LASIK in Patients With Herpes Simplex Virus

From EyeWiki


 

Overview

Since LASIK was approved in the United States, there has been a question of whether it is safe to perform in a patient with herpes simplex virus (HSV) related ocular disease. As a large majority of the population (60-90%) is seropositive for HSV-1, this question is extremely relevant, yet there is only a small body of literature examining the potential complications of LASIK in a patient with a history of ocular herpes.

Currently the US FDA does not consider a history of HSV ocular infection an absolute contraindication to LASIK surgery, but it does cite a history of ocular HSV symptoms as a potential source of complications.

Ocular Manifestations of HSV

Ocular HSV usually presents as keratitis, an infection and inflammation of the superficial layer of the cornea. Herpetic keratitis, if left untreated, can lead to significant corneal scarring and vision loss, and is one of the leading causes of blindness worldwide[1].

Pathogenesis

Primary infection occurs via direct contact of mucus membranes to the viral particles. Latency occurs once the virus itself in the sensory neurons and travels retrograde to the sensory ganglia, where it integrates within the host genome and remains for the duration of the host’s life. Primary infection is not believed to lead to ocular involvement, rather ocular symptoms occur when latency is disrupted[2].

When latency is disrupted, infectious viral particles travel anterograde down the neuron and manifest as infection. Reactivation of HSV in skin and mucosal infections is linked with increased stress, trauma, fever, UV exposure and recent infection, however reactivation of ocular HSV infection has not been linked to these factors[3].

Ocular HSV reactivation is linked to excimer laser treatment, topical ocular medications such as epinephrine, beta-blockers and prostaglandins, and immunosuppression, most notably immunosuppression with topical ocular corticosteroids[3].

Epidemiology

Antibodies to HSV can be found in over 90% of the population, however far fewer develop symptoms of infection, and of those a small minority ever experience ocular involvement [4].

The estimated incidence of ocular HSV-1 infection is 12-31/100,000 annually. The prevalence in the US is 150/100,000, with 20,000 new cases and 48,000 episodes reported annually[5],[6].

Those who do experience ocular HSV are likely to experience recurrent symptoms. Recurrence of the ocular HSV is reported at 9% at one year, 23% at two years, 40% at three years and 67% at 10 years[4],[7].

Presentation

Herpetic keratitis presents acutely as pain, blurred vision and watery discharge[8].

Diagnosis

Diagnosis can usually be made via slit-lamp examination, which usually reveals dendritic lesions of the cornea.

Laboratory testing is usually not needed, but can be performed if clinical suspicion is high and presentation is atypical. Laboratory specimens should be taken by scraping the epithelial lesions. Serologic testing is not helpful due to a high prevalence in the general population[4].

Types of Disease

Herpetic keratitis is by far the most common presentation of ocular HSV infection[9]. While ocular herpes infection can manifest in alternate ways (herpetic blepharitis, conjunctivitis, retinitis or scleritis), these presentations are rare. There are four recognized types of herpetic keratitis.

Epithelial Keratitis

Epithelial keratitis is the most common form of ocular HSV infection. Disease presents as dendritic lesions or geographic ulcerations of the cornea, which can be seen with fluorescein dye. With treatment, symptoms resolve in two to three weeks[10].

Stromal Keratitis

Stromal keratitis rarely occurs with an initial presentation of ocular HSV infection, but becomes increasingly common with recurrent infections (up to 20-60%)9. Stromal disease can occur due to the virus itself or due to the immune mediated inflammatory response to infection[11].

Endotheliitis

Endotheliitis (formerly disciform keratitis) is corneal stromal edema with underlying endothelial keratic precipitates. It is a common form of recurrent HSV ocular disease and is thought to be related to immune reaction to the virus, rather than the virus itself[12].

Keratouveitis

While uveitis is a common condition, when it occurs with keratitis, HSV infection should be considered the most likely etiology.

Treatment

Treatment of HSV keratitis is based on whether symptoms are due to active disease or related to an immune response.

Epithelial Keratitis

Topical and oral antiviral medications are equally effective in treating of epithelial keratitis due to HSV reactivation[13]. Combination therapy with both topical and oral antivirals has not been shown to be any more effective or improve outcomes than treatment with one or the other.

Stromal Keratitis

Antivirals with topical corticosteroids is the standard of care for treatment of stromal keratitis[14].

Endotheliitis

Topical corticosteroids with antiviral therapy are an effective treatment for endotheliitis caused by HSV reactivation[15].

Keratouveitis

Treatment should be tailored to address the keratitis (see above), and the uveal component will resolve with adequate treatment of corneal component.

Recurrence Prophylaxis

Preventing recurrence is critical, as repeated reactivation of ocular HSV can result in corneal scarring and eventually visual impairment. In randomized-controlled trials, oral acyclovir has proved effective in reducing the number of ocular HSV outbreaks in patients with a documented history of ocular HSV[16].

Reactivation of HSV After LASIK

Animal models have linked both PRK and LASIK to reactivation of ocular HSV in rabbits, yet there is only a spattering of reports of post-LASIK HSV reactivation in humans. To further convolute the picture, recent retrospective studies have failed to show a connection between HSV reactivation and LASIK, and several reports indicate that perioperative antivirals may be adequate to prevent reactivation in these patients.

Animal Models

LASIK and PRK have both been shown to reactivate ocular HSV and induce viral shedding in rabbits[17].

Case Reports

The literature contains several reported cases of post-LASIK HSV reactivation. Three patients had a history of ocular herpes, two had a history of herpes labialis and one reported no previous herpetic disease. Reactivation occurred on postoperative day one in two patients, within two months in two patients and after two years in one patient. No patient was pretreated with antivirals, and only one patient received antiviral medication postoperatively (prior to symptom onset). Symptoms fully resolved in all cases with antiviral therapy[18],[19],[20],[21],[22].

Case Series and Studies

Two small case studies found no reactivation of HSV after perioperative administration of antiviral therapy in patients with a documented history of ocular HSV infection. The value of these studies is limited by the small number of patients included (3 in one study and 5 in the second)[23],[24].

In a retrospective examination of 48 patients with a history of ocular herpes, no patient experienced HSV reactivation during the postoperative window (range of 1-28 months) despite only 13 patients receiving perioperative antiviral treatment, and 10 patients receiving pre and postoperative antiviral therapy[18].

Antiviral Prophylaxis

Antiviral therapy has long been known to significantly reduce the reactivation of genital and orofacial HSV infection, and is also effective in prophylaxis and treatment of ocular HSV16. There is a small, but growing, body of literature that seems to support the theory that judicious use of pre, peri and post-LASIK antiviral treatment significantly reduces the risk of HSV reactivation in both animal models and in clinical practice.

Twice daily injections of acyclovir, beginning one day prior to LASIK surgery and extending seven days, were found to significantly reduce the incidence of HSV reactivation and the number of days of viral shedding in rabbits .

In several small case studies of LASIK in patients with a history of herpetic keratitis, perioperative antiviral treatment was administered and no patient developed reactivation of ocular HSV. All patients had been free of ocular symptoms for at least one year at the time of surgery[23],[24].

In a retrospective study of 48 LASIK patients with a history of ocular herpes infection, thirteen were perioperative antiviral therapy. None of the patients in the study developed reactivation of HSV keratitis during the follow-up window[18].

Recommendations

There is no consensus on the safety of LASIK surgery in patients with a history of ocular HSV infection, although the limited data does allow for some reasonable recommendations and assumptions.

Each year there are an estimated 48,000 occurrences of herpetic keratitis[4]. With the overwhelming popularity of LASIK surgery, the expected incidence of HSV reactivation following LASIK would be expected to be significantly higher. Either HSV reactivation following LASIK is an uncommon complication, or it is an under-recognized phenomena. Clearly more research is needed to elucidate this discrepancy. In the meantime, providers must decide how to handle patients with a history of herpetic keratitis who are requesting LASIK. Using the data available, several recommendations seem reasonable[18].

  1. Prospective patients should be symptom free at the time of surgery and should also be at least one year removed from any prior ocular or labial HSV outbreak[18].
  2. Prospective patients should not have any evidence of stromal disease on examination[18].
  3. Prospective patients should have normal topography, pachymetry and corneal sensitivity[18].
  4. Perioperative and postoperative antiviral therapy should be given to all patients with a history of ocular HSV infection[18].
  5. Patients should be well informed regarding the remote risk of HSV reactivation following LASIK[18].

