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1From the Institute of Ophthalmology, University College London (UCL), London, United Kingdom; the 2State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; 3Glaucoma Research Unit, Moorfields Eye Hospital, London, United Kingdom; and the 4Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.
| Abstract |
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METHODS. Clustered random sampling was used to select adults aged 50 years and older in Liwan District, Guangzhou. Gonioscopy was performed on all the subjects. The geometric angle width was graded in the superior and inferior quadrants, according to the Spaeth system. In addition, apparent and true iris insertion was classified in four quadrants with static and dynamic gonioscopy. The peripheral iris profile was described as steep, regular, concave, and plateau. Data are presented for all phakic right eyes. Secondary or iatrogenic cases were excluded in the analysis of peripheral anterior synechiae (PAS).
RESULTS. Among 1405 participants in the study, data from 1330 (95%) right eyes were available for analysis. Iridotrabecular angles (ITA)
20° were present in 36.9% (95% CI: 34.3%40.0%) of eyes superiorly and in 27.9% (95% CI: 25.5%30.4%) inferiorly. Narrower ITAs were more common in the older people (sex-adjusted odds ratio [OR] = 1.1 per year of life; P < 0.001) and the women (age-adjusted OR = 2.5, P < 0.001). Apparent iris insertion of grade A or B (with pigmented trabecular meshwork not visible) by quadrant was observed in 27.2% superiorly, 12.0% nasally, 7.7% inferiorly, and 14.2% temporally. Narrow angles (in which pigmented trabecular meshwork was not visible in three or more quadrants) were identified in 11.0% (95% CI: 9.3%12.7%) of right eyes. Overall, 33.3% of eyes had a steep iris profile, 54.2% were normal, 2.7% were concave, and 10.1% were graded plateau. PAS were seen in 30 of 146 (20.5%) eyes with narrow angles and in 7 (0.6%) of 1184 eyes with angles that did not meet criteria for narrow angles. PAS were more likely with narrower angles, with 0%, 0.3%, and 1.9% of eyes with a mean ITA of 40°, 30 °, and 20°, respectively, having PAS as opposed to 12.6% and 27.5% for those with ITA 10 ° and 0°, respectively.
CONCLUSIONS. Ten percent of this population of southern Chinese persons 50 years of age and older had narrow angles. PAS were present in one fifth of these people. From these cross-sectional data, it is unclear which of these individuals are at highest risk of the development of primary angle-closure (PAC) glaucoma. Longitudinal studies are necessary to determine appropriate strategies for preventing this potentially blinding outcome.
No data outlining the characteristics of iridotrabecular angle (ITA) anatomy according to modern classification systems are available for mainland China. Researchers studying Singapore Chinese and Mongolians have documented high rates of anatomically narrow ITAs (approximately 6.5% among people aged 40 years and over for both populations).5 Extrapolating these results to China, Foster estimated the number of persons in China at high risk of angle-closure to be approximately 28 million. Epidemiologic data on ACG in China are limited.
We therefore performed a population-based study of glaucoma prevalence and risk factors in Guangzhou, China. We report on both the gonioscopic anatomy of people with and without primary angle closure (PAC), detailing variation by age and sex, and on the association of peripheral anterior synechiae (PAS) with gonioscopic findings.
