Herpes simplex virus has a predilection for the trigeminal ganglion, where the virus can lay dormant for years or actively replicate during a reactivation episode [11]. Trigeminal innervation of the corneal surface provides sensation and supplies growth factors to maintain the integrity of the corneal epithelium [12]. A herpetic eye infection can, therefore, create a neurotrophic state where damage of the corneal surface occurs by a decrease in reflex tear production, alteration of the blink response, and a lack of epitheliotropic growth factors (e.g., neuropeptides). A neurotrophic cornea is a major risk factor for the development of a non-healing epithelial defect [12].

Herpes simplex epithelial keratitis is typically treated by topical or systemic antiviral medications. All of the commonly used topical antiviral medications today, including trifluridine, acyclovir, and ganciclovir, have been shown to cause local toxicity and punctate epithelial erosions [13]. Their mechanism of action involves interfering with viral DNA replication. Trifluridine, the most commonly used topical antiviral agent in the United States, is more likely to be incorporated by host DNA and, therefore, can prevent epithelial cell proliferation along with viral replication [14]. Although topical antiviral medications can decrease the time to healing in herpes simplex epithelial keratitis, local toxicity may limit their efficacy, and oral antiviral medications may be preferred. If topical antivirals were used by the referring ophthalmologist, epithelial toxicity may have retarded the reparative process.

The length of treatment with topical antiviral medications could have also affected the chances of epithelial healing in this patient. It has been estimated that only about half of all corneal epithelial defects from herpes simplex keratitis, regardless of antiviral type and route (oral versus topical) used, heal within 1 week on treatment [15]. Therefore, typically about 2 weeks of treatment is recommended, as failure to heal after this time can reflect incomplete treatment of the viral infection. An important point is that herpetic epithelial diseases rarely need to be treated with topical antivirals more than 2 weeks (except in immune-compromised cases), and if prolonged therapy is needed, oral antivirals are the preferred method of therapy.

The patient’s topical therapy was discontinued and instead was treated with oral acyclovir 400 mg 5×/day until the viral infection was thought to be completely cleared. This resulted in some healing of the corneal epithelium. However, there was still a non-healing defect afterward. Despite the use of 50% autologous serum, the defect did not heal.

As in all cases of neurotrophic keratitis , adequate lubrication of the ocular surface is crucial in minimizing epithelial cell loss from the mechanical trauma of eyelid blinking [12]. Preservative-free artificial tear solutions, applied frequently throughout the day, can be used as a substitute for the tear film, which is often disrupted in neurotrophic eyes for the reasons mentioned above. Punctal plugs should be used liberally in all cases of neurotrophic keratopathy. In recalcitrant cases, a lateral tarsorrhaphy is used to decrease corneal exposure and minimize blinking-related trauma to the epithelium. A lateral tarsorrhaphy that extends far enough to cover the entire epithelial defect is one of the most effective, and underutilized, treatments available for persistent epithelial defects (Table).

Amniotic membrane transplantation (as a graft or as a bandage) is effective in hastening corneal epithelial healing and has been shown to result in similar rates of epithelial defect closure to those of tarsorrhaphy and contact lens application [16]. Soft bandage contact lenses are generally not recommended for prolonged periods in neurotrophic cases not only because they can anesthetize the cornea further but also because the patients may not recognize a worsening of their condition (e.g., infectious keratitis), resulting in a potential delay in presentation [17]. On the other hand, scleral contact lenses are quite effective and may be used as an alternative to tarsorrhaphy for persistent epithelial defects; however, they require special expertise for fitting and very close follow-up.