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Analysis of ocular fluid in patients with ranibizumab-recalcitrant neovascular age-related macular degeneration who have serum anti-ranibizumab antibodies

  • Medical Ophthalmology
  • Published:
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Abstract

Purpose

To evaluate whether anti-drug antibodies (ADAs) are present in the ocular fluid of patients with ranibizumab-recalcitrant neovascular age-related macular degeneration (nAMD).

Methods

Two serum ADA-positive ranibizumab-recalcitrant patients and two serum ADA-negative controls were recruited from patients with nAMD treated with ranibizumab monotherapy. Recalcitrance was defined as persistent fluid after ≥6 monthly ranibizumab injections. Serum and aqueous humor ADAs were detected by enzyme-linked immunosorbent assay and immunoprecipitation, respectively.

Results

Two of 156 ranibizumab-treated patients were ADA-positive. The patients received six and 14 ranibizumab injections, respectively, up to 4 weeks prior to blood collection. The serum ADA concentration was estimated to be approximately 50,000 ng/mL. Neutralizing ADAs were confirmed in both samples. A specific band was detected by immunoprecipitation only in ADA-positive samples, consistent with the results of enzyme-linked immunosorbent assay. Based on an assessment of the degree of sensitivity of commercially available anti-ranibizumab antibodies, it was estimated that the immunoprecipitation method could detect ADA levels >30 ng. Nevertheless, ADAs were not detected in the aqueous humor of either the experimental or control group.

Conclusion

In the aqueous humor, ADAs are either not present or are present at a lower concentration than that which can be detected by immunoprecipitation. This presumably reflects the fact that blood ADA is the product of systemic circulation clearance through anterior elimination of intravitreal ranibizumab. Based on our results, ADAs do not return to the eye in sufficient quantities to interfere with the action of ranibizumab in the vitreous cavity.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank Youngjae Lee of the Korea Advanced Institute of Science and Technology for his technical advice and support.

Funding

This work was supported by Inha University Hospital Research Grant.

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Authors and Affiliations

  1. Department of Ophthalmology, Inha University School of Medicine, 27 Inhang-ro, Jung-gu, 22332, Incheon, Republic of Korea

    Kanghoon Lee, Soyoung Lee, Soyeon Jung & Hee Seung Chin

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Contributions

Conceptualization: Kanghoon Lee, Hee Seung Chin; methodology: Kanghoon Lee, Soyoung Lee, Hee Seung Chin; formal analysis and investigation: Kanghoon Lee, Soyoung Lee, Soyeon Jung, Hee Seung Chin; writing—original draft preparation: Kanghoon Lee, Soyoung Lee, Soyeon Jung, Hee Seung Chin; Resources: Soyeon Jung, Hee Seung Chin. All authors read and approved the final manuscript.

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Correspondence to Hee Seung Chin.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the 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 Ethics Committee of Inha University Hospital (No. 202106031).

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

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Lee, K., Lee, S., Jung, S. et al. Analysis of ocular fluid in patients with ranibizumab-recalcitrant neovascular age-related macular degeneration who have serum anti-ranibizumab antibodies. Graefes Arch Clin Exp Ophthalmol 261, 3581–3587 (2023). https://doi.org/10.1007/s00417-023-06146-6

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