Keratitis

Diagnostic approach

• Eye examination
• Slit-lamp examination
• Fluorescein staining

Red flag features

• Severe eye pain
• Vision loss
• Hypopyon
• Corneal infiltrate or ulcer
• Corneal perforation

Management checklist

• Discontinue contact lens use.
• Provide analgesia for corneal pain.
• Bacterial keratitis: manage based on severity
• HSV keratitis: manage based on anatomical location of corneal involvement
• HZV keratitis: antiviral therapy for herpes zoster
• Photokeratitis: erythromycin OR bacitracin
• Refer to ophthalmology within 24 hours.

Keratitis is inflammation of the cornea. It is most commonly caused by bacteria; other causes include viruses (e.g., HSV, VZV), fungi, acanthamoebae, and UV exposure. Keratitis almost always manifests with eye pain. Other symptoms include eye redness, foreign body sensation, watery or purulent discharge, and blurry vision. Diagnosis is usually based on clinical findings, including from slit-lamp examination and fluorescein staining, but advanced diagnostic studies (e.g., corneal scrapings for microscopy, culture, and/or PCR) may be required. Treatment is based on the underlying cause and typically requires next-day ophthalmology follow-up.

Bacterial keratitis is the most common form of keratitis (∼ 90%). ^[1]

Etiology ^[2]

Causative pathogens differ between geographical regions. Polymicrobial keratitis can occur, especially after corneal trauma.

• Staphylococcus spp. (e.g., Staphylococcus aureus, Staphylococcus epidermidis)
• Pseudomonas spp. (e.g., Pseudomonas aeruginosa)
• Streptococcus spp. (e.g., Streptococcus pneumoniae)

Staphylococci and P. aeruginosa are the most common causes of bacterial keratitis in contact lens users. ^[3][4]

Risk factors ^[2]

• Contact lens use
• Poor contact lens hygiene
• Recent ocular trauma
• Recent ocular or eyelid surgery
• Immunocompromise

Clinical features ^[2]

• Progressive pain
• Eye redness
• Foreign body sensation
• Purulent discharge
• Photophobia
• Blurry vision
• Excessive tearing
• Conjunctival injection

Subtypes and variants

Pseudomonas keratitis

• Caused by P. aeruginosa
• Fulminant course with severe ulceration ^[5]
• Corneal perforation within 72 hours ^[4]

Diagnosis ^[2]

• Perform clinical evaluation of the painful red eye.
• Characteristic findings on slit-lamp examination and fluorescein staining include:
  • Corneal epithelial defects (e.g., corneal infiltrate, corneal ulcer)
  • Corneal stroma infiltration and inflammation
  • Anterior chamber reaction (e.g., cells and flare, hypopyon)
• Advanced diagnostic studies (e.g., corneal scrapings for microscopy, culture, and/or PCR) may be obtained by ophthalmology.

Treatment ^[2][6]

Approach ^[6]

• Discontinue contact lens use.
• Consult ophthalmology for the following: ^[2]
  • Diagnostic uncertainty
  • Severe or refractory disease
  • Elevated intraocular pressure
• Initiate topical antibiotics for bacterial keratitis.
• Consider topical cycloplegics (e.g., cyclopentolate).
• Consider topical corticosteroids under specialist guidance. ^[7][8]
• Provide analgesia for corneal pain.
• Evaluate for indications for hospital admission for bacterial keratitis.

Topical antibiotics for bacterial keratitis ^[6]

The choice of antibiotic therapy is based on severity and the risk of vision loss.

