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1From the Singapore National Eye Centre and Singapore Eye Research Institute; the 2Institute of Ophthalmology, University College London, United Kingdom; the 3Glaucoma Research Unit, Moorfields Eye Hospital, London, United Kingdom; the 4Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre, Singapore; the 5Departments of Ophthalmology and 6Community, Occupational and Family Medicine, National University, Singapore.
| Abstract |
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METHODS. Chinese people (n = 2000), aged 40 to 79 years, were selected from the Singapore electoral register. Of the 1717 considered eligible for examination, 1232 participated, representing a response rate of 71.8%. IOP was estimated with Goldmann applanation tonometry. The drainage angle was assessed with static and dynamic gonioscopy. The optic nerve was examined at high magnification through a dilated pupil with a fundus contact lens or a +78-D lens. Static automated visual field testing was performed on subjects with suspected glaucoma. GON was diagnosed on the basis of structural and functional abnormalities of the optic nerve.
RESULTS. The main independent determinants of higher IOP were higher systolic blood pressure (P < 0.001), quadrants of any peripheral anterior synechiae (PAS, P = 0.02) and width of the drainage angle (P = 0.049). A 100-µm increase in corneal thickness was associated with an increase in mean IOP of 1.5 to 1.8 mm Hg (P < 0.001). Odds of GON increased 1.2 times per 1-mm Hg increase in screening IOP. A clear association between corneal thickness and GON was not identified.
CONCLUSIONS. Clinical IOP estimates are related to systolic blood pressure and corneal thickness. Variation in IOP with angle width may suggest that trabecular compaction significantly contributes to causes of the increase in IOP, independent of angle-closure. GON is an IOP-related phenomenon among Chinese Singaporeans.
Both ocular and systemic factors influence clinical estimates of IOP. Central corneal thickness (CCT) correlates with measured IOP in populations.9 10 Studies comparing manometric IOP measurements with estimates obtained using tonometers have shown an error related to CCT.11 12 The clinical implications of this phenomenon are underlined by the finding that patients with ocular hypertension (OHT) have significantly thicker corneas than do patients with glaucoma and people with normal eyes.13 A decrease in CCT with age has been documented in people of East Asian origin,10 14 15 offering an attractive explanation for the decrease in IOP with age in East Asians. A recent longitudinal study suggested that CCT was a significant, independent predictor of transition from OHT to definite glaucoma, raising the question of exactly how CCT, OHT, and glaucoma are related.16
Systolic blood pressure (sBP), age, female gender, the use of alcohol or tobacco smoking, family history of glaucoma, and higher body mass index (BMI) have been found to be positively associated with IOP.17 18 A modest association between POAG and BP has been described, although the effect is modified by age, with a stronger correlation in older people. When the perfusion pressure (BP minus IOP) was calculated, a strong inverse correlation was found with POAG. This is regarded as an indication that a failure of autoregulation is partially responsible for the development of POAG.19
In light of the reported differences between Europeans and East Asians in distribution of IOP and the relationship between IOP and GON, we sought to characterize the distribution of IOP in a Chinese population, with particular reference to ocular features such as CCT.
| Methods |
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A slit lamp (Model BQ 900; Haag-Streit, Bern, Switzerland) was used to examine the anterior segment for evidence of secondary glaucoma and to detect ischemic sequelae of primary angle closure. IOP was estimated with an applanation tonometer (Goldmann model; Haag-Streit). The cornea was anesthetized with 0.5% amethocaine hydrochloride mixed with 1 drop of 2% sodium fluorescein (Minims; Chauvin Pharmaceuticals, Romford, UK). Three readings were made, and the median taken as the pressure for that eye. Gonioscopy was performed with a Goldmann-type one-mirror lens (Model 902; Haag-Streit) at x25 magnification with low ambient illumination. The width of the iridotrabecular recess was graded according to the angle subtending between the plane of the trabecular surface and a tangent extended from the junction between the outer and middle thirds of the iris. The estimate of the angle was divided into five categories: 0°, 10°, 20°, 30°, and 40° or more, recorded as grades 0 to 4 in each quadrant. Peripheral anterior synechiae (PAS) were recorded as present or absent in four quadrants after either dynamic examination with a Goldmann-type gonioscope. If a high pressure gradient across the iris was encountered, an indentation examination was performed with a four-mirror gonioscope (Sussmann model; Ocular Instruments, Bellevue, WA). A cumulative angle width score was derived by summing the grade in four quadrants to give a total score of 0 to 16.
