Anti-VEGF treatment for severe retinopathy of prematurity

• Project/Area Number: 17K11440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kindai University
• Principal Investigator: KUSAKA Shunji 近畿大学, 医学部, 教授 (60260387)
• Co-Investigator(Kenkyū-buntansha): 國吉 一樹 近畿大学, 医学部, 講師 (30234470) ; 杉岡 孝二 近畿大学, 大学病院, 准教授 (50399119)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 未熟児網膜症 / 血管内皮増殖因子 / 抗VEGF治療 / VEGF / 網膜光凝固 / 低出生体重児 / ranibizumab / bevacizumab / サイトカイン / 再燃 / 新生血管 / 硝子体

Outline of Final Research Achievements

Anti-vascular endothelial growth factor (VEGF) therapy was performed for infants with severe retinopathy of prematurity (ROP). Reactivation was observed in 20.9% of 43 eyes of 22 infants after ranibizumab injection and 13.5% of 37 eyes of 21 infants after bevacizumab injection（P=0.556）. Multivariate logistic regression analyses revealed that anti-VEGF therapy at 35 weeks or younger post-conceptional age (OR, 7.524; 95% CI, 1.494–37.89; p = 0.014) and aggressive posterior ROP (OR, 5.532; 95% CI, 1.049–29.17; p = 0.044) were the significant risk factors for reactivation.

Academic Significance and Societal Importance of the Research Achievements

未熟児網膜症は小児失明原因の第一位を占める重要な疾患である。治療法として従来から網膜光凝固が行われてきたが、治療後の近視化、視野狭窄などの欠点があった。これに対し、近年、これらの欠点がない薬物療法（抗VEGF治療）が薬剤の適応外使用として登場した。また、2019年11月に抗VEGF治療薬であるranibizumabが未熟児網膜症の治療薬として承認された。本研究は承認前の段階からranibizumab, それ以前に使用されていたbevacizumabの治療成績や再燃因子を多数例で詳細に検討したもので今後の抗VEGF治療の普及に際して参考となる価値の高い成果であると考えられる。

Research Products

• [Journal Article] Early vitrectomy to reverse macular dragging in a one-month-old boy with familial exudative vitreoretinopathy. (2019)
  • Author(s): Iwata A, Kusaka S, Ishimaru M, Kondo H, Kuniyoshi K.
  • Journal Title: Am J Ophthalmol Case Rep Volume: 15 Pages: 10041-10041
  • DOI: 10.1016/j.ajoc.2019.100493
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Stage 4A未熟児網膜症に対する硝子体手術後再手術例の検討 (2019)
  • Author(s): 歌村 翔子, 国吉 一樹, 立花 都子, 日下 俊次
  • Organizer: 第58回日本網膜硝子体学会総会
• [Presentation] 〔シンポジウム〕未熟児網膜症診断・治療の最前線：外科的治療 (2019)
  • Author(s): 日下 俊次
  • Organizer: 第73回日本臨床眼科学会
• [Presentation] Vitrectomy and/or Anti-VEGF for ROP (2019)
  • Author(s): Shunji Kusaka
  • Organizer: 19th Euretina Congres
• [Presentation] Pediatric Retina (2019)
  • Author(s): Shunji Kusaka, Mohamed Mahgoub Mogazhi, Antonio Ciardelli, Mohamed Mahgoub Mogazhi, Antonio Ciardelli,Zuhal Ozen Tunay
  • Organizer: Mediterranean retina MeetingⅧ
• [Presentation] 〔特別講演〕難治性網膜疾患に対する治療 (2019)
  • Author(s): 日下 俊次
  • Organizer: Advance in Pediatric Retina Course
  • Invited
• [Presentation] 〔特別講演〕未熟児網膜症の診断と治療 (2019)
  • Author(s): 日下 俊次
  • Organizer: 第8回大阪西部眼科病診連携の会
  • Invited
• [Presentation] 〔特別講演〕小児に対する白内障・硝子体手術 (2019)
  • Author(s): 日下 俊次
  • Organizer: 第429回大阪眼科集談会
  • Invited
• [Presentation] 網膜疾患-最近の話題- (2019)
  • Author(s): 日下 俊次
  • Organizer: 大阪府医師会医学会学術講演会
• [Presentation] Pediatric Retinal Diseases (2019)
  • Author(s): Shunji Kusaka
  • Organizer: Asia-Pacific Academy of Ophthalmology
• [Presentation] Intravitreal ranibizumab:serum VEGF concentration change and recurrence rate(as compared with bevacizumab) (2018)
  • Author(s): Shunji Kusaka
  • Organizer: Vietnam ROP Workshop
• [Presentation] Intravitreal ranibizumab: serum VEGF concentration change and recurrence rate (as compared with bevacizumab) (2018)
  • Author(s): Shunji Kusaka
  • Organizer: Vietnam ROP Workshop
  • Int'l Joint Research
• [Presentation] Surgical Intervention in ROP: Indications and Outcomes (2017)
  • Author(s): Shunji Kusaka
  • Organizer: The 11th APVRS/Congress of APVRS 2017
  • Int'l Joint Research