Association of IL-4 with pachychoroid neovasculopathy

Abstract

The purpose of this study was to identify the inflammatory cytokines that were associated with pachychoroid neovasculopathy (PNV). Seventy-five eyes of 75 patients with PNV, 145 eyes of 145 patients with neovascular age-related macular degeneration without pachyvessels, and 150 eyes of 150 normal subjects were examined for the levels of intraocular cytokines. In eyes with PNV, the levels of IL-1α, IL-1β, IL-2, IL-4, IL-10, and VEGF were significantly higher than that of the controls. Logistic regression analysis showed that the highest association with the pachyvessels was found for IL-4, IL-2, and IL-1α. In eyes with PNV, the levels of IL-4, IL-2, IL-5, IL-13, IL-1α, and IL-1β were significantly higher in eyes with both increased choroidal thickness and choroidal vessel diameter. The strongest correlation with the choroidal thickness and vessel diameter was observed for IL-4. In PNV eyes with polypoidal lesions, the levels of IL-4, IL-17, and TNFβ were significantly correlated with the number of polypoidal lesions. Of these cytokines, IL-4 was especially associated with the thickness of the choroidal vessels and the formation of polypoidal lesions. We conclude that IL-4 is most likely involved in establishing the clinical characteristics of PNV and polypoidal vascular remodeling.

Figure 1

Levels of cytokines in the aqueous humor of eyes with pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), typical age-related macular degeneration (typical AMD), and normal subjects. In PNV (red bar), the level of IL-1α, IL-1β, IL-2, IL-4, IL-10, and VEGF were significantly higher than that of the control eyes (white bar). In the PCV eyes (blue bar), IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, and VEGF were significantly higher than that of the control eyes. The levels of IL-1α, IL-2, IL-8, IL-10, IL-17, and VEGF were higher in eyes with typical age-related macular degeneration (AMD; green bar) than in the normal control eyes. PNV, pachychoroid neovasculopathy; PCV, polypoidal choroidal vasculopathy; typical AMD, typical age-related macular degeneration. Data are the means (pg/ml) and standard error of the means. PNV, n = 75; PCV, n = 93; typical AMD, n = 52; control, n = 150. ANOVA and post hoc test (Dunnett).

Figure 2

Structural equation modeling path diagrams for associations among IL-4 level and disease characteristics. Associated cytokines and pathological choroidal features associated with pachychoroid neovasculopathy and neovascular age-related macular degeneration are shown in the path diagram using structural equation modeling. Subretinal hemorrhage, subretinal fibrosis, and type 1 MNV were coded as 0/1. IL-4, subfoveal thickness, and polypoidal lesions were coded as 0/1/2/3 based on quintile. Structural equation modeling construction with the inclusion of clinical characteristics was conducted by assessment using fitting indices, Akaike information criteria (AIC), and Bayesian information criteria (BIC). Arrows are shown with coefficients of association and P-values in the path diagram. Comparative fit index: 1.000, root mean square error of approximation: < 0.001, MNV: macular neovascularization, polypoidal lesions: numbers of polypoidal lesions at the macular lesion. ns, not significant, n = 220.

Figure 3

Representative case of pachychoroid neovasculopathy. (a) Fundus photograph of a 62-year-old female patient showing a retinal pigment epithelium (RPE) abnormality and a subretinal hemorrhage in the macular area. Large choroidal vessels can be seen on the nasal and temporal side of the macular area. (b) OCT image showing choroidal thickening, dilated choroidal pachyvessels with inner choroidal attenuation (asterisks). The dotted line represents the choroid-sclera interface. An RPE detachment can be seen at the fovea. (c) Fluorescein angiogram showing window defects and some discharge in the macular area in the early phase (22 s). (d)–(g) Indocyanine green angiogram showing dilated choroidal vessels with focal choroidal hyperpermeability and macular neovascularization (MNV) with polypoidal lesions at the macular area. (d; 14 s, e; 17 s, f; 29 s, g; 10 min 28 s).