| Methods |
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Slit lamp (SL-8Z; Topcon, Tokyo, Japan; with a D1x digital image system; Nikon, Tokyo, Japan) gonioscopy was performed by using a Goldmann-type, one-mirror lens (Haag Streit, Bern, Switzerland) at x25 magnification with low ambient illumination by the same observer (MH), whose observations were standardized against those of an experienced gonioscopist (PJF). A narrow vertical beam 1 mm in length was offset vertically for superior and inferior quadrants, horizontally for nasal and temporal quadrants. Care was taken to prevent light from falling on the pupil. Small movements of the lens were made, if necessary, to visualize the drainage angle over the convexity of the iris, taking care not to cause inadvertent indentation. Dynamic examination with increased illumination using the Goldmann lens was performed after static gonioscopy of all four quadrants was completed. In cases in which iridotrabecular contact could not be satisfactorily reversed, a four-mirror lens was used (Carl Zeiss Meditec, Oberkochen, Germany). Angle width was estimated in the superior and inferior quadrants as the angle in degrees between a tangent to the surface of the trabecular meshwork (TM) and a tangent to the peripheral third of the iris and then was recorded in five-point categories (0°, 10°, 20°, 30°, and
40°). This grading of geometric angle width was adapted from the Shaffer system7 with an attempt to standardize the reporting and make it comparable to data in other studies, although we did employ Spaeths principle of estimating angle width between the TM and the peripheral third of the iris. Furthermore, iris insertion was recorded as: A (anterior to Schwalbes line), B (behind Schwalbes line), C (at the scleral spur), D (with a narrow, visible ciliary body band), and E (with a very wide ciliary body band). The point of presenting contact between the iris and the posterior surface of the corneoscleral coat before indentation was recorded as the "apparent" iris insertion, whereas the point of contact identified during dynamic examination was recorded as the "true" iris insertion.8 Dynamic gonioscopy was also used to identify the existence and extent of PAS and pathologic changes of angles (including iris stomal pigment deposition on TM). The iris profile was classified as steep, plateau, regular, and concave, with the grade chosen to best reflect the entire 360° architecture. The plateau iris profile was added to the traditional Spaeth grading scheme and was deemed to be present if the iris rose steeply from its point of insertion but then made an abrupt angulation away from the corneoscleral wall, resulting in a relatively deep axial anterior chamber and a centrally flat iris plane.
The overall angle status was further classified as narrow or not. A narrow angle (synonymous with suspect PAC and an occludable angle) was defined as one in which the posterior, usually pigmented, TM was hidden from view during static gonioscopy (i.e., apparent iris insertion).
All data are presented for right phakic eyes only. Given that the gonioscopic angle width and iris insertion are ordinal variables but do not comply with normal distribution, the Wilcoxon rank test was used for comparison between two groups, the Wilcoxon Kruskal-Wallis test for multiple-group comparison, and the Wilcoxon signed rank test for matched-pair comparison.9 The
2 test was used to test the similarity of the proportions. A regression model was fitted with a mean of angle width on superior and inferior quadrants as an outcome, with age and sex as explanatory variables. Logistic regression was used when assessing for factors associated with the posterior pigmented TMs being visible in more than one quadrant.
| Results |
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50 years participated in the study, representing 75.3% of those eligible. As reported previously, younger men and older persons were less likely to participate.6 Gonioscopy data on the right eye were not available in 28 subjects, including: 2 who refused, 16 subjects who were seen at home, 4 who were unable to tolerate gonioscopy, 4 with corneal opacity, and 2 for other reasons. Aphakic and pseudophakic eyes (47 eyes) were also excluded, leaving data on 1330 right eyes available for analysis. The mean age was 64.9 years (range, 5083), and 755 (56.8%) subjects were women.
Agreement on Gonioscopic Examination
The agreement using Shaffer grading of angle width of the superior and inferior quadrants between the study gonioscopist (MH) and another experienced examiner (PJF) was assessed based on masked grading of 28 eyes of 28 subjects. Weighted
statistics (±SE) for Shaffer grades of superior and inferior quadrants were 0.63 ± 0.18 and 0.62 ± 0.25, respectively. The superior quadrant grades by PJF (mean = 2.59) were narrower than for MH (mean = 2.81) but the difference was not statistically significant (Wilcoxon rank test, P = 0.31). Differences in grading the inferior quadrant were similar. The
statistics for the Spaeth apparent iris insertion grade in the superior, inferior, nasal, and temporal quadrants were 0.69 ± 0.24, 0.84 ± 0.37, 0.71 ± 0.35, and 0.77 ± 0.29, respectively. The
statistic for the iris profile was found to be 0.81 for the steep, 0.93 for the regular, and 0.71 for the plateau profile. No case involved a concave profile in this small group of subjects, thus preventing an evaluation of that profile. Because of the low number of persons with narrow angles in the initial standardization, we repeated the comparison in laser iridotomy treated and untreated eyes, with a weighted
of 0.82 for the determination of narrow angles in 44 eyes.
