Extension study of the safety and efficacy of CLS-TA for treatment of macular oedema associated with non-infectious uveitis (MAGNOLIA).

PURPOSE: To assess the extended efficacy and safety of suprachoroidal triamcinolone acetonide injectable suspension (CLS-TA) among patients with macular oedema (ME) secondary to non-infectious uveitis (NIU). METHODS: Patients with uveitic ME were treated with suprachoroidal CLS-TA at baseline and week 12 of the Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial (PEACHTREE) study. Time to rescue was evaluated over 24 additional weeks for MAGNOLIA. Safety data, visual acuity and retinal central subfield thickness (CST) reduction were also evaluated. Of the 53 eligible patients (46 CLS-TA and 7 control), 33 patients were enrolled (28 CLS-TA and 5 control). RESULTS: Over the entire 48-week period for PEACHTREE and MAGNOLIA, the median time to rescue therapy was 257 days versus 55.5 days for the CLS-TA and sham-control arms, respectively. Of 28 CLS-TA treated patients who participated in MAGNOLIA, 14 (50%) did not require rescue therapy through approximately 9 months after the second treatment. Among CLS-TA patients not requiring rescue, there was a mean gain of 12.1 letters and mean CST reduction of 174.5 µm at week 48. No serious adverse events related to study treatment were observed. CONCLUSION: Approximately 50% of patients did not require additional treatment for up to 9 months following the last CLS-TA administration.

[Clinical features and therapy of uveitis in childhood]. / A gyermekkori uveitis klinikai jellemzoi és terápiája.

Introduction: Uveitis is characterized by inflammation of the middle layer of the eye. Its overall incidence is low. Autoimmune diseases and infections are the most common underlying diseases. Out of the autoimmune diseases, juvenile idiopathic arthritis is associated most frequently with uveitis. The topical ophthalmological treatment may fail in a significant proportion of the patients and immunomodulatory therapy may be required. Aim and method: In a retrospective study, data of 33 children diagnosed and treated with uveitis at the Department of Pediatrics and Ophthalmology, University of Pécs during the last 5 years were collected and analyzed. Results: The mean age of the patients was 9.3 (0.3-17.8) years. Boys and girls were equally affected with an exception of patients with juvenile idiopathic arthritis where female predominance was found. An underlying disease could be identified in 60% of the cases (20/33). Uveitis was associated in 12 patients with juvenile idiopathic arthritis, in 2 patients with Behcet's disease and in a single case with inflammatory bowel disease. Infections have been proven in 5 patients. The autoimmune diseases caused an eye inflammation typically in anterior localization, in contrast to the infections that resulted in posterior uveitis. The majority of the patients required systemic treatment. 3 of them received systemic corticosteroid and 18 patients methotrexate as disease-modifying antirheumatic drug. 13 children with severe disease activity required biological therapy (adalimumab injection). Remission could be achieved in 1.45 (0.75-2.5) months. Conclusion: Pediatric uveitis is of great importance. Early diagnosis, adequate therapy and follow-up require multidisciplinary cooperation. Orv Hetil. 2019; 160(34): 1335-1339.

Dendritic cells mediate the anti-inflammatory action of omega-3 long-chain polyunsaturated fatty acids in experimental autoimmune uveitis.

We previously showed that dietary omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs) suppress inflammation in mice with experimental autoimmune uveitis (EAU). We have now investigated the role of antigen presenting cells (APCs) in this action of ω-3 LCPUFAs. C57BL/6 mice were fed a diet supplemented with ω-3 or ω-6 LCPUFAs for 2 weeks, after which splenocytes were isolated from the mice and cocultured with CD4+ T cells isolated from mice with EAU induced by injection of a human interphotoreceptor retinoid-binding protein peptide together with complete Freund's adjuvant. The proliferation of and production of interferon-γ and interleukin-17 by T cells from EAU mice in vitro were attenuated in the presence of splenocytes from ω-3 LCPUFA-fed mice as compared with those from mice fed ω-6 LCPUFAs. Splenocyte fractionation by magnetic-activated cell sorting revealed that, among APCs, dendritic cells (DCs) were the target of ω-3 LCPUFAs. Adoptive transfer of DCs from mice fed ω-3 LCPUFAs attenuated disease progression in EAU mice as well as the production of pro-inflammatory cytokines by T cells isolated from these latter animals. The proliferation of T cells from control Balb/c mice was also attenuated in the presence of DCs from ω-3 LCPUFA-fed mice as compared with those from ω-6 LCPUFA-fed mice. Furthermore, T cell proliferation in such a mixed lymphocyte reaction was inhibited by prior exposure of DCs from mice fed an ω-6 LCPUFA diet to ω-3 LCPUFAs in vitro. Our results thus suggest that DCs mediate the anti-inflammatory action of dietary ω-3 LCPUFAs in EAU.

