Introduction

Herpetic keratoconjunctivitis is a viral infection that affects the eyes and is a significant cause of blindness worldwide. It is primarily caused by Herpes Simplex Virus type 1 (HSV-1), and less frequent cases arise from Varicella-Zoster Virus (VZV). It affects both the conjunctiva (the thin layer that covers the surface of the eye) and cornea, and is significant for its recurrence. Once the initial infection subsides, the virus remains inactive in the trigeminal ganglion and can be reactivated repeatedly, each episode potentially leading to deterioration of the eye surface.

Although symptoms may resolve with proper treatment during an acute flare, the repeated damage from each episode, such as scarring, corneal thinning, and neovascularisation, may eventually lead to irreversible vision loss. Widely developing elective ocular procedures such as LASIK, as well as the vast use of contact lenses, have made awareness and management of this condition even more critical. The cornea is a thin transparent structure which focuses light onto the retina. Corneal damage occurs due to infection, inflammation, or trauma. Corneal involvement refers to the deterioration of its clarity or structure due to epithelial damage, immune responses, or direct injury. These injuries compromise the cornea’s barrier function, making it vulnerable to further abuse.

Causes and types of corneal involvement

Infectious causes

• Herpes Simplex Keratitis (HSK): HSV-1 is the primary cause. Initial infection involves the outermost layer of the corneum and is followed by viral dormancy in the trigeminal ganglion. When reactivated, the virus causes repeated corneal ulcers, connective tissue inflammation, or issues involving blood vessels. Severe and rare cases may affect both eyes, resulting in corneal melting or perforation^1,5
• Herpes Zoster Ophthalmicus (HZO): reactivation of VZV along the ophthalmic branch of the trigeminal nerve results in pain, skin eruptions, and deep ocular involvement
• Other microbial infections: bacterial, fungal, and Acanthamoeba infections are commonly seen in contact lens users. These often progress rapidly, producing corneal ulcers and scarring if not addressed early²

Non-infectious triggers

• Dry Eye Syndrome: Prolonged dryness damages the epithelium and makes the eyes vulnerable to viral reactivation
• Autoimmune diseases: Disorders such as Sjögren’s syndrome and Mooren’s ulcer incite immune-mediated damage, paving the way for the reactivation of dormant virus⁴
  Chemical and mechanical trauma: Burn injuries or physical trauma damage the protective barrier of the cornea, paving the way for viral or bacterial pathogens

Medical causes

• Surgical interventions: Ophthalmic surgeries (LASIK, corneal cross-linking, cataract procedures) may trigger HSV reactivation in patients with previous infections, especially in the absence of antiviral medication⁹
• Contact lens abuse: Improper use of contact lenses, such as overuse, poor cleaning, or wearing them overnight, can lead to microtears and amplify the risk of infection²

Pathophysiology of corneal damage and healing

HSV penetrates the corneal surface at the onset of infection and later remains inactive within the nerves. Fever, injury, ultraviolet (UV) light exposure, or emotional stress are some of the common factors that trigger reactivation of the virus. This in turn results in epithelial lesions and inflammation. Although the immune system acts effectively in controlling the virus, the damage to the cornea cannot be reversed.

Repeated inflammation may cause:

• Loss of epithelial integrity
• Destruction of connective tissue
• Formation of scar tissue
• Growth of abnormal blood vessels (neovascularisation)

Eventually, frequent episodes can damage corneal nerves, resulting in neurotrophic keratopathy, a condition marked by reduced sensation, poor healing, and recurrent ulcers.⁴

