By the year 2020, primary angleclosure glaucoma (PACG) will account for half of the 11 million people who are estimated to be bilaterally blind from glaucoma.1 China is home to the majority of people with PACG worldwide. An estimated 28.2 million primary angle-closure suspects (PACS) and 9.1 million individuals with primary angle closure (PAC) live in that country. The former have two or more quadrants in which the posterior trabecular meshwork is not visible under static gonioscopy. The latter have the same finding but also peripheral anterior synechiae and/or elevated IOP.2 All of these individuals are at risk of developing PACG. Where better, then, for large-scale research on this subject?
BACKGROUND
Fortunately, PACG is a detectable and preventable disease. Successful prevention depends largely on implementing feasible screening programs, targeting people at greatest risk of developing an acute angleclosure attack or PACG, and taking effective prophylactic measures as early as possible.
So far, data are limited on the natural history of asymptomatic eyes with narrow angles on gonioscopy. Wilensky and colleagues3 enrolled 129 mostly European-derived subjects with “occludable” angles and a central anterior chamber depth (measured by optical pachymetry) of less than 2 mm in a prospective study over a 5-year period. Eight patients (6.2%) developed acute angle closure, and 17 (13.2%) developed either appositional closure or peripheral anterior synechiae in at least 0.5 clock hours of the superior quadrant (median follow-up, 2.7 years). Based on the long-term observation of 50 PACS, Thomas et al4 reported that the 5-year incidence of PAC was 22%. Although these reports provide some indication of an increased risk among the people studied, the relatively small size of the studies and the somewhat subjective nature of the outcomes limit clinicians' and scientists' understanding of the natural history of PAC.
Laser peripheral iridotomy (LPI) prevents acute angleclosure attacks in the fellow eyes of patients who have suffered acute angle closure in one eye5 (Figure 1). There is still no conclusive evidence, however, that LPI benefits people with asymptomatic angle closure. In fact, the procedure may have adverse outcomes, including the more rapid development of lenticular opacity6-8 and damage to the corneal endothelium9 as well as patients' dissatisfaction with glare.10
Given the possible harm of the widespread use of LPI and the fact that budgets for preventive services are limited, the effectiveness of LPI for the prevention of PACG in PACS must be clearly demonstrated before large-scale case-detection and treatment programs are initiated. An adequate number of people must be studied for a sufficient period of time to answer the question definitively.
THE ZHONGSHAN ANGLE CLOSURE PREVENTION TRIAL
The Zhongshan Angle Closure Prevention Trial (ZAP trial; trial registration information: ISRCTN45213099, www.controlled-trials.com/ISRCTN45213099) is a collaborative project between the Zhongshan Ophthalmic Center, Moorfields Eye Hospital/University College London, and The Wilmer Eye Institute at Johns Hopkins University in Baltimore. The purpose of this prospective randomized controlled trial is to assess the efficacy and safety of LPI in preventing the development of PAC as well as acute angle closure. The study population was identified after screening more than 11,000 older Chinese persons (range, 50-70 years) living in Guangzhou, the capital city of Guangdong Province in southern China. Participants were randomized to receive LPI in one eye, and the other eye was left untreated. This study will answer important questions about the natural history of PAC and will determine the benefits and harms of prophylactic LPI. Furthermore, it will identify factors at baseline associated with developing acute or chronic angle closure.
To the best of my fellow researchers' and my knowledge, the ZAP trial is the largest single-site clinical trial in ophthalmology. Eight hundred ninety people have been randomized and treated in one eye with LPI, and they will be observed for a minimum of 36 months after the laser treatment. During the follow-up period, participants will be examined 2 weeks, 6 months, 18 months, and 36 months after laser treatment. Baseline and followup examinations include tonometry, grading of limbal anterior chamber depth, anterior segment optical coherence tomography, assessment with a scanning peripheral anterior chamber depth analyzer, ultrasound biomicroscopy, ultrasound A-scan, dark-room prone provocative testing, gonioscopy, specular microscopy, and fundus photography.
CONCLUSION
The ZAP trial has already started to offer insight into the behavior of eyes with angle closure. We have determined that they have less IOP elevation after a 15-minute dark-room prone provocative test than eyes with open angles. We have also found that eyes with shallower anterior chambers and those requiring more energy to complete the LPI are at higher risk of developing an acute increase in IOP immediately after the iridotomy.
Further analyses will increase our understanding of the mechanisms of angle closure in Chinese populations as well as the changes in anatomy and IOP induced by LPI. Ultimately, this trial will identify the magnitude of the risk of leaving eyes with suspected PAC untreated. It will also help to identify which specific angle-closure populations are at greatest risk and require prophylactic iridotomy.
David S. Friedman, MD, MPH, PhD, is the Alfred Sommer professor of ophthalmology in the Wilmer Eye Institute and a professor of international health and epidemiology in the Johns Hopkins Bloomberg School of Public Health in Baltimore. He is also a senior ophthalmologist with Helen Keller International in New York. Dr. Friedman may be reached at (410) 614-1342; david.friedman@jhu.edu.
