Eye Diseases > Cornea

Keratitis

Evidence-based assessment and management of corneal inflammation. Comprehensive guide covering etiology, pathogenesis, classification, diagnosis, and treatment protocols for optometry practice.

📑 Table of Contents

ILLUSTRATION

Clinical Illustration

OVERVIEW

Overview

Keratitis is an acute or chronic inflammation of the cornea caused by infectious or non-infectious etiologies. It presents with corneal opacification, infiltration, and vascularization, often accompanied by conjunctival injection and anterior chamber inflammation. Keratitis ranges from superficial epithelial involvement to full-thickness stromal disease and requires prompt recognition and appropriate management to prevent visual complications and preserve corneal clarity.

Keratitis is among the leading causes of corneal blindness worldwide. Infectious keratitis accounts for an estimated 1.5–2 million cases annually globally, with the highest burden in South and Southeast Asia, sub-Saharan Africa, and parts of Latin America. In industrialized nations, contact lens wear accounts for approximately 30–40% of all microbial keratitis cases. Herpes simplex virus is the most common cause of infectious keratitis in high-income countries, with a recurrence rate of approximately 10% per year after an initial episode. Fungal keratitis predominates in tropical regions, often following agricultural ocular trauma.

SECTION 1

Etiology

Infectious Causes

Bacterial: Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Neisseria gonorrhoeae
Viral: Herpes simplex virus (HSV), Varicella-zoster virus (VZV), Adenovirus, Measles
Fungal: Aspergillus, Fusarium, Candida, Cryptococcus (particularly in immunocompromised patients)
Parasitic: Onchocerca volvulus (river blindness), Acanthamoeba (contact lens-related)
Chlamydial: Chlamydia trachomatis, Chlamydia psittaci

Non-Infectious Causes

Autoimmune: Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematosus, Behçet disease
Toxic/Chemical: Chemical burns, acid/alkali injury, medications (topical antiglaucoma agents, antibiotics)
Mechanical: Corneal abrasion, foreign body, dry eye syndrome, trichiasis
Allergic: Vernal keratoconjunctivitis, atopic keratoconjunctivitis, drug allergy
Photochemical: UV exposure (arc eye, welding injury), phototoxic reactions
Graft rejection: In corneal transplant recipients
Neurotrophic: Reduced corneal sensation leading to keratitis

SECTION 2

Pathogenesis

Infectious Keratitis

Microbial invasion: Organisms penetrate the corneal epithelium through abrasion, poor hygiene, or contact lens wear
Inflammation: Host immune response triggers recruitment of neutrophils, macrophages, and lymphocytes
Stromal involvement: Enzymes released by organisms and inflammatory cells degrade corneal collagen and proteoglycans
Corneal neovascularization: Growth factors trigger new blood vessel formation from limbal vessels
Scarring: Persistent inflammation and collagen remodeling result in Haze and opacity

Non-Infectious Keratitis

Non-infectious keratitis occurs through:

Mechanical trauma: Direct epithelial damage followed by inflammatory cascade
Chemical injury: Protein denaturation and cell death with progressive corneal damage
Autoimmune attack: T cells and antibodies target corneal antigens, causing epithelial disruption
Photochemical: UV-induced DNA damage and epithelial necrosis
Neurotrophic deficiency: Loss of sensory nerves and their neuroprotective factors leads to epithelial breakdown

SECTION 3

Classification

By Anatomical Depth

Epithelial keratitis: Limited to corneal epithelium; typically superficial, may resolve without scarring
Stromal keratitis: Involves corneal stroma; results in opacification and potential scarring
Endothelial keratitis: Posterior keratitis involving Descemet membrane and endothelium; associated with anterior uveitis

By Etiology

Infectious: Bacterial, viral, fungal, parasitic keratitis
Non-infectious: Autoimmune, toxic, mechanical, allergic, photochemical

By Pattern

Central keratitis: Axial involvement with visual potential compromise
Peripheral keratitis: Limbal or peripheral involvement; better visual prognosis
Diffuse keratitis: Widespread corneal involvement

By Pathogen Pattern (Key Morphological Features)

