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      Fuchs' Uveitis: Failure to Associate Vitritis and Disc Hyperfluorescence with the Disease is the Major Factor for Misdiagnosis and Diagnostic Delay

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          Abstract

          Purpose:

          Fuchs' uveitis is often diagnosed with substantial delay at the origin of deleterious consequences such as unnecessary treatment. The aim of the study was to analyse the type and frequency of posterior inflammatory and fluorescein angiographic signs in Fuchs' uveitis in conjunction with the other clinical signs and evaluate their respective importance in the diagnosis of the disease. In particular, diagnostic delay and erroneous diagnoses were investigated.

          Patients and Methods:

          Patients seen in our centers between 1995 and 2008 with the diagnosis of Fuchs' uveitis were analysed. The data collected included age, initial and final visual acuities, clinical findings at presentation, mean diagnostic delay, erroneous diagnoses, laser flare photometry values, fundus and fluorescein angiography manifestations and ocular complications.

          Results:

          One hundred and five patients were included. The mean age at diagnosis was 34 years. Twelve patients (11.4%) had bilateral involvement. The mean diagnostic delay was 3.04 ± 4.30 years. The most frequent clinical signs were vitreous infiltration (97.40%), typical Fuchs' keratic precipitates (94.90%), crystalline lens opacities or cataract (47%), heterochromia (42.60%), ocular hypertension or glaucoma (12.80%). The mean laser flare photometry value at presentation was 9.85 ± 6.28 ph/ms. Thirty-nine patients (37.14%) had undergone fluorescein angiography showing disc hyperfluorescence in 97.7% and peripheral retinal vascular leakage in 13.6%.

          Conclusions:

          Fuchs' uveitis is significantly underdiagnosed likely because vitreous involvement was previously described but not commonly recognized as an association with Fuchs' uveitis in the clinician's mind and therefore has often been given a different diagnostic label. Moreover, the very frequent inflammatory signs on fluorescein angiography such as disc hyperfluorescence and more rarely peripheral retinal vascular leakage, which has not been typically associated with Fuchs' uveitis, appear to represent an additional factor leading to misdiagnosis. Such clinical findings need to be publicised in order to reduce misdiagnosis, and diagnostic delay.

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          Most cited references35

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          Clinical features of cytomegalovirus anterior uveitis in immunocompetent patients.

          To describe the clinical presentation of cytomegalovirus (CMV) anterior uveitis in human immunodeficiency virus (HIV)-negative patients. Retrospective, interventional case series. HIV-negative patients with anterior uveitis associated with elevated intraocular pressure (hypertensive anterior uveitis) seen at the Singapore National Eye Centre had their aqueous analyzed for viral deoxyribonucleic acid by polymerase chain reaction, and their records were reviewed for demographic data, ocular findings, laboratory results, and treatment. Aqueous was obtained from 105 of 106 eligible eyes. Twenty-four eyes demonstrated positive results for CMV (22.8%). Eighteen eyes had Posner-Schlossman syndrome (PSS; 75%) at presentation, five eyesba had Fuchs heterochromic iridocyclitis (FHI; 20.8%), and one eye had a presumed herpetic anterior uveitis. Twelve of the 24 eyes were treated with ganciclovir. Of the 12 who completed treatment, all responded clinically, and their aqueous demonstrated negative results for CMV on repeat testing. However, nine had recurrences within eight months of stopping treatment and required further courses of ganciclovir. The 81 CMV-negative eyes included 30 with PSS, 11 with FHI, 27 with uveitic glaucomas of unknown cause, and 13 with presumed herpetic anterior uveitis. CMV anterior uveitis is not uncommon in our immunocompetent patients and it may present as a recurrent acute or chronic inflammation, resembling PSS, herpetic anterior uveitis, or FHI.
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            Fuchs heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor.

            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). Retrospective case-control study. 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. 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). 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.
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              Rubella virus is associated with fuchs heterochromic iridocyclitis.

              To determine whether rubella virus (RV) is involved in the pathogenesis of Fuchs heterochromic iridocyclitis (FHI). Retrospective patient-controlled study. Intraocular immunoglobulin G production against RV, herpes simplex virus (HSV), varicella zoster virus (VZV), and Toxoplasma gondii was determined in the aqueous humor of 14 patients with FHI, 13 control subjects with herpetic uveitis anterior, and 19 control subjects with ocular toxoplasmosis by calculation of the Goldmann-Witmer coefficient (GWC). All patients and control subjects were seropositive for RV. Intraocular antibody production (GWC >3) against RV was found in 13 of 14 patients (93%) with FHI. Intraocular antibody production against HSV, VZV, or T gondii was not detected. None of the control subjects with herpetic uveitis anterior or with toxoplasma chorioretinitis had a positive GWC for rubella virus (P < .0001, Fisher exact test). Rubella virus, but not HSV, VZV, or T gondii, is associated with FHI.
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                Author and article information

                Journal
                Middle East Afr J Ophthalmol
                MEAJO
                Middle East African Journal of Ophthalmology
                Medknow Publications (India )
                0974-9233
                0975-1599
                Oct-Dec 2009
                : 16
                : 4
                : 239-244
                Affiliations
                [1 ]Inflammatory and Retinal Eye Diseases, Center for Ophthalmic Specialized Care (COS); Lausanne, Switzerland
                [2 ]Memorial A. de Rothschild, Clinique Générale-Beaulieu, Geneva, Lausanne, Switzerland
                [3 ]University of Lausanne, Lausanne, Switzerland
                Author notes
                Corresponding Author: Dr. Carl P. Herbort, Inflammatory and Retinal Eye Diseases, Center for Ophthalmic Specialized Care (COS), 6 Rue de la Grotte, CH-1003 Lausanne, Switzerland. E-mail: carl.herb@ 123456bluewin.ch
                Article
                MEAJO-16-239
                10.4103/0974-9233.58424
                2855664
                20404990
                c8a5a7d3-2a6a-424b-8a10-6bee0fd8c52a
                © Middle East African Journal of Ophthalmology

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Symposium - Uveitis Update

                Ophthalmology & Optometry
                fuchs' uveitis,vitritis,diagnostic delay,laser flare photometry,disc hyperfluorescence,fundus fluorescein angiography

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