Herpes simplex virus type 1 DNA in human corneas: what are the virological and clinical implications?

The study by Remeijer et al. [1] conducted at the Rotterdam Eye Hospital in The Netherlands and reported in this issue of the Journal significantly enhances our knowledge of herpes simplex virus type 1 (HSV-1) DNA in human corneas and provides important clinical information about the consequences of HSV-1 DNA in the cornea. Patient medical records were reviewed for relevant clinical information , including data on graft survival after penetrating keratoplasty (PKP). HSV-1 DNA, as quantified by real-time polymerase chain reaction (PCR), was detected in 40 (48%) of 83 patients with a history of herpetic keratitis (HK; hereafter referred to as " patients with HK ") and in 15 (4%) of 367 patients without a history of HK (hereafter referred to as " patients without HK ") (table 1). HSV-1 DNA copies in all corneas were quantified , and the corneas of patients with HK were found to contain ∼100 times more virus than the corneas of patients without HK. Furthermore, the corneal HSV-1 DNA load correlated with increased age both in patients with HK and in patients without HK. Steroid use before PKP was also found to increase the viral load. Graft survival was not statistically different between patients with HK (56 [67%] of 83 patients) and patients without HK (260 [71%] of 367 patients). Although the presence or absence of HSV-1 DNA was not correlated with graft failure, the viral load in patients with HK was associated with a lack of success. This finding leads us to the question, How does a higher viral load increase graft failure? The rate of graft failure among patients with HK who had high viral loads suggests the following 3 possibilities. The first possibility is that the patients harbored in their neurons a latent strain of HSV-1 that could be characterized as a high pheno-typic reactivator. High phenotypic reacti-vators are known to undergo significantly more reactivation episodes than low phe-notypic reactivators [8, 9]. The second possibility is that the corneal rim in the transplant recipient contained an amount of HSV-1 DNA sufficient to initiate rep-lication, migrate to the transplanted cornea , reactivate, and initiate an immune response , leading to graft rejection. The third possibility is a combination of the first 2 possibilities. Graft failure occurred in patients with HK who were receiving intense antiviral and anti-inflammatory therapy both pre-operatively and postoperatively [10, 11]. This long-term combination therapy is often unsuccessful in …