Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial. Prophylactic laser treatment in early age related maculopathy reduced the incidence of exudative complications. Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of nonexudative age-related macular degeneration: two-year results of a randomized pilot study. Prophylactic treatment of age-related macular degeneration report number 1: 810-nanometer laser to eyes with drusen. Unilaterally eligible patients. A pilot randomized controlled study on the effect of laser photocoagulation of confluent soft macular drusen. Laser photocoagulation for macular soft drusen. Updated results.
To evaluate the efficacy and safety of low-intensity laser treatment in the prevention of visual acuity (VA) loss among participants with bilateral large drusen.
                Multicenter randomized clinical trial. One eye of each participant was assigned to treatment, and the contralateral eye was assigned to observation.
                A total of 1052 participants who had > or =10 large (>125 microm) drusen and VA> or =20/40 in each eye enrolled through 22 clinical centers.
                The initial laser treatment protocol specified 60 barely visible burns applied in a grid pattern within an annulus between 1500 and 2500 mum from the foveal center. At 12 months, eyes assigned to treatment that had sufficient drusen remaining were retreated with 30 burns by targeting drusen within an annulus between 1000 and 2000 mum from the foveal center.
                Proportion of eyes at 5 years with loss of > or =3 lines of VA from baseline. Secondary outcome measures included the development of choroidal neovascularization or geographic atrophy (GA), change in contrast threshold, change in critical print size, and incidence of ocular adverse events.
                At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had VA scores > or = 3 lines worse than at the initial visit (P = 1.00). Cumulative 5-year incidence rates for treated and observed eyes were 13.3% and 13.3% (P = 0.95) for choroidal neovascularization and 7.4% and 7.8% (P = 0.64) for GA, respectively. The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed eyes (P = 0.40). The critical print size doubled in 29.6% of treated eyes and in 28.4% of observed eyes (P = 0.70). Seven treated eyes and 14 observed eyes had an adverse event of a > or =6-line loss in VA in the absence of late age-related macular degeneration or cataract.
                As applied in the Complications of Age-Related Macular Degeneration Prevention Trial, low-intensity laser treatment did not demonstrate a clinically significant benefit for vision in eyes of people with bilateral large drusen. To investigate the effect of prophylactic laser treatment on drusen area and incidence of exudative lesions in patients with soft drusen maculopathy.
                In a prospective study, patients with early age related maculopathy (ARM) and good visual acuity were randomized to laser treatment or to a control group. Each group consisted of two subgroups: a fellow eye group and a bilateral drusen group. At 3 years, 36 of 38 enrolled patients remained in the study. Photocoagulation was performed with an argon green laser, approximately 100 mild laser burns being placed on and between the drusen in a perifoveal temporal horseshoe-shaped area. Both cases and controls were subjected to fundus colour photographs and fluorescein angiograms at regular intervals, and the drusen area was calculated in both photographs and angiograms. At baseline, there were no significant differences (p > 0.3-0.8) in drusen area between the groups.
                In the treatment group, mean drusen area decreased significantly in the fundus photographs as well as in the angiograms (p < 0.001). Visual acuity and colour contrast sensitivity (CCS) did not change significantly. All these results are valid also for the subgroups. In the control group, however, mean drusen area increased significantly (p < 0.001). Mean visual acuity decreased significantly (p < 0.01) as did the colour contrast sensitivity along the tritan axis (p = 0.02). For the fellow eye control group (n = 7), the increase in drusen area in fundus photographs and the decrease in CCS along the tritan axis were not statistically significant (p = 0.57 and p = 0.37, respectively). Furthermore, at 3 years, five patients in the control group showed exudative lesions (1/7 in the fellow eye group and 4/12 in the bilateral drusen group), whereas no such complications occurred in the treatment group. One patient developed a small atrophy, however. Thus, there is now a significant difference (p = 0.047), however with a large 95% confidence interval, 0.06-0.46, regarding exudative complications between the treated group and the control group in our small patient material.
                Perifoveal mild laser treatment causes a reduction in drusen area in patients with soft drusen maculopathy and may lower the incidence of exudative lesions. This pilot study collected preliminary information on the effectiveness and safety of infrared (810-nm) diode laser macular grid photocoagulation in patients with nonexudative age-related macular degeneration (AMD). Results from this pilot study were used in designing a larger, multicenter, randomized clinical trial.
                A multicenter, randomized, controlled, clinical trial.
                A total of 229 eyes of 152 patients with AMD were enrolled in the pilot study. Seventy-five patients with 1 eye eligible (75 eyes) were enrolled in the unilateral arm of the study; 77 patients with both eyes eligible (154 eyes) were enrolled in the bilateral arm of the study. In the unilateral study arm, 32 eyes were randomized to the observation group, 27 eyes were treated with visible endpoint burns, and 16 eyes were treated with invisible endpoint (subthreshold) lesions. In the bilateral study arm, 77 eyes were in the observation group, 36 eyes were treated with visible burns, and 41 eyes were treated with subthreshold (invisible) lesions.
                Eyes were treated with infrared (810-nm) diode laser macular grid photocoagulation using either visible burns or subthreshold (invisible) lesions and compared to eyes receiving no treatment.
                Reduction of drusen, change in visual acuity, and rate of choroidal neovascularization (CNV) membrane formation.
