Overview

Keratitis is caused by the inflammation of the cornea, which is the dome-shaped tissue on the front of the eye covering the pupil and iris. This condition may be caused by oedema of the cornea, inflammatory cell infestation, and congestion of cilia. Corneal ulceration may also develop, potentially progressing to corneal blindness.

Keratitis can be classified into infectious and non-infectious types. Infectious keratitis is caused by microbial agents, including bacteria (the most common cause), viruses, fungi, and parasites. Non-infectious keratitis may result from trauma to the cornea, foreign bodies, dry eye disease, or allergic reactions.

Keratitis is particularly concerning in immunocompromised individuals, such as those with HIV/AIDS, diabetes mellitus, organ transplant recipients, patients undergoing chemotherapy, and individuals on long-term immunosuppressive therapy. The cornea is protected by both innate and adaptive immune mechanisms. Adaptive immunity involves Langerhans cells and cytokines. In immunocompromised patients, these defence mechanisms are diminished or dysregulated, increasing susceptibility to severe infections and complications.

This article will explore the causes of keratitis, the key clinical features, and the diagnostic and treatment challenges in immunocompromised patients.

Causes and risk factors

Keratitis is classified into infectious and non-infectious forms based on the underlying cause. Infectious keratitis includes microbial keratitis and viral keratitis.¹ Microbial keratitis involves bacteria, fungi, and parasites, with bacteria being the most common agents.

Risk factors for bacterial keratitis include contact lens use, ocular trauma, previous ocular surgery, and a history of keratitis. In developed countries, contact lens wear is the leading risk factor, while in developing countries, trauma predominates.² Common bacterial pathogens include Staphylococcus aureus, Streptococcus pneumoniae, atypical mycobacteria, Moraxella, and Nocardia.

Herpes simplex virus (HSV-1) is responsible for the occurrence of Herpes Simplex Keratitis (HSK), a major cause of monocular infectious blindness. The individual’s immune status influences susceptibility. Immunosuppressed patients are at increased risk, and children may experience more severe complications owing to stronger immune-mediated inflammatory responses.³ 

Herpes Zoster Keratitis (HZK) arises from reactivation of Varicella Zoster Virus and may affect any corneal layer. It is more common in immunocompromised patients. COVID-19 vaccination has been associated with a potential predisposition to Herpes Zoster Ophthalmicus.⁴ 

Adenoviral keratitis is mostly associated with conjunctivitis and may present with conjunctival haemorrhages. Preauricular lymphadenopathy is an important diagnostic feature. 

Fungal keratitis is a serious condition that may result in severe vision loss. Candida albicans keratitis is more frequently identified in immunocompromised patients. Risk factors include corneal trauma, contact lens-related injury, systemic disease, and topical corticosteroid use. 

Microsporidial keratitis causes keratoconjunctivitis, endophthalmitis, and stromal keratitis in both immunocompetent and immunocompromised individuals.⁵ It is difficult to distinguish this from viral keratitis. 

Acanthamoeba keratitis, caused by free-living amoebae, is relatively rare but severe.

Non-infectious keratitis may result from foreign bodies, collagen vascular diseases, xerophthalmia, or corneal ulcers.

Clinical features

Common symptoms of keratitis include:

• Blurred vision
• Redness
• Photophobia (light sensitivity)
• Localised corneal ulceration
• Localised corneal oedema
• Elevated intraocular pressure
• Keratoconjunctivitis
• Endophthalmitis
• Eyelid ptosis
• Stromal keratitis
• Pain

Diagnosis of keratitis

Keratitis is diagnosed using a combination of clinical examination, microbiological investigations, and advanced diagnostic tools.

Clinical examination

A detailed history and clinical examination are essential. In microbial keratitis, clinical features alone may be insufficient to identify the causative agent, necessitating microbiological testing. Many cases present with ambiguous findings. Standard evaluation of corneal ulcers includes characterising the ulcer and performing corneal scraping for laboratory analysis.⁶ 

A history of recurrent cold sores may support a diagnosis of HSK.⁷

• Epithelial HSK typically shows dendritic ulceration
• Stromal HSK is associated with lipid keratopathy and corneal vascularisation

HZK is often diagnosed clinically. Xerophthalmia is also typically identified clinically.

