斎藤克也, 飯島裕幸. 網膜細動脈瘤の黄斑部病変と視力予後. 日本眼科学会雑誌. 1997;101:148-51.
Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group.
Arch Ophthalmol. 1997 Apr;115(4):486-91.
Abstract/Text
OBJECTIVE: To provide clinical management guidelines for eyes with central retinal vein occlusion.
DESIGN: Prospective cohort study with randomized clinical trials of specific subgroups of patients. Three-year follow-up every 4 months.
SETTING: Nine ophthalmology practices.
PATIENTS: Seven hundred twenty-five patients with central vein occlusion.
MAIN OUTCOME MEASURES: Iris neovascularization (INV), neovascular glaucoma, and visual acuity.
RESULTS: Visual acuity outcome was largely dependent on initial acuity. Sixty-five percent of patients with initially good visual acuity (20/40 or better) maintained visual acuity in the same range at the end of the study. Patients with intermediate initial acuity (20/50-20/200) showed a variable outcome: 19% improved to better than 20/50, 44% stayed in the intermediate group, and 37% had final visual acuity worse than 20/200. Patients who had poor visual acuity at the first visit (< 20/200) had an 80% chance of having a visual acuity less than 20/200 at final visit, whether perfused or nonperfused initially. In the first 4 months of follow-up, 81 (15%) of the 547 eyes with perfusion converted to ischemia. During the next 32 months of follow-up, an additional 19% of eyes were found to have converted to ischemia for a total of 34% after 3 years. The development of nonperfusion or ischemia was most rapid in the first 4 months and progressed continuously throughout the entire duration of follow-up. Iris neovascularization of at least 2-clock hours, and/or angle neovascularization (ANV) developed in 117 (16%) of the 714 eyes. Sixty-one of the 117 eyes that had INV/ANV were initially categorized as nonperfused or indeterminate; 56 of the 117 eyes were initially categorized as perfused. When INV/ANV occurred, it was treated promptly with panretinal photocoagulation. The strongest predictors of INV/ANV were visual acuity (P < .001) and the amount of nonperfusion seen by fluorescein angiogram (P < .001). For eyes initially categorized as nonperfused or indeterminate, 35% (61/176) developed INV/ANV, compared with 10% (56/538) for eyes initially categorized as perfused. Other risk factors were venous tortuosity (P = .02), extensive retinal hemorrhage (P = .07), and duration less than 1 month (P = .08). Neovascular glaucoma that was unsuccessfully managed with medical treatment developed in only 10 eyes. No eye was enucleated.
CONCLUSIONS: Visual acuity at baseline is a strong predictor of visual acuity at 3 years for eyes with good vision and eyes with poor vision, but a poor predictor for intermediate acuities. Visual acuity is also a strong predictor for the development of INV/ANV, as is nonperfusion. During the course of follow-up, one third of the eyes with perfusion converted to eyes with ischemia. Clinical management guidelines, developed from these and previously reported Central Vein Occlusion Study data, are presented.
Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Branch Vein Occlusion Study Group.
Arch Ophthalmol. 1986 Jan;104(1):34-41.
Abstract/Text
The Branch Vein Occlusion Study is a multicenter, randomized, controlled clinical trial designed to answer several questions regarding the management of complications of branch vein occlusion. This report addresses the questions, "Can peripheral scatter argon laser photocoagulation prevent the development of neovascularization?" and "Can peripheral scatter argon laser photocoagulation prevent vitreous hemorrhage?" To answer the first question, 319 eyes were assigned randomly to either a treated or an untreated control group. Comparing treated patients with control patients (average follow-up time, 3.7 years), the development of neovascularization was significantly less in treated eyes (P = .009, log rank test). To answer the second question, 82 eyes were assigned randomly to either a treated or untreated control group. Comparing treated patients with control patients (average follow-up time, 2.8 years), the development of vitreous hemorrhage was significantly less in treated eyes (P = .005, log rank test). Although the Branch Vein Occlusion Study was not designed to determine whether peripheral scatter treatment should be applied before rather than after the development of neovascularization, data accumulated in this study suggest that peripheral scatter treatment should be applied after the development of neovascularization rather than before the development of neovascularization. Because the occurrence of vitreous hemorrhage was lessened by peripheral scatter argon laser photocoagulation, we recommend laser photocoagulation for patients with branch vein occlusion who have developed neovascularization and who meet the eligibility criteria of this study.
Anne E Fung, Geeta A Lalwani, Philip J Rosenfeld, Sander R Dubovy, Stephan Michels, William J Feuer, Carmen A Puliafito, Janet L Davis, Harry W Flynn, Maria Esquiabro
An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration.
Am J Ophthalmol. 2007 Apr;143(4):566-83. doi: 10.1016/j.ajo.2007.01.028.
Abstract/Text
PURPOSE: To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD).
DESIGN: Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study.
METHODS: In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab.
RESULTS: At month 12, the mean visual acuity improved by 9.3 letters (P < .001) and the mean OCT central retinal thickness decreased by 178 microm (P < .001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary.
CONCLUSION: This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.
Geeta A Lalwani, Philip J Rosenfeld, Anne E Fung, Sander R Dubovy, Stephen Michels, William Feuer, Janet L Davis, Harry W Flynn, Maria Esquiabro
A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study.
Am J Ophthalmol. 2009 Jul;148(1):43-58.e1. doi: 10.1016/j.ajo.2009.01.024. Epub 2009 Apr 18.
Abstract/Text
PURPOSE: To assess the long-term efficacy of a variable-dosing regimen with ranibizumab in the Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular Age-Related Macular Degeneration (AMD) Treated with intraOcular Ranibizumab (PrONTO) Study, patients were followed for 2 years.
DESIGN: A 2-year prospective, uncontrolled, variable-dosing regimen with intravitreal ranibizumab based on OCT.
METHODS: In this open-label, prospective, single-center, uncontrolled clinical study, AMD patients with neovascularization involving the central fovea and a central retinal thickness (CRT) of at least 300 microm as measured by OCT were enrolled to receive 3 consecutive monthly intravitreal injections of ranibizumab (0.5 mg) [Lucentis; Genentech Inc, South San Francisco, California, USA]. During the first year, retreatment with ranibizumab was performed at each monthly visit if any criterion was fulfilled such as an increase in OCT-CRT of at least 100 microm or a loss of 5 letters or more. During the second year, the retreatment criteria were amended to include retreatment if any qualitative increase in the amount of fluid was detected using OCT.
RESULTS: Forty patients were enrolled and 37 completed the 2-year study. At month 24, the mean visual acuity (VA) improved by 11.1 letters (P < .001) and the OCT-CRT decreased by 212 microm (P < .001). VA improved by 15 letters or more in 43% of patients. These VA and OCT outcomes were achieved with an average of 9.9 injections over 24 months.
CONCLUSIONS: The PrONTO Study using an OCT-guided variable-dosing regimen with intravitreal ranibizumab resulted in VA outcomes comparable with the outcomes from the phase III clinical studies, but fewer intravitreal injections were required.
Peter A Campochiaro, Jeffrey S Heier, Leonard Feiner, Sarah Gray, Namrata Saroj, Amy Chen Rundle, Wendy Yee Murahashi, Roman G Rubio, BRAVO Investigators
Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study.
Ophthalmology. 2010 Jun;117(6):1102-1112.e1. doi: 10.1016/j.ophtha.2010.02.021. Epub 2010 Apr 15.
Abstract/Text
PURPOSE: To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO).
DESIGN: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.
PARTICIPANTS: A total of 397 patients with macular edema following BRVO.
METHODS: Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections.
MAIN OUTCOME MEASURES: The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).
RESULTS: Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7-18.5) and 18.3 (16.0-20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1-9.5) in the sham group (P<0.0001 for each ranibizumab group vs sham). The percentage of patients who gained > or =15 letters in BCVA at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups and 28.8% in the sham group (P<0.0001 for each ranibizumab group vs sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA of > or =20/40 compared with sham patients (41.7%; P<0.0001 for each ranibizumab group vs sham); and CFT had decreased by a mean of 337 microm (0.3 mg) and 345 microm (0.5 mg) in the ranibizumab groups and 158 microm in the sham group (P<0.0001 for each ranibizumab group vs sham). The median percent reduction in excess foveal thickness at month 6 was 97.0% and 97.6% in 0.3 mg and 0.5 mg groups and 27.9% in the sham group. More patients in the sham group (54.5%) received rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with BRVO.
CONCLUSIONS: Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events.
Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
David M Brown, Peter A Campochiaro, Robert B Bhisitkul, Allen C Ho, Sarah Gray, Namrata Saroj, Anthony P Adamis, Roman G Rubio, Wendy Yee Murahashi
Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.
Ophthalmology. 2011 Aug;118(8):1594-602. doi: 10.1016/j.ophtha.2011.02.022.
Abstract/Text
PURPOSE: Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO).
DESIGN: Prospective, randomized, sham injection-controlled, double-masked, multicenter trial.
PARTICIPANTS: A total of 397 patients with macular edema after BRVO.
METHODS: Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met.
MAIN OUTCOME MEASURES: The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed.
RESULTS: Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5-18.4) and 18.3 (15.8-20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6-14.6) in the sham/0.5 mg group (P<0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified.
CONCLUSIONS: At month 12, treatment with ranibizumab as needed during months 6-11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.