Although anti-vascular endothelial growth factor (anti-VEGF) therapy has provided a tremendous advancement in the treatment of neovascular (wet) age-related macular degeneration (AMD), the need for frequent injections over an indefinite period of time has placed a tremendous burden on patients, caregivers, physicians and healthcare providers, such as the UK's National Health Service (NHS).

Choroidal neovascularization (CNV) is a result of over-expression of vascular endothelial growth factor, recruitment of inflammatory cells, and fibroblasts. Radiation is known preferentially to damage proliferating endothelial cells. Epimacular brachytherapy is an AMD therapy that utilizes a novel surgical device to deliver targeted beta radiation to active AMD lesions. Unlike anti-VEGF agents, radiation is thought to eliminate CNV vessels permanently, rather than simply suppress them. For this reason, the device offers the prospect of a one-off operation, rather than a lifetime of intravitreal injections entailing considerable expense, patient inconvenience, and a small but cumulative risk of complications.

Early studies of radiation

The therapeutic potential of radiation for CNV has been recognized for many years. Despite this, early attempts to deliver radiation using external beams had variable success, perhaps because it was found to be difficult to target the small CNV lesions without causing collateral damage. Subsequent studies — using an extraocular radioactive plaque positioned on the external sclera surface — confirmed a biological response, but results were often only marginally better than the natural history, and far less successful than modern anti-VEGF therapy.

Successive attempts to provide a more focal delivery under the retina had only limited success, as the very process of accessing the subretinal space caused damage. By contrast, epimacular brachytherapy — which involves the delivery of beta radiation via a vitrectomy procedure — has the potential to provide a highly targeted delivery of beta radiation without surgical damage to the retina.

Details of the procedure

Figure 1

The epimacular brachytherapy device, which was developed by NeoVista Inc., is designed to allow intraocular, epimacular, focal delivery of radiation to the CNV lesion while minimizing the amount of radiation delivered to surrounding structures and the healthy retina. Initial trials suggest the treatment is safe and effective, with results remaining stable over time.

The device consists of a hand piece with a 20-gauge cannula, within which resides a retractable radiation source (the radioactive isotope strontium-90).

Figure 2

Before the device is inserted into the eye, the surgeon undertakes a pars plana vitrectomy. Once the vitreous has been removed, the surgeon positions the device into the mid-vitreous cavity and the radioactive source is moved down the cannula into position (Figure 1). The cannula is then positioned directly over the CNV lesion using fluorescein angiography guidance (Figure 2). The device is held in position for approximately four minutes and then removed. Surgery is usually undertaken using local anaesthetic in a day case setting.

Table 1

Because beta radiation decreases exponentially with increasing distance from the source, the delivery of radiation to neighbouring structures is low. Hence, the macular lesion receives 24 Gy, the optic nerve receives 2.4 Gy, and the lens receives 0.0006 Gy (Table 1). To date, at three years of follow-up, no cases of radiation retinopathy have been observed; this is to be expected, as the radiation exposure levels are below known safety thresholds: the total dose received by the patients is less than the radiation delivered by a routine chest X-ray.