• Small (< 1 mm) peripheral infiltrates, minimal anterior chamber reaction
  • Non-contact lens wearers
    • Levofloxacin (off-label) ^[6]
    • OR ciprofloxacin (off-label) ^[6]
    • OR polymyxin B/trimethoprim (off-label) ^[6]
  • Contact lens wearers
    • Levofloxacin (off-label) ^[6] OR ciprofloxacin (off-label) ^[6]
    • AND polymyxin B/trimethoprim (off-label) ^[6]
• Medium (1.0–1.5 mm) peripheral infiltrates, mild anterior chamber reaction
  • Levofloxacin (off-label) ^[6] OR ciprofloxacin (off-label) ^[6]
  • AND polymyxin B/trimethoprim (off-label) ^[6]
• Large (> 1.5 mm) peripheral infiltrates, moderate to severe anterior chamber reaction ^[6]
  • Fortified tobramycin OR fortified gentamicin
  • AND fortified cefazolin OR fortified vancomycin

Disposition ^[2][9][10]

• Refer to ophthalmology within 24 hours.
• Indications for hospital admission for bacterial keratitis ^[6]
  • Severe eye pain
  • Vision-threatening keratitis
  • Impending corneal perforation
  • Concerns about treatment adherence

Prevention ^[2]

• Education on contact lens hygiene
• Prophylactic topical antibiotic therapy for corneal abrasions in contact lens wearers or following trauma

Complications ^[2]

• Vision loss
• Corneal perforation
• Corneal scarring
• Endophthalmitis
• Elevated intraocular pressure

Herpes simplex keratitis

Etiology ^[11][12]

• More commonly HSV-1 than HSV-2
• Usually results from latent infection rather than primary infection

Clinical features ^[10][11]

• Typically unilateral
• Eye pain
• Eye redness
• Foreign body sensation
• Clear discharge
• Photophobia
• Blurry vision
• Corneal hypesthesia

Subtypes and variants ^[11]

The subtypes of HSV keratitis are based on the anatomical location of corneal involvement.

• Epithelial HSV keratitis
• Stromal HSV keratitis
• Endothelial HSV keratitis

Diagnosis ^[6][11][13]

• Perform clinical evaluation of the painful red eye.
• Characteristic findings on slit-lamp examination and fluorescein staining include:
  • Epithelial HSV keratitis
    • Dendritic keratitis: corneal epithelial defect shaped in a thin, linear, tree-like pattern with terminal bulbs
    • Geographic ulcer: corneal ulcer in a large, map-like pattern
  • Stromal HSV keratitis
    • Corneal stromal haziness with stromal edema
    • May occur with or without adjacent or overlying corneal epithelial ulcer
  • Endothelial HSV keratitis
    • Corneal stromal and epithelial edema in a disc-shaped pattern with keratic precipitates
    • No marked anterior chamber reaction
• Consider diagnostics of HSV infection if there is diagnostic uncertainty.
• Advanced diagnostic studies (e.g., corneal scrapings for microscopy, culture, and/or PCR) may be obtained by ophthalmology.

Treatment ^[11][12][13]

Approach

• Initiate subtype-specific medical therapy.
• Avoid topical corticosteroid monotherapy.
• Provide analgesia for corneal pain.
• Refer to ophthalmology within 24 hours.

Epithelial HSV keratitis

• Topical antiviral therapy: trifluridine ^[11] OR ganciclovir ^[11]
• OR oral antiviral therapy
  • Dendritic keratitis
    • Acyclovir (off-label) ^[11]
    • OR valacyclovir (off-label) ^[11]
    • OR famciclovir (off-label) ^[11]
  • Geographic ulcer
    • Acyclovir (off-label) ^[11]
    • OR valacyclovir (off-label) ^[11]
    • OR famciclovir (off-label) ^[11]

Topical corticosteroids should not be used in the treatment of epithelial HSV keratitis. ^[11]

Stromal HSV keratitis

• Stromal HSV keratitis without corneal ulcer
  • Topical prednisolone (off-label) ^[11]
  • PLUS prophylactic oral antiviral therapy
    • Acyclovir (off-label) ^[11]
    • OR valacyclovir (off-label) ^[11]
• Stromal HSV keratitis with corneal ulcer
  • Topical prednisolone (off-label) ^[11]
  • PLUS oral antiviral therapy
    • Acyclovir (off-label) ^[11]
    • OR valacyclovir (off-label) ^[11]

Endothelial HSV keratitis

• Topical prednisolone (off-label) ^[11]
• PLUS oral antiviral therapy
  • Acyclovir (off-label) ^[11]
  • OR valacyclovir (off-label) ^[11]

Herpes zoster keratitis ^[14]

See also "Herpes zoster ophthalmicus."

