Monisha E. Nongpiur

Lens Vault, Thickness, and Position in Chinese Subjects with Angle Closure

PURPOSE To investigate the association of lens parameters-specifically, lens vault (LV), lens thickness (LT), and lens position (LP)-with angle closure. DESIGN Prospective, comparative study. PARTICIPANTS One hundred two Chinese subjects with angle closure (consisting of primary angle closure, primary angle-closure glaucoma, and previous acute primary angle closure) attending a glaucoma clinic and 176 normal Chinese subjects with open angles and no evidence of glaucoma recruited from an ongoing population-based cross-sectional study. METHODS All participants underwent gonioscopy and anterior-segment optical coherence tomography (AS OCT; Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure LV, defined as the perpendicular distance between the anterior pole of the crystalline lens and the horizontal line joining the 2 scleral spurs, on horizontal AS OCT scans. A-scan biometry (US-800; Nidek Co, Ltd, Tokyo, Japan) was used to measures LT and to calculate LP (defined as anterior chamber depth [ACD] +1/2 LT) and relative LP (RLP; defined as LP/axial length [AL]). MAIN OUTCOME MEASURES Lens parameters and angle closure. RESULTS Significant differences between angle-closure and normal eyes were found for LV (901±265 vs. 316±272 μm; P<0.001), LT (4.20±0.92 vs. 3.90±0.73 mm; P = 0.01), LT-to-AL ratio (0.18±0.04 vs. 0.16±0.03; P<0.001), ACD (2.66±0.37 vs. 2.95±0.37 mm; P<0.001), and AL (22.86±0.93 vs. 23.92±1.37 mm; P<0.001), but no significant differences were found for LP (4.76±0.51 vs. 4.90±0.54 mm; P = 0.34) or RLP (0.21±0.02 vs. 0.20±0.02; P = 0.14). After adjusting for age, gender, ACD, LT, and RLP, increased LV was associated significantly with angle closure (odds ratio [OR], 48.1; 95% confidence interval [CI], 12.8-181.3, comparing lowest to highest quartile), but no association was found for LT (OR, 1.78; 95% CI, 0.76-4.16), LP (OR, 1.94; 95% CI, 0.59-6.31), or RLP (OR, 2.08; 95% CI, 0.66-6.57). There was low correlation between LV and LT (Pearsons correlation coefficient [PCC], 0.17), between LV and RLP (PCC, 0.08), or between LV and LP (PCC, 0.2). CONCLUSIONS Eyes with angle closure have thicker lenses with greater LV compared with normal eyes. The LV, which represents the anterior portion of the lens, is a novel parameter independently associated with angle closure after adjusting for age, gender, ACD, and LT.

Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR) = 1.22; P = 5.33 × 10−12), rs3753841 in COL11A1 (per-allele OR = 1.20; P = 9.22 × 10−10) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR = 1.50; P = 3.29 × 10−9). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Novel Association of Smaller Anterior Chamber Width with Angle Closure in Singaporeans

PURPOSE To describe variations in anterior chamber width (ACW) and investigate its association with the presence of narrow angles. DESIGN Cross-sectional study. PARTICIPANTS We recruited 2047 subjects aged 50 years or more from a community polyclinic and 111 subjects with primary angle closure (PAC) or primary angle closure glaucoma (PACG) from an eye hospital in Singapore. METHODS All participants underwent gonioscopy, anterior chamber depth (ACD) and axial length (AL) measurement (IOLMaster; Carl Zeiss, Jena, Germany), and anterior-segment optical coherence tomography (AS-OCT, Visante, Carl Zeiss Meditec, Dublin, CA). Customized software was used to measure the ACW, defined as the distance between the scleral spurs in the horizontal (nasal-temporal) axis of AS-OCT scans. An eye was deemed to have narrow angles if the posterior trabecular meshwork was not visible for at least 180 degrees on non-indentation gonioscopy with the eye in the primary position. MAIN OUTCOME MEASURES Anterior chamber width and narrow angles. RESULTS Data on 1465 community-based subjects were available for analysis. Anterior chamber width was significantly smaller in women compared with men (11.70 mm vs. 11.81 mm, respectively, P<0.001) and decreased significantly with age (P for trend <0.001). Significant predictors of smaller ACW were lower educational level, lower body mass index, shorter AL, shallower ACD, and Chinese race. Of the 1465 subjects, 315 (21.5%) had narrow angles on gonioscopy. Mean ACW was smaller in eyes with narrow angles compared with those without narrow angles (11.60 mm vs. 11.80 mm, P<0.001). The age- and gender-adjusted odds ratio for the highest quartile compared with the lower 3 quartiles of ACW with the presence of narrow angles was 3.4 (95% confidence interval, 2.3-5.0; P for trend <0.001). Hospital-based subjects with PAC/PACG had even smaller ACW than community subjects with narrow angles (11.33 mm vs. 11.60 mm, P<0.001). CONCLUSIONS In this cross-sectional study, ACW was smaller in women, Chinese persons, and older persons, and was associated with narrow angles in 2 different study populations. These data suggest that a smaller ACW may represent a novel risk indicator for angle closure.

