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Effectiveness depends on stage of the disease, mechanism of angle closure
San Francisco-Recognition that angle-closure disease represents different stages and involves different mechanisms is helpful for understanding why laser peripheral iridotomy (LPI) is not always enough.
“LPI is the mainstay of managing angle-closure disease, but its effectiveness depends on the stage of the disease as well as the mechanism of angle closure,” said Sunita Radhakrishnan, MD, private practice, Glaucoma Center of San Francisco. “Iridotomy is only effective for treating eyes with pupillary block, and even then, additional treatment is usually required for most patients with primary angle closure (PAC) or PAC glaucoma (PACG).”
Terminology to describe the different stages of angle-closure disease was first published in 2002 and divides the condition into PAC suspect (PACS), PAC, and PACG. The person whose PACS is diagnosed has an anatomically narrow angle but a normal IOP and optic disc, whereas in a patient with PAC, there is evidence of trabecular meshwork dysfunction.
This category can be further divided into the chronic asymptomatic form where there may be presence of peripheral anterior synechiae (PAS) and/or elevated IOP or the acute form manifested by an angle-closure attack. PACG refers to patients who have developed glaucomatous cupping of the optic nerve.
Just as the outcomes for treating angle-closure disease depend on the stage, so do the goals. For PACS and PAC, the goal is to modify the anterior segment anatomy to prevent trabecular damage and future disc damage. Once glaucoma is present, the main goal is to lower IOP, which may or may not be achieved solely by modifying the anterior segment anatomy.
Reviewing the literature on outcomes of LPI for the different stages of angle-closure disease, Dr. Radhakrishnan noted that among patients with PACS, up to one-third of eyes still have residual angle closure as evidenced by gonioscopy or imaging. These results can be explained by non-pupillary block mechanisms, such as plateau iris, a thick peripheral iris, or high lens vault.
“Nevertheless, pupillary block and non-pupillary block mechanisms co-exist in most of these patients and very few PACS need further intervention after LPI,” Dr. Radhakrishnan said.
She noted that in three studies with follow-up ranging from 1 to 4 years postLPI, no patients experienced an acute angle-closure attack, and in two studies, there were no patients whose disease progressed to PAC.
“In the third study, 22% of eyes progressed to PAC, but the progression was due to the presence of PAS, and no patients developed IOP elevation or required further treatment,” she said.
The same three studies included data on outcomes of patients with PAC after LPI, and in two studies, the majority of patients required additional treatment for increased IOP. And, in one of those two studies, 9% of eyes progressed to PACG.
“However, the latter cases were mainly explained by noncompliance with medication, and there were no eyes that experienced an acute angle-closure attack during follow-up ranging to 4 years,” Dr. Radhakrishnan said.
Studies investigating outcomes of eyes with acute PAC treated with LPI showed that during 2 to 6 years of follow-up, 20% to 60% of eyes continued to have elevated IOP, and in one study, 48% of eyes went on to develop PACG. The variation in outcomes among these studies may be explained in part by differences in the timing of the intervention since the onset of the attack, Dr. Radhakrishnan said.
“When you treat is very important,” Dr. Radhakrishnan said. “In 2004, Aung et al. reported a 48% rate of progression to PACG, the median duration of symptoms in this study was 3 days, and LPI was performed within 3 days of presentation.
“In a later study from the same group, the median duration of symptoms was less than 24 hours, eyes were treated within 1 day of presentation, and the rate of progression was only 12%,” she said.
With one exception, studies of patients with PACG show that almost all (≥83%) required additional treatment after LPI. Evidence from two studies comparing patients with and without a previous attack of angle closure show the latter history increased the likelihood of needing additional intervention after LPI.
Most patients with PAC or PACG requiring further treatment after LPI can be managed with medications and with the same agents that are used to treat patients with open-angle glaucoma, Dr. Radhakrishnan said.
Iridoplasty is another option to consider for addressing the non-pupillary block mechanism of angle-closure disease. While its long-term efficacy is not well-defined, clinical experience indicates its benefit is short-lived. This may explain the wide variation in usage of iridoplasty, Dr. Radhakrishnan said.
Surgical treatment for angle closure has traditionally been with filtering surgery with or without cataract extraction. Recently, however, there is increasing evidence that cataract extraction alone is a good option to treat eyes with angle closure.
“Removing the lens makes perfect anatomical sense in these eyes that tend to have a thicker lens with a high anterior lens vault,” Dr. Radhakrishnan said.
She added that results from two randomized controlled trials also show that early cataract surgery is helpful intervention for an acute angle-closure attack. In these studies, eyes undergoing phacoemulsification had better long-term IOP control than those treated by iridotomy or iridectomy.
“Nevertheless, in weighing the risk of operating in an inflamed eye versus the benefits, many suggest waiting at least 1 month after the acute attack is abolished before performing surgery,” Dr. Radhakrishnan said.
An ongoing study will provide insight about the efficacy of clear lens extraction in eyes with angle closure. Known as the EAGLE trial and under way at 30 sites in the United Kingdom and Asia, it is enrolling eyes with PAC and PACG. All eyes will undergo LPI and are being randomly assigned to early lens extraction or conventional therapy thereafter.
“Presence of cataract is not a criterion for enrollment,” Dr. Radhakrishnan concluded. “Therefore, many eyes in the study will undergo clear lens extraction.”
Sunita Radhakrishnan, MD
Dr. Radhakrishnan has no financial interest in the subject matter. This article was adapted from Dr. Radhakrishnan’s presentation during the 17th annual Glaucoma Symposium at Glaucoma 360º in association with the Glaucoma Research Foundation and Ophthalmology Times.