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Graefe's Archive for Clinical and Experimental Ophthalmology

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31.03.2023 | Retinal Disorders

Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration

verfasst von: Ryo Terao, Ryo Obata, Atsushi Okubo, Shuichiro Aoki, Keiko Azuma, Tazbir Ahmed, Satoru Inoda, Yuto Hashimoto, Ryota Takahashi, Hana Yoshida, Manami Misawa, Hironori Takahashi, Hidenori Takahashi

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 9/2023

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Abstract

Purpose

To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration.

Methods

Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI +) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI −) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay.

Results

C–C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI + than in IVBrIOI − and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI − compared to that in IVBrIOI + and IVA. In the IVBrIOI + group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI − group.

Conclusion

The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr.

Apte RS (2021) Age-related macular degeneration. N Engl J Med 385:539–547. https://doi.org/10.1056/NEJMcp2102061CrossRefPubMedPubMedCentral

Schmidt-Erfurth U, Waldstein SM (2016) A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration. Prog Retin Eye Res 50:1–24. https://doi.org/10.1016/j.preteyeres.2015.07.007CrossRefPubMed

Schmidt-Erfurth U, Chong V, Loewenstein A, Larsen M, Souied E, Schlingemann R, Eldem B, Mones J, Richard G, Bandello F, European Society of Retina S (2014) Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol 98:1144–1167. https://doi.org/10.1136/bjophthalmol-2014-305702CrossRef

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY, Group MS (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431. https://doi.org/10.1056/NEJMoa054481CrossRef

Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U, View, Groups VS (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548. https://doi.org/10.1016/j.ophtha.2012.09.006CrossRef

Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG, Hawk IHS (2020) HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 127:72–84. https://doi.org/10.1016/j.ophtha.2019.04.017CrossRefPubMed

Dugel PU, Singh RP, Koh A, Ogura Y, Weissgerber G, Gedif K, Jaffe GJ, Tadayoni R, Schmidt-Erfurth U, Holz FG (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. https://doi.org/10.1016/j.ophtha.2020.06.028CrossRefPubMed

Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, Brown DM, Chong V, Nguyen QD, Ho AC, Ogura Y, Simader C, Jaffe GJ, Slakter JS, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Sowade O, Zeitz O, Norenberg C, Sandbrink R, Heier JS (2014) Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology 121:193–201. https://doi.org/10.1016/j.ophtha.2013.08.011CrossRefPubMed

Iyer PG, Peden MC, Suner IJ, Patel N, Dubovy SR, Albini TA (2020) Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: a clinicopathologic case study. Am J Ophthalmol Case Rep 20:100989. https://doi.org/10.1016/j.ajoc.2020.100989CrossRefPubMedPubMedCentral

10.

Haug SJ, Hien DL, Uludag G, Ngoc TTT, Lajevardi S, Halim MS, Sepah YJ, Do DV, Khanani AM (2020) Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep 18:100680. https://doi.org/10.1016/j.ajoc.2020.100680CrossRefPubMedPubMedCentral

11.

Jain A, Chea S, Matsumiya W, Halim MS, Yasar C, Kuang G, Sepah YJ, Khanani AM, Do DV, Nguyen QD (2020) Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations. Am J Ophthalmol Case Rep 18:100687. https://doi.org/10.1016/j.ajoc.2020.100687CrossRefPubMedPubMedCentral

12.

Baumal CR, Spaide RF, Vajzovic L, Freund KB, Walter SD, John V, Rich R, Chaudhry N, Lakhanpal RR, Oellers PR, Leveque TK, Rutledge BK, Chittum M, Bacci T, Enriquez AB, Sund NJ, Subong ENP, Albini TA (2020) Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology 127:1345–1359. https://doi.org/10.1016/j.ophtha.2020.04.017CrossRefPubMed

13.

Maruko I, Okada AA, Iida T, Hasegawa T, Izumi T, Kawai M, Maruko R, Nakayama M, Yamamoto A, Koizumi H, Tamashiro T, Terao N, Wakugawa S, Mori R, Onoe H, Tanaka K, Wakatsuki Y, Itagaki K, Kasai A, Ogasawara M, Sekiryu T, Shintake H, Sugano Y, Japan AMDRC (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. https://doi.org/10.1007/s00417-021-05136-wCrossRefPubMedPubMedCentral

14.

