Aqueous humour proteins and treatment outcomes of anti-VEGF therapy in neovascular age-related macular degeneration

Yusuke Arai,Shinichi Sakamoto,Xue Tan,Satoru Inoda,Yuji Inoue,Hidenori Takahashi,Yujiro Fujino,Yasuo Yanagi,Hidetoshi Kawashima,Alfred S Lewin

doi:10.1371/journal.pone.0229342

Abstract

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = -0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P < 0.001) and IL-10 (β coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.

Highlights

Among C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein (IP-10), monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand (CCL11), interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9), selected based on previous clinical and animal studies [12,13,14], we found that pro-inflammatory cytokines are elevated in the aqueous humour of neovascular age-related macular degeneration (nAMD) patients, while MMP-9 levels are decreased [13]
Worse best-corrected visual acuity (BCVA) was associated with increased Central retinal thickness (CRT) (r = 0.43, P = 0.020), induced protein 10 (IP-10) (r = 0.44, P = 0.016), MCP-1 (r = 0.54, P = 0.0025), and IL-6 (r = 0.44, P = 0.018) in univariate analysis (Table 1)
Multiple regression analysis after stepwise variable selection demonstrated that besides male sex (β coefficient = −0.088, i.e. regression coefficient was −0.088 logarithm of minimum angle of resolution (logMAR) for men [as 1] vs women [as 0], P = 0.040) and CRT (β coefficient = 0.00051 logMAR per μm, P = 0.027), logMCP-1 (β coefficient = 0.44, i.e. baseline BCVA worsened by 0.44 logMAR per logMCP-1, P < 0.001) and logIL-10 (β coefficient = −0.16, P = 0.033) were independently associated with baseline BCVA (Table 1)

Summary

Objectives

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration using the concentrations of aqueous humour proteins at baseline and during treatment

Methods

Results

Discussion

Conclusion