Red Eye — Differential Diagnosis

Infectious (surface)

• Viral: adenovirus dominates; spread by fomites and hand-to-eye contact. Herpes simplex produces a dendritic ulcer; varicella-zoster reactivation in V1 gives herpes zoster ophthalmicus, with Hutchinson sign (nasociliary tip vesicles) predicting globe involvement.
• Bacterial: staphylococci, streptococci, Haemophilus in children. Neisseria gonorrhoeae causes hyperacute conjunctivitis and is the one organism that can invade an intact cornea; Chlamydia trachomatis causes chronic follicular disease in adults and, in endemic regions, trachoma.
• Contact-lens–associated keratitis: Pseudomonas aeruginosa (biofilm on lens/case) and Acanthamoeba (tap water, swimming, homemade saline).

Immune-mediated

• Allergic: IgE/mast-cell histamine release in atopic patients.
• Anterior uveitis: HLA-B27–associated spondyloarthropathies (ankylosing spondylitis, reactive arthritis, IBD, psoriatic arthritis), sarcoidosis, syphilis, tuberculosis, juvenile idiopathic arthritis.
• Scleritis: rheumatoid arthritis and granulomatosis with polyangiitis are the classic systemic drivers; scleritis may be the presenting sign of the vasculitis.

Mechanical/pressure

• Angle closure: pupillary block in a crowded anterior segment.
• Trauma: abrasion, foreign body, UV arc eye from welding or snow glare.

Non-modifiable risk factors

• Anatomy and demographics: hyperopia, shallow anterior chamber, short axial length, age over 50, female sex, and East Asian or Inuit ancestry all raise angle-closure risk (AAO Primary Angle Closure Disease Preferred Practice Pattern).
• Genetics/systemic disease: HLA-B27 status, atopy, autoimmune connective tissue disease.

Modifiable risk factors

• Contact lens behaviors: overnight wear, extended-wear lenses, water exposure, poor case hygiene — the highest-yield modifiable risk in the microbial keratitis stem.
• Drugs that dilate the pupil: anticholinergics, sympathomimetics, tricyclics, and topiramate (idiosyncratic ciliochoroidal effusion) can precipitate acute closure; dim light and prolonged near work do the same.
• Sexual exposure for gonococcal/chlamydial disease, anticoagulants and Valsalva for subconjunctival hemorrhage, and smoking/dry environments for ocular surface disease.

• Conjunctival hyperemia and vasodilation: In conjunctivitis (infectious or allergic), local inflammatory mediators (histamine, prostaglandins, cytokines) cause vasodilation of conjunctival vessels, producing the classic diffuse redness that blanches with topical phenylephrine
• Ciliary muscle inflammation and spasm: In acute anterior uveitis and iritis, immune-mediated inflammation of the ciliary body causes photophobia, pain, and accommodation problems; ciliary flush (deep episcleral redness) occurs due to inflammation of vessels in the ciliary muscle region
• Intraocular pressure elevation: In acute angle-closure glaucoma, mechanical obstruction of aqueous outflow through the trabecular meshwork by the iris causes rapid IOP elevation (often >40-50 mmHg), leading to corneal edema, mid-dilated unresponsive pupil, and severe pain
• Corneal epithelial disruption and infectious invasion: In keratitis and corneal abrasion, loss of the protective epithelial barrier allows bacterial or viral invasion; inflammation and neovascularization produce deep anterior chamber redness and pain
• Episcleral and scleral inflammation: In episcleritis and scleritis, inflammation of deeper vascular layers produces nodular or diffuse redness that does NOT blanch with phenylephrine; scleritis involves actual tissue necrosis and is associated with systemic autoimmune diseases
• Subconjunctival hemorrhage: Rupture of conjunctival vessels creates blood beneath the conjunctiva without associated inflammation, producing painless bright red appearance

• Bacterial conjunctivitis: Unilateral or bilateral purulent discharge (thick, yellow-green), conjunctival injection, mild foreign body sensation, minimal pain, preserved vision; often follows viral prodrome or exposure to contaminated materials; Staphylococcus aureus and Streptococcus pneumoniae are most common
• Viral conjunctivitis (adenovirus most common): Watery discharge, follicular conjunctivitis (small lymphoid aggregates on tarsal conjunctiva), preauricular lymphadenopathy, photophobia, affected eye often follows URI symptoms; highly contagious
• Allergic conjunctivitis: Intense itching (cardinal symptom), giant papillae on upper tarsal conjunctiva, chemosis, ropy mucoid discharge; seasonal or perennial course depending on allergen exposure; typically bilateral
• Acute anterior uveitis/iritis: Severe photophobia and pain, blurred vision, small pupil (miotic), ciliary flush (deep redness at limbus), keratic precipitates on endothelium (WBCs); often unilateral; associated with HLA-B27, sarcoidosis, TB, or idiopathic
• Acute angle-closure glaucoma: EMERGENCY presentation—sudden severe eye pain, blurred vision with halos around lights, nausea/vomiting, fixed mid-dilated pupil (4-6 mm), corneal edema (hazy appearance), extremely elevated IOP; typically unilateral; more common in hyperopic Asian and Inuit populations
• Corneal abrasion/keratitis: Foreign body sensation, tearing, photophobia, blepharospasm; may have visible defect on fluorescein staining; bacterial keratitis presents with infiltrate and hypopyon (pus level in anterior chamber)
• Scleritis: Deep boring eye pain (often severe enough to wake patient), photophobia, localized or diffuse scleral nodules; redness does NOT blanch with phenylephrine; associated with rheumatoid arthritis, granulomatosis with polyangiitis (GPA), syphilis; posterior scleritis may present with exudative retinal detachment
• Episcleritis: Sectoral redness, mild discomfort (not severe pain), nodular or diffuse inflammation; self-limited; redness may blanch with phenylephrine
• Subconjunctival hemorrhage: Painless bright red area beneath conjunctiva, vision unaffected, no discharge; may follow trauma, anticoagulation, or bleeding disorder but often spontaneous and benign
• Important clinical pearl: The presence of photophobia with pain suggests intraocular inflammation (uveitis, acute glaucoma, or corneal pathology) rather than conjunctivitis; copious purulent discharge is characteristic of bacterial conjunctivitis, while watery discharge with lymphadenopathy suggests viral etiology

• Visual acuity assessment: CRITICAL first step—preserved vision with mild irritation favors conjunctivitis or episcleritis, while decreased vision with pain raises concern for uveitis, keratitis, angle-closure glaucoma, or scleritis; count fingers or light perception in severe cases
• External examination and lid eversion: Inspect for vesicles (HSV keratitis), foreign bodies, ptosis, and exudate; evert upper lid to visualize tarsal conjunctiva (follicles in viral, papillae in allergic, giant papillae in vernal or giant papillary conjunctivitis)
• Fluorescein and rose bengal staining: Fluorescein highlights corneal epithelial defects (abrasions, ulcers appear green); rose bengal stains devitalized cells and may show filaments in dry eye syndrome; absence of staