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Prophylactic laser peripheral iridotomy (LPI) traditionally has been recommended for primary angle-closure suspect (PACS) patients to prevent progression to angle closure. However, mass laser intervention is costly and thus requires substantial evidence to support this as a broad prophylactic strategy.
The landmark Zhongshan Angle Closure Prevention (ZAP) trial1 was a randomized clinical trial that recruited 889 subjects with bilateral PACS, aged between 50 to 70 years, through community-based screening in Guangzhou, China and explored the benefit of treating PACS eyes with LPI. Bilateral PACS patients were treated with LPI in one randomly selected eye, with the fellow eye serving as an untreated control.
Six-year report of ZAP study and a recent five-year findings from Singapore Asymptomatic Narrow Angles Laser Iridotomy Study (ANA-LIS)2 LPI achieved a 50% reduction in the six-year risk of progression to primary angle closure (PAC) in PACS. Given the low incidence rate of outcomes that have no immediate threat to vision, these studies did not recommend widespread prophylactic laser peripheral iridotomy for primary angle-closure suspects. The number needed to treat to stop one case of PACS from converting to PAC was 44 at year six (in the ZAP trial) and 22 at year five (in ANA-LIS). However, these studies lacked the statistical power necessary to make risk assessment and recommendations for clinicians which PACS patients would benefit from LPI.
In the extended report from the ZAP trial, Yuan et al. completed a 14-year follow-up of the study to identify the risk factors related to PACS progression with or without LPI. Three hundred and ninety LPI-treated eyes and 388 control eyes were lost to follow-up. Thirtythree LPI-treated eyes (4.27 eyes per 1000 eye-years) and 105 control eyes (13.59 eyes per 1000 eye-years) reached the primary endpoint (Hazard ratio:0.31, P < 0.01). We would need to treat 12 PACS to prevent 1 PAC occurrence over 14 years. Again, the benefit of treatment was achieved mainly by reducing the development of peripheral anterior synechiae (conversion to PAC). Primary angle-closure glaucoma was found in two LPI-treated eyes and four control eyes. Within them, 1 LPI-treated eye and five control eyes progressed to acute angle closure.
The main limitation of the study is the generalizability of the results
They conducted Risk Assessment in treated and untreated PACS eyes. Higher IOP, shallower limbal anterior chamber depth (LACD), and greater central anterior chamber depth were associated with an increased risk of end points developing in untreated eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI.
The main limitation of the study is the generalizability of the results. The study cohort was entirely comprised of Chinese subjects, and therefore, the results may not be fully generalizable to other racial and ethnic groups. This ethnicity is considered a high-risk group for angle-closure disease. Interestingly, only 12% of PACS progressed after 14 years, which is much lower than other reports which ranged from 9-22 % in a five-year follow-up.2-4 Of note, in the ANALIS study, 9.5% of patients with PACS progressed over five years of follow-up.2 The only study conducted for > 10 years reported a 35% progression rate of PACS in Inuit patients.5 These differences may be related to the hospital-based population of some of these studies and more lenient definitions of end-point. Nonetheless, the low incidence rate observed in the ZAP study does not align with the high prevalence of PACG in the Chinese population.
As the annual incidence of PAC was low and AAC and PACG were relatively rare in the community-based population with PACS over the long term, clinicians should assess the risk factors for progression when treating patients with PACS and prophylactic LPI should be recommended preferentially to those at the highest risk of angle closure
The current report confirms that Laser Peripheral Iridotomy is safe and results in a two-third decrease in PAC occurrence after LPI over 14 years. As the annual incidence of PAC was low and AAC and PACG were relatively rare in the community-based population with PACS over the long term, clinicians should assess the risk factors for progression when treating patients with PACS and prophylactic LPI should be recommended preferentially to those at the highest risk of angle closure.