Researchers say EBRT shows new promise for treatment of eyes with subfoveal CNV

By Cheryl Guttman

Fort Lauderdale - High-dose external beam radiotherapy (EBRT) can be a safe and effective treatment for subfoveal choroidal neovascularisation (CNV) associated with age-related macular degeneration (AMD), according to two new studies.
Researchers from the University of Nottingham reported their findings at the annual meeting of the Association for Research in Vision and Ophthalmology.

They noted that subfoveal recurrences of predominantly classic CNV post-EBRT can be treated safely with verteporfin (Visudyne) photodynamic therapy (PDT), and the antecedent EBRT appears to reduce the need for PDT re-treatments.

The data comes from two case-control studies. One trial showed visual acuity was maintained up to two years of follow-up in 24 eyes treated with the radiotherapy dose of 20 Gy while it worsened progressively in a group of age- and sex-matched controls.

Twelve-month follow-up was available for all subjects and showed vision decreased minimally in the radiotherapy group by 0.1 LogMAR units; that change from baseline was significantly less than the mean loss of 0.5 LogMAR units observed in the control group.

The combination trial included nine eyes of eight patients who underwent radiotherapy using the same 20 Gy dose followed four to 24 months later with PDT. At quarterly follow-up visits conducted over the next 12 months, visual acuity remained stable in the eyes receiving combination treatment and change from baseline vision was not significantly different compared to that in a control group of 20 eyes receiving PDT alone.

However, the radiotherapy-treated eyes received significantly fewer PDT treatments during the 12-month period compared to controls: 2.44 and 3.3, respectively, according to Andrew Browning FRCOphth, Specialist Registrar, Department of Ophthalmology, Queen's Medical Centre, Nottingham, UK.

Higher dose produces lasting effects
Previous randomised, controlled trials found that radiotherapy using relatively low total doses between 12 Gy and 16 Gy had some short-term benefit on vision, but that was not sustained during longer follow-up.

In these studies, radiotherapy with a total dose of 20 Gy appears to allow patients to maintain stable vision for up to two years and is safe as long as the dose is properly fractionated and the beam angulated adequately to avoid anterior segment exposure in both eyes, said Anna Bhan FRCOphth and Parwez Hossain FRCOphth, Clinical Lecturers, Department of Ophthalmology, Nottingham University.

"Interest in radiotherapy has declined after disappointing results were obtained in some trials and with anticipation of PDT. However, PDT requires multiple treatments, and in the UK where it is not eligible for NHS funding, PDT is affordable for only a fraction of appropriate candidates.

"We believe EBRT can be a valuable and safe alternative treatment when properly delivered," said Winfried MK Amoaku MB, PhD, Senior Lecturer in Ophthalmology, University of Nottingham.
He noted that some eyes do not respond to EBRT and some develop recurrent leakage. Follow-up PDT might be an appropriate intervention in those settings.

"Until recently, we had no treatment options available for eyes failing EBRT, but the experience of this small pilot study indicates they can be treated safely with PDT and that the preceding EBRT might allow reduction in the number of PDT sessions needed.
"We feel this justifies further investigation of the benefits of combined radiotherapy and PDT for patients with subfoveal CNV," Dr Amoaku added.

The radiotherapy study included 24 eyes of 24 consecutive patients having one eye with AMD-related subfoveal CNV not previously treated with laser photocoagulation (study eye) and a fellow eye with visual acuity of 6/24 or less secondary to advanced exudative disease.
EBRT treatment was initiated in all eyes within two weeks of obtaining a baseline fluorescein angiogram. The control group included 24 eyes matched by patient age and sex.

All eyes completed quarterly evaluations during an initial year of follow-up. Among the EBRT-treated eyes, mean visual acuity changed from 0.72 LogMAR units at baseline to 0.9 LogMAR units at 12 months.

Learning lessons from oncology
Interest in the combined treatment approach of EBRT followed by PDT was based on the recognition that the two modalities act by different mechanisms of action that may be complementary in improving outcomes and appreciation of the value of combination regimens in the treatment of neoplastic disease.

"In oncology, multi-modal therapy combining radiotherapy and anti-tumour chemotherapy agents is more effective than a single treatment modality alone. When treating CNV, PDT can produce vascular occlusion, and by targeting proliferating endothelial cells within the neovascular membrane, radiotherapy might inhibit vessel recanalisation and further angiogenesis.

"Therefore, these strategies used together might result in more rapid and complete regression of the CNV complex with improved visual outcomes and a fewer number of treatment sessions of PDT," Dr Amoaku said.

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