HSV epithelial keratitis: Dendritic ulcer with terminal end-bulbs, or geographic ulcer pattern; stains with fluorescein and rose bengal
HSV stromal keratitis: Immune-mediated; necrotizing or non-necrotizing (interstitial) stromal involvement without active viral replication in stroma
Bacterial keratitis: Dense white/yellow stromal infiltrate with overlying epithelial defect; purulent discharge; rapid progression within hours to days
Fungal keratitis: Feathery infiltrate borders, satellite lesions, immune ring infiltrate, hypopyon; follows corneal trauma (especially vegetable matter) or topical steroid use
Acanthamoeba keratitis: Radial keratoneuritis (pathognomonic — perineural infiltrates visible on slit lamp); early pseudodendrites; ring infiltrate in later stages; pain disproportionate to early clinical findings

SECTION 4

Risk Factors

Patient Factors

Contact lens wear (especially extended wear and poor hygiene)
Compromised immunity (HIV/AIDS, chemotherapy, immunosuppressive therapy)
Diabetes mellitus
Dry eye syndrome or aqueous tear deficiency
Ocular surface disease
Previous corneal trauma or surgery
Eyelid abnormalities (trichiasis, entropion, lagophthalmos)
Neurotrophic disorders (diabetes, herpes zoster)
Chronic systemic disease (rheumatoid arthritis, Sjögren syndrome)

Environmental Factors

Trauma or foreign body penetration
Chemical or thermal burns
Excessive UV exposure
Environmental pathogens (water exposure, soil contamination)
Occupational hazards

SECTION 5

Signs

External Findings

Conjunctival injection (hyperemia)
Chemosis (conjunctival swelling)
Eyelid edema
Photophobia
Preauricular lymphadenopathy (viral keratitis)

Corneal Signs

Epithelial defect: Punctate epithelial erosions (PEE), focal or diffuse abrasion; stains with fluorescein
Stromal infiltrate: Focal or diffuse white areas in stroma; indicates infection or inflammation
Corneal opacity/haze: Loss of corneal clarity from edema, scarring, or infiltrate
Corneal neovascularization: New blood vessel growth from limbal vessels into corneal stroma
Hypopyon: White material in anterior chamber (WBC infiltration) in severe bacterial or fungal infections
Descemet fold: Wrinkling of Descemet membrane from stromal edema
Corneal ulceration: Excavation of stromal tissue; indicates active infection

Anterior Chamber Signs

Anterior chamber reaction (AC cells and flare)
Keratic precipitates (KP)
Iris inflammation
Posterior synechiae (in severe cases)

SECTION 6

Symptoms

Ocular pain - ranging from mild discomfort to severe pain (severity correlates with epithelial involvement)
Foreign body sensation - typically worse with blinking
Photophobia - particularly pronounced in bacterial keratitis
Tearing/epiphora - reflex tearing in response to corneal irritation
Discharge - purulent in bacterial infections; clear/scant in viral or non-infectious
Blurred or hazy vision - depends on location and extent of opacity
Redness - may be acute or progressive
Haloes or glare - from corneal roughness or edema

Clinical Pearl: Neurotrophic Presentation

A large epithelial defect or frank corneal ulceration accompanied by absent or minimal pain should immediately raise suspicion for neurotrophic keratitis. Unlike infectious keratitis, patients may have little discomfort despite severe corneal pathology. Common causes include prior herpes simplex or zoster infection, diabetes mellitus, and prior corneal surgery (including LASIK). Corneal sensation testing with a cotton wisp is mandatory in all keratitis evaluations; the Cochet-Bonnet esthesiometer provides quantitative assessment when available. Failure to recognize neurotrophic disease leads to inappropriate antibiotic therapy and delayed healing.

SECTION 7

Complications

Corneal Complications

Corneal scarring: Permanent loss of corneal clarity from fibrosis (in 30-50% of bacterial keratitis cases)
Corneal perforation: Full-thickness corneal loss; requires emergent surgical intervention
Corneal thinning: Stromal degradation with risk of ectasia or perforation
Vascularization: Permanent ghost vessels; impairs corneal clarity
Corneal neovascularization: Abnormal blood vessel growth with risk of recurrent inflammation
Anacanthous changes: Loss of corneal nerves with progressive neurotrophic deficiency

