Evaluation of activity and severity of uveitis in children based on comprehensive biochemistry analysis

AIM: To investigate the role of proteolytic enzymes and their inhibitors in endogenous uveitis in children and develop new diagnostic criteria. MATERIAL AND METHODS: A total of 76 children (135 eyes) aged 3 to 17 years with uveitis were examined. All children underwent standard ophthalmological examination, posterior segment optical coherence tomography (OCT) was performed if required. Location, course, and activity of uveitis were assessed as per criteria developed by the International Uveitis Study Group. All patients underwent tear and serum biochemistry analysis, aqueous humor was tested if surgical treatment was required. Alpha-2-macroglobulin (α2-MG), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), urokinase-type plasminogen activator (uPA), and plasminogen (PG) levels were determined. Concentrations of α2-MG were measured by an enzymatic method using a specific substrate Nα-benzoyl-DL-arginine 4-nitroanilide (DL-BAPNA). MMP-9, TIMP-1, uPA, and PG levels were determined using an enzyme linked immunosorbent assay (ELISA). A total of 64 children (84.2%) were followed-up. The analysis included 1143 tear, 283 serum, and 79 aqueous humor samples. RESULTS: Active uveitis was found to be associated with activation of proteolytic enzymes and their inhibitors resulting in increased tear uPA levels, as well as increased uPA, MMP-9, and TIMP-1 levels in aqueous humor. Tear uPA level exceeds 80.7 pg/mL in active uveitis, ranges from 46.6 to 80.6 pg/mL in moderate/subactive disease, is less than or equal to 46.5 pg/mL in inactive phase/remission; it is one of the objective criteria to determine uveitis activity. In patients with panuveitis, tear MMP-9, PG, and α2-MG levels were higher compared to the children with anterior and peripheral uveitis. CONCLUSION: New data on the role of the proteolysis system in the pathogenesis of endogenous uveitis in children have been obtained. New criteria for assessing uveitis activity and severity have been established based on proteolytic enzymes and their inhibitors levels in tear fluid. The obtained results can be used to develop targeted therapy.