Recurrence of Herpes Simplex Keratitis in Corneal Grafts
Corresponding Author: Jawahar Lal Goyal, Department of Ophthalmology, Sharda Hospital, Greater Noida, Uttar Pradesh, India, Phone: +91 9560954118, e-mail: firstname.lastname@example.org
How to cite this article: Sharma N, Goyal JL, Gahlot A. Recurrence of Herpes Simplex Keratitis in Corneal Grafts. AMEI’s Curr Trends Diagn Treat 2023;7(1):14–16.
Source of support: Nil
Conflict of interest: None
Patient consent statement: The author(s) have obtained written informed consent from the patient for publication of the case report details and related images.
Received on: 27 January 2023; Accepted on: 28 April 2023; Published on: 20 July 2023
Recurrence of herpes simplex virus (HSV) keratitis is a possible complication of keratoplasty done for corneal scars resulting from herpes simplex keratitis. Prognosis is often poor. A couple of months ago, a 38-year-old woman with penetrating keratoplasty operated for herpes simplex keratitis two years back presented to us with corneal oedema in the left eye with vision of counting fingers at one foot. We prescribed her topical steroids, and she improved significantly but she failed to come for follow-up regularly. Last week, she presented to us again and had unfortunately developed epithelial dendritic keratitis (stain positive) along with minimal corneal oedema. This time, we treated her with topical acivir and discontinued previously prescribed steroids. She responded dramatically well to acivir with disappearance of dendrites, within 4 days, but her corneal oedema increased again. Hence, we have started her on oral steroids along with topical acivir, mild topical steroids, and hypersol. She improved her vision from 3/60 to 6/24. She is now on regular follow-up.
Keywords: Case report, Corneal grafts, Herpes simplex virus, Penetrating keratoplasty.
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.
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.
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.
1. Borkar DS, Gonzales JA, Tham VM, et al. Association between atopy and herpetic eye disease: Results from the pacific ocular inflammation study. JAMA Ophthalmol 2014;132(3):326–331. DOI: 10.1001/jamaophthalmol.2013.6277.
3. Nijm LM, Feldman BH, Kozak A, et al. Herpes Simplex Epithelial Keratitis. American Academy of Ophthalmology. Available from: https://eyewiki.aao.org/Herpes_Simplex_Epithelial_Keratitis. Last Accessed date: 06 March 2023.
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.
5. Ching SST, Feder RS, Hindman HB, et al. Herpes simplex epithelial keratitis. Preferred practice pattern clinical questions. Am Acad Ophthalmol 2012;1–8.
6. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev 2015;1:CD002898.
7. Kalogeropoulos D, Geka A, Malamos K, et al. New therapeutic perceptions in a patient with complicated herpes simplex virus 1 keratitis: A case report and review of the literature. Am J Case Rep 2017;18:1382–1389. DOI: 10.12659/ajcr.906506.
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.
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.