Is It Microbial or Viral?

Infectious keratitis is one of the leading causes of blindness worldwide.¹ It can be classified as either microbial (bacterial, parasitic, or fungal) or viral. Despite diverse etiologies, it can be challenging for clinicians to determine the underlying organism based on signs or symptoms alone. Microbial and viral corneal infections can share similar findings and often present with nonspecific symptoms, such as pain, redness, light sensitivity, and decreased vision. This article breaks down the different types of keratitis, with information on causes, diagnosis, and treatment.

MICROBIAL KERATITIS

In the United States, contact lens wear is the leading risk factor for the development of microbial keratitis.² The most common type of microbial keratitis is bacterial.

Polymerase chain reaction tests can be used to confirm an initial diagnosis and/or to identify the type of pathogen in suspected microbial keratitis. The use of polymerase chain reaction tests has become more common because of their ease of use and quick turnaround.

Bacterial Causes

The bulk of bacterial keratitis cases involve small, noncentral ulcers that can be managed with topical antibiotics and frequent follow-up.¹ As with most corneal infections, potential risk factors include contact lens wear, ocular surface disease, trauma, and ocular surgery.^1,2

The organisms to blame vary depending on location and cause of infection. Common culprits in the United States include Gram-negative bacteria such as Pseudomonas aeruginosa and Gram-positive bacteria such as Staphylococcus aureus (Figure 1), Coagulase-negative staphylococci, and Streptococcus pneumonia. Many cases are polymicrobial.² Bacteria such as P. aeruginosa are known to cause larger, less defined, and more suppurative infiltrates. Other potentially defining characteristics of Gram-negative keratitis include rapid progression and tissue destruction and more severe inflammation in the first 48 hours, despite therapy.^1,3

Treatment of bacterial infections depends on the severity of the patient’s condition. According to the ARMOR study, antimicrobial resistance data should be considered when selecting an empirical treatment for bacterial keratitis.⁴

The American Academy of Ophthalmology’s Bacterial Keratitis Preferred Practice Pattern recommends obtaining smears and cultures in the following incidences¹:

1. Large (≥ 2 mm) and/or central (≤ 3 mm) corneal infiltrate with significant stromal involvement or melting

2. Grade 1 or more cells in the anterior chamber

3. History of corneal surgery

4. Atypical clinical features

5. Multiple corneal infiltrates

Fortified antibiotics should be considered for large and visually significant corneal infiltrates, especially if a hypopyon is present.¹ Fortified antibiotics are not always easily accessible because they require a compounding pharmacy and are typically higher in cost than commercially available antibiotics.

The adjunctive use of steroids remains controversial but may be considered further along in the treatment process for bacterial keratitis to help reduce inflammation and subsequent scarring.^1,2,5

Parasitic Causes

Acanthamoeba is a microscopic protozoa (aka unicellular eukaryote) that can be free-living or parasitic. It is found worldwide in environmental sources such as soil and water.⁶ Risk factors for Acanthamoeba keratitis include trauma, poor hygiene, and inadequate contact lens care.³ In the United States, about 85% of cases occur in contact lens wearers. Given Acanthamoeba’s presence in water, clinicians should advise patients to remove their contact lenses before swimming and showering.

Acanthamoeba keratitis often has a poor prognosis because it is difficult to diagnose and even more difficult to treat. It can mimic other microbial infections, which can add to the delay in its diagnosis.^1,3 A defining symptom is pain that is disproportionate to clinical findings. Other potential signs include an irregular epithelium, pseudodendrites, ring-shaped infiltrates, and radial keratoneuritis.^1,3,7Acanthamoeba can be detected through cultures, corneal scrapings, polymerase chain reaction tests, and confocal microscopy. Most treatment protocols involve a combination of biguanides, diamidines, antibiotics, and antifungals and can take months to resolve the infection.^3,7

Fungal Causes

Fungal keratitis can be challenging to identify (Figure 2).³ Anterior segment OCT imaging of the cornea is becoming a great tool for differentiating between pathogens, with fungal keratitis often appearing as small or large cystic spaces on corneal OCT imaging.

A common association of fungal keratitis is corneal injuries that involve vegetative matter, such as soil. Additionally, fungal keratitis can be seen in immunocompromised patients or those who’ve had ocular surgery.⁸ Two main categories of fungal pathogens are molds or filamentous fungi, such as fusarium and aspergillus, and yeasts such as candida. They vary in prevalence based on location, with molds being seen more often in tropical and subtropical climates.^3,8

Signs of fungal keratitis include corneal lesions with feathery or fuzzy borders, satellite lesions, endothelial plaques, and pigment in corneal lesions. Not developing a dense infiltrate as quickly and/or not responding to antibiotics may also indicate fungal keratitis.^3,8

The best opportunity for recovery is early identification and aggressive antifungal treatment.³ Treatment of fungal infections is challenging given that options are limited in availability, have poor penetration with an intact epithelium, and are toxic to the ocular surface.⁸

Three of the most common topical treatments for fungal ulcers are natamycin (Natacyn, Santen), amphotericin B, and voriconazole. Natamycin is the only FDA-approved medication for fungal keratitis in the United States, and it is the preferred treatment for fusarium. Amphotericin B has greater fungicidal activity toward yeasts such as Candida albicans.⁸ Voriconazole is available topically and orally; however, one study showed that adding oral voriconazole to a topical antifungal treatment regimen did not provide additional benefit.⁹

VIRAL KERATITIS

Viral keratitis is one of the most prevalent forms of infectious keratitis. There are a plethora of DNA and RNA viruses that can have corneal involvement.³ Two of the most common offenders seen in clinic are herpes simplex virus (HSV) and varicella zoster virus (VZV).¹⁰

Both HSV and VZV keratitis can involve multiple corneal layers, including the epithelium, stroma, and endothelium.⁹ In the epithelium, findings can be more distinctive compared with other layers.³ For example, one of the manifestations of HSV epithelial keratitis is the classic branching dendrite that stains brightly with fluorescein centrally and has terminal end bulbs that stain with rose bengal. In VZV epithelial keratitis, mucus plaques, or pseudodendrites can also be branching but will have a more elevated or “stuck-on” appearance that lacks central ulceration.³ Pseudodendrites are not exclusive to VZV and can be associated with other forms of infectious keratitis, such as Acanthamoeba keratitis.⁷

Treatment of HSV or VZV keratitis will vary depending on the structures involved. For example, HSV epithelial keratitis can be treated with topical or oral antivirals, while HSV stromal disease typically involves the use of oral antivirals and topical steroids.^4,10

USE THE CLUES TO DIAGNOSE AND TREAT

Depending on the clinical setting, optometrists are likely to encounter at least one form of infectious keratitis in their careers. Although the case may not be straightforward, it is critical to consider all the pieces of the puzzle to quickly identify the cause and offer proper treatment to help maximize visual outcomes. It is also imperative to recognize when referral to an ophthalmologist is the best option.