Etiology ^[14]

• Reactivation of herpes zoster virus
• Occurs in the ophthalmic division of the trigeminal nerve

Clinical features ^[10][14][15]

• Prodrome: headache, fever, malaise
• Eye
  • Unilateral
  • Eye pain
  • Eye redness
  • Photophobia
  • Foreign body sensation
  • Blurry vision
• Associated skin findings
  • Vesicular rash in the V1 dermatome
  • Hutchinson sign of the nose

Diagnosis ^[14]

• Perform clinical evaluation of the painful red eye.
• Characteristic findings on slit-lamp examination and fluorescein staining include:
  • After 2 days: punctate corneal epithelial defects
  • After 4–6 days: punctate corneal epithelial defects resolving or coalescing into a pseudodendritic pattern.
  • After 1–2 weeks: anterior stromal infiltrates
• Advanced diagnostic studies (e.g., corneal scrapings for microscopy, culture, and/or PCR) may be obtained by ophthalmology.

Treatment ^[6][14][15]

• Initiate oral antiviral therapy for herpes zoster (e.g., acyclovir; , valacyclovir).
• Apply ophthalmic antibiotic ointment to skin lesions (e.g., bacitracin or erythromycin ^[6]).
• Provide supportive care, e.g.:
  • Apply warm compresses to the periocular skin three times a day.
  • Provide analgesia for corneal pain.
  • Administer refrigerated preservative-free artificial tears as needed.
• Refer to ophthalmology within 24 hours.

Adenovirus

See “Epidemic keratoconjunctivitis.”

Etiology ^[16]

Acanthamoeba keratitis is caused by Acanthamoeba infection.

Epidemiology ^[16]

• Rare (∼ 1.5% of microbial keratitis) ^[17]
• Most commonly associated with poor contact lens hygiene

Clinical features ^[16][18]

• Typically unilateral
• Severe pain
• Eye redness
• Photophobia
• Epiphora
• Vision loss

Misdiagnosis of Acanthamoeba keratitis is common. If a patient's symptoms do not improve after empiric treatment for other forms of keratitis, assess for Acanthamoeba keratitis. ^[16]

Diagnosis ^[16]

• Perform clinical evaluation of the painful red eye.
• Characteristic findings on slit-lamp examination and fluorescein staining include:
  • Corneal epithelial infiltrates
  • Corneal stromal infiltrates
  • Pseudodendrites
  • Radial keratoneuritis
  • Ring-shaped corneal stromal infiltrate (late finding)
• Consult ophthalmology for advanced diagnostic studies (e.g., corneal scrapings for microscopy, culture, and/or PCR).

Treatment ^[16][19]

Given the diagnostic challenge of Acanthamoeba keratitis, initiate diagnostic work-up and management in consultation with ophthalmology in patients with high clinical suspicion or confirmed cases.

• Initiate topical antiseptic (e.g., chlorhexidine, polyhexamethylene biguanide) AND propamidine.
• Consider topical cycloplegics (e.g., cyclopentolate).
• Consider oral anti-acanthamoebal agents (e.g., miltefosine, voriconazole).
• Avoid topical corticosteroids in the early stages of treatment. ^[2][18]
• Provide analgesia for corneal pain.
• Discontinue contact lens use and counsel on proper contact lens hygiene.
• Refer to ophthalmology within 24 hours.

Acanthamoeba keratitis refractory to treatment may require corneal transplantation or enucleation. ^[16]

Etiology ^[20][21]

• Common pathogens
  • Molds (e.g., Fusarium, Aspergillus)
  • Yeasts (e.g., Candida)
• Risk factors
  • Corneal injuries, especially caused by organic material
  • Contact lens use
  • Topical corticosteroid use
  • Ocular surface disease
  • Immunocompromise

Clinical features ^[6]

• Eye pain
• Eye redness
• Foreign body sensation
• Eye discharge
• Photophobia
• Blurry vision
• Excessive tearing

Diagnosis ^[6][21]

• Perform clinical evaluation of the painful red eye.
• Characteristic findings on slit-lamp examination and fluorescein staining include:
  • White corneal stromal infiltrate with a feathery border
  • Satellite lesions surrounding infiltrate
  • Anterior chamber reaction (e.g., cells and flare, hypopyon)
• Consult ophthalmology for advanced diagnostic studies (e.g., corneal scrapings for microscopy, culture, and/or PCR).

Treatment ^[6]

Given the diagnostic challenge of fungal keratitis, initiate diagnostic work-up and management in consultation with ophthalmology in patients with high clinical suspicion or confirmed cases.

• Initiate topical antifungals (e.g., natamycin, amphotericin B, voriconazole).
• Consider topical cycloplegics (e.g., cyclopentolate).
• Consider oral antifungal agents (e.g., fluconazole, itraconazole).
• Avoid topical corticosteroids.
• Provide analgesia for corneal pain.
• Discontinue contact lens use and counsel on proper contact lens hygiene.
• Refer to ophthalmology within 24 hours.

Photokeratitis ^[22]

• Definition: corneal epithelial damage caused by severe UV light radiation
• Etiology: significant UV exposure without protective eyewear (e.g., in occupations such as welding and during activities such as ; tanning and high-altitude sports) ^[22][23]
• Pathophysiology: UV damage leads to apoptosis and desquamation of the corneal epithelium. ^[22]
• Clinical features ^[22]
  • Onset within a few hours of UV exposure
  • Bilateral eye involvement
  • Severe eye pain
  • Eye redness
  • Foreign body sensation
  • Photophobia
  • Blurred vision
  • Excessive tearing
• Diagnosis ^[6]
  • Perform clinical evaluation of the painful red eye.
  • Characteristic findings on slit-lamp examination and fluorescein staining include:
    • Bilateral, confluent, punctate corneal epithelial defects
    • Spares the palpebral conjunctiva
  • Make a clinical diagnosis.
• Treatment ^[6]
  • Initiate topical prophylactic antibiotics (e.g., erythromycin ^[6], bacitracin ^[6]).
  • Administer refrigerated preservative-free artificial tears as needed.
  • Consider topical cycloplegics (e.g., cyclopentolate).
  • Provide analgesia for corneal pain.
  • Avoid contact lens use.
  • Prevent further UV exposure.
  • Refer to ophthalmology within 24 hours.
• Prognosis: resolves within a few days
• Prevention: UV-blocking eyewear

Exposure keratopathy

• Definition: keratitis caused by the inability to completely close the eyelids resulting in corneal drying
• Etiology: mainly caused by damage to the facial nerve (e.g., from a stroke)

Neurotrophic keratopathy

• Definition: keratitis as a result of corneal sensory loss due to paralysis of the 1^sttrigeminal branch
• Etiology
  • Nerve damage
  • Tumor in the nerve path region
  • Chronic herpes infection
• Clinical features
  • Decreased vision; dry eye
  • Early stage: absent corneal reflex; decreased tear break-up time; dry spots on corneal surface
  • Late stage: central circular/oval nonhealing corneal ulcer
  • Complication: corneal perforation
• Treatment
  • Early stage: artificial tears
  • Late stage: prophylactic antibiotic drops; tarsorrhaphy ; amniotic membrane transplantation and conjunctival flap