New Treatment for Macular Degeneration: Radiation Therapy

Promising CSCCC protocol provides option for some patients afflicted with a form of macular degeneration which can not be treated with conventional laser therapy.

What is macular degeneration?
Macular degeneration can be hereditary or traumatic, but is most commonly age-related and results in a loss of central vision. It can occur in either or both eyes at any age. Pathologic changes include spots of pigmentation or a moth-eaten appearance of the macula.

Age-related macular degeneration (ARMD) is the leading cause of blindness in the United States. Roughly ten percent of the population will develop ARMD, usually in both eyes. Approximately ten percent of these people will have the "wet" form (hemorrhagic exudative), which accounts for the majority of cases of severe ARMD. Wet ARMD is usually attributed to the overabundant formation of local blood vessels (choroidal neovascularization). The opacity formed by this process is called the choroidal neovascular membrane (CNVM) and blocks central vision.

The natural history of wet ARMD is characterized by relentless progression and resultant severe visual loss (defined as uncorrectable visual loss to less than 20/200) within three years in the majority of affected patients.

Standard treatment options for ARMD
A minority of eyes with wet ARMD have a well-defined, reasonably small, well-located CNVM. Focal laser therapy is of use in such cases.

In contrast, up to 90% of eyes with wet ARMD have features that render them unsuitable for laser therapy.

Radiation therapy as a treatment option
Low dose irradiation is known to have a stabilizing effect on the cells that support and line blood vessels and cause wet ARMD. Such radiation has been used to treat other benign inflammatory eye problems for many years.

Two recently reported pilot studies from Northern Ireland and the Netherlands suggest a favorable effect following radiation therapy for wet ARMD. Each saw, in a significant number of patients, regression of the CNVM and a beneficial visual impact.

The CSCCC/CSMC Protocol
Recognizing the poor visual prognosis of eyes with these severe forms of wet ARMD, and encouraged by the promising results of the reported pilot studies, we at Cedars-Sinai Medical Center and The Cedars-Sinai Comprehensive Cancer Center have designed a clinical trial to determine the effectiveness of radiotherapy in eyes with a visually symptomatic, large and/or poorly defined subfoveal neovascular membrane in ARMD. Eligible patients who consent to this trial will be given low dose external beam radiation therapy (1,440 centiGray or "rads" in 8 fractions).

The treatment in this study is a standard therapy and is not experimental in and of itself. Low dose external beam radiation therapy has been used in selected patients with a variety of other benign ophthalmic disorders and its potential toxicities are minimal and well defined. Previously these were largely limited to the possibility of cataract formation. With the modern techniques utilized by the Cedars-Sinai Comprehensive Cancer Centerâs Radiation Oncology Department, including careful immobilization and CT-based three-dimensional planning, that risk can be minimized.

Eligibility for protocol participation
To be eligible to participate in this study, patients must meet the following criteria:

• Fifty years of age or older
• Wet ARMD on ophthalmic physical examination performed by one of the participating ophthalmologist investigators
• Visual symptoms in the study eye attributable to the wet ARMD
• Duration of ARMD-related visual symptoms in the study eye for six months or less
• Corrected distance visual acuity of less than 20/50 but better than 5/200 in the study eye
• Absence of any other ophthalmic disorder(s) likely to affect visual acuity in t he study eye (e.gs., diabetic retinopathy, retinal vein occlusion, clinically significant cataract)

Enrolling in protocol
Prior to enrollment in the study, every patient will undergo a baseline examination by a participating member of the Retina-Vitreous Associates Medical Group. Patients and referring physicians with additional queries are invited to contact either of the principal co-investigators as follows:

Features of wet ARMD that render them unsuitable for laser therapy:
include choroidal neovascular membrane that is angiographically poorly defined, subfoveal, or extrafoveal, or extrafoveal but large (defined as greater than two optic disc areas in size). The visual prognosis for such eyes is far worse. Transvitreal excision and anti-angiogenic drug therapy have been attempted, but have proven fruitless. Until now, there has been no effective treatment.

Pilot Studies:
Hart et al. demonstrated that radiotherapy of one eye, in patients with bilateral CNVM, decreased the size of subsequent disciform scar formation as compared to the untreated eye. In addition, distance and near visual acuities in radiotherapy treated eyes were significantly better than that of untreated fellow eyes. Finger et al. evaluated 137 patients and found that radiotherapy was associated with decreased hemorrhages, exudates, and leakage of neovascular membranes. Freire et al. treated 41 patients with ARMD and found that the majority had improved or regained stable vision following irradiation. This occurred by inducing regression and/or promoting inactivation of the subretinal neo-vessels, resulting in reabsorption of fluid and blood. This reduced the risk for further leakage, bleeding, or subretinal fibrosis, and often resulted in the maintenance of better central vision.