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Jayant Iyer, Bijin Au, Suisheng Tang, John Connolly, Rupesh Agrawal, Tun Kuan Yeo, Stephen Teoh; Longitudinal Cytokine Analysis of Aqueous Humor in CMV Retinitis - The CMV Retinitis Intravitreal Ganciclovir Singapore Study (CRIGSS). Invest. Ophthalmol. Vis. Sci. 2013;54(15):2880.
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To perform longitudinal analysis of cytokine, chemokine and growth factor levels in the aqueous humor of patients with cytomegalovirus retinitis (CMVR) through the course of treatment with intravitreal ganciclovir.
Aqueous humor samples were collected from HIV-positive patients with CMVR scheduled to undergo weekly intravitreal ganciclovir therapy as part of the prospective CMV Retinitis Intravitreal Ganciclovir Singapore Study (CRIGSS) over the course of 1 year. Aqueous humor samples were drawn and analyzed for these patients pre-treatment (0 weeks) and at certain points during course of therapy - 4 weeks, 14 weeks and 18 weeks. Full data across all the time points was obtained and analyzed. Aqueous humor was comprehensively analyzed for 41 cytokine and chemokine factors using real-time PCR with the FlexMAP 3D (Luminex®) platform and assessed using the Milliplex Human Cytokine® kit.
Nine patients have been recruited of which 6 patients have completed the study at all 4 time-points. Longitudinal assessment of samples from 6 patients across the 4 time points using repeated measure ANOVA revealed decreasing levels of MCP-1 (p=0.04) and IL-8 (p=0.04) through the course of intravitreal gancivlovir therapy. Further analysis revealed one of the six subjects to have minimal decrease in these cytokine levels suggestive of possible resistance to ongoing treatment.
This data identifies underlying intraocular immunological response through course of treatment in patients with CMVR. Earlier detailed cytokine analysis as part of CRIGSS had already revealed a unique immunologic signature in aqueous of CMVR. Study of aqueous cytokines through the course of treatment has now identified 2 cytokines as potential markers of treatment response. Further longitudinal analysis of CMVR patients would shed more light on underlying immunological mechanisms in treatment response or resistance, and help in prognostication of the disease. This may lead to development of novel and more targeted treatment strategies for CMVR management in the near future.
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