Recurrence of Herpes Simplex Keratitis in Corneal Grafts

SUMMARY

Recurrent herpes simplex virus (HSV) keratitis is a potential complication following keratoplasty for corneal scars resulting from previous herpes simplex keratitis. Unfortunately, the prognosis for this condition is often unfavorable. Recently, we encountered a case involving a 38-year-old woman who had undergone penetrating keratoplasty two years ago for corneal scarring due to herpes simplex keratitis. She presented to us a few months ago with corneal edema in her left eye and had a visual acuity of counting fingers at a distance of one foot. Initially, we prescribed topical steroids, which led to significant improvement. However, the patient did not adhere to regular follow-up visits.

Last week, she returned with the development of epithelial dendritic keratitis (positive staining) and minimal corneal edema. This time, we initiated treatment with topical acivir (acyclovir) and discontinued the previously prescribed steroids. The patient responded remarkably well to acivir, with the dendrites disappearing within four days. Unfortunately, her corneal edema returned. Consequently, we decided to administer oral steroids in addition to topical acivir, mild topical steroids, and hypersol. This combined approach resulted in a notable improvement in her vision, increasing from 3/60 to 6/24. The patient is currently undergoing regular follow-up visits to monitor her progress.

CASE DESCRIPTION

A 38-year-old female, a housewife residing in Sakipur, Greater Noida, experienced an episode of herpes simplex keratitis (HSK) in her left eye two years ago, leading her to undergo penetrating keratoplasty at Rajender Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi.

According to her records from three months ago, her best-corrected visual acuity (BCVA) was 6/18, with a clear graft and no medication. However, she presented to our hospital two months ago with complaints of pain, redness, watering, and a decrease in vision, for one week. She denied having any fever, history of trauma, or systemic illness.

Upon examination, her vision in the right eye was 6/6, while in the left eye, it was 3/60. She had mild blepharospasm and ciliary congestion in the left eye. The host corneal rim had mild edema and was non-vascularized. The junction between the host tissue and the graft showed mild edema, with 8 out of 16 sutures were intact. The corneal graft (8 mm) appeared moderately edematous, ectatic, non-vascularized, and hazy due to edema. Corneal sensations were impaired, no abnormal endothelial deposits were observed (Fig. 1). Fundus details were not visible.

After duration of 2 years following penetrating keratoplasty, the patient experienced the onset of corneal edema without any preceding illness, hence the diagnosis of graft rejection was made. The patient was prescribed topical steroids (Moxi-PD) to be administered one hourly for 3 days, followed by every two hours for the next four days. After 1 week, her best-corrected visual acuity (BCVA) improved to 6/18, and the corneal edema was also reduced. However, the patient was lost to follow-up and returned only after a gap of one and a half month with pain, redness, watering, and a decrease in vision in the left eye.

On examination, fluorescein staining revealed epithelial dendritic keratitis with minimal corneal edema. Topical steroids were discontinued. The patient was then diagnosed with a recurrence of herpes simplex keratitis in the graft (Fig. 1). Systemic Acyclovir at a dosage of 400 mg five times a day, topical 3% acivir eye ointment five times a day, and prophylactic tobramysin eye drops four times a day were started.

After 4 days, the patient’s vision deteriorated to counting fingers at a distance of one foot. The previously observed dendritic lesions had disappeared, and the fluorescein stain was negative. However, there was an increase in corneal edema (Fig. 2). As a result, the use of topical acivir was discontinued. Instead, the patient was prescribed Gatifloxacin-Prednisolone eye drops to be administered every hour for 3 days, followed by every 2 hours after 4 days. Additionally, eye ointment containing sodium chloride and oral steroids were added to the treatment regimen.

After 1 week of follow-up, the patient’s vision showed improvement, reaching 6/24. The graft also cleared up, displaying minimal edema (Figs 3 and 4). No signs of endothelial deposits were observed. On fundus examination, mild medial haze was noted. The optic disc had a normal cup-to-disc ratio of 0.3:1, and the vessels appeared normal. The macula also appeared normal.

DISCUSSION

Herpetic keratitis can manifest as either a unilateral or bilateral condition, bilateral involvement being more common in patients atopy due to immune dysregulation and increased susceptibility to viral infections.¹ The characteristic presentation of herpes keratitis includes the presence of classic dendritic lesions with terminal bulbs. Recurrent activations of the virus within the sensory ganglion can result in corneal scarring, necrosis, and diminished sensation, leading to a condition known as neurotrophic keratitis.

