Corneal Ulcer

Defect in the surface epithelium of the cornea that involves the underlying stroma

• Potentially vision-threatening ocular emergency

---

Etiology

Corneal ulcers affect all groups but are much more common in those who wear contact lenses, especially extended wear lenses.

Bacterial Corneal Ulcer:

Most common etiology of corneal ulcers is infectious, with bacterial pathogens responsible for a majority of the cases. Ulcers start as keratitis (inflammation of the cornea) after a break in the corneal epithelium allows bacteria to enter.

• Corneal breaks: Contact lens wear, corneal abrasions, and other ocular trauma
• Other risk factors: Diabetes, prior ocular surgery, chronic ocular disease, use of corticosteroids, contaminated ocular medications, and agricultural work
• Common bacterial pathogens:
  • Staphylococcus aureus
  • Coag negative staphylococcus
  • Pseudomonas aeruginosa
  • Polymicrobial keratitis: Usually includes Staphylococcus epidermidis and Staphylococcus fusarium

Viral Corneal Ulcer:

• HSV: M/C cause of unilateral infectious corneal blindness in the developed world.
• Varicella-zoster virus (VZV)
• Cytomegalovirus (CMV)

Fungal Corneal Ulcer:

Fungal etiologies account for only 5 to 10% of all corneal infections. They are more common in warmer, humid parts of the country and are most often precipitated by trauma to the cornea with subsequent exposure to plant or vegetable material.

• Commonly implicated species: Aspergillus, Fusarium, Scedosporium apiospermum, phaeohyphpmycetes, Candida albicans, and other Candida species.

Protozoan Corneal Ulcer:

• Acanthamoeba: Free-living protozoan found in freshwater and in soil that can cause keratitis and corneal ulcers primarily in contact lens wearers.

Autoimmune disease:

Few corneal ulcers are of noninfectious etiology.

• Peripheral ulcerative keratitis (PUK): Associated with many systemic diseases.
  • #2 M/C ocular complication of autoimmune disorders (M/C anterior uveitis)
  • Common associations: Collagen vascular diseases (50% PUK cases) & rheumatoid arthritis
  • Other conditions: Wegener granulomatosis, relapsing polychondritis, polyarteritis nodosa, Churg-Strauss syndrome, and microscopic polyangiitis

---

Pathology

Stages of Corneal Ulcer:

Corneal infections often start as epithelial ulceration. This is followed by stromal infiltration by polymorphonuclear (PMN) and lymphomononuclear cells, which in turn causes the destruction of Bowman’s layer and then stromal necrosis. In severe cases, there can be perforation of the Descemet’s membrane. Suppurative infections lead to infiltrates in the anterior two-thirds of the stroma and abscess formation. Epithelial regeneration, vascularization, edema, giant cell reaction, myofibroblatic transformation and stromal remodeling (scarring), and round cell infiltration can occur with chronic infections.

• Stage of progressive infiltration
• Stage of active ulceration
• Stage of regression
• Stage of cicatrization

Adenoviral Keratoconjunctivitis

• Stage 1- It lasts for 7 to 10 days and characterized by diffuse punctate epithelial keratitis. 
• Stage 2- After 7 days, subepithelial to anterior stromal infiltrates appear. NK cells are the first to come in action and further involve cell-mediated immunity.
• Stage 3- This is characterized by persistent subepithelial to anterior stromal infiltrates.

Complications

• Toxic iridocyclitis
• Secondary glaucoma
• Descemetocele
• Perforation of corneal ulcer

Sequelae of Corneal Perforation:

• Iris prolapse, anterior dislocation of lens
• Anterior capsular cataract
• Corneal fistula
• Purulent uveitis
• Intraocular hemorrhage
• Corneal scarring- nebula, macula, leucoma, adherent leucoma
• Keratectasia
• Disorganized anterior chamber
• Autoevisceration, phthisis bulbi

---

Presentation

Bacterial corneal ulcer:

Present with rapid onset of pain, photophobia, and conjunctival injection, and a variable degree of vision loss.

• Slit-lamp exam: Clearly defined infiltrates with stromal inflammation and edema

Viral corneal ulcer:

Present similarly to the patient with bacterial keratitis. They will often have foreign body sensation, photophobia, conjunctival injection, and blurred vision.

• Slit-lamp exam: Classical dendritic lesions with fluorescein uptake

Fungal corneal ulcer:

More indolent course and often do not have the impressive conjunctival injection seen with bacterial infections.

• Slit lamp exam: Gray-white feathery dry appearing lesions with irregular margins. Ulcers due to yeast appear as superficial, white, raised colonies with clearly defined borders.

Acanthamoeba keratitis:

Classically present with pain out of proportion to physical exam findings. Severe photophobia is also common.

• Slit lamp: Diffuse punctate epithelial lesions, dendritic-like lesions, or ring-shaped infiltrates
• Definitive diagnosis is made with direct scraping, histology, or PCR identification of Acanthamoeba DNA.

Peripheral ulcerative keratitis (PUK):

Patients may already carry a diagnosis of an underlying autoimmune disease or the corneal ulcer may be the first manifestation of the disease. The patient may have stigmata of their underlying disease, such as swollen and tender joints or rashes.

• Slit lamp: Crescent-shaped lesion located in the limbal region of the corneal
• Evaluation in these patients would include a full ophthalmologic examination as well as lab work and imaging to help diagnose or monitor the underlying autoimmune condition.

Differential diagnosis:

The differential diagnosis for the patient presenting with red, painful eye includes corneal abrasions, nonulcerative keratitis, foreign body, iritis, acute angle-closure glaucoma, chemical burns, episcleritis, scleritis, and anterior uveitis.[6]

---

Management

An ophthalmologist should see all patients presenting with corneal ulcers within 12 to 24 hours. Emergent ophthalmologic consultation should be considered for a culture of the ulcer to guide antibiotic selection for suspected bacterial ulcers.

Bacterial keratitis and corneal ulcers:

Due to growing antibiotic resistance of common ocular pathogens corneal culture and sensitivity testing is recommended for all corneal ulcers, especially those that are large, central, and correlate with significant stromal involvement.

• First-line: Topical antibiotics, most commonly with fluoroquinolones such as ciprofloxacin or ofloxacin.
• Severe cases: Hospitalization with systemic (ceftriaxone) + topical therapy

Viral corneal ulcer:

Topical antivirals and adjuvant topical steroids

• HSV: Topical antivirals (trifluridine/acyclovir) and adjuvant topical steroids
• VZV and CMV keratitis: Topical antivirals (Ganciclovir). Oral acyclovir or valacyclovir are additional options. Oral valganciclovir is the treatment of choice for CMV stromal keratitis, but the patient requires close monitoring while on this medication due to significant side effects such as aplastic anemia.

Fungal corneal ulcer:

Fungal ulcers tend to have worse outcomes than bacterial as there are far fewer treatment options.

• DOC: Natamycin (topical polyene)
• Alternative: Amphotericin (limited use due to toxicity)
• Voriconazole (triazole)

Acanthamoeba keratitis and corneal ulcers:

• Epithelial debridement
• Antiamoebic therapy (3-4 months):
  • Chlorhexidine and polihexametilen biguanide (PHMB): Effective against trophozoites and cysts
  • Severe cases: Additional agents (diamidines, fluconazole, itraconazole, neomycin, and iodine-containing medications) used

Peripheral ulcerative keratitis:

Associated autoimmune and collagen vascular diseases should be treated with systemic immunosuppressants and cytotoxic agents and requires co-management by both a rheumatologist and ophthalmologist.. These patients need careful monitoring and frequent bloodwork while on these immunosuppressant medications.

Supplementary treatment:

Simple debridement of necrotic debris in conjunction with intensive topical therapy may help facilitate drug penetration especially of anti-fungal agents.

• Cycloplegic agents: Reduce ciliary spasm and produce mydriasis, thereby relieving pain and preventing synechiae formation.
  • Atropine sulphate 1%, homatropine 1% or cyclopentolate 1%
• Anti-glaucoma medications (for high IOP)
• Oral analgesics (for pain if needed)

Perforated ulcers:

• Tissue adhesive using N-butyl cyanoacrylate with a bandage contact lens is useful in cases with marked thinning or perforation less than 2mm..
• Penetrating keratoplasty is performed in cases with advanced disease at presentation where there is no response to medical therapy or when a large perforation is present.