Herpes simplex keratitis is a frequent and potentially blinding disease characterized by recurrent corneal involvement with the herpes simplex virus (HSV). Currently, it is the leading cause of infectious corneal ulcers and blindness in the world. There are several types of herpes simplex virus, out of which, the two common types that affect humans are the HSV-1 and HSV-2; HSV-1 is normally present in the oral, labial and ocular region, whereas HSV-2 affects genital region. Primary infection with HSV occurs through contact with mucocutaneous surfaces, a time which the virus may not be evident. Primary infection of HSV occurs, and the virus is transported to the dorsal root ganglia, although it may later become active and recur as subsequent infections in the same dermatome. 

HSK can occur as the initial episode of ocular herpes simplex virus or as recurrent episode. After the primary infection in the eye, further infection develops in the eye and, through the trigeminal nerve to the trigeminal ganglion. This gets activated by the virus bringing it back to the cornea, in this case leading to inflammation of the structures of the eye such as the conjunctiva, cornea, the front chamber of the eye, the iris, the lens, vitreous body and the retina. 

• Frequency in the United States
  HSV-1 antibodies are present in 50 to 90% of all the adults within the United States suggesting that they have been previously infected by the virus. The estimated prevalence of ocular HSV infection is 0.15%. The estimated incidence of new cases of ocular HSV each year ranges from 17,000 to 20,000, and over 28,000 reactivation cases occur annually. Ocular HSV is a major cause of blindness in the U.S; approximately 500,000 patients are affected with HSV ocular disease. 
• International Occurrence
  Around the world, HSV infection is rather high, approximately a third of citizens get recurrent infections and most individuals present with mucocutaneous lesions such as oral herpes. 
• Sex- and Age-Related Demographics
  Concerning the sex distribution, herpes simplex has been reported to slightly affect more males. HSV eye disease usually affects adults and, in most instances, it manifests many years after the primary infection, and the average age of presentation is between 40 and 50 years. In children, herpetic keratitis tends to affect the epithelium and stroma of the cornea and carries a risk of bilateral disease and frequently recurring attacks, leading to amblyopia. 

HSV belongs to DNA virus and is easily transmitted among people mainly through close contact with lesions or secretions which contain the viruses. Oral – ocular disease is normally esteemed due to HSV-1 while genital disease is normally esteemed because of HSV-2. However, HSV-2 can also cause ocular infection through direct mouth to genital contact, and it can also be transmitted through genital HSV-2 infected mothers during delivery. 

First episodes of HSV-1 are usually seen in mucocutaneous form of trigeminal nerve which may appear like a viral pharyngitis. Subsequently, the virus invades epithelial cells and moves up to neural ganglia via nerve axons to get residing in the trigeminal ganglion. This implies that subsequent ocular disease can occur in an individual without having to have a primary ocular HSV infection. 

Recurrent ocular HSV has classically been described to originate from reactivation in the trigeminal ganglion, with the virus spreading towards the ocular tissues through the nerve axons, resulting in a lytic infection. 

The causes of various manifestations of HSV keratitis are as follows: 

• Infectious epithelial keratitis: This may occur because of heightened viral replication within the corneal epithelial cell layer. 
• Neurotrophic keratopathy: This condition is not well understood, and it is thought to be the result of multiple factors. 
• Necrotizing stromal keratitis: Originates from direct infection of the corneal stroma, which causes formation of a robust inflammatory reaction in the host. This condition was said to be associated with the use of topical corticosteroids that lack antiviral properties may contribute to the development of this condition. 
• Immune stromal keratitis: From an antibody-complement dependent process which occurs mainly with retained viral antigen or altered host antigens in the stroma. 
• Endothelitis: Traditionally assumed to be an immunological response to antigens in endothelial cells, however the contribution of the active virus engagement is still a factor of debate. 

Like most herpes viral infections, the prognosis for HSV keratitis is usually favorable if the disease is adequately managed. Small and simple dendritic ulcers do not need treatment and usually heal within a few days. Localized infection with the yeast can be easily treated with two weeks topical antifungal agents sometimes with local curettage as needed. Yet, epithelial or disciform keratitis lasting for a long time ends with scarring, vascularization, and in some cases, the loss of vision’s acuity. 

Age Groups Affected 

Children: Often seen with first episode herpes gingiva stomatitis and ocular lesions can result from auto inoculation. 

Adults: Mainly involving recurrent herpes simplex keratitis in the third and fifth decades of the affected person’s life. 

• Visual Acuity Assessment: This test involves measuring both distance and near visual acuity to assess how keratitis might affect eyesight. 
• External Examination: Assess the eyelids, lashes, and the periocular skin for erythema or edema. 

• Immunocompromised Individuals: Higher risk of developing complications and of having a more serious and frequent illness. 
• Contact Lens Wearers: These groups are more susceptible to infections because they are likely to have corneal injuries and prolonged exposure to the pathogens. 
• Stress or Immune Suppression: Previously identified factors that cause the viral particles to become active resulting in flare-ups. 

•  Mild to Moderate Cases: Usually manifested by symptoms such as pain that is localized on one side of the eye, redness and hypersensitivity to light. 
• Severe Cases: May present in dendritic or geographical corneal ulceration and reduces the vision acuity if not controlled early. 

Antiviral Therapy: 

Topical Antivirals: Application of trifluridine or ganciclovir gel immediately after day of the procedure to reduce the viral shedding and replication in the corneal tissue. 

Systemic Antivirals: For severe or recurrent forms systemic antiviral such as acyclovir, valacyclovir or famciclovir may be prescribed and incorporated in topical preparations. 

