Skip to main content

Advertisement

SpringerLink
Log in

Baseline characteristics associated with the incidence of intraocular inflammation after the intravitreous injection of brolucizumab

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate baseline characteristics associated with the incidence of intraocular inflammation (IOI) after the intravitreal injection of brolucizumab (IVBr) for the treatment of neovascular age-related macular degeneration (nAMD).

Methods

This retrospective study included 66 eyes of 62 consecutive patients with nAMD who received IVBr (18 eyes were treatment naïve and 48 eyes had switched from other anti-vascular endothelial growth factor [VEGF] therapy). Baseline clinical characteristics were compared in non-IOI and IOI groups.

Results

Although a dry macula was achieved at a high rate even 6 months after IVBr, IOI occurred in 8 of 66 eyes (12.1%; all had switched therapy) during the study period. Baseline characteristics including age, sex, nAMD type, lens status, visual acuity, central macular thickness, and a history of diabetes did not differ between the groups. The number of previous anti-VEGF injections before IVBr was greater in the IOI group (P = 0.004), and the ratio of patients with a laser flare-cell photometry (LFCP) value over 15 photon count per millisecond (pc/ms) was higher in the IOI group (P = 0.017). Multivariate logistic regression analysis showed that a greater number of previous anti-VEGF injections (odds ratio [OR]: 1.12, P = 0.006; area under the curve: 0.82, cut-off score: 14.0) and an LFCP value over 15 pc/ms (OR: 81.6, P = 0.031) were significantly associated with the incidence of IOI after IVBr.

Conclusion

A number of previous anti-VEGF injections greater than 14 and an LFCP value more than 15 pc/ms might be useful predictors of the incidence of IOI after IVBr in eyes with nAMD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The principal investigator, Keisuke Hoshi, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The data that support the findings of this study are available from the corresponding author, Hiroshi Kunikata, and the principal investigator, Keisuke Hoshi, upon reasonable request.

References

  1. Wong WL, Su X, Li X et al (2014) Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2:e106–e116

    Article  PubMed  Google Scholar 

  2. Mitchell P, Liew G, Gopinath B, Wong TY (2018) Age-related macular degeneration. Lancet 392:1147–1159

    Article  PubMed  Google Scholar 

  3. Wormald R, Evans J, Smeeth L, Henshaw K (2007) Photodynamic therapy for neovascular age-related macular degeneration. Cochrane Database Syst Rev CD002030.

  4. Brown DM, Kaiser PK, Michels M et al (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444

    Article  CAS  PubMed  Google Scholar 

  5. Rofagha S, Bhisitkul RB, Boyer DS et al (2013) Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology 120:2292–2299

    Article  PubMed  Google Scholar 

  6. Traine PG, Pfister IB, Zandi S et al (2019) Long-term outcome of intravitreal aflibercept treatment for neovascular age-related macular degeneration using a “treat-and-extend” regimen. Ophthalmol Retina 3:393–399

    Article  PubMed  Google Scholar 

  7. Nguyen QD, Das A, Do DV et al (2020) Brolucizumab: evolution through preclinical and clinical studies and the implications for the management of neovascular age-related macular degeneration. Ophthalmology 127:963–976

    Article  PubMed  Google Scholar 

  8. Dugel PU, Singh RP, Koh A et al (2021) HAWK and HARRIER: ninety-six-week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 128:89–99

    Article  PubMed  Google Scholar 

  9. Matsumoto H, Hoshino J, Mukai R et al (2021) Short-term outcomes of intravitreal brolucizumab for treatment-naïve neovascular age-related macular degeneration with type 1 choroidal neovascularization including polypoidal choroidal vasculopathy. Sci Rep 11:6759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Haensli C, Pfister IB, Garweg JG (2021) Switching to brolucizumab in neovascular age-related macular degeneration incompletely responsive to ranibizumab or aflibercept: real-life 6 month outcomes. J Clin Med 10

  11. Monés J, Srivastava SK, Jaffe GJ et al (2021) Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology 128:1050–1059

    Article  PubMed  Google Scholar 

  12. Haug SJ, Hien DL, Uludag G et al (2020) Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep 18:100680

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jain A, Chea S, Matsumiya W et al (2020) Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations. Am J Ophthalmol Case Rep 18:100687

