Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy

Yasir Jamal Sepah; Diana V Do; Marina Mesquida; Bann-Mo Day; Steven Blotner; Rubbia Afridi; Muhammad Sohail Halim; Kyu Hong; Eric Wakshull; Sascha Fauser; Ivaylo Stoilov; Quan Dong Nguyen; HARBOR; READ-3 Investigators

doi:10.1038/s41433-024-03015-2

Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy

Eye (Lond). 2024 Apr 15. doi: 10.1038/s41433-024-03015-2. Online ahead of print.

Authors

Collaborators

P Abraham, D V Alfaro 3rd, A Antoszyk, M Antworth, B Baker, C Baker, M Balles, D Boyer, W Bridges Jr, D M Brown, B Busbee, M Busquets, C Chan, N Chaudhry, S Chen, J Christoforidis, T Ciulla, W L Clark, T Cleland, T Connor, A Daccache, A Dessouki, K Diddie, B Doft, R Dreyer, D W Faber, L Feiner, R Feldman, P Ferrone, G Fox, S Foxman, R Frenkel, A Fung, R Gallemore, T Ghuman, V Gonzalez, A Gordon, C Gordon, S Gupta, S Hariprasad, J Heier, A Ho, D Holmes, J Huang, J P Hubschman, H Hudson, D Ie, R Johnson, R Katz, S Kiss, J Kitchens, G Kokame, E Lit, M Liu, J K Luu, M MacCumber, S Madreperla, D Marcus, A Martidis, J Martinez, M Michels, D Miller, L Morse, M Nasir, Q Nguyen, S Oliver, K Olsen, S Patel, P Pavan, J Pearlman, J Prenner, C Regillo, E Reichel, R Rosa, S Rose, S Sadda, M Samuel, L Singerman, M Singer, R Singh, G Stoller, I Suner, A Tabassian, B Taney, A Thach, M Thomas, M Tolentino, D Tom, P Tornambe, R Torti, S Truong, T Verstraeten, A Wagner, K Wald, P Weber, P Weishaar, M Wieland, D Williams, T Wong, M Wood, J Wroblewski, K Zhang, D V Do, E Lit, E Kruger, J Pollack, L Halperin, M Bennett, D Boyer, D Callanan, K Zhang, A Symons, P Abraham

Affiliations

¹ Byers Eye Institute, Spencer Center for Vision Research, Stanford University, Palo Alto, CA, USA.
² Roche Pharma Research and Early Development, Basel, Switzerland.
³ Genentech Inc., South San Francisco, CA, USA.
⁴ Ocular Imaging Research and Reading Center, Sunnyvale, CA, USA.
⁵ Genentech Inc., South San Francisco, CA, USA. stoilovi@gene.com.
⁶ Byers Eye Institute, Spencer Center for Vision Research, Stanford University, Palo Alto, CA, USA. ndquan@stanford.edu.

PMID: 38622330
DOI: 10.1038/s41433-024-03015-2

Abstract

Background: This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy.

Methods: Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12.

Main outcome measure: association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA).

Results: In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters.

Conclusions: Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.

Abstract

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