Inoda S, Takahashi H, Inoue Y, Tan X, Tampo H, Arai Y, Yanagi Y, Kawashima H (2022) 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. https://doi.org/10.1007/s00417-021-05445-0CrossRefPubMed

15.

Joo JH, Kim H, Shin JH, Moon SW (2021) Aqueous humor cytokine levels through microarray analysis and a sub-analysis based on optical coherence tomography in wet age-related macular degeneration patients. BMC Ophthalmol 21:399. https://doi.org/10.1186/s12886-021-02152-6CrossRefPubMedPubMedCentral

16.

Sijssens KM, Rijkers GT, Rothova A, Stilma JS, Schellekens PA, de Boer JH (2007) Cytokines, chemokines and soluble adhesion molecules in aqueous humor of children with uveitis. Exp Eye Res 85:443–449. https://doi.org/10.1016/j.exer.2007.06.011CrossRefPubMed

17.

Martin CM, Lacomba MS, Molina CI, Chamond RR, Galera JM, Estevez EC (2000) Levels of soluble ICAM-1 and soluble IL-2R in the serum and aqueous humor of uveitis patients. Curr Eye Res 20:287–292CrossRefPubMed

18.

Spindler J, Zandi S, Pfister IB, Gerhardt C, Garweg JG (2018) Cytokine profiles in the aqueous humor and serum of patients with dry and treated wet age-related macular degeneration. PLoS One 13:0203337. https://doi.org/10.1371/journal.pone.0203337CrossRef

19.

Abu El-Asrar AM, Berghmans N, Al-Obeidan SA, Gikandi PW, Opdenakker G, Van Damme J, Struyf S (2020) Local cytokine expression profiling in patients with specific autoimmune uveitic entities. Ocul Immunol Inflamm 28: 453–462 https://doi.org/10.1080/09273948.2019.1604974

20.

Park J, Kim JT, Lee SJ, Kim JC (2020) The anti-inflammatory effects of angiogenin in an endotoxin induced uveitis in rats. Int J Mol Sci 21 https://doi.org/10.3390/ijms21020413

21.

Garcia-Otero X, Mondelo-Garcia C, Gonzalez F, Perez-Fernandez R, Avila L, Antunez-Lopez JR, Gonzalez-Barcia M, Adan A, Aguiar P, Otero-Espinar FJ, Bermudez MA, Fernandez-Ferreiro A (2021) Anti-inflammatory effect of tacrolimus/hydroxypropyl-beta-cyclodextrin eye drops in an endotoxin-induced uveitis model. Pharmaceutics 13 https://doi.org/10.3390/pharmaceutics13101737

22.

Wilkerson RG (2022) Drug hypersensitivity reactions. Emerg Med Clin North Am 40:39–55. https://doi.org/10.1016/j.emc.2021.09.001CrossRefPubMed

23.

Phillips EJ, Bigliardi P, Bircher AJ, Broyles A, Chang YS, Chung WH, Lehloenya R, Mockenhaupt M, Peter J, Pirmohamed M, Roujeau JC, Shear NH, Tanno LK, Trubiano J, Valluzzi R, Barbaud A (2019) Controversies in drug allergy: testing for delayed reactions. J Allergy Clin Immunol 143:66–73. https://doi.org/10.1016/j.jaci.2018.10.030CrossRefPubMed

24.

Dispenza MC (2019) Classification of hypersensitivity reactions. Allergy Asthma Proc 40:470–473. https://doi.org/10.2500/aap.2019.40.4274CrossRefPubMed

25.

Isabwe GAC, Garcia Neuerde Las Vecillas Sanchez L, Lynch DM, Marquis K, Castells M, M (2018) Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes. J Allergy Clin Immunol 142(159–170):152. https://doi.org/10.1016/j.jaci.2018.02.018CrossRef

26.

Morgenstern-Kaplan D, Vasquez-Echeverri E, Carrillo-Martin I, Chiarella SE, Gonzalez-Estrada A (2021) Cytokine-release hypersensitivity reaction after the first dose of benralizumab for severe eosinophilic asthma. Ann Allergy Asthma Immunol 127:701–702. https://doi.org/10.1016/j.anai.2021.08.006CrossRefPubMed

27.