    Article  PubMed  PubMed Central  Google Scholar 

  14. Khoramnia R, Figueroa MS, Hattenbach L-O et al (2022) Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD. Graefes Arch Clin Exp Ophthalmol 260:1843–1856

    Article  CAS  PubMed  Google Scholar 

  15. Baumal CR, Bodaghi B, Singer M et al (2021) Expert opinion on management of intraocular inflammation, retinal vasculitis, and vascular occlusion after Brolucizumab treatment. Ophthalmol Retina 5:519–527

    Article  PubMed  Google Scholar 

  16. Yannuzzi LA, Wong DW, Sforzolini BS et al (1999) Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration. Arch Ophthalmol 117:1503–1510

    Article  CAS  PubMed  Google Scholar 

  17. Maruko I, Iida T, Saito M et al (2007) Clinical characteristics of exudative age-related macular degeneration in Japanese patients. Am J Ophthalmol 144:15–22

    Article  PubMed  Google Scholar 

  18. Singerman LJ, Brucker AJ, Jampol LM et al (2005) Neovascular age-related macular degeneration: roundtable. Retina 25:S1–S22

    Article  PubMed  Google Scholar 

  19. Barthelmes D, Nguyen V, Daien V et al (2018) Two year outcomes of “treat and extend” intravitreal therapy using Aflibercept preferentially for Neovascular age-related macular degeneration. Retina 38:20–28

    Article  CAS  PubMed  Google Scholar 

  20. Berg K, Pedersen TR, Sandvik L, Bragadóttir R (2015) Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology 122:146–152

    Article  PubMed  Google Scholar 

  21. Cohen SY, Dubois L, Tadayoni R et al (2009) Results of one-year’s treatment with ranibizumab for exudative age-related macular degeneration in a clinical setting. Am J Ophthalmol 148:409–413

    Article  CAS  PubMed  Google Scholar 

  22. Guex-Crosier Y, Pittet N, Herbort CP (1995) Sensitivity of laser flare photometry to monitor inflammation in uveitis of the posterior segment. Ophthalmology 102:613–621

    Article  CAS  PubMed  Google Scholar 

  23. Herbort CP, Guex-Crosier Y, de Ancos E, Pittet N (1997) Use of laser flare photometry to assess and monitor inflammation in uveitis. Ophthalmology 104:64–71

    Article  CAS  PubMed  Google Scholar 

  24. Tadayoni R, Sararols L, Weissgerber G et al (2021) Brolucizumab: a newly developed anti-VEGF molecule for the treatment of neovascular age-related macular degeneration. Ophthalmologica 244:93–101

    Article  CAS  PubMed  Google Scholar 

  25. Mukai R, Matsumoto H, Akiyama H (2021) Risk factors for emerging intraocular inflammation after intravitreal brolucizumab injection for age-related macular degeneration. PLoS ONE 16:e0259879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Maruko I, Okada AA, Iida T et al (2021) Brolucizumab-related intraocular inflammation in Japanese patients with age-related macular degeneration: a short-term multicenter study. Graefes Arch Clin Exp Ophthalmol 259:2857–2859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rossi S, D’Amico M, Capuano A et al (2006) Hyperglycemia in streptozotocin-induced diabetes leads to persistent inflammation and tissue damage following uveitis due to reduced levels of ciliary body heme oxygenase-1. Mediators Inflamm 2006:60285

    Article  PubMed  PubMed Central  Google Scholar 

  28. Shimura M, Yasuda K (2010) Macular ischaemia after intravitreal bevacizumab injection in patients with central retinal vein occlusion and a history of diabetes and vascular disease. Br J Ophthalmol 94:381–383

    Article  PubMed  Google Scholar 

  29. Baumal CR, Spaide RF, Vajzovic L et al (2020) Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab. Ophthalmology 127:1345–1359

    Article  PubMed  Google Scholar 

  30. Witkin AJ, Hahn P, Murray TG et al (2020) Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis 4:269–279

    Article  PubMed  PubMed Central  Google Scholar 

  31. Subhi Y, Krogh Nielsen M, Molbech CR et al (2019) Association of CD11b+ monocytes and anti-vascular endothelial growth factor injections in treatment of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. JAMA Ophthalmol 137:515–522

