What are the differential diagnoses and treatments for conjunctivitis?

Differential Diagnosis of Conjunctivitis

Conjunctivitis must be classified as either infectious (viral or bacterial) or noninfectious (allergic, mechanical/irritative/toxic, immune-mediated, or neoplastic), with the critical first step being to differentiate true conjunctivitis from more serious causes of red eye that threaten vision. 1

Primary Classification Framework

Infectious Conjunctivitis

Viral Conjunctivitis (Most Common Overall)

• Presents with abrupt onset, often starting unilateral but becoming sequentially bilateral within days 2
• Follicular reaction on inferior tarsal conjunctiva is the distinctive finding 2
• Watery discharge, preauricular lymphadenopathy (especially with adenovirus), and concurrent upper respiratory infection 2, 3
• Subconjunctival hemorrhages, chemosis, eyelid swelling and erythema may be present 2
• Self-limited course, typically resolving in 5-14 days 2
• Severe cases may develop pseudomembranes, subepithelial corneal infiltrates, or conjunctival scarring 2

Bacterial Conjunctivitis (Second Most Common Infectious Cause)

• Mucopurulent discharge with matted eyelids on waking is the hallmark 2, 4, 3
• Papillary rather than follicular reaction distinguishes it from viral 2
• Can be unilateral or bilateral 2
• Mattering and adherence of eyelids, lack of itching, and no history of prior conjunctivitis are strongest predictive factors 4
• Most uncomplicated cases resolve in 1-2 weeks without treatment 4
• May be associated with concurrent bacterial otitis media, sinusitis, or pharyngitis in children 2

Special High-Risk Bacterial Forms Requiring Urgent Treatment:

• Gonococcal conjunctivitis: Marked eyelid edema, severe hyperpurulent discharge, rapid progression, risk of corneal perforation 1, 2
• Chlamydial conjunctivitis: Follicular reaction in adults, no follicles in neonates, requires systemic treatment and evaluation of sexual partners 1, 2
• Neonatal conjunctivitis: Any conjunctivitis in neonate requires prompt evaluation and may need hospitalization for parenteral therapy 2

Herpes Simplex Virus Conjunctivitis

• Usually unilateral (bilateral in atopic, pediatric, or immunocompromised patients) 2
• Vesicular rash or ulceration of eyelids, dendritic epithelial keratitis on cornea 2

Noninfectious Conjunctivitis

Allergic Conjunctivitis (Affects Up to 40% of Population)

• Itching is the most consistent and distinctive sign 4, 5
• Bilateral presentation with eyelid edema, periorbital hyperpigmentation ("allergic shiners"), chemosis 1
• Watery discharge with mild mucous component, papillary palpebral reaction 1
• Environmental allergen exposure history (grasses, pollens) 1

Subtypes include: 1

• Seasonal/perennial allergic conjunctivitis
• Vernal conjunctivitis
• Atopic conjunctivitis
• Giant papillary conjunctivitis (GPC) - associated with contact lens wear

Mechanical/Irritative/Toxic Conjunctivitis

Key entities to recognize: 1

• Dry eye (keratoconjunctivitis sicca) and blepharitis are the most frequent causes of conjunctival inflammation 1
• Superior limbic keratoconjunctivitis (SLK)
• Blepharoconjunctivitis
• Rosacea conjunctivitis
• Contact lens-related keratoconjunctivitis
• Floppy eyelid syndrome (should prompt sleep study for sleep apnea) 1
• Giant fornix syndrome
• Medication-induced/preservative-induced keratoconjunctivitis (long-term eye drop use with preservatives) 5

Immune-Mediated and Rare Forms

• Ligneous conjunctivitis: Thick, firm/woody pseudomembranous structures on palpebral conjunctiva, caused by plasminogen deficiency, may be inherited in autosomal recessive pattern 1, 2

