Abstract

PurposeThe aim of this study is to determine the efficacy of quantitative real-time PCR (qPCR) and clinical characteristics to diagnose ocular cytomegalovirus (CMV) infections.MethodsThe technical factors were assessed by the outcomes of the qPCR assay at five institutions in Japan using the WHO International Standard of cytomegalovirus. The clinical factors were assessed by examining the aqueous humor samples of 197 eyes of 197 consecutive patients suspected of CMV using the receiver operating characteristics (ROCs).ResultsAll of the institutions had excellent detection efficacy, although the copy number ranged from 0.82 to 4.66 copies/IU. In the clinical samples, CMV was detected in 51 eyes, and the amount of CMV DNA was significantly higher for CMV retinitis. In corneal diseases, the amount of CMV DNA was significantly associated with frequency of recurrences and IOP elevations. The sensitivity and specificity of qPCR for the diagnosis was 90.0 and 98.7%, respectively. For the corneal and anterior uveitis types of CMV diseases, the area under the curve (AUC) of qPCR was 0.95 and 0.96, followed by frequency of recurrences with AUC of 0.89 and 0.82, and IOP elevations with AUC of 0.78 and 0.76. Unclassified cytomegalovirus detection, which did not meet diagnostic criteria of CMV corneal endotheliitis, anterior uveitis, or retinitis, was 4.6%, and it was significantly associated with corneal diseases and history of corneal transplantation.ConclusionsqPCR with standardization is specific and accurate; however, the inclusion and knowledge of the clinical characteristics improve the diagnostic efficacy.

Highlights

  • Ocular infections caused by cytomegalovirus (CMV) are wellknown to lead to CMV retinitis in immune-compromised patients

  • The results showed that the area under the curve (AUC) for the diagnostic efficacy of CMV quantitative real-time PCR (qPCR) for aqueous samples was 0.98 for ocular CMV infections, and no other single clinical sign matched this high AUC

  • This indicated that qPCR for CMV is the most efficient single diagnostic method to detect ocular CMV infections, and Clinicians generally rely on the clinical signs for their diagnosis

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Summary

Introduction

Ocular infections caused by cytomegalovirus (CMV) are wellknown to lead to CMV retinitis in immune-compromised patients. In immune-competent patients, CMV corneal endotheliitis and CMV uveitis have been diagnosed mainly in elderly individuals. The clinical signs of CMV can be observed in non-HIV patients with retinitis [1]. CMV infections of the anterior segment are relatively rare and often misdiagnosed. CMV corneal endotheliitis can present as bullous keratopathy or keratitis after years of recurrent episodes. CMV uveitis can present as Fuchs heterochromic iridocyclitis or Posner-Schlossman syndrome with recurrences of elevations of the intraocular pressures (IOPs) [2]. For CMV corneal endotheliitis, the hallmark signs of the disease are endothelial cell loss, coin-shaped lesions, IOP elevations, and owl’s eye appearance of the lesions. An earlier study showed that these signs had a highly positive predictive value

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