Dry Eye Dx and Tx

Herpes Simplex and Dry Eye

Dry Eye Dx and Tx

Herpes Simplex and Dry Eye


Herpes Simplex virus (HSV) keratitis is a plague for patients and a management challenge for clinicians. The myriad of clinical presentations makes the possibility of its existence ever-present with each new case corneal pathology that enters our offices. Dormant Herpes Simplex infection within the trigeminal ganglion may reactivate, manifesting as infectious and/or immunologic etiologies such as epithelial keratitis, neurotrophic keratopathy, stromal keratitis, and endothelialitis.

The herpes virus is a DNA virus; therapeutic agents interfere with its DNA transcription, hence halting viral replication within infected corneal cells. New to the therapeutic market is Zirgan ganciclovir ophthalmic gel (Bausch + Lomb), preserved with benzalkonium chloride, that selectively targets DNA viral replication in active corneal epithelial disease. Zirgan is a welcome alternative to the thimerosal-preserved, nonselective antiviral Viroptic trifluridine ophthalmic solution (GlaxoSmithKline).

Herpetic Stromal Keratitis

Stromal corneal inflammation (interstitial stromal keratitis, ISK) may be a primary manifestation of herpetic disease or may arise secondary to epithelial, neurotrophic, or endothelial forms of herpetic disease. ISK is commonly a chronic, recurrent, frustrating entity for both practitioner and patient. It is generally accepted that the underlying mechanism of ISK is inflammation arising from retained viral antigen within the stroma. Steroid therapy is indicated for herpetic stromal disease to avoid stromal scarring, uveitis, trabeculitis, secondary glaucoma, and cataracts.

Triggers for HSV reactivation from latency include stress, lack of sleep, shoulder stiffness, and physical fatigue with reactivation rates highest between spring and summer (Shimomura, 2008). Interestingly, there is an association between quiescent stromal herpetic keratitis and dry eye. It was demonstrated that both eyes of patients who have herpetic HSV keratitis were dry, even if the keratitis was in only one eye. Patients with unilateral quiescent HSV stromal keratitis had significantly lower bilateral tear production as demonstrated via Schirmer testing as compared to age-matched normals (Simard-Lebrun et al, 2010). Supporting this, an earlier study proposed that patients who have herpetic stromal keratitis may suffer demyelination of both trigeminal root entry zones as a result of unilateral eye infection by the herpes virus or that dryness predisposes the eye to herpetic infection or recurrent inflammation (Keijeser et al, 2002).

Reducing the HSK-Dry Eye Cycle

The concept that the "stress" of dry eye predisposes an individual to HSV infection or disease reactivation is interesting. Corroborating evidence for this comes from Sheppard and colleagues (2009) who found that prophylactic punctal cautery or topical administration of cyclosporine 0.05% (Restasis, Allergan) in patients who have simultaneous stromal HSK and dry eye disease each provide significant benefit by minimizing HSK frequency and duration of recurrences. Cyclosporine is an immunomodulator that inhibits activation of T cells. Understanding that the pathological mechanism of stromal HSK is not active viral infection but viral antigens initiating a T-lymphocytic destruction of the stroma also helps explain the suggested success of cyclosporine for stromal HSK.

It is important to recognize that the use of Restasis has not been studied by Allergan and its use in cases of HSK is considered off-label. Hopefully ongoing study will elucidate the role and treatment of dry eye as related to HSV keratitis. It is an intriguing circle. CLS

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Dr. Mastrota is secretary of the newly formed Ocular Surface Society of Optometry (OSSO). She is center director at the New York Office of Omni Eye Services and is a consultant to Allergan, AMO, B+L, Inspire, Noble Vision, and Cynacon Ocusoft. You can reach her at