strontium-radioisotopes and Wet-Macular-Degeneration

Although anti-vascular endothelial growth factor (VEGF) treatment offers better outcomes than the natural history of neovascular age-related macular degeneration (ARMD), a less burdensome, less expensive, and more durable treatment is needed.. To assess the efficacy and safety of epimacular brachytherapy (EMB) for chronic, active, neovascular ARMD.. The Macular Epiretinal Brachytherapy vs Ranibizumab (Lucentis) Only Treatment (MERLOT) pivotal device trial was conducted at 24 National Health Service hospitals across the UK. Patients who had neovascular ARMD and received intravitreal ranibizumab were enrolled between November 10, 2009, and January 30, 2012. Eligible patients were randomized 2:1 and were stratified by lens status and angiographic lesion type to receive either EMB plus as-needed ranibizumab or as-needed ranibizumab monotherapy. Participants were followed up monthly for 24 months and then assessed at a final visit at month 36. Masking of participants and clinicians was not possible, but best-corrected visual acuity (BCVA) and imaging were analyzed by masked assessors. Analysis followed the intent-to-treat approach.. Pars plana vitrectomy with 24 Gy EMB plus as-needed ranibizumab vs as-needed ranibizumab monotherapy.. Coprimary outcomes were the number of as-needed ranibizumab injections and the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA with a noninferiority margin of -5 ETDRS letters. Secondary outcomes were the percentage of participants losing fewer than 15 ETDRS letters and gaining 0 or more or 15 or more ETDRS letters and the mean change in angiographic total lesion size, choroidal neovascularization size, and foveal thickness on optical coherence tomography.. Of 363 participants, 329 (90.6%) completed 24 months of follow-up (222 participants in the EMB group and 107 in the ranibizumab group). The mean (SD) age of the combined groups was 76.5 (7.4) years. The mean (SD) number of ranibizumab injections was 9.3 (6.7) in the EMB group and 8.3 (4.5) in the ranibizumab group, with a difference of 1.0 injection (95% CI, -0.3 to 2.3; P = .13). The mean (SD) BCVA change was -11.2 (15.7) ETDRS letters in the EMB group and -1.4 (10.9) ETDRS letters in the ranibizumab group, with a difference of 9.8 ETDRS letters (95% CI, -6.7 to -12.9). In the EMB group, 65.6% of participants (160 of 244) lost fewer than 15 ETDRS letters vs 86.6% (103 of 119) in the ranibizumab group, with a difference of 21% (95% CI, 12.4%-29.5%; P < .001). Microvascular abnormalities occurred in 20 of 207 eyes (9.7%) in the EMB group and 1 of 97 eyes (1.0%) in the ranibizumab group. These abnormalities occurred outside the foveal center, and there were no unexpected safety concerns.. The MERLOT trial found that despite the acceptable safety of EMB, it did not reduce the number of ranibizumab injections and was associated with worse visual acuity than anti-VEGF treatment alone; these results do not support EMB use as an adjunct treatment for chronic, active neovascular ARMD.. ClinicalTrials.gov Identifier: NCT01006538.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Brachytherapy; Choroidal Neovascularization; Chronic Disease; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Intravitreal Injections; Macula Lutea; Male; Radiotherapy Dosage; Ranibizumab; Retreatment; Strontium Radioisotopes; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Vitrectomy; Wet Macular Degeneration

To assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD).. Phase 3 randomized controlled trial.. Patients (n = 363) with neovascular AMD already receiving intravitreal ranibizumab injections.. Either pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n = 224) or ongoing PRN ranibizumab monotherapy (n = 119).. The coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB.. The mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P = 0.068). The mean VA change was -4.8 letters in the EMB arm and -0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups, -6.6 to -1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P = 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm(2) versus 0.4 mm(2) in the ranibizumab arm (P = 0.27). The CNV size decreased by 0.5 mm(2) in the EMB arm and by 1.3 mm(2) in the ranibizumab arm (P = 0.27). The OCT foveal thickness decreased by 1.0 μm in the EMB arm and by 15.7 μm in the ranibizumab arm (P = 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable.. These results do not support the use of EMB for chronic, active, neovascular AMD. Safety is acceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Brachytherapy; Chronic Disease; Female; Fluorescein Angiography; Humans; Intravitreal Injections; Macula Lutea; Male; Middle Aged; Radiation Injuries; Ranibizumab; Retina; Salvage Therapy; Strontium Radioisotopes; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Vitrectomy; Wet Macular Degeneration

