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Clinical science
Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy
  1. Shinichi Sakamoto1,
  2. Hidenori Takahashi1,2,3,
  3. Xue Tan2,
  4. Yuji Inoue1,2,
  5. Yoko Nomura2,
  6. Yusuke Arai1,
  7. Yujiro Fujino3,
  8. Hidetoshi Kawashima1,
  9. Yasuo Yanagi4,5,6
  1. 1 Department of Ophthalmology, Jichi Medical University, Shimotsuke, Tochigi, Japan
  2. 2 Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  3. 3 Department of Ophthalmology, Japan Community Health Care Organization Tokyo Shinjuku Medical Center, Tokyo, Japan
  4. 4 Department of Medical Retina, Singapore National Eye Centre, Singapore, Singapore
  5. 5 Department of Medical Retina, Singapore Eye Research Institute, Singapore, Singapore
  6. 6 Department of Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS, Medical School, National University of Singapore, Singapore, Singapore
  1. Correspondence to Professor Hidenori Takahashi, Department of Ophthalmology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0431, Japan; takahah-tky{at}umin.ac.jp

Abstract

Purpose To determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD).

Methods This prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and third (2 months later) injections. Controls were 80 eyes with cataracts without retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon-γ-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1), CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin-10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex cytokine assays.

Results Mean ages of the patients with AMD and controls were 73 and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men, respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean concentrations of cytokines in aqueous humour in patients with neovascular AMD before the first and third ranibizumab injections were as follows (in pg/mL): CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6; MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015 (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations of all cytokines decreased significantly after two consecutive ranibizumab injections, except for MMP-9, which increased significantly.

Conclusions After two monthly consecutive antivascular endothelial growth factor injections, inflammatory cytokine levels in the aqueous humour of the eyes with AMD were strongly suppressed, while MMP-9 levels increased.

  • aqueous humour
  • macula
  • inflammation
  • retina

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bjophthalmol-2017-310284

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    Footnotes

    • Twitter @takaha4

    • Contributors HT designed the study, collected and analysed data, and drafted the manuscript. YY designed the study and revised the manuscript. SS, XT, YI, YN, YA, YF and HK revised the manuscript.

    • Funding This work was supported by a KAKENHI grant from the Japan Society for the Promotion of Science, Grant Number 15K10899.

    • Competing interests Shinichi Sakamoto, Xue Tan, Yoko Nomura, Yusuke Arai: None. Hidenori Takahashi: Lecturer’s fees from Kowa Pharmaceutical, Novartis Pharmaceuticals, Bayer Yakuhin, and Santen Pharmaceutical, educational presentation fee from Tochigi Prefectural Ophthalmologists Association, grants from Bayer Yakuhin and Novartis Pharma, unrelated to this work. YujiInoue: Lecturer’s fees from Kowa Pharmaceutical, Novartis Pharmaceuticals, Bayer Yakuhin, and Santen Pharmaceutical, educational presentation fee from Tochigi Prefectural Ophthalmologists Association, unrelated to this work. YujiroFujino: Lecturer’s fees from ALCON JAPAN LTD. and Otsuka Pharmaceutical, educational presentation fee from Tokyo Association of Ophthalmologists, unrelated to this work. Hidetoshi Kawashima: Lecturer’s fees from Kowa Pharmaceutical, Novartis Pharmaceuticals, and Santen Pharmaceutical, educational presentation fee from Tochigi Prefectural Ophthalmologists Association, unrelated to this work. Yasuo Yanagi: Lecturer’s fees from Novartis Pharmaceuticals, Bayer Yakuhin, MSD, and Santen Pharmaceutical, grants from Bayer Yakuhin, Santen Pharmaceutical, and Novartis Pharma, advisory board member for Novartis Pharmaceuticals and Bayer Yakuhin, unrelated to this work.

    • Patient consent Obtained.

    • Ethics approval JCHO.

    • Provenance and peer review Not commissioned; externally peer reviewed.