What is the differential diagnosis for a patient presenting with a red eye?

Differential Diagnosis of Red Eye

The differential diagnosis of red eye includes infectious causes (viral, bacterial, chlamydial, gonococcal conjunctivitis), allergic conjunctivitis, non-infectious inflammatory conditions (blepharitis, dry eye, iritis, scleritis), acute angle-closure glaucoma, corneal pathology (keratitis, abrasion, foreign body), subconjunctival hemorrhage, and less commonly, ocular malignancies or systemic inflammatory diseases. 1, 2, 3

Immediate Red Flags Requiring Urgent Ophthalmology Referral

Before considering the full differential, identify patients who need same-day ophthalmology evaluation:

• Visual loss or decreased visual acuity 2, 3
• Moderate to severe ocular pain (not relieved by topical anesthetics) 2, 3, 4
• Corneal involvement (opacity, loss of transparency, or visible corneal damage) 2, 3, 4
• Severe purulent discharge (especially if unilateral, suggesting gonococcal infection) 2, 3
• Photophobia with pain (suggests corneal or intraocular pathology) 4, 5
• History of herpes simplex virus eye disease 2, 3
• Immunocompromised state 2, 3
• Recent ocular surgery or trauma 2, 4
• Distorted or irregular pupil 4

Infectious Conjunctivitis

Viral Conjunctivitis

• Presentation: Abrupt onset, initially unilateral but frequently becomes sequentially bilateral within days, watery discharge, follicular reaction on inferior tarsal conjunctiva, preauricular lymphadenopathy 1, 2
• Associated features: Concurrent upper respiratory infection, subconjunctival hemorrhages, chemosis, eyelid swelling 1, 2
• Natural history: Self-limited, resolving within 5-14 days 1, 2
• Severe complications: Pseudomembranes, subepithelial corneal infiltrates (especially with epidemic keratoconjunctivitis), conjunctival scarring 1, 2

Bacterial Conjunctivitis

• Presentation: Unilateral or bilateral, purulent or mucopurulent discharge with matted eyelids upon waking, papillary (not follicular) reaction 1, 2
• Associated features: May have concurrent otitis media, sinusitis, or pharyngitis (especially in children) 1, 2
• Preauricular lymphadenopathy: Less common than viral unless caused by hypervirulent organisms 2

Gonococcal Conjunctivitis

• Presentation: Marked eyelid edema, severe bulbar conjunctival injection, copious purulent discharge, preauricular lymphadenopathy 1, 2
• Critical complication: Can rapidly progress to corneal infiltrate, ulcer, and perforation 1, 2, 3
• Management: Requires systemic antibiotic therapy in addition to topical treatment, with daily follow-up until resolution 2, 3

Chlamydial Conjunctivitis

• Presentation: Chronic follicular conjunctivitis, often with concurrent urethritis or cervicitis in sexually active adults 2
• Management: Requires systemic treatment; topical therapy alone is inadequate. Evaluation and treatment of sexual partners is mandatory 2, 3

Herpes Simplex Virus (HSV) Conjunctivitis

• Presentation: Usually unilateral (bilateral in atopic, pediatric, or immunocompromised patients), watery discharge, mild follicular reaction 1, 2
• Distinctive signs: Vesicular rash or ulceration of eyelids, dendritic epithelial keratitis of cornea or conjunctiva 1, 2
• Complications: Stromal keratitis, corneal scarring, neovascularization, uveitis, retinitis 1

Varicella Zoster Virus (VZV)

• Presentation: Usually unilateral, vesicular dermatomal rash involving eyelids, conjunctival injection, follicular reaction 1
• Distinctive signs: Vesicles at limbus (especially in primary infection), pleomorphic or non-excavated pseudodendritic keratitis 1
• Late complications: Corneal scarring, corneal anesthesia, dry eye, cicatricial ectropion 1

Molluscum Contagiosum

• Presentation: Typically unilateral, mild to severe follicular reaction, punctate epithelial keratitis, corneal pannus if long-standing 1
• Distinctive signs: Single or multiple shiny, dome-shaped umbilicated lesions on eyelid skin or margin 1
• Risk factors: Immunocompromised state (especially HIV) predisposes to multiple/large lesions 1

Allergic Conjunctivitis

• Presentation: Bilateral involvement, itching as the most prominent and distinguishing symptom, watery discharge with mild mucous component, chemosis 1, 2
• Associated features: History of atopy, asthma, eczema, seasonal or perennial pattern depending on allergen exposure, concurrent allergic rhinitis 1, 2
• Physical findings: Papillary reaction (not follicular), absence of preauricular lymphadenopathy, no matted eyelids 2
• Subtypes: Seasonal allergic conjunctivitis (pollen exposure), perennial allergic conjunctivitis (dust mites, pet dander), vernal keratoconjunctivitis (chronic, vision-threatening, pediatric/adolescent males), atopic keratoconjunctivitis (vision-threatening, older adults with eczema) 1

Non-Infectious Inflammatory Conditions

Blepharitis

• Presentation: Bilateral eyelid margin inflammation, crusting, burning sensation, associated with chronic conjunctivitis 1
• Associated features: Meibomian gland dysfunction, recurrent styes, seborrheic dermatitis 6

