AMD BRACHYTHERAPY

Following a promising phase I/II safety trial, a minimally invasive episcleral brachytherapy device for treating neovascular age-related macular degeneration (AMD) has completed a complementary observational study, said Laurence J Marsteller MD, CEO of Salutaris Medical Devices, who previewed results at the Ophthalmology Futures Europe Forum 2014 in London.

The new study used imaging technologies to evaluate the distance from the device’s radiation source to target lesions, potentially improving efficacy by precisely calculating
radiation doses.

Ionizing radiation therapy is widely used outside ophthalmology for its anti-angiogenic as well as anti-inflammatory and anti-fibrotic effects, often with anti-VEGF compounds, Dr Marsteller noted. Early results with Salutaris’ SMD-1 episcleral brachytherapy device as well as large trials of epimacular brachytherapy and beam radiation suggest radiation may also be useful for treating wet AMD.

“The mechanism of action goes beyond anti-VEGF and may reduce the treatment burden (of frequent intraocular injections). For many patients it could be ‘one and done’,” Dr Marsteller said.

Precision dosing

Brachytherapy irradiates tissues by placing a radioisotope seed near the target. The SMD-1 device uses Beta radiation from a strontium-90 source because it has a very short range, falling off more than 90 per cent between 1.0mm and 4.0mm from the source, greatly reducing radiation to non-target tissues, Dr Marsteller said.

The SMD-1 device consists of a curved cannula with a fibre-optic light at the tip. The surgeon inserts it through a small conjunctival incision into the sub-Tenon’s space, and uses a handheld indirect ophthalmoscope to place the lighted tip directly behind the target lesion. Using a plunger, a seed of strontium-90 is advanced from a shielded vault on the device handle to the tip, and held there until a prescribed radiation dose is delivered, usually for about five minutes. At no time does the probe penetrate the globe.

In the earlier phase I/II trial conducted at the University of Arizona, Tucson, US, three out of the four treatment-naïve patients and one of the two chronically treated wet AMD patients improved their best corrected visual acuity levels two years after SMD-1 treatment (range: +4 to +25 ETDRS letters), Dr Marsteller said.

In addition, two treatment-naïve patients did not require any further PRN anti-VEGF injections beyond two initial injections mandated by the protocol. While the sample is small, the results are consistent with reduced anti-VEGF injection need observed in trials of epimacular and beam radiation treatments, where patients with classic lesions and early proliferative disease responded best.

Episcleral advantages

The minimally invasive episcleral procedure takes about 15 minutes and can be done in an outpatient clinic with no capital or continuing operating costs, Dr Marsteller said. Patient discomfort is minimal and only about half required a single stitch to close the conjunctival incision. “It is an elegantly simple surgical device,” he said.

The SMD device is unlike the epimacular probe that requires vitrectomy, with related endophthalmitis and cataract risk. Furthermore, the epimacular probe is inserted anteriorly, exposing the retina to more radiation than does the SMD-1’s posterior placement, Dr Marsteller noted.

Trial data also suggest the epimacular probe is difficult to hold steady, possibly resulting in unreliable dosing and uneven results, while the episcleral probe is inherently stable.

Still, the extremely short range of Beta radiation requires extremely precise placement and timing. The second SalutarisMD study, conducted at Moorfields Eye Hospital in London, used ultrasound to measure the total distance from sclera to choroid to retina, and optical coherence tomography to determine the distance from lesion apex to retina.

In future interventional trials, combining this data will allow calculation of the precise dwell time to deliver a therapeutic dose of 24Gy to the entire lesion while holding retina surface exposure to less than 18Gy, which is within safety limits, Dr Marsteller said.

“This ensures consistent, accurate dosing individualised to each patient and independent of the operator. We believe the advantage of consistent radiation dosimetry and individualised targeting will improve patient outcomes,” Dr Marsteller added.

To contact Laurence Marsteller, email Joanne Vitali of Salutaris Medical Devices: jvitali@salutarismd.com