Association of IL-4 with pachychoroid neovasculopathy.

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-1ß, 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-1ß 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 TNFß 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.

Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration.

Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.

Effectiveness of real-time PCR for diagnosis and prognosis of varicella-zoster virus keratitis.

PURPOSE: To determine the efficacy of real-time PCR for the diagnosis and prognosis of varicella-zoster virus (VZV) keratitis. STUDY DESIGN: Retrospective case series. METHODS: Patients: 545 consecutive patients with keratitis were examined to quantify copy numbers of VZV DNA by real-time PCR. Association of copy numbers of VZV DNA to clinical signs and disease course was assessed by logistic regression analysis and Cox proportional hazard model. RESULTS: Of the 545 eyes, 38 (6.9%) were diagnosed as VZV keratitis. The median copy number of the VZV DNA was 104.19 copies; this number was significantly associated with diagnosis of VZV keratitis with the highest odds ratio of 3390 (for median copy) compared to the clinical signs. The diagnostic accuracy of the VZV DNA copy indicated good diagnostic value of area under the curve (0.92) by receiver operating characteristic analysis, and detection of unrelated VZV DNA from the cornea was very rare (0.2%). When the VZV DNA copy and clinical signs were assessed for association with the disease course of herpes zoster ophthalmicus, the disease duration was significantly prolonged in VZV keratitis cases with higher numbers of VZV DNA copies, iritis, and history of recurrences. The amount of VZV DNA led to a continuous risk of prolonged disease duration until the ocular inflammation subsided (hazard ratio 0.17, 95% CI 0.07-0.42, for median copies). CONCLUSIONS: Higher VZV DNA copy numbers are associated with the refractoriness of VZV keratitis, and its evaluation may be a useful way to clinically diagnose and manage VZV keratitis.