Microbiological evaluation

Microbiological workup includes smear examination and culturing corneal scrapings on various media.⁸ These may include blood agar, chocolate agar, cooked meat medium, and Sabouraud agar. Gram staining identifies organisms in 60–75% of bacterial cases.² When results remain unclear, a corneal biopsy may be required.

Viral culture is considered the gold standard for diagnosing epithelial HSK due to its high specificity.³

Fungal keratitis is diagnosed using staining and corneal scraping cultures. Direct microscopy helps identify fungal filaments. Additional media such as brain–heart infusion and thioglycollate broth may be used.

In vivo confocal microscopy is a non-invasive imaging technique that enables real-time detection of filamentous fungi or Acanthamoeba cysts, providing earlier diagnosis.⁹

Microsporidial keratitis can be identified using calcofluor white and Ziehl–Neelsen staining. Transmission electron microscopy offers precise identification of microsporidial spores.

Polymerase chain reaction (PCR)

The polymerase chain reaction (PCR) test is used extensively to diagnose microbial keratitis. It is a sensitive, rapid molecular technique used to detect specific DNA sequences, offering quicker results than staining or culture. However, limitations include false positives, high costs, and technical expertise requirements.^10,11

PCR is particularly useful for diagnosing atypical mycobacteria and Nocardia species.¹²

In viral keratitis, PCR can detect HSV DNA from corneal scrapings or swabs, although it cannot differentiate viral shedding from active infection.

PCR is also effective in diagnosing HZK, fungal keratitis, and Acanthamoeba keratitis, allowing early initiation of targeted therapy.

Future diagnostic directions

Emerging technologies include metagenomic next-generation sequencing (NGS), which can identify all microorganisms present in a sample and is useful in complex or atypical cases.

Deep-learning algorithms are being explored for automated diagnosis of microbial keratitis. Artificial intelligence also facilitates remote ophthalmic assessment.

Management of keratitis

Bacterial keratitis

The treatment for bacterial keratitis starts with topical antibiotics. Cycloplegic agents can be applied for anterior chamber inflammation. Fortified cefazolin or vancomycin, combined with fluoroquinolones, tobramycin or gentamicin, provides broad coverage against gram-positive and gram-negative organisms. Topical corticosteroids may be introduced after 2–3 days of antibiotics, once the causative organism has been identified.^12-14

Viral keratitis

• HSK: Topical acyclovir (five times daily) and oral antivirals are used to prevent recurrence. Topical steroids may be added for stromal disease
• HZK: Primarily treated with oral acyclovir
• Recurrent infections: Lubricants and prophylactic antibiotics may be used
• Neurotrophic ulcers: Treated with serum therapy, amniotic membrane transplantation, or tarsorrhaphy
• Adenoviral keratitis: Highly contagious; strict hygiene is essential

Fungal keratitis

Treatment includes topical antifungals, cycloplegics, and antibiotics for secondary bacterial infections. Surgery may be required in advanced cases.^13,14

• Microsporidial keratitis: Often treated with therapeutic penetrating keratoplasty
• Filamentous fungi: Treated with topical natamycin
• Candida keratitis: Treated with amphotericin B
• Aspergillus keratitis: Voriconazole may be used alongside natamycin

Acanthamoeba keratitis is treated with topical polyhexamethylene biguanide or chlorhexidine. Severe cases may require therapeutic penetrating keratoplasty.

Non-infectious keratitis

• Foreign body keratitis: Immediate removal under local anaesthesia
• Shield ulcers: Treated with topical steroids, cyclosporine, and lubricants
• Peripheral ulcerative keratitis: Managed with topical steroids and systemic immunosuppressants
• Xerophthalmia: Managed with vitamin A supplementation per WHO guidelines

Summary

Keratitis is inflammation of the cornea and can be severe in immunocompromised individuals due to impaired immune defences. It can be infectious (bacterial, viral, fungal, parasitic) or non-infectious. Bacterial keratitis is the most common infectious form. Viral keratitis may be caused by HSV, HZV, or adenovirus, while fungal keratitis may be caused by numerous fungal pathogens.

Diagnosis involves clinical assessment, microbiological studies, PCR, and emerging technologies such as NGS and artificial intelligence. Management varies depending on the causative organism and may involve antibiotics, antivirals, antifungals, steroids, lubricants, or surgery. Prompt diagnosis and effective treatment are essential to prevent complications and preserve vision.