Differential Diagnosis of Viral-Induced Anterior Uveitis.

Diagnosis of uveitis is often challenging, but can be easy in typical viral-induced anterior uveitis (VIAU). Associated symptoms and signs are an important source of information. Certain classical clinical features such as keratic precipitates (KPs) distribution, iris atrophy, elevated intraocular pressure (IOP), and unilaterality are commonly used to support the diagnosis of VIAU. However, many etiologies of anterior uveitis may to a certain extent mimic VIAU, especially the ones with unilateral granulomatous KPs and elevated IOP. This review begins with how the clinician can differentiate viral from nonviral anterior uveitis, and subsequently focuses on the key features which may aid in differentiating among the different viruses that cause VIAU.

Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers.

PURPOSE: To evaluate diagnostic methods and clinical signs of CMV anterior uveitis (AU), a rarely described entity in Europe. METHODS: We included patients with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer coefficient (GWc) for CMV. RESULTS: We report 21 patients with unilateral uveitis (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc was the only positive test in 6/9 patients (66,6%). When PCR alone was performed (without GWc) in the first tap, repeated aqueous taps were needed, twice in five cases and thrice in one case. CONCLUSION: Combining PCR and GWc were very helpful to confirm the clinical diagnosis of CMV AU. In case of very high clinical suspicion and negative results, repeated tap seems to be recommended.

Topical Ganciclovir in Cytomegalovirus Anterior Uveitis.

PURPOSE: To study the effects of topical ganciclovir 0.15% gel on cytomegalovirus (CMV) anterior uveitis in a tertiary uveitis referral center in Brussels, Belgium. METHODS: A retrospective study of patients with a clinical diagnosis of CMV anterior uveitis/endotheliitis demonstrated by a positive polymerase chain reaction and/or Goldmann-Witmer coefficient (GWc). RESULTS: We report a series of 15 patients presenting clinical characteristics of CMV anterior uveitis. Patients had a pretreatment follow-up of 13.00 ± 12.78 months and a posttreatment follow-up of 42.64 ± 31.23 months. The 14 non-Asian patients (93.3%) had clinical characteristics of Posner-Schlossman syndrome, and the only Asian patient (6.7%) had keratic precipitates like Fuchs heterochromic iridocyclitis. At presentation, uveitis was unilateral in all patients, visual acuity (VA) was 0.91 ± 0.25, and all patients had an increased intraocular pressure (IOP), with a mean IOP of 41.40 ± 10.35 mmHg. At the end of the follow-up, 5 patients (33.3%) had glaucoma, 2 needed glaucoma surgery (13.3%). The mean final VA was 0.93 ± 0.11; 13 patients (86.5%) reached a final VA of 0.7 to 1. Patients had a significantly lower number of recurrences/year posttreatment (0.76 ± 0.57) than in the pretreatment period (3.76 ± 2.44) (P = 0.001). The mean time to recurrence increased from 4.03 months before treatment to 12.58 months after treatment (P = 0.003). CONCLUSION: Our results suggest that patients treated with 0.15% topical ganciclovir have a decreased frequency of CMV anterior uveitis recurrences, most preserve a relatively good central vision over time. However, glaucoma is a frequent and severe complication.

Clinical Outcome of Hypertensive Uveitis.

Purpose. To review the clinical outcome of patients with hypertensive uveitis. Methods. Retrospective review of uveitis patients with elevated intraocular pressure (IOP) > 25 mmHg and >1-year follow-up. Data are uveitis type, etiology, viral (VU) and nonviral uveitis (NVU), IOP, and medical and/or surgical treatment. Results. In 61 patients, IOP values are first 32.9 mmHg (SD: 9.0), highest 36.6 mmHg (SD: 9.9), 3 months after the first episode 19.54 mmHg (SD: 9.16), and end of follow-up 15.5 mmHg (SD: 6.24). Patients with VU (n = 25) were older (50.6 y/35.7 y, p = 0.014) and had more unilateral disease (100%/72.22% p = 0.004) than those with NVU (n = 36). Thirty patients (49.2%) had an elevated IOP before topical corticosteroid treatment. Patients with viral uveitis might have higher first elevated IOP (36.0/27.5 mmHg, p = 0,008) and maximal IOP (40.28/34.06 mmHg, p = 0.0148) but this was not significant when limited to the measurements before the use of topical corticosteroids (p = 0.260 and 0.160). Glaucoma occurred in 15 patients (24.59%) and was suspected in 11 (18.03%) without difference in viral and nonviral groups (p = 0.774). Conclusion. Patients with VU were older and had more unilateral hypertensive uveitis. Glaucoma frequently complicates hypertensive uveitis. Half of the patients had an elevated IOP before topical corticosteroid treatment.

P2Y2R deficiency attenuates experimental autoimmune uveitis development.

