Iridotomy an effective prophylactic in PACS, but risk of glaucoma progression low

Undergoing prophylactic laser peripheral iridotomy (LPI) for primary angle-closure suspect (PACS) can reduce the risk of progression, although the likelihood of developing glaucoma without treatment is low overall, as shown in a Singapore study.

In a cohort of 480 patients (mean age 62.8 years, 75.8 percent female, 92.7 percent Chinese) with bilateral asymptomatic PACS, progression to primary angle closure (PAC) or primary angle-closure glaucoma (PACG) over 5 years occurred less frequently in eyes treated with LPI than eyes that were left untreated (5.0 percent vs 9.4 percent; incidence rate [IR], 11.65 vs 21.84 per 1,000 eye-years; p=0.001). PAC was defined as the presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mm Hg, or both or acute angle closure (AAC). [Ophthalmology 2022;doi:10.1016/j.ophtha.2021.08.017]

LPI almost halved the risk of progression to PAC or PACG (hazard ratio [HR], 0.55 (95% confidence interval [CI], 0.37–0.83; p=0.004). This benefit was mainly mediated through a reduction in the incidence of peripheral anterior synechiae (5-year incidence, 1.3 percent with LPI vs 4.9 percent without treatment; p<0.001).

Progression to PACG, specifically, was uncommon in both groups (0.6 percent with LPI vs 1.5 percent without treatment; p=0.23), and even fewer eyes developed IOP >21 mm Hg or AAC (0.2 percent vs 0.4 percent; p=0.57).

Risk factors for progression included older age (HR, 1.06 per year, 95 percent CI, 1.03–1.10; p<0.001) and higher baseline IOP (HR, 1.35 per mm Hg, 95 percent CI, 1.22–1.50; p<0.0001). The number needed to treat (NNT) to prevent progression with LPI was 22 (95 percent CI, 12.8–57.5).

In the study, each patient underwent prophylactic LPI in one randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years.

Observation without LPI reasonable

The best direct comparison to the current study is the ZAP trial, according to the investigators. ZAP also mainly focused on a southern Chinese population and reported a similarly low incidence of progression to primary angle-closure disease over 6 years: 4.2 per 1,000 eye-years with LPI vs 8.0 per 1,000 eye-years without treatment, which is much lower than that reported in the current study. [Lancet 2019;393:1609-1618]

“Both our study and the ZAP trial found LPI to be safe for PACS,” and that the vast majority of progression occurred due to development of peripheral anterior synechiae, as the investigators pointed out.

“Due to the limited beneficial effect of LPI, the ZAP trial authors did not recommend widespread use of LPI in asymptomatic PACS. The evidence from the current study also suggests a limited benefit for prophylactic LPI in asymptomatic PACS, [given the relatively high] NNT and [that] almost all the benefit was for visually insignificant angle changes,” they said. “There would be no benefit of treatment in either study if peripheral anterior synechiae had not been chosen as an endpoint.”

While the investigators acknowledged the need to identify a subset of PACS individuals who would most benefit from prophylactic LPI, they stressed that the absence of a clear risk predictor in the current study underscores careful consideration of performing LPI in all asymptomatic PACS, given the cost of treatment and possible post-LPI management involved.

Despite the presence of study limitations, including the fact that not all patients completed the 5 years of follow-up, “our findings confirm much of what was reported in the ZAP trial, further supporting the recommendation that observation without LPI is a reasonable option for PACS,” the investigators said.