Investigative Ophthalmology & Visual Science Cover Image for Volume 60, Issue 9
July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Trends for poorer vision outcomes in nAMD and DME patients with higher aqueous humor levels of IL-6
Author Affiliations & Notes
  • Yasir Jamal Sepah
    Byers Eye Institute, Palo Alto, California, Palo Alto, California, United States
  • Quan Dong Nguyen
    Byers Eye Institute, Palo Alto, California, Palo Alto, California, United States
  • Diana V Do
    Byers Eye Institute, Palo Alto, California, Palo Alto, California, United States
  • Bann-mo Day
    Genentech, Inc., South San Francisco, California, United States
  • Eric Wakshull
    Genentech, Inc., South San Francisco, California, United States
  • Ivaylo Stoilov
    Genentech, Inc., South San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Yasir Jamal Sepah, Eyepoint (F), Genentech (F), Kodiak (F), Regeneron (F), Santen (F); Quan Nguyen, Astellas (F), Eyepoint (F), Genentech (F), Gilead (F), Regeneron (F), Sanofi (F), Santen (F); Diana Do, Eyepoint (F), Genentech (F), Kodiak (F), Regeneron (F), Santen (F); Bann-mo Day, Genentech (E), Genentech (I); Eric Wakshull, Genentech (E), Genentech (I); Ivaylo Stoilov, Genentech (E), Genentech (I)
  • Footnotes
    Support  The READ 3 trial was supported by funding from JDRF International; materials in kind (drug) provided by Genentech, Inc, a member of the Roche Group. The HARBOR trial and the current analysis was funded by Genentech, Inc.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4938. doi:
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      Yasir Jamal Sepah, Quan Dong Nguyen, Diana V Do, Bann-mo Day, Eric Wakshull, Ivaylo Stoilov; Trends for poorer vision outcomes in nAMD and DME patients with higher aqueous humor levels of IL-6. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4938.

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Abstract

Purpose : To measure the interleukin 6 (IL-6) levels in the aqueous humor of patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); Compare vison outcomes with anti-vascular endothelial growth factor (anti-VEGF) monotherapy between “high” and “low” IL-6 concentration groups.

Methods : In the READ3 study 152 patients with DME were randomized 1:1 to receive 0.5 mg or 2.0 mg ranibizumab q4 for 24 months. Aqueous humor samples from 131 eyes were collected at baseline, Months 3, 6, 9 and 12. In the HARBOR study 1097 patients with nAMD were randomized 1:1:1:1 to receive 0.5 mg or 2.0 mg ranibizumab q4 or PRN for 24 months. Matching aqueous and serum samples collected at study month 2 (after the third monthly/loading ranibizumab injection) were available from 36 patients. Functional outcomes were assessed as change from baseline in BCVA (ETDRS letters). Wilcoxon rank-sum test was used to compare concentrations. Spearman rank correlation coefficient was used to evaluate correlations between IL-6 levels and functional outcomes.

Results : IL-6 levels did not appear to be affected by VEGF inhibition. After 3 ranibizumab injections the median IL-6 concentration in aqueous humor was 24.7 pg/ml in patients with DME and 6.0 pg/ml in patients with nAMD. There was no correlation between aqueous and serum IL-6 levels in patients with nAMD. In READ3 at all time points there appears to be a negative correlation between the baseline IL-6 level and BCVA: the higher the baseline IL-6 levels rank, the lower the BCVA levels tend to rank at every time point (Figure 1). In the HARBOR trial nAMD patients with the highest aqueous IL-6 levels on average lost 9 BCVA letters by the end of the study, while the rest of patients maintained vision (Figure 2).

Conclusions : Analyses from two different groups of patients with DME and nAMD identify potential trend of poorer vision outcomes with anti-VEGF monotherapy in patients with higher aqueous levels of IL-6.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

READ3: Change in BCVA from baseline by IL-6 Levels (High = top 25%; Low = bottom 75%)

READ3: Change in BCVA from baseline by IL-6 Levels (High = top 25%; Low = bottom 75%)

 

HARBOR: Change in BCVA from month 2 by IL-6 Levels (High = top 25%; Low = bottom 75%)

HARBOR: Change in BCVA from month 2 by IL-6 Levels (High = top 25%; Low = bottom 75%)

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