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      Aqueous humor polymerase chain reaction in uveitis – utility and safety

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          Abstract

          Background

          To study the value and safety of aqueous humor polymerase chain reaction (PCR) analysis for Herpes simplex, varicella zoster, cytomegalovirus, Epstein-Barr virus and Toxoplasma gondii in patients with uveitis.

          Methods

          Records of 45 consecutive patients with anterior and posterior uveitis who underwent AC paracentesis with PCR were reviewed. The main outcome measure was frequency of PCR positivity. Secondary outcomes were alteration of treatment, safety of paracentesis, and correlation of keratitic precipitates with PCR positivity,

          Results

          The overall PCR positivity was 48.9 % (22/45). Therapy was changed because of the PCR results in 14/45 patients (37.7 %). One patient experienced a paracentesis related complication (1/45, 2.2 %) without long-term sequelae.

          Conclusion

          Aqueous PCR altered the diagnosis and treatment in over a third of our patients and was relatively safe. Aqueous PCR should be considered for uveitis of atypical clinical appearance, recurrent severe uveitis of uncertain etiology, and therapy refractory cases.

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          Most cited references37

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          Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis.

          Aniki Rothova, Lenneke De Visser, Margje Schuller … (2008)
          To assess the clinical usefulness of aqueous fluid analysis for the diagnosis and treatment of patients suspected of having infectious posterior uveitis (PU). Case-control study. From 2002 through 2005, 152 eyes from 152 patients with active PU (16 of whom were immunosuppressed) underwent diagnostic aqueous testing. As controls, 20 patients with Fuchs' heterochromic uveitis and 20 patients with age-related cataract were included. Aqueous samples were examined by real-time polymerase chain reaction (PCR) and by pathogen-specific analysis of intraocular antibody production (Goldmann-Witmer coefficient [GWC]) for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and the parasite Toxoplasma gondii. Results of aqueous analysis and any adverse effects of aqueous sampling. Correlations between the results of aqueous testing and clinical characteristics as well as the treatment of patients. Of 152 patients, 44 (29%) had positive results for at least one diagnostic assay (37/136 [28%] immunocompetent and 7/16 [44%] immunocompromised patients). None of the controls had positive results using PCR or GWC. A positive result was obtained predominantly in patients with focal chorioretinitis (37/87 [40%]) and in extensive retinitis (7/9 [78%]), whereas in multifocal chorioretinitis, neuroretinitis, and retinal vasculitis only a few samples demonstrated positive results (2/19, 1/29, and 0/10, respectively). Of 37 immunocompetent PU patients with positive results, 28 (76%) cases were caused by T. gondii, whereas viral infections were most common in immunocompromised patients (5/7 [71%]). In immunocompetent and toxoplasmosis PU patients, GWC was the most informative assay (34/37 [92%] and 28/30 [93%], respectively), in contrast to immunosuppressed patients (PCR positive in 5/7 and GWC positive in 4/7). Independent of the immune status of patients, positive PCR results were observed more frequently in viral infections than in toxoplasmosis (P<0.001). As a consequence of aqueous analysis, change of treatment was necessary in 36 patients (24%). None of the patients experienced complications during or after aqueous sampling. Despite the posterior location of inflammation, aqueous analyses with PCR and GWC for HSV, VZV, CMV, and T. gondii revealed an infectious cause in 29% of patients with PU.
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            Acute retinal necrosis: clinical features, early vitrectomy, and outcomes.

            Jost Hillenkamp, Bernhard Nölle, Claudia Bruns … (2009)
            To determine the viral diagnosis and the outcome of eyes with acute retinal necrosis (ARN) treated with intravenous acyclovir and oral prednisolone alone or combined with early vitrectomy and intravitreal acyclovir lavage. Nonrandomized, retrospective, interventional, comparative, consecutive series. A cohort of 27 human immunodeficiency virus-negative patients with ARN comprising 24 unilateral and 3 bilateral cases. Vitreous biopsy for viral diagnosis. Twenty eyes were treated with intravenous acyclovir in combination with oral prednisolone (group A). Ten eyes were treated additionally with early vitrectomy, intravitreal acyclovir lavage, laser demarcation of necrotic retinal areas when feasible-with or without scleral buckling, and gas or silicone oil tamponade (group B). Vitrectomy was performed in all cases of secondary rhegmatogenous retinal detachment (RD). Results of vitreous biopsy, rate of RD, rate of phthisis bulbi, and course of best-corrected visual acuity (BCVA). Varicella zoster virus (VZV) was detected in 26 eyes, followed by herpes simplex virus (5 eyes), and Epstein-Barr virus (2 eyes, in conjunction with VZV). An RD developed in more eyes in group A (18 of 20 eyes) than in group B (4 of 10 eyes; P = 0.007). In 2 of 20 eyes in group A and in 0 of 10 eyes in group B, phthisis bulbi developed without a significant difference between groups A and B. Mean BCVA (logarithm of the minimum angle of resolution) at first visit was 1.09 (standard deviation [SD], 0.83), and mean final BCVA was 1.46 (SD, 0.88) without significant difference between groups A and B. Varicella zoster virus is the leading cause of ARN. Visual prognosis is guarded. Early vitrectomy with intravitreal acyclovir lavage was associated with a lower incidence of secondary RD; however, it did not improve mean final visual acuity.
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              Polymerase chain reaction analysis of aqueous and vitreous specimens in the diagnosis of posterior segment infectious uveitis.

