Epithelial keratitis is the most common clinical presentation of ocular infection by HSV, accounting for 70% to 80% of all cases.6,7
The recurrence rate of HSV epithelial keratitis may be greater in diabetics, atopes, corneal transplant recipients, and people with immunosuppression. 8–11
Topical application of TFT is the gold standard in the treatment of HSV keratitis, and foscarnet eye drops (3%) are equivalent to TFT eye drops in the treatment of acyclovir-resistant cases,12
although cytotoxicity limits their use.13,14
Herpes infections continue to be prevalent; in the HEDS15
trial, acyclovir prevented only 40% of recurrences and resistance to nucleoside analogs has been reported,16
especially in immunocompromised transplant recipients and AIDS patients. Therefore, it is important to explore new treatment options with alternative mechanisms of antiviral action.
In this study, the severity of keratitis caused by a TK-negative mutant of HSV-1 was less severe than wild type HSV-1 McKrae; the TK-negative mutant virus had a HSV-1 KOS background and KOS is known as a less virulent strain compared with McKrae. Despite this difference in pathogenicity between the two viruses, regardless of virus strains used, from PI days 6–10, topical apoEdp effectively reduced the severity of epithelial keratitis to a significantly decreased level compared with placebo-treated eyes. In our mouse study, we also observed a delay in antiviral activity, i.e., clearance of infectious virus (see Fig. 4, IOVS 49:4263–4268, 2008).
The treatment currently available for moderate or severe cases of HSK includes topical corticosteroids to prevent irreversible corneal damage. However, this treatment has the potential for complications such as corneal melting, glaucoma, and cataract.17
We previously reported that the topical application of 1% apoEdp in mice had a potent anti-inflammatory effect without any toxicity. 1
Our results demonstrated that a novel topical ocular antiviral peptide (apoEdp) exhibited similar therapeutic effects compared with foscarnet and TFT with no observed toxicity. We have tested this against both HSV-1 and HSV-2 and have found concentrations in which there is high synergism (data not shown). We suggest that a combination treatment of herpetic epithelial keratitis with topical apoEdp along with an oral antiviral nucleoside could emerge as an improvement over single-drug treatment or as an alternative treatment for clinically resistant cases.