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. Indirect scatter laser photocoagulation to subfoveal choroidal neovascularization in age-related macular degeneration. Macular scatter ('grid') laser treatment of poorly demarcated subfoveal choroidal neovascularization in age-related macular degeneration. Results of a randomized pilot trial. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group. Grid laser treatment of occult choroidal neovascularization in age related macular degeneration. Proton therapy for exudative age-related macular degeneration: a randomized, sham-controlled clinical trial. [Radiotherapy of exudative senile macular degeneration. A prospective controlled study]. Radiotherapy for subfoveal choroidal neovascularization in age-related macular degeneration: a randomized clinical trial. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Radiotherapy for age-related macular degeneration: is there a benefit for classic CNV? Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group. Verteporfin therapy of subfoveal occult choroidal neovascularization in AMD using delayed light application: one-year results of the VALIO Study. Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.
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. Occult choroidal neovascularization (CNV), poorly defined on fluorescein angiography, is present in the majority of patients with exudative complications of age-related macular degeneration. For patients who present with this type of subfoveal CNV but who have useful visual acuity, no form of treatment is of proven benefit. Accordingly, a pilot randomized trial of indirect laser treatment was performed. The rationale of this treatment was to inhibit the CNV through laser-induced effects on the retinal pigment epithelium.
                Patients with occult subfoveal CNV without retinal pigment epithelial detachment and with visual acuity of 20/200 or better were randomized to treatment or control groups. A grid of laser burns was applied to the macula beyond the area of serous retinal detachment and of angiographically defined occult CNV.
                After an average follow-up of 38 months, there was no difference in mean final visual acuity (0.12 treated, 0.14 control) or clinical outcome between treated and untreated groups. Fluorescein angiography showed gradual enlargement in the occult CNV in 58% of eyes in both groups. A decrease in visual acuity to worse than 20/200 (54% of treated, 50% of control eyes) was associated with ingrowth of well-delineated CNV (6 treated, 7 control eyes) or progression to a fibroglial or atrophic scar (11 treated, 8 control eyes).
                No benefit was demonstrated for scatter photocoagulation of the macula in patients with age-related macular degeneration and occult subfoveal CNV with initially good visual acuity. There were, however, no complications related to treatment. To determine the effects of macular scatter ("grid") laser photocoagulation compared with observation on the visual function of eyes with subfoveal choroidal neovascularization (CNV) that has poorly demarcated boundaries and to provide preliminary data for the evaluation of the feasibility and design of a larger, definitive trial.
                Randomized pilot clinical trial.
                Two tertiary care retinal referral practices.
                Symptomatic individuals with subfoveal CNV secondary to age-related macular degeneration in whom fluorescein angiography showed occult CNV with poorly demarcated boundaries; classic CNV was allowed but did not need to be present for entry into the study.
                Change in visual acuity from baseline to specified time periods.
                Fifty-two eyes were assigned to observation. Fifty-one eyes were assigned randomly to treatment consisting of macular scatter ("grid") laser photocoagulation to the area of CNV. The treatment protocol for 8 of these eyes also included confluent laser photocoagulation to areas of classic CNV. The average visual acuity decrease from baseline was greater in the treated than in the observed group. The difference between these groups was greatest within the first year after study enrollment. At 24 months, slightly more than 40% of the eyes in each group had lost 6 or more lines of visual acuity. Similar results were noted for the subgroup of eyes initially with angiographic features of occult CNV but no classic CNV.
                These short-term study results suggest that macular scatter ("grid") laser treatment is not beneficial and is possibly harmful compared with observation for symptomatic subfoveal CNV with poorly demarcated boundaries in age-related macular degeneration. With or without treatment, a significant proportion of these patients are at risk of severe visual loss within 2 years of seeking treatment, even when the eye initially has occult CNV and no classic CNV. To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) can safely reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD).
                Two multicenter, double-masked, placebo-controlled, randomized clinical trials.
                Twenty-two ophthalmology practices in Europe and North America.
                Patients with subfoveal CNV lesions caused by AMD measuring 5400 microm or less in greatest linear dimension with evidence of classic CNV and best-corrected visual acuity of approximately 20/40 to 20/200.
                Six hundred nine patients were randomly assigned (2: 1) to verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) administered via intravenous infusion of 30 mL over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50J/cm2 at an intensity of 600 mW/cm2 over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the CNV lesion. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fuorescein leakage. The primary outcome was the proportion of eyes with fewer than 15 letters lost (approximately <3 lines of loss), adhering to an intent-to-treat analysis.
                In each group, 94% of patients completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month-12 examination, 246 (61%) of 402 eyes assigned to verteporfin compared with 96 (46%) of 207 eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline (P<.001). In subgroup analyses, the visual acuity benefit (< 15 letters lost) of verteporfin therapy was clearly demonstrated (67% vs 39%; P<.001) when the area of classic CNV occupied 50% or more of the area of the entire lesion (termed predominantly classic CNV lesions), especially when there was no occult CNV. No statistically significant differences in visual acuity were noted when the area of classic CNV was more than 0% but less than 50% of the area of the entire lesion. Few ocular or other systemic adverse events were associated with verteporfin treatment, compared with placebo, including transient visual disturbances (18% vs 12%), injection-site adverse events (13% vs 3%), transient photosensitivity reactions (3% vs 0%), and infusion-related low back pain (2% vs 0%).
