This article was originally published in a sponsored newsletter.
Herpes simplex keratitis (HSK) is primarily caused by the herpes simplex virus type 1 (HSV-1), though HSV-2 can also be implicated, particularly in neonates. The virus initially infects the corneal epithelium, leading to inflammation and necrosis of infected cells. After the initial infection in the ocular area, the HSV-1 virus travels to the trigeminal ganglion via the first branch of the trigeminal nerve (V1; a sensory nerve) and remains dormant within the neurons. Stimuli such as stress or immunosuppression can reactivate the virus, leading to recurrent episodes of keratitis. During reactivation, the virus travels back to the cornea and causes recurrent infection and further damage to the ocular surface.
The initial epithelial infection may cause dendritic ulcers—branching lesions that are characteristic of HSV keratitis. If left untreated or if the infection recurs, these ulcers can lead to stromal keratitis, which involves deeper layers of the cornea and can result in significant scarring, thinning and even perforation. Chronic or recurrent infections may also lead to poor healing, increased risk of secondary infections and neurotrophic keratopathy where the corneal surface becomes desensitized. HSV infection can also result in anterior uveitis, iridocyclitis, complicated cataracts, vitritis and retinal detachment, which can quickly progress to corneal perforation or blindness if left unchecked. Overall, HSK is a leading cause of infectious blindness worldwide due to its recurrent nature and the potential for permanent corneal damage.
Risk factors for HSV keratitis include a history of previous HSV eye infections, immunocompromised states and systemic conditions such as atopic dermatitis. In patients with a history of HSV keratitis, certain factors are known to trigger reactivation of the virus. Common triggers include:
- Immunosuppression through emotional or physical stress, conditions that compromise the immune system or medications such as corticosteroids or chemotherapy.
- Upper respiratory infections and other febrile illnesses.
- Ultraviolet light exposure, especially intense sunlight.
- Eye injury or surgery.
HSK is primarily diagnosed based on clinical features, but laboratory tests such as polymerase chain reaction (PCR) can provide definitive evidence of HSV infection. PCR can detect HSV DNA in ocular specimens (i.e., corneal scraping, tear fluid, aqueous humor) to distinguish between HSV-1 and HSV-2. Other, less-preferred diagnostic studies include viral culture, direct fluorescent antibody testing, immunohistochemistry, serology, tear analysis and anterior chamber paracentesis.
Treatment for HSV keratitis involves antiviral therapy, which can be administered topically (e.g., trifluridine [Viroptic, Pfizer] or ganciclovir gel [Zirgan, Bausch + Lomb]), orally (e.g., acyclovir, valacyclovir or famciclovir) or both, depending on the severity of the disease and whether patients can tolerate the older generation topical anti-virals. Ganciclovir gel is dosed only 5 times per day vs. 9 times per day with trifluridine. Ganciclovir gel is also comforting to the ocular surface due to its formulation. These factors may improve compliance in several of our patients.
The choice between topical and oral antivirals depends on several factors. Topical agents are effective for epithelial disease, but may be less effective in stromal keratitis and can cause epithelial toxicity with prolonged use. Oral antivirals are preferred for stromal involvement, due to their ability to reduce inflammation and decrease the risk of recurrence without the same level of ocular surface toxicity. However, oral antivirals can have potential systemic side effects, particularly in patients with renal impairment.
Managing recurrent HSV keratitis presents several challenges. Preventing recurrences is difficult, especially in patients with frequent episodes. Long-term oral antiviral prophylaxis may be necessary, but patient adherence can be a concern. Recurrent infections increase the risk of corneal scarring and subsequent vision loss that may require corneal transplantation in severe cases. Long-term antiviral therapy, while effective in preventing recurrences, carries risks of drug resistance and potential side effects, requiring careful management.
