Clinical Research of Ultrasound Ciliary Plasty and Implications for Clinical Practice

European Ophthalmic Review, 2016;10(2):108–12 DOI: https://doi.org/10.17925/EOR.2016.10.02.108

Abstract:

Ultrasound ciliary plasty (UCP) is a novel, non-invasive procedure for the control of intraocular pressure (IOP) in patients with openangle glaucoma (OAG), and is particularly useful for refractory glaucoma after failed filtering surgery and patients with elevated risk of surgical failure due to high risk of conjunctival bleb scarring. A meta-analysis was performed of seven clinical trials, involving 251 patients, which evaluated the efficacy and safety of the procedure. The procedure was effective in reducing mean IOP across all indications and IOP reductions were similar in patients with refractory and non-refractory glaucoma. Safety and tolerability were good, with conjunctival hyperaemia being the most common side effect. Serious complications were rare. Procedures using the second-generation therapy probe were associated with superior reproducibility of IOP reduction compared with the first-generation probe. In summary, the procedure is a promising and effective treatment option for patients with refractory and non-refractory OAG.
Keywords: High-intensity focused ultrasound (HIFU), intraocular pressure (IOP), open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), ciliary body, ultrasound ciliary plasty (UCP)
Disclosure: Philippe Denis has been a consultant to Alcon, Alimera, Allergan, Eye Tech Care, Istar and Théa, received travel support from Alcon, Alimera, Allergan, Eye Tech Care, Istar, MSD, Pfizer and Théa, and been a lecturer for Alcon, Alimera, Allergan, Eye Tech Care, Istar, MSD, Pfizer, Théa and Zeiss.
Compliance with Ethics Guidelines: This metaanalysis involves a review of the literature and did not involve any studies with human or animal subjects performed by the author.
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.
Acknowledgments: Medical writing assistance was provided by Catherine Amey at Touch Medical Media, UK, funded by Eye Tech Care.
Received: October 10, 2016 Accepted November 02, 2016
Correspondence: Philippe Denis, Service d’Ophtalmologie - Bâtiment R, Hôpital de la Croix-Rousse 103, Grande Rue de la Croix-Rousse, 69317 LYON cédex 04, France. E: philippe.denis@chu-lyon.fr
Support: The publication of this article was supported by Eye Tech Care. The views and opinions expressed are those of the authors and do not necessarily reflect those of Eye Tech Care. The authors provided Eye Tech Care with the opportunity to review the article for scientific accuracy before submission. Any resulting changes were made at the author’s discretion.
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.


Interest in the application of ultrasound as treatment for glaucoma began in the 1980s. Following recent breakthroughs in the field of high-intensity focused ultrasound (HIFU) technology, a new procedure, known as ultrasound ciliary plasty (UCP) has been developed for selective, precise and gentle structural modification of the ciliary body, with sparing of the adjacent ocular structures.1–3 The procedure uses a sterile, single-use therapy probe and a positioning cone, and is performed as follows: with the patient lying in the supine position, a polymer coupling cone is positioned on the eye globe, achieving good placement of the six active piezoelectric elements (ultrasound transducers) with respect to distance and centration (see Figure 1). Contact with the eye is maintained through a low-level vacuum (225 mmHg), which is applied by means of a suction ring at the cone base. A ring-shaped treatment probe (30 mm in diameter and 15 mm in height), which contains six transducers, is inserted in the upperportion of the coupling cone.

Three probe models with different diameters are available to account for differences in ocular anatomy. The probe size is determined for each patient, either by ultrasound bio-microscopy (UBM) imaging or optical coherence tomography (OCT) of the anterior segment or by biometry performed at baseline.3 The 4 ml cavity that is created between the eye, cone and treatment probe is filled with sterile, saline solution at room temperature (BSS, Alcon Inc., Fort Worth, TX, USA, or equivalent product). The six elliptical cylinder-shaped impacts are centred on an 11–13 mm diameter circle, depending on the ring diameter chosen, and spread over the eye circumference, while avoiding the nasal–temporal meridian. A second-generation probe has now been developed and differs from the original version in its broader active transducer area (4 mm instead of 2.5 mm) and more precise temperature calibration of each single transducer. Other enhancements of the second-generation probe include: optimised suction and centring on the eye globe; improved coupling of ultrasound due to removal of air bubbles in the liquid which could disturb the ultrasound beam; optimised ergonomics and improved clip to attach the probe into the cone.

Several prospective clinical studies on UCP treatment have been performed with a follow-up of up to 12 months (see Table 1). These studies have all supported the effectiveness of the procedure in reducing intra-ocular pressure (IOP) in patients with glaucoma.4–9 This article describes a metaanalysis of the clinical trial data to date, with a focus on the second-generation probe compared with the previous one. In addition, patient outcome is compared for refractory patients after failed filtering surgery versus surgery naïve patients.

Methods
Data were pooled from seven clinical trials evaluating the first- or second-generation probe (five and two trials, respectively). Criteria for selection included refractory or non-refractory glaucoma patients with IOP >21 mmHg. Refractory means that the patient had at least one failed attempt at filtering surgery. As per the study protocols, glaucoma medications were kept constant for at least two months after the procedure and could then be adjusted at the physician’s discretion to achieve the target IOP. Patient response rate and IOP reduction were analysed by a Chi-squared test for statistical significance.

Results
Patients

Collectively, data from 251 patients (160 male: 91 female) were included in the meta-analysis: 141 and 110 from the studies of the first- and second-generation probe, respectively. Out of the 251 patients, 133 (53%) had refractory glaucoma and 118 (47%) were naïve of filtering surgery. The mean age of the patients was 63 years old (standard deviation ±13 years). The majority of patients (211 patients, 84%) were diagnosed with primary open-angle glaucoma (OAG) and the remainder (40 patients, 16%) had secondary glaucoma. Of the studies analysing the secondgeneration probe (n=110), 90 (82%) patients were of Indian ethnicity.

Efficacy The device, with either first- or second-generation probes, was effective in reducing the mean IOP across all indications (see Figure 2). As Figure 3 shows the average IOP reduction for the second-generation at six-months follow-up was 35% and thus higher than for the first- generation probe at 29%. The success rate, defined as IOP reduction of at least 20% compared to baseline with no medication added, was 54% for the first-generation and 64% for the second-generation probe, respectively (see Figure 4) (the p-value indicates a trend to a higher responder rate for the second-generation).

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Keywords: High-intensity focused ultrasound (HIFU), intraocular pressure (IOP), open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), ciliary body, ultrasound ciliary plasty (UCP)