Radiation therapy for neovascular age-related macular degeneration

Abstract

Antivascular endothelial growth factor (anti-VEGF) therapies represent the standard of care for most patients presenting with neovascular (wet) age-related macular degeneration (neovascular AMD). Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET). Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002), with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.

A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)

“…An innovative, stereotactic, low-voltage X-ray system is currently of interest. 116 It is likely to require a hub-and-spoke model of delivery (newly diagnosed patients attending a first visit at a hub centre and returning to a local spoke centre for subsequent review and further anti-VEGF if required) because of the high capital cost and maintenance of the device. If this method of delivering radiotherapy were to reduce markedly the need for further anti-VEGF injections it could be a cost-effective way of reducing both drug costs and the workload of managing patients with nAMD.…”

Brachytherapy in Neovascular AMD

“…The apoptotic effect of radiation is due to its direct action on the cellular DNA. Radiation leads to ruptures in the single or double strands of DNA and disturbs the purine base pairs, changes that affect cell division and directly modify the cell cycle [43,44]. Radiation also creates free radicals and reactive oxygen products that induce additional indirect DNA damage.…”

“…Unlike the studies in the 1990s that evaluated radiation alone, recent trials have been designed to evaluate whether radiation might work synergistically with intravitreal anti-VEGF drugs, a rationale based on previous evidence [44,53], to reduce the treatment burden of wet AMD. The ideal endpoints for radiation in this scenario would be to reduce the CNV lesions faster, preserve visual acuity, and extend the treatment interval between injections.…”

Stereotactic Radiotherapy for Polypoidal Choroidal Vasculopathy: A Pilot Study

“…Radiotherapy has been proposed for the management of nAMD as it can induce regression of new vessels and inhibit both inflammation and fibrosis [12]. Previous attempts to employ external beam radiation in nAMD treatment produced equivocal results due to the difficulties in obtaining accurate targeting and the inability to avoid collateral damage to surrounding tissues by dispersed energy [13]. Stereotactic radiotherapy (SRT) is the term given to X-ray devices that direct beams from different angles relative to the target area.…”