Atypical herpes simplex keratitis: frequency, clinical presentations and treatment results

  • Elif ErdemEmail author
  • İbrahim İnan Harbiyeli
  • Gökhan Öztürk
  • Oğuzhan Oruz
  • Arbil Açıkalın
  • Meltem Yağmur
  • Reha Ersöz
  • Fügen Yarkın
Original Paper



To determine herpes simplex virus (HSV) DNA positivity in corneal scraping samples obtained from patients with microbial keratitis whose findings were not specific for HSV keratitis and to evaluate these particular cases with respect to clinical features and antiviral treatment results.


Records of patients with microbial keratitis treated in a tertiary eye care hospital within the 3-year period were evaluated retrospectively. Real-time polymerase chain reaction (PCR) was used to identify HSV DNA. Smear slides were evaluated by light microscopy. Patients with typical presentations and histories of HSV keratitis were excluded.


Two hundred and seventy-six eyes of 276 patients were included in the study. HSV-1 DNA was detected in 25 eyes (9%). In these 25 eyes, the initial diagnosis was fungal or bacterial keratitis. The mean symptom duration was 20 ± 14 days (2–60 days). The risk factors were ocular surgery (20%), blepharitis (16%), trauma (8%) and contact lens wear (4%); however, the majority of patients did not have any specific cause for keratitis (52%). Clinical features were variable and not typical for any particular etiology. Culture and microscopic examinations revealed bacteria and/or fungi in 6 patients in addition to herpes infection. Antiviral treatment was successful in 72% of patients.


Herpetic corneal infections can present without typical dendritic or geographic ulcers and may be masked by other infections. Real-time PCR is a useful method for rapid and definitive diagnosis. HSV infection should be considered for microbial keratitis without specific risk factors, with negative culture results and poor response to antimicrobial agents.


Microbial keratitis Herpes simplex virus Polymerase chain reaction 



This study was funded by government.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest for this study.

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10792_2019_1226_MOESM1_ESM.docx (145 kb)
Management algorithm for atypical herpetic keratitis (DOCX 144 kb)


  1. 1.
    Bradley H, Markowitz LE, Gibson T et al (2014) Seroprevalence of herpes simplex virus types 1 and 2: United States, 1999–2010. J Infect Dis 209:325–333CrossRefGoogle Scholar
  2. 2.
    Whitley RJ, Roizman B (2001) Herpes simplex virus infections. Lancet 357:1513–1518CrossRefGoogle Scholar
  3. 3.
    Tsatsos M, MacGregor C, Athanasiadis I et al (2016) Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents. Clin Exp Ophthalmol 44:824–837CrossRefGoogle Scholar
  4. 4.
    Beyer CF, Arens MQ, Hill JM et al (1989) Penetrating keratoplasty in rabbits induces latent HSV-1 reactivation when corticosteroids are used. Curr Eye Res 8:1323–1329CrossRefGoogle Scholar
  5. 5.
    Hudu SA, Alshrari AS, Syahida A et al (2016) Cell culture, technology: enhancing the culture of diagnosing human diseases. J Clin Diagn Res 10:1–5CrossRefGoogle Scholar
  6. 6.
    Hwang KA, Ahn JH, Nam JH (2018) Diagnosis of viral infection using real-time polymerase chain reaction. J Bacteriol Virol 48:1–13CrossRefGoogle Scholar
  7. 7.
    Azher TN, Yin XT, Tajfirouz D et al (2017) Herpes simplex keratitis: challenges in diagnosis and clinical management. Clin Ophthalmol 11:185–191CrossRefGoogle Scholar
  8. 8.
    Subhan S, Jose RJ, Duggirala A et al (2004) Diagnosis of herpes simplex virus-1 keratitis: comparison of Giemsa stain, immunofluorescence assay and polymerase chain reaction. Curr Eye Res 29:209–213CrossRefGoogle Scholar
  9. 9.
    Farhatullah S, Kaza S, Athmanathan S, Garg P et al (2004) Diagnosis of herpes simplex virus-1 keratitis using Giemsa stain, immunofluorescence assay, and polymerase chain reaction assay on corneal scrapings. Br J Ophthalmol 88:142–144CrossRefGoogle Scholar
  10. 10.
    Barrado L, Suarez MJ, Pérez-Blázquez E et al (2014) Could polymerase chain reaction tests on conjunctival swabs be useful to diagnose herpetic keratitis? Enferm Infecc Microbiol Clin 32:28–30CrossRefGoogle Scholar
  11. 11.
    El-Aal AM, El Sayed M, Mohammed E et al (2006) Evaluation of herpes simplex detection in corneal scrapings by three molecular methods. Curr Microbiol 52:379–382CrossRefGoogle Scholar
  12. 12.
    Taravati P, Lam D, Van Gelder RN (2013) Role of molecular diagnostics in ocular microbiology. Curr Ophthalmol Rep 1:1–13CrossRefGoogle Scholar
  13. 13.
    Satpathy G, Behera HS, Sharma A et al (2018) A 20-year experience of ocular herpes virus detection using immunofluorescence and polymerase chain reaction. Clin Exp Optom 101:648–651CrossRefGoogle Scholar
  14. 14.
    Mackay M (2004) Real-time PCR in the microbiology laboratory. Clin Microbiol Infect 10:190–212CrossRefGoogle Scholar
  15. 15.
    Kalezic T, Mazen M, Kuklinski E et al (2018) Herpetic eye disease study: lesson learned. Curr Opin Ophthalmol 29:340–346CrossRefGoogle Scholar
  16. 16.
    Koizumi N, Nishida K, Adachi W et al (1999) Detection of herpes simplex virus DNA in atypical epithelial keratitis using polymerase chain reaction. Br J Ophthalmol 83:957–960CrossRefGoogle Scholar
  17. 17.
    Tei M, Nishida K, Kinoshita S (1996) Polymerase chain reaction of herpes simplex virus in tear fluid from atypical herpetic epithelial keratitis after penetrating keratoplasty. Am J Ophthalmol 122:732–735CrossRefGoogle Scholar
  18. 18.
    Garweg JG, Russ CE, Shellhorn M et al (2003) HSV-1 antigens and DNA in the corneal explant buttons of patients with non-herpetic or clinically atypical herpetic stromal keratitis. Graefe’s Arch Clin Exp Ophthalmol 241:734–739CrossRefGoogle Scholar
  19. 19.
    Kaye S, Choudhary A (2006) Herpes simplex keratitis. Prog Retin Eye Res 25:355–380CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Ophthalmology Department, Faculty of Medicine, Balcali HospitalCukurova UniversitySaricam, AdanaTurkey
  2. 2.Virology Department, Faculty of Medicine, Balcali HospitalCukurova UniversitySaricam, AdanaTurkey
  3. 3.Pathology Department, Faculty of Medicine, Balcali HospitalCukurova UniversitySaricam, AdanaTurkey

Personalised recommendations