Infectious Complications

Secondary bacterial infection: Superinfection of non-infectious keratitis
Ascended endophthalmitis: Intraocular infection (risk with perforation)
Orbital cellulitis: Deep inflammation extending posteriorly

Inflammatory Complications

Anterior uveitis: Spillover inflammation into anterior chamber
Posterior synechiae: Adhesions between iris and lens from severe anterior uveitis
Elevated intraocular pressure: From inflammation or posterior synechiae
Intermediate/posterior uveitis: In systemic inflammatory conditions (Behçet, HLA-B27 associated)

Visual Complications

Refractive errors: Induced astigmatism from corneal scarring or edema
Amblyopia: In children with unilateral or bilateral involvement
Corneal blindness: Central scarring or extensive vascularization affecting vision

SECTION 8

Systemic Relations and Complications

Associated Systemic Diseases

Rheumatoid arthritis: Associated with peripheral keratitis and scleritis; may evolve to keratolysis
Sjögren syndrome: Causes dry eye with secondary keratitis from epithelial breakdown
Behçet disease: Recurrent keratitis; may include stromal infiltration and anterior uveitis
Systemic lupus erythematosus: Epithelial keratitis and central ulceration can occur
Diabetes mellitus: Predisposes to keratitis via epithelial fragility and reduced immunity
HIV/AIDS: Increased risk of opportunistic infections including CMV, fungal, and herpetic keratitis
Herpes zoster ophthalmicus: Post-herpetic keratitis and neurotrophic keratopathy
Graft-versus-host disease (GVHD): Chronic GVHD causes cicatricial keratoconjunctivitis
Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Acute mucocutaneous reaction with severe keratitis
Atopic dermatitis: Vernal keratoconjunctivitis and shield ulcers
Onchocerciasis: Parasitic keratitis with scarring leading to blindness in endemic areas

Systemic Infectious Pathogens

Tuberculosis: Can cause interstitial keratitis (late TB keratitis) and anterior uveitis
Syphilis: Causes interstitial keratitis, rarely presents in modern era with adequate penicillin access
Chlamydia trachomatis: Leading cause of preventable blindness globally; causes active keratitis and trichiasis
Leprosy: Causes marginal keratitis and anterior uveitis
Measles: Causes epithelial keratitis during acute viral infection

Systemic Medications

Isotretinoin: Causes severe dry eye and keratitis risk
Immunosuppressive agents: Chemotherapy, TNF inhibitors increase infection risk
Antiglaucoma medications: (especially latanoprost, bimatoprost) can cause allergic keratitis with chronic use

SECTION 9

Diagnosis

Clinical History

Onset (acute vs. insidious), duration, unilateral or bilateral
Contact lens wear history (type, wear schedule, hygiene)
Recent trauma, foreign body exposure
Ocular surgery or procedures
Systemic disease (diabetes, autoimmune, immunocompromised state)
Ocular disease history (herpes, dry eye, blepharitis)
Medication use (topical and systemic)
Sexual history (relevant for herpes, gonorrhea)

Slit Lamp Examination (Gold Standard)

Fluorescein staining: Identify epithelial defects (green staining), classify pattern
Lissamine green or rose bengal: Stains dead/degenerating cells (use with caution in active infection)
Slit beam examination: Assess infiltrate depth, location, extent; evaluate for anterior chamber reaction
Assess corneal sensation: Use cotton wisp or touch test (reduced sensation suggests herpes or neurotrophic disease)
Examine lid margin: Check for abnormalities predisposing to keratitis

Microbiology and Cultures

Routine bacterial culture: Gold standard for bacterial keratitis; allows susceptibility testing
Gram stain: Useful for immediate identification; guides empiric therapy
Fungal culture: Indicated for immunocompromised, recent trauma, or steroid use; slow growing (2-4 weeks)
Viral culture/PCR: HSV and VZV testing for suspected herpetic keratitis
Acanthamoeba culture/staining: Specific testing for resistant contact lens-related keratitis

Imaging

Anterior segment OCT: Newer imaging for detailed corneal architecture; helps assess epithelial loss, stromal infiltrate depth
In vivo confocal microscopy: Enables direct cellular-level visualization without corneal scraping; particularly valuable for Acanthamoeba keratitis (cysts visible as double-walled spheres 15–25 µm in diameter), fungal hyphae, and assessment of corneal nerve density in neurotrophic keratitis; increasingly used to reduce the need for invasive diagnostic procedures in resistant or atypical cases
Photography: Documentation for disease progression monitoring
Corneal topography: May show irregularity from keratitis; useful for measuring induced astigmatism

Adjunctive Testing

Anterior chamber paracentesis: If hypopyon present and organism identification needed for severe cases
Corneal biopsy: Rarely performed; reserved for resistant cases with diagnostic uncertainty
Intraocular pressure measurement: Exclude secondary glaucoma

Diagnostic Criteria for Bacterial Keratitis (Practical Assessment)

Stromal infiltrate with anterior chamber reaction
Epithelial defect overlying or adjacent to infiltrate
Purulent exudate (may be absent in early stages)
Pain and photophobia out of proportion to findings (suggests infection)
Risk factors for infection (contact lens wear, trauma, immunocompromised state)

SECTION 10

Management

General Supportive Care

Discontinue contact lens wear immediately
Cold compresses for symptom relief
Artificial tears for dry eye component
Systemic analgesia (NSAIDs, acetaminophen) for pain management
Eye patching (controversial; may slow epithelial healing; generally avoided in infectious keratitis)
Photophobia management (dark sunglasses, reduced lighting)

Bacterial Keratitis

Empiric broad-spectrum therapy before culture results:
- Fluoroquinolone (4th generation: moxifloxacin or gatifloxacin) every 1-2 hours while awake
- Fortified antibiotics if severe infection (cephalosporin + aminoglycoside or fluoroquinolone)
Culture-directed therapy: Based on sensitivity; may be de-escalated after results
Duration: Typically 7-14 days; extended if healing is slow or infection deep
Severe pseudomonal infection: Consider systemic fluoroquinolone (ciprofloxacin) as adjunct

Viral Keratitis (HSV/VZV)

Topical antiviral: Trifluridine (1%) every 2 hours while awake and once at bedtime for epithelial keratitis
Systemic antiviral: Oral acyclovir 400-800mg 4-5 times daily for severe disease or immunocompromised
Stromal HSV keratitis: Topical corticosteroids (prednisolone 1% 4-6 times daily) AFTER epithelial healing confirmed
Avoid topical antivirals in stromal disease: Limited efficacy; may impede healing
Long-term prophylaxis: Consider acyclovir 400mg BID for frequently recurrent disease

Fungal Keratitis

Topical antifungal: Natamycin 5% suspension every 1-2 hours initially (initial choice for corneal infection)
Alternative antifungals: Voriconazole, fluconazole (if natamycin unavailable)
Systemic therapy: Voriconazole or fluconazole for severe or deep keratitis
Duration: Often prolonged (several weeks to months); monitor for slow response
Avoid topical steroids: Unless endorsed by specialist; can worsen fungal infection
Surgical referral: May require debulking or keratoplasty if not responding to medical therapy

Acanthamoeba Keratitis

Topical agents: Polyhexamethylene biguanide (PHMB) or chlorhexidine, plus topical propamidine isethionate
Challenging to treat: Often requires prolonged therapy (months); high risk of corneal scarring
Urgent referral to specialist: Most optometrists/general ophthalmologists manage with referral
Systemic therapy: Oral itraconazole or voriconazole may be adjunctive

Non-Infectious Keratitis

Dry eye keratitis: Intensive lubrication (artificial tears, ointment), punctal plugs if severe
Autoimmune/interstitial keratitis: Topical and systemic corticosteroids; consult rheumatology if indicated
Chemical burns: Immediate irrigation, topical antibiotics, systemic vitamin C, referral to specialty care
Allergic keratitis: Topical mast cell stabilizers (cromolyn sodium), antihistamines; topical steroids for acute exacerbation
Neurotrophic keratitis: Protective strategies (lubricants, bandage contact lens), nerve growth factor (in some centers), surgical intervention if severe

Adjunctive Therapies

Collagenase inhibitors: Doxycycline or tetracycline may slow progression of infectious keratitis
Prostaglandin analogs: May promote epithelial healing in some conditions
Bandage soft contact lens: Protects epithelium and provides comfort; contraindicated in bacterial infection
Topical corticosteroids: Use cautiously; may worsen bacterial/fungal infection; appropriate in viral stromal disease and non-infectious causes

