Aqueous humour cytokine profiles in retinal vein occlusion: a comparative study of acute, chronic recurrent, and control eyes

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PURPOSE: This study aimed to characterize inflammatory cytokine profiles in recurrent retinal vein occlusion (RVO) and to describe subtype- and phase-specific patterns relative to controls. METHODS: This was retrospective study conducted from September 2010 to September 2022 at the Japan Community Healthcare Organization Tokyo Shinjuku Medical Center and Jichi Medical University. Aqueous humour (AqH) was collected immediately before intravitreal bevacizumab, ranibizumab or aflibercept injections from patients with RVO. We included an acute group (RVO onset within 3 months) and a recurrent group (patients with disease duration of ≥ 1 year). Using a multiplex cytokine assay, we measured the concentrations of nine cytokines and VEGF. The results were compared with controls after adjusting for sex, age, axial length, and posterior vitreous detachment. RESULTS: AqH samples from 30 acute branch RVO (BRVO), 31 recurrent BRVO, 25 acute central RVO (CRVO), 20 recurrent CRVO, and 81 cataract surgery eyes without retinal disease (as controls) were used. In recurrent BRVO, MCP-1, CXCL13, and CCL11 levels were significantly lower than those in control eyes (all, P < 0.05). Similarly, in recurrent CRVO, MCP-1, CXCL12, CXCL13, CCL11, and CXCL1 levels were significantly reduced compared with controls (all, P < 0.05), whereas IL-6 levels were significantly elevated (P < 0.05). In acute RVO, cytokine alterations compared with controls were limited. Acute BRVO showed decreased MCP-1, CXCL13, and CCL11 levels (all, P < 0.05), while acute CRVO exhibited increased IL-6 and IP-10 levels (all, P < 0.05). CONCLUSIONS: Inflammatory cytokine profiles in recurrent RVO differ between BRVO and CRVO and are characterized by reduced levels of multiple inflammatory cytokines compared with controls. These findings highlight distinct inflammatory features of recurrent RVO and provide a basis for future studies investigating disease progression and treatment resistance. TRIAL REGISTRATION: UMIN000020718 https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_his_list.cgi?recptno=R000023907 . KEY MESSAGES: WHAT IS KNOWN: While anti- endothelial growth factor (VEGF) therapy is effective for treating cystic macular oedema (CME) secondary to retinal vein occlusion (RVO), the condition is not confined to the acute phase. The frequent chronicity and recurrence of CME imply that other pathological factors, beyond VEGF, are involved. Furthermore, preceding research on acute RVO has documented increased levels of inflammatory cytokines, including IL-6, IL-8, and MCP-1. WHAT IS NEW: Inflammatory cytokine profiles differ between branch RVO and central RVO in both acute and recurrent cases when each is explained relative to controls using multivariable-adjusted analyses. In particular, recurrent RVO is characterized by reduced levels of several inflammatory cytokines compared with controls, indicating a distinct inflammatory profile in the recurrent phase and providing insights into disease progression.

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