The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γand IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.

Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer’s patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut–eye axis.

Purpose: TO assess the diagnostic yield of vitreous fluid analysis and the therapeutic effect of pars plana vitrectomy in patients with suspected intraocular inflammation. Methods: During 2004–2008, pars plana vitrectomy was performed in 89 patients (101 eyes) out of 1233 patients with uveitis. Vitreous specimens were analyzed by cytologic and histopathologic examination, microbiologic culture, polymerase chain reaction, antibody determination, and flow cytometry. Vitrectomy was performed in 85 eyes for both diagnostic and therapeutic purposes; the remaining 16 eyes underwent only diagnostic pars plana vitrectomy. Preoperative and postoperative best-corrected Snellen visual acuity was compared. Results: Preoperative diagnoses were infection in 40 patients, malignant masquerade syndrome in 10 patients, and idiopathic uveitis in 39 patients. Vitreous analysis contributed to the determination of diagnosis in 54 patients (61%). Final diagnoses were infection in 42 patients, malignant masquerade syndrome in 6 patients, benign masquerade syndrome in 16 patients, and idiopathic uveitis in 25 patients. Vitreous fluid collected from each eye underwent approximately 2.2 (range 1–6) laboratory tests. Therapeutic reasons for vitrectomy were the treatment of complications of uveitis in 42 eyes and/or intravitreal application of anti-infectious or cytostatic drugs in 49 eyes. Overall, the visual acuity improved in 45% of eyes, remained unchanged in 45% of eyes, and decreased in 10% of eyes in 3 months after surgery. Conclusions: Pars plana vitrectomy with carefully selected testing is a valuable tool for assessment of diagnosis in a large proportion of patients with uveitis. Moreover, the therapeutic effect of vitrectomy can improve the visual outcomes in these patients.

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.

Purpose: To present a possible coincidence of cytomegalovirus retinitis and intraocular lymphoma in a patient with systemic non-Hodgkin’s lymphoma. Case presentation: A 47-year-old woman presented with decreased visual acuity associated with white retinal lesions in both eyes. A history of pneumonia of unknown aetiology closely preceded the deterioration of vision. Five years previously the patient was diagnosed with follicular non-Hodgkin’s lymphoma. She was treated with a chemotherapy regimen comprised of cyclophosphamide, adriamycin, vincristin, and prednisone with later addition of the anti-CD20 antibody rituximab. She experienced a relapse 19 months later with involvement of the retroperitoneal lymph nodes, and commenced treatment with rituximab and ⁹⁰Y-ibritumomab tiuxetan. A second relapse occurred 22 months after radioimmunotherapy and was treated with a combination of fludarabine, cyclophosphamide, and mitoxantrone followed by rituximab. The patient experienced no further relapses until the current presentation (April, 2010). Pars plana vitrectomy with vitreous fluid analysis was performed in the right eye. PCR testing confirmed the presence of cytomegalovirus in the vitreous. Atypical lymphoid elements, highly suspicious of malignancy were also found on cytologic examination. Intravenous foscarnet was administered continually for three weeks, followed by oral valganciclovir given in a dose of 900 mg twice per day. In addition, the rituximab therapy continued at three monthly intervals. Nevertheless, cessation of foscarnet therapy was followed by a recurrence of retinitis on three separate occasions during a 3-month period instigating its reinduction to the treatment regime after each recurrence. Conclusions: Cytomegalovirus retinitis is an opportunistic infection found in AIDS patients as well as in bone marrow and solid organ transplant recipients being treated with systemic immunosuppressive drugs. This case presents a less common incidence of cytomegalovirus retinitis occurring in a patient with non-Hodgkin’s lymphoma. We demonstrated a possible coexistence of cytomegalovirus retinitis and intraocular lymphoma in this particular patient. The final diagnosis was based on clinical manifestations together with the course of uveitis and its response to treatment alongside the results of vitreous fluid analysis. This report highlights the importance of intraocular fluid examination in cases with nonspecific clinical manifestations. Such an examination allows for the detection of simultaneously ongoing ocular diseases of differing aetiologies and enables the prompt initiation of effective treatment.

Background: Acute anterior uveitis (AAU) is a relatively common extra-musculoskeletal manifestation of axial spondyloarthritis (axSpA); however, data on the prevalence of active sacroiliitis in patients with AAU are limited. Methods: 102 patients with AAU and 39 healthy subjects (HS) underwent clinical assessment and sacroiliac joint MRI. Patients with absence of active sacroiliitis were reassessed after two years. International Spondyloarthritis Society (ASAS) classification criteria for axSpA (regardless of patient’s age) and expert opinion for definitive diagnosis of axSpA were applied. Results: Although chronic back pain was equally present in both groups, bone marrow edema (BME) in SIJ and BME highly suggestive of axSpA was found in 52 (51%) and in 33 (32%) patients with AAU compared with 11 (28%) and none in HS, respectively. Out of all AAU patients, 41 (40%) patients fulfilled the ASAS classification criteria for axSpA, and 29 (28%) patients were considered highly suggestive of axSpA based on clinical features. Two out of the 55 sacroiliitis-negative patients developed active sacroiliitis at the two-year follow-up. Conclusions: One-third of patients with AAU had active inflammation on SIJ MRI and clinical diagnosis of axSpA. Therefore, patients with AAU, especially those with chronic back pain, should be referred to a rheumatologist, and the examination should be repeated if a new feature of SpA appears.