Associations of inflammatory cytokines with choroidal neovascularization in highly myopic eyes.

PURPOSE: To determine the relationships between the levels of intraocular inflammatory cytokines and the clinical characteristics of myopic choroidal neovascularization (mCNV) in eyes with myopic maculopathy. METHODS: One hundred eyes of 100 cases, including 51 mCNV eyes, 14 highly myopic eyes without choroidal neovascularization, and 35 normal subjects, were studied. The intraocular levels of choroidal neovascularization-related cytokines, like vascular endothelial growth factor, MCP-1, IL-8, IL-10, and IL-23, were determined. RESULTS: The levels of vascular endothelial growth factor and IL-8 were significantly higher in eyes with mCNV than in high myopia eyes without mCNV with significant odds ratio of 2.00 and 2.25 per quartile, respectively (P < 0.05). When myopic lesions of patients with mCNV were classified into 3 categories based on the severity, IL-8 and MCP-1 were significantly elevated depending on the presence of maculopathy (P < 0.05). Vascular endothelial growth factor was significantly elevated in eyes of Category 2. An advancement of the maculopathy category was significantly associated with the need for multiple treatment of intravitreal bevacizumab (P < 0.05). In 12 eyes that required multiple intravitreal bevacizumab, the MCP-1 level was significantly elevated. CONCLUSION: The significant associations of mCNV in highly myopic eyes with elevated levels of vascular endothelial growth factor or inflammatory cytokines and maculopathy lesions strongly suggest an involvement of inflammation in the etiology of mCNVs.

Associations of IL-23 with polypoidal choroidal vasculopathy.

PURPOSE: To determine the relationship between the levels of intraocular inflammatory cytokines and polypoidal choroidal vasculopathy (PCV). METHODS: Prospective cohort study. Sixty-two patients with PCV and 36 control subjects were studied. The levels of cytokines, chemokines, and growth factors in the aqueous humor samples from PCV patients and control subjects were assessed for significant associations with PCV. Logistic regression analysis was used to compute the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles. RESULTS: In PCV patients, IL-4, IL-10, and IL-23 were significantly higher than in the controls. Logistic analyses showed a significantly high risk for IL-23 (OR for the highest quartile compared with the lowest quartile: 16.3; 95% CI: 3.5-75.2), VEGF (5.7; 1.2-26.1), and IL-4 (4.0; 1.3-12.7). IL-10 and IL-4, but not IL-23, were significantly correlated with the VEGF levels in PCV patients (IL-10: ρ = 0.477, IL-4: ρ = 0.281). The elevated levels of IL-5, IL-10, IL-4, IL-23, and IL-1α were found to be significantly associated with exudative lesion(s) in the fluorescein angiograms. CONCLUSIONS: The significant associations between elevated levels of IL-23 with PCV and its activity strongly suggest an involvement of inflammatory processes in the etiology of PCV, presumably independent of VEGF. (www.umin.ac.jp/ctr number, UMIN000003854.).

Multivariate analyses of inflammatory cytokines in eyes with branch retinal vein occlusion: relationships to bevacizumab treatment.

PURPOSE: To characterize the differential expression of intraocular inflammatory cytokines in eyes with branch retinal vein occlusion (BRVO) and to assess their roles as prognostic determinants of BRVO. METHODS: A prospective cohort study of 38 eyes with BRVO. Aqueous humor samples were collected just before the intravitreal injection of bevacizumab and were assessed for 18 cytokines, chemokines, and growth factors. For control, aqueous humor was collected from 28 eyes before cataract surgery. RESULTS: In the aqueous of eyes with BRVO, the IL-23, IL-8, IL-6, IL-15, IL-12, and IL-17 levels were significantly higher than that in control eyes. Pretreatment visual acuity was significantly correlated with the concentrations of IL-8, IL-10, IL-2, IL-1ß, IL-5, IL-6, IL-23, IL-4, MCP-1, IL-1α, IL-12, IL-13, IFN-γ, and IL-15. The pretreatment nonperfused area (NPA) was significantly correlated with the concentrations of IL-8, IL-2, MCP-1, and IL-6. Logistic regression analyses revealed significant associations between the BRVO and the concentrations of IL-8, IL-23, IL-12, IL-15, IL-10, IL-1ß, and IL-13. IL-8 had the highest odds ratio (OR) and was significantly associated with NPA, central retinal thickness (CRT), and visual acuity. Bevacizumab treatment significantly improved visual acuity and CRT after 1 month. Refractoriness to bevacizumab (defined as CRT recovery 1 month after treatment by <90%) was significantly associated with the IL-12 level. CONCLUSIONS: Of the induced cytokines in eyes with BRVO, IL-8 was the most significantly associated with the disease parameters of BRVO. IL-12 is most likely a factor that blocks the effect of bevacizumab treatment. (www.umin.ac.jp/ctr number, UMIN000003854.).