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by Philip Filner, Ph. D.
DRY AND WET FORMS
Age related macular degeneration occurs most commonly in a "dry" form. No effective
treatment has yet been developed for the dry form. Only about 10-15% of cases are the "wet" form, but about 90% of cases of macular degeneration which progress to legal
blindness are instances of the wet form. In the case of the wet form, neovascularization, i.e. abnormal proliferation of blood vessels, occurs behind the macula, accompanied by
damage-causing leakage from the blood vessels into the macula. In the center of the macula is the region called the fovea. Neovascularizations of the macula are classified as
extrafoveal or subfoveal.
LASER SURGERY
In extrafoveal instances of the wet form, laser surgery can be used to slow neovascularization and leakage by killing the proliferating blood vessels in very small spots, a treatment
called photocoagulation. Unfortunately, the process also kills cells of the overlying macula within the same spot. Laser surgery is frequently done more than once on a patient,
usually when the patient notices a further deterioration of central vision.
Photocoagulation is usually not used on subfoveal neovascularizations because photocoagulation
within the area of the fovea causes a substantial, immmedate, irreversible decrease in vision.
IONIZING RADIATION
Ionizing radiation can also be used to kill cells. While the laser essentially cooks the cells
exposed to its tightly focused beam, ionizing radiation is usually administered in a beam large enough to expose most of the eye. It causes changes in the structures of a small
fraction of molecules in each exposed cell. Because some molecules are essential to cellular life processes, and their functions have very specific chemical structure requirements,
the molecules with altered structures interfere with the normal life processes of the cell. A moderate dose of ionizing radiation can slow cellular life processes, including
proliferation. A higher dose can stop essential life processes, i.e. kill cells. Because proliferating cells are usually more sensitive to ionizing radiation than are
non-proliferating cells, ionizing radiation is commonly used to retard/stop abnormal proliferations of cells which are life-threatening, i.e. cancerous tumors.
Ionizing
radiation cannot be conveniently focused as a laser can. Rather, the beam of radiation can be kept to a limited size by passing it through absorbing barriers, each with an aligned
opening. The size of the opening selected for a treatment, hence the extent of exposure of tissue not in the macula, depends on the intensity of the available beam.
Some types
of ionizing radiation, notably X-rays, have high penetrating power, so only part of the radiation is absorbed by tissue, and all levels of tissue in line with the beam are exposed and
affected. Other types of ionizing radiation, such as protons, have very limited penetrating power, and stop abruptly after passing through a certain amount of tissue mass.
Consequently, cells near the limit of tissue mass for the incoming beam absorb most of the radiation, while tissues further along the path of the beam are exposed to far less
radiation and suffer very little damage.
While the proton beam has the advantage of mainly affecting cells near the beam's penetration limit, it has the disadvantage that
proton beam sources are not as widely available as xray sources.
IONIZING RADIATION STUDIES
In 1993, a group at the University of Belfast in Northern Ireland reported that they had tried X-rays on a small number patients
with the wet form of macular degeneration and subfoveal vascularization. Their positive results have been supported by several similar studies with X-rays done by other research
teams, at sites in Europe and the U.S..
In 1996, a group at Loma Linda University in California reported results from irradiation with a proton beam. Studies have been done at
two dosage levels, each on a small number of patients with the wet form of macular degeneration and subfoveal neovascularization. The results reported for proton irradiation are
similar to the results reported for x-ray irradiation.
Some results of these radiation studies:
Immediate vision loss did not result from the treatment. This would be expected if the cells proliferating in the
neovascularizations were more sensitive to ionizing radiation than were non-proliferating cells in the overlying fovea. In the Belfast study, which had control (i.e. untreated)
and treated patients, 6 of 7 (86%) control patients exhibited decreased visual acuity in followup observations after 1 year, while 12 of 19 (63%) treated patients had stable or
improved visual acuity after 1 year. Because of the very small size of these samples, this apparent difference could be a chance result, i.e. two random fluctuations from a common
mean expected for "no difference". In the proton irradiation study, which lacked control patients, after 1 year, 11 of 19 (58%) treated patients reported stable or
improved visual acuity. In the proton irradiation study, objective evidence of a treatment response was obtained by fluorescein angiography, which showed reduced lesion size or no
leakage in 10 of 19 (53%) patients. A higher dose of proton irradiation yielded positive results in higher percentages of patients.
TENTATIVE CONCLUSIONS
Several small studies of the effects of ionizing
radiation on the wet, subfoveal form of macular degeneration indicate that such a treatment may be able to stabilize the visual acuity of most patients, without an immediate loss of
visual acuity like that caused by laser surgery on subfoveal neovascularizations.
A large scale study is needed to establish the true worth of treatment with ionizing
radiation, as well as the optimal radiation source and dose level. The study should include as controls both untreated and placebo-treated patients. It should include enough patients
to permit detection of statistically significant differences between treated and control patients. The study should involve more than one dosage level, exposure regime, and radiation
source. Observations should be made by individuals not aware of which patients received which treatments. Followup observations should span at least 2 years.
A study involving
300 patients was started in 1995 at the Medical College of Georgia.
LITERATURE CITATIONS
X-rays Chakravarthy, U. Houston, R. F., Archer, D. B. Treatment of age-related subfoveal neovascular membrane by teletherapy; a
pilot study Br. J. Ophthalmol. 77:265-273(1993).
Bergink, G.J., Deutman, A. F., van den BVroek, J. F., van Daal, W. A.J. Radiation Therapy for subfoveal choroidal neovascular
membranes in age-reklated macular degeneration. A pilot study. Graefes Arch. Clin. Exp. Ophthalmol. 232:591-598(1994).
Brady, L. W., M.D. Radiotherapy in Macular Degenerartion
Int. J. Radiation Oncology Biology Physics 36:963(1996).
Protons Yonemoto, L.T., D.D., Slater, J.D., M.D., Friedrichsen, E.J., M.D., Loredo, L. N., M.D., Ing, J., M.D.,
Archambeau, J. O., M.D., F.A.C.R., Teichman, S., B.S.N., Moyers, M.F., Ph. D., Blacharski, P. A., M.D. and Slater, J. M., M.D., F.A.C.R. Phase I/II Study of Proton Beam Irradiation
for the Treatment of Subfoveal Choroidal Neovascularization in Age-Related macular Degeneration: Treatment Techniques and Preliminary Results Int. J. Radiation Oncology Biology
Physics 36:867-871 (1996). |
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