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Factors associated with ocular adverse event after immune checkpoint inhibitor treatment

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Abstract

Ocular adverse events (OAEs) including vision-threatening intraocular inflammation after immune checkpoint inhibitor (ICI) treatment have been increasingly reported; however, the risk factors associated with OAEs remain elusive. Here, we determined the factors associated with OAEs after ICI treatment. We analyzed 40 consecutive patients who experienced OAEs after ICI treatments. The OAEs included anterior uveitis, chorioretinitis, papillitis, foveal interdigitation zone thickening/serous retinal detachment (IZT/SRD), retinal vascular occlusion, and strabismus and ptosis. Of 40 patients, 18 (45%) were treated with atezolizumab, 13 (33%) with pembrolizumab, 7 (18%) with nivolumab, 1 (3%) with ipilimumab/nivolumab, and the other 1 (3%) with durvalumab/tremelimumab. BRAF/MEK inhibitors were concurrently used in 19 (48%) patients. Occurrence of intraocular inflammation was significantly associated with previous ocular surgery and trauma history (P = 0.015) and pembrolizumab use (P = 0.031). Neuro-ophthalmic complications and IZT/SRD were associated with brain metastasis (P = 0.005) and treatment with BRAF/MEK inhibitor (P < 0.001), respectively. In extensive literature review for clinical cases, we identified seven cases with intraocular inflammation, which were not observed with ipilimumab treatment, that occurred after a change of the drug to pembrolizumab. Collectively, these findings provide better understandings of OAEs after ICI treatment.

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Abbreviations

ICI:

Immune checkpoint inhibitor

IQR:

Interquartile range

IZT:

Interdigitation zone thickening

OAE:

Ocular adverse event

SRD:

Serous retinal detachment

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Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) under grant funded by the Korea government (Ministry of Science and ICT) (NRF-2019R1A2C2002393). The funding organization had no role in the design or conduct of this research.

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Authors and Affiliations

  1. Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, Republic of Korea

    Yong Joon Kim, Jihei Sara Lee, Junwon Lee, Tae-im Kim, Suk Ho Byeon & Christopher Seungkyu Lee

  2. Department of Ophthalmology, Konyang University College of Medicine, Daejeon, Republic of Korea

    Sung Chul Lee

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  1. Yong Joon Kim
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  2. Jihei Sara Lee
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Contributions

YJK, SCL, and CSL conceived the study. Clinical data collection and interpretation were done by YJK, JSL, JL, SCL, TK, SHB, and CSL. YJK and CSL wrote the manuscript.

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Correspondence to Christopher Seungkyu Lee.

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The authors declare no potential conflicts of interest.

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This study was reviewed and approved by the Institutional Review Board of Severance Hospital, Seoul Korea (approval number: 4-2019-1100).

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The requirement for informed consent for the retrospective study was waived by the Institutional Review Board.

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Kim, Y.J., Lee, J.S., Lee, J. et al. Factors associated with ocular adverse event after immune checkpoint inhibitor treatment. Cancer Immunol Immunother 69, 2441–2452 (2020). https://doi.org/10.1007/s00262-020-02635-3

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