Metronidazole Attenuates the Intensity of Inflammation in Experimental Autoimmune Uveitis.

Autoimmune uveitis is a serious sightthreatening disease that in many cases fails to respond to conventional immunosuppressive or biological therapy. Experimental models used in research allow more detailed study of pathogenesis of the autoimmune process and testing new therapeutic strategies. Recent results show that infection can trigger autoimmune diseases, and some commensal microorganisms are essential in causing disease activity. The aim of this work was to assess the effect of broadspectrum antibiotics - combination of metronidazole and ciprofloxacin or metronidazole alone - on the intensity of intraocular inflammation in experimental autoimmune uveitis (EAU). EAU was induced in mouse strain C57BL/6J by interphotoreceptor retinoid- binding protein in complete Freund's adjuvant and pertussis toxin. The grade of uveitis was assessed clinically and histologically in haematoxylin and eosin- stained tissues. Lymphocytes and macrophages were detected in cryosections using the immunoperoxidase method with antibodies. The therapy was commenced one week before EAU induction and continued throughout the experiment. In addition, metronidazole treatment was also started two weeks before EAU induction. Antibiotics significantly reduced the intensity of uveitis compared to the control group (P < 0.05). The effects of combination of ciprofloxacin and metronidazole and of metronidazole alone were similar when the therapy started one week before EAU induction (P < 0.05). Metronidazole commenced two weeks before EAU induction and throughout the experiment suppressed the intensity of EAU with even higher statistical significance (P < 0.0001). It can be assumed that the high protective effect of metronidazole on EAU intensity may be due not only to its antimicrobial effect, but also to its immunomodulatory activity.

Effect of Uveitis on the Development of Keratopathy: A Population-Based Cohort Study.

Purpose: The purpose of this study was to evaluate the effect of uveitis on the development of various keratopathies via the use of the National Health Insurance Research Database (NHIRD) in Taiwan. Methods: Approximately 1 million patients were randomly sampled from the registry of the NHIRD. Patients diagnosed with uveitis by ophthalmologists were enrolled in the study group after exclusion. Each individual in the study group was age and sex matched to four non-uveitis individuals who serve as the control group. In addition to keratopathy, other possible risk factors and medications were included in the multivariate model, and the effects of different subtypes of uveitis for developing keratopathies were also analyzed. Results: A total of 4773 uveitis patients (2662 male and 2111 female) and 19,092 non-uveitis patients (10,648 male and 8444 female) were enrolled. There were 406 events of keratopathy in the study group, and another 764 events occurred in the control group. A higher incidence rate was found in the study group after adjustment (adjusted hazard ratio [aHR]: 1.772), with a greater cumulative probability (P < 0.0001). For the subgroup analysis, anterior uveitis (aHR = 1.765) and panuveitis (aHR = 3.386) increased the risk of developing keratopathies. Moreover, male sex was associated with a higher aHR than female sex for developing keratopathies in the study group. Conclusions: The presence of uveitis significantly elevates the risk for developing keratopathy.

Outcomes of non-infectious Paediatric uveitis in the era of biologic therapy.

