Iridoplasty for plateau iris syndrome: a systematic review

Introduction

Of the nearly 67 million patients with glaucoma worldwide, primary angle-closure glaucoma (PACG) is a major cause of blindness, and it is estimated that 5.3 million people will suffer from blindness secondary to PACG in 2021.1 Relative pupillary block is considered to be the primary mechanism for angle closure, making laser peripheral iridotomy (LPI) a treatment of choice in PACG. LPI is able to significantly increase angle width and to lower intraocular pressure (IOP) in people with narrow angles.2 3 However, several studies reported patients with persistent angle closure after LPI (around 58%–80% of cases) in which the most common underlying mechanism was plateau iris.2 4

Tornquist et al5 first described the plateau iris configuration in 1958 on a young woman with high IOP and a flat iris surface. Gonioscopic examination revealed a closed-angle with a double-hump iris. Then plateau iris was classified by Wand et al6 in 1977, differentiating ‘plateau iris syndrome’ from ‘plateau iris configuration’. The ‘configuration’ refers to a preoperative condition with a gonioscopically confirmed narrow-angle and a flat iris. In most cases, the narrow angle associated with the plateau iris configuration was opened by a peripheral iridotomy. ‘Plateau iris syndrome’ (PIS) refers to a persistently narrow angle capable of closure despite a patent iridotomy resolving the associated relative pupillary block component. Wand et al7 confirmed and illustrated their observations in 1993 with histological and ultrasound biomicroscopy (UBM) exploration, showing an anteriorly displaced ciliary body that may secondarily rotate and push forward the peripheral iris root into the trabecular meshwork, causing angle narrowing or closure with a flat iris. As a consequence, PIS is now regarded as one of the mechanisms of angle-closure glaucoma.8

In 1982, after observing angle widening in front of an iridotomy site, Ritch9 proposed repeated non-transfixing spots on the iris periphery, describing the first argon laser peripheral iridoplasty (ALPI). ALPI contracts the peripheral iris tissues, pulling the iris away from the trabecular meshwork and reducing the area of iris–trabecular contact. Although ALPI is still considered as a laser treatment for PIS management, since 1982 and the first ALPI description, only a few studies have been conducted on this technique for PIS management.

The purpose of this study was to evaluate the efficacy and safety of ALPI on IOP lowering, angle opening and the number of medications in PIS by reviewing the available published literature.

Patients and methods

We conducted a systematic review of studies evaluating the efficacy of ALPI in PIS. The published literature was searched using the following keywords: (“Plateau iris” AND “Laser iridoplasty”) OR (“Plateau iris” AND “Gonioplasty”) OR “Iridoplasty”. We analysed all the prospective and retrospective cohorts evaluating ALPI in documented chronic ACG caused by PIS. We included studies that evaluated IOP lowering, angle opening and/or the number of medications with a 1-month minimum follow-up. A total of 41 articles were analysed of which 33 were excluded (figure 1). The reasons for exclusion are detailed in online supplementary annex 1. We provided an individual and an overall analysis for 1-year and 6-year outcomes. Weighted mean IOP (WM_IOP) was calculated for 1-year and 6-year outcomes using each study’s final IOP weighted by the number of eyes included in the final evaluation:

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Results

To date, there have been no randomised controlled trials evaluating the use of iridoplasty in chronic angle-closure caused by PIS. We included seven retrospective case series4 9–15 and one prospective observational case–control study16 published between 2004 and 2017. The study characteristics are described in table 1. A total of 170 eyes of 147 patients were analysed. The eight studies were conducted on patients with chronic angle-closure persistent after laser peripheral iridotomy. Three studies included both PIS and lens-induced angle closure11 13 16 and five evaluated PIS only.4 10 12–15 17 One study provided a 1-month follow-up,15 five studies a 12-month follow-up,11–13 16 two studies had a long-term follow-up of more than 6 years4 17 and the longest one provided 92.4 months of mean follow-up.10

The ALPI procedure was not standardised and differed slightly between studies: spot sizes varied from 200 to 500 µm, energy levels from 200 to 550 mW and exposure times from 100 to 500 ms (table 2). The number of spots was specified in four studies and varied from 20 to 50.10 14–16 The procedures were performed in one session, except for Ouazzani et al,15 who performed ALPI in two sessions, with or without a contact lens to put non-overlapping spots on 360° of the peripheral iris. The primary efficacy outcome was a clear iris contraction for each laser application in all the studies presented. All procedures included postoperative steroidal or non-steroidal anti-inflammatory drugs and IOP control 45–60 min after the procedure.

