Elsevier

Ophthalmology

Volume 106, Issue 12, 1 December 1999, Pages 2239-2247
Ophthalmology

A prospective, randomized, double-masked trial on radiation therapy for neovascular age-related macular degeneration (RAD study)☆

Presented in part at the Association for Research in Vision and Ophthalmology annual meeting, Fort Lauderdale, Florida, May 1999; and at the American Academy of Ophthalmology annual meeting, Orlando, Florida, October 1999.
https://doi.org/10.1016/S0161-6420(99)90522-5Get rights and content

Abstract

Objective

To determine the efficacy of external beam radiation therapy on choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD).

Design

Multicenter, parallel, randomized, double-masked clinical trial performed at nine ophthalmic and radiotherapeutic centers.

Participants

Two hundred five patients were randomly assigned either to treatment with 8 fractions of 2 Gy external beam irradiation (n = 101) or to control with 8 fractions of 0 Gy (sham treatment, n = 104). Both patients and ophthalmologists were masked with regard to applied treatment. Patients with subfoveal classic or occult CNV, visual acuity of 20/320 or greater on the Early Treatment Diabetic Retinopathy Study chart, lesion size of 6 disc areas or less, history of visual symptoms of 6 months or less, and absence of foveal hemorrhage were recruited.

Intervention

In the treatment group, external beam irradiation with 8 fractions of 2 Gy was performed, whereas in the control group, sham treatment with 8 fractions of 0 Gy was applied.

Main outcome measures

Primary outcome measure was the difference in visual acuity between baseline and after 1 year of follow-up.

Results

One hundred eighty-three patients (89.3%) completed the 1-year follow-up. The mean reduction in visual acuity was 3.5 ± 4.7 lines in 88 patients of the 8- × 2-Gy treatment group and 3.7 ± 3.8 lines in 95 patients of the 8- × 0-Gy control group. This difference was not statistically significant (P = 0.53, Mann-Whitney U test). At 1 year, 51.1% of treated patients and 52.6% of control subjects lost three or more lines (P = 0.88). Visual acuity in the presence of classic CNV dropped by 3.7 ± 4.4 lines in 33 patients of the treatment group versus 4.3 ± 3.9 lines in 36 patients of the control group (P = 0.47). Visual acuity in 114 patients with occult CNV dropped by 3.4 ± 4.9 in the treatment group (55 patients) versus 3.4 ± 3.8 lines in the control group (59 patients) (P = 0.80).

Conclusions

In this randomized study, radiation therapy at a dose of 16 Gy applied in 8 fractions of 2 Gy provided no benefit as a treatment for subfoveal CNV secondary to ARMD at 1 year.

Section snippets

Study design

The protocol for this study was approved by the Ethics Committees of all participating institutions, and the studies adhere to the Declaration of Helsinki. Nine ophthalmologic and radiotherapeutic tertiary referral centers in Germany enrolled patients in this study. Informed consent was obtained from each patient before recruitment into the trial.

Patient selection and inclusion and exclusion criteria

Consecutive patients from the clinic population of the nine participating centers were selected. Patients had to be 50 years of age or older and be

Recruitment and randomization

A total of 205 patients were recruited between February 1996 and October 1997. A total of 101 patients were randomly allocated to treatment with 8 × 2 Gy, and 104 to the 8 × 0 Gy placebo treatment (control group). Figure 1 gives an account of all randomized patients.

Demographic data

In Table 1, the demographic data of the patients recruited into the study are summarized. The proportion of men and women in both groups was not significantly different (male: treatment group, 38%; control group, 42%; female:

Discussion

In this study, VA change was compared in patients treated with radiation therapy to control subjects receiving sham treatment. External randomization was performed to ensure masking of both patients and ophthalmologists. Only radiation therapists were informed about treatment allocation. The dose regimen of 16 Gy of 6 MV photons in 8 fractions applied in this randomized, double-masked trial did not preserve VA. The mean reduction in VA was 3.5 ± 4.7 lines in the 8 × 2 Gy treatment group and 3.7

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    ☆

    Supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany (grant # Vo 437/3-1), and by the State of Baden-Württemberg, Heidelberg, Germany (grant # 88/94).

    ∗

    Members of the RAD Study Group and their affiliations are listed in the Appendix at the end of this article.

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    [email protected]

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    Copyright © 1999 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved.