Anatomical Changes and Predictors of Angle Widening After Laser Peripheral Iridotomy: The Zhongshan Angle Closure Prevention Trial

PURPOSE: To assess anatomical changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment OCT (AS-OCT) and angle opening based on gonioscopy in mainland Chinese primary angle closure suspects (PACS). DESIGN: Prospective observational study. PARTICIPANTS: 454 subjects aged 50 to 70 years with PACS. METHODS: Subjects received clinical examinations including gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. PACS was defined as inability to visualize pigmented trabecular meshwork in two or more quadrants on static gonioscopy. LPI was performed on one eye per subject in a superior (between 11 to 1 o'clock) or temporal or nasal (at or below 10:30 or 1:30 o'clock) location. Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Multivariable linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in continuous measurements of mean angle opening distance (AOD750), poor angle widening, defined as the lowest quintile of change in mean AOD750, and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomical changes and predictors of angle widening and opening after LPI. RESULTS: 454 subjects were included in the analysis. 219 received superior LPIs and 235 received temporal or nasal LPIs. There were significant changes among most biometric parameters (p<0.006) after LPI, including greater AOD750 (p<0.001). 120 eyes (26.4%) had residual PACS after LPI. In multivariable regression analysis, several baseline parameters, including superior LPI location (p=0.004), smaller AOD750 (p<0.001), and greater iris curvature (p<0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (OR=2.60, p<0.0001) and greater baseline AOD750 (OR=2.58, 0.1 mm increment, p<0.001) were most predictive of poor angle widening based on AS-OCT. Smaller mean gonioscopy grade (OR=0.34, 1 grade increment) was most predictive of poor angle opening based on gonioscopy. CONCLUSIONS: Superior LPI location results in significantly greater angle widening based on AS-OCT compared to temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomical changes after LPI

Ocular Biometric Risk Factors for Progression of Primary Angle Closure Disease: The Zhongshan Angle Closure Prevention Trial

PURPOSE: To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). DESIGN: Prospective observational study. PARTICIPANTS: 643 mainland Chinese aged 50 to 70 years with untreated PACS. METHODS: Participants received baseline clinical examinations including gonioscopy, anterior segment OCT (AS-OCT) imaging (Visante OCT, Carl Zeiss Meditec, Dublin, CA), and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. PACS was defined as inability to visualize pigmented trabecular meshwork in two or more quadrants based on static gonioscopy. PAC was defined as development of elevated intraocular pressure (IOP) > 24 mmHg or peripheral anterior synechiae (PAS). Progression was defined as development of PAC or an acute angle closure (AAC) attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. MAIN OUTCOME MEASURES: Progression from PACS to PAC or AAC over 6 years. RESULTS: 643 untreated eyes (609 non-progressors, 34 progressors) of 643 ZAP participants were included in the primary analysis. In a multivariable model with continuous parameters, narrower horizontal angle opening distance 500 μm from the scleral spur (AOD500; OR=1.10 per 0.01 mm decrease, p=0.03), flatter horizontal iris curvature (IC; OR=1.96 per 0.1 mm decrease, p=0.01), and older age (OR=1.11 per year increase, p=0.01) at baseline were significantly associated with progression (AUC=0.73). Smaller cumulative gonioscopy score was not associated with progression (OR=1.03 per 1 modified Shaffer grade decrease; p=0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR=3.10, p=0.002) and IC (OR=2.48, p=0.014) measurements and aged 59 years and older (OR=2.68, p=0.01) at baseline had higher odds of progression (AUC=0.72). CONCLUSIONS: Ocular biometric measurements can help risk stratify patients with early angle closure for more severe disease. AS-OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not

The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis

Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of$100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of$55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care