Risk factors for recurrence

Recurrence in herpetic keratoconjunctivitis is quite common, shifting its focus on prevention rather than management. People with compromised immunity, such as those who are HIV-infected or are undergoing corticosteroid therapy, are more prone to frequent and more severe viral reactivations.¹ The risk of recurrence elevates when patients fail to complete the entire course of prescribed antiviral medications, as stopping treatment prematurely can enable the virus to reactivate.³ Moreover, corneal graft recipients may be infected with various strains of HSV, which complicates both diagnosis and treatment.⁵ External factors, such as exposure to UV light, fever, and hormonal changes, particularly during menstruation, are well-established triggers that reactivate the dormant virus.⁶ Misuse of corticosteroids, especially without simultaneous antiviral coverage, can result in uncontrolled viral replication, thereby exacerbating the infection.⁶ Additionally, unclean contact lenses or excessive wear can also trigger recurrence episodes as they cause mechanical irritation of the cornea.² Identifying and managing these triggers is essential for effective long-term disease control and the preservation of vision.

Clinical presentation and diagnostic approach

Symptoms of infection:

• Redness
• Eye pain
• Light sensitivity
• Blurred vision
• Excess tearing
• Sensation of a foreign object in the eye

Signs on examination:

• Classic dendritic ulcers, which are sores similar to branches of a tree
• Connective tissue becomes cloudy
• Reduced corneal reflexes
• Vascular growth in the cornea

The most common tests to diagnose epithelial defects are slit-lamp examination and fluorescein dye. Confirmation can be achieved using PCR to detect HSV DNA or confocal microscopy.¹⁰ Cultures and immunofluorescence testing offer additional, though less sensitive, options. A complete and elaborate clinical history is crucial to differentiate it from other eye diseases.

Management and prevention strategies

During acute episodes of herpetic keratoconjunctivitis, early treatment plays a vital role in preventing viral replication and minimising ocular damage. Antiviral drugs, such as topical ganciclovir and systemic medications like acyclovir or valacyclovir, are the first-choice medicines as they help reduce the viral load. When the deep layers, such as connective tissue or blood vessels, are involved, corticosteroids are recommended for their anti-inflammatory action. They should always be taken along with antiviral agents to prevent viral exacerbation.⁶ Supportive measures such as topical antibiotics are given if a bacterial coinfection is suspected, cycloplegics to relieve ciliary spasm and improve comfort, and lubricants which manage dryness and protect the outer surface.

Preventive and maintenance care aim to minimise recurrence and long-term damage. Long-term antiviral treatment with oral acyclovir (typically 400 mg twice daily) is recommended for patients with a history of repeated episodes or those who have undergone corneal transplantation, as it aids in reducing the risk of flare-ups and graft rejection.^7,8 In patients with neurotrophic keratopathy or dry eye, treatments such as artificial tears, punctal occlusion using plugs, or autologous serum eye drops are administered to promote epithelial healing.

In advanced and non-healing cases, surgery is the best choice of treatment. Amniotic membrane grafts to encourage regeneration of the epithelium, while penetrating keratoplasty (PKP), or full-thickness corneal transplantation, is suitable for cases with significant scarring or thinning. It is important to note that even after transplantation, HSV can recur, threatening the graft survival.⁸

Long-term care and maintenance involve not only medication and other interventions but also patient education. Regular monitoring is crucial to rule out recurrences. Strict adherence to therapy and implementing preventive strategies can significantly reduce complications and safeguard vision.¹⁰

Prognosis and complications

Repeated infections of herpetic keratoconjunctivitis can endanger vision as it causes permanent corneal scarring and opacification. In severe cases, the damage may result in corneal thinning and eventual rupture or perforation. Chronic involvement of the eyes can cause dryness, discomfort, and inflammation, contributing to long-term ocular surface disorders. Additionally, herpes simplex virus (HSV) remains a main indication for corneal transplantation, and without continuous antiviral therapy, there is a notably high chance of graft rejection and recurrence.⁸

Conclusion

Herpetic keratoconjunctivitis is a chronic, vision-threatening condition. It needs careful observation throughout life. Even with effective antiretroviral therapy, the risk of recurrence remains higher. Early treatment, proper medication, awareness and education with watchfulness help in managing this condition effectively. Ongoing research and targeted therapies can offer hope for the future.