Herpes Stromal Keratitis: Erosion of Ocular Immune Privilege by Herpes Simplex Virus

Jared E Knickelbein; Kristine-Ann Buela; Robert L Hendricks


Future Virology. 2010;5(6):699-708. 

In This Article

HSK Epidemiology & Clinical Disease

Herpes simplex virus infection can involve many, if not all, parts of the visual axis, with the majority of disease affecting the ocular surface, namely the cornea. Excluding neonatal infections, more than 95% of ocular HSV infections are caused by HSV-1.[9] HSV-1 can cause pathology in all three layers of the cornea; however, stromal involvement is generally considered the most serious, owing to the risk of irreversible stromal scarring and subsequent visual loss. In developed countries, the incidence and prevalence of herpetic ocular surface disease has been estimated to be 5.9–20.7 and 149 per 100,000 person-years, respectively.[10] While HSK represents only approximately 2% of primary ocular HSV-1 infections, it accounts for 20–46% of recurrent disease.[11,12]

Herpes stromal keratitis can present in one of two forms: necrotizing or non-necrotizing stromal keratitis. In necrotizing disease, both live virus and the host immune system are thought to drive stromal necrosis, which is usually accompanied by an overlying epithelial defect.[13] Inflammation in the absence of infectious virus is thought to mediate non-necrotizing stromal keratitis, in which the epithelium is usually not affected. Of the two types of HSK, the non-necrotizing form is much more common; however, it is likely that these two types of HSK represent a spectrum of disease rather than two distinct pathologies.

As discussed in detail later, HSK is an immunomediated pathology, dependent mainly on CD4 T cells. Thus, it is particularly interesting to assess HSK and HSV recurrences in patients with compromised immune systems, such as patients with HIV or AIDS. Unfortunately, very few studies have been published investigating this situation. In a retrospective cohort study, Hodge et al. found no statistical difference in the incidence of HSK in patients who were HIV positive or not.[14] The recurrence rate of HSV-1-mediated corneal disease was statistically increased in the HIV-positive cohort. However, this statistic included both epithelial and stromal HSV involvement. Given the CD4 T-cell-mediated pathology underlying HSK, it is interesting to speculate that recurrences of stromal disease may actually be less common in HIV or AIDS patients, who have decreased numbers of CD4 T cells. In fact, this phenomenon has been suggested by two small clinical trials, although these studies were limited by small numbers of subjects and, thus, inadequate power to achieve statistical significance.[15,16]


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