Effect on IOP

After ALPI, IOP decreased from −6.7 mm Hg (−30%) after 1 month15 to −2.8 mm Hg (−19%) (p=0.01),12 −3.4 mm Hg (−19%) (p<0.01),11 −3.6 mm Hg (−20%) (p<0.01),13 −4.4 (−21%) (p=0.012)4 and −7.9 mm Hg (−32%) (p<0.001)16 after 1 year. After a mean follow-up of 6 years, Ritch et al17 did not find any significant IOP change as compared with baseline (+0.2 mm Hg), similar to Peterson et al,4 who found a −1.6 mm Hg (p=0.38) non-significant IOP variation. Moreover, in this study, 36% eyes underwent filtering surgery and 41% eyes phacoemulsification. After 7.5 years of follow-up, Romito et al10 found a −1.56 mm Hg (−10%) (p>0.01) variation. IOP changes are presented in table 3.

Table 3

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IOP and angle widening variations (IOP in mm Hg)

In studies with at least 1 year of follow-up, weighted IOP decreased from 19.6 mm Hg at baseline to 15.6 mm Hg at the last visit after ALPI, providing a −4.0 mm Hg or −20% IOP variation.4 11–13 16 In the studies with a 6-year follow-up, weighted mean IOP varied from 18.7 mm Hg to 18.5 mm Hg at the last visit after ALPI, providing a −0.2 mm Hg or 1% variation4 17 (figure 2).

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Figure 2

Weighted mean IOP variation (IOP, intraocular pressure; n year, indicate follow-up time).

Discussion

PIS is a common cause of chronic angle-closure glaucoma, and ALPI is presented by some authors as a safe and non-invasive procedure for IOP control and angle opening. Our study is the first review evaluating the efficacy of ALPI in PIS since Ng et al18 published a Cochrane meta-analysis in 2012 demonstrating the lack of clinical outcomes on ALPI. At that time, only the Ritch et al17 retrospective cohort study published in 2004 was available. Seven years later, there is still no randomised control trial published on ALPI efficacy and safety on chronic angle-closure caused by PIS. Unfortunately, the recent cohort studies contribute little, non-standardised information with results often combining PIS and lens-induced angle closure,11 13 16 that in 2019 does not allow us to draw a firm conclusion on the role of ALPI in PIS.

The first ALPI procedures were proposed by Ritch9 in 1982 to treat medically unresponsive angle-closure attack. Their observations were based on angle-closure glaucoma without distinguishing the underlying mechanisms. The aim of ALPI was to contract iris peripheral stroma to decrease its contact with the trabecular meshwork. These iris changes following ALPI were confirmed histopathologically in 1993 in a case report. Sassani et al19 theorised that heat-induced shrinkage of collagen may be responsible for the short-term response to ALPI and that the healing characterised by the contraction of the fibroblastic membrane may promote long-term angle opening. Ritch et al20 then extended ALPI indications to PIS, explaining that an anteriorly positioned ciliary body pushing the iris root forward towards the trabecular meshwork could be flattened by lower power, longer duration and large laser spot sizes, causing deep contraction burns. Iridocorneal angle morphology change before and after ALPI was evaluated with AS-OCT by Lim et al on 60 eyes with persistent occludable angle after LPI regardless of the angle-closure mechanism. Using the Anterior Segment Analysis Program, a significant increase in iridocorneal angle parameters was found: angle opening distance (AOD500 and AOD750), trabecular iris surface area (TISA500 and TISA750), anterior chamber volume and anterior chamber area (ARA500 and ARA750). However, no significant changes were observed on central anterior chamber parameters: anterior chamber width, anterior chamber depth and lens vault, illustrating the action of ALPI on the peripheral iridocorneal angle morphology.

The spot sizes might explain the disappointing results found by Peterson et al4 and Singh et al,12 given that they used smaller spots and a shorter exposure time than Ritch et al17 and Romito et al.10 Nevertheless, these authors explained their laser protocols as preventing adverse events. Ramakrishnan et al16 were the only authors to show transient photophobia following an ALPI procedure, and no other adverse events were reported in the other published studies on PIS. Espana et al21 presented a series of 12 eyes in eight patients with persistent iris dilatation after an ALPI procedure for acute angle-closure. Only one patient had a decrease in visual acuity, but seven of the eight patients declared blurred vision. The pupillary response to pilocarpine instillation was minimal or absent and mydriasis eventually resolved in all eyes without treatment within 1 year. The reversibility of these complications should reassure the patients and the ophthalmologist on ALPI tolerance. Moreover, in the study reported by Espana, ALPI was performed for an acute angle-closure that could be by itself responsible for persistent iris dilation.

Despite non-significant long-term results, Peterson et al4 compared their results to the Ritch et al17 cohort. They noted a higher baseline IOP (mean IOP, 21.3 mm Hg) with fewer eyes on IOP-lowering medications (seven eyes, 33%, on one to two medications) in the Peterson’s cohort, compared with Ritch’s study (mean IOP, 18 mm Hg with 100% of eyes on IOP-lowering medication). In addition, seven eyes (33%) in Peterson’s study had peripheral anterior synechiae (PAS), and two eyes (9%) had glaucomatous damage before ALPI, whereas PAS were not documented, and no eyes had glaucomatous damage in the Ritch et al study. It is noteworthy that Peterson’s cohort had more advanced disease than the patients from the Ritch et al study.

Based on Ouazzani et al’s observations,15 iridoplasty seems to have a rapid effect on lowering IOP, which seems maintained after 1 year. To date, Gomes Prado et al13 is the only study excluding hypotensive medication bias with no change in treatment during the 11.8 months of follow-up. However, long-term IOP management seems more difficult. Ritch showed three eyes (13%) with gradual angle narrowing 5–9 years after initial ALPI, but the angle reopened after a second ALPI treatment. Romito et al10 declared five eyes (10%) requiring a new ALPI for gradual angle reclosure 60.2 months after the first procedure. The author attributed this angle closure to the gradual lens growth and every secondary procedure was successful. Six eyes (10%) also required phacoemulsification justified by significant loss of vision. Peterson et al’s management of angle narrowing was different with eight (36%) eyes requiring filtering surgery and nine (41%) eyes requiring phacoemulsification within 6 years of follow-up. All eyes had controlled IOP after cataract extraction, and five out of nine eyes were free of IOP-lowering medications 3 months after surgery. Cataract surgery attenuated anterior positioning of the ciliary processes in eyes with primary angle-closure, concomitant with significant opening of the angle.22 However, Viet Tran et al23 showed the persistence of iridociliary apposition after phacoemulsification in a series of six patients with PIS previously treated with LPI and ALPI. These studies show the low probability of IOP resolution after phacoemulsification as a standalone procedure in PIS.

The ciliary bodies’ anteposition is the initial cause of angle-closure physiopathology in PIS. However, the ALPI mechanism is only based on the thinning of the superficial iris tissue at the level of the crowded angle24 and has no impact on the ciliary body anteposition, which might explain the poor long-term outcomes. Hollander et al25 hypothesised that shrinking the ciliary processes with endoscopic cyclophotocoagulation (ECP) creates a space that will accommodate the thickened peripheral iris during pupillary dilation and prevent angle closure. In a series of nine eyes of six patients with PIS, they showed a significant IOP reduction from 25.2 mm Hg to 17.1 mm Hg (p<0.05) with a lowering in the number of medications after a 73-month follow-up. Moreover, the angles were opened in UBM only in areas treated with ECP with corresponding flattened ciliary processes. This invasive procedure could become an advantageous treatment for patients with PIS and a persistent occludable angle or uncontrolled IOP due to PIS.

Conclusion

ALPI does lower IOP in chronic angle-closure PIS over the short term and may widen the iridocorneal angle. These effects may be associated with a short-term reduction in the number of medications. Nevertheless, these observations are based on small retrospective cohort studies with a 1-year follow-up and there is no current evidence of long-term efficacy among the three long-term cohort studies available. Moreover, the effects of ALPI on visual field progression have never been studied. As a consequence, there is no strong scientific evidence as yet to advocate ALPI as a treatment of chronic angle-closure caused by PIS.