strontium-radioisotopes and Macular-Degeneration

Beta radiation has a long history as a treatment modality in ophthalmology. It is a convenient and practical method of applying radiation and has the advantage of minimal tissue penetration. There has been a recent resurgence in the use of beta radiation in other areas in medicine, such as the prevention of restenosis after coronary artery stenting. Beta radiation has been shown in vitro and in vivo to inhibit proliferation of human Tenon's fibroblasts, which enter a period of growth arrest but do not die. Effects on the cell cycle controller p53 have been shown to be important in this process. In ophthalmology, beta radiation has been used widely for the treatment of pterygium and is under evaluation for treatment of age-related macular degeneration and for controlling wound healing after glaucoma drainage surgery. In this latter role, beta radiation may be particularly appropriate for use in developing countries to improve the results of trabeculectomy while potentially avoiding some of the side effects of other antimetabolites.

Topics: Aged; Beta Particles; Brachytherapy; Cicatrix; Glaucoma; Humans; Lens, Crystalline; Macular Degeneration; Middle Aged; Pterygium; Strontium Radioisotopes; Wound Healing

Topics: Brachytherapy; Drug Implants; Humans; Macular Degeneration; Palladium; Radioisotopes; Retinal Neovascularization; Strontium Radioisotopes

The purpose of this study was to evaluate the short-term safety and feasibility of intraocular, epiretinal delivery of beta radiation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration for 12 months. A 3-year follow-up period is planned to assess the long-term safety of the procedure.. In this nonrandomized, multicenter feasibility study, 34 treatment-naïve patients with predominantly classic, minimally classic, or occult lesions due to subfoveal choroidal neovascularization secondary to age-related macular degeneration received a single treatment with either 15 Gray (Gy) (8 patients) or 24 Gy (26 patients) beta radiation (strontium-90) using a novel intraocular delivery device. Adverse events and safety endpoints were observed and recorded. Visual acuity was measured preoperatively and postoperatively using standard Early Treatment Diabetic Retinopathy Study vision charts.. Twelve months after treatment, no adverse events associated with exposure to radiation were observed. All patients in both 15 Gy (n = 4) and 24 Gy cohorts (n = 17) who met inclusion criteria and were treated according to protocol lost fewer than three lines of vision. Fifty percent (2/4) of the 15 Gy-treated patients and 76% (13/17) of the 24 Gy-treated patients improved or maintained their visual acuity at 12 months. In the 24 Gy group, 29% (5/17) gained three lines or more in visual acuity. The mean change in visual acuity observed at month 12 was +10.3 letters in the 24 Gy study cohort and -1.0 letters in the 15 Gy cohort.. The short-term safety and efficacy of intraocular, epiretinal delivery of beta radiation for the treatment of subfoveal choroidal neovascularization was promising in this small study group and should be studied in a larger cohort of patients.

Topics: Aged; Aged, 80 and over; Choroidal Neovascularization; Feasibility Studies; Female; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Humans; Macular Degeneration; Male; Middle Aged; Radiotherapy Dosage; Retina; Strontium Radioisotopes; Treatment Outcome; Visual Acuity

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.

Topics: Aged; Brachytherapy; Choroidal Neovascularization; Contrast Sensitivity; Exudates and Transudates; Female; Fluorescein Angiography; Humans; Macular Degeneration; Male; Radiotherapy Dosage; Strontium Radioisotopes; Treatment Outcome; Visual Acuity

To determine if epimacular brachytherapy is associated with reduced retinal sensitivity or choroidal nonperfusion.. A prospective intervention case series of 12 participants with neovascular age-related macular degeneration requiring frequent ranibizumab underwent vitrectomy and epimacular brachytherapy. The Strontium 90/Yttrium 90 source delivered a single 24-Gy dose at the center of the treatment zone. The dose attenuated with increasing distance from the source. Microperimetry and indocyanine green angiography were performed at baseline and 12 months. The main outcome measures were mean sensitivity and choroidal nonperfusion. A linear mixed model was used to assess the association between the dose of radiation and the change in mean sensitivity.. Mean visual acuity remained within 1 letter of baseline at 12 months (-0.33 ± 13.2 letters). There was no statistically significant change in mean sensitivity within the neovascular age-related macular degeneration lesion area (gain of 0.94 ± 3.25 dB; P = 0.339) or in neighboring unaffected retina (0.66 ± 4.14 dB; P = 0.594), defined using fluorescein angiography. Within the lesion area, mean sensitivity improved by an average of 0.23 ± 0.16 dB (P = 0.006) for every additional gray of radiation received. Indocyanine green angiography failed to demonstrate any choroidal nonperfusion or radiation damage at 12 months after the treatment.. Stable retinal sensitivity in areas not manifestly affected by neovascular age-related macular degeneration suggests that epimacular brachytherapy does not damage retinal function. The presence of a dose response suggests that the positive effect of epimacular brachytherapy relates more to beta irradiation than vitrectomy.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Brachytherapy; Dose-Response Relationship, Radiation; Female; Fluorescein Angiography; Humans; Indocyanine Green; Linear Models; Macular Degeneration; Male; Middle Aged; Prospective Studies; Radiation Injuries; Ranibizumab; Retina; Sensory Thresholds; Strontium Radioisotopes; Tomography, Optical Coherence; Visual Acuity; Visual Field Tests; Visual Fields; Vitrectomy; Yttrium Radioisotopes

To evaluate the long-term safety and visual acuity outcomes associated with epimacular strontium 90 brachytherapy combined with intravitreal bevacizumab for the treatment of subfoveal choroidal neovascularization because of age-related macular degeneration.. Thirty-four treatment-naive patients with predominantly classic, minimally classic, and occult subfoveal choroidal neovascularization lesions participated in this prospective, 2-year, nonrandomized multicenter study. Subjects from 1 center (n = 19) were reconsented and followed-up for 3 years. Each subject received a single 24-Gy beta irradiation treatment via an intraocular delivery device and 2 planned injections of bevacizumab at treatment and 1 month later. Additional bevacizumab therapy was permitted based on prespecified retreatment criteria. Adverse events were observed, and best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study vision charts. Subjects were evaluated every 3 months during the first year of follow-up and every 6 months during Years 2 and 3 of follow-up.. All 34 subjects were followed-up for 24 months and 19 were followed-up through 36 months. With up to 24 months of follow-up, 12 of 24 phakic patients (50%) exhibited ≥ 2 grades of progression in Lens Opacification Classification System (LOCS) II lens classification; 5 eyes underwent cataract extraction before the Month 36 visit. There was 1 case of nonproliferative retinopathy identified at 36 months of follow-up that did not have an adverse effect on visual acuity, was stable at 43 months of follow-up, and was isolated to the parafoveal region. Mean best-corrected visual acuity demonstrated an average gain of +15.0 and -4.9 letters at 12 months and 24 months, respectively; the drop in mean gain at Month 24 was largely attributable to cataract formation. At 36 months (n = 19), the mean best-corrected visual acuity was +3.9, 90% (17 of 19) of eyes had lost <15 letters from baseline, 53% (10 of 19) had gained ≥ 1 letter, and 21% (4 of 19) had gained ≥ 15 letters. Through 36 months, 11 eyes required additional bevacizumab retreatment therapy and received a mean of 3.0 injections (range, 2-7 injections).. Epimacular brachytherapy shows promise as a therapeutic option for subfoveal neovascular age-related macular degeneration. The procedure was safe and well tolerated, with a reasonable risk-benefit profile that warrants further study in larger subject populations. The most common adverse event was cataract progression/formation. Surgical complications are similar to those expected from standard vitrectomy trials. This novel device is currently being evaluated in two prospective, randomized, controlled trials in treatment-naive subjects (CABERNET) and in subjects already treated with anti-vascular endothelial growth factor therapy (MERLOT).

Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Brachytherapy; Choroidal Neovascularization; Combined Modality Therapy; Feasibility Studies; Female; Humans; Macular Degeneration; Male; Middle Aged; Prospective Studies; Radiotherapy Dosage; Strontium Radioisotopes; Visual Acuity; Yttrium Radioisotopes

This study evaluated the short-term safety and feasibility of epiretinal strontium-90 brachytherapy delivered concomitantly with intravitreal bevacizumab for the treatment of subfoveal CNV due to AMD for 12 months. A 3-year follow-up is planned.. In this prospective, non-randomised, multicentre study, 34 treatment-naïve patients with predominantly classic, minimally classic and occult subfoveal CNV lesions received a single treatment with 24 Gy beta radiation (strontium-90) and two injections of the anti-VEGF antibody bevacizumab. Adverse events were observed. BCVA was measured using standard ETDRS vision charts.. Twelve months after treatment, no radiation-associated adverse events were observed. In the intent-to-treat (ITT) population, 91% of patients lost <3 lines (15 ETDRS letters) of vision at 12 months, 68% improved or maintained their BCVA at 12 months, and 38% gained >/=3 lines. The mean change in BCVA observed at month 12 was a gain of 8.9 letters.. The safety and efficacy of intraocular, epiretinal brachytherapy delivered concomitantly with anti-VEGF therapy for the treatment of subfoveal CNV secondary to AMD were promising in this small study population. Long-term safety will be assessed for 3 years. This regimen is being evaluated in a large, multicentre, phase III study.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Brachytherapy; Choroidal Neovascularization; Combined Modality Therapy; Female; Humans; Macular Degeneration; Male; Middle Aged; Pilot Projects; Prospective Studies; Radiopharmaceuticals; Safety; Strontium Radioisotopes; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity

The purpose of this study is to perform an extensive investigation of an approximately 2.5 mm long 90Sr/90Y source designed for treating wet age-related macular degeneration.. As part of this investigation, a NIST-traceable absorbed dose to water calibration technique was established, and a source deployment verification test was developed. The influence of treatment cannula construction tolerance on the measurements as well as the dose delivered to the patient was investigated using the Monte Carlo code MCNP5. Variation between production cannulae was quantified experimentally using a well-type ionization chamber, and additional measurements along with Monte Carlo calculations of the collimating insert used for source deployment verification were performed to validate the model.. Maximum variation in the integrated target dose was seen when the source was shifted laterally within the treatment cannula. For the well chamber measurements, the observed standard deviation in ionization current for a single source placed in different reference cannulae was +/-0.3%, with a maximum observed range of less than +/-0.5%. Clinical cannulae in the collimating insert showed an average of 17.8% +/-0.4% of the reference signal when sources were fully deployed compared to 18.5% predicted by Monte Carlo calculations. This discrepancy has been attributed primarily to construction of the collimator since the collimation gap was observed to be approximately 0.025-0.075 mm smaller than specified. Construction tolerance of the well chamber insert as well as position tolerance of the cannula tip were both investigated, and their influence on the predicted signal was quantified. Additional measurements along with Monte Carlo based calculations of the collimating insert with polyethylene spacers added to the setup were performed to validate the Monte Carlo model. The shimmed Monte Carlo and measured data agree to within 1%, which is a magnitude difference of approximately 0.1% of the reference signal.. This investigation confirms that the signal for an acceptably deployed source in the collimating insert is between 17.5% and 21.5% of the reference signal, as calculated using Monte Carlo models. Clinical cannulae for which the source deployment verification measurement falls outside the acceptable range should not be used to treat patients.

Topics: Brachytherapy; Computer Simulation; Equipment Design; Equipment Failure Analysis; Humans; Macular Degeneration; Models, Biological; Models, Statistical; Organ Specificity; Prostheses and Implants; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Computer-Assisted; Relative Biological Effectiveness; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

To evaluate the feasibility of using confocal scanning laser tomography in the analysis of macular topography in patients with subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD) and to analyze quantitatively the changes in topography after local strontium-plaque radiation therapy.. Prospective case series.. A total of 16 eyes with subfoveal choroidal neovascular membranes (CNVM) treated with strontium-90 (90Sr)-plaque radiation therapy and 16 fellow eyes of 16 patients were examined.. Confocal scanning laser analysis of macular surface topography before and after irradiation of the macula was performed.. Parameters describing the height and volume of the retinal elevation in the macula were measured.. The maximum height of the macular lesion at baseline was 0.25 mm (standard deviation [SD], 0.12 mm) in eyes showing regression of the CNVM during follow-up and 0.34 mm (SD, 0.19 mm) in eyes showing continued growth of the CNVM. During follow-up, a mean decrease in the maximum height of the macular lesion ranging from 0.03 to 0.10 mm occurred in eyes with regression of the CNVM, whereas the mean maximum height increased by 0.07 to 0.15 mm during follow-up visits in eyes with continued growth of the CNVM. All parameters describing the mean height and volume of the lesion also decreased significantly in patients showing angiographic regression, whereas they increased or remained unchanged in patients with continuous growth of the CNVM despite irradiation. The corresponding parameters also were higher in fellow eyes with untreated CNVM than in eyes without exudative AMD.. Confocal scanning laser tomography can be used to monitor the amount of the change in neurosensory detachment in AMD. The parameters obtained by confocal scanning laser tomography correlate with CNVM perfusion after 90Sr-plaque radiation therapy. This technology is a useful tool for objective evaluation of morphologic change after institution of new therapeutic methods for the treatment of AMD.

Topics: Aged; Aged, 80 and over; Brachytherapy; Choroidal Neovascularization; Feasibility Studies; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Humans; Lasers; Macular Degeneration; Middle Aged; Prospective Studies; Retina; Retinal Detachment; Strontium Radioisotopes; Tomography; Visual Acuity

To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration.. Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing.. At 12 months visual acuity had improved or remained the same in 9/ 20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18, 72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months.. Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM.

Topics: Aged; Aged, 80 and over; Brachytherapy; Choroidal Neovascularization; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Fundus Oculi; Humans; Macular Degeneration; Middle Aged; Radiation Dosage; Reading; Strontium Radioisotopes; Treatment Outcome; Visual Acuity

To determine the effect of focal strontium-90 plaque radiotherapy on subfoveal choroidal neovascularization in patients with age-related macular degeneration.. Twenty patients with age-related macular degeneration, presenting with a recent subfoveal neovascular membrane, were treated with local episcleral radiotherapy using a strontium-90 applicator. The applicator was applied to the sclera under the macular region and held there tightly for 54 min to obtain a dose of 15 Gy at a depth of 1.75 mm. The main parameters evaluated at follow-up after 3, 6 and 12 months were visual acuity and changes in fluorescein angiography. Twelve untreated patients with the same criteria were followed as controls.. Early effects of radiation could be seen at 3 months, but became more obvious after follow-up for 6 and 12 months. At 6 months, regression of the choroidal neovascularization was detected in 14/19 patients (74%) as a decrease in the size of the lesion or as diminished leakage in late-phase fluorescein angiography. Likewise, in 14/19 patients (74%) at 12 months the neovascular membrane was partially or totally occluded. In all patients showing regression of the choroidal neovascular membrane, the neurosensory detachment had also dried. Visual acuity was unchanged (within 1 line) or improved in 11/20 (55%) and 9/20 (45%) treated patients after 6 and 12 months, respectively. In the controls, the choroidal neovascularization had increased in size in 9/12 patients (75%) at the last follow-up (mean 12.0 months). Visual acuity was unchanged in 3/12 patients (25%).. Local low-energy beta irradiation with a strontium-90 applicator can induce regression of choroidal neovascularization. The effect of irradiation is seen as a decrease in the size of the choroidal neovascular membrane and disappearance of the neurosensory detachment and exudates.

Topics: Aged; Aged, 80 and over; Brachytherapy; Choroid; Dose-Response Relationship, Radiation; Female; Fluorescein Angiography; Follow-Up Studies; Fovea Centralis; Fundus Oculi; Humans; Macular Degeneration; Male; Middle Aged; Neovascularization, Pathologic; Strontium Radioisotopes; Treatment Outcome; Visual Acuity

To evaluate the correlation between the central visual field and changes in fluorescein angiography and fundus photography in patients treated with strontium plaque radiotherapy for subfoveal exudative age related macular degeneration (AMD).. Octopus program 34 automated static perimetry, fluorescein angiography, and colour fundus photography were performed on 19 patients at baseline and at 12 months after strontium-90 plaque therapy. A schematic picture outlining the areas of hyperfluorescent neovascular membranes and subretinal blood was drawn of a projected 30 degrees fundus fluorescein angiogram. This drawing was superimposed on the size adjusted Octopus visual field. The changes in retinal sensitivity were calculated and related to angiographic changes.. Three of the 19 patients had a reliability factor (RF) > 15% and were excluded from further analysis. In the remaining 16 patients the mean defect (MD) and loss variance (LV) values remained unchanged in patients showing regression of the choroidal neovascular membrane (CNVM) to irradiation at 12 months. MD was 7.7 (SD 1.7) at baseline and 7.6 (1.9) at 12 months (p = 0.86), and LV was 32.6 (13.9) at baseline and 32.4 (15.7) at 12 months (p = 0.94). However, in patients with progression of the CNVM at 12 months, both the MD and LV increased significantly during the 12 month follow up (MD from 7.3 (2.9) to 13.1 (3.6) (p = 0.05) and LV from 31.0 (22.9) to 71.8 (24.1) (p = 0.017)). When comparing the mean retinal sensitivity in the area of the primary CNVM (including classic, occult, and haemorrhagic components), the results were analogous: in patients with a regression of the CNVM after irradiation the mean sensitivity remained almost unchanged. It was 10.3 (6.4) dB at baseline and 9.4 (7.3) dB at 12 months (p = 0.58). In five out of 11 patients (45%) with regression of the CNVM, the mean retinal sensitivity even improved by 2.0-5.0 dB in the area of the original lesion during follow up. Instead, in patients showing progression of the CNVM at 12 months, there was a significant loss in mean retinal sensitivity--from 9.9 (4.6) dB at baseline to 1.0 (1.1) dB at 12 months (p = 0.019). The mean retinal sensitivity in the area of the irradiated but clinically normal retina during follow up was not significantly altered (21.5 dB at baseline, 19.7 dB at 12 months (p = 0.10)).. Regression of subfoveal choroidal membranes in AMD after focal strontium irradiation is connected with stabilisation or even improvement of retinal sensitivity in central visual field measured by automated perimetry. Strontium plaque irradiation does not change the sensitivity in clinically normal paramacular retina during a 12 month follow up.

Topics: Aged; Aged, 80 and over; Brachytherapy; Cell Membrane; Choroid Diseases; Fluorescein Angiography; Humans; Macular Degeneration; Retinal Vessels; Strontium Radioisotopes; Visual Acuity; Visual Field Tests; Visual Fields