Critical Red Flags Requiring Ophthalmology Referral

Immediate referral is indicated for: 2, 3

• Visual loss or decreased vision
• Moderate or severe pain (not relieved by topical anesthetics)
• Severe purulent discharge
• Corneal involvement (keratitis, infiltrate, ulcer)
• Conjunctival scarring
• Lack of response to therapy
• Recurrent episodes
• History of HSV eye disease
• Immunocompromised state
• Recent ocular surgery
• Vesicular rash on eyelids or nose
• Distorted pupil
• History of rheumatologic disease
• Neonatal conjunctivitis

Diagnostic Approach

History must focus on: 2

• Duration of symptoms
• Character of discharge (watery vs. mucopurulent vs. purulent)
• Unilateral vs. bilateral presentation
• Presence of itching (suggests allergic)
• Matted eyelids on waking (suggests bacterial)
• Concurrent upper respiratory infection (suggests viral)
• Contact lens wear
• Sexual history (for chlamydia/gonorrhea risk)
• Environmental allergen exposure

Physical examination must evaluate: 2

• Conjunctival injection pattern
• Type of discharge
• Presence of follicles (viral) vs. papillae (bacterial/allergic)
• Preauricular lymphadenopathy (viral)
• Corneal involvement with fluorescein staining
• Eyelid abnormalities

Treatment Algorithm

Viral Conjunctivitis

• No antimicrobial treatment required; viral conjunctivitis is self-limited 2, 4
• Supportive care with artificial tears for symptomatic relief 2, 3
• Topical antihistamines may be used for symptomatic relief 2
• Cold compresses 3
• Patient education about high contagiousness; minimize contact with others for 10-14 days from symptom onset 2
• Strict hand hygiene with soap and water, avoid sharing towels/pillows, disinfect surfaces with EPA-registered hospital disinfectant 2
• Avoid indiscriminate use of topical antibiotics as viral conjunctivitis will not respond to antibacterial agents 2

Bacterial Conjunctivitis

• Mild bacterial conjunctivitis is usually self-limited and may resolve without specific treatment 2, 4
• For moderate to severe bacterial conjunctivitis, a 5-7 day course of broad-spectrum topical antibiotic is usually effective 2
• No evidence demonstrates superiority of any particular topical antibiotic agent 2
• Moxifloxacin 0.5% ophthalmic solution: one drop in affected eye 3 times daily for 7 days (FDA-approved for bacterial conjunctivitis with clinical cure rates of 66-69% and microbiological eradication rates of 84-94%) 6
• Delayed antibiotic prescribing has similar symptom control as immediate prescribing 3
• Topical antibiotics decrease duration and allow earlier return to school/work 4

Special bacterial cases requiring systemic treatment: 2, 4

• Gonococcal conjunctivitis: requires systemic antibiotics
• Chlamydial conjunctivitis: requires systemic treatment plus evaluation of sexual partners
• Neonatal conjunctivitis: may require hospitalization for parenteral therapy

Allergic Conjunctivitis

• Topical antihistamines with mast cell-stabilizing activity are the treatment of choice 2, 3
• Allergen avoidance 2
• Allergen-specific immunotherapy is beneficial in reducing symptoms, more effective in children than adults 2
• Multidisciplinary approach with pediatricians, internists, and allergists recommended 2

Contact Lens-Related Conjunctivitis

• Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis 6
• Appropriate lens care and frequent lens replacement reduce risk of giant papillary conjunctivitis 2

Common Pitfalls to Avoid

• Avoid indiscriminate use of topical antibiotics or corticosteroids, which may lead to unnecessary side effects and delayed diagnosis of underlying conditions 2
• Chronic and/or recalcitrant conjunctivitis may indicate underlying malignancy (sebaceous or squamous cell carcinoma) and requires further evaluation 2
• Inadequate patient education about contagiousness leads to community spread 2
• Failing to recognize that dry eye and blepharitis are the most frequent causes of conjunctival inflammation, requiring treatment directed at the underlying problem rather than the conjunctivitis itself 1
• Missing systemic conditions (atopy, gonorrhea, rheumatologic disease) that cause secondary conjunctival inflammation 1