Diagnosis → Ophthalmology

Keratitis

Etiology

Cause [43s][eci]

• Bacterial: Staphylococcus spp. (direct invasion or antigen-mediated), Streptococcus spp. (blocked nasolacrimal duct), Pseudomonas aeruginosa (contact lens–related), Serratia spp., Haemophilus influenzae, Moraxella spp., Enterobacteriaceae, MRSA, Nocardia spp., nontuberculous mycobacteria (post-surgical)

• Fungal: Fusarium spp., Aspergillus spp., Candida spp. (post-transplant, immunocompromised); dematiaceous fungi, Curvularia spp.

• Viral: HSV, VZV, adenovirus, EBV, enterovirus

• Parasitic: Acanthamoeba spp., microsporidia, Onchocerca volvulus, Pythium

• Non-infectious:

  • Trauma: Trichiasis, foreign body, Giant papillary conjunctivitis

  • Immune-mediated connective tissue disease: Rheumatoid arthritis, sarcoidosis, granulomatosis with polyangiitis, polyarteritis nodosa, systemic lupus erythematosus, ocular rosacea, vernal/atopic keratoconjunctivitis

  • Neurotrophic corneal ulcer: Herpes zoster ophthalmicus, trigeminal nerve damage

  • Exposure keratopathy --> Xerophthalmia

  • Toxic/medication-related: NSAIDs, anesthetics, preservatives, corticosteroids

Pathophysiology [43s]

1. Disruption of corneal epithelial barrier → loss of the primary defense mechanism

   • Contact lens wear, trauma, surgery, ocular surface disease, Vitamin A deficiency

2. Pathogen adherence and stromal invasion

   • Inflammation --> polymorphonuclear leukocytes and macrophages

   • Inflammatory cells --> Proteases/hydrolase/toxins --> Tissue destruction

   • Starts with epithelial ulceration: Usually seen in HSV → dendritic ulceration

   • Stromal infiltration: Immune-mediated disciform or necrotizing stromal keratitis

3. Host inflammatory response

   • Corneal edema

   • Leukocyte infiltration

   • Neovascularization

   • Anterior chamber reaction (hypopyon in bacterial/fungal)

   • Severe pain

Risk Factors [eci]

• Contact lens wear

• Ocular trauma

• Previous ocular surgery

• Ocular surface disease: dry eye, blepharitis, neurotrophic keratopathy, lid malposition

• Topical corticosteroids

• Systemic immunosuppression / HIV

• Substance abuse

• Developing-world with limited access to care

Complications [43s]

• Corneal scarring and opacification

• Corneal melting (keratolysis) --> thinning --> perforation:

  • Endophthalmitis

  • Iris prolapse

  • Anterior dislocation of the lens

  • Anterior capsular cataract

  • Corneal fistula

  • Purulent uveitis

  • Intraocular hemorrhage

  • Corneal scarring- nebula, macula, leucoma, adherent leucoma

  • Keratectasia

  • Disorganized anterior chamber

  • Autoevisceration

  • Phthisis bulbi

• Secondary glaucoma

• Iridocyclitis

• Cataract

• Recurrent disease

• Permanent monocular blindness

Epidemiology

Incidence per 100.000 [oss][pnc][wtb][k1w]

Default

Approach

• Slit-lamp examination: Ulcer size, location, depth, and margins of infiltrate/ulcer, fluorescein staining, anterior chamber reaction

  • Bacterial: suppurative infiltrate >1 mm, indistinct edges, epithelial defect, hypopyon

  • Fungal: feathery borders, fixed hypopyon, satellite lesions

  • HSV epithelial: characteristic dendritic ulcer with terminal bulbs

  • Acanthamoeba: ring infiltrate, perineural infiltrates, severe pain, contact lens history

• Corneal scraping for smear and culture (gold standard):

  • Infiltrate is central and/or >2 mm with stromal involvement or melting

  • Chronic or unresponsive to empiric broad-spectrum antibiotics

  • History of corneal surgery or transplant

  • Multifocal infiltrates

  • Sight-threatening/severe presentation

• Corneal smear stains:

  • Gram stain (bacteria; sensitivity 60–75%)

  • Giemsa stain (bacteria, fungi, Acanthamoeba; sensitivity 40–85% for fungi)

  • Calcofluor white-KOH (fungi, Acanthamoeba)

  • Acid-fast stain (Mycobacteria, Nocardia)

• Corneal culture

• PCR/NAAT

  • HSV/VZV NAAT (high sensitivity 70–100%)

  • Acanthamoeba NAAT (most sensitive)

  • Multiplex PCR for bacteria if culture-negative

  • Do not use on contact lens case/solution (high false-positive rate)

• In vivo confocal microscopy: sensitivity 80–94% for fungal keratitis

• Anterior segment OCT: Measure of infiltrate size, depth, and corneal thinning

Treatment

1. Remove contact lenses immediately [43s]

2. Obtain corneal scrapings for smear and culture before starting antimicrobials

3. Cycloplegic agent (cyclopentolate or atropine 1%)

4. Xerophthalmia: Vitamin A supplementation

5. Mild bacterial keratitis

   • Topical fluoroquinolone monotherapy 3–4 times/day

   • Ciprofloxacin 0.3%

   • Ofloxacin 0.3%

   • Levofloxacin 1.5%

   • MRSA: Vancomycin or topical linezolid 0.2%

   • Pseudomonas: Oral doxycycline is added and topical imipenem-cilastatin

   • Nocardia: Topical fortified amikacin (2.5%)

   • Atypical mycobacteria: Topical fortified amikacin (4%) or Clarithromycin (2%)

6. Severe/central bacterial keratitis (infiltrate >2 mm, stromal melting, hypopyon)

   • Complete coverage against both gram-positive and gram-negative organisms

   • Fortified cefazolin 5%

   • Tobramycin

   • Gentamicin

7. Protozoal keratitis: Biguanides and pentamidine

8. Oomycete keratitis: Topical linezolid (0.2%) + topical and oral azithromycin

9. Fungal keratitis: Albendazole (400 mg twice daily for 3-4 weeks) and topical fumagillin

10. Viral keratitis: Topical Acyclovir 3% x 5 (+ oral Acyclovir 400 mg x 5)

11. Herpes zoster ophthalmicus: Oral Acyclovir 800 mg x 5 for 1 week

12. Local causes --> correction of pathology:

    • Trichiatic lashes: electrolysis of eyelash hair root follicle

    • Distichiasis: lid splitting procedure

    • Entropion: lid everting procedure

    • Giant papillary conjunctivitis: Topical steroids + topical cyclosporine + lubricants

    • Removal of a foreign body

13. Systemic causes: Topical and oral steroids or methotrexate

14. Perforated corneal ulcer:

    • Cyanoacrylate tissue adhesive glue or amniotic membrane graft

Differential diagnoses

Blepharitis, Conjunctivitis, Corneal abrasion, Corneal ulcer, Endophthalmitis, Entropion, Foreign body, Glaucoma, Herpes zoster, Iridocyclitis, Keratoconjunctivitis sicca, Nasolacrimal duct obstruction, Periorbital cellulitis, Rosacea, Scleritis, Sebaceous carcinoma, Stevens-Johnson syndrome, Subconjunctival hemorrhage, Toxic epidermal necrolysis