今日の臨床サポート

眼底出血

著者: 飯島裕幸 山梨大学医学部眼科学教室

監修: 沖波聡 倉敷中央病院眼科

著者校正/監修レビュー済:2020/05/14
患者向け説明資料

概要・推奨   

  1. 網膜中心静脈閉塞症(CRVOでは初診時視力が不良であれば、最終視力も不良である。非虚血型CRVOであっても、1/3は経過中に虚血型CRVOに移行する。血管新生緑内障(NVG発生の予兆である前眼部新生血管(NV、すなわち虹彩新生血管(INV)と隅角新生血管(ANV)は16%に生じ、その時点で汎網膜レーザー光凝固治療(PRP)を行えば、NVGを予防できる(推奨度1)
  1. 虚血型の網膜静脈分枝閉塞症(BRVOでは、虚血網膜で産生される血管新生サイトカイン、VEGFの影響で、発症後数年以内に、網膜血管から硝子体に立ち上がるNVを生じて硝子体出血を生じる危険性がある。200~500μmの凝固径で1凝固斑の間隔をあけて虚血網膜部位を覆う散発凝固scatter photocoagulationはVEGFの発生母地を破壊し、NV発生を抑制する。治療時期はNVの発生を確認した時点でよいとされている(推奨度1)
  1. 滲出型加齢黄斑変性(AMDに対する抗VEGF薬治療の維持期管理では、OCTによる検査結果をもとに再投与の判断を行ってよい。フルオレセイン蛍光眼底造影検査は必ずしも必要ない(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
飯島裕幸 : 特に申告事項無し[2021年]
監修:沖波聡 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)。

病態・疫学・診察

疾患情報  
  1. 眼底検査にて、点状、斑状、刷毛状の網膜出血がみられる。出血の部位は、網膜前、網膜内、網膜下(<図表>)、網膜色素上皮下、脈絡膜のいずれかの層、または複数の層にみられる。
 
網膜構造と出血部位

種々の網膜層内の出血部位を網膜の模式図内に示した。

出典

img1:  著者提供
 
 
 
  1. 原因として、網膜静脈閉塞症(<図表>)、糖尿病網膜症(<図表>)、網膜細動脈瘤(<図表>)、高血圧網膜症(<図表>)、加齢黄斑変性(AMD)(<図表>)などがある。
 
網膜細動脈瘤

下耳側動脈に1乳頭径大の白色の網膜細動脈瘤がみられ、周囲の網膜出血と黄斑浮腫を伴っている。

出典

img1:  著者提供
 
 
 
  1. 出血の病態として、血管壁の脆弱性に由来するもの(糖尿病網膜症、網膜細動脈瘤)、血圧上昇によるもの(高血圧網膜症、網膜細動脈瘤)、静脈内圧上昇(網膜静脈閉塞症)によるものなどがある。
  1. 網膜下出血は、視細胞障害を来して、不可逆性の視力視野障害を来しやすい。
  1. 網膜前出血は、吸収すれば視力は回復する。
  1. 網膜静脈閉塞症では、急性期の黄斑浮腫にて視力障害を来すとともに、晩期合併症である硝子体出血や血管新生緑内障(NVG)での視機能障害が問題となる。
問診・診察のポイント  
  1. 視覚異常について、視力障害、中心暗点、上下いずれかの中心視野障害、飛蚊症などのいずれであるかを左右眼に分けて確認する(網膜の血管異常では、両眼性であっても左右眼で異なる病態のことも少なくない。AMDでは中心暗点、網膜静脈分枝閉塞症(BRVO)では上下いずれかの半視野障害、硝子体出血を伴っていれば飛蚊症を訴えることが多い)。

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文献 

著者:
雑誌名: 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.

PMID 9109757  Arch Ophthalmol. 1997 Apr;115(4):486-91.
著者:
雑誌名: 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.

PMID 2417579  Arch Ophthalmol. 1986 Jan;104(1):34-41.
著者: 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
雑誌名: 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.

PMID 17386270  Am J Ophthalmol. 2007 Apr;143(4):566-83. doi: 10.1016/j・・・
著者: Geeta A Lalwani, Philip J Rosenfeld, Anne E Fung, Sander R Dubovy, Stephen Michels, William Feuer, Janet L Davis, Harry W Flynn, Maria Esquiabro
雑誌名: 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.

PMID 19376495  Am J Ophthalmol. 2009 Jul;148(1):43-58.e1. doi: 10.1016・・・
著者: Peter A Campochiaro, Jeffrey S Heier, Leonard Feiner, Sarah Gray, Namrata Saroj, Amy Chen Rundle, Wendy Yee Murahashi, Roman G Rubio, BRAVO Investigators
雑誌名: 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.
PMID 20398941  Ophthalmology. 2010 Jun;117(6):1102-1112.e1. doi: 10.10・・・
著者: 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
雑誌名: 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.
PMID 21684606  Ophthalmology. 2011 Aug;118(8):1594-602. doi: 10.1016/j・・・

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