Surgical Interventions (Specialist Consultation)

Conjunctival flap: Covers defect, promotes healing in neurotrophic keratitis
Keratoplasty: Corneal transplantation for severe scarring or perforation
Cauterization: Of infectious foci in fungal/resistant infections
Amniotic membrane transplantation: Promotes epithelial healing and modulates inflammation

Follow-Up Frequency

Severe bacterial keratitis: Daily evaluation until infiltrate resolves
Moderate keratitis: Every 2-3 days until epithelialization; then weekly
Mild cases: Weekly until resolution; monthly follow-up for several months to monitor scarring
Post-healing: Continued monitoring for recurrence, especially in viral keratitis

SECTION 11

Prognosis

Visual Outcomes

Peripheral keratitis: Generally excellent prognosis; minimal visual impact
Central keratitis: Depends on depth and associated scarring; may result in refractive error or reduced visual acuity
Epithelial keratitis: May resolve without permanent scarring with appropriate treatment
Stromal keratitis: High risk of scarring; prognosis depends on etiology and promptness of treatment
Posterior/endothelial keratitis: May result in corneal edema and decompensation

Timeline for Healing

Epithelial healing: Typically 3-7 days for uncomplicated epithelial defects
Stromal infiltrate resolution: 2-6 weeks; fungal and Acanthamoeba infections slower
Scar maturation: Up to 12 months; progressive improvement possible
Complete resolution: May take months to years; permanent sequelae common with severe infection

Factors Affecting Prognosis

Favorable factors:

Peripheral involvement
Epithelial disease only
Early diagnosis and appropriate treatment
Good compliance with medication
Immunocompetent host

Unfavorable factors:

Central/axial involvement
Deep stromal infiltration
Severe anterior chamber reaction
Fungal or Acanthamoeba infection
Immunocompromised state
Delayed diagnosis or inappropriate initial therapy
Perforation
Persistent epithelial defect

Infection-Specific Prognosis

Bacterial (responsive strains): Good prognosis with appropriate antibiotics; scarring less common than fungal
Pseudomonal keratitis: High risk of perforation and severe scarring; aggressive treatment required
HSV keratitis: Generally good prognosis for epithelial disease; stromal disease may leave scarring
Fungal keratitis: Poor prognosis; high scarring rate and vision-threatening complications even with treatment
Acanthamoeba keratitis: Guarded prognosis; often requires months of treatment and significant scarring occurs

SECTION 12

Differential Diagnosis

Condition	Key Features	Distinguishing Points
Corneal Abrasion	Punctate epithelial defect; intact stroma	No AC reaction, no infiltrate, no fever or systemic symptoms
Corneal Erosion (Recurrent)	Epithelial fragility; episodic breakdown	No infiltrate, no pain at onset, history of trauma or dystrophy
Epithelial Dystrophy	Recurrent anterior stromal haze	Chronic, bilateral, often hereditary; no acute infection signs
Scleritis/Episcleritis	Episcleral or scleral inflammation	Anterior scleritis can extend to cornea; sectoral pattern; severe pain
Marginal Keratitis	Limbal infiltrate adjacent to cornea	Associated with blepharitis; clear zone from limbus; non-infectious
Corneal Foreign Body	Visible embedded particle	Clear history of trauma; particle visible with magnification
Allergic Keratoconjunctivitis	Seasonal or perennial conjunctivitis; papillae	Shield ulceration in severe cases; no infiltrate in early disease; itching prominent
Uveitis (Anterior)	Anterior chamber reaction prominent	No obvious corneal infiltrate; posterior synechia; KPs; iris involvement
Iritis from Keratitis	Keratitis with AC reaction	Definable corneal infiltrate and epithelial defect distinguishes from isolated uveitis
Chemical Burn	Epithelial sloughing; anterior chamber involvement	Clear history of chemical exposure; may involve conjunctiva and anterior structures
Punctate Keratitis (Non-infectious)	Multiple punctate epithelial erosions	No stromal infiltrate; may be medication-related; resolves with cessation
Stellar Keratopathy	Star-shaped corneal scarring	Chronic finding; no active infection; history of prior trauma or HSV keratitis

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