BACKGROUND: There is a paucity of data on the ocular outcomes in paediatric non-infectious uveitis since the introduction of the biologic agents. The purpose of this study was to outline the clinical characteristics of children with non-infectious uveitis and determine the visual outcomes and ocular complication rates in the modern era. METHODS: Children with non-infectious uveitis from January 2011 to December 2015 were identified. Data was collected at baseline, 1, 3, 5, and 10 years post diagnosis. The incidence rates of visual impairment, structural ocular complications and surgical intervention were calculated. Using logistic regression the association between various baseline characteristics and later visual impairment was investigated. RESULTS: Of the 166 children, 60.2% (n = 100) had a systemic disease association. 72.9% (n = 121) children received methotrexate, 58 children progressed to a biologic. The incidence rates of visual acuity loss to > 0.3 LogMAR (6/12) and to ≥1.0 LogMAR (6/60) were 0.05/Eye Year (EY) and 0.01/EY, respectively. Visual outcomes in the Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) and Idiopathic Uveitis cohorts were not statistically significant. Of the 293 affected eyes, posterior synechiae was the predominant complication on presentation, while cataract had the highest incidence rate (0.05/EY). On direct comparison, children with JIA-U were statistically significantly more likely to develop glaucoma while children with Idiopathic Uveitis were statistically significantly more likely to develop macular oedema. CONCLUSION: One third of children received a biological therapy, reflecting increasing utilisation and importance of biological agents in the management of inflammatory conditions. Rates of visual impairment and ocular complications are an improvement on previously published data.

Uveítis por bisfosfonatos: ¿un raro efecto secundario? / Uveitis due to bisphosphonates: a rare side effect?

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In vivo multi-modal imaging of experimental autoimmune uveoretinitis in transgenic reporter mice reveals the dynamic nature of inflammatory changes during disease progression.

BACKGROUND: Experimental autoimmune uveoretinitis (EAU) is a widely used experimental animal model of human endogenous posterior uveoretinitis. In the present study, we performed in vivo imaging of the retina in transgenic reporter mice to investigate dynamic changes in exogenous inflammatory cells and endogenous immune cells during the disease process. METHODS: Transgenic mice (C57Bl/6 J Cx 3 cr1 (GFP/+) , C57Bl/6 N CD11c-eYFP, and C57Bl/6 J LysM-eGFP) were used to visualize the dynamic changes of myeloid-derived cells, putative dendritic cells and neutrophils during EAU. Transgenic mice were monitored with multi-modal fundus imaging camera over five time points following disease induction with the retinal auto-antigen, interphotoreceptor retinoid binding protein (IRBP1-20). Disease severity was quantified with both clinical and histopathological grading. RESULTS: In the normal C57Bl/6 J Cx 3 cr1 (GFP/+) mouse Cx3cr1-expressing microglia were evenly distributed in the retina. In C57Bl/6 N CD11c-eYFP mice clusters of CD11c-expressing cells were noted in the retina and in C57Bl/6 J LysM-eGFP mice very low numbers of LysM-expressing neutrophils were observed in the fundus. Following immunization with IRBP1-20, fundus examination revealed accumulations of Cx3cr1-GFP(+) myeloid cells, CD11c-eYFP(+) cells and LysM-eGFP(+) myelomonocytic cells around the optic nerve head and along retinal vessels as early as day 14 post-immunization. CD11c-eYFP(+) cells appear to resolve marginally earlier (day 21 post-immunization) than Cx3cr1-GFP(+) and LysM-eGFP(+) cells. The clinical grading of EAU in transgenic mice correlated closely with histopathological grading. CONCLUSIONS: These results illustrate that in vivo fundus imaging of transgenic reporter mice allows direct visualization of various exogenously and endogenously derived leukocyte types during EAU progression. This approach acts as a valuable adjunct to other methods of studying the clinical course of EAU.

Risk factors for developing glaucoma among patients with uveitis: a nationwide study in Taiwan.