Corticosteroids: 

Topical Corticosteroids: When administered orally after the viruses are replication to calm the inflammation which may cause sclerosis formation.
Systemic Corticosteroids: Given in high doses and only for the severe patients because of the possible boost in the rate of replication of the virus.

Supportive Therapy: 

Artificial Tears: For application of lubricants to decrease the manifestations of dryness and to treat the corneal epithelial diseases.
Pain Management: Use of non–steroidal anti-inflammatory drugs or applying something cold on the pain and swelling.

Procedural Interventions: 

Debridement: Debridement to enhance the likelihood of antiviral effectiveness, because dead tissues or invasive pathogens need to be removed.
Surgical Options: In a worst-case scenario where the scarring has become severe, or the structures have been perforated, further action entails the use of the amniotic membrane transplantation or therapeutic keratoplasty.

Long-term Management: 

Suppressive Therapy: They may make decisions for long-term oral antiviral therapy for episodes and manage to keep corneal clarity.
Monitoring and Follow-up: More follow ups for recovery, review vision and to monitor any side effects. 

Ophthalmology

Cold Compresses: In cases where the closure of eyelids is possible, cooling with ice packs may be helpful in reducing congestion, as well as for providing symptomatic relief in the early stages. 

Eye Hygiene: Stress proper handling and cleaning of the eyes pointing out that attempting to remove crusting by rubbing or using harsh soap can worsen the situation and lead to secondary bacterial infection. 

Artificial Tears: The application of preservative-free artificial tears can help to reduce dryness and sustain appropriate lubrication on the corneal abrasion, therefore promoting epithelial cell regeneration. 

UV Protection: Counsel the patient to use protective eyewear such as sunglasses while in the sun as UV light can bring on the virus. 

Avoidance of Triggers: Inform the patient the following: Common trigger factors are stress, exposure to sunlight, and from contact lenses if any should avoid it. 

Ophthalmology

• Trifluridine ophthalmic solution 1% (Viroptic): It is a structural analogue of thymidine that works by interfering with the synthesis of viral DNA due to its ability to bind with viral DNA polymerase. It has excellent penetration through the cornea and equally it has high effectiveness rate (healing rate of 95%) than other topical agents. If no improvement of symptoms is observed in 7-14 days, it is necessary to switch to other treatments. 
• Valacyclovir (Valtrex): It is an antiviral agent easily hydrolyzed into acyclovir, that gives similar effects to acyclovir at higher serum concentrations with reduced oral doses. It is more expensive than acyclovir, but its administration is less frequent and the efficacy of the medication is comparable to acyclovir when it comes to treating ocular herpes. The dose that provides the best outcomes in treating ocular herpes remains unknown. 
• Famciclovir (Famvir): It is a substrate which is metabolised to penciclovir which exercises it antiviral effect through the inhibition of viral DNA synthesis and replication. Well known for the genital herpes suppression, its effectiveness for HSV keratitis is still under investigation. 
• Acyclovir (Zovirax): Like vidaforin, acyclovir is a synthetic guanosine that needs first to be phosphorylated by viral thymidine kinase. Because it accumulates in HSV-infected cells, the replication of viral DNA is halted by preventing viral DNA polymerase from functioning without proving to be poisonous to normal cells. Systemic oral acyclovir at a dose of two gm per day for 10 days is as effective as topical agents in treating epithelial keratitis with nearly zero ocular side effects. 
• Ganciclovir ophthalmic gel 0. 15% (Zirgan, Vitrasert): It is an acyclic nucleoside which when delivered into virus infected cells is phosphorylated to active forms by host kinases. This again prevents HSV replication through competing with the viral DNA polymerases and incorporating into typical viral DNA in a position which is not favorable for DNA continuation. Having the virostatic effect, ganciclovir is active only to the replicating virus like acyclovir. 

Ophthalmology

• Debridement: The removal of necrotic epithelial tissue or infectious material from the cornea by mechanical debridement is helpful in burning lesions and assists in the healing process and decrease viral load in cases of persistent epithelial defect and dendritic ulcerations. 
• Corneal Scraping: If massive viral replication or nonhealing ulcers are present, superficial corneal scrapings under local anesthesia might be made to improve the response of the viral pathogens to the antiviral treatment. 
• Amniotic Membrane Transplantation: In this operation, a translucent, blue-colored thin film of fresh amniotic sac is carefully laid over the cornea to form a protective bandage as it heals and reduces inflammation while promoting epithelial growth. It may be useful in conditions with injury of the epithelium or prolonged inflammation. 
• Corneal Patch Grafting: In some chronic or extensive corneal ulcers, a patch graft comprising of donor corneal tissue can be utilized to cover the ulcerated region with an aim of healing the ulcer and minimizing the probabilities of perforation. 
• Therapeutic Keratoplasty: In very special and severe situations when there is intense scar formation or corneal perforation then therapeutics keratoplasty (transplantation of corneal) is required to reconstruct corneal structure and for better vision. 

Ophthalmology

The overall approach to the management of herpes simplex keratitis is therefore divided into various subphases for optimum therapy and prevention of recurrence.  

First, during the acute stage, the choice of an antiviral agent such as trifluridine or ganciclovir in the form of gel is clearly required to prevent the replication of the virus and reduce the manifestations of the disease. The following steps include assessment of the client’s reaction to the treatment, changes in the therapy plan, and supportive care that could involve eye irrigation and application of artificial tears.  

The chronic or recurrent cases may necessitate the long-term low dose oral antiviral therapy to minimize the flare ups and careful observation for complications such as corneal scarring. In all phases of management, patient education on factors causing flares and compliance with treatment can be very helpful in improving the overall quality of life of the patient with this chronic viral ailment to the eyes.