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Rodrigo A Brant Fernandes,1 Luci Meire P Silva,1 Diego Torres Dias,1 Rafael Henrique Pereira,2 Rubens Belfort Jr,1,2 Tiago Santos Prata1–31Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, São Paulo, SP, Brazil; 2IPEPO/Vision Institute – SP, São Paulo, SP, Brazil; 3Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USAPurpose: To evaluate the therapeutic non-inferiority between two ophthalmic latanoprost 0.005% solutions (Arulatan®, [ALT] versus the reference drug Xalatan®, [XLT]) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).Patients and methods: This was a 12-week Phase IV, experimental, randomized, parallel-group, double-masked clinical trial. Consecutive patients with POAG or OH from the Glaucoma Service of Instituto Paulista de Estudos e Pesquisas em Oftalmologia (São Paulo, Brazil) were enrolled between July and December 2017. The primary outcome of the study was an analysis of therapeutic non-inferiority between ALT versus XLT at 12 weeks, while secondary outcomes were mean intraocular pressure (IOP) change from baseline at 2, 6 and 12 weeks, mean IOP at 2, 6 and 12 weeks, and topical and systemic side effects. Statistical significance was set at P

The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-β. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4+ Foxp3+ and CD25highFoxp3+ T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-β and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4+ Foxp3+ and CD25highFoxp3+ T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-γ secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-β cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease. [ABSTRACT FROM AUTHOR]

To evaluate the role of IFN-γ (interferon gamma) in IL-12- (interleukin-12)-induced inhibition of the inflammatory response in the eye during endotoxin-induced uveitis (EIU). C57BL/6 wild type mice and IFN-γ-deficient (GKO) mice were injected with 250 μg of Salmonella typhymurium endotoxin as a model for EIU. Animals were then injected intraocularly with 100 ng of rIL-12 or the equivalent volume of Phosphate-buffer saline (PBS). Histopathologic grading of disease was performed 12, 36 and 72 h after endotoxin injection. Chemokine mRNA expression in the eye was evaluated by reverse transcriptase-polymerase chain reaction. Depletion of NK1.1+ cells in vivo was performed using a PK136 antibody. Depletion of IFN-γ was performed using the R4-6A2 antibody. C57BL/6 mice treated with rIL-12 intraocularly were protected from the development of EIU. Neutralization of IFN-γ with a monoclonal antibody abrogated such protection. The IL-12 protective effects were lost in NK1.1-depleted mice. Intraocular IL-12 decreased the expression of keratinocyte-derived chemokines (KC) gene but had no effect on macrophage inflammatory protein (MIP-2) gene. The protective effect of IL-12 during EIU occurs through production of IFN-γ by NK1.1+ cells. IL-12-induced higher levels of IFN-γ are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an intracellular parasite whose life cycle may include the man as an intermediate host. Close to a billion people are infected with this parasite worldwide. Ocular lesions may occur in up to 25% of those individuals infected. The infection may occur intra-uterus, through the placenta when the mother is infected during pregnancy. The parasite may also infect adults after the ingestion of contaminated food products, most notably meats or water. We have shown that although congenital and post-natal (acquired) infection results in similar ocular lesions, the immunological mechanisms behind the development of disease are different. On the other hand, contrary to published data obtained in mice, we were unable to find evidence that the T. gondii express superantigen activity for human lymphocytes. Our findings are important because they suggest that superantigen activity is not important as a pathological mechanism in human disease. Our data also suggest that, whereas the ocular lesion caused by infection after birth is the result of an excessive or dysfunctional immune response, the lesions caused by congenital infection may be due to a lack of an appropriate response to the parasite. [ABSTRACT FROM AUTHOR]

A letter on the case of using Intravitreal triamcinolone acetonide (IVTA) as a supplement in treating ocular toxoplasmosis is presented. Toxoplasmosis lesions are usually treated with anti-Toxoplasma drugs and oral corticosteroids. However the letter reports that in the event of inadvisability of using anti-Toxoplasma drugs, the usage of IVTA injection is suggested as a supplement. Furthur investigations on the use of

A response by F. B. Aggio and colleagues to a letter to the editor about their article "Intravitreal Triamcinolone Acetonide as an Adjunct in the Treatment of Severe Ocular Toxoplasmosis" is presented.