Age-related macular degeneration: long-term results of radiotherapy for subfoveal neovascular membranes. Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration. Randomized trial of radiation for age-related macular degeneration. A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation. [Radiotherapy of exudative senile macular degeneration. A prospective controlled study]. Radiotherapy for subfoveal choroidal neovascularization in age-related macular degeneration: a randomized clinical trial. [The results of randomized controlled trial of low-dose radiation for wet-type age-related macular degeneration on a 1 year term basis]. Sham radiation in clinical trials assessing radiotherapy for exudative age-related macular degeneration. Strontium plaque brachytherapy for exudative age-related macular degeneration: three-year results of a randomized study. Proton therapy for exudative age-related macular degeneration: a randomized, sham-controlled clinical trial. Radiotherapy for age-related macular degeneration: is there a benefit for classic CNV?
To study results of 2-year follow-up of radiotherapy for subfoveal choroidal neovascular membrane associated with age-related macular degeneration.
                In a randomized prospective clinical study, 101 patients received a low-dose radiotherapy or no treatment. In the treatment group, subfoveal choroidal neovascular membranes were treated with 20 Gy of 6-MV photons to the macula of the affected eye.
                The overall complete follow-up rate was 84.2% (85/101). No measurable treatment-related morbidity was seen during or after treatment. Mean changes in log of minimal angle of resolution (logMAR) of visual acuity and area of choroidal neovascular membrane for 2-year follow-up were +0.226 +/- 0.373 and 143.5 +/- 53.1% in the treatment group, and +0.563 +/- 0.370 and 190. 3 +/- 81.4% in the control group; a significant difference was found (P <.0001; P =.0008). In patients with smaller choroidal neovascular membrane (</=1.5 mm(2)) or better visual acuity (>/=60/200) at baseline, the treatment group showed a significantly smaller increase in area of choroidal neovascular membrane and a significantly smaller decrease in LogMAR visual acuity for 2 years, whereas there was no significant difference in patients with larger choroidal neovascular membrane (>1.5 mm(2)) or poorer visual acuity (<60/200).
                Radiotherapy appeared to have a favorable treatment effect in eyes with subfoveal neovascular membrane associated with AMD. Favorable factors for radiotherapy were a smaller area of choroidal neovascular membrane and better visual acuity. To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration.
                A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only.
                Three United Kingdom-based hospital units.
                Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better.
                Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed.
                The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed.
                At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P =.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P =.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients.
                The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration. To assess external beam radiation efficacy for subfoveal neovascularization associated with age-related macular degeneration.
                All patients were evaluated in the same institution. In this prospective trial, 27 eyes (27 patients) with subfoveal neovascularization associated with age-related macular degeneration were randomized to either single fraction radiation (750 centigray) or observation. Endpoints were assessed by fluorescein angiography and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Examiners were masked to patient treatment status. Parametric and nonparametric statistical analyses were performed.
                Twenty-seven patients were entered into the trial with a mean age of 76 years (range, 64 to 89) and a mean follow-up of 17 months (range, 7 to 32). The visual acuity loss was slightly less in the irradiated group, a finding of borderline significance (P < .046). There was no significant difference in fluorescein angiographic evidence of subretinal neovascular membrane change in the control group vs the irradiated group.
                External beam radiation, at this dose and fractionation, did not appear harmful. There was slightly less visual loss in irradiated eyes. No difference in fluorescein angiographic characteristics of subfoveal neovascularization size or progression in eyes with age-related macular degeneration was noted. The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD.
                Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion.
                At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P = 0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P = 0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P = 0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at least 12 months (P = 0.5, log rank test). No side effects were observed.
                Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited. Despite the successful therapy of subretinal neovascular membranes by laserphotocoagulation there are many problems to be overcome. In the case of subfoveolar neovascularization, photocoagulation leads to a sudden decrease in visual acuity. Recently radiotherapy is considered as an alternative. Complications and effectivity were evaluated in this prospective and randomized trial. The initial results are presented.