Witkin AJ, Hahn P, Murray TG, Arevalo JF, Blinder KJ, Choudhry N, Emerson GG, Goldberg RA, Kim SJ, Pearlman J, Schneider EW, Tabandeh H, Wong RW (2020) Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis 4:269–279. https://doi.org/10.1177/2474126420930863CrossRefPubMedPubMedCentral

28.

Demerath E, Towne B, Blangero J, Siervogel RM (2001) The relationship of soluble ICAM-1, VCAM-1, P-selectin and E-selectin to cardiovascular disease risk factors in healthy men and women. Ann Hum Biol 28:664–678. https://doi.org/10.1080/03014460110048530CrossRefPubMed

29.

Hayashi S, Watanabe N, Nakazawa K, Suzuki J, Tsushima K, Tamatani T, Sakamoto S, Isobe M (2000) Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries. Circulation 102:1710–1717. https://doi.org/10.1161/01.cir.102.14.1710CrossRefPubMed

30.

Jaakkola K, Jalkanen S, Kaunismaki K, Vanttinen E, Saukko P, Alanen K, Kallajoki M, Voipio-Pulkki LM, Salmi M (2000) Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans. J Am Coll Cardiol 36:122–129. https://doi.org/10.1016/s0735-1097(00)00706-3CrossRefPubMed

31.

Chen YH, Lightman S, Eskandarpour M, Calder VL (2022) Adhesion molecule targeted therapy for non-infectious uveitis. Int J Mol Sci 23 https://doi.org/10.3390/ijms23010503

32.

Avaylon J, Lee S, Gallemore RP (2020) Case series on initial responses to intravitreal brolucizumab in patients with recalcitrant chronic wet age-related macular degeneration. Int Med Case Rep J 13:145–152. https://doi.org/10.2147/IMCRJ.S252260CrossRefPubMedPubMedCentral

33.

Tietz J, Spohn G, Schmid G, Konrad J, Jampen S, Maurer P, Schmidt A, Escher D (2015) Affinity and potency of RTH258 (ESBA1008), a novel inhibitor of vascular endothelial growth factor A for the treatment of retinal disorders. Invest Ophthalmol Vis Sci 56:1501–1501

34.

Chakraborty D, Sheth JU, Mondal S, Boral S (2022) Role of intravitreal brolucizumab with intravitreal rtPA and pneumatic displacement for submacular hemorrhage: a case series. Am J Ophthalmol Case Rep 25:101390. https://doi.org/10.1016/j.ajoc.2022.101390CrossRefPubMedPubMedCentral

35.

Tadayoni R, Sararols L, Weissgerber G, Verma R, Clemens A, Holz FG (2021) Brolucizumab: a newly developed anti-VEGF molecule for the treatment of neovascular age-related macular degeneration. Ophthalmologica 244:93–101. https://doi.org/10.1159/000513048CrossRefPubMed

36.

Takahashi H, Nomura Y, Nishida J, Fujino Y, Yanagi Y, Kawashima H (2016) Vascular endothelial growth factor (VEGF) concentration is underestimated by enzyme-linked immunosorbent assay in the presence of anti-VEGF drugs. Invest Ophthalmol Vis Sci 57:462–466. https://doi.org/10.1167/iovs.15-18245CrossRefPubMed

37.

Becher B, Spath S, Goverman J (2017) Cytokine networks in neuroinflammation. Nat Rev Immunol 17:49–59. https://doi.org/10.1038/nri.2016.123CrossRefPubMed

Titel: Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration
verfasst von: Ryo Terao
Ryo Obata
Atsushi Okubo
Shuichiro Aoki
Keiko Azuma
Tazbir Ahmed
Satoru Inoda
Yuto Hashimoto
Ryota Takahashi
Hana Yoshida
Manami Misawa
Hironori Takahashi
Hidenori Takahashi
Publikationsdatum: 31.03.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 9/2023
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-023-06038-9

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Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Cytokine profiles in the aqueous humor following brolucizumab administration for exudative age-related macular degeneration

Abstract

Purpose

Methods

Results

Conclusion

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Abstract

Purpose

Methods

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