Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy
Authors: Sepah Yasir Jamal , Do Diana V. , Mesquida Marina , Day Bann-Mo , Blotner Steven , Afridi Rubbia , Halim Muhammad Sohail , Hong Kyu , Wakshull Eric , Fauser Sascha , Stoilov Ivaylo , Dong Nguyen Quan ,   on behalf of the HARBOR, Abraham P. , Alfaro D. V. , Antoszyk A. , Antworth M. , Baker B. , Baker C. , Balles M. , Boyer D. , Bridges W. , Brown D. M. , Busbee B. , Busquets M. , Chan C. , Chaudhry N. , Chen S. , Christoforidis J. , Ciulla T. , Clark W. L. , Cleland T. , Connor T. , Daccache A. , Dessouki A. , Diddie K. , Doft B. , Dreyer R. , Faber D. W. , Feiner L. , Feldman R. , Ferrone P. , Fox G. , Foxman S. , Frenkel R. , Fung A. , Gallemore R. , Ghuman T. , Gonzalez V. , Gordon A. , Gordon C. , Gupta S. , Hariprasad S. , Heier J. , Ho A. , Holmes D. , Huang J. , Hubschman J. P. , Hudson H. , Ie D. , Johnson R. , Katz R. , Kiss S. , Kitchens J. , Kokame G. , Lit E. , Liu M. , Luu J. K. , MacCumber M. , Madreperla S. , Marcus D. , Martidis A. , Martinez J. , Michels M. , Miller D. , Morse L. , Nasir M. , Nguyen Q. , Oliver S. , Olsen K. , Patel S. , Pavan P. , Pearlman J. , Prenner J. , Regillo C. , Reichel E. , Rosa R. , Rose S. , Sadda S. , Samuel M. , Singerman L. , Singer M. , Singh R. , Stoller G. , Suner I. , Tabassian A. , Taney B. , Thach A. , Thomas M. , Tolentino M. , Tom D. , Tornambe P. , Torti R. , Truong S. , Verstraeten T. , Wagner A. , Wald K. , Weber P. , Weishaar P. , Wieland M. , Williams D. , Wong T. , Wood M. , Wroblewski J. , Zhang K. ,   READ-3 Investigators, Do D. V. , Lit E. , Kruger E. , Pollack J. , Halperin L. , Bennett M. , Boyer D. , Callanan D. , Zhang K. , Symons A. , Abraham P. 
Published: April 2024

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.