Microbial keratitis

Summary

Microbial Keratitis is an inflammation of the cornea secondary to infection. In this article, we will discuss the various forms of microbial keratitis, including their presenting features and management.

Bacterial Keratitis

Aetiology

In most cases, bacterial keratitis only occurs where the ocular defences have been compromised, for example following an abrasion. It is typically common for this reason in contact lens wearers, particularly those who use soft lenses. The most common pathogens include:

• Pseudomonas aeruginosa

• Staphylococcus aureus

Some bacteria however are able to penetrate through the intact corneal epithelium, without there being a prior abrasion or defect. A nice way to remember this is the organisms that can create a “CNHL”

Cornyebacterium

Haemophilus

Neisseria species (gonorrhoea and meningitis

Listeria

Bacterial keratitis seldom occurs in healthy, normal eyes. Risk factors include:

• Contact lens wear

• Trauma

• Ocular surface disease: e.g. dry eye, chronic blepharitis, trichiasis, entropion, exposure, severe allergic eye disease, corneal anaesthesia

• Vitamin A deficiency and immunosuppression

⭐ Pseudomonas aeruginosa is responsible for >60% of contact-lens associated keratitis!

Clinical features

Pain, conjunctival injection, photophobia, blurred vision, mucopurulent discharge, hypopyon, anterior chamber flare

Diagnosis

Corneal scraping may be useful, particularly in cases of epithelial defects. Samples can be placed in various culture media in order to highlight the various possible organisms, a summarised table can be found below.

Management

• Discontinuation of contact lenses

• Empirical broad spectrum antibiotics to be initiated before culture sensitivities are back, usually a fluoroquinolone

• Most cases may be managed with a low intensity antibiotic and/or topical steroid, with a pause in contact lens use.

• Prevention: correct contact lens use education, and use of protective eye wear during sports and other dangerous activities

A case of bacterial keratitis caused by Pseudomonas aeruginosa. Note the diffuse conjunctival infection and mucopurulent discharge. Image courtesy of Bouhenni et al

Fungal Keratitis

Aetiology

Fungal keratitis is a major cause of visual loss in developing and tropical countries. There are two main types of fungus that can cause keratitis:

• Yeasts (e.g, Candida), more common in temperate climates

• Filamentous fungi (e.g. Fusarium and Aspergillus), more common in tropical climates

Risk factors include:

• Long term topical steroids (often associated in corneal transplant patients)

• Systemic immunosuppression, diabetes

• Trauma, particularly involving organic/agricultural material

• Contact lenses

Clinical features

• Symptoms often have a more gradual onset

• Stromal infiltrates with fluffy margins

• Satellite lesions

• Feathery branch-like or ring shaped extensions

• Candida infection typically is characterised by a small ulcer with an expanding infiltrate in a ‘collar stud’ formation

Diagnosis

Corneal scrapes (see table below) using Sabourand dextrose agar will grow fungal organisms. Polymerase chain reaction (PCR) is rapid and highly sensitive. Confocal microscopy may allow in vivo visualisation of the organisms

Management

General education measures on contact lens hygiene are important, as for bacterial keratitis. Topical antifungal agents: first line for candida infection is amphotericin B, and first line for filamentous species is natamycin. In some cases, a broad spectrum antibiotic may be considered to prevent bacterial co-infection.

Differentiating fungal keratitis (left) with feathery margins, from bacterial keratitis (right) displaying a defined margin. Image courtesy of Leck et al

(A) Multiple satellite infiltrations (arrow) in the left eye. (B) One week later, the infiltration size increased; endothelium plaques and hypopyon (arrow) were also noted. Image courtesy of Huang et al

Herpes Simplex Keratitis

💡 Herpes eye disease is the most common cause of infectious blindness in the developed world

Aetiology

Herpes simplex virus (HSV) is a double-stranded DNA virus encased by a cuboidal capsule. After primary infection by the virus, it is carried to the sensory root ganglion for the dermatome where the virus is incorporated into host DNA and remains latent. Stressors such as fever, stress, infection or trauma may result in reactivation where the virus is shed to the periphery via the sensory axons, as it uses host DNA to replicate. Symptoms depend on the pattern of reactivation, which can be far away from the initial infection site.

We will cover two types of of corneal inflammation due to HSV: epithelial keratitis and disciform (endothelial) keratitis.

Epithelial keratitis

This form of keratitis is associated with HSV reactivation and active virus replication. It is characterised by the classical “linear-branching” dendritic (tree-like) ulcer, most frequently located centrally and staining well with fluoroscein. Virus laden cells at the margins of the ulcer stain well with rose bengal. Reduced corneal sensation is characteristic of a viral keratitis.

A case of HSV keratitis, with the characteristic dendritic, branching ulcer, staining well with fluroscein. Image courtesy of Gilani et al

Disciform (endothelial) keratitis

The aetiology of this type of keratitis is more complex: thought to result from a hypersensitivity reaction of the cornea to the HSV antigen as opposed to direct infection. Discomfort tends to be of a milder and more gradual onset than in epithelial disease. Characteristic signs include central circular stromal oedema, keratic precipitates, and a Wessely ring: this is an antigen/antibody complex within the stroma.

