What are the differential diagnoses for ocular redness?

Differential Diagnosis for Eye Redness

The most common causes of eye redness are conjunctivitis (infectious or allergic), blepharitis, dry eye syndrome, subconjunctival hemorrhage, and corneal abrasion, but your immediate priority is to identify vision-threatening emergencies requiring same-day ophthalmology referral. 1, 2

Immediate Red Flag Assessment (RAPID Criteria)

Before considering benign causes, rule out emergencies by checking for any of these features that mandate urgent ophthalmology referral within 24 hours: 3, 4, 5

• Redness with Acuity loss (sudden visual decline) 4
• Pain (moderate-to-severe ocular pain) 4
• Intolerance to light (photophobia) 4
• Damage to cornea (fluorescein uptake, ulceration, haze, opacity, or purulent discharge) 4

Additional emergency features include: 5, 2

• Proptosis or painful extraocular movements 5
• Distorted pupil or afferent pupillary defect 5, 2
• Corneal involvement on fluorescein staining 5
• Copious purulent discharge (possible gonococcal infection) 5, 2

Systematic Diagnostic Approach

Step 1: Assess Pattern and Laterality

Unilateral redness suggests: 3, 5, 6

• Viral conjunctivitis (adenoviral—often becomes bilateral within days) 5
• Herpes simplex keratitis 5, 2
• Corneal abrasion or foreign body 2
• Iritis/uveitis 2, 7
• Acute angle-closure glaucoma 2
• Scleritis 1

Bilateral redness suggests: 1, 3, 8

• Allergic conjunctivitis 1, 8
• Bacterial conjunctivitis 1
• Dry eye syndrome 1, 7
• Blepharitis 1
• Medication/preservative-induced keratoconjunctivitis 4
• Dupilumab-related ocular surface disease (DROSD) in patients on dupilumab 1, 4

Step 2: Characterize Discharge Type

The presence and character of discharge is critical for narrowing the differential: 3, 5

• Purulent/mucopurulent discharge: Bacterial conjunctivitis (including gonococcal if copious) 1, 5
• Watery discharge: Viral conjunctivitis or allergic conjunctivitis 1, 5
• Mucoid discharge: Allergic conjunctivitis or dry eye 1
• No discharge: Consider dry eye syndrome, subconjunctival hemorrhage, episcleritis, scleritis, or early viral conjunctivitis 3, 5, 7

Step 3: Examine for Associated Signs

Perform fluorescein staining in every case to detect corneal involvement that may not be clinically apparent. 5

Look for these specific findings: 1, 3, 5

• Follicles (inferior tarsal conjunctiva): Viral conjunctivitis, chlamydial infection 1, 3
• Papillae (superior tarsal conjunctiva): Allergic conjunctivitis, giant papillary conjunctivitis from contact lenses 1, 3
• Preauricular lymphadenopathy: Viral conjunctivitis (especially HSV) or Parinaud oculoglandular syndrome 3, 5
• Vesicular eyelid lesions: Herpes zoster ophthalmicus 5
• Dome-shaped umbilicated lesions on eyelid: Molluscum contagiosum 5
• Chemosis: Allergic or viral conjunctivitis 1, 3

Step 4: Assess Redness Pattern

The distribution of redness provides diagnostic clues: 3

• Diffuse pattern: Conjunctivitis (infectious or allergic) 3
• Sectoral/localized pattern: Localized irritation, episcleritis 3
• Perilimbal (circumcorneal) pattern: Iritis, keratitis, acute glaucoma, scleritis 1, 3

Common Differential Diagnoses

Infectious Conjunctivitis

Viral (most commonly adenoviral): 1, 5

• Watery discharge, follicular reaction, preauricular lymphadenopathy 1, 5
• Often begins unilaterally, becomes bilateral within days 5
• Self-limiting within 5-14 days 1, 5
• Management: Supportive care only (cool compresses), no antibiotics needed 1, 3

Bacterial: 1, 5

• Purulent or mucopurulent discharge 1, 5
• May remain unilateral 3
• Management: Topical broad-spectrum antibiotics 1, 2

