Background To investigate the prevalence, risk factors and characteristics of plateau iris configuration (PIC) among American Caucasian, American Chinese and mainland Chinese.
Methods This multicentre, cross-sectional study of non-glaucomatous subjects (40–80 years) included 111 American Caucasian, 116 American Chinese and 110 mainland Chinese. Prevalence of PIC based on ultrasound biomicroscopy imaging was compared among the different ethnic groups. Risk factors and anterior segment optical coherence tomography-measured iris and angle parameters in eyes with PIC were compared.
Results The prevalence of PIC was 25.2% in American Caucasian, 24.1% in American Chinese and 20.9% in mainland Chinese (p=0.73). The presence of PIC was associated with more positive spherical equivalence (OR=1.31, p=0.002) and shorter axial length (OR=0.75, p=0.04). There were significant differences in angle recess area (ARA) (p=0.04), IT750 (p=0.007) and IT2000 (p<0.001) between Chinese and Caucasians who have PIC.
Conclusions The prevalence of PIC did not differ among American Caucasian, American Chinese and mainland Chinese. PIC was associated with non-myopia and shorter axial length. Chinese eyes with PIC had smaller ARA and thicker irides than Caucasian ones. PIC might be a physiological variation of the iris and ciliary body that exists in normal eyes, both in Chinese and Caucasians.
Statistics from Altmetric.com
Glaucoma is the leading cause of irreversible blindness worldwide. In 2010, there were 60.5 million people with primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG), which is predicted to increase to 79.6 million by 2020.1 ,2 Population studies report the prevalence of PACG to be approximately 0.4% in Caucasians over 40 years old.3 ,4 The prevalence of glaucoma is known to be higher in Asians. In a study of Chinese subjects older than 50 years, the prevalence of POAG and PACG was 2.1% and 1.5%, respectively.5
Although patients with plateau iris are often asymptomatic, plateau iris configuration (PIC) has been recognised as one of the anatomical mechanisms of angle closure development along with pupillary block. PIC-associated anterior chamber characteristics include a normal central anterior chamber depth (ACD), a flat iris plane, an iris root that angles sharply forward, and anteriorly positioned or large ciliary processes.6–9 After PIC was initially described,10 ,11 some researchers reported its prevalence among PACG patients as 30% in Singapore,12 30% in India,13 47.8% in China14 and 37.0% in Japan.15 In addition, recent research also reported PIC in POAG.16 These prior studies were in subjects from Asia. There have been no prior studies of plateau iris in a non-glaucomatous Caucasian cohort.
In this study, we examined the prevalence and risk factors for PIC in non-glaucomatous eyes from American Caucasian, American Chinese and mainland Chinese subjects using ultrasound biomicroscopy (UBM). In addition, we compared anterior segment optical coherence tomography (ASOCT) parameters in Caucasian and Chinese eyes with PIC.
Sample and population
This multicentre, cross-sectional study was conducted from May 2008 to December 2010 at the University of California at San Francisco (UCSF) in the USA, and the Zhongshan Ophthalmic Center in Guangzhou, China. All subjects in the USA were consecutively recruited from the General Ophthalmology Service at UCSF, which is a tertiary care centre, although patients seen in this clinic represent a primary clinic population since patients are seen for routine annual checkups and do not represent referrals from other ophthalmologists in the community. The participants in mainland China were recruited from an ongoing population study conducted at Zhongshan Ophthalmic Center, a university-based practice in which patients are seen for primary eye care. Throughout our recruitment process, enrolment rate at the San Francisco study site was more than 70%. At our Guangzhou study site, every one out of 10 subjects in the ongoing population study were selected to constitute our mainland subgroup in this study, and the recruitment rate was greater than 90%. Approximately 120 subjects were recruited for American Caucasian, American Chinese and mainland Chinese separately. Within each group, there were 30 subjects in each age subgroup: 40–50, 50–60, 60–70 and 70–80 years. The inclusion criteria were: (1) American Caucasian (specifically, European derived) descent, American Chinese (both parents of Chinese descent) or mainland Chinese living in Guangdong province, (2) age 40–80 years old and (3) willingness and ability to participate in all components of the study. Exclusion criteria were: (1) history of glaucomatous diseases including PACG and primary angle closure or current use of glaucoma medications, (2) history of ocular surgery or laser therapy, (3) pseudophakia or aphakia, (4) current ocular infection or active inflammation or (5) high refractive error defined as spherical equivalent (SE) <−8.00 dioptres (D) or >+4.00 D.
This study was approved by the Institutional Review Board of the UCSF (IRB: H10260-32107) and the Zhongshan Ophthalmic Center in Guangzhou. Written informed consent was obtained from all participants.
The anterior segment of all subjects was imaged using UBM (model P45, Paradigm Medical, Salt Lake City, Utah, USA). All UBM examinations performed at Guangzhou, China, were conducted by a single experienced UBM examiner (DW). DW later came to San Francisco to be the coordinator of the study. The exact same protocol was followed by an experienced UBM operator, SCL, under the direction of DW. All subjects were imaged under standardised dark conditions with illuminations below 1 lux in the supine position. After topical anaesthesia instillation, an eyecup was placed and saline or hydroxypropyl methylcellulose (Gonak, Akorn Inc, Somerset, New Jersey, USA) was used as the coupling agent. The probe was placed perpendicular to the ocular surface, and images of all four quadrants were obtained. Variation in accommodation was minimised by asking participating subjects to fixate on a target on the ceiling with the contralateral eye. Only images in which the scleral spur, drainage angle, ciliary body and a half chord of the iris could be clearly visualised were accepted.
For each subject, anterior segment parameters were also obtained by ASOCT (Visante OCT, Carl Zeiss Meditec, Dublin, California, USA) under dark room conditions and analysed with the Zhongshan Angle Assessment Program (Guangzhou, China). Parameters assessed in this study included angle opening distance at 500 and 750 microns from the scleral spur (AOD500 and AOD750), trabecular iris surface area at 500 and 750 microns from the scleral spur (trabecular-iris space area and TISA750), iris thickness at 750 and 2000 microns from the scleral spur (IT750 and IT2000), and angle recess area at 750 microns from the scleral spur (ARA). All parameters from the ASOCT were analysed by taking the mean of the nasal and temporal angles.
Images from the right eye were used for analysis. The left eye's data were used when the right eye did not meet the inclusion criteria. The presence or absence of PIC was determined based on UBM images. Within a quadrant, PIC was defined if the eye has all three of the following criteria: 1) anteriorly directed ciliary body which supports the peripheral iris, 2) an absent ciliary sulcus, and 3) a central flat iris plane. In a given eye, if at least two quadrants fulfilled the criteria for PIC, then the eye was classified as having PIC. Two observers independently assessed all UBM images. One of the two observers evaluated the images again 2 weeks later. A single trained observer performed ASOCT image analyses in a standardised manner which have been reported in a previous study.17
Other related exams
All subjects underwent a detailed slit-lamp exam by a well-qualified ophthalmologist where both vertical and horizontal cup to disc ratios and gonioscopy were included. Axial length (AL), ACD and lens thickness (LT) by ultrasonic biometry (E-Z Scan A/B 5500+, Sonomed Inc, Lake Success, New York, USA) were measured. SE (SE=spherical power + ½ cylindrical power), intraocular pressure (IOP) measurement by Goldmann applanation tonometry and central corneal thickness (CCT) measurement by ultrasound pachymetry were also conducted. On gonioscopy, the anterior chamber angle width was determined in each of the four quadrants using the Shaffer classification scheme. Narrow angle was defined if at least two quadrants were grade 0, 1 or 2 by Shaffer classification.
We compared the distribution of demographic variables and ocular characteristics between each of the three study groups using one-way analysis of variance (ANOVA) tests. The Pearson's χ2 test was used to evaluate whether the prevalence of PIC was different in each of the three study groups. Within each study group, we compared the distribution of demographic variables and ocular characteristics between subjects with and without PIC using independent-sample t tests (continuous) and χ2 tests (categorical variable). Multivariate logistic regression models were created to examine the independent association between demographic/ocular factors and presence/absence of PIC. Subjects were divided into five groups based on SE: 1=marked myopia (<−6 to −8 D), 2=moderate myopia (<−3 to −6 D) and 3=low myopia (<−0.5 to −3 D); 4=emmetropia (−0.5 to <+2 D); and 5=hyperopia (≥+2 D). AOD500, AOD750, TISA500, TISA750, IT750, IT2000 and ARA in patients who have PIC were compared between the Caucasian and Chinese cohorts using multivariate linear regressions, adjusting for age, gender, SE and AL. Results were considered statistically different if the p value was <0.05. κ Test was calculated to determine the intraobserver and inter-observer reproducibility in diagnosing plateau iris. All statistical analyses were performed using the Statistical Package for Social Sciences software (SPSS V.16.0, SPSS Inc, Chicago, Illinois, USA).