Dry Eye Disease

• Presentation: Bilateral burning, foreign body sensation, paradoxical tearing, conjunctival injection without discharge 1, 3
• Risk factors: Advanced age, female gender, autoimmune disease, medications (antihistamines, diuretics), environmental factors 1

Iritis (Anterior Uveitis)

• Presentation: Unilateral (usually), deep ocular pain, photophobia, blurred vision, perilimbal (ciliary) injection 4, 5
• Physical findings: Constricted or irregular pupil, cells and flare in anterior chamber on slit-lamp examination 4

Scleritis

• Presentation: Severe, boring ocular pain radiating to face/head, deep episcleral and scleral vessel injection, bluish-red discoloration 4, 5
• Associated features: Often associated with systemic autoimmune disease (rheumatoid arthritis, granulomatosis with polyangiitis) 4

Corneal Pathology

Keratitis

• Presentation: Unilateral pain, photophobia, foreign body sensation, decreased vision, conjunctival injection, corneal opacity or infiltrate 1, 2, 4
• Risk factors: Contact lens wear (especially overnight wear), trauma, dry eye, immunosuppression 4, 5
• Urgent referral required: All cases of suspected keratitis need ophthalmology evaluation 2, 3

Corneal Abrasion/Foreign Body

• Presentation: Acute onset after trauma, severe pain, foreign body sensation, tearing, photophobia, unilateral 4, 5
• Diagnosis: Fluorescein staining reveals epithelial defect 4

Other Causes

Acute Angle-Closure Glaucoma

• Presentation: Severe unilateral pain, nausea/vomiting, blurred vision with halos around lights, mid-dilated fixed pupil, corneal edema, markedly elevated intraocular pressure 4, 5
• Emergency: Requires immediate ophthalmology referral to prevent permanent vision loss 4, 5

Subconjunctival Hemorrhage

• Presentation: Painless, bright red blood under conjunctiva, no discharge, normal vision, often spontaneous or after Valsalva/trauma 4, 5
• Benign: Self-resolving over 1-2 weeks, no treatment needed unless recurrent or associated with trauma 4

Ocular Malignancies

• Squamous Cell Carcinoma: Chronic unilateral conjunctival hyperemia, thickened lesion, may be misdiagnosed as chronic blepharoconjunctivitis 1
• Melanoma: Painless pigmented or non-pigmented lesion, vascular prominence, history of UV exposure or previous melanoma 1

Dupilumab-Related Ocular Surface Disorders (DROSD)

In patients on dupilumab therapy for atopic dermatitis:

• Common diagnoses: Conjunctivitis (49% of DROSD cases), dry eye (36%), keratitis (38%), blepharitis (29%) 1
• Urgent referral criteria: Worsening visual acuity, ocular pain, photophobia, visible corneal damage 1
• Note: No unique ocular pathology specific to dupilumab; diagnose as per routine ophthalmology practice 1

Key Differentiating Features

Unilateral vs. Bilateral

• Unilateral: Consider HSV, bacterial (often), corneal pathology, iritis, acute glaucoma, scleritis, foreign body, trauma 1, 2, 3
• Bilateral: Viral conjunctivitis (often sequential), allergic conjunctivitis, dry eye, blepharitis 1, 2

Discharge Characteristics

• Watery: Viral conjunctivitis, allergic conjunctivitis, early bacterial 1, 2
• Purulent/mucopurulent: Bacterial conjunctivitis, gonococcal conjunctivitis 1, 2
• Mucoid: Allergic conjunctivitis, dry eye 2, 6
• No discharge: Subconjunctival hemorrhage, episcleritis, scleritis, iritis, glaucoma, dry eye 3, 4

Follicles vs. Papillae

• Follicles (inferior tarsal conjunctiva): Viral conjunctivitis, chlamydial conjunctivitis, molluscum contagiosum, toxic conjunctivitis 1, 2
• Papillae: Bacterial conjunctivitis, allergic conjunctivitis, giant papillary conjunctivitis (contact lens-related) 1, 2

Preauricular Lymphadenopathy

• Present: Viral conjunctivitis (especially adenovirus), HSV, gonococcal conjunctivitis 1, 2
• Absent: Allergic conjunctivitis, most bacterial conjunctivitis (except hypervirulent organisms) 2

Common Pitfalls to Avoid

• Do not prescribe antibiotics for viral conjunctivitis: They provide no benefit and may cause unnecessary toxicity and antibiotic resistance 2, 3
• Do not miss gonococcal conjunctivitis: Severe purulent discharge in a sexually active adult or neonate requires immediate systemic treatment to prevent corneal perforation 2, 3
• Do not use topical corticosteroids without ophthalmology supervision: Risk of elevated intraocular pressure, cataract formation, worsening HSV infection, and prolonged viral shedding 2
• Do not overlook unilateral presentation: This should prompt consideration of serious pathology beyond simple conjunctivitis 3, 4
• Do not ignore contact lens wear: Raises concern for bacterial keratitis, which requires urgent ophthalmology referral 3, 4
• Do not dismiss chronic or recalcitrant conjunctivitis: May indicate underlying malignancy (sebaceous or squamous cell carcinoma) requiring biopsy 2