We aimed to study the role of the nucleotide receptor P2Y2R in the development of experimental autoimmune uveitis (EAU). EAU was induced in P2Y2+/+ and P2Y2-/- mice by immunization with IRBP peptide or by adoptive transfer of in vitro restimulated semi-purified IRBP-specific enriched T lymphocytes from spleens and lymph nodes isolated from native C57Bl/6 or P2Y2+/+ and P2Y2-/- immunized mice. Clinical and histological scores were used to grade disease severity. Splenocytes and lymph node cell phenotypes were analyzed using flow cytometry. Semi-purified lymphocytes and MACS-purified CD4+ T lymphocytes from P2Y2+/+ and P2Y2-/- immunized mice were tested for proliferation and cytokine secretion. Our data show that clinical and histological scores were significantly decreased in IRBP-immunized P2Y2-/- mice as in P2Y2-/- mice adoptively transfered with enriched T lymphocytes from C57Bl/6 IRBP-immunized mice. In parallel, naïve C57Bl/6 mice adoptively transferred with T lymphocytes from P2Y2-/- IRBP-immunized mice also showed significantly less disease. No differences in term of spleen and lymph node cell recruitment or phenotype appeared between P2Y2-/- and P2Y2+/+ immunized mice. However, once restimulated in vitro with IRBP, P2Y2-/- T cells proliferate less and secrete less cytokines than the P2Y2+/+ one. We further found that antigen-presenting cells of P2Y2-/- immunized mice were responsible for this proliferation defect. Together our data show that P2Y2-/- mice are less susceptible to mount an autoimmune response against IRBP. Those results are in accordance with the danger model, which makes a link between autoreactive lymphocyte activation, cell migration and the release of danger signals such as extracellular nucleotides.

TNFα suppresses IFNγ-induced MHC class II expression on retinal pigmented epithelial cells cultures.

PURPOSE: One major consequence of retinal pigment epithelium (RPE) cell activation during autoimmune uveitis is the induction of MHC II molecules expression at their surface. IFNγ is regarded as the main cytokine involved in this induction. As TNFα plays a central role in autoimmune uveitis, we investigated its effects on IFNγ-mediated MHC II induction on RPE cells. METHODS: Retinal pigment epithelium cells (ARPE-19) were stimulated with IFNγ, TNFα and the anti-TNFα antibody infliximab. The expression of MHCII and ICAM-1 was analysed by flow cytometry. The activation and expression of IRF-1 and STAT-1, two proteins involved in IFNγ-signalling pathway, were analysed by WB. Class II transactivator (CIITA) expression was monitored by qRT-PCR and immunoprecipitation. RESULTS: TNFα inhibits IFNγ-induced MHC II expression on ARPE cells in a dose-dependent manner. Infliximab completely reverses the inhibitory effect of TNFα. We did not observe an inhibitory effect of TNFα on the expression of ICAM-1 induced by IFNγ. Similarly, IFNγ-induced STAT1 phosphorylation and IRF1 expression were not affected by TNFα. On the contrary, we found that TNFα suppresses IFNγ-induced CIITA mRNA accumulation and protein expression. CONCLUSION: TNFα inhibits IFNγ-induced MHC II expression in RPE cells. This inhibitory effect was reversed by infliximab and was not because of a global inhibition of IFNγ -mediated RPE cell activation but rather to a specific down-regulation of CIITA expression. Those findings are consistent with the role of TNFα in the resolution of inflammation and might help to elucidate the complex development of autoimmune uveitis.

Extracellular nucleotides and interleukin-8 production by ARPE cells: potential role of danger signals in blood-retinal barrier activation.

PURPOSE: RPE cell activation is an important feature of autoimmune uveitis. This investigation focused on whether extracellular nucleotides could contribute to this activation, and the effects of ATPgammaS, UTP, and UDP on the production of IL-8 by RPE cells was studied in relation to their expression of functional P2Y receptors. METHODS: ARPE-19 cells were cultured with ATPgammaS, UTP, UDP, and TNF. IL-8 gene transcription and protein production were measured by semiquantitative RT-PCR and ELISA. Western blot analysis and RT-PCR were used to investigate ERK 1/2 activation and P2Y expression. Changes in intracellular calcium and cAMP concentration were analyzed by spectrofluorometry and radioimmunoassay. RESULTS: Stimulation of ARPE-19 cells with ATPgammaS, UTP, and UDP induced IL-8 gene transcription and protein secretion. TNFalpha induction of IL-8 secretion was also increased by ATPgammaS, UTP, and UDP. Nucleotide induction of IL-8 production was blocked by PD98059, and all nucleotides stimulated ERK 1/2 phosphorylation. P2Y(2) and P2Y(6) mRNAs were detected in ARPE-19 cells. All tested nucleotides induced a pulse of intracellular calcium. CONCLUSIONS: ATPgammaS, UTP, and UDP stimulate both basal and TNFalpha-induced IL-8 secretion in RPE cells through an ERK 1/2-dependent pathway. The results suggest that those effects are mediated by P2Y(2) and P2Y(6) receptors.