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Review Glaucoma Ultrasound Cycloplasty in Glaucoma – Mechanisms of Action and their Possible Impact on Intraocular Pressure Kin Sheng Lim Ophthalmology Department at St Thomas’ Hospital, London, UK U ltrasound cycloplasty (UCP) is a procedure based on high-intensity focused ultrasound (HIFU) for refractory and non-refractory glaucoma in cases for which surgery is not suitable. UCP may bring about a reduction in intraocular pressure (IOP) via multiple mechanisms of action that result in a decrease in aqueous humour production and increase in aqueous humour evacuation. UCP appears to have a favourable safety profile compared with cyclo-destructive methods, with no phthisis bulbi, no induced cataract, and no persistent hypotony. In 103 patients with refractory and non-refractory glaucoma who underwent UCP, 94 (91%) achieved an initial reduction in IOP, and in 65 patients (63.1%), treatment success was achieved whereby the IOP remained low. However, in 22 patients (21.4%), at 3 months, the IOP rose to near the original level, indicating treatment failure: ‘early failure’. In the remaining 7 patients (6.8%), a slow rise in IOP occurred over 6 months following the procedure: ‘late failure’. The differences in IOP changes in these 94 patients may be in part explained by: (i) a reduction in the uveoscleral–transscleral openings in some patients, leading to an eventual rise in the initially decreased IOP; (ii) a possible re-epithelialisation of the ciliary processes taking place in some cases; and/or (iii) that the circumference of 160° UCP treatment might not be sufficient for all patients. The first 3 months following the UCP procedure are therefore critical since treatment success or failure is determined within this timeframe. Keywords Intraocular pressure (IOP), glaucoma, ciliary body, ultrasound cycloplasty (UCP), mechanism of action, high-intensity focused ultrasound (HIFU) Disclosure: Kin Sheng Lim has received research funding from EYE TECH CARE and is a consultant for Alcon, Novartis, Ivantis and iSTAR. This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors Acknowledgements: Medical writing support, including preparation of the drafts under the guidance of the author, was provided by Catherine Amey, Touch Medical Media. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 12 May 2017 Accepted: 5 June 2017 Citation: European Ophthalmic Review, 2017;11(1):35–9 Corresponding Author: Kin Sheng Lim, Ophthalmology Department at St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH, UK. E: shenglim@gmail.com Support: The publication of this article was supported by EYE TECH CARE. The views and opinions expressed in the article are those of the author and not necessarily those of EYE TECH CARE. TOU CH MED ICA L MEDIA High-intensity focused ultrasound (HIFU) was first used to treat brain pathologies, such as Parkinson’s disease In the 1940s. 1 HIFU was later used in the 1990s in ophthalmological practice to treat intraocular pressure (IOP), traumatic capsular tears, glaucoma, retinal detachment and vitreous haemorrhage. 2–7 HIFU has been used to treat both benign and malignant lesions of various solid tumours, 8,9 and its potential has been recognised to transform treatment for a spectrum of other serious medical conditions. 10 Indeed, focused ultrasound is under research or has already received regulatory approval for over 50 medical conditions in Europe, the US and Asia. In total, more than 115,000 patients have been treated with focused ultrasound, within the fields of oncology, endocrine and brain disorders, and women’s health, among others. 10 Ultrasound cycloplasty (UCP) as a HIFU procedure is CE marked for both refractory and non-refractory glaucoma, where surgery is unsuitable. This review will explore the likely mechanisms of action of UCP and the consequences of these mechanisms on IOP change in patients with glaucoma. Ultrasound cycloplasty and its mechanisms of action for its efficacy in glaucoma Several studies published on the UCP technique have mentioned its possible mechanisms of action, both on the reduction of the aqueous humour production and on aqueous humour evacuation increase, as will be discussed. First mechanism of action – aqueous humour production decrease UCP (Figure 1) has been developed for selective and non-aggressive structural modification of the ciliary processes, with sparing of the adjacent structures. 11–13 Unlike diode laser treatment, controlled thermal coagulation is facilitated with HIFU, enabling good targeting of the tissue to be treated as well as precise temperature control. Further, in contrast to cyclo-destructive methods, ultrasound treatment induces a remodelling of the ciliary body whereby epithelial cell layers are removed with preservation of the blood–aqueous barrier and no apparent explosion of ciliary processes (Figures 2 and 3). Scanning electron microscopy of vascular corrosion cast following UCP treatment shows interruption of ciliary body’s and pars plana microvasculature (Figure 4) in the treated zone (untreated areas are intact). The iris, iris root, major and minor arterial iris circles appeared untouched. 35