Ocular herpetic disease is primarily caused by HSV-1, which enters the cornea through the trigeminal nerve following oral infection.² Initially, the infection may be asymptomatic, but patients may eventually present with acute follicular conjunctivitis and upper respiratory infection. After the primary infection, the virus travels along the axons of sensory nerves and establishes as latent infection in the trigeminal ganglion, where it remains indefinitely. Subsequently, the virus can reactivate at any point along the branches of the trigeminal nerve, leading to various ocular complications and morbidity.²

Herpes simplex virus keratitis is characterized by the presence of multiple epithelial lesions, initially present as a coarse, punctate epithelial keratitis. The characteristic feature of HSV keratitis is the occurrence of small arborizing epithelial dendrites on the corneal surface. These dendrites possess terminal bulbs, allowing them to be differentiated from pseudo dendrites seen in herpes zoster keratitis. Importantly, the dendrites follow the nerve pattern of the cornea, aiding in the diagnosis of HSV keratitis.³

Fluorescein staining reveals the ulcer bed in HSV keratitis, while the swollen corneal epithelium at the ulcer’s edge typically stains with Rose Bengal. The presence of multiple dendrites can sometimes merge to form a geographic epithelial ulcer.⁴ Additionally, mild conjunctival injection, ciliary flush, mild stromal edema, and subepithelial white blood cell infiltration may be observed. In primary HSV epithelial keratitis, spontaneous resolution is possible, but antiviral medication is often prescribed to expedite recovery and potentially reduce long-term complications.⁵

The primary approach to treatment involves the use of antiviral medications, which can be administered orally as acyclovir, valacyclovir, or famciclovir for a duration of 10–14 days. Alternatively, topical antiviral medications can also be employed.⁶ One option is topical ganciclovir 0.15%, which is FDA approved for the treatment of acute herpetic keratitis. It is typically applied five times a day until the corneal ulcer heals, after which the frequency is tapered to three times a day for another week. Another topical therapy option is trifluridine 1%, which can be prescribed eight times a day. However, caution should be exercised to discontinue the use of antiviral drops within 10–14 days due to potential corneal toxicity.

In addition to antiviral therapy, epithelial debridement of the dendrites can be performed to aid in reducing the viral load. The use of an amniotic membrane can also be beneficial in promoting epithelial healing and minimizing scar formation when used alongside antiviral treatment.⁷

The herpetic eye disease study (HEDS) has indicated that the long-term use of oral antivirals for prophylaxis can potentially reduce the risk of recurrent HSV keratitis.^8–10

In cases where significant scarring affects visual acuity, a penetrating keratoplasty can be considered as a treatment option once the HSV keratitis is in a quiescent stage.

The prognosis for HSV keratitis is generally favorable; however, it can vary significantly depending on the severity of the disease, the number of recurrences, and the timing of treatment.

MY LEARNING POINTS

Herpetic stromal keratitis is a common indication for corneal transplantation; however, this patient group carries a relatively high risk of graft failure. In this particular case, I faced a dilemma regarding the use of steroids. If no steroids were administered, the corneal edema would increase. However, we were scared using topical steroids due to the risk of recurrence. We used both topical and systemic antivirals as well as systemic and topical steroids to get the clear graft. Finally the vision improved to 6/18. Topical and systemic antivirals for a period of 3 months are required to avoid recurrence and maintain clarity of the graft in addition to low dose topical steroids.

REFERENCES

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2. Roozbahani M, Hammersmith KM. Management of herpes simplex virus epithelial keratitis. Curr Opin Ophthalmol 2018;29(4):360–364. DOI: 10.1097/ICU.0000000000000483.

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4. White ML, Chodosh J. Herpes simplex virus keratitis: A treatment guideline. AAO compendium of evidence-based eye care; 2014. Available from: http://www.aao.org/clinical-statement/herpes-simplex-virus-keratitis-treatment-guideline. Last Accessed on: 26 October 2015.

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8. Austin A, Lietman T, Rose-Nussbaumer J. Update on the management of infectious keratitis. Ophthalmology 2017;124(11):1678–1689. DOI: 10.1016/j.ophtha.2017.05.012.

9. Liesegang TJ, Melton LJ, Daly PJ, et al. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol 1989;107(8):1160–1165. DOI: 10.1001/archopht.1989.01070020226030.