                There are 76 patients (51 women, 25 men, average age 77.7 +/- 8.6 years) included in the prospective randomized study. All of them show subfoveolar neovascular membranes in FLA and a decrease in visual acuity between 0.05 and 0.5. They were randomly assigned to either the radiotherapy or the control group. Radiotherapy was done within 6 days by 6 x 2 Gy (6 MV photons). The follow-up was at 4 weeks, after 3 months, after 6 months and then every 6 months after the end of radiotherapy. On average the follow-up is at 15.1 months.
                Concerning age and visual acuity before therapy, the control group and the radiotherapy group were not significantly different. At 4 weeks after radiotherapy, visual acuity was 0.13 +/- 0.46 (LogMAR). After 12 months, visual acuity at a distance was 0.11 +/- 0.30 in the therapy group and 0.09 +/- 0.13 (P = 0.838) in the control group. Patients with a preoperative visual acuity better than 0.2 improved more after radiotherapy. Metamorphopsy improved in 75% of the therapy group. The following complications could be observed: In the control group 3 patients suffered subretinal bleeding, in the radiotherapy group 3 patients, respectively.
                At present, the follow-up is too short to recommend radiotherapy as a standard procedure in the case of subfoveolar neovascularization. The results in patients with a better preoperative visual acuity encourage us to continue this study. To report results of 18-month follow up of external beam radiation therapy with photons for subfoveal classic or occult choroidal neovascularization (CNV) in age-related macular degeneration (ARMD).
                Randomized clinical trial.
                A total of 161 patients with subfoveal CNV in ARMD were recruited in a prospective double-masked study. The posterior pole of the afflicted eye was given 1 Gy (4 x 0.25 Gy) in the control group and 8 Gy (4 x 2 Gy) or 16 Gy (4 x 4 Gy) in the treatment groups. At the time of treatment, and 6, 12, and 18 months post treatment, best-corrected visual acuity (BCVA), reading ability, and CNV size were measured.
                At the completion of the study 150 (93.2%), 139 (86.3%), and 137 (85.1%) patients were followed for 6, 12, and 18 months, respectively. The mean number of lines lost in the BCVA was -1.69, -2.2, and -3.23 in the 1 Gy group; -0.94, -1.25, and -1.73 in the 8 Gy group; -0.51, -0.67, and -1.93 in the 16 Gy group. The difference was significant after 12 months (P =.016 for 8 Gy vs. 1 Gy; P =.006 for 16 Gy vs. 1 Gy), and 18 months (P =.011 for 8 Gy vs. 1 Gy; P =.05 for 16 Gy vs. 1 Gy). The patients with classic CNV, or with an initial distance visual acuity >or=20/100, benefited more from treatment. A significant difference was not found between control group and treatment groups in the reading ability and in the CNV size. No radiation-associated side effects were reported thus far.
                The number of lines lost in the BCVA was less in the 8 Gy and 16 Gy treatment groups than in the control group during the complete follow up examination. Radiation therapy with 8 Gy and 16 Gy, without showing any difference in efficacy, resulted in a near stabilization of the BCVA in patients with subfoveal classic or occult CNV in ARMD. Further studies are necessary to determine the significance of repeated radiotherapy series with a dose of 8 Gy to improve the effect on the CNV size and thereby to prolong stabilization of distance visual acuity. Evaluation of low dose radiation therapy to the wet-type age-related macular degeneration (AMD) located at the fovea centralis.
                Patients were irradiated with 10 fractions of 2 Gy external beam or just observed. Between the treated(39) and untreated (31) cases, there was no significant difference in gender, age, initial visual acuity, or size of the neovascular membrane.
                With the follow-up of 12 months, the visual acuity was significantly well preserved and the size of the neovascular membrane was decreased.
                These results indicate that low dose irradiation is effective for the wet-type AMD of the stage we treated in the present study. To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study.
                Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment?
                Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation.
                Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group. To determine the efficacy of strontium plaque (Sr90) brachytherapy for age-related macular degeneration (AMD) with subfoveal choroidal neovascularization (CNV).
                Randomized clinical trial.
                Eighty-eight eyes of 86 patients with subfoveal CNV secondary to AMD were randomized either to plaque radiotherapy or to observation.
