Japanese Journal of Ophthalmology

, Volume 62, Issue 4, pp 425–431 | Cite as

Effectiveness of real-time PCR for diagnosis and prognosis of varicella-zoster virus keratitis

  • Kodai Inata
  • Dai Miyazaki
  • Ryu Uotani
  • Daisuke Shimizu
  • Atsuko Miyake
  • Yumiko Shimizu
  • Yoshitsugu Inoue
Clinical Investigation



To determine the efficacy of real-time PCR for the diagnosis and prognosis of varicella-zoster virus (VZV) keratitis.

Study design

Retrospective case series.


Patients: 545 consecutive patients with keratitis were examined to quantify copy numbers of VZV DNA by real-time PCR. Association of copy numbers of VZV DNA to clinical signs and disease course was assessed by logistic regression analysis and Cox proportional hazard model.


Of the 545 eyes, 38 (6.9%) were diagnosed as VZV keratitis. The median copy number of the VZV DNA was 104.19 copies; this number was significantly associated with diagnosis of VZV keratitis with the highest odds ratio of 3390 (for median copy) compared to the clinical signs. The diagnostic accuracy of the VZV DNA copy indicated good diagnostic value of area under the curve (0.92) by receiver operating characteristic analysis, and detection of unrelated VZV DNA from the cornea was very rare (0.2%). When the VZV DNA copy and clinical signs were assessed for association with the disease course of herpes zoster ophthalmicus, the disease duration was significantly prolonged in VZV keratitis cases with higher numbers of VZV DNA copies, iritis, and history of recurrences. The amount of VZV DNA led to a continuous risk of prolonged disease duration until the ocular inflammation subsided (hazard ratio 0.17, 95% CI 0.07–0.42, for median copies).


Higher VZV DNA copy numbers are associated with the refractoriness of VZV keratitis, and its evaluation may be a useful way to clinically diagnose and manage VZV keratitis.


Varicella-zoster virus keratitis Real-time PCR Herpes zoster ophthalmicus 



Yoshitsugu Inoue: This work was supported by Grant-in-Aid 25462755 and 17K11481 for Scientific Research from the Japanese Ministry of Education, Science, and Culture.

Conflicts of interest

K. Inata, None; D. Miyazaki, None; R. Uotani, None; D. Shimizu, None; A. Miyake, None; Y. Shimizu, None; Y. Inoue, None.

Supplementary material

10384_2018_604_MOESM1_ESM.pdf (68 kb)
Supplementary material 1 (PDF 67 kb)


  1. 1.
    Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc. 2007;82:1341–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Tran KD, Falcone MM, Choi DS, Goldhardt R, Karp CL, Davis JL, et al. Epidemiology of herpes zoster ophthalmicus: recurrence and chronicity. Ophthalmology. 2016;123:1469–75.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Liesegang TJ. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115:S3–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Kang JH, Ho JD, Chen YH, Lin HC. Increased risk of stroke after a herpes zoster attack: a population-based follow-up study. Stroke. 2009;40:3443–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Lin HC, Chien CW, Ho JD. Herpes zoster ophthalmicus and the risk of stroke: a population-based follow-up study. Neurology. 2010;74:792–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Bouhassira D, Chassany O, Gaillat J, Hanslik T, Launay O, Mann C, et al. Patient perspective on herpes zoster and its complications: an observational prospective study in patients aged over 50 years in general practice. Pain. 2012;153:342–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Kaufman SC. Anterior segment complications of herpes zoster ophthalmicus. Ophthalmology. 2008;115:S24–32.CrossRefPubMedGoogle Scholar
  8. 8.
    Cohen EJ, Kessler J. Persistent dilemmas in zoster eye disease. Br J Ophthalmol. 2016;100:56–61.CrossRefPubMedGoogle Scholar
  9. 9.
    Zaal MJ, Volker-Dieben HJ, Wienesen M, D’Amaro J, Kijlstra A. Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus. Am J Ophthalmol. 2001;131:25–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Kakimaru-Hasegawa A, Kuo CH, Komatsu N, Komatsu K, Miyazaki D, Inoue Y. Clinical application of real-time polymerase chain reaction for diagnosis of herpetic diseases of the anterior segment of the eye. Jpn J Ophthalmol. 2008;52:24–31.CrossRefPubMedGoogle Scholar
  11. 11.
    Kandori M, Miyazaki D, Yakura K, Komatsu N, Touge C, Ishikura R, et al. Relationship between the number of cytomegalovirus in anterior chamber and severity of anterior segment inflammation. Jpn J Ophthalmol. 2013;57:497–502.CrossRefPubMedGoogle Scholar
  12. 12.
    Ikeda Y, Miyazaki D, Yakura K, Kawaguchi A, Ishikura R, Inoue Y, et al. Assessment of real-time polymerase chain reaction detection of Acanthamoeba and prognosis determinants of Acanthamoeba keratitis. Ophthalmology. 2012;119:1111–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Koizumi N, Miyazaki D, Inoue T, Ohtani F, Kandori-Inoue M, Inatomi T, et al. The effect of topical application of 0.15% ganciclovir gel on cytomegalovirus corneal endotheliitis. Br J Ophthalmol. 2017;101:114–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Weidmann M, Meyer-Konig U, Hufert FT. Rapid detection of herpes simplex virus and varicella-zoster virus infections by real-time PCR. J Clin Microbiol. 2003;41:1565–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Miyazaki D, Uotani R, Inoue M, Haruki T, Shimizu Y, Yakura K, et al. Corneal endothelial cells activate innate and acquired arm of anti-viral responses after cytomegalovirus infection. Exp Eye Res. 2017;161:143–52.CrossRefPubMedGoogle Scholar
  16. 16.
    Sy A, McLeod SD, Cohen EJ, Margolis TP, Mannis MJ, Lietman TM, et al. Practice patterns and opinions in the management of recurrent or chronic herpes zoster ophthalmicus. Cornea. 2012;31:786–90.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Cohrs RJ, Mehta SK, Schmid DS, Gilden DH, Pierson DL. Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts. J Med Virol. 2008;80:1116–22.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wilson A, Sharp M, Koropchak CM, Ting SF, Arvin AM. Subclinical varicella-zoster virus viremia, herpes zoster, and T lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation. J Infect Dis. 1992;165:119–26.CrossRefPubMedGoogle Scholar
  19. 19.
  20. 20.
    Kaufman HE, Azcuy AM, Varnell ED, Sloop GD, Thompson HW, Hill JM. HSV-1 DNA in tears and saliva of normal adults. Invest Ophthalmol Vis Sci. 2005;46:241–7.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Miserocchi E, Fogliato G, Bianchi I, Bandello F, Modorati G. Clinical features of ocular herpetic infection in an italian referral center. Cornea. 2014;33:565–70.CrossRefPubMedGoogle Scholar
  22. 22.
    Donahue JG, Choo PW, Manson JE, Platt R. The incidence of herpes zoster. Arch Intern Med. 1995;155:1605–9.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Ophthalmological Society 2018

Authors and Affiliations

  • Kodai Inata
    • 1
  • Dai Miyazaki
    • 1
  • Ryu Uotani
    • 1
  • Daisuke Shimizu
    • 1
  • Atsuko Miyake
    • 1
  • Yumiko Shimizu
    • 1
  • Yoshitsugu Inoue
    • 1
  1. 1.Division of Ophthalmology and Visual Science, Faculty of MedicineTottori UniversityYonago TottoriJapan

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