                Since verteporfin therapy of subfoveal CNV from AMD can safely reduce the risk of vision loss, we recommend verteporfin therapy for treatment of patients with predominantly classic CNV from AMD. Laser photocoagulation treatment of occult choroidal neovascularization (CNV) in age related macular degeneration has been up to now discouraging. We report a randomized clinical trial comparing 'grid' laser treatment versus the natural course in 24 eyes with this kind of neovascularization. In 12 eyes a low energy scatter photocoagulation was applied to the areas of presumed CNV and abnormal retinal pigment epithelium, sparing the fovea. The follow-up ranged from 1 to 3 years. At the three months follow-up visit, the subretinal exudation appeared reduced in 40% of the treated eyes and in none of the control eyes. During the period of follow-up the occult CNV turned to classic CNV in 4 treated and in 4 untreated eyes. At the last examination (average follow-up 18 months), anatomical and functional conditions were not significantly different in the two groups. Our data fail to show a beneficial long-term effect of grid laser treatment for occult CNV; no iatrogenic complications were seen in our series. 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. 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. A clinical trial has been conducted to evaluate the effect on vision of laser treatment (argon green or krypton red lasers, assigned randomly) compared with no treatment of eyes with subfoveal choroidal neovascularization associated with age-related macular degeneration. Three months after enrollment, the visual acuity of 37 (20%) of 184 laser-treated eyes had decreased 6 or more lines from the baseline level, while only 19 (11%) of 178 untreated eyes had suffered such large decreases (P = .01, chi 2 test). However, 24 months after enrollment, the visual acuity of only 23 (20%) of 114 laser-treated eyes had decreased by 6 or more lines from baseline compared with 41 (37%) of 112 untreated eyes (P less than .01, chi 2 test). On average, after 24 months, visual acuity of laser-treated eyes had decreased 3 lines from baseline, and visual acuity of untreated eyes had decreased 4 lines (P = .003, t test). Laser-treated eyes retained contrast threshold for large letters at or near baseline levels through 36 months of follow-up examinations, while the contrast threshold of untreated eyes worsened. Persistent or recurrent neovascularization was observed in 51% of the laser-treated eyes by 24 months after initial treatment but was not associated with decreased visual acuity. None of the findings suggested a reason to favor either the argon green or krypton red wavelength. Laser treatment of subfoveal neovascular lesions that meet the eligibility criteria for this study is recommended if both the patient and the ophthalmologist are prepared for a large decrease in visual acuity immediately after treatment. 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. The Age-Related Macular Degeneration Study-Krypton Laser (AMDS-K) is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with macular degeneration that have either choroidal neovascularization 1 to 199 microns from the center of the foveal avascular zone or choroidal neovascularization 200 microns or farther from the foveal avascular zone center with blood and/or blocked fluorescence extending within 200 microns of the foveal avascular zone center. Recruitment ended in December 1987 after 247 patients had been assigned to photocoagulation and 249 patients had been assigned to no treatment. At 3 years after randomization, 49% (86/174) of treated eyes, in contrast to 58% (98/169) of untreated eyes, had lost six or more lines of visual acuity. The average visual acuity of treated and untreated eyes at that time was 20/200 and 20/250, respectively. The benefit of laser treatment was largest among patients without evidence of hypertension and diminished to no apparent benefit among patients who had highly elevated blood pressure and/or used antihypertensive medication. Treatment of lesions meeting the AMDS-K eligibility criteria in eyes of patients with no hypertension is recommended. However, treatment cannot be recommended uniformly for patients with definite hypertension having lesions similar to those of patients enrolled in the AMDS-K. To compare photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) using either standard or delayed light application.
                Phase II, multicenter, masked, randomized clinical trial.
                Sixty patients with occult with no classic choroidal neovascularization (CNV) resulting from age-related macular degeneration were assigned randomly (1:1) to verteporfin infusion followed by light application either at 15 minutes (standard light) or 30 minutes (delayed light) after the start of the infusion. The assigned treatment was repeated every three months if fluorescein leakage was detected.
                At month 12, patients lost a mean of 15.7 letters and 11.4 letters from baseline in the standard and delayed light groups, respectively (P = .38). Twelve (52%) of 23 patients in the standard light group and 11 (42%) of 26 in the delayed light group lost at least 15 letters of visual acuity (P = .57).
                There were no statistically significant differences between verteporfin therapy using the delayed light regimen of 30 minutes or the standard light regimen of 15 minutes in eyes with occult with no classic CNV. To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration.
                Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial.
                Nineteen ophthalmology practices in North America and Europe.
                Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas.
                We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis.
                One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF.
                Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.
In the medium to long term laser photocoagulation of CNV slows the progression of visual loss in people with neovascular AMD. However, it is associated with an increased risk of visual loss immediately after treatment and this period may be longer in people with subfoveal AMD. With the advent of modern pharmacological therapies, and concern for the impact of iatrogenic scotoma in subfoveal CNV, laser photocoagulation of subfoveal CNV is not recommended. No studies have compared photocoagulation with modern pharmacological agents for AMD for non-subfoveal CNV.