Angle closure glaucoma: a mechanistic review.

Purpose of review With recent advances in imaging techniques such as anterior segment optical coherence tomography and ultrasound biomicroscopy, there is a better understanding of nonpupil block mechanisms and novel risk factors contributing to the pathogenesis of angle closure glaucoma. Recent findings Recent studies suggest that multiple anatomical and physiological factors interplay in the pathogenesis of angle closure glaucoma. The association of greater iris convexity, area and thickness with narrow angles could result in a more anterior bowing and crowding of the peripheral iris. Other novel anatomic parameters such as greater lens vault, smaller anterior chamber width, area and volume, independently increase the risk of having angle closure. Dynamic increase or lesser reduction in iris volume during dilation supports the theory of physiological predisposition to the disease process. Choroidal expansion has been demonstrated in untreated and treated, acute and chronic primary angle closure eyes. It remains unknown whether this finding is a cause or effect in this condition. Summary With a wider availability of imaging tools and a better understanding of risk factors and mechanisms, clinicians maybe able to more accurately identify those at greater risk of developing angle closure disease and tailor their treatment according to the predominant factor(s) involved.

Increased iris thickness and association with primary angle closure glaucoma

Aims To investigate the relationship between quantitative iris parameters and angle closure disease. Methods Participants with angle closure were recruited prospectively from glaucoma clinics. Anterior segment optical coherence tomography (AS-OCT) was performed under standardised dark conditions. Customised software was used on horizontal AS-OCT scans to measure iris thickness at 750 um (IT750) and 2000 um (IT2000) from the sclera spur, maximal iris thickness (ITM) and cross-sectional area of the iris (I-Area). Results 167 Angle closure (consisting of 50 primary angle-closure (PAC), 73 primary angle closure glaucoma (PACG) and 44 fellow eyes of acute PAC) and 1153 normal participants were examined. After adjusting for age, sex, pupil size and anterior chamber depth, mean IT750 (0.499 vs 0.451 mm, p<0.001), IT2000 (0.543 vs 0.479 mm, p<0.001), ITM (0.660 vs 0.602 mm, p<0.001) and I-Area (1.645 vs 1.570 mm2, p=0.014) were significantly greater in angle closure (combined groups) versus normal eyes. Multivariate adjusted odd ratios (OR) of each parameter for the angle closure as compared with normal eyes were: IT750 OR1.7 (95% CI 1.1 to 2.7, p=0.032); IT2000 OR2.2 (95% CI 1.3 to 3.8, p=0.006) and ITM OR2.2 (95% CI 1.3 to 3.6, p=0.003), respectively, per 0.1 unit increase. Conclusions Increased iris thickness is associated with angle closure.

Anterior segment optical coherence tomography parameters in subtypes of primary angle closure.

PURPOSE To compare anterior segment parameters, assessed by anterior segment optical coherence tomography (ASOCT), in subjects categorized as primary angle closure suspect (PACS), primary angle closure (PAC), primary angle closure glaucoma (PACG), and previous acute PAC (APAC); and to identify factors associated with APAC. METHODS This was a prospective ASOCT study of 425 subjects with angle closure (176 PACS, 66 PAC, 125 PACG, and 58 APAC). Customized software was used to measure ASOCT parameters, including angle opening distance (AOD750), trabecular-iris space area (TISA750), anterior chamber depth, width, area and volume (ACD, ACW, ACA, ACV), iris thickness (IT750), iris area (IAREA), and lens vault (LV). Mean differences in anterior segment parameters were evaluated by analysis of covariance (ANCOVA) adjusted for age, sex, and pupil diameter (PD). RESULTS Comparison among the different subgroups showed that ACD, ACA, and ACV were smallest, and IT750 thickest in the APAC group compared with the other subgroups (P < 0.001). LV was greatest in the APAC group (1218 ± 34 μm) followed by PAC (860 ± 31 μm), PACG (845 ± 23 μm), and PACS (804 ± 19 μm), respectively (P = <0.001). While the APAC group had the narrowest angles, the PACS group had the widest (P < 0.001 for both AOD750 and TISA750). Logistic regression showed that greater LV (P = <0.001), narrower TISA750 (P = <0.001), and thicker IT750 (P = 0.007) were the major determinants of APAC. CONCLUSIONS Eyes with APAC had the narrowest angles, smallest anterior segment dimensions, thickest iris, and largest LV compared with PACS, PAC, and PACG. LV, TISA750, and IT750 were the major determinants of APAC.

Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations

Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent. We have followed up on all suggestive signals of association with CCT (P < 10(-4)) from the previously reported meta-analysis comprising Indians and Malays in a sample of Chinese individuals (n= 2681). In the combined sample (n= 7711), strong evidence of association was observed at four novel loci: IBTK on chromosome 6q14.1; CHSY1 on chromosome 15q26.3; and intergenic regions on chromosomes 7q11.2 and 9p23 (8.01 × 10(-11) < λ(GC) corrected P(meta) < 8.72 × 10(-8)). These four new loci explain an additional 4.3% of the total CCT variance across the sample cohorts over and above that of previously identified loci. We also extend on a previous finding at a fifth locus (AKAP13) where a new single-nucleotide polymorphism (rs1821481, P(meta) = 9.99 × 10(-9)) was found to be significantly more informative compared with the previously reported rs6496932 (P(meta) = 3.64 × 10(-5)). Performing association analysis in Asians may lead to the discovery of ethnic-specific genes that control CCT, offering further mechanistic insights into the regulation of CCT. In addition, it may also provide several candidate genes for interrogation for POAG, keratoconus and possible racial/ethnic variations.

Determinants of Angle Width in Chinese Singaporeans

PURPOSE To investigate determinants of angle width and derive mathematic models to best predict angle width. DESIGN Population-based, cross-sectional study. PARTICIPANTS A total of 1067 Chinese subjects aged ≥40 years. METHODS Participants underwent gonioscopy, A-scan biometry, and imaging by anterior segment optical coherence tomography (ASOCT, Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure ASOCT parameters. Linear regression modeling was performed with trabecular-iris space area at 750 μm (TISA750) and angle opening distance at 750 μm (AOD750) from the scleral spur as the 2 dependent angle width variables. By using a combination of ASOCT and biometric parameters, an optimal model that was predictive of angle width was determined by a forward selection regression algorithm. Validation of the results was performed in a separate set of community-based clinic study of 1293 persons aged ≥50 years. MAIN OUTCOME MEASURES Angle width and biometric parameters. RESULTS The mean age (standard deviation) of the population-based subjects was 56.9 (8.5) years, and 50.2% were male. For TISA750, the strongest determinants among ASOCT and A-scan independent variables were anterior chamber volume (ACV, R(2)=0.51), followed by anterior chamber area (ACA, R(2)=0.49) and lens vault (LV, R(2)=0.47); for AOD750, these were LV (R(2)=0.56), ACA (R(2)=0.55), and ACV (R(2)=0.54). The R(2) values for anterior chamber depth and axial length were 0.39 and 0.27 for TISA750, respectively, and 0.46 and 0.30 for AOD750, respectively. An optimal model consisting of 6 variables (ACV, ACA, LV, anterior chamber width [ACW], iris thickness at 750 μm, and iris area) explained 81.4% of the variability in TISA750 and 85.5% of the variability in AOD750. The results of the population-based study were validated in the community-based clinic study, where the strongest determinants of angle width (ACA, ACV, and LV) and the optimal model with 6 variables were similar. CONCLUSIONS Angle width is largely dependent on variations in ACA, ACV, and LV. A predictive model comprising 6 quantitative ASOCT parameters explained more than 80% of the variability of angle width and may have implications for screening for angle closure.

Determinants of Anterior Chamber Depth: The Singapore Chinese Eye Study

PURPOSE Recent advances in anterior segment imaging have enabled the measurement of novel ocular biometric parameters, such as lens vault (LV), posterior corneal arc length (PCAL), and iris area. The aims of this study were to identify the determinants of anterior chamber depth (ACD) and to ascertain the relative importance of these determinants in Chinese persons in Singapore. DESIGN Population-based, cross-sectional study. PARTICIPANTS One thousand sixty Chinese participants recruited from the Singapore Chinese Eye Study. METHODS All subjects underwent AS optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure the AS-OCT parameters. Anterior chamber depth was determined using IOLMaster (Carl Zeiss Meditec). Univariate and multivariate regression analyses were performed to assess the association between ACD with ocular biometric and systemic parameters. A stepwise selection algorithm was used to identify sequentially the contribution of each independent variable. MAIN OUTCOME MEASURES Anterior chamber depth and ocular biometric parameters. RESULTS The mean age (±standard deviation) of participants was 56.9±8.57 years and 50.5% were men. The mean ACD was 3.24±0.35 mm. The strongest determinants of ACD were LV (R(2) = 0.582; P<0.001) and PCAL (partial R(2) = 0.186; P<0.001). For every 10-μm increase in LV and every 1-mm increase in PCAL, ACD changed by -0.008 mm (95% confidence interval [CI], -0.009 to -0.008 mm; P<0.001) and 0.525 mm (95% CI, 0.468-0.583 mm; P<0.001), respectively. The 8 most highly associated variables (including LV, PCAL, axial length, age, and iris area) explained 80.5% of the variability in ACD, but when excluding LV and PCAL, the other 6 variables explained only 3.7% of the variability in ACD. After controlling for LV and PCAL, axial length was a poor determinant of ACD (partial R(2) = 0.006), whereas lens thickness was not associated independently with ACD. CONCLUSIONS Lens vault and PCAL explained 76.8% of the variability in ACD. When information about LV and PCAL were available, axial length was a poor determinant of ACD, whereas lens thickness was not associated independently with ACD. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Changes in Japanese eyes after laser peripheral iridotomy: an anterior segment optical coherence tomography study.

The aim was to investigate the changes in anterior segment parameters, as assessed by anterior segment optical coherence tomography in Japanese subjects after laser peripheral iridotomy (LPI).