Gonioscopic Angle Width
The angle width was narrower in the women than in the men, and less in the older persons in both the superior and inferior quadrants (Wilcoxon Kruskal-Wallis test, P = 0.001, Table 1 ). The superior quadrant was significantly more narrow than the inferior (Wilcoxon sign-rank test for matched observations, P < 0.001). Using angle width as a continuous variable, and adjusting for sex, we found the angle width to decrease by 0.4 Shaffer grades for each 10 years of age. Adjusting for age, the women had on average a 0.5 Shaffer grade shallower angle than did the men.
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2 test; P < 0.001) and tended to be higher in the women than in the men (men: 59.0%, women 72.5% in the superior quadrant;
2 test, P < 0.001).
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80 years, compared with those aged 50 to 59 years were 2.94 (P < 0.001), 4.17 (P < 0.001), and 4.97 (P < 0.001; Table 3 ). The age-adjusted OR was 2.00 in the women relative to the men (P < 0.001). When those eyes with narrow angles and elevated intraocular pressure (IOP) or PAS and those with GON were excluded, the overall prevalence of narrow angles was 11.0% (95% CI: 9.3%12.7%). This rate of narrow angles increased to 17.5% (95% CI: 15.5%19.6%) if a less-stringent definition was used (posterior TM not present in two or more quadrants).
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2 test, P < 0.001).
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2 test; P < 0.001; Table 5 ). The proportion of steep profiles increased with age, from 19.3% in those aged 50 to 59 years to 47.8% in those aged 80+ years (
2, P < 0.001). However, the proportion decreased in the
80-year female group, although not in the older men. The proportion of concave profiles was higher in men but was not associated with age. In a univariate analysis, plateau iris configuration was more common in the women (11.6%) than in the men (8.1%,
2, P = 0.033). Using multiple logistic regression to examine the association between iris profile, age, and sex, the adjusted OR of a steep profile increased: 2.19 (P < 0.001), 3.48 (P < 0.001), and 3.79 (P < 0.001) among people aged 60 to 69, 70 to 79, and
80 years, respectively, compared with those aged 50 to 59 years. The women were twice as likely as the men to have a steep iris profile (OR: 2.14; P < 0.001, adjusted for age). The pattern was repeated among those with a plateau iris profile. The ORs (adjusted for sex) for the persons aged 60 to 69, 70 to 79, and
80 years (versus those aged 5059 years) were 3.05 (P < 0.001), 3.36 (P < 0.001), and 3.94 (P < 0.001). In the women, the odds of a plateau iris configuration were 48% greater than in the men, after adjustment for age differences (OR: 1.48; P < 0.001).
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| Discussion |
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50 years older supports previous findings7 8 that angle width is narrowest in the superior quadrant and widest in the inferior quadrant. This variation in angle width by quadrant has been postulated to be an artifact that is due to gravitational forces in the sitting position and to indentation of the superior cornea by the upper eyelid.10 Ultrasound biomicroscopy (UBM) data (obtained in the supine position) from examinations of this cohort suggest that the superior and inferior quadrants are narrowest when this imaging modality is used (He M, Foster PJ, Friedman DS, unpublished data, 2006). These inconsistent findings between gonioscopy and UBM suggest that gravitational forces certainly may play a role in producing a wider inferior angle. However, placing the water bath cup in the eye for UBM may also lead to artifacts, and so one cannot interpret these findings as being truly indicative of in vivo anatomy. We believe that the artifact induced by the eyecups on the limbus is not likely to have caused the findings, because the probe was in the center of the eye up as subjects gazed in the direction of the target, and care was taken to make sure that the eyecup was not pressing on the cornea.
The proportions of angles graded as Shaffer 2 or narrower was 37.9% in the superior and 27.9% in the inferior quadrant in the current cohort. This rate is much higher than has been reported in an older white population in the United States, although gonioscopy was not standardized in that study (3.8%, N = 5219, age
55 years),11 and is similar to that found in a clinic-based Vietnamese in California. (47.8%, N = 178, age
55 years).12 One study in Canadian Eskimos (61.1%, N = 18, age
40 years)13 reported even higher rates of narrow angles in a younger cohort, a finding that is expected given the very high rates of PAC glaucoma (PACG) in this population.
We also found that the drainage angles were narrower in the older people and the women in our study, consistent with other reports in multiple populations.14 15 16 This higher prevalence of narrow angles certainly contributes to the higher rates of PAC/PACG in these groups.
