Fuchs heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor.

PURPOSE To characterize the polyspecific intraocular antibody synthesis in aqueous humor of patients with chronic inflammatory diseases of the eye and to detect the causative antigen in Fuchs heterochromic cyclitis (FHC). DESIGN Retrospective case-control study. METHODS Intraocular antibody synthesis is detected in aqueous humor with the Antibody Index [AI] (improved Goldmann-Witmer Index) and quantified as specific antibody fraction, F(s) (intraocular specific antibody concentration in percent of intraocular total immunoglobulin G in aqueous humor). Virus detection is by nested polymerase chain reaction. RESULTS Fifty-two eyes of 52 patients with clinically defined FHC (aged 16-73 years) had an intraocular synthesis of rubella antibodies (AI > or =1.5). The rubella genome was detected in 5 (18%) of 28 aqueous humor samples investigated, or in 5 (56%) of 9 patients aged <40 years. Oligoclonal IgG was synthesized in 34 (87%) of 39 eyes. Unaffected fellow eyes (n = 3) or cerebrospinal fluid (n = 2) were normal. In FHC the median rubella AI = 20.6 (total range 1.5-309) was seven times higher than in multiple sclerosis (MS) patients (n = 15) with uveitis intermedia or periphlebitis retinae. In MS the intraocular rubella antibody synthesis (frequency 73%) is part of a polyspecific immune response (increased measles AI in 80%, varicella zoster virus AI in 47%, herpes simplex virus AI in 23%). The median rubella-F(s) = 2.6% in FHC (range = 0.14%-45.9%) was approximately 40 times higher than in MS, consistent with a virus-driven antibody response in FHC. Noninflammatory controls (50 senile cataracts) had neither an intraocular rubella antibody synthesis (normal AI < or =1.4) nor rubella antigen in aqueous humor. The rubella AI was normal in all patients with an intraocular toxoplasmosis (n = 24), anterior uveitis (n = 27), herpes simplex virus iritis (n = 25), and varicella zoster virus iritis (n = 14). CONCLUSIONS Fuchs heterochromic cyclitis is a rubella virus-driven disease with persistence of the virus preferentially detected in the younger patients. The proposed laboratory supported diagnosis of FHC is based on the increased rubella Antibody Index. The virus etiology gives a rationale for omitting the ineffective corticosteroid therapy of FHC.