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tugal-Tutkun I, Herbort CP (2010) Laser flare photometry: a noninvasive, objective, and quantitative method to measure intraocular inflammation. Int Ophthalmol 30:453–464

    Article  PubMed  Google Scholar 

  33. Agrawal R, Keane PA, Singh J et al (2016) Comparative analysis of anterior chamber flare grading between clinicians with different levels of experience and semi-automated laser flare photometry. Ocul Immunol Inflamm 24:184–193

    PubMed  Google Scholar 

  34. Tugal-Tutkun I, Cingü K, Kir N et al (2008) Use of laser flare-cell photometry to quantify intraocular inflammation in patients with Behçet uveitis. Graefes Arch Clin Exp Ophthalmol 246:1169–1177

    Article  PubMed  Google Scholar 

  35. Jiang S, Liu X, Luo L et al (2011) Serum levels of Th17-related cytokines in Behcet disease patients after cataract surgery. Mol Vis 17:1425–1430

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Funatsu H, Yamashita H, Noma H et al (2002) Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol 133:70–77

    Article  CAS  PubMed  Google Scholar 

  37. Noma H, Mimura T, Shimada K (2014) Role of inflammation in previously untreated macular edema with branch retinal vein occlusion. BMC Ophthalmol 14:67

    Article  PubMed  PubMed Central  Google Scholar 

  38. Noma H, Mimura T, Tatsugawa M, Shimada K (2013) Aqueous flare and inflammatory factors in macular edema with central retinal vein occlusion: a case series. BMC Ophthalmol 13:78

    Article  PubMed  PubMed Central  Google Scholar 

  39. Saito M, Kobori H, Nozuki N et al (2022) A case of intraocular inflammation after intravitreal brolucizumab injection monitored by laser flare-cell photometer. Am J Ophthalmol Case Rep 28:101727

    Article  PubMed  PubMed Central  Google Scholar 

  40. Taipale C, Lindholm J-M, Tuuminen R (2018) Aqueous flare as a marker of retinal disease activity after anti-VEGF injections. Acta Ophthalmol 96:e1043–e1044

    Article  PubMed  Google Scholar 

  41. Busch M, Pfeil JM, Dähmcke M et al (2022) Anti-drug antibodies to brolucizumab and ranibizumab in serum and vitreous of patients with ocular disease. Acta Ophthalmol 100:903–910

    Article  CAS  PubMed  Google Scholar 

  42. Hautamäki A, Luoma A, Immonen I (2016) Anterior chamber flare during bevacizumab treatment in eyes with exudative age-related macular degeneration. Retina 36:2183–2190

    Article  PubMed  Google Scholar 

  43. Streilein JW (2003) Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 74:179–185

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This paper was supported by JST grants from JSPS KAKENHI Grants-in-Aid for Scientific Research (C) (H.K. 17K11445 and M.Y. 23K09055) and COI-NEXT (JPMJPF2201). The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-Machi, Aoba-Ku, Sendai, 980-8574, Japan

    Keisuke Hoshi, Hiroshi Kunikata, Naoko Aizawa, Masayuki Yasuda, Tatsu Okabe, Hiroki Takizawa & Toru Nakazawa

  2. Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan

    Hiroshi Kunikata & Toru Nakazawa

  3. Division of Clinical Cell Therapy Center for Advanced Medical Research and Development, Tohoku University Graduate School of Medicine, Sendai, Japan

    Toshiaki Abe

  4. Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Japan

    Toru Nakazawa

  5. Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Toru Nakazawa

Authors
  1. Keisuke Hoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroshi Kunikata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naoko Aizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masayuki Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tatsu Okabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroki Takizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshiaki Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Toru Nakazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Involved in design and conduct of the study were (HK); preparation, collection, management, analysis, and interpretation of the data (KH, HK, NA, MY, TO, HT, TA and TN); and approval of the manuscript (TN). HK, NA and MY wrote the main manuscript text. KH and NA prepared all tables and all figures, and all authors reviewed the manuscript.

Corresponding author

Correspondence to Hiroshi Kunikata.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hoshi, K., Kunikata, H., Aizawa, N. et al. Baseline characteristics associated with the incidence of intraocular inflammation after the intravitreous injection of brolucizumab. Int Ophthalmol 43, 4701–4709 (2023). https://doi.org/10.1007/s10792-023-02870-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-023-02870-4

Keywords

Search

Navigation