Aqueous humor cytokine levels in retinal vein occlusion patients with suboptimal response to anti-VEGF therapy and the correlation with OCT imaging biomarkers.

PURPOSE: To assess the differences in baseline and longitudinal cytokine profiles among super responders, slow responders, and non-responders in patients with retinal vein occlusion-macular edema (RVO-ME) and evaluate the association of cytokines with biomarkers identified on optical coherence tomography (OCT).

METHODS

Forty-four patients with RVO-ME and 37 patients with cataract were enrolled. Aqueous humor samples were collected before the first and second anti-vascular endothelial growth factor (VEGF) injections. The aqueous samples were analyzed for cytokine levels using multiplex immunoassay. OCT-based response categories were defined as super responders, slow responders, and non-responders according to ME resolution. Central retinal thickness (CRT), subretinal fluid (SRF), hyperreflective foci (HRF), disorganization of retinal inner layers (DRIL), and disorganization of retinal outer layers (DROL) were obtained for analysis.

RESULTS

At baseline, RVO patients exhibited elevated VEGF, placental growth factor (PIGF), angiopoietin-2 (Ang-2), interleukin-6 (IL-6), IL-8, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) compared with controls (p < 0.01). Super responders showed significantly lower baseline Ang-2 and IL-6 (p = 0.027 and 0.034, respectively) than slow and non-responders. Patients with severe edema and high HRF were likely to have higher levels of IL-6 (p < 0.05). Patients who presented with SRF or DROL at baseline showed higher levels of IL-6 and Ang-2 (p < 0.05). Multivariate linear regression revealed that the presence of SRF was associated with higher baseline Ang-2 (p = 0.029), and high HRF number was associated with higher baseline IL-6 (p = 0.048). After initial injection, non-responders still retained higher Ang-2 and IL-6 concentrations (p = 0.012 and p = 0.040, respectively) than super responders.

CONCLUSION

Ang-2 and IL-6 expression in aqueous humor were associated with specific OCT features and treatment response in RVO-ME. Lower baseline Ang-2 and IL-6 levels may predict superior anti-VEGF response, while persistently elevated levels were correlated with non-response.

TRANSLATIONAL RELEVANCE: Intraocular cytokines were found to be correlated with both the responsiveness to anti-VEGF therapy and OCT imaging biomarkers. This correlation suggested a potential connection to the underlying pathways and their significance in the prognosis of RVO, thereby facilitating personalized anti-VEGF therapy.