Herpes simplex keratitis is caused by recurrent infection of the cornea by herpes simplex virus (HSV). The virus is most commonly transmitted by droplet transmission, or less frequently by direct inoculation. Herpes keratitis remains the leading infectious cause of corneal ulcers and blindness worldwide.
HSV is enveloped and has a linear double-stranded DNA genome. It has two subtypes: HSV-1 and HSV-2, each affecting different regions of the body. The following etiological factors are responsible for the spread of the disease:
Primary infection may become latent, which may be reactivated later in life due to a variety of stressors such as fever, trauma, immunosuppression, hormonal change and radiation exposure, etc.
Herpetic eye disease is the most prevalent infectious cause of corneal blindness in developed countries. Seroprevalence of HSV-1 is over 50% in the US while more than 75% in Germany. Approximately 10 million people worldwide may have herpetic eye disease. The global incidence (rate of new disease) of herpes keratitis is about 1.5 million, including 40000 new cases of severe monocular visual impairment or blindness each year.
Dendritic keratitis showed the most frequent recurrences (56.3%), followed by stromal keratitis (29.5%), and geographical lesions (9.8%). The greater the number of previous attacks, the greater the risk of recurrence. It also depends upon various external insults, e.g., fever, trauma, etc.
Corneal epithelial cells express specific receptors (Nectin 1, HVEM and PILR-alpha, etc.) that facilitate viral entry into the cells. Primary infection with the virus is commonly subclinical, and the only manifestation may be mild, self-limiting blepharoconjunctivitis. The cornea is rarely involved in primary infection. During this phase, however, the virus is carried to the sensory ganglion for that dermatome (e.g., trigeminal ganglion) and becomes latent. Recurrent infection occurs when this latent virus becomes reactivated (due to a variety of stressors such as fever, trauma, immunosuppression, etc.) in the ophthalmic branch of trigeminal ganglion and subsequently results in shedding at the corneal surface. Recurrence may be limited to the epithelium with the virus replicating in and destroying epithelial cells (dendritic/geographical keratitis). Or it may go on to involve the deeper endothelial layer (disciform/stromal keratitis). Another theory for the development of the endothelial disease is that it is essentially an autoimmune response. Studies showed that HSV-1 protein represented an antigenic mimic that triggered an immune reaction against the corneal antigens.
The patient may give a history of previous episodes, corneal abrasion due to contact lens wear, or oral or nasal sores. They might be taking topical or systemic steroids. The patient might have a history of immune deficiency state, or even recent fever or sun/UV exposure.
It is commonly subclinical, and the only manifestation may be mild, self-limiting blepharoconjunctivitis, marked by inflammatory vesicles or ulcers and can include lesions in the corneal epithelium. Mild fever, malaise, or upper respiratory tract infection may also be present.
Dendritic/Geographical keratitis presents with pain, foreign-body sensation, light sensitivity, redness, and blurred vision. Corneal sensations eventually get reduced. Patients with Disciform keratitis may experience similar symptoms. However, discomfort and redness tend to be milder than epithelial disease. They also complain of haloes around lights.
Any or all of the following may characterize infection:
A nonhealing epithelial defect, sometimes after prolonged topical treatment. May be associated with stromal melting and perforation.
Vesicles on eyelids/skin, conjunctivitis, uveitis and/or retinitis.
Workup of HSV keratitis proceeds in the following manner:
Treatment depends upon the type of disease from which the patient is suffering.
It is the same as that of persistent epithelial defects. The use of steroids should remain at a bare minimum.
The treatment is broadly similar to that of disciform keratitis, but much aggressive antiviral therapy may be beneficial.
Keratoplasty is the last resort when the disease causes irreversible corneal damage. However, recurrence of the disease of rejection threatens the survival of grafts.
Prophylaxis should merits consideration in patients with frequent recurrences or those with bilateral disease. Acyclovir 400 mg twice daily is standard, but if necessary, a higher dose is an option. Oral valaciclovir or famciclovir are alternatives to acyclovir. Prophylaxis reduces the rate of recurrence by about 50%.
The prognosis of HSV keratitis is generally favorable with therapy. The majority of dendritic ulcers heal spontaneously without treatment. Mild to moderate disease recovers with just 2 weeks of topical therapy reinforced with debridement if needed. However, prolonged epithelial or disciform keratitis may lead to scarring and vascularization, and visual acuity may be lost.
Patient education should focus on the avoidance of overcrowding and poor hygiene. Hand-eye contact should be avoided as much as possible, particularly scratching the eye with dirty hands. Regular handwashing should be encouraged. Infected individuals should keep themselves isolated from close family and friends to avoid spread. Once the patient has the diagnosis, they need to understand its nature and mode of propagation along with necessary preventive measures. They should also receive adequate counsel about possible complications due to inadequate treatment compliance.
The physician should always consider herpetic corneal disease in any patient presenting with keratitis. Often, the dendritic lesion may show some days after the initial conjunctivokeratitis.