A high proportion of those with narrow angles in primary gaze had a true iris insertion at the level of the scleral spur or the ciliary body. In fact, only 18 right eyes had a true insertion grade A (anterior to Schwalbes line) or grade B (behind Schwalbes line) in the superior quadrant, with only six eyes satisfying these criteria in the inferior quadrant. These cases with grade A or B "true" iris insertion, diagnosed using dynamic gonioscopy, all had pathologic PAS, indicating that tight apposition of iris to the angle is associated with PAS formation and damage to angle structures. While this can be said about angles with high "true" iris insertion, the effect of appositional closure in dim conditions on the long-term health of the eye remains unknown.
In a clinic-based study comparing the level of iris insertion in white and East Asian populations,17 investigators reported that East Asian persons had 27%, 69%, and 4% grade C, D, and E iris insertion at the circumference from 12 to 6 oclock on the right eye, respectively. The proportions with C, D, and E insertions in our study population is remarkably similar (36%, 55%, and 7% for grade C, D, and E superiorly and 20%, 71%, and 9% inferiorly, respectively). Comparison of these proportions with those reported in white persons suggests that East Asian people have a more anteriorly located iris insertion. Although some have argued that this disparity is due to a tendency of the iris insertion to move anteriorly over time, so-called "creeping" angle-closure,17 18 we believe this theory is speculative and requires longitudinal observations to confirm or deny.
The clinical grading of iris profile used in the present study was adapted from the Spaeth system8 by adding an additional grade, plateau, to the original three categories of steep, regular, and concave. In general, a steep iris profile is believed to be due to relative pupil block causing forward bowing of the iris. In this study, the proportion with a steep iris profile increased with age, from 19% in subjects 50 to 59 years of age, to 48% in those 80+. Also, the women were nearly twice as likely as men to have a steep iris profile. A concave profile was seen in only 2.7% of the studied population, and those having it tended to be younger. A plateau configuration was present in approximately 15% of all age groups, with a slightly higher proportion of the women having this iris appearance. However, this observation must be interpreted with some caution, as the classification of "plateau" iris profile made using gonioscopy describes only the anterior surface of the iris and is somewhat subjective. Without ultrasound examination, it is not possible to determine the cause of iris angulation.
PAS provide perhaps the best evidence that the presence of a narrow angle leads to adverse sequelae and is a likely harbinger of a poorer outcome. The rate of PAS in Shaffer grade 4 angles was 0%, increasing to 1.9% in grade 2, with a further sharp increase to 12.6% in grade 1 and 27.5% in grade 0. This increasing prevalence of PAS in angles that appear more narrow before compression or manipulation with the gonioscopy lens suggests that those with narrower angles are at higher risk of the development of problems secondary to anatomically narrow angles. Others have reported a similar doseresponse increase in prevalence of PAS.19 It can be at times difficult to differentiate between areas of atypical iris dysgenesis (congenital), iris processes, and PAS (acquired). Only a prospective study can determine whether these structures are genuinely acquired, pathologic phenomena and whether their presence reflects an increased risk of raised IOP and subsequent glaucomatous optic neuropathy.
In summary, our study provides further detailed epidemiologic data on the gonioscopic characteristics in an adult population in an urban area of mainland China. First, we confirmed a higher rate of narrow angles and more anterior iris insertion in this Chinese cohort when compared with European-derived populations. Second, we confirmed that narrowing of the drainage angle is more common in older people and women. Third, we estimated that the rate of narrow angles in this adult Chinese population aged
50 could be as high as 11.0%, highlighting the need to use gonioscopy to assess the angle status carefully in clinical practice. Designing optimal screening strategies and assessing the viability of prophylactic treatment for this large proportion of the older Chinese population remains a major challenge for the public health sector.
| Footnotes |
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Submitted for publication March 22, 2006; revised May 17, 2006; accepted September 18, 2006.
Disclosure: M. He, None; P.J. Foster, None; J. Ge, None; W. Huang, None; D. Wang, None; D.S. Friedman, None; P.T. Khaw, 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: Mingguang He, Department of Preventive Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou 510060, Peoples Republic of China; mingguang_he{at}yahoo.com.
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