To evaluate the safety and efficacy of epimacular brachytherapy for the treatment of chronic, active neovascular age-related macular degeneration.. A prospective, multicenter, interventional noncontrolled clinical trial recruited 53 participants with previously treated neovascular age-related macular degeneration. Participants underwent pars plana vitrectomy with a single 24 Gray dose of epimacular brachytherapy, delivered using an intraocular cannula containing a Strontium 90/Yttrium 90 source that was positioned over the active lesion. Participants were retreated with ranibizumab, administered monthly as needed, using predefined retreatment criteria. Coprimary outcomes at 24 months were the proportion of participants losing <15 Early Treatment of Diabetic Retinopathy Study letters and mean number of ranibizumab retreatments.. Over 24 months, 68.1% lost <15 letters with a mean of 8.7 ranibizumab retreatments. Mean change in visual acuity was -6.3 (standard deviation, 18.9) letters. There was one case of nonproliferative radiation retinopathy.. The apparent reduction in ranibizumab retreatment was less evident in Year 2 than Year 1, with the moderate reduction in visual acuity extending into the second year. Although radiation retinopathy occurred in one case, it was not vision threatening and safety remained acceptable.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Brachytherapy; Chronic Disease; Epiretinal Membrane; Female; Fluorescein Angiography; Humans; Intravitreal Injections; Male; Middle Aged; Prospective Studies; Radiotherapy Dosage; Radiotherapy, Adjuvant; Ranibizumab; Strontium Radioisotopes; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Yttrium Radioisotopes

To report the fluorescein angiography (FA) and optical coherence tomography (OCT) results of a clinical trial of epimacular brachytherapy (EMBT) used for the treatment of neovascular age-related macular degeneration (AMD).. Pivotal multicenter, active-controlled, randomized clinical trial.. A total of 494 participants with treatment-naïve, neovascular AMD.. Participants with classic, minimally classic, and occult lesions were randomized to receive (a) EMBT and 2 mandated monthly ranibizumab injections followed by pro re nata (PRN) ranibizumab or (b) 3 mandated monthly ranibizumab injections followed by mandated quarterly plus PRN ranibizumab. Participants underwent FA at screening and at months 1, 6, 12, 18, and 24. Optical coherence tomography scans were undertaken monthly for 24 months. The FA and OCT images were analyzed at respective independent reading centers.. Change at 24 months in mean FA total lesion size and choroidal neovascularization (CNV) size and change in mean OCT centerpoint thickness.. The mean (standard deviation) changes in FA total lesion size in the EMBT and control arms were +1.9 (8.7) and -3.0 (7.2) mm(2), respectively, with a mean change in total CNV size of +0.4 (8.4) and -4.7 (6.5) mm(2), respectively. Mean (standard deviation) changes in OCT centerpoint thickness were -144 (246) and -221 (185) μm, respectively. Retrospective subgroup analyses showed no significant difference between treatment arms in mean centerpoint thickness in some subgroups, including eyes with classic lesions. The control arm showed a significantly larger reduction in mean total lesion size and mean CNV size than the EMBT arm in all subgroups analyzed. Nine eyes in the EMBT arm showed features consistent with mild, nonproliferative radiation retinopathy, but with a mean gain of 5.0 Early Treatment Diabetic Retinopathy Study letters.. Both FA and OCT suggest that EMBT with PRN ranibizumab results in an inferior structural outcome than quarterly plus PRN ranibizumab. Some subgroup analyses suggest that classic lesions may be more responsive than occult lesions, although generally both subgroups are inferior to ranibizumab. A non-vision-threatening radiation retinopathy occurs in 2.9% of eyes over 24 months, but longer follow-up is needed.. Proprietary or commercial disclosure may be found after the references.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Brachytherapy; Combined Modality Therapy; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Male; Radiation Injuries; Ranibizumab; Retina; Strontium Radioisotopes; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Vitrectomy; Wet Macular Degeneration

