Overview

Keratitis is one of the most common eye illnesses, resulting in partial or total vision loss.

While various viruses have been found to cause keratitis (e.g., rhabdoviruses, coxsackieviruses, herpesviruses) are the most common cause of viral keratitis. 

Early detection of viral keratitis is advantageous for disease management and responsiveness to therapy.

Introduction

The cornea, the clear layer of tissue covering the pupil and iris, becomes inflamed when keratitis strikes.

Microbial or ulcerative keratitis is distinguished by corneal epithelial defect and suppurative stromal infiltration.¹

Infectious keratitis, a subtype of microbial keratitis, can be brought on by bacterial, fungal, viral, or parasitic infections of the cornea.
Viral keratitis (VK) is the most common among infectious keratitis.

The HSV is the most common cause of viral keratitis.

Others include the beta-herpesvirus cytomegalovirus (CMV), the alpha-herpes varicella-zoster virus (VZV), and the gamma-herpesvirus Epstein-Barr virus (EBV).¹

Around 6 million people worldwide suffer from corneal conditions, including infectious keratitis, which impair vision, according to the most current World Health Organisation (WHO) data.

Keratitis due to herpes

Herpes simplex virus is of two types: type 1 and type 2. The genitalia are the primary site of infection for HSV-2, whereas the eyes are more frequently affected by HSV-1.

Four subtypes of herpes simplex keratitis (HSK) are distinguished by the kind of corneal layer that is damaged or the neuronal cell infection: epithelial, stromal, endothelial, or neurotrophic keratitis (Holland and Schwartz, 1999).¹

One form of stromal keratitis that primarily affects the stroma and has minimal effect on the eye's endothelium or epithelium is called interstitial keratitis.

Epithelial keratitis - granular spots, progressing to punctate lesions and then to branching dendritic lesions loaded with active viruses

Stromal keratitis -  ≥ 20–48% of ocular HSV cases, causes scarring and neovascularisation of the cornea.

Endothelial keratitis -  inflammation of the endothelium occurs, leading to endothelial dysfunction rather than stromal inflammation.

Neurotrophic keratitis damages the nerves which innervate the cornea, resulting in reduced sensitivity.

Keratitis due to CMV

Symptoms include anterior chamber inflammation, ocular oedema, and coin-shaped keratin precipitates.

Usually, there is no impact on the cornea's outermost layers. In addition, patients may develop anterior uveitis, endothelial cell loss, and elevated intraocular pressure.

The presence of stromal keratouveitis followed by opaque, branching epitheliopathy without ulcers was noted in spite of oral and topical antiviral therapy.¹ 

In an AIDS patient, CMV stromal keratitis was separately noted and resolved with systemic ganciclovir treatment.

Keratitis due to VZV

The production of smaller, less terminal bulb-like pseudodendrites, also known as punctate keratitis, is a clinical symptom of corneal epithelia.

The nature of corneal lesions has been described as pleomorphic, raised, and grey. In the affected eye, patients with VZV keratitis describe pain, tears, and a feeling of a foreign body.

Keratitis due to EBV

EBV keratitis might manifest as dendritic epithelial lesions. Symptoms associated with stromal keratitis include decreased vision, photophobia, corneal irritation, and ring-shaped or multifocal granular anterior stromal opacities that do not extend to adjacent stromal regions.

What happens in viral keratitis?

Among other things, elderly people have fragile corneal epithelium, poor lacrimal drainage, altered lids and conjunctival bacteria, altered immunological responses, and decreased corneal sensitivity.³

Due to these age-related changes, older patients may be more vulnerable to specific keratitis-causing substances. Viral keratitis can be treated topically with antiviral medications and adjuvant topical corticosteroids ⁴

For infection management and visual rehabilitation, corneal transplantation may be necessary for infectious keratitis.⁵

In most affluent countries, viral keratitis is the leading cause of unilateral infectious corneal blindness, with herpes simplex keratitis accounting for 1.5 million cases worldwide.

The goal of safe, effective treatment is to relieve symptoms, promote corneal repair, and speed up visual recovery.⁸

Herpetic keratitis is frequently linked to neurotrophic keratopathy, which can lead to poor corneal healing, a higher chance of developing IK, and further corneal problems like melting and perforation.⁶

Risk factors

Contact lens wear, trauma and ocular surface diseases are the three most common risk factors of IK.

Diagnosis

Keratitis is diagnosed based on a comprehensive slit lamp examination and subsequent laboratory tests. Patients can provide corneal samples using a swab, spatula, scalpel, or spud.

