strontium-radioisotopes and Chronic-Disease

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 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

Topics: Adolescent; Adult; Chronic Disease; Follow-Up Studies; Humans; Osteomyelitis; Radiography; Radionuclide Imaging; Strontium Radioisotopes; Wound Healing

Topics: Animals; Chronic Disease; Endocrine Glands; Female; Injections, Intraperitoneal; Male; Neoplasms, Experimental; Radiation Injuries, Experimental; Rats; Strontium Radioisotopes

Topics: Acute Disease; Animals; Arthus Reaction; Cardiac Catheterization; Choroid; Chronic Disease; Disease Models, Animal; Eye; Immunization; Inflammation; Injections; Microspheres; Rabbits; Regional Blood Flow; Serum Albumin, Bovine; Strontium Radioisotopes; Uvea; Uveitis; Vitreous Body

Topics: Adolescent; Adult; Chronic Disease; Diagnosis, Differential; Fascia; Fasciotomy; Female; Fractures, Bone; Humans; Ischemia; Leg; Leg Injuries; Male; Muscular Diseases; Necrosis; Pain; Physical Exertion; Sports Medicine; Strontium Radioisotopes

Topics: Adult; Aged; Americium; Bone and Bones; Calcium; Chronic Disease; Densitometry; Female; Gamma Rays; Humans; Male; Methods; Middle Aged; Minerals; Radiography; Radius; Sarcoidosis; Sex Factors; Spine; Strontium Radioisotopes; Time Factors

Topics: Acute Disease; Bone and Bones; Bone Diseases; Bone Neoplasms; Breast Neoplasms; Chronic Disease; Citrates; Female; Femur Head Necrosis; Humans; Neoplasm Metastasis; Osteomyelitis; Phosphates; Radionuclide Imaging; Strontium Radioisotopes; Technetium; Whole-Body Counting