To evaluate the safety and efficacy of epimacular brachytherapy (EMBT) for the treatment of neovascular age-related macular degeneration (AMD).. Multicenter, randomized, active-controlled, phase III clinical trial.. Four hundred ninety-four participants with treatment-naïve neovascular AMD.. Participants with classic, minimally classic, and occult lesions were randomized in a 2:1 ratio to EMBT or a ranibizumab monotherapy control arm. The EMBT arm received 2 mandated, monthly loading injections of 0.5 mg ranibizumab. The control arm received 3 mandated, monthly loading injections of ranibizumab then quarterly injections. Both arms also received monthly as needed (pro re nata) retreatment.. The proportion of participants losing fewer than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters from baseline visual acuity (VA) and the proportion gaining more than 15 ETDRS letters from baseline VA.. At 24 months, 77% of the EMBT group and 90% of the control group lost fewer than 15 letters. This difference did not meet the prespecified 10% noninferiority margin. This end point was noninferior using a 20% margin and a 95% confidence interval for the group as a whole and for classic and minimally classic lesions, but not for occult lesions. The EMBT did not meet the superiority end point for the proportion of participants gaining more than 15 letters (16% for the EMBT group vs. 26% for the control group): this difference was statistically significant (favoring controls) for occult lesions, but not for predominantly classic and minimally classic lesions. Mean VA change was -2.5 letters in the EMBT arm and +4.4 letters in the control arm. Participants in the EMBT arm received a mean of 6.2 ranibizumab injections versus 10.4 in the control arm. At least 1 serious adverse event occurred in 54% of the EMBT arm, most commonly postvitrectomy cataract, versus 18% in the control arm. Mild, nonproliferative radiation retinopathy occurred in 3% of the EMBT participants, but no case was vision threatening.. The 2-year efficacy data do not support the routine use of EMBT for treatment-naïve wet AMD, despite an acceptable safety profile. Further safety review is required.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Brachytherapy; Female; Fluorescein Angiography; Follow-Up Studies; Humans; Intravitreal Injections; Macula Lutea; Male; Middle Aged; Radiotherapy Dosage; Ranibizumab; Strontium Radioisotopes; Treatment Outcome; Visual Acuity; Wet Macular Degeneration; Yttrium Radioisotopes

To report the optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) results of the Macular Epiretinal Brachytherapy in Treated Age-Related Macular Degeneration study.. Prospective, multicenter, interventional, noncontrolled clinical trial.. Fifty-three eyes of 53 participants with chronic, active neovascular age-related macular degeneration (AMD) requiring frequent anti-vascular endothelial growth factor retreatment.. Participants underwent pars plana vitrectomy with a single 24-gray dose of epimacular brachytherapy (EMB), delivered with an intraocular, handheld, cannula containing a strontium 90/yttrium 90 source positioned over the active lesion. Participants were retreated with ranibizumab administered monthly as needed, using predefined retreatment criteria. Patients underwent FFA at baseline, month 1, and month 12. Patients underwent optical coherence tomography (OCT) at baseline and then monthly for 12 months. The FFA and OCT images were evaluated by independent, central reading facilities.. Change in OCT centerpoint thickness and angiographic lesion size 12 months after EMB.. Mean centerpoint thickness increased by 50 μm, from 186 to 236 μm (P = 0.292), but 70% of participants had an increase of less than the mean, with a median increase of only 1.8 μm. The FFA total lesion size increased slightly by 0.79 mm(2), from 14.69 to 15.48 mm(2) (P = 0.710). Total choroidal neovascularization (CNV) area increased by 1.17 mm(2), from 12.94 to 14.12 mm(2) (P = 0.556). The classic CNV area decreased substantially by 3.70 mm(2), from 3.90 to 0.20 mm(2) (P<0.01). Predominantly classic lesions showed the greatest response, with mean Early Treatment Diabetic Retinopathy Study visual acuity improving by 1.5 letters (versus -4.0 for all participants combined); mean centerpoint thickness decreased by 43 μm (P = 0.875). The angiographic and OCT response did not correlate with lesion size at baseline.. In chronic, active, neovascular AMD, EMB is associated with nonsignificant changes in centerpoint thickness and FFA total lesion size over 12 months.

Topics: Brachytherapy; Epiretinal Membrane; Fluorescein Angiography; Humans; Macula Lutea; Prospective Studies; Radiotherapy Dosage; Strontium Radioisotopes; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Vitrectomy; Wet Macular Degeneration; Yttrium Radioisotopes

To evaluate the safety and efficacy of epimacular brachytherapy (EMB) for the treatment of chronic, active, neovascular age-related macular degeneration (AMD).. Prospective, multicenter, interventional, noncontrolled clinical trial.. Fifty-three eyes of 53 participants with neovascular AMD requiring frequent anti-vascular endothelial growth factor (VEGF) retreatment.. Participants underwent pars plana vitrectomy with a single 24-Gy dose of EMB delivered using an intraocular, handheld cannula containing a strontium 90/yttrium 90 source positioned over the active lesion. Participants were retreated with ranibizumab administered monthly as needed, using predefined retreatment criteria. Optical coherence tomography (OCT) was undertaken monthly, with images assessed by an independent reading center.. Coprimary outcomes at 12 months were proportion of participants with stable vision (losing <15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and mean number of anti-VEGF retreatments.. Before enrollment, participants had received an average of 12.5 anti-VEGF injections. After a single treatment with EMB, 81% maintained stable vision, with a mean of 3.49 anti-VEGF retreatments in 12 months. Mean ± standard deviation change in visual acuity was -4.0±15.1 ETDRS letters. Mean ± standard deviation OCT central retinal thickness increased by 50±179 μm. Common adverse events included conjunctival hemorrhage (n = 38), cataract (n = 16), resolving vitreous hemorrhage (n = 6), and eye pain (n = 5).. Epimacular brachytherapy produces stable visual acuity in most participants with previously treated, active disease. Epimacular brachytherapy may reduce the need for frequent anti-VEGF retreatment.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Brachytherapy; Chronic Disease; Female; Fluorescein Angiography; Humans; Intravitreal Injections; Male; Middle Aged; Prospective Studies; Radiotherapy Dosage; Ranibizumab; Retina; Strontium Radioisotopes; Tomography, Optical Coherence; Treatment Outcome; Visual Acuity; Vitrectomy; Wet Macular Degeneration; Yttrium Radioisotopes

To evaluate clinical feasibility, safety, and efficacy of epiretinal strontium-90 brachytherapy in subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) in eyes unresponsive to repeated anti-VEGF injections.. A retrospective, single-center study on patients treated with strontium-90 brachytherapy for CNV secondary to neovascular AMD. Patients underwent pars plana vitrectomy with a single 24 Gy dose brachytherapy. They were re-treated with anti-VEGF injections on an as-needed basis if subretinal or intraretinal fluid was detected on optical coherence tomography imaging.. Twenty-two patients were treated, and 20 completed 12 months of follow-up. Ten patients maintained stable vision, eight gained vision, and two lost more than three Snellen lines. The mean best corrected visual acuity change from baseline was -8 ± 5.7 letters. A mean of 5.5 ± 4.4 anti-VEGF injections were administered throughout 12 months.. Epimacular brachytherapy is feasible in clinical practice. While some patients benefit from the treatment and need significantly fewer as-needed injections, others appear not to react to irradiation treatment after 1 year of follow-up. Larger numbers of patients are needed to evaluate therapeutic efficacy and to determine which patients can benefit from combined radiation and anti-VEGF therapy.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Brachytherapy; Choroidal Neovascularization; Combined Modality Therapy; Feasibility Studies; Female; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Humans; Male; Middle Aged; Radiotherapy Dosage; Retrospective Studies; Strontium Radioisotopes; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Vitrectomy; Wet Macular Degeneration