What is the differential diagnosis for a patient presenting with red, painful, itchy eyes?

Differential Diagnosis for Red, Painful, Itchy Eyes

The differential diagnosis for red, painful, itchy eyes includes conjunctivitis (viral, bacterial, or allergic), keratitis, blepharitis, dry eye syndrome, acute angle closure glaucoma, scleritis, episcleritis, and less commonly, uveitis or orbital inflammatory disease. 1, 2, 3

Primary Diagnostic Categories

Conjunctivitis (Most Common)

Conjunctivitis is the most common cause of red eye and presents with eye discharge, redness, and varying degrees of pain, photophobia, and itching. 1, 3, 4

Viral Conjunctivitis:

• Most common overall cause of infectious conjunctivitis 4
• Variable presentation at onset 4
• Usually self-limited, resolving in 10-14 days 1
• Does not respond to antibacterial agents 1
• Highly contagious; requires patient education about hand hygiene and avoiding close contact 1

Bacterial Conjunctivitis:

• Second most common infectious cause 4
• Key distinguishing features: mattering and adherence of eyelids on waking, lack of itching, and no history of prior conjunctivitis 4
• Most uncomplicated cases resolve in 1-2 weeks without treatment 4
• Hyperacute bacterial conjunctivitis (gonococcal) is vision-threatening and requires immediate systemic therapy 1

Allergic Conjunctivitis:

• Encountered in up to 40% of the population 4
• Itching is the most consistent and distinguishing sign 1, 5, 4, 6
• Chemosis (conjunctival swelling) is the leading clinical sign 5
• Subtypes include seasonal/perennial allergic conjunctivitis, vernal conjunctivitis, and atopic conjunctivitis 1, 5

Keratitis (Corneal Inflammation)

Bacterial Keratitis:

• Presents with pain, redness, photophobia, and foreign body sensation 2
• Suppurative stromal infiltrates with indistinct edges (>1 mm) are hallmark findings 2
• Anterior chamber reaction often present, even without visible epithelial defect 2
• Risk factors: contact lens wear (especially overnight), recent ocular trauma, previous corneal surgery, dry eye, immunosuppression 2
• Requires immediate empiric broad-spectrum topical antibiotics and re-evaluation within 24 hours 2

Herpes Simplex Keratitis:

• Typically presents unilaterally 2
• Can be sight-threatening 1
• Critical pitfall: topical corticosteroids can worsen herpetic keratitis 1

Blepharitis and Meibomian Gland Dysfunction

• Inflammation at the eyelid margin junction 1
• One of the most frequent causes of conjunctival inflammation 1
• Treatment should be directed at the underlying eyelid problem rather than just treating conjunctival symptoms 1

Dry Eye Syndrome

• Presents with irritation, itching, soreness, ocular discomfort, burning, or intermittent blurred vision 1
• Most frequent cause of conjunctival inflammation alongside blepharitis 1
• Symptoms often have inconsistent correlation with clinical signs, making diagnosis challenging 1
• Can coexist with other conditions (aqueous deficiency and evaporative types often mixed) 1

Acute Angle Closure Glaucoma

• Presents with sudden onset of severe pain, redness, congestion, decreased vision, and corneal edema 1
• Very high intraocular pressure 1
• Vision-threatening emergency requiring immediate treatment 1
• Risk factors: hyperopia, shallow anterior chamber, older age 1

Scleritis and Episcleritis

• Scleritis causes severe, boring pain that may radiate to the face 3
• Can be associated with systemic autoimmune diseases 3
• Requires aggressive management to prevent vision loss 3

Uveitis

• Predominantly anterior uveitis in patients on immune checkpoint inhibitors 1
• Presents with blurred vision, photophobia, eye redness, and pain 1
• Can occur with other immune-related adverse events, especially colitis 1

Orbital Inflammatory Disease

• Encompasses idiopathic orbital inflammatory syndrome, IgG4-related disease, and cellulitis 7
• May present with eyelid swelling, proptosis, pain with eye movements, and diplopia 1, 7
• Warning signs requiring urgent ophthalmology referral: eyelid swelling with pain and erythema, proptosis, movement restriction, vision changes 1

Critical Red Flags Requiring Emergency Referral

Immediate ophthalmology consultation needed for: 1, 2, 3

• Severe pain not relieved with topical anesthetics
• Vision loss or acute visual changes
• Corneal involvement (infiltrates, ulceration, opacity)
• Copious purulent discharge
• Traumatic eye injury
• Recent ocular surgery
• Distorted pupil
• Signs of herpes infection
• Very high intraocular pressure

Diagnostic Approach

Key examination findings to differentiate causes:

• Presence of itching strongly suggests allergic etiology 1, 4, 6
• Mattering/crusting on waking suggests bacterial conjunctivitis 4
• Stromal infiltrates distinguish bacterial keratitis from simple abrasion 2
• Mid-dilated, asymmetric pupil suggests acute angle closure 1
• Unilateral presentation should raise suspicion for herpes simplex keratitis or other serious pathology 2

Special populations requiring heightened vigilance:

• Contact lens wearers: higher risk for bacterial keratitis, especially with overnight wear 2
• Immunocompromised patients: increased risk for severe infections 2
• Patients on immune checkpoint inhibitors: consider immune-related ocular adverse events 1
• Patients with atopic dermatitis on dupilumab: monitor for dupilumab-related ocular surface disorders 1

Common Pitfalls to Avoid

• Never patch an eye with suspected infection or in contact lens wearers 2
• Do not assume absence of visible epithelial defect excludes serious pathology 2
• Avoid topical corticosteroids until organism identified and infection responding to therapy 2
• Do not start corticosteroids before ophthalmology exam in suspected immune-related ocular adverse events, as this may worsen infectious causes or mask accurate diagnosis 1
• Indiscriminate use of topical antibiotics should be avoided, as viral conjunctivitis will not respond and mild bacterial conjunctivitis is often self-limited 1