Although viral culture is considered the gold standard for epithelial HSK, its low sensitivity limits its application in clinical settings. PCR on corneal scrapings from an active lesion may be a more sensitive and faster diagnostic approach.³  

Treatment

Idoxuridine (IDU) was the first antiviral drug used to treat herpes simplex keratitis and was introduced by 1962.²

Since then, Idoxuridine has been used to treat epithelial herpes simplex keratitis.⁷
According to the HEDS, corticosteroids reduced the average duration of stromal keratitis symptoms from 72 days to 26 days.

Ocular and orofacial HSV disease relapse rates were decreased after a year of daily acyclovir medication, according to the HEDS Acyclovir Prevention Trial.¹

Glucocorticoids and antiviral nucleoside analogues: Acyclovir (ACV), a nucleoside analogue that functions as a competitive inhibitor of the viral DNA polymerase, is commonly used.
ACV analogues include trifluridine, cidofovir, brincidofovir, ganciclovir, and valacyclovir.
Topical trifluorothymidine can alleviate necrotising keratitis in patients.

Glucocorticoids prescribed include prednisolone, dexamethasone and loteprednol. They reduce inflammation and pain at the site of infection, but do not target the viral infection directly.¹

Corneal gluing is a procedure in which cyanoacrylate-based adhesive is used to seal small, < 3 mm wide perforations in the cornea.

Amniotic membrane transplants (AMTs)  are used for neurotrophic ulcers to heal and provide growth factors.

Anterior lamellar transplants have better outcomes than penetrating keratoplasty operations, but they are inferior when patients have deep scarring of the cornea or endothelial involvement.¹

Intrastromal injection of Bevacizumab could result in the regression of neovascularisation in patients with neurotrophic keratitis secondary to HSV infection. ²

Omnilenz® was used to manage corneal epithelium defects successfully.

A special hydrogel contact lens to carry Acyclovir and Valacyclovir was designed by  Varela-Garcia et al.

PROSE special contact lenses were designed for clearing chronic corneal opacities.

Topical Tacrolimus helps to improve visual acuity and reduce corneal inflammation, neovascularisation, and cornea scarring.²

Von Willebrand factor helps to deliver therapeutics to prevent scarring and poor vision secondary to a damaged corneal surface.

Live-attenuated vaccines are used in preventing outbreaks of HSK.

Topical steroids reduce the risk of stromal progression of HSK by up to 60%.

Herpetic keratitis is the leading cause of cornea ulcer and corneal perforation in the world. Recurrence of the condition predisposes the individual to developing cornea ulcer and perforation.

Topical therapeutic management is plagued with many factors, including corneal epithelial toxicity to antiviral drops and the development of tolerance.²

Drops formulated from peripherally derived autologous blood help to heal Herpes simplex keratitis, of neurotrophic HSV keratitis.

Oral treatment may be preferable in patients who have ocular surface disease or a poor tear film. Avoid systemic treatment in patients known to have poor renal function.⁷

Aciclovir 3% ointment, five times a day for seven days, then three times a day for 7 days.⁴

Aciclovir 400 mg orally, five times a day for 7–10 days.

Ganciclovir 0.15%, 5 times daily until the ulcer has healed, then three times a day for 7 days.

Trifluridine 1% solution, 4–8 times a day.

Idoxuridine 0.5% ointment or IDU 1% solution, 5 times a day.

Prophylaxis regimen for prevention

Aciclovir 400 mg orally twice a day.

For Herpes zoster ophthalmicus - Oral aciclovir 800 mg five times a day for 7 days.

For non-ocular involvement at onset, treatment must start within 72 hours of the onset of blisters.

Topical  Aciclovir 3% ointment, five times a day for seven days, then twice a day until dendrites have resolved.⁷

Topical ganciclovir Ganciclovir 0.15%, five times a day, until the ulcer is healed.

Systemic valacyclovir 1 g orally three times a day for 7 days.

Systemic famciclovir 500 mg orally three times a day for 7 days.

For CMV retinitis, Systemic treatment includes: Systemic oral valganciclovir. Induction dose: 900 mg orally twice a day for 14–21 days, followed by a maintenance dose of 900 mg orally once a day.⁷

Systemic intravenous ganciclovir Induction dose: 5 mg/kg/dose every 12 hours for 1–21 days, followed by a maintenance dose of 5 mg/kg once a day.

Intravitreal ganciclovir - 2.5 mg in 0.1 ml once a week.

Conclusion

Despite being mostly preventable and treatable, infectious keratitis (IK) is the fifth most common cause of blindness globally, making it a serious global health concern.
Thus, prompt and precise identification is crucial for managing the condition and avoiding irreversible corneal damage.
It is generally acknowledged that senior patients should utilise oral antiviral drugs with greater caution because of the higher likelihood of changed pharmacodynamics.

The precise risk factors for infectious keratitis in the elderly, such as systemic disorders and abnormalities affecting the surface of the eyes, require further investigation.
Treatment recommendations tailored to the aged are required, taking into account their particular physiological changes and any comorbidities.