There were 337 subjects analysed in the study including 111 American Caucasian, 116 American Chinese and 110 mainland Chinese. The mean ages for these study groups were 59.8±11.6, 59.8±12.3 and 59.4±11.7 years, respectively (p=0.82), and the percentages of women were 45.1%, 51.7% and 54.5%, respectively (p=0.68). Comparisons of SE, AL, LT and ACD among the three ethnic groups showed significant differences (all p<0.001). American Caucasians were found overall to have more myopia, longer AL, thinner lens and deeper anterior chamber.
Figure 1 presents the prevalence of PIC in each of the three groups, with 25.2% in American Caucasian, 24.1% in American Chinese and 20.9% in mainland Chinese (p=0.73). The intraobserver and inter-observer reproducibility for diagnosing plateau iris was good (κ=0.815 and 0.874, respectively).
Table 1 presents the demographic and ocular characteristics of subjects with and without PIC for each of the three groups. In the American Caucasian group, when comparing subjects with PIC with those without, SE was more positive (−0.28 vs −1.88 D, p<0.0001), ACD was shallower (3.22 vs 3.46 mm, p=0.01), AL was shorter (23.26 vs 24.56 mm, p<0.0001) and proportion of eyes with narrow angle was greater (39.2% vs 15.6%, p=0.015). In the American Chinese group, subjects with PIC had more positive SE (0.12 vs −1.82 D, p<0.0001) and shorter AL (23.34 vs 24.45 mm, p=0.007) than their non-PIC counterparts. In the mainland Chinese group, subjects with PIC were also found to have more positive SE (0.72 vs −0.20 D, p=0.007).
When factors such as SE, ACD, AL, LT, IOP and CCT were compared between American Chinese and mainland Chinese, no significant differences were detected. We therefore combined the two groups to form one ethnic Chinese group. Among the entire study population, PIC was associated with SE (OR=1.31, p=0.002) and AL (OR=0.75, p=0.04), but not with age (p=0.27), gender (p=0.69), ethnicity (p=0.054), ACD (p=0.65), LT (p=0.44), IOP (p=0.43), CCT (p=0.59) or narrow angle (p=0.79). Ethnicity here refers to a comparison between the combined ethnic Chinese group and Caucasians.
Study subjects were divided into five groups based on their SE: 1=marked myopia (<−6 to −8 D), 2=moderate myopia (<−3 to −6 D) and 3=low myopia (<−0.5 to −3 D); 4=emmetropia (−0.5 to <+2 D); and 5=hyperopia (≥+2 D) (figure 2). Significant difference in PIC prevalence was detected among the five groups using ANOVA. We combined groups 1, 2 and 3 to form a myopia group, and groups 4 and 5 to form a non-myopia group, based on pair-wise comparisons. The ORs of non-myopia in eyes with PIC is 4.90 (95% CI 1.95 to 12.31) in American Caucasian, 4.14 (95% CI 1.59 to 10.74) in American Chinese, 3.69 (95% CI 1.02 to 9.36) in mainland Chinese and 4.29 (95% CI 2.36 to 7.77) in the entire study population as shown in table 2.
Comparisons of mean ARA, IT750 and IT2000 in subjects with PIC between Caucasian and Chinese were shown in table 3. After adjusting for age, gender, AL and SE, there were significant differences in ARA (p=0.04), IT750 (p=0.007) and IT2000 (p<0.001) between Chinese and Caucasians who have PIC. Chinese who have PIC were also found to have smaller AOD500, AOD750, TISA500 and TISA750 than their Caucasian counterparts, though these difference were not statistically significant.
PIC has been reported as an anatomical variant of iris and ciliary processes in glaucomatous eyes.7 ,8 Possible mechanisms of PIC formation was suggested to be anterior rotation of the ciliary processes caused by forward pushing of the lens–zonule complex.6 ,18 ,19 Based on our previous study, the prevalence of plateau iris in patients who underwent laser peripheral iridotomy was 33.3% in Asian and 32.1% in Caucasians,20 similar to those studies done in Singapore, India, China and Japan.12–15 In this multicentre, cross-sectional study of subjects without glaucoma, we found the prevalence of PIC to be 25.2% in American Caucasians, 24.1% in American Chinese and 20.9% in mainland Chinese subjects. To our best knowledge, our findings suggest for the first time that PIC exists in glaucomatous eyes and in normal non-glaucomatous eyes. This is also the first report of PIC prevalence in Caucasian non-glaucomatous eyes.