Gonococcal (hyperacute): 1, 5

• Copious purulent discharge, marked eyelid edema, risk of corneal perforation 1, 5
• Management: Immediate systemic therapy and urgent ophthalmology referral 1, 5

Allergic Conjunctivitis

Seasonal/perennial: 1, 8

• Bilateral itching (strong indicator), watery discharge, chemosis 1, 3
• Papillary reaction on tarsal conjunctiva 1, 8
• Dark infra-orbital circles (allergic facies), Morgan-Dennie lines 5
• Management: Topical antihistamines, mast cell stabilizers, cold compresses 1, 3

Non-Infectious Causes

Dry eye syndrome: 1, 7

• Most frequent cause of chronic conjunctival inflammation 1
• May be primary or secondary (Sjögren's syndrome, medications) 7
• Requires specific treatment to prevent complications 7

Blepharitis: 1

• Most frequent cause of conjunctival inflammation alongside dry eye 1
• Treatment directed at underlying eyelid disease 1

Subconjunctival hemorrhage: 2

• Bright red blood under conjunctiva, no discharge, no pain 2
• Benign, self-resolving 2

Medication-induced: 4

• Preservative toxicity from topical medications 4
• Conjunctival injection, punctal edema, inferior fornix follicles 4

Dupilumab-related ocular surface disease (DROSD): 1, 4

• Bilateral conjunctival/limbal redness in patients on dupilumab 1, 4
• Multiple diagnoses possible: conjunctivitis (49%), keratitis (38%), dry eye (36%), blepharitis (29%) 1
• Unilateral symptoms are very unlikely to be dupilumab-related 1, 4

Vision-Threatening Conditions Requiring Urgent Referral

Herpes simplex keratitis: 5, 2

• Unilateral watery discharge, follicular reaction, preauricular lymphadenopathy 5
• Can progress to corneal scarring and perforation if untreated 5
• Never prescribe topical corticosteroids before excluding HSV 5

Acute angle-closure glaucoma: 2

• Severe pain, blurred vision, halos around lights, mid-dilated fixed pupil 2

Iritis/anterior uveitis: 2, 9

• Perilimbal injection, photophobia, pain, small pupil 2
• May be presenting sign of systemic disease (e.g., syphilis) 9

Scleritis: 1, 2

• Deep, boring pain worse at night, painful eye movements 1
• Violaceous hue to redness 1

Corneal ulcer/keratitis: 2, 7

• Fluorescein uptake, infiltrate, pain, photophobia 2

Preseptal vs. orbital cellulitis: 5

• Preseptal: eyelid erythema/edema/tenderness without proptosis or vision changes 5
• Orbital: proptosis, ophthalmoplegia, vision loss, fever—requires emergent hospitalization 5

Critical Pitfalls to Avoid

• Do not prescribe topical antibiotics for viral or allergic conjunctivitis—no benefit and risk of toxicity/resistance 1, 4
• Do not use topical corticosteroids without excluding HSV (look for vesicles, watery discharge, follicles) 5
• Do not continue corticosteroids >2 weeks without ophthalmology supervision and IOP monitoring 4, 5
• Do not assume absence of discharge excludes infection—early viral conjunctivitis may have minimal discharge 5
• Do not overlook serious conditions like uveitis, acute glaucoma, or scleritis that can present with red eye 3, 2
• Do not delay ophthalmology referral for lack of improvement after 3-4 days of appropriate therapy 4, 5

When to Refer to Ophthalmology

Same-day/urgent (within 24 hours): 4, 5, 2

• Any RAPID criterion present 4
• Suspected HSV/VZV with vesicles 5
• Severe purulent discharge 5
• Immunocompromised patient 5

Within 4 weeks: 4

• Severe onset redness requiring tacrolimus 4
• Children <7 years with any ocular symptom 4
• Chronic/recurrent symptoms 4

Routine follow-up (3-4 days): 4, 5

• Presumed viral conjunctivitis without red flags to assess improvement 4, 5