PURPOSE: To investigate the incidence and risk factors for developing ocular hypertension or glaucoma needing treatment among uveitis patients in Taiwan. METHODS: The nationwide database-derived retrospective cohort study was designed using Taiwan's National Health Insurance Research Database. From 1 million representative samples randomly selected from the beneficiaries of the National Health Insurance program, all patients with a diagnosis of uveitis were identified. Only newly onset uveitis patients who were diagnosed after January 1, 2002 and had no prior diagnosis of glaucoma were included in the study, and were followed up until December 31, 2008 or the last day that they were covered by the program. A patient was defined as having glaucoma as soon as both a diagnosis of glaucoma or ocular hypertension as well as a claim for medical or surgical treatment of glaucoma was found. Risk factors for developing glaucoma at the time of, or after the uveitis incidence were evaluated and discussed. RESULTS: Initially, 5757 newly diagnosed uveitis patients were enrolled in the study. Of these patients, 488 (8.5%) were also diagnosed with glaucoma at the time of uveitis incidence. Patients aged 17 to 64 years, of male sex and diagnosed with anterior uveitis were more likely to have glaucoma at the time of the uveitis incidence. Among the remaining 5269 patients, 351 (6.7%) patients developed glaucoma during the follow-up period. Significant risk factors included increasing age, having been diagnosed with anterior uveitis, having more than an average number of ophthalmic claims within the first 3 months, and complications with corneal edema. A stratified analysis showed that having a history of receiving intraocular surgery is also a risk factor for the development of glaucoma among adult patients. CONCLUSIONS: The development of glaucoma in uveitis patients is noteworthy and is associated with several demographic and clinical factors. To minimize the visual impairment caused by uveitis-related glaucoma, clinicians should pay more attention to those uveitis patients who are at high risk for developing glaucoma.

Impact of IL-1 signalling on experimental uveitis and arthritis.

BACKGROUND: Uveitis, or inflammatory eye disease, is a common extra-articular manifestation of many systemic autoinflammatory diseases involving the joints. Anakinra (recombinant interleukin (IL)-1 receptor antagonist (Ra)) is an effective therapy in several arthritic diseases; yet, few studies have investigated the extent to which IL-1 signalling or IL-1Ra influences the onset and/or severity of uveitis. OBJECTIVE: To seek possible links between arthritis and uveitis pathogenesis related to IL-1 signalling. METHODS: The eyes of IL-1Ra-deficient BALB/c mice were monitored histologically and by intravital videomicroscopy to determine if uveitis developed along with the expected spontaneous arthritis in ankles and knees. Expression levels of IL-1R and its negative regulators (IL-1Ra, IL-1RII, IL-1RAcP and single Ig IL-1R-related molecule) in eye and joint tissues were compared. Differences in uveitis induced by intraocular injection of lipopolysaccharide (LPS) in mice lacking IL-1R or IL-1Ra were assessed. RESULTS: Deficiency in IL-1Ra predisposes to spontaneous arthritis, which is exacerbated by previous systemic LPS exposure. The eye, however, does not develop inflammatory disease despite the progressive arthritis or LPS exposure. Organ-specific expression patterns for IL-1Ra and negative regulators of IL-1 activity were observed that appear to predict predisposition to inflammation in each location in IL-1Ra knockout mice. The eye is extremely sensitive to locally administered LPS, and IL-1Ra deficiency markedly exacerbates the resulting uveitis. CONCLUSION: This study demonstrates that IL-1Ra plays an important role in suppressing local responses in eyes injected with LPS and that there is discordance between murine eyes and joints in the extent to which IL-1Ra protects against spontaneous inflammation.

Therapeutic targeting of STAT3 (signal transducers and activators of transcription 3) pathway inhibits experimental autoimmune uveitis.

Mice with targeted deletion of STAT3 in CD4(+) T-cells do not develop experimental autoimmune uveitis (EAU) or experimental autoimmune encephalomyelitis (EAE), in part, because they cannot generate pathogenic Th17 cells. In this study, we have used ORLL-NIH001, a small synthetic compound that inhibits transcriptional activity of STAT3, to ameliorate EAU, an animal model of human posterior uveitis. We show that by attenuating inflammatory properties of uveitogenic lymphocytes, ORLL-NIH001 inhibited the recruitment of inflammatory cells into the retina during EAU and prevented the massive destruction of the neuroretina caused by pro-inflammatory cytokines produced by the autoreactive lymphocytes. Decrease in disease severity observed in ORLL-NIH001-treated mice, correlated with the down-regulation of α4ß1 and α4ß7 integrin activation and marked reduction of CCR6 and CXCR3 expression, providing a mechanism by which ORLL-NIH001 mitigated EAU. Furthermore, we show that ORLL-NIH001 inhibited the expansion of human Th17 cells, underscoring its potential as a drug for the treatment of human uveitis. Two synthetic molecules that target the Th17 lineage transcription factors, RORγt and RORα, have recently been suggested as potential drugs for inhibiting Th17 development and treating CNS inflammatory diseases. However, inhibiting STAT3 pathways completely blocks Th17 development, as well as, prevents trafficking of inflammatory cells into CNS tissues, making STAT3 a more attractive therapeutic target. Thus, use of ORLL-NIH001 to target the STAT3 transcription factor, thereby antagonizing Th17 expansion and expression of proteins that mediate T cell chemotaxis, provides an attractive new therapeutic approach for treatment of posterior uveitis and other CNS autoimmune diseases mediated by Th17 cells.

Primera manifestación oftalmológica de una sepsis por Klebsiella. Importancia de la sospecha diagnóstica precoz / Endogenous endophthalmitis as a first clinical manifestation of Klebsiella sepsis. The importance of an early diagnosis

Caso clínico: Paciente diabético que desarrolla una uveítis unilateral con un foco de coriorretinitis en el ojo derecho asociada a fiebre y disminución de la visión. Sospechándose una endoftalmitis endógena se realizaron pruebas complementarias encontrándose abscesos hepáticos con biopsia positiva para Klebsiella. La afectación ocular se fue resolviendo gracias a antibioticoterapia intravenosa y al drenaje percutáneo de los abscesos. Conclusión: La endoftalmitis endógena por Klebsiella es un hallazgo poco frecuente con consecuencias graves. Un diagnóstico y un tratamiento antibioticoterápico tempranos pueden mejorar el cuadro aunque la visión resultante suele ser pobre(AU)

Case report: A diabetic patient who developed a unilateral uveitis with a chorioretinitis patch in his right eye associated with decreased visual acuity and fever. Endogenous endophthalmitis was suspected and complementary tests were performed, finding hepatic abscesses with Klebsiella isolation in the biopsy. The ocular disorder slowly improved with intravenous therapy and guided percutaneous liver drainage. Conclusion: Endogenous Klebsiella endophthalmitis is an uncommon condition with severe complications. An early diagnosis and aggressive antibiotic therapy can ameliorate the final course but the visual outcome still remains poor(AU)

Regulatory effects of IFN-ß on the development of experimental autoimmune uveoretinitis in B10RIII mice.

BACKGROUND: Experimental autoimmune uveoretinitis (EAU) serves as a model for human intraocular inflammation. IFN-ß has been used in the treatment of certain autoimmune diseases. Earlier studies showed that it ameliorated EAU; however, the mechanisms involved in this inhibition are still largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: B10RIII mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 161-180 in Complete Freund's adjuvant. Splenocytes from different time points after immunization were used to evaluate the expression of IFN-ß. An increased expression of IFN-ß was observed during EAU and its highest expression was observed on day 16, 3 days after the peak of intraocular inflammation. Splenocytes and draining lymph node cells from mice immunized with IRBP(161-180) on day 13 and control mice were activated with anti-CD3/anti-CD28 antibodies or IRBP(161-180) to evaluate the production of IFN-γ and IL-17. The results showed that IFN-γ and IL-17 were significantly higher in immunized mice as compared to the control mice when exposed to anti-CD3/anti-CD28 antibodies. However, the production of IFN-γ and IL-17 was detected only in immunized mice, but not in the control mice when stimulated with IRBP(161-180). Multiple subcutaneous injections of IFN-ß significantly inhibited EAU activity in association with a down-regulated expression of IFN-γ, IL-17 and an enhanced IL-10 production. In an in vitro system using cells from mice, IFN-ß suppressed IFN-γ production by CD4(+)CD62L(-) T cells, IL-17 production by CD4(+)CD62L(+/-) T cells and proliferation of CD4(+)CD62L(+/-) T cells. IFN-ß inhibited the secretion of IL-6, but promoted the secretion of IL-10 by monocytes. IFN-ß-treated monocytes inhibited IL-17 secretion by CD4(+)CD62L(+/-) T cells, but did not influence IFN-γ expression and T cell proliferation. CONCLUSIONS/SIGNIFICANCE: IFN-ß may exert its inhibitory effect on EAU by inhibiting Th1, Th17 cells and modulating relevant cytokines. IFN-ß may provide a potential treatment for diseases mediated by Th1 and Th17 cells.

Risk factors for the development of macular edema in noninfectious uveitis.

PURPOSE: Macular edema (ME) is a vision-limiting complication of uveitis. The aim of the present study was to identify risk factors for the development of ME. METHODS: This was an observational, cross-sectional study including 350 patients with noninfectious uveitis. Data were acquired by using a questionnaire. Associations with ME were analyzed for age,alcohol consumption, coffee consumption, cardiovascular risk factors, and level of education. RESULTS: On univariate analysis, patients with ME were older (p<0.001, odds ratio [OR] 1.03) and had a longer history of uveitis (p=0.006, OR 1.03). Patients with university certificate or high school diploma had a significantly reduced risk (OR 0.25, p<0.001) to develop ME compared to patients with less education. For smoking, the number of pack-years was significantly but weakly associated with the presence of ME (p=0.02, OR 1.02). Smokers with a smoking history of more than 20 pack-years had a higher risk for ME (OR = 2.46, confidence interval 1.2-5.2). Daily coffee consumption predisposed to ME (p=0.02, OR 2.1). Arterial hypertension, body mass index, alcohol consumptions, and hypercholesterinemia were not associated with ME. Multivariate analysis confirmed age, coffee consumption,and low education to be risk factors for ME, whereas smoking was lost on multivariate analysis. CONCLUSIONS: Age, low level of education, daily coffee consumption, and possibly smoking are risk factors for ME in patients with noninfectious uveitis.

Association of systemic steroids and mycophenolate mofetil as rescue therapy for uveitic choroidal neovascularization unresponsive to the traditional immunosuppressants: interventional case series.

To study the efficacy of systemic steroids (SS) associated with mycophenolate mofetil (MMF) for the control of juxta/sub-foveal uveitic choroidal neovascularization (CNV) unresponsive to the traditional immunosuppressive agents. Patients with juxta/sub-foveal uveitic CNV unresponsive to the traditional immunosuppressive drugs were treated with SS and MMF. The study was designed as a prospective, consecutive, open-label, interventional case series. Visual gain and loss were defined as improving or worsening of two or more lines of best-corrected visual acuity (BCVA), respectively. CNV size outcome was dichotomized as "increased" or "stable/reduced", if increased >200 µm(2), or reduced ≥ 200 µm(2) or not modified by 200 µm(2), respectively. Nine cases (12 eyes) have been considered; ages ranged from 27 to 56 years. The mean follow-up time was 18.2 ± 2.9 months (min: 14 months, max: 23 months). At base-line, the mean BCVA was 0.3 ± 0.17, improving up to 0.57 ± 0.25 and to 0.63 ± 0.22 (P < 0.001, paired t-test) at the 6 and 12-month follow-ups, respectively. At the last follow-up, all the patients had stable/improved BCVA (P < 0.0001, Fisher's exact test) and stable/reduced lesion size (P < 0.0001, Fisher's exact test). None of the patients complained of any severe adverse event during the treatment. The combination of SS and MMF seems to be a promising strategy in order to control uveitic CNVs unresponsive to the traditional immunosuppressive agents. Further studies are needed to validate the data of this case series.

Upregulated IL-21 and IL-21 receptor expression is involved in experimental autoimmune uveitis (EAU).

PURPOSE: Interleukin (IL)-21 has recently been shown to play a vital role in the development of many autoimmune diseases. Our study is designed to investigate the alteration and possible function of IL-21 in the development of an experimental autoimmune uveitis (EAU) model. METHODS: EAU was induced in B10.RIII mice by subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) 161-180 emulsified with complete Freund's adjuvant (CFA) and evaluated by clinical and histopathologic observation. IL-21 and IL-21R mRNA expressions in cells of draining lymph node (DLN) and spleen in EAU and control mice were determined by reverse transcription-PCR. The frequencies of interleukin-21 receptor positive cells were also examined using flow cytometry. IL-17 levels in the supernatant of the cell culture upon IL-21 stimulation were assayed by enzyme-linked immunosorbent assay. RESULTS: Results showed that EAU was successfully induced by IRBP161-180. Expression of IL-21 mRNA was significantly increased in cells of DLN and spleen in EAU compared with recovery phase mice and normal controls. IL-21R was also found upregulated in DLN and spleen cells of EAU mice by reverse transcription-PCR and flow cytometry. Cells in EAU cultured with IL-21 combined with transforming growth factor-beta induced increased production of IL-17. CONCLUSION: The findings revealed that increased IL-21 and IL-21R expression may be involved in the development of EAU, possibly by promoting IL-17 secretion.

A sulfated disaccharide derived from chondroitin sulfate proteoglycan protects against inflammation-associated neurodegeneration.

Chondroitin sulfate proteoglycan (CSPG), a matrix protein that occurs naturally in the central nervous system (CNS), is considered to be a major inhibitor of axonal regeneration and is known to participate in activation of the inflammatory response. The degradation of CSPG by a specific enzyme, chondroitinase ABC, promotes repair. We postulated that a disaccharidic degradation product of this glycoprotein (CSPG-DS), generated following such degradation, participates in the modulation of the inflammatory responses and can, therefore, promote recovery in immune-induced neuropathologies of the CNS, such as experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune uveitis (EAU). In these pathologies, the dramatic increase in T cells infiltrating the CNS is far in excess of the numbers needed for regular maintenance. Here, we show that CSPG-DS markedly alleviated the clinical symptoms of EAE and protected against the neuronal loss in EAU. The last effect was associated with a reduction in the numbers of infiltrating T cells and marked microglia activation. This is further supported by our in vitro results indicating that CSPG-DS attenuated T cell motility and decreased secretion of the cytokines interferon-gamma and tumor necrosis factor-alpha. Mechanistically, these effects are associated with an increase in SOCS-3 levels and a decrease in NF-kappaB. Our results point to a potential therapeutic modality, in which a compound derived from an endogenous CNS-resident molecule, known for its destructive role in CNS recovery, might be helpful in overcoming inflammation-induced neurodegenerative conditions.

Vitamin E in the treatment of uveitis-associated macular edema.

PURPOSE: To investigate whether high-dose alpha-tocopherol (vitamin E) could reduce vision loss and retinal thickening associated with uveitis-associated cystoid macular edema. DESIGN: A double-masked, randomized study. METHODS: Uveitis patients with macular edema seen at the NIH were randomized and received either 1600 IU/day of vitamin E or placebo for 4 months. Visual acuity and retinal thickening were collected for the efficacy and the safety of the high dose of vitamin E. RESULTS: Changes in visual acuity and retinal thickening. CONCLUSIONS: Four-month oral supplementation with 1600 IU/d of vitamin E had no apparent effect on uveitis-associated macular edema or visual acuity in this small study.

Syphilitic uveitis in patients infected with human immunodeficiency virus.

BACKGROUND: This work investigates the incidence and clinical features of syphilitic uveitis in patients infected with human immunodeficiency virus (HIV). MATERIAL AND METHODS: We retrospectively reviewed syphilitic uveitis in patients coinfected with HIV that presented at a referral center between July 2001 and November 2003. RESULTS: Twelve patients (20 eyes) were included. The ocular manifestations of syphilis led to the discovery of HIV-1 seropositivity in three patients. All patients were male and homosexual. One patient has been previously treated for syphilis with benzathine penicillin G. One patient presented with anterior uveitis and 11 patients had panuveitis or posterior uveitis. Necrotizing retinitis was noted in seven eyes (35%), posterior placoid chorioretinitis in six eyes (30%) and optic nerve involvement in five eyes (25%). Of nine patients with available cerebrospinal fluid (CSF) studies, seven (77.8%) had CSF abnormalities. Eleven patients were treated with intravenous penicillin G and one with intravenous ceftriaxone sodium. One patient required a second course of antibiotics to control uveitis. Ocular inflammation decreased and visual acuity improved in all nine patients for whom follow-up was available after treatment. CONCLUSION: Manifestations of syphilitic uveitis in HIV-infected patients are multiple, with high frequencies of posterior uveitis, posterior placoid chorioretinitis, necrotizing retinitis and optic nerve involvement. Syphilitic uveitis in HIV-infected patients seems to have a more severe course and may relapse despite high-dose intravenous penicillin therapy.