References

  1. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea 2001; 20(1):1
  2. Cunningham AL, Diefenbach RJ, Miranda-Saksena M, et al. The cycle of human herpes simplex virus infection: virus transport and immune control. J Infect Dis 2006; 194 suppl1:S11
  3. 3.0 3.1 Herpetic Eye Disease Study Group. Predictors of recurrent herpes simplex virus keratitis. Cornea 2001: 20:123
  4. 4.0 4.1 4.2 4.3 Leisegang TJ, Melton J, Daly PJ, Ilstrup DM. Epidemiology of ocular herpes simplex: incidence in Rochester Minnesota 1950-1982. Arch Ophthalmol 1989; 107:1155-1159
  5. Young RC, Hidge DO, Liesegang TJ, Baratz KH. Incidence, recurrence and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota 1976-2007: the effect of oral antiviral prophylaxis. Arch Ophthalmol. 2010; 128:1178
  6. Laetoulle M, Auquier P, Conrad H, et al. Incidence of herpes simplex virus keratitis in France. Ophthalmology 2005;112:888
  7. Shuster JJ, Kaufman HE, Nesburn AB. Statistical analysis of the rate of recurrence of herpesvirus ocular epithelial disease. Am J Ophthalmol 1981;91:328
  8. Sugar A. Herpes simplex keratitis. UpToDate. Nov 2011
  9. Holland EJ, Schwartz GS. Classification of herpes simplex virus keratitis. Cornea 1999;18:144
  10. Cook SD. Herpes simplex virus in the eye. Br J Ophthalmol 1992;76:365
  11. Inoue Y. Immunologic aspects of herpetic stromal keratitis. Semin Ophthalmol. 2008;23:221
  12. Suzuki T, Ohashi Y. Corneal endotheliitis. Semin Ophthalmol. 2008;23:235.
  13. Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex vius keratitis: a systematic review. Ocul Surf 2007;5:240
  14. Knickelbein JE, Hendricks RL, Charukamnoetkanok P. Management of herpes simplex virus stromal keratitis: an evidence-based review. Surv Ophthalmol 2009; 54:226
  15. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: A Controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology 1994;101:1883
  16. Herpetic Eye Disease Study Group. Acyclovir and the prevention of recurrent herpes simplex virus eye disease. N Engl J Med 1998:339;300
  17. Dhaliwal DK, Romanowski EG, Yates KA, et al. Experimental laser in situ keratomileusis induces the reactivation of latent herpes simplex virus. Am J Ophthalmol 2001;131:506-507
  18. 18.0 18.1 18.2 18.3 18.4 18.5 18.6 18.7 18.8 Rojas-Silva V, Rodriguez-Conde R, Cobo-Soriano R. Laser in situ keratomileusis in patients with a history of ocular herpes. J Cataract and Refract Surg 2007;33:1855-1859
  19. Davidorf JM. Herpes simplex keratitis after LASIK [letter]. J Refract Surg 1998;14:667
  20. Perry HD, Doshi SJ, Donnenfeld ED. Herpes simplex reactivation following laser in situ keratomileusis and subsequent corneal perforation. CLAO J 2002;28:69-71
  21. Gomez Garcia S, Pinero Bustamonte AM, Gutierrez Sanchez E, et al. Herpes simplex keratitis following laser in sity keratomileusis. Arch Soc Esp Oftalmol 2004;79:139-142
  22. Levy J, Lapid-Gortzak R, Klemperer Itamar et al. Herpes simplex virus keratitis after laser in sity keratomileusis. J Refract Surg 2006;22:509-511
  23. 23.0 23.1 Jarade EF, Tabbara KF. Laser in situ keratomileusis in eyes with inactive herpetic keratitis. Am J Ophthalmol 2001; 132:779-780
  24. 24.0 24.1 de Rojas Silva MV, Diez-Feijoo E, Javaloy J, et al. Prophylactic perioperative antiviral therapy for LASIK in patients with inactive herpetic disease. J Refract Surg 2005; 22:404-405