Furthermore, we found two factors associated with PIC, namely, SE and AL. Specifically, those eyes with shorter AL or higher SE were predisposed to higher prevalence of PIC, which makes sense mechanistically. Previous studies done in patients with PIC7 ,13 ,15 ,21 showed similar results to our current study, where plateau iris syndrome eyes were found to be more likely to be non-myopic and have shorter AL. In fact, based on our analysis, emmetropic and hyperopic eyes are 2.82 times more likely to have PIC when compared with myopic eyes, suggesting that myopia might be a protective factor against PIC formation. Moreover, in this study of normal non-glaucomatous eyes, the average SE of subjects who had PIC was similar to those of glaucoma patients in previous studies. However, the average AL of subjects who have PIC in our study is longer than those reported previously in glaucoma patients with PIC. We therefore hypothesise that the longer AL can potentially provide longer distance between the iris and trabecular meshwork, even in the event of anterior angulations of the ciliary processes, which in turn helps to prevent angle closure formation. This is consistent with previous reports, where among patients with PIC, those with narrow angles had shorter AL than those with POAG.22 On the other hand, we did not find any difference in AL between patients who had PIC and those who did not among mainland Chinese subjects. This can be explained by the higher number of non-myopic eyes in this particular group.
For ASOCT-measured parameters, AOD500, AOD750 and TISA750 of eyes with PIC were not significantly different between Caucasian and Chinese. We therefore hypothesise that the configuration of the anterior chamber angle in eyes with PIC is similar between the two ethnicities. In addition, in PIC eyes we found that Chinese irides (IT750 and IT2000) were thicker than Caucasians, consistent with what was previously reported.17 ,23 We then deduced that similar trends might be found about more peripheral irides. Specifically, Chinese might have thicker peripheral irides closer to the angle root than Caucasians. This might further lead to smaller ARA in Chinese. With smaller ARA, the irides in Chinese eyes with PIC are more likely to be closer to the functional trabecular meshwork, especially in the case of increasing pressure in the posterior chamber, resulting in clinically significant angle closure in Chinese eyes with PIC than their Caucasian counterparts.
There are limitations to our study. We recruited people over the age of 40 years, and so even though PIC was previously reported in patients as young as 12 years old,24 we are not able to present prevalence of PIC in a younger population. All subjects in the USA were consecutively recruited from the General Ophthalmology Service at UCSF. Although we have made conscious efforts to recruit healthy individuals who presented for annual check-ups, subjects who were clinic-based might still differ significantly from those participants recruited from a population study such as those recruited in China. This difference might obscure our findings in some ways, and future studies where patients from multiple study sites were all recruited from population studies might be needed to further verify the findings in our current study. Since primary angle closure suspects were not excluded from the study population, this might impose a limitation where irides of subjects who were angle closure suspects were more likely classified as having PIC, though efforts were made to have two masked reviewers analyse each UBM image independently based on the same set of criteria. We are also not certain if SE distribution in our study subjects is representative of the local ethnic population. In future studies, we intend to recruit patients based on SE to further extrapolate the relationship between SE and PIC formation.
In summary, although the prevalence of PIC did not differ among American Caucasian, American Chinese and mainland Chinese, smaller ARA and thicker irides were found in Chinese who have PIC as compared with their Caucasian counterparts, potentially leading to more clinically significant angle closure. The prevalence of PIC in myopic eyes is lower than in non-myopic eyes. Longer AL is a protective factor while higher SE is a risk factor for PIC. Moreover, since the prevalence of PIC did not differ between Caucasian and ethnic Chinese, and the Chinese are known to have higher risk of angle closure, there are likely other important contributory factors to angle closure development, such as iris thickness and lens vault, particularly in the Chinese. Additionally, PIC might be a physiological variation of the iris and ciliary body that exists in normal eyes, both in Chinese and Caucasians.
YL and YEW contributed equally.
Contributors Authors included on this paper fulfil the criteria of authorship. And there is no one else who fulfils the criteria but has not been included as an author. Contributions were as follows YL: study design, patient recruitment, image and statistical analysis, manuscript preparation. YEW: study design, image gathering, imaging analysis, manuscript preparation, manuscript revisions. DW: patient recruitment, imaging gathering, manuscript revision. GH: study design, patient recruitment, imaging gathering. MGH: Patient recruitment, manuscript revision. MQ: manuscript revision. SL (corresponding): study design, manuscript preparation, manuscript revision, corresponding author.
Funding This work was supported by National Eye Institute, Grant number EY002162 and National Natural Science Foundation of China, Grant number 81260147. The sponsor or funding organisation had no role in the design or conduct of this research.
Competing interests None.
Patient consent Obtained.
Ethics approval UCSF.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.