Inflammatory eye disease: Pre-treatment assessment of patients prior to commencing immunosuppressive and biologic therapy: Recommendations from an expert committee.

AIM: To outline recommendations from an expert committee on the assessment and investigation of patients with severe inflammatory eye disease commencing immunosuppressive and/or biologic therapy. METHOD: The approach to assessment is based on the clinical experience of an expert committee and a review of the literature with regard to corticosteroids, immunosuppressive drug and biologic therapy and other adjunct therapy in the management of patients with severe sight-threatening inflammatory eye disease. CONCLUSION: We recommend a careful assessment and consultative approach by ophthalmologists or physicians experienced in the use of immunosuppressive agents for all patients commencing immunosuppressive and/or biologic therapy for sight threatening inflammatory eye disease with the aim of preventing infection, cardiovascular, metabolic and bone disease and reducing iatrogenic side effects.

Anti-inflammatory treatment of uveitis with biologicals: new treatment options that reflect pathogenetic knowledge of the disease.

BACKGROUND: Endogenous uveitis is a sight-threatening disease. In addition to corticosteroids, immunosuppressive agents are commonly used to treat patients with severe course. Immunosuppressive drugs act nonspecifically, rather than providing a specific interaction with the critical pathogenetic pathways of uveitis. Better knowledge of the basic mechanisms underlying uveitis and of the molecules that are important for regulating inflammation has helped to create new and more specific treatment approaches. Biological therapy for inflammatory diseases employs substances that interfere with specific molecules or pathways induced in the body during the inflammatory process. METHODS: This review gives an overview on molecules that play a critical role in the pathogenetic process of uveitis, as has been observed in patients or the respective animal models, and summarizes the current experience with biologicals for the treatment of uveitis refractive to conventional immunosuppressives.

Labrafil--a new adjuvant for peptide-specific oral tolerance in rat experimental autoimmune uveitis.

Application of soluble antigen via the oral route results in systemic antigen-specific tolerance, a therapeutic approach that has already been used for uveitis patients. In the Lewis rat experimental autoimmune uveitis (EAU) can be induced by active immunisation with retinal antigens such as retinal soluble antigen (S-Ag) or interphotoreceptor retinoid-binding protein (IRBP) and peptides thereof. These normally pathogenic antigens can also be used to induce oral tolerance. In order to optimize oral tolerance induction we analysed the effect of Labrafil M 2125 CS, an orally administrable composition for pharmaceutical use, consisting of fatty acid esters and glycerides and capable of forming micro emulsions. Feeding peptide emulsified in Labrafil M 2125 CS/PBS prior to immunisation significantly improved oral tolerance compared to feeding peptide in PBS only. We observed a delayed onset of disease, reduced intraocular inflammation and less retinal destruction. Application of Labrafil M 2125 CS without tolerogen had no effect. Combined feeding of peptide with Labrafil M 2125 CS even allowed 10-fold reduction of the tolerogenic peptide dose. Furthermore, the effect of Labrafil M 2125 CS upon oral tolerance was dose-dependent, a peptide emulsion containing 0.5-2% Labrafil M 2125 CS achieved a maximal enhancement of oral tolerance induction, suggesting that Labrafil M 2125 CS might be a useful adjuvant to enhance therapeutic use of oral tolerance.

The uveitogenic potential of retinal S-antigen in horses.

PURPOSE: To investigate the uveitogenic potential of retinal S-antigen (S-Ag) in horses. METHODS: Horses were immunized subcutaneously with S-Ag or BSA as control antigen, emulsified in complete Freund's adjuvant. Simultaneously, Bordetella pertussis was given intravenously. Antigen specific T- and B-cell responses were analyzed in a 3-day interval. Disease development was judged clinically and histopathologically. Two identical booster immunizations were given every 4 weeks to test induction of recurrences. RESULTS: T- and B-cell responses specific for S-Ag were observed in all immunized horses but were absent in control animals. However, uveitis developed in only one of five animals. Reimmunization with S-Ag did not lead to a uveitic relapse in this horse. All other horses of the S-Ag- and BSA-treated groups neither showed any signs of uveitis, nor had inflammatory infiltrates of the inner eye. CONCLUSIONS: In contrast to interphotoreceptor retinoid-binding protein (IRBP), S-Ag is a weak autoantigen in horses. Even though S-Ag immunization leads to the activation of autoreactive T- and B-cells, infiltration of the inner eye and induction of uveitis are controlled in most horses.

Uveitis in horses induced by interphotoreceptor retinoid-binding protein is similar to the spontaneous disease.

Equine recurrent uveitis (ERU) is an inflammatory eye disease with high similarity to uveitis in man. It is the only spontaneous animal model for uveitis and the most frequent eye disease in horses affecting up to 10% of the population. To further investigate the pathophysiology of ERU we now report the establishment of an inducible uveitis model in horses. An ERU-like disease was elicited in seven out of seven horses by injection of interphotoreceptor retinoid-binding protein (IRBP) in complete Freund's adjuvant. Control horses did not develop uveitis. The disease model is characterized by a highly reproducible disease course and recurrent episodes with an identical time course elicited in all horses by repeated IRBP injections. The histology revealed the formation of lymphoid follicle-like structures in the eyes and an intraocular infiltration dominated by CD3(+) lymphocytes, morphological patterns typical for the spontaneous disease. Antigen-specific T cell proliferation of PBL was monitored prior to clinical uveitis and during disease episodes. An initial T cell response to IRBP-derived peptides was followed by epitope spreading to S-antigen-derived peptides in response to subsequent immunizations. Thus, horse experimental uveitis represents a valuable disease model for comparative studies with the spontaneous disease and the investigation of immunomodulatory therapeutic approaches after onset of the disease.