Diagnosis

Diagnosis for HSV keratitis is usually clinical, however corneal scrapings can be placed in viral culture media, with Giemsa stain.

Management

Epithelial keratitis: Topical aciclovir. Topical steroids are avoided: this is because they increase the risk of corneal perforation.

Disciform keratitis: Topical/oral aciclovir, with topical steroids, ensuring that the epithelium is intact before commencing.

💡 Review corneal anatomy to understand the different layers targeted by these two forms of HSV keratitis, to help better remember the symptoms and features!

Acanthamoeba Keratitis

Aetiology

Acanthaemoeba are a protozoa species found in soil, , dust, fresh water sources), brackish water (such as a marsh), and sea water. It is a feared complication in contact lens wearers, resulting from swimming or showering in contacts, or rinsing them in tap water.

Clinical features

Patients usually report pain which is out of proportion to the clinical picture. Early signs are not too specific and misdiagnosis with herpetic or fungal keratitis can be made. The pathognomonic sign is perineural infiltrates, which may coalesce to form ring abscess.

Diagnosis

Corneal scrapings again can be cultured using periodic acid–Schiff or calcofluor white. Immunohistochemistry, PCR and in vivo confocal microscopy are also options.

Management

Acanthamoeba cysts are resistant to most antimicrobial agents. Polyhexamethylene biguanide (PHMB) or chlorhexidine have been proven to be amoebicidal. Topical steroids should be avoided during active infection. Pain control with NSAIDs may be of symptomatic benefit.

Characteristic ring shaped infiltrate seen in Acanthamoeba keratitis, Image courtesy of Chomicz et al

Summary

	History	Clinical features
Bacterial	Contact lens wear, trauma, or ocular surface disease	Conjunctival injection, mucopurulent discharge, anterior chamber flare, hypopyon if severe. Epithelial defect may be present
Fungal	Trauma involving agricultural material, immunosuppression, contact lens wear	Feathery branch like extensions, satellite lesions
Viral	Primary infection is normally in childhood with a mild systemic infection. Reactivation results in ocular disease	Punctate/stellate pattern, linear branching with reduced corneal sensation
Protozoa	Contact lens wear, history of swimming/showering	Pain out of proportion with clinical findings, characteristic perineural infiltrates, which may coalesce to form ring abscess

Culture media for corneal scrapings

Blood agar	Most bacteria and fungi (except Haemophilus, Neisseria, Moraxella)
Chocolate agar	Fastidious bacteria (e.g. Haemophilus, Neisseria, Moraxella, the ones not picked up on blood agar)
Sabouraud agar	Fungi
Non-nutrient agar seeded with E.coli	Acanthamoeba
Cooked meat broth	Streptococci, Meningococci
Lowenstein-Jensen	Mycobacteria, Nocardia

Stains for corneal scrapings

Gram	Bacteria, fungi
Giemsa	Bacteria, fungi, acanthamoeba
Calcofluor white	Acanthamoeba, fungi
Ziehl-Neelson stain	Mycobacterium, nocardia
Grocott-Gomori methenamine silver	Fungi, acanthamoeba
Periodic-acid Schiff (PAS)	Fungi, acanthaemoeba

References

1. Salmon, John F., and Jack J. Kanski. Kanski’s Clinical Ophthalmology: A Systematic Approach. Ninth Edition, Elsevier, 2020.

2. Bouhenni, Rachida, et al. ‘Proteomics in the Study of Bacterial Keratitis’. Proteomes, vol. 3, no. 4, Dec. 2015, pp. 496–511. PubMed Central, https://doi.org/10.3390/proteomes3040496.

3. Leck, Astrid, and Matthew Burton. ‘Distinguishing Fungal and Bacterial Keratitis on Clinical Signs’. Community Eye Health, vol. 28, no. 89, 2015, pp. 6–7. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579991/.

4. Huang, Yi-Hsun, et al. ‘Early Diagnosis and Successful Treatment of Cryptococcus Albidus Keratitis: A Case Report and Literature Review’. Medicine, vol. 94, no. 19, May 2015, p. e885. PubMed, https://doi.org/10.1097/MD.0000000000000885

5. Gilani, Christopher J., et al. ‘Differentiating Urgent and Emergent Causes of Acute Red Eye for the Emergency Physician’. The Western Journal of Emergency Medicine, vol. 18, no. 3, Apr. 2017, pp. 509–17. PubMed, https://doi.org/10.5811/westjem.2016.12.31798

6. Chomicz, Lidia, et al. ‘Emerging Threats for Human Health in Poland: Pathogenic Isolates from Drug Resistant Acanthamoeba Keratitis Monitored in Terms of Their In Vitro Dynamics and Temperature Adaptability’. BioMed Research International, vol. 2015, 2015, p. 231285. PubMed, https://doi.org/10.1155/2015/231285