In the past, there was considerable excitement about the use of radiation therapy in AMD. Early devices, however, had poor targeting necessitating high radiation levels. Moreover, most of the early radiation studies were performed without combination therapy.

Newer systems-such as an intraocular device (EpiRad, NeoVista Inc.) and a non-invasive, low-energy stereotactic X-ray platform (IRay, Oraya Therapeutics)-offer better targeting, lower radiation doses, and combination therapy with anti-vascular endothelial growth factor (VEGF) agents.

"Ionizing radiation therapy and anti-VEGF therapy appear to work in synergy because radiation is antiangiogenic, anti-inflammatory, and antifibrotic and is used frequently in cancer therapy," said Dr. Kaiser, professor of ophthalmology, Cleveland Clinic Lerner College of Medicine, and director, Digital OCT Reading Center, Cole Eye Institute, Cleveland. "This device allows delivery of low-dose, low-energy X-ray radiation to the macula in a defined, controlled manner."

The technology uses a contact lens that stabilizes and tracks eye movements. Three independent radiation beams (for a total of 16 to 24 Gy) are applied through the sclera at the inferior pars plana onto the macula over a period of 10 to 20 minutes during an office visit. No shielding is needed, and the radiation dose is similar to standing in sunlight for 15 minutes.

A phase I pilot trial was performed in Mexico City to determine the safety, efficacy, and biologic effect of the device in patients with choroidal neovascularization (CNV) less than 11 MPS disc areas associated with exudative AMD. All patients had a visual acuity of 20/40 to 20/320 upon enrollment in the study. Patients were divided into two cohorts: those who were treatment naïve and those who had been treated previously with anti-VEGF injections and needed further therapy.

Study protocol

The study protocol called for the patients to receive an injection of ranibizumab (Lucentis, Genentech) at baseline and, within 14 days of the injection, 16 Gy of radiation delivered with the device. The patients received a second injection of ranibizumab and were treated on an as-needed protocol based on any of the following findings: increase in thickness of 100 µm on spectral-domain optical coherence tomography (SD-OCT); appearance of new hemorrhages; new CNV; or a decrease in the visual acuity of 10 or more ETDRS letters.

Twenty-eight patients were included in the study, 15 of whom were treatment naïve and 13 of whom had received previous AMD treatment.

"The safety profile, the primary endpoint, was excellent with no evidence of radiation-related adverse retinal findings at 14 months of follow-up and no evidence of IOP increases related to the device," he said. "Mild transient superficial keratopathy related to the placement of [a vacuum-coupled contact lens interface] (I-Guide, Oraya) was seen. The results showed a nice improvement in vision of about 1.5 lines that was sustained at 12 months."

At 12 months, almost half the patients gained 15 letters or more. No patients had a moderate loss of vision. The increase in visual acuity was reflected by the SD-OCT findings.

"The SD-OCT results showed that there was a mean decrease in the central subfield thickness at 12 months," he said. In addition, the patient treatment burden decreased.

"There was a dramatic reduction in the need for anti-VEGF therapy after the loading dose at the initiation of therapy," he said. "An average of less than one additional injection was needed with the majority of patients not requiring any additional injections."

The only adverse event was mild superficial keratopathy from contact lens placement.

"After 14 months of follow-up, there was no evidence of radiation-related adverse events," he said. "There appears to have been a biologic effect in all lesion types: early lesion, previously treated lesions, and old and new previously untreated lesions."

Radiation therapy in combination with anti-VEGF therapy seemed to extend the durability of the treatment effect, he added.