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. 2018 Dec;256(12):2413-2420.
doi: 10.1007/s00417-018-4111-9. Epub 2018 Aug 27.

Diagnostic efficacy of real-time PCR for ocular cytomegalovirus infections

Dai Miyazaki  1 , Daisuke Shimizu  2 , Yumiko Shimizu  2 , Yoshitsugu Inoue  2 , Tomoyuki Inoue  3 , Shiro Higaki  4 , Mayumi Ueta  5 , Sunao Sugita  6 ; Real-time PCR for ocular cytomegalovirus infection study group
Collaborators, Affiliations

Diagnostic efficacy of real-time PCR for ocular cytomegalovirus infections

Dai Miyazaki et al. Graefes Arch Clin Exp Ophthalmol. 2018 Dec.

Abstract

Purpose: The aim of this study is to determine the efficacy of quantitative real-time PCR (qPCR) and clinical characteristics to diagnose ocular cytomegalovirus (CMV) infections.

Methods: The 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).

Results: All 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.

Conclusions: qPCR with standardization is specific and accurate; however, the inclusion and knowledge of the clinical characteristics improve the diagnostic efficacy.

Keywords: Anterior uveitis; Corneal endotheliitis; Cytomegalovirus; Real-time PCR; Retinitis.

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Conflict of interest statement

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Figures

Fig. 1
Fig. 1
Disease type-dependent cytomegalovirus DNA amounts at the first presentation. CMV retinitis showed significantly higher cytomegalovirus DNA than other types of CMV infections. CMV DNA amount of shedding was significantly lower than those of ocular CMV infections. *P = 0.01; **P = 0.005; ***P = 0.002; ****P = 0.001; *****P = 0.000
Fig. 2
Fig. 2
Receiver operating characteristics regression analysis of cytomegalovirus real-time PCR of aqueous humor and clinical signs for corneal disease type and uveitis type of disease. Cytomegalovirus real-time PCR showed excellent area under the curve (AUC) of 0.98. a For the clinical signs of corneal disease type, the number of recurrences and IOP elevations had good AUCs of 0.89 and 0.78, respectively. b For the anterior uveitis type of disease, the number of recurrences had a good AUC of 0.82, followed by IOP elevation (AUC 0.76)
See this image and copyright information in PMC

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