                At 12 months after treatment, 62% of eyes treated with visible burns had a clinically significant reduction in drusen, whereas this proportion (65%) was reached in 18 months for eyes treated with subthreshold lesions. At 24 months' follow-up, treated eyes had a significant reduction in drusen compared to observation eyes (P < 0.0001). Visual acuity was significantly improved in treated eyes at 12, 18, and 24 months compared to observation eyes (P < 0.001). Choroidal neovascularization formation was similar in treated and observation eyes through 24 months' follow-up. Complications included CNV associated with six eyes treated with visible burns and a juxtafoveal laser scar in one eye treated with visible burns.
                Infrared (810-nm) diode laser macular grid photocoagulation in patients with nonexudative AMD significantly reduces drusen levels (P < 0.0001) and significantly improves visual acuity (P < 0.001) when either visible endpoint burns or subthreshold endpoint lesions are used. Complications were fewer using subthreshold endpoint lesions. A larger, multicenter, prospective clinical trial with longer follow-up is needed to determine the efficacy of treatment in reducing the rate of CNV formation. Data from this clinical pilot study have been used to design the Prophylactic Treatment of AMD Trial (PTAMD), a multicenter, randomized, prospective clinical trial currently in progress comparing subthreshold (invisible) treatment to observation in eyes with nonexudative AMD. To determine the effects of subthreshold 810-nm-diode laser treatment on the rate of development of choroidal neovascularization (primary end point) and the effect on visual acuity (VA) in participants with multiple large drusen in one eye and a preexisting neovascular age-related macular degeneration (AMD) lesion in the other.
                Multicenter, prospective, randomized controlled trial.
                Two hundred forty-four patients > or =50 years of age and with a neovascular or advanced AMD lesion in one eye and, in the fellow "study" eye, (1) at least 5 drusen > or = 63 mum in diameter, (2) Early Treatment Diabetic Retinopathy Study best-corrected VA (BCVA) of 20/63 or better, and (3) no evidence of neovascularization at baseline.
                Patients were randomized to treatment or observation of their study eye at each of 22 centers. At each visit, the protocol specified that BCVA, a complete retinal examination, and fluorescein angiography be documented. Treated eyes had a grid of 48 extrafoveal, subthreshold diode (810 nm) laser spots, 125 mum in diameter, placed in an annulus outside of the foveola. Patients were seen at baseline and at 3, 6, 12, 18, 24, 30, and 36 months after randomization. No retreatments were allowed.
                Development of choroidal neovascularization (as confirmed by fluorescein angiography) and change in BCVA.
                Throughout follow-up, the rate of choroidal neovascularization events in treated eyes consistently exceeded that in observed eyes. At 1 year, the difference was 15.8% versus 1.4% (P = 0.05). Most of the intergroup differences in choroidal neovascularization events occurred during the first 2 years of follow-up. Treated eyes showed a higher rate of VA loss (> or =3 lines) at 3- and 6-month follow-ups relative to observed eyes (8.3% vs. 1% and 11.4% vs. 4%, respectively; Ps = 0.02, 0.07). After 6 months, no significant differences were observed in VA loss between groups.
                Prophylactic subthreshold 810-nm-diode laser treatment to an eye with multiple large drusen in a patient whose fellow eye has already suffered a neovascular event places the treated eye at higher risk of developing choroidal neovascularization. We advise against using prophylactic subthreshold diode laser treatment in these eyes. The authors determined the effect of photocoagulation of drusen on visual acuity and progression to subretinal neovascular membranes (SRNV).
                One of paired eyes was randomized to photocoagulation with other eye to control in 27 patients having symmetrical maculopathy and visual acuities, aged 46 to 81 years (mean, 69.7 years); follow-up 1 to 6 years (mean, 3.2 years).
                Final visual acuity was improved in treated eye or decreased in control eye in 12 patients, equal in 13 patients, and decreased in treated eye in 2 patients (P < 0.006). Progression to SRNV was less with treatment.
                Laser photocoagulation of confluent soft macular drusen may improve long-term visual prognosis. To update the results of a study on the disappearance of macular soft drusen after laser treatment in the natural evolution of age-related macular degeneration.
                A total of 46 patients with confluent soft drusen and pigmentary changes were studied prospectively. Group 1 was composed of 30 patients with bilateral drusen; the authors randomly assigned one eye of each patient for treatment and the fellow eye for the control. In 16 patients a choroidal neovascular membrane was present in one eye, and treatment was applied to the fellow eye (group 2). Argon green laser treatment was applied directly to the soft drusen in the temporal macula.
                All treated drusen disappeared in a mean of 3.5 months after treatment, and untreated drusen disappeared in all but three patients in an average of 8.5 months. After an average period of 3 years, only one control eye and none of the treated eyes in group 1 developed a choroidal neovascular membrane (P = 0.500). In group 2, neovascularization occurred in 18% of the patients. The initial improvement in Snellen acuity after subfoveal drusen disappearance diminished as a consequence of cataract progression.
                Although no definitive conclusions should be made because of the small number of patients studied, results seem to show that this treatment does not reduce the risk of choroidal neovascularization in the treated eye of patients with a history of exudative disease in the fellow eye. It may be effective in patients with high-risk bilateral soft drusen, that is, in less advanced stages of the disease.
The trials included in this review confirm the clinical observation that laser photocoagulation of drusen leads to their disappearance. However, there is no evidence that this subsequently results in a reduction in the risk of developing CNV, geographic atrophy or visual acuity loss.