Primary angle closure glaucoma (PACG) is a leading cause of blindness worldwide, and more common in women and people from East Asia. In the UK PACG is responsible for approximately 1 in 6 glaucomas, and despite this relatively high prevalence it remains underdiagnosed. PACG is often asymptomatic until the very late stages of the disease, progressively leading to visual field defect if intraocular pressure (IOP) is not reduced in time. A narrow or closed iridocorneal angle is the characteristic sign assessed on gonioscopy in this condition. Previous studies have found that PACG accounts for 10–20% of all referrals to glaucoma units in the UK [1].
PACG treatment aims to reduce IOP by means of ocular hypotensive agents, laser treatment (laser peripheral iridotomy, laser peripheral iridoplasty [LPlp]), and surgical options (e.g., lens extraction, trabeculectomy).
This Cochrane Corner summarises the evidence collected and appraised in two recent Cochrane Reviews on the management of chronic PACG, specifically focusing on lens extraction and LPlp.
Ong et al. [2] summarised the evidence on the efficacy of lens extraction (with or without cataract) on PACG from eight RCTs. Lens extraction can aid IOP control, by relieving the pupillary block mechanism and by reducing the angle crowding. How lens extraction performs in comparison with other conventional treatment in PACG, is still to be systematically determined.
Only one trial, the Effectiveness in Angle-closure Glaucoma of Lens Extraction (EAGLE) [3] compared clear lens extraction (CLE) with laser peripheral iridotomy (standard care) as an initial intervention in people over 50 years of age. Participants were recruited from UK, Australia and Southeast Asia. This review used raw data collected in the EAGLE study [3] to carry out an analysis limited to 263 participants with PACG out of 419 enrolled. One-hundred and fifty-five participants who had primary angle closure (PAC), but no glaucoma, were not included in this review. EAGLE data provided moderate-certainty evidence that CLE was more effective than laser iridotomy, reduced visual field damage progression (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.13–0.91; 216 eyes), required fewer IOP-lowering medications (mean difference [MD] −0.70, 95% CI −0.89 to −0.51; 263 eyes; moderate-certainty evidence), while achieving a similar IOP reduction (−0.03 mmHg, −2.34 to 2.32; 257 eyes; moderate-certainty evidence) at 12 months.
In the same review, three studies compared phacoemulsification with combined phaco-trabeculectomy, in participants with cataract and PACG. Data were only available for one study (63 eyes). In this study, low-certainty evidence suggested that there was little to no difference between groups in mean change in IOP from baseline (MD −0.60 mmHg, 95% CI −1.99 to 0.79), and number of IOP-lowering medications at 12 months (MD 0.00, 95% CI −0.42 to 0.42).
Bayliss et al. [4] conducted another review on LPIp for PAC and PACG, excluding acute attacks. LPlp is traditionally used as a second line intervention when laser iridotomy is not decisive. It works by causing a contraction of the iris stroma peripheral to the burn and by a cross-sectional thinning of the iris stroma.
Four trials were included in this review (252 people, mostly from East Asia), evaluating the effectiveness of LPlp in either the primary or secondary management of PACG [5,6,7,8]. The trials followed participants for between 3 and 12 months. The evidence suggests that adding LPIp to iridotomy may make little or no difference to IOP (2 trials, 174 people), as well as to the need for medicines and further laser or surgical treatment after 12 months (1 trial, 126 people). There was no evidence on whether LPIp slows disease progression or improves quality of life because no study investigated these outcomes. In the same review, one small trial (22 people) compared LPIp, as a secondary treatment, to no treatment. This trial was not robust enough to determine which option is better. Another trial on 80 people compared LPIp with medication. There was low-certainty evidence that there may be little to no difference between the effects of LPIp and travoprost 0.004% on disease progression, IOP, and the need for medicines or further laser or surgical treatment after 12 months.
Imaging technologies showed that LPIp was associated with a widening of the anterior chamber angle. Complications after LPIp were mild and uncommon, except for one case of malignant glaucoma. Reported complications included hyphema, post-laser IOP spikes, reduction in corneal endothelial cell count, non-significant reduction in visual acuity, transient atonic pupil, corneal endothelium burn, and persistent uveitis.
The certainty of information to assess effectiveness of LPIp was low due to lack of masking of participants, personnel and outcome assessors, and imprecision (wide 95% CIs or insufficient overall sample size). Indirectness was also a concern since data at 24 months which was the primary time point of the review, were not available.
The conclusion of the Cochrane Review is that LPIp provides little to no benefit over comparators in the management of people with non-acute PAC or PACG. The authors of the review also proposed that, despite uncertainties, the existing evidence doesn’t justify research efforts in further trials of LPIp as an intervention for people with non-acute PAC or PACG.
What are the clinical implications of these two Cochrane Reviews? Should CLE be offered or considered in people with PACG when there is a small risk of severe complications? We would suggest an individualised approach for people over 50 years of age. Can the results of the EAGLE trial inform management decisions of people younger than 50 years and those who were not included in the trial? The short answer would be no. Can we predict the effectiveness of the intervention according to ocular or demographic characteristics? Further research is needed.
Regarding LPIp, are changes in anterior chamber depth important if there is no difference in IOP considering that the procedure is relatively safe? We don’t know.
Overall PACG is a leading cause of blindness worldwide and currently underdiagnosed and under-researched. Further evidence regarding diagnosis [9] and treatment options are needed, ideally from RCTs. Observational evidence should also be collected on the evolving management of PACG.
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Acknowledgements
The contribution of the IRCCS Fondazione G.B. Bietti in this paper was supported by the Italian Ministry of Health and by Fondazione Roma. The supporting organisation had no role in the design or conduct of this research.
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Michelessi, M., Azuara-Blanco, A. & Virgili, G. Cochrane Corner: evidence on the management of primary angle closure glaucoma. Eye 36, 684–685 (2022). https://doi.org/10.1038/s41433-021-01848-9
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DOI: https://doi.org/10.1038/s41433-021-01848-9