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Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid/drusen perspective

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Abstract

Purpose

To classify macular neovascularization (MNV) based on pachychoroid and drusen features and to examine the aqueous humor cytokine signatures of each group.

Methods

In total, 106 consecutive eyes with treatment-naïve MNV and 104 control eyes were examined. The aqueous humor concentrations of 15 cytokines were compared among the MNV groups classified based on the presence of drusen and/or pachychoroid features. Multidimensional scaling analysis was used to visualize the similarity level of the MNV subtypes according to their cytokine profiles.

Results

Thirty-one, 18, 43, and 10 eyes were classified into the pachychoroid-associated, drusen-associated, pachychoroid/drusen-associated, and non-drusen/non-pachychoroid MNV groups, respectively. Compared with the control group, cytokines were differently upregulated among the MNV groups. CRP and CXCL12 were significantly upregulated in all MNV groups, whereas CXCL13 and IL-8 were significantly upregulated in three MNV groups, excluding the non-pachychoroid/non-drusen-associated MNV group. Ang-2 was significantly upregulated in three MNV groups except the drusen-associated MNV group. PlGF was significantly upregulated in the pachychoroid-associated and drusen-associated MNV groups. CCL-2 was significantly upregulated in the pachychoroid-associated and pachychoroid/drusen-associated MNV groups. VEGF was downregulated in the pachychoroid-associated and drusen-associated MNV groups, respectively. Multidimensional scaling analysis showed a distinct cytokine profile for each MNV group.

Conclusion

All MNV groups showed distinct cytokine profiles. Eyes with “neovascular age-related macular degeneration with drusen and concomitant pachychoroid” may share a similar etiology to those with “pachychoroid neovasculopathy” and “choroidal neovascularization with drusen,” but have a distinct etiology to those without these. These findings suggest the importance of evaluating drusen and the choroid during the diagnosis of neovascular age-related macular degeneration.

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Acknowledgements

We thank Satoko Tominaga, Ryota Takahashi, and Kosuke Nagaoka for their participation in this study.

Funding

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

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Authors and Affiliations

  1. Department of Ophthalmology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0431, Japan

    Satoru Inoda, Hidenori Takahashi, Yuji Inoue, Hironobu Tampo, Yusuke Arai, Yasuo Yanagi & Hidetoshi Kawashima

  2. Department of Ophthalmology Japan Community Healthcare Organization, Tokyo Shinjuku Medical Center, Shinjuku-ku, Tokyo, Japan

    Hidenori Takahashi & Xue Tan

  3. Singapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore

    Yasuo Yanagi

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  1. Satoru Inoda
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by SI, HT, and YY. The first draft of the manuscript was written by SI. All authors provided input on previous versions of the manuscript and have read and approved the final manuscript.

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Correspondence to Hidenori Takahashi.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the institutional review boards of the Japan Community Healthcare Organization Tokyo Shinjuku Medical Center and Jichi Medical University (CU20-R007, H22-3)

Consent to participate

Informed consent was obtained from all individual participants included in this study.

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The authors affirm that human research participants provided informed consent for publication of the images in Figures 1a, 1b, and 1c.

Conflict of interest

SI, XT, HT, and YA have no relevant financial or non-financial interests to disclose.

HT is a consultant to Kowa Pharmaceutical, Novartis Pharmaceutical, Bayer Pharmaceutical, Senju Pharmaceutical, Pfizer Pharmaceutica, and Santen Pharmaceutical, and a founder of DeepEyeVision Inc.

YI is a consultant to Novartis Pharmaceuticals, Mitsubishi-Tanabe Pharmaceutical, and the Tochigi Prefectural Ophthalmologists Association.

YY is a consultant to Novartis Pharmaceuticals, Bayer Yakuhin, Santen Pharmaceuticals, and Senju Pharmaceutical.

HK is a consultant to Kowa Pharmaceutical, Novartis Pharmaceuticals, Santen Pharmaceutical, Mitsubishi-Tanabe Pharmaceutical, Senju Pharmaceutical, and the Tochigi Prefectural Ophthalmologists Association.

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Inoda, S., Takahashi, H., Inoue, Y. et al. Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid/drusen perspective. Graefes Arch Clin Exp Ophthalmol 260, 747–758 (2022). https://doi.org/10.1007/s00417-021-05445-0

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