              Darlene Miller, Gary W Harper, Joyce C Schiffman … (2008)
              To assess polymerase chain reaction (PCR) analysis of intraocular fluid as a test for infectious uveitis of the posterior segment in a representative patient population. Retrospective, interventional case series. One hundred and thirty-three patients with possible infectious chorioretinitis underwent PCR testing of aqueous or vitreous in a university setting. Baseline characteristics predictive of test positivity were identified. Positive and negative predictive values were calculated. Four hundred and thirty-three PCR tests of 105 aqueous and 38 vitreous specimens (mean, 3.3 tests per patient) identified 77 of the 95 patients with a final clinical diagnosis of infectious uveitis (81%). Herpes simplex virus, varicella zoster virus, and cytomegalovirus PCR analysis were performed in almost all cases, with fewer tests for toxoplasmosis or Epstein-Barr virus. Clinical features associated with positive PCR results were retinal vascular inflammation (P < .001), optic nerve involvement (P = .008), immunocompromised state (P = .039), and extensive retinitis (P = .002). Cases sampled within one week of presentation were more likely to have positive PCR results than those sampled later (P = .071). The predictive value of positive and negative tests was 98.7% and 67.9%, respectively, in this patient group. Alteration in treatment based on PCR and syphilis serologic results led to resolution in 25 of 26 patients after treatment was changed. PCR testing is a useful adjunct in the diagnosis of infectious causes of posterior uveitis. Cases with vascular or optic nerve inflammation, extensive retinitis, or immunocompromise are more likely to have positive PCR results and may benefit from PCR testing of aqueous humor.
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                Author and article information

                Contributors
                Argyrios Chronopoulos: +41 22 382 83 94 , argyrios.chronopoulos@hcuge.ch
                Daniel Roquelaure: daniel.roquelaure@hcuge.ch
                Georges Souteyrand: georges.souteyrand@hcuge.ch
                Jörg Dieter Seebach: Joerg.Seebach@hcuge.ch
                James Scott Schutz: js485squid@yahoo.com
                Gabriele Thumann: gabriele.thumann@hcuge.ch , gabriele.thumann@unige.ch
                Journal
                Journal ID (nlm-ta): BMC Ophthalmol
                Journal ID (iso-abbrev): BMC Ophthalmol
                Title: BMC Ophthalmology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2415
                Publication date (Electronic): 28 October 2016
                Publication date PMC-release: 28 October 2016
                Publication date Collection: 2016
                Volume: 16
                Electronic Location Identifier: 189
                Affiliations
                [1 ]Department of Ophthalmology, University Hospitals and School of Medicine, Geneva, Switzerland
                [2 ]Division of Immunology and Allergy, University Hospitals and School of Medicine, Geneva, Switzerland
                Article
                Publisher ID: 369
                DOI: 10.1186/s12886-016-0369-z
                PMC ID: 5084402
                PubMed ID: 27793120
                SO-VID: 8dc27c41-c89f-4c90-a2cd-4382df1ac4ca
                Copyright © © The Author(s). 2016
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 30 July 2016
                Date accepted : 20 October 2016
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2016

                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: uveitis,anterior uveitis,posterior uveitis,anterior chamber paracentesis,polymerase chain reaction (pcr)
                Data availability:
                ScienceOpen disciplines: Ophthalmology & Optometry
                Keywords: uveitis, anterior uveitis, posterior uveitis, anterior chamber paracentesis, polymerase chain reaction (pcr)

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