The treatment of HSV1 ocular infections using quantitative real‐time PCR results

Abstract

ABSTRACT.Purpose: Herpes stromal keratitis is a serious condition and the most frequent cause of unilateral blindness. The real-time PCR is an accurate and fast diagnostic method for an analysis of infectious agents causing keratitis and keratouveitis. The aim of the study was to assess the relationship between clinical symptoms, treatment efficacy monitoring and viral quantity in corneal swabs determined by quantitative real-time PCR method. The real-time PCR method was used as well for the detection of other viral eye pathogens. Methods: A total of 212 patients (136 men and 76 women) suspect of having herpes simplex virus (HSV) keratitis or keratouveitis were included in the study. The detection and quantitative analysis of the viral DNA were performed using the EliGene HSV1 RT kit, and the result was correlated with the clinical picture of the disease. The patients were routinely treated with acyclovir applied locally or, alternatively, in systemic administration. In a case of acyclovir treatment resistant keratitis, the patients were treated with local ganciclovir (Virgan gel ophth 0.15%). Results: A total of 636 analyses of the viral DNA were performed; 85 patients were positive for HSV1 (198 detected). There were 16 acyclovir resistant cases of keratitis (14%). Conclusions: The real-time PCR appears as a fast and accurate method for an exact identification of the viral DNA in patients with herpes stromal keratitis. The introduction of the quantification is important for the treatment evaluation and for the specification of a so-called acyclovir resistant keratitis. A longterm systemic administration in maintenance doses may lead to the resistance and repeated, frequent relapses of the disease.

Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

“…Strains of herpes simplex virus that are not readily susceptible to acyclovir and other antivirals are becoming more prevalent, particularly among immunocompromised patients and during intermittent antiviral therapy (Zhang 2007). Virological resistance is one of the reasons for therapeutic unresponsiveness in suspected herpetic keratitis, a dilemma that may lead to the selection of an alternative antiviral (Hlinomazová 2010). If resistant ocular HSV strains continue to emerge (Choong 2010; Hlinomazová 2010) the applicability of this review may need to be modified.…”

“…Virological resistance is one of the reasons for therapeutic unresponsiveness in suspected herpetic keratitis, a dilemma that may lead to the selection of an alternative antiviral (Hlinomazová 2010). If resistant ocular HSV strains continue to emerge (Choong 2010; Hlinomazová 2010) the applicability of this review may need to be modified.…”

Concomitant herpes simplex virus and cytomegalovirus endotheliitis in immunocompetent patient

“…There has been a changeover from a common PCR with a sensitivity of approximately 100 genomic DNAs to nested PCR methods with a sensitivity of 1–10 genomic DNAs. Nowadays, clinical laboratories proceed generally to real-time PCR methods, which have, if a correct design is used, same or even better sensitivity than the nested PCR 15. Indeed, real-time PCR has successfully been used to diagnose HSV,11 CMV retinitis16 and VZV retinitis 17…”

Time Profile of Viral DNA in Aqueous Humor Samples of Patients Treated for Varicella-Zoster Virus Acute Retinal Necrosis by Use of Quantitative Real-Time PCR

“…For example, in some reported cases, PCR was positive 2 weeks after high-dose acyclovir administration (for VZV; it was then negative at 4 weeks) (40), 20 days after antiviral intravenous acyclovir (for HSV2; viral load, 4.5 ϫ 10 2 copies/ml) (19), after 36 days of acyclovir treatment (for VZV; 1.2 ϫ 10 3 at day 43) (20), 2 weeks (HSV2, 1.9 ϫ 10 4 copies/ml) and 6 months after treatment (acyclovir 14 days intravenously and orally for 3 months, 1.4 ϫ 10 3 copies/ml), and then negative at 10 months (33). In herpetic keratitis, it is difficult to reduce the viral load quickly despite clinical improvements (41). Also, our data are consistent with the absence of a reduction in HSV1 DNA copy numbers in tears by treatment with 500 mg of valacyclovir daily for 30 days (42), whereas 400 mg of acyclovir can significantly reduce the number of HSV keratic recurrences (31).…”