                Radiotherapy was given as episcleral brachytherapy using Sr90 plaques. Two different plaque types were used. Plaque I had a diameter of 8 mm and delivered a dose of 15 Gy at a depth of 1.75 mm in 54 minutes. With plaque II, the corresponding values were 4 mm, 12.6 Gy, and 11 minutes. The control group was observed without any treatment.
                The primary outcome measure was visual acuity at 6, 12, 24, and 36 months. Other outcome variables were contrast sensitivity, fluorescein angiographic, and clinically evaluated changes in the macula.
                Eighty-two patients (84 eyes [95%]) completed the 1-year follow-up, and 80 (93%) and 74 (86%) patients completed the 2- and 3-year follow-ups, respectively. At 6 months, visual loss of > or =3 lines occurred in 20% of treated patients and 42% of control patients (P = 0.031). At 12 months, a visual loss of > or =3 lines occurred in 45% (treated) and 56% (controls) (P = 0.325); at 24 months, in 73% and 71% (P = 0.914); and at 36 months, in 80% and 84% of patients (P = 0.591), respectively. Patients irradiated with plaque I had better results: a visual loss of > or =3 lines occurred in 6% at 6 months (P = 0.008, relative to controls), in 18% at 12 months (P = 0.007), in 59% at 24 months (P = 0.348), and in 71% at 36 months (P = 0.212). In patients treated with plaque II, the corresponding values were 29% (P = 0.032), 65% (P = 0.459), 83% (P = 0.317), and 80% (P = 0.687) at 6, 12, 24, and 36 months, respectively.
                The short-term clinical course of exudative AMD is affected by Sr90 brachytherapy, but by 12 months, there was no treatment benefit. This article contains additional online-only material available at http://www.ophsource.org/periodicals/ophtha. To examine the effect of proton beam irradiation on subfoveal choroidal neovascular membranes (CNVM) associated with age-related macular degeneration (AMD).Randomized, prospective, sham-controlled, double-masked treatment trial.
                Thirty-seven subjects with subfoveal CNVM due to AMD were randomly assigned to 16-Gy proton irradiation delivered in two fractions 24 hours apart or to sham control treatment. Recruitment was halted at 37 subjects for ethical reasons regarding randomization to sham treatment when Food and Drug Administration approval of Visudyne was anticipated.
                Proton irradiation was associated with a trend toward stabilization of visual acuity, but this association did not reach statistical significance. No correlations were found within the fluorescein angiography data, including greatest linear dimension of CNVM total size, area of active leakage, area of associated subretinal hemorrhage, and intensity.
                With the acceptance of photodynamic therapy, future studies will require more complex design and larger sample size to determine whether radiation can play either a primary or adjunctive role in treating these lesions. To evaluate the efficacy of radiotherapy in the treatment of subfoveal classic and occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD) under strict fixation control.
                Twenty-seven eyes of 27 patients with subfoveal CNV as a result of AMD were treated with a total dose of 20 Gy in 10 fractions (10 well-defined, 17 occult). Fixation monitoring was achieved by installing a TV camera with an attached fixation light 3 cm from the cornea of the eye being treated. Visual acuity and fluorescein angiography were obtained before and 6 months after treatment. Fifteen eyes of 15 patients served as controls (4 well-defined, 11 occult).
                After 6 months the treated group showed an average decrease in visual acuity of 27%; the control group experienced a decrease of 31%. Membrane size increased by 56% in the treated group and by 28% in the control group. There was no statistically significant difference. Within the subgroup analysis, however, patients with classic CNV suffered significantly less visual loss than in the control group.
                Radiation therapy under optimized treatment conditions by fixation monitoring failed to control further growth in membrane size in both classic and occult CNV. Regarding visual acuity, however, patients with classic CNV seem to benefit from radiation treatment compared to the natural course.
This review currently does not provide convincing evidence that radiotherapy is an effective treatment for neovascular AMD. If further trials are to be considered to evaluate radiotherapy in AMD then adequate masking of the control group must be considered.