosis, or peak.11,12 This tight distribution of SER largely results from the matching of AL to corneal power during emmetropization.13,14 Detailed biometric evaluation of the eye in an unbiased population sample is needed to elucidate these relationships and underlying reasons for changes in AL, other ocular biometric parameters, and refractive error with age. This study describes the distribution of AL and other ocular biometric parameters as measured using the IOL Master in the Blue Mountains Eye Study (BMES) population-based cohort. These data will help to provide comprehensive age and gender norms for this instrument in older European Caucasian persons.
Materials and Methods Study Population The BMES is a population-based cohort study of vision and common eye diseases in a suburban Australian population aged 49 years or older at baseline. The study was approved by the University of Sydney Human Research Ethics Committee and was conducted adhering to the tenets of the Helsinki Declaration. Signed informed consent was obtained from all participants at each examination. Survey methods and procedures have been described.15,16 Briefly, at baseline (1992–1994) 3654 of 4433 eligible residents (82.4%) aged 49 years or older living in the Blue Mountains area, west of Sydney, were examined. At the 5-year followup, 2335 of the 3111 surviving participants (75.1%) were reexamined during 1997 to 1999. After 10 years, 1952 baseline participants (53.4% of the original cohort, 76.6% of survivors) were reexamined during 2002 to 2004.
Procedures Comprehensive eye examinations at each visit included measurement of the logarithm of the minimum angle of resolution visual acuity for each eye, followed by subjective refraction for those with visual acuity ⬍54 letters.16 The AL was measured only at the 10-year examination using an IOL Master, which uses signals from the tear film and retinal pigment epithelium to measure AL. The system automatically adjusts for differences in distance between the inner limiting membrane and the retinal pigment epithelium, so that the displayed AL is directly comparable to that obtained using immersion ultrasound. Five valid readings of AL and ACD and 3 readings of K1 and corneal diameter (white to white [WTW]) were taken. The ACD was defined as the distance from the anterior corneal surface to the anterior lens surface, whereas corneal power was measured in 2 meridians, the greatest and least radii of curvature (K1, K2). Because K1 and K2 had similar correlation coefficients, only K1 readings are included and are reported as corneal power in diopters (D). The refractive index value used for this conversion by the IOL Master is n⫽1.3375. Myopia was defined as SER ⬍ ⫺0.5 D, hyperopia was defined as SER ⬎ ⫹0.5 D, and emmetropia was defined as SER between – 0.5 D and ⫹0.5 D.
SER was calculated by summating the spherical plus half the cylindrical refraction, and expressed in diopters. Measures of spread, including kurtosis and skew, were derived. Distributions for SER and ocular biometric parameters were tested for normality with the Kolmogorov-Smirnov test and were considered significantly different from normal for P⬍0.01. Correlations between SER and AL and other biometric variables were calculated using the Pearson correlation coefficient, and 95% confidence intervals (CIs) are presented. Group trend tests were used to assess any significant trends across age groups for each variable.
Results Of the 1952 baseline BMES participants reexamined at 10 years, AL could be measured with the IOL Master in 1561 participants, of whom 28 had incomplete data and 212 were pseudophakic and thus were excluded from this analysis. This left 1321 phakic subjects, 749 women (56.7%) and 572 men (43.3%), who had valid ocular biometry measurements.
Distribution of Ocular Biometry Figure 1 shows the distribution of AL in the BMES population. The mean AL was 23.44 mm (95%CI, 23.38 –23.50). The AL distribution in the whole population was skewed toward the right (positively) and was peaked, with a kurtosis of 5.44 and significant Kolmogorov-Smirnov test for deviation from normality (P⬍0.01). The mean AL in women was 23.19 mm (95%CI, 23.11–23.27), and the mean AL in men was 23.76 mm (95%CI, 23.68 –23.84), showing a statistically significant gender-related difference (P⬍ 0.0001). Table 1 shows mean AL, other biometric parameters, and SER with 95%CI, stratified by age group. Table 2 shows this distribution also stratified by gender. Mean AL decreased across age categories (P for trend ⫽ 0.005). Each decade of age was associated with a decrease of 0.09 mm in mean AL in men and women combined (P ⫽ 0.0159), whereas the corresponding decrease was 0.12 mm per decade (P ⫽ 0.0176) in women, but only 0.02 mm per decade (P ⫽ 0.6319) in men. The test for trend across age groups was significant for women (P for trend ⫽ 0.009) but not for men (P for trend ⫽ 0.527). Figures 2 and 3 show the distributions of K1 and ACD. The mean K1 was 43.38 D, and the mean ACD was 3.24 mm. The distribution of K1 was essentially normal, whereas the distribution of ACD was positively skewed and peaked, and close to normal.
Statistical Analysis Statistical analyses were performed using SAS software (SAS Inc., Cary, NC). Because there is a high correlation between the 2 eyes for refractive and biometric parameters, and the findings were similar for the 2 eyes, data from right eyes only are presented. The
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Figure 1. Distribution of axial length in the BMES population. BMES ⫽ Blue Mountains Eye Study; KS ⫽ Kolmogorov-Smirnov.
Fotedar et al 䡠 Distribution of Axial Length in the BMES Population Table 1. Age Distribution of Axial Length, Ocular Biometry, and Spherical Equivalent Refraction in the Blue Mountains Eye Study Population, Presented with 95% Confidence Intervals Whole Population (n ⴝ 1321)
Variable Age (yrs) N AL (mm) ACD (mm) K1 (D) WTW (mm) SER (D)
59–64 226 23.60 (23.45–23.76) 3.20 (3.15–3.24) 43.42 (43.23–43.62) 12.10 (12.04–12.16) 0.09 (–0.22–0.40)
65–74 603 23.44 (23.35–23.52) 3.13 (3.10–3.16) 43.44 (43.32. 43.55) 12.09 (12.06–12.13) 0.75 (0.57–0.92)
75–84 422 23.39 (23.30–23.48) 3.05 (3.02–3.09) 43.33 (43.19–43.48) 12.02 (11.98–12.06) 1.09 (0.90–1.28)
P Values 85⫹ 70 23.23 (22.96–23.49) 2.89 (2.82–2.97) 43.85 (43.49–44.21) 11.93 (11.83–12.03) 0.59 (0.05–1.13)
0.005 ⬍0.0001 0.5425 0.0001 ⬍0.0001
ACD ⫽ anterior chamber depth; AL ⫽ axial length; D ⫽ diopters; K1 ⫽ corneal curvature; SER ⫽ spherical equivalent refraction; WTW ⫽ corneal diameter (white to white).
The distribution of WTW had a mean of 12.06 mm and was also close to normal. The mean K1 was 43.53 mm in women (95%CI, 43.41– 43.65) and 43.27 mm (95%CI, 43.13– 43.41) in men, P ⫽ 0.0246. The ACD and WTW decreased across the age groups (P⬍0.0001 and P ⫽ 0.0001, respectively), but there was no significant age-related change in K1 (P ⫽ 0.542), as shown in Table 1. The distribution of AL, SER, and other ocular biometric parameters, stratified by age and gender, is shown in Table 2.
Distribution of Spherical Equivalent Refraction The mean SER was 0.58 D, and the distribution of SER was highly peaked and skewed toward the left (negatively), as shown in Figure 4. In Table 1, the mean SER is stratified by age and shows a hyperopic shift, followed by a myopic shift across age groups (P⬍0.0001) as previously reported.30 Overall, the mean SER in women (0.66 D) did not differ significantly from that in men (0.48 D), P ⫽ 0.094. In Table 2, the age-related change in SER per decade of age was highly significant in the overall population (P⬍0.0001) and in women (P ⫽ 0.0003) separately, and was of lower magnitude, but still significantly different in men (P ⫽ 0.0216).
Relationships among Axial Length, Spherical Equivalent Refraction, and Other Ocular Biometric Parameters Table 3 shows Pearson correlation coefficients of ocular biometric parameters with SER and AL. Significant correlations with SER were found for AL and ACD, but not for K1 or WTW. After adjusting for ocular biometric parameters, age and sex, the negative correlation between AL and SER persisted.
Discussion The introduction of partial coherence laser interferometry (IOL Master) has made possible noncontact high-resolution IOL power calculations before cataract surgery,17 particularly measurements of AL, which lead to accurate calculation of IOL power and refractive outcome.18,19 Despite its widespread use, there are actually few population-based data from older samples describing IOL Master norms on the distribution of AL. This study provides such data in an older population.
Table 2. Age and Gender Distribution of Axial Length, Ocular Biometry, and Spherical Equivalent Refraction in the Blue Mountains Eye Study Population, with 95% Confidence Intervals Variable
P for Trend*
Age (yrs) N AL (mm) ACD (mm) K1 (D) WTW (mm) SER (D)
All ages 749 23.20 (23.12–23.28) 3.06 (3.04–3.09) 43.74 (43.63–43.85) 12.00 (11.97–12.03) 0.82 (0.65–0.99)
59–64 122 23.37 (23.12–23.61) 3.15 (3.09–3.12) 43.64 (43.37–43.90) 12.05 (11.96–12.14) 0.25 (–0.24–0.75)
Women (n ⫽ 749) 65–74 338 23.25 (23.13–23.37) 3.10 (3.07–3.14) 43.78 (43.63–43.94) 12.02 (11.98–12.07) 0.65 (0.39–0.92)
75–84 242 23.08 (22.97–23.19) 3.00 (2.96–3.04) 43.66 (43.48–43.84) 11.97 (11.92–12.02) 1.37 (1.12–1.61)
85⫹ 47 23.03 (22.74–23.31) 2.88 (2.80–2.96) 44.06 (43.64–44.49) 11.82 (11.70–11.94) 0.72 (0.04–1.39)
0.006 ⬍0.0001 0.4376 0.0012 0.0004
Age (yrs) N AL (mm) ACD (mm) K1 (D) WTW (mm) SER (D)
All ages 572 23.75 (23.67–23.83) 3.16 (3.13–3.19) 43.01 (42.89–43.13) 12.14 (12.11–12.18) 0.62 (0.47–0.78)
59–64 104 23.88 (23.70–24.06) 3.25 (3.18–3.32) 43.17 (42.88–43.46) 12.16 (12.07–12.24) ⫺0.09 (⫺0.46–0.27)
Men (n ⫽ 572) 65–74 265 23.68 (23.57–23.79) 3.16 (3.12–3.21) 42.99 (42.82–43.16) 12.19 (12.14–12.24) 0.87 (0.66–1.08)
75–84 180 23.81 (23.66–23.95) 3.12 (3.06–3.18) 42.90 (42.67–43.12) 12.08 (12.02–12.14) 0.72 (0.43–1.00)
85⫹ 23 23.63 (23.09–24.17) 2.92 (2.76–3.09) 43.42 (42.76–44.07) 12.12 (11.95–12.30) 0.35 (⫺0.62–1.32)
0.626 0.0001 0.650 0.0823 0.056
ACD ⫽ anterior chamber depth; AL ⫽ axial length; D ⫽ diopters; K1 ⫽ corneal curvature; SER ⫽ spherical equivalent refraction; WTW ⫽ corneal diameter (white to white). *P trend test for age groups.
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Figure 2. Distribution of corneal power in diopters in the BMES population. BMES ⫽ Blue Mountains Eye Study; KS ⫽ Kolmogorov-Smirnov.
The technology for measuring ocular biometric parameters has undergone immense changes from the measurement of AL either indirectly11 or directly with radiography20 to the use of ultrasound21,22 and partial coherence laser interferometry (IOL Master). Biometry data from ultrasound and laser interferometry differ from those derived using contact methods in that lens thickness cannot be measured directly by the IOL Master. Axial length measured by ultrasound is reported to be significantly shorter than when measured using noncontact techniques because of indentation with the former,23 compared with IOL Master measures, which are noncontact and assessed along the visual axis using a fixation beam.24 Because the IOL Master uses an infrared light source rather than a 10-MHz sound beam, measurement accuracy is potentially increased from 0.10 mm to between 0.02 and 0.01 mm, an approximate 5-fold improvement.17 Greater precision, resolution, accuracy, and reproducibility of AL measurements using the IOL Master have been documented compared with other methods.25,26
Distribution of Axial Length, Other Ocular Biometry Variables, and Spherical Equivalent Refraction We confirm previous data that AL was not normally distributed in the general population, with a positive skew and a significant kurtosis (5.44). Skew has been reported in the distribution of AL in the Reykjavik Eye Study,27 and Stenstrom28 reported a bimodal distribution of AL, which became normal after excluding eyes with myopic crescents, a
Figure 4. Distribution of SER in diopters in the BMES population. BMES ⫽ Blue Mountains Eye Study; KS ⫽ Kolmogorov-Smirnov; SER ⫽ spherical equivalent refraction.
condition that would normally be associated with excessive ocular elongation. However, kurtosis in the distribution of AL has not been reported in other studies on adults, so this is the first report of the appearance of significant kurtosis in the distribution of AL. This differs from the situation in children examined in the Sydney Myopia Study,29 in whom the level of kurtosis was very low at the age of 6 years (0.5). However, unpublished estimates of kurtosis in the distribution of AL in the 12-year-old Sydney Myopia Study sample suggest that some kurtosis was appearing (2.09), suggesting that kurtosis in the distribution of AL may gradually increase after the age of 6 years. At this stage, it is not clear whether the appearance of kurtosis in the distribution of AL has a particular biological significance, and what mechanisms might be involved, well after the highly kurtotic distribution of SER has been established. Ocular biometry parameters such as K1 were generally normally distributed, as in the Reykjavik Eye Study27 and the Sydney Myopia Study.29 Anterior chamber depth, however, was slightly peaked in our population, as opposed to the normal distribution in children. The distribution of SER was highly peaked at approximately ⫹1.0 D and was skewed to the left, similar to findings from the Sydney Myopia Study.29 Table 4 compares ocular biometric data and SER obtained in different studies of older populations. Statistically significant gender differences in AL, K1, and ACD (unadTable 3. Correlation of Ocular Biometric Parameters with Spherical Equivalent Refraction, Axial Length, and Anterior Chamber Depth in the Blue Mountains Eye Study†
SER (D) AL (mm) ACD (mm)
Figure 3. Distribution of ACD in the BMES population. ACD ⫽ anterior chamber depth; BMES ⫽ Blue Mountains Eye Study; KS ⫽ KolmogorovSmirnov.
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AL (mm)
ACD (mm)
K1 (D)
WTW (mm)
⫺0.688* — —
⫺0.222* 0.424* —
⫺0.086 ⫺0.445* ⫺0.035
⫺0.017 0.343* 0.360*
ACD ⫽ anterior chamber depth; AL ⫽ axial length; D ⫽ diopters; K1 ⫽ corneal curvature in diopters; SER ⫽ spherical equivalent refraction; WTW ⫽ corneal diameter (white to white). *P⬍0.0001. † All values reported are crude values only.
Fotedar et al 䡠 Distribution of Axial Length in the BMES Population Table 4. Comparison of Ocular Biometric Data and Spherical Equivalent Refraction Obtained by Different Studies Mean AL (mm) Study Name LALES
14
Method
N
A scan
5588
Mongolia42
A scan
1617
Reykjavik13
A scan
723
Tanjong Pagar, Singapore2
A scan
1004
BMES
IOL Master
1321
Women 23.18* (⫹1.02) 23.08*,† (⫾1.20) 23.20* (⫺0.98) 22.98* (⫾1.16) 23.20* (⫾1.07)
Men 23.65 (⫾0.94) 23.43 (⫾1.06) 23.74 (⫾1.01) 23.54 (⫾1.10) 23.75 (⫾0.96)
Mean K1 (D) Women 43.95* (⫾1.6) 44.24* — 43.73* (⫾1.42) 7.59*,‡ (⫾0.24) 43.68* (⫾1.46)
Men 43.35 (⫾1.64) 43.65 — 43.41 (⫾1.36) 7.73 (⫾0.29) 42.98 (⫾1.45)
Mean ACD (mm) Women 3.36* (⫾0.34) 2.77* — 3.08* (⫾0.34) 2.81* (⫾0.42) 3.06* (⫾0.33)
Men 3.48 (⫾0.34) 2.87 — 3.20 (⫾0.37) 2.99 (⫾0.45) 3.04 (⫾0.37)
Mean SER (D) Women §
0.18 (⫾2.04) ⫺0.08 (⫾2.09) 1.28* (⫾2.12) ⫺0.56 (⫾2.89) 0.66 (⫾2.38)
Men 0.02 (⫾1.66) ⫺0.06 (⫾2.04) 1.05* (⫾2.19) ⫺0.40 (⫾2.41) 0.48 (⫾1.89)
Numerical values in brackets are SD. ACD ⫽ anterior chamber depth; AL ⫽ axial length; BMES ⫽ Blue Mountains Eye Study; D ⫽ diopters; K1 ⫽ corneal curvature; LALES ⫽ Los Angeles Latino Eye Study; SD ⫽ standard deviation. *P⬍0.0001. † Age adjusted. ‡ Corneal curvature in mm. § P ⫽ 0.001.
justed) were found in all these populations, but there were no gender-related differences found in SER, apart from the Los Angeles Latino Eye (LALES) and Reykjavik Studies. Some ethnicity relationships are also evident from Table 4, because the 2 Caucasian populations (Reykjavik and BMES) had similar and longer AL compared with the East Asian population groups in Singapore and Mongolia, which also had smaller ACDs, although these differences were slight.
Gender and Age Relationships We showed that the mean AL in men (23.75 mm) was significantly greater than in women (23.20 mm). Similar gender differences in the mean AL for men (23.74 mm) and women (23.20 mm) were reported by the Reykjavik Eye Study31 and in the LALES population32 (23.65 mm in men and 23.18 mm in women). Presumably it represents an adjustment to the slightly flatter corneas in men. From age 59 years, AL decreased with age in women but not in men, whereas AL has been reported to decrease in both genders in other populations.1,31,32 The decrease in ACD is uniform and can be seen in both genders, and is possibly associated with lens thickening,13 but we could not investigate this hypothesis because the IOL Master does not perform lens thickness measurements. Interpreting these changes is complex and would need to account for secular changes in height and education between age cohorts, as well as possible longitudinal changes.
Ocular Biometry Correlations The finding of a statistically significant inverse linear relationship between AL and SER is consistent with previous findings.33– 40 The LALES reported that the strongest determinants of SER across the age spectrum were AL and K1. By examining the relationship of ocular biometric variables with AL, we found a significant negative correlation of K1 with AL,
also reported by other studies.33,39 – 41 We also found a positive correlation between AL and ACD, which could be due to a tendency for shorter eyes to have smaller anterior chambers. In conclusion, this study provides normative ocular biometry and refractive data and their interrelationships in a large, representative older white Caucasian population. The finding of a non-Gaussian leptokurtotic AL distribution differs from the expected normal distribution but is similar to the non-Gaussian distribution of SER, which presumably is being actively modulated by other ocular biometric parameters. Our finding of a non-normal distribution of AL in this elderly population is potentially important and suggests active modulation of AL at some stage after the establishment of the leptokurtic distribution of SER, without any development of kurtosis in the distribution of AL, in the early years of childhood.
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server and interobserver reliability. J Cataract Refract Surg 2001;27:1961– 8. Lam AK, Chan R, Pang PC. The repeatability and accuracy of axial length and anterior chamber depth measurements from the IOLMaster. Ophthalmic Physiol Opt 2001;21:477– 83. Olsen T, Arnarsson A, Sasaki H, et al. On the ocular refractive components: the Reykjavik Eye Study. Acta Ophthalmol Scand 2007;85:361– 6. Stenstrom S. Investigation of the variation and the correlation of the optical elements of human eyes. Am J Optom Arch Am Acad Optom 1948;25:218, passim. 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. Fotedar R, Mitchell P, Burlutsky G, Wang JJ. Relationship of 10-year change in refraction to nuclear cataract and axial length findings from an older population. Ophthalmology 2008;115:1273– 8. 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. 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. Carney LG, Mainstone JC, Henderson BA. Corneal topography and myopia: a cross-sectional study. Invest Ophthalmol Vis Sci 1997;38:311–20. Garner LF, Meng CK, Grosvenor TP, Mohidin N. Ocular dimensions and refractive power in Malay and Melanesian children. Ophthalmic Physiol Opt 1990;10:234 – 8. Goss DA, Cox VD, Herrin-Lawson GA, et al. Refractive error, axial length, and height as a function of age in young myopes. Optom Vis Sci 1990;67:332– 8. Grosvenor T, Scott R. Role of the axial length/corneal radius ratio in determining the refractive state of the eye. Optom Vis Sci 1994;71:573–9. Goh WS, Lam CS. Changes in refractive trends and optical components of Hong Kong Chinese aged 19 –39 years. Ophthalmic Physiol Opt 1994;14:378 – 82. Strang NC, Schmid KL, Carney LG. Hyperopia is predominantly axial in nature. Curr Eye Res 1998;17:380 –3. Fledelius HC. Corneal curvature radius: oculometric considerations with reference to age and refractive change. Acta Ophthalmol Suppl 1988;185:74 –7. Lam CS, Goh WS, Tang YK, et al. Changes in refractive trends and optical components of Hong Kong Chinese aged over 40 years. Ophthalmic Physiol Opt 1994;14:383– 8. Cook NR, Rosner BA. Screening rules for determining blood pressure status in clinical trials: application to the trials of hypertension prevention. Am J Epidemiol 1993;137:1341–52. Wickremasinghe S, Foster PJ, Uranchimeg D, et al. Ocular biometry and refraction in Mongolian adults. Invest Ophthalmol Vis Sci 2004;45:776 – 83.
Footnotes and Financial Disclosures Originally received: January 13, 2009. Final revision: July 16, 2009. Accepted: July 23, 2009. Available online: January 19, 2010. 1
2
Manuscript no. 2009-50.
Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
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Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia. 3 ARC Centre of Excellence in Vision Science, Australian National University, Canberra, Australia. 4 Discipline of Orthoptics, Faculty of Health Sciences, University of Sydney, Sydney, Australia.
Fotedar et al 䡠 Distribution of Axial Length in the BMES Population Presented in part at: the Royal Australian and New Zealand College of Ophthalmology conference, November 2007, Perth, Australia. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Supported by the National Health and Medical Research Council, Canberra, Australia (Grant Nos. 974159 and 211069). IGM was sup-
ported by the ARC Centre of Excellence in Vision Science (COE561903). Correspondence: Paul Mitchell, MD, PhD, FRANZCO, Centre for Vision Research, Department of Ophthalmology, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia. E-mail: paul_mitchell@ wmi.usyd.edu.au.
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Cataract surgery is the most commonly performed surgical procedure in the United States and other developed countries. With advances in surgical techniques, intraocular lens (IOL) design, and instruments, there is now an increased expectation from surgeons and patients for precise postoperative refractive results. To meet these expectations, attention to accurate biometry measurements, particularly axial length (AL), is critical.1 However, the distribution and determinants of AL have been assessed in only a few population-based studies of older persons,2– 4 of which only one study has examined a predominantly European Caucasian (“white”) sample. Notably, no population studies to date have reported AL distribution measured using non-contact partial coherence laser interferometry (Zeiss IOL Master, Carl Zeiss AG, Oberkochen, Germany), now used routinely © 2010 by the American Academy of Ophthalmology Published by Elsevier Inc.
by ophthalmologists worldwide to estimate IOL power before cataract surgery.5– 8 IOL Master measurements are considered more accurate and reproducible than applanation ultrasound, using contact techniques.9,10 Furthermore, the IOL Master also predicts postoperative refraction better than ultrasound biometry, particularly for close ranges.1 Increased accuracy of AL measurement using appropriate IOL power calculations (Holladay and SRK-T formulae for AL 22.0 –24.0 mm, and Hoffer for shorter AL) should lead to improved cataract surgical outcomes. The distribution of AL and other ocular biometric parameters, for example, the corneal radius of curvature or corneal power (K1) and anterior chamber depth (ACD), follow a common Gaussian curve, whereas spherical equivalent refraction (SER) in the general population has a nonISSN 0161-6420/10/$–see front matter doi:10.1016/j.ophtha.2009.07.028
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Gaussian leptokurtic distribution. This type of distribution has a positive excess kurtosis, or peak.11,12 This tight distribution of SER largely results from the matching of AL to corneal power during emmetropization.13,14 Detailed biometric evaluation of the eye in an unbiased population sample is needed to elucidate these relationships and underlying reasons for changes in AL, other ocular biometric parameters, and refractive error with age. This study describes the distribution of AL and other ocular biometric parameters as measured using the IOL Master in the Blue Mountains Eye Study (BMES) population-based cohort. These data will help to provide comprehensive age and gender norms for this instrument in older European Caucasian persons.
Materials and Methods Study Population The BMES is a population-based cohort study of vision and common eye diseases in a suburban Australian population aged 49 years or older at baseline. The study was approved by the University of Sydney Human Research Ethics Committee and was conducted adhering to the tenets of the Helsinki Declaration. Signed informed consent was obtained from all participants at each examination. Survey methods and procedures have been described.15,16 Briefly, at baseline (1992–1994) 3654 of 4433 eligible residents (82.4%) aged 49 years or older living in the Blue Mountains area, west of Sydney, were examined. At the 5-year followup, 2335 of the 3111 surviving participants (75.1%) were reexamined during 1997 to 1999. After 10 years, 1952 baseline participants (53.4% of the original cohort, 76.6% of survivors) were reexamined during 2002 to 2004.
Procedures Comprehensive eye examinations at each visit included measurement of the logarithm of the minimum angle of resolution visual acuity for each eye, followed by subjective refraction for those with visual acuity ⬍54 letters.16 The AL was measured only at the 10-year examination using an IOL Master, which uses signals from the tear film and retinal pigment epithelium to measure AL. The system automatically adjusts for differences in distance between the inner limiting membrane and the retinal pigment epithelium, so that the displayed AL is directly comparable to that obtained using immersion ultrasound. Five valid readings of AL and ACD and 3 readings of K1 and corneal diameter (white to white [WTW]) were taken. The ACD was defined as the distance from the anterior corneal surface to the anterior lens surface, whereas corneal power was measured in 2 meridians, the greatest and least radii of curvature (K1, K2). Because K1 and K2 had similar correlation coefficients, only K1 readings are included and are reported as corneal power in diopters (D). The refractive index value used for this conversion by the IOL Master is n⫽1.3375. Myopia was defined as SER ⬍ ⫺0.5 D, hyperopia was defined as SER ⬎ ⫹0.5 D, and emmetropia was defined as SER between – 0.5 D and ⫹0.5 D.
SER was calculated by summating the spherical plus half the cylindrical refraction, and expressed in diopters. Measures of spread, including kurtosis and skew, were derived. Distributions for SER and ocular biometric parameters were tested for normality with the Kolmogorov-Smirnov test and were considered significantly different from normal for P⬍0.01. Correlations between SER and AL and other biometric variables were calculated using the Pearson correlation coefficient, and 95% confidence intervals (CIs) are presented. Group trend tests were used to assess any significant trends across age groups for each variable.
Results Of the 1952 baseline BMES participants reexamined at 10 years, AL could be measured with the IOL Master in 1561 participants, of whom 28 had incomplete data and 212 were pseudophakic and thus were excluded from this analysis. This left 1321 phakic subjects, 749 women (56.7%) and 572 men (43.3%), who had valid ocular biometry measurements.
Distribution of Ocular Biometry Figure 1 shows the distribution of AL in the BMES population. The mean AL was 23.44 mm (95%CI, 23.38 –23.50). The AL distribution in the whole population was skewed toward the right (positively) and was peaked, with a kurtosis of 5.44 and significant Kolmogorov-Smirnov test for deviation from normality (P⬍0.01). The mean AL in women was 23.19 mm (95%CI, 23.11–23.27), and the mean AL in men was 23.76 mm (95%CI, 23.68 –23.84), showing a statistically significant gender-related difference (P⬍ 0.0001). Table 1 shows mean AL, other biometric parameters, and SER with 95%CI, stratified by age group. Table 2 shows this distribution also stratified by gender. Mean AL decreased across age categories (P for trend ⫽ 0.005). Each decade of age was associated with a decrease of 0.09 mm in mean AL in men and women combined (P ⫽ 0.0159), whereas the corresponding decrease was 0.12 mm per decade (P ⫽ 0.0176) in women, but only 0.02 mm per decade (P ⫽ 0.6319) in men. The test for trend across age groups was significant for women (P for trend ⫽ 0.009) but not for men (P for trend ⫽ 0.527). Figures 2 and 3 show the distributions of K1 and ACD. The mean K1 was 43.38 D, and the mean ACD was 3.24 mm. The distribution of K1 was essentially normal, whereas the distribution of ACD was positively skewed and peaked, and close to normal.
Statistical Analysis Statistical analyses were performed using SAS software (SAS Inc., Cary, NC). Because there is a high correlation between the 2 eyes for refractive and biometric parameters, and the findings were similar for the 2 eyes, data from right eyes only are presented. The
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Figure 1. Distribution of axial length in the BMES population. BMES ⫽ Blue Mountains Eye Study; KS ⫽ Kolmogorov-Smirnov.
Fotedar et al 䡠 Distribution of Axial Length in the BMES Population Table 1. Age Distribution of Axial Length, Ocular Biometry, and Spherical Equivalent Refraction in the Blue Mountains Eye Study Population, Presented with 95% Confidence Intervals Whole Population (n ⴝ 1321)
Variable Age (yrs) N AL (mm) ACD (mm) K1 (D) WTW (mm) SER (D)
59–64 226 23.60 (23.45–23.76) 3.20 (3.15–3.24) 43.42 (43.23–43.62) 12.10 (12.04–12.16) 0.09 (–0.22–0.40)
65–74 603 23.44 (23.35–23.52) 3.13 (3.10–3.16) 43.44 (43.32. 43.55) 12.09 (12.06–12.13) 0.75 (0.57–0.92)
75–84 422 23.39 (23.30–23.48) 3.05 (3.02–3.09) 43.33 (43.19–43.48) 12.02 (11.98–12.06) 1.09 (0.90–1.28)
P Values 85⫹ 70 23.23 (22.96–23.49) 2.89 (2.82–2.97) 43.85 (43.49–44.21) 11.93 (11.83–12.03) 0.59 (0.05–1.13)
0.005 ⬍0.0001 0.5425 0.0001 ⬍0.0001
ACD ⫽ anterior chamber depth; AL ⫽ axial length; D ⫽ diopters; K1 ⫽ corneal curvature; SER ⫽ spherical equivalent refraction; WTW ⫽ corneal diameter (white to white).
The distribution of WTW had a mean of 12.06 mm and was also close to normal. The mean K1 was 43.53 mm in women (95%CI, 43.41– 43.65) and 43.27 mm (95%CI, 43.13– 43.41) in men, P ⫽ 0.0246. The ACD and WTW decreased across the age groups (P⬍0.0001 and P ⫽ 0.0001, respectively), but there was no significant age-related change in K1 (P ⫽ 0.542), as shown in Table 1. The distribution of AL, SER, and other ocular biometric parameters, stratified by age and gender, is shown in Table 2.
Distribution of Spherical Equivalent Refraction The mean SER was 0.58 D, and the distribution of SER was highly peaked and skewed toward the left (negatively), as shown in Figure 4. In Table 1, the mean SER is stratified by age and shows a hyperopic shift, followed by a myopic shift across age groups (P⬍0.0001) as previously reported.30 Overall, the mean SER in women (0.66 D) did not differ significantly from that in men (0.48 D), P ⫽ 0.094. In Table 2, the age-related change in SER per decade of age was highly significant in the overall population (P⬍0.0001) and in women (P ⫽ 0.0003) separately, and was of lower magnitude, but still significantly different in men (P ⫽ 0.0216).
Relationships among Axial Length, Spherical Equivalent Refraction, and Other Ocular Biometric Parameters Table 3 shows Pearson correlation coefficients of ocular biometric parameters with SER and AL. Significant correlations with SER were found for AL and ACD, but not for K1 or WTW. After adjusting for ocular biometric parameters, age and sex, the negative correlation between AL and SER persisted.
Discussion The introduction of partial coherence laser interferometry (IOL Master) has made possible noncontact high-resolution IOL power calculations before cataract surgery,17 particularly measurements of AL, which lead to accurate calculation of IOL power and refractive outcome.18,19 Despite its widespread use, there are actually few population-based data from older samples describing IOL Master norms on the distribution of AL. This study provides such data in an older population.
Table 2. Age and Gender Distribution of Axial Length, Ocular Biometry, and Spherical Equivalent Refraction in the Blue Mountains Eye Study Population, with 95% Confidence Intervals Variable
P for Trend*
Age (yrs) N AL (mm) ACD (mm) K1 (D) WTW (mm) SER (D)
All ages 749 23.20 (23.12–23.28) 3.06 (3.04–3.09) 43.74 (43.63–43.85) 12.00 (11.97–12.03) 0.82 (0.65–0.99)
59–64 122 23.37 (23.12–23.61) 3.15 (3.09–3.12) 43.64 (43.37–43.90) 12.05 (11.96–12.14) 0.25 (–0.24–0.75)
Women (n ⫽ 749) 65–74 338 23.25 (23.13–23.37) 3.10 (3.07–3.14) 43.78 (43.63–43.94) 12.02 (11.98–12.07) 0.65 (0.39–0.92)
75–84 242 23.08 (22.97–23.19) 3.00 (2.96–3.04) 43.66 (43.48–43.84) 11.97 (11.92–12.02) 1.37 (1.12–1.61)
85⫹ 47 23.03 (22.74–23.31) 2.88 (2.80–2.96) 44.06 (43.64–44.49) 11.82 (11.70–11.94) 0.72 (0.04–1.39)
0.006 ⬍0.0001 0.4376 0.0012 0.0004
Age (yrs) N AL (mm) ACD (mm) K1 (D) WTW (mm) SER (D)
All ages 572 23.75 (23.67–23.83) 3.16 (3.13–3.19) 43.01 (42.89–43.13) 12.14 (12.11–12.18) 0.62 (0.47–0.78)
59–64 104 23.88 (23.70–24.06) 3.25 (3.18–3.32) 43.17 (42.88–43.46) 12.16 (12.07–12.24) ⫺0.09 (⫺0.46–0.27)
Men (n ⫽ 572) 65–74 265 23.68 (23.57–23.79) 3.16 (3.12–3.21) 42.99 (42.82–43.16) 12.19 (12.14–12.24) 0.87 (0.66–1.08)
75–84 180 23.81 (23.66–23.95) 3.12 (3.06–3.18) 42.90 (42.67–43.12) 12.08 (12.02–12.14) 0.72 (0.43–1.00)
85⫹ 23 23.63 (23.09–24.17) 2.92 (2.76–3.09) 43.42 (42.76–44.07) 12.12 (11.95–12.30) 0.35 (⫺0.62–1.32)
0.626 0.0001 0.650 0.0823 0.056
ACD ⫽ anterior chamber depth; AL ⫽ axial length; D ⫽ diopters; K1 ⫽ corneal curvature; SER ⫽ spherical equivalent refraction; WTW ⫽ corneal diameter (white to white). *P trend test for age groups.
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Figure 2. Distribution of corneal power in diopters in the BMES population. BMES ⫽ Blue Mountains Eye Study; KS ⫽ Kolmogorov-Smirnov.
The technology for measuring ocular biometric parameters has undergone immense changes from the measurement of AL either indirectly11 or directly with radiography20 to the use of ultrasound21,22 and partial coherence laser interferometry (IOL Master). Biometry data from ultrasound and laser interferometry differ from those derived using contact methods in that lens thickness cannot be measured directly by the IOL Master. Axial length measured by ultrasound is reported to be significantly shorter than when measured using noncontact techniques because of indentation with the former,23 compared with IOL Master measures, which are noncontact and assessed along the visual axis using a fixation beam.24 Because the IOL Master uses an infrared light source rather than a 10-MHz sound beam, measurement accuracy is potentially increased from 0.10 mm to between 0.02 and 0.01 mm, an approximate 5-fold improvement.17 Greater precision, resolution, accuracy, and reproducibility of AL measurements using the IOL Master have been documented compared with other methods.25,26
Distribution of Axial Length, Other Ocular Biometry Variables, and Spherical Equivalent Refraction We confirm previous data that AL was not normally distributed in the general population, with a positive skew and a significant kurtosis (5.44). Skew has been reported in the distribution of AL in the Reykjavik Eye Study,27 and Stenstrom28 reported a bimodal distribution of AL, which became normal after excluding eyes with myopic crescents, a
Figure 4. Distribution of SER in diopters in the BMES population. BMES ⫽ Blue Mountains Eye Study; KS ⫽ Kolmogorov-Smirnov; SER ⫽ spherical equivalent refraction.
condition that would normally be associated with excessive ocular elongation. However, kurtosis in the distribution of AL has not been reported in other studies on adults, so this is the first report of the appearance of significant kurtosis in the distribution of AL. This differs from the situation in children examined in the Sydney Myopia Study,29 in whom the level of kurtosis was very low at the age of 6 years (0.5). However, unpublished estimates of kurtosis in the distribution of AL in the 12-year-old Sydney Myopia Study sample suggest that some kurtosis was appearing (2.09), suggesting that kurtosis in the distribution of AL may gradually increase after the age of 6 years. At this stage, it is not clear whether the appearance of kurtosis in the distribution of AL has a particular biological significance, and what mechanisms might be involved, well after the highly kurtotic distribution of SER has been established. Ocular biometry parameters such as K1 were generally normally distributed, as in the Reykjavik Eye Study27 and the Sydney Myopia Study.29 Anterior chamber depth, however, was slightly peaked in our population, as opposed to the normal distribution in children. The distribution of SER was highly peaked at approximately ⫹1.0 D and was skewed to the left, similar to findings from the Sydney Myopia Study.29 Table 4 compares ocular biometric data and SER obtained in different studies of older populations. Statistically significant gender differences in AL, K1, and ACD (unadTable 3. Correlation of Ocular Biometric Parameters with Spherical Equivalent Refraction, Axial Length, and Anterior Chamber Depth in the Blue Mountains Eye Study†
SER (D) AL (mm) ACD (mm)
Figure 3. Distribution of ACD in the BMES population. ACD ⫽ anterior chamber depth; BMES ⫽ Blue Mountains Eye Study; KS ⫽ KolmogorovSmirnov.
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AL (mm)
ACD (mm)
K1 (D)
WTW (mm)
⫺0.688* — —
⫺0.222* 0.424* —
⫺0.086 ⫺0.445* ⫺0.035
⫺0.017 0.343* 0.360*
ACD ⫽ anterior chamber depth; AL ⫽ axial length; D ⫽ diopters; K1 ⫽ corneal curvature in diopters; SER ⫽ spherical equivalent refraction; WTW ⫽ corneal diameter (white to white). *P⬍0.0001. † All values reported are crude values only.
Fotedar et al 䡠 Distribution of Axial Length in the BMES Population Table 4. Comparison of Ocular Biometric Data and Spherical Equivalent Refraction Obtained by Different Studies Mean AL (mm) Study Name LALES
14
Method
N
A scan
5588
Mongolia42
A scan
1617
Reykjavik13
A scan
723
Tanjong Pagar, Singapore2
A scan
1004
BMES
IOL Master
1321
Women 23.18* (⫹1.02) 23.08*,† (⫾1.20) 23.20* (⫺0.98) 22.98* (⫾1.16) 23.20* (⫾1.07)
Men 23.65 (⫾0.94) 23.43 (⫾1.06) 23.74 (⫾1.01) 23.54 (⫾1.10) 23.75 (⫾0.96)
Mean K1 (D) Women 43.95* (⫾1.6) 44.24* — 43.73* (⫾1.42) 7.59*,‡ (⫾0.24) 43.68* (⫾1.46)
Men 43.35 (⫾1.64) 43.65 — 43.41 (⫾1.36) 7.73 (⫾0.29) 42.98 (⫾1.45)
Mean ACD (mm) Women 3.36* (⫾0.34) 2.77* — 3.08* (⫾0.34) 2.81* (⫾0.42) 3.06* (⫾0.33)
Men 3.48 (⫾0.34) 2.87 — 3.20 (⫾0.37) 2.99 (⫾0.45) 3.04 (⫾0.37)
Mean SER (D) Women §
0.18 (⫾2.04) ⫺0.08 (⫾2.09) 1.28* (⫾2.12) ⫺0.56 (⫾2.89) 0.66 (⫾2.38)
Men 0.02 (⫾1.66) ⫺0.06 (⫾2.04) 1.05* (⫾2.19) ⫺0.40 (⫾2.41) 0.48 (⫾1.89)
Numerical values in brackets are SD. ACD ⫽ anterior chamber depth; AL ⫽ axial length; BMES ⫽ Blue Mountains Eye Study; D ⫽ diopters; K1 ⫽ corneal curvature; LALES ⫽ Los Angeles Latino Eye Study; SD ⫽ standard deviation. *P⬍0.0001. † Age adjusted. ‡ Corneal curvature in mm. § P ⫽ 0.001.
justed) were found in all these populations, but there were no gender-related differences found in SER, apart from the Los Angeles Latino Eye (LALES) and Reykjavik Studies. Some ethnicity relationships are also evident from Table 4, because the 2 Caucasian populations (Reykjavik and BMES) had similar and longer AL compared with the East Asian population groups in Singapore and Mongolia, which also had smaller ACDs, although these differences were slight.
Gender and Age Relationships We showed that the mean AL in men (23.75 mm) was significantly greater than in women (23.20 mm). Similar gender differences in the mean AL for men (23.74 mm) and women (23.20 mm) were reported by the Reykjavik Eye Study31 and in the LALES population32 (23.65 mm in men and 23.18 mm in women). Presumably it represents an adjustment to the slightly flatter corneas in men. From age 59 years, AL decreased with age in women but not in men, whereas AL has been reported to decrease in both genders in other populations.1,31,32 The decrease in ACD is uniform and can be seen in both genders, and is possibly associated with lens thickening,13 but we could not investigate this hypothesis because the IOL Master does not perform lens thickness measurements. Interpreting these changes is complex and would need to account for secular changes in height and education between age cohorts, as well as possible longitudinal changes.
Ocular Biometry Correlations The finding of a statistically significant inverse linear relationship between AL and SER is consistent with previous findings.33– 40 The LALES reported that the strongest determinants of SER across the age spectrum were AL and K1. By examining the relationship of ocular biometric variables with AL, we found a significant negative correlation of K1 with AL,
also reported by other studies.33,39 – 41 We also found a positive correlation between AL and ACD, which could be due to a tendency for shorter eyes to have smaller anterior chambers. In conclusion, this study provides normative ocular biometry and refractive data and their interrelationships in a large, representative older white Caucasian population. The finding of a non-Gaussian leptokurtotic AL distribution differs from the expected normal distribution but is similar to the non-Gaussian distribution of SER, which presumably is being actively modulated by other ocular biometric parameters. Our finding of a non-normal distribution of AL in this elderly population is potentially important and suggests active modulation of AL at some stage after the establishment of the leptokurtic distribution of SER, without any development of kurtosis in the distribution of AL, in the early years of childhood.
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Footnotes and Financial Disclosures Originally received: January 13, 2009. Final revision: July 16, 2009. Accepted: July 23, 2009. Available online: January 19, 2010. 1
2
Manuscript no. 2009-50.
Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Sydney, Australia.
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Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia. 3 ARC Centre of Excellence in Vision Science, Australian National University, Canberra, Australia. 4 Discipline of Orthoptics, Faculty of Health Sciences, University of Sydney, Sydney, Australia.
Fotedar et al 䡠 Distribution of Axial Length in the BMES Population Presented in part at: the Royal Australian and New Zealand College of Ophthalmology conference, November 2007, Perth, Australia. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Supported by the National Health and Medical Research Council, Canberra, Australia (Grant Nos. 974159 and 211069). IGM was sup-
ported by the ARC Centre of Excellence in Vision Science (COE561903). Correspondence: Paul Mitchell, MD, PhD, FRANZCO, Centre for Vision Research, Department of Ophthalmology, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia. E-mail: paul_mitchell@ wmi.usyd.edu.au.
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