Herpes keratitis is a very common infection that is often first seen by the primary care provider, nurse practitioner, or the emergency department physician. These clinicians should always consult with the ophthalmologist before starting any treatment. The disease needs to be dealt with in time to avoid morbidity. Coordination among healthcare professionals is vital for better patient outcome. Ophthalmologists, opticians, dermatologists, nurses, and pharmacists all need to work in coherence to tackle the disease and all the possible complications. Even after treatment, the patient should be closely followed until the symptoms have subsided, and the visual acuity is normal. Surgeons also need to be onboard since surgery may be the only last resort. Interprofessional communication is the key to manage the problem at its core appropriately.
An interprofessional healthcare team approach is necessary. The physicians will decide the course of treatment and prescribe appropriate therapy. Nursing can assist in patient education about the disease, as well as assess therapeutic effectiveness and patient compliance. Pharmacists should verify dosing and perform medication reconciliation to ensure the absence of drug-drug interactions. Any concerns form nursing or pharmacy should be reported to the treating physicians promptly. Herpes keratitis management will be optimized by this type of interprofessional, collaborative approach, leading to better patient outcomes. [Level 5]
|||Xu F,Sternberg MR,Kottiri BJ,McQuillan GM,Lee FK,Nahmias AJ,Berman SM,Markowitz LE, Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006 Aug 23; [PubMed PMID: 16926356]|
|||Rabenau HF,Buxbaum S,Preiser W,Weber B,Doerr HW, Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am Main area, Germany. Medical microbiology and immunology. 2002 Mar; [PubMed PMID: 12005327]|
|||Liesegang TJ, Epidemiology and natural history of ocular herpes simplex virus infection in Rochester, Minnesota, 1950-1982. Transactions of the American Ophthalmological Society. 1988; [PubMed PMID: 2979036]|
|||Darougar S,Hunter PA,Viswalingam M,Gibson JA,Jones BR, Acute follicular conjunctivitis and keratoconjunctivitis due to herpes simplex virus in London. The British journal of ophthalmology. 1978 Dec; [PubMed PMID: 737165]|
|||Labetoulle M,Auquier P,Conrad H,Crochard A,Daniloski M,Bouée S,El Hasnaoui A,Colin J, Incidence of herpes simplex virus keratitis in France. Ophthalmology. 2005 May; [PubMed PMID: 15878072]|
|||Shah A,Farooq AV,Tiwari V,Kim MJ,Shukla D, HSV-1 infection of human corneal epithelial cells: receptor-mediated entry and trends of re-infection. Molecular vision. 2010 Nov 20; [PubMed PMID: 21139972]|
|||Shimeld C,Hill TJ,Blyth WA,Easty DL, Passive immunization protects the mouse eye from damage after herpes simplex virus infection by limiting spread of virus in the nervous system. The Journal of general virology. 1990 Mar; [PubMed PMID: 2156001]|
|||Liesegang TJ, Classification of herpes simplex virus keratitis and anterior uveitis. Cornea. 1999 Mar; [PubMed PMID: 10090358]|
|||Knickelbein JE,Hendricks RL,Charukamnoetkanok P, Management of herpes simplex virus stromal keratitis: an evidence-based review. Survey of ophthalmology. 2009 Mar-Apr; [PubMed PMID: 19298901]|
|||Zhao ZS,Granucci F,Yeh L,Schaffer PA,Cantor H, Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science (New York, N.Y.). 1998 Feb 27; [PubMed PMID: 9478893]|
|||Darougar S,Wishart MS,Viswalingam ND, Epidemiological and clinical features of primary herpes simplex virus ocular infection. The British journal of ophthalmology. 1985 Jan; [PubMed PMID: 3965025]|
|||JONES BR, The clinical features of viral keratitis and a concept of their pathogenesis. Proceedings of the Royal Society of Medicine. 1958 Nov; [PubMed PMID: 13614398]|
|||Green LK,Pavan-Langston D, Herpes simplex ocular inflammatory disease. International ophthalmology clinics. 2006 Spring; [PubMed PMID: 16770152]|
|||Chang EJ,Dreyer EB, Herpesvirus infections of the anterior segment. International ophthalmology clinics. 1996 Summer; [PubMed PMID: 8989597]|
|||Wilhelmus KR, Diagnosis and management of herpes simplex stromal keratitis. Cornea. 1987; [PubMed PMID: 3319411]|
|||Chodosh J,Banks MC,Stroop WG, Rose bengal inhibits herpes simplex virus replication in vero and human corneal epithelial cells in vitro. Investigative ophthalmology [PubMed PMID: 1321799]|
|||Spencer WH,Hayes TL, Scanning and transmission electron microscopic observations of the topographic anatomy of dendritic lesions in the rabbit cornea. Investigative ophthalmology. 1970 Mar; [PubMed PMID: 4313568]|
|||Porter SM,Patterson A,Kho P, A comparison of local and systemic acyclovir in the management of herpetic disciform keratitis. The British journal of ophthalmology. 1990 May; [PubMed PMID: 2191712]|
|||Pavan-Langston D,Foster CS, Trifluorothymidine and idoxuridine therapy of ocular herpes. American journal of ophthalmology. 1977 Dec; [PubMed PMID: 413436]|