CCT was measured with an optical pachymeter (Device I; Haag-Streit) mounted on the slit lamp. The touch method of measuring CCT was used throughout. CCT was measured from the anterior to the posterior endothelial surface using x1.6 objective magnification with +2.5-D eyepiece addition, read to the nearest 0.01 mm. CCT was measured three times in each eye and the median taken as the representative value for that eye. The subject was instructed to maintain a steady gaze in the primary position. The brightest, narrowest illumination beam possible was used. The measurements of axial CCT were made, with the pupil margin used as a point of reference to ensure accurate centration. Anterior chamber depth (ACD), lens thickness (LT), and axial length (AL) of the globe were measured by A-mode ultrasound (Compuscan LT; Storz, St. Louis, MO). The mean of sixteen individual measurements for each parameter was taken. If the SD was less than or equal to 0.13 mm, the measurements were repeated up to three times.
Systemic blood pressure was measured in the right arm of seated subjects by a nurse using a mercury sphygmomanometer. Subjects height was measured without shoes, and weight in kilograms recorded using bathroom scales with a digital display. BMI was calculated as (height in m)2/weight in kilograms. Demographic and socioeconomic data were recorded with a standardized questionnaire that has been described.21
The method of diagnosing glaucoma has been described.20 22 In this analysis, the cases of glaucoma reported herein were diagnosed according to both characteristic structural and functional evidence of optic neuropathy, or (if visual function was affected to the extent that automated field testing was not feasible) evidence of severe structural disc damage. After pharmacological dilation of the pupils, The optic disc was examined at a slit lamp with a fundus contact lens and x40 magnification. The vertical dimensions of the disc and cup were measured with an eyepiece graticule etched in 0.1-mm units (Haag-Streit). A threshold central 30° visual field (30-2 pattern) test was performed (Model 750; Humphrey Instruments, San Leandro, CA). A glaucoma hemifield test (GHT) result outside normal limits and a cluster of four contiguous points on the pattern deviation plot (P < 5% of occurring in age-matched normal subjects) not crossing the horizontal meridian were considered compatible with glaucoma.
Backward linear regression analysis was used to assess the relationship between demographic factors (age and gender), systemic variables (sBP, dBP, height and weight), and ocular factors (CCT, ACD and LT) and the estimates of IOP. Multiple logistic regression was used to examine the relationship between GON and screening IOP, corrected for age and gender.
| Results |
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0.001). There was no significant difference in mean CCT between genders (P = 0.78). Table 3 shows age- and gender-specific mean sBP and dBP. Multiple linear regression (BP on age and gender) shows that mean sBP increased by 11 mm Hg per decade (P < 0.001) and had a tendency to be higher (2.8 mm Hg) in women than in men, although this was not statistically significant (P = 0.057). By contrast, dBP did not increase significantly with age (0.7 mm Hg/decade, P = 0.07), but was higher in men than women by 2.5 mm Hg (P = 0.003).
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| Discussion |
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Both CCT and sBP were found to have a significant positive association with measured IOP. Of the two of these, sBP appears to be the more important factor in determining the measured IOP. We did not detect a consistent relationship between age, height, weight, or BMI and IOP, after correcting for other factors. The finding of an association between CCT and IOP estimates suggests a measurement error caused by variation in corneal thickness. We have documented a positive association between CCT and IOP in Mongolians. An increase of 10 µm in CCT was associated with an increase of 0.19 mm Hg and 0.24 mm Hg in right and left eyes, respectively.10 The corresponding figures for Chinese Singaporeans were 0.15 and 0.19 mm Hg. These data initially do not seem very indicative. To appreciate the implication of the data fully, they must be considered in the context of the interindividual variation in CCT in this population. The SD of corneal thickness in each decade of our study population was fairly uniform at approximately 30 µm. Hence, 95% of the members of a decade age-group would be encompassed within a range of 120 µm (and, necessarily, 5% of the population would lie outside this range). This suggests that, in Chinese Singaporeans, a variations of between 1.8 mm Hg (from right eye data) and 2.3 mm Hg (from left eye data) in IOP estimates made with the Goldmann tonometer are attributable to the variation in CCT among people of the same age. There was a small but highly significant decrease in CCT with age, being equivalent to 23 µm between the ages of 40 and 80 years. This age-related difference, superimposed on the interindividual differences in CCT within each age group, may result in a difference in IOP estimates of up to 2.7 mm Hg between a 40-year-old man with a CCT of 2 SD above the mean (i.e., upper end of the normal range) and an 80-year-old whose CCT was 2 SD below the mean (i.e., lower end of the normal range).
In a random, population-based sample of residents of Rotterdam, The Netherlands, Wolfs et al.9 found that an increase in CCT of 10 µm was associated with an increase in population mean IOP of 0.19 mm Hg. Although the Dutch study and our work in Mongolia and Singapore used different methods of measuring CCT, the similarity in the calculated effect of CCT on IOP measurements is striking. In the Dutch cohort, with a mean age of 72 years, the mean CCT was 537 µm.9 In subjects in Mongolia aged 70 or more years (mean, 75.1), the mean CCT was 475 µm right eye and 493 µm left eye. Among the Singapore cohort, mean CCT was 535 µm among people in their 70s, a negligible difference from the Dutch.
It appears that variation in IOP estimates obtained by applanation tonometry is significantly influenced by interindividual variation in CCT. The relationship between IOP and GON in East Asian people is probably impossible to understand fully without recourse to manometric investigation. In just such a study, we found that both applanation and handheld tonometry (Tonopen; Mentor, Norwell, MA) significantly underestimate true IOP. However, there was no demonstrable association between ocular dimensions or corneal thickness and IOP in the small number of subjects examined. It was assumed that the relatively small effect of ocular biometric factors was masked by a larger effect, probably attributable to the mechanical properties of ocular tissues (most likely an index of rigidity/deformability).23
To the best of our knowledge, the finding of a small but statistically significant inverse association between IOP and width of the drainage angle is unique in population studies. Eyes with wider angles have a lower IOP, probably reflecting a greater outflow facility in wider angles, attributable to altered microarchitecture of the trabecular beams. Trabecular compaction caused by increasing lens thickness and reduced zonular traction on the ciliary body is one possible explanation. This is biologically plausible, given the decline in IOP that often occurs after cataract surgery24 and the effect of pilocarpine on IOP through traction on the scleral spur.
There seems to be no doubt that an elevated IOP confers an increased risk of glaucoma. Cross-sectional studies in European whites estimate the prevalence of GON as 7% in the range of 25 to 29 mm Hg, and 14% in the 30 to 34 mm Hg.25 Among otherwise normal subjects with an IOP more than mean + 2 SD, the incidence of glaucomatous visual field loss is approximately 1% per year.26 27 The risk of POAG damage increases nonlinearly at higher IOP; compared with an IOP less than 22 mm Hg, the relative risk (RR) with an IOP of 22 to 29 mm Hg is 12.9 and with IOP of 30 mm Hg or more, the RR is 40.5 Between 30% and 50% of GON in a population occurs in those individuals with a screening IOP of population mean + 2 SD or less. This is not difficult to reconcile, when considering the large number of people with IOP in the normal range and, proportionally, the much smaller number of people with GON. The ratio reverses at higher levels of IOP (Fig. 1) , although this observation emphasizes the weakness of an approach that considers IOP to be a diagnostic criterion for glaucoma.
A relationship between cross-sectional IOP measurements and the presence of glaucoma has also been shown in Japanese people.4 The findings in this study are intriguing when one considers that, first, open-angle glaucoma is the main form of GON in Japanese people and second that mean IOP in this large population study was found to be 13.3 mm Hg (measured by air-puff tonometer). Cases diagnosed as normal-tension glaucoma outnumbered POAG by a ratio of 4.5:1. However, the division between high and normal IOP was placed at 21 mm Hg. This figure was derived from a European population and was obtained by taking an IOP 2 SD above the mean. If the same approach were adopted for the Japanese population, an IOP of 18 or 19 mm Hg would seem more appropriate. Our data suggest that Chinese Singaporean people have an IOP that is typically slightly lower than that in persons of white European background. However, we also found a clear association between cross-sectional IOP measurements and glaucoma in Chinese Singaporeans. Figure 3 shows the relationship between screening IOP and prevalence of GON in selected clinic- and population-based studies.
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| Acknowledgements |
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| Footnotes |
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Submitted for publication January 6, 2003; revised March 24, 2003; accepted April 6, 2003.
Disclosure: P.J. Foster, None; D. Machin, None; T.-Y. Wong, None; T.-P. Ng, None; J.F. Kirwan, None; G.J. Johnson, None; P.T. Khaw, None; S.K.L. Seah, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked "advertisement" in accordance with 18 U.S.C.
1734 solely to indicate this fact.
Corresponding author: Steve K. L. Seah, Glaucoma Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751; snecss{at}pacific.net.sg.
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