Multicenter Clinical Trial of Ultrasonic Circular Cyclo Coagulation in glaucoma patients without previous filtering surgery. Results at 12 months

PURPOSE

To evaluate the safety and efficacy of HIFU (high-intensity focused ultrasound) delivered by a miniaturized annular therapy

probe in order to perform the new UC3 procedure (Ultrasound Circular Cyclo Coagulation) in patients with glaucoma naïve of

previous filtering surgery.

METHODS

HIFU device (EyeOP1 – EyeTechCare

– France) : A ring shaped therapy

probe containing six active

piezoelectric elements was inserted in

a coupling cone made of polymer.

Each of the six transducers had a

segment of a 10.2 mm radius cylinder

with a 4,5 mm width and a 7 mm

length (surface area of about 35 mm²).

RESULTS: IOP reduction

CONCLUSIONS

Ultrasound Circular Cyclo Coagulation (UC3 procedure) of the ciliary body using HIFU (high-intensity focused

ultrasound) delivered by a ring-shaped miniaturized therapy probe seems to be an effective and well tolerated method

to reduce intraocular pressure in glaucoma patients naïve of previous glaucoma surgery.

The single step procedure is fast (2 minutes) and easy to perform.

Florent Aptel 1, Philippe Denis 2, Jean-Francois Rouland 3, Jean-Paul Renard 4, Alain Bron 5

1-Centre Hospitalier Universitaire de Grenoble, Department of Ophthalmology, Grenoble, France

2-Hospices Civils de Lyon, Hôpital de le Croix-Rousse, Lyon, France

3-Centre Hospitalier Universitaire de Lille, Department of Ophthalmology, Lille, France

4-Hôpital du Val de Grâce, Paris, France

5-Centre Hospitalier Universitaire de Dijon, Department of Ophthalmology, Dijon, France

Ultrasound Biomicroscopy

Safety and tolerability

References:

Aptel F, Béglé A, Razavi A, Romano F, Charrel T, Chapelon JY, Denis P, Lafon C. Short- and long-term effects on the ciliary body and the aqueous outflow pathways of high-

intensity focused ultrasound cyclocoagulation. Ultrasound Med Biol. 2014 Sep;40(9):2096-106.

Aptel F, Dupuy C, Rouland JF. Treatment of refractory open-angle glaucoma using ultrasonic circular cyclocoagulation: a prospective case series. Curr Med Res Opin. 2014

Aug;30(8):1599-605.

Aptel F, Charrel T, Lafon C, Romano F, Chapelon JY, Blumen-Ohana E, Nordmann JP, Denis P. Miniaturized high-intensity focused ultrasound device in patients with

glaucoma: a clinical pilot study. Invest Ophthalmol Vis Sci. 2011 Nov 11;52(12):8747-53.

Charrel T, Aptel F, Birer A, Chavrier F, Romano F, Chapelon JY, Denis P, Lafon C. Development of a miniaturized HIFU device for glaucoma treatment with conformal

coagulation of the ciliary bodies. Ultrasound Med Biol. 2011 May;37(5):742-54.

Aptel F, Charrel T, Palazzi X, Chapelon JY, Denis P, Lafon C. Histologic effects of a new device for high-intensity focused ultrasound cyclocoagulation. Invest Ophthalmol Vis

Sci. 2010 Oct;51(10):5092-8.

Disclosure : FA (Eyetechcare C,) PD (Eyetechcare C), JFR (Eyetechcare R), JPR (No), AB (No)

E-mail : aptel_florent@hotmail.com

UBM showed frequent cystic involution of the ciliary body and a suprachoroidal fluid space.

Figure 5 : Ultrasound biomicroscopy examinations taken at month 3 showing two ultrasound- induced lesions in the superior (A) and inferior (B) circumference of one

patient with complete success. Note that the areas of treatment are located at the junction of the sclera and the base of the ciliary body (Aviso 50 MHz probe, Quantel

Medical, Clermont-Ferrand, France).

No major intra- or post-operative complications occurred. Macular edema was observed in two patients with complete

spontaneous recovery. Clinical examinations showed few signs of intraocular inflammation. No cataract formation, ocular

hypotony and ocular phtysis occurred.

Procedures: Prospective non comparative

interventional clinical study (EyeMust-3) performed in 5

glaucoma centers in France. Thirty eyes of 30 patients

(25 primary open-angle glaucoma and 5 secondary

glaucoma), with intraocular pressure (IOP) > 21 mmHg,

naïve of previous filtering glaucoma surgeries, were

sonicated with a therapy probe comprising 6

piezoelectric transducers.

The 6 transducers were activated with a 6-second

exposure time.

Complete ophthalmic examinations were performed

before the procedure, and at 1 day, 1 week, 1, 2, 3, 6

and 12 months after.

Primary outcomes were surgical success (defined as

IOP reduction from baseline ≥ 20% and IOP > 5mmHg)

at the last follow-up visit, and vision-threatening

complications. Secondary outcomes were mean IOP at

each follow-up visits compared to baseline, medication

use, and complications.

The six transducers were placed at

regular intervals on the circumference

of the ring and oriented in order to

create a focal zone consisting of 6

elliptic cylinders regularly disposed in

an 11, 12 or 13 mm diameter circle

superimposed on the ciliary body.

RESULTS: IOP reduction

All patients Responding patients

Mean Glaucoma

medication

Mean Glaucoma

medication

Mean Preop IOP 28.2 ± 7.2 3.6 28.2 ± 7.2 2.9

Mean Postop IOP% IOP reduction (n patients)

1 day20.0 ± 7.3

-29% (n=28)3.6

17.0 ± 5.9-43% (n=19)

3.1

1 week17.1 ± 6.2

-39% (n=30)3.6

16.4 ± 6.0-43% (n=27)

2.9

1 month22.9 ± 8.7

-19% (n=29)3.7

17.9 ± 5.1-38% (n=17)

3.4

2 months19.9 ± 7.0

-29% (n=27)3.5

16.6 ± 3.4-38% (n=20)

3.2

3 months19.4 ± 6.9

-31% (n=26)3.3

17.1 ± 5.6-40% (n=20)

3.1

6 months20.2 ± 7.3

-28% (n=25)3.2

17.7 ± 5.9-37% (n=19)

2.6

12 months19.6 ± 7.9

-30% (n=22)3.1

16.9 ± 3.4-37% (n=19)

2.7

Figure 4: Ultrasound biomicroscopy showing the ciliary body and ciliary processes before treatment with simulation (on the right) of the focal zone induced by the 13 mm diameter ring

(Aviso 50 MHz probe, Quantel Medical, Clermont-Ferrand, France) and comparison (on the left) with the other sizes available (11 and 12mm).

(*) Success in responding patients is defined by an IOP reduction > 20% or IOP <21mmHg with IOP

decrease >4 mmHg

Success rate : 66% (19/30) at 12 months

Figure 3 : Top left : the therapy device comprising two elements: the probe (left) with the 6 piezoelectric elements and the positioning cone (right); Bottom left : the cone in place

showing a ring of visible sclera; when this ring is regular the position is correct and then maintained by a mild vacuum system; Bottom Right : the probe has been inserted in the cone,

and the device has been filled with physiological solution via the well in the middle. The treatment sequence can start.

Figure 1: Left: Low resolution SEM showing one lesion spatially limited including 12 adjacent ciliary processes, 6 months (A) after sonication, compared to control. Right:: Low

magnification SEM images of vascular corrosion cast performed after intravascular injection of methacrylate resin and after tissue dissolution showing in an untreated eye and a treated

eye, showing a focal defect of the ciliary body microvasculature (Aptel et al, Ultr Med Biol 2014).

Age (yrs): mean (SD)

[range]

62.9 (16.8)

[21-87]

Gender (male/female) 17 / 13

Type of Glaucoma

- Primary Open Angle Glaucoma

- Secondary Glaucoma*(Trauma (1), Iris plateau (1) Fuchs Syndrom (1), Aniridia (1), Mixed

(1))

25 / 30

5 / 30

Previous glaucoma Treatment(total of procedures)

- Trabeculoplasty SLT

- Trabeculoplasty ALT

- Trabeculectomy/deep sclerectomy

- Diode cyclo-photocoagulation

7 / 30 (23%)

1 / 30

0 / 30

0 / 30

Lens status (Phakic, PseudoPhakic, Aphakic) 21 / 8 / 1

Number of preoperative hypotensive therapies:mean (SD) [range]

3.6 (1.7)

[0-6]

Preoperative hypotensive therapies by systemic

carbonic anhydrase inhibitors

11 / 30

Table 1 : Population

Because of the lack of IOP reduction, filtering surgeries were performed in 7 patients within 1 year after the HIFU procedure

T044

Annual Congress of European Association for Vision and Eye Research (EVER)– Nice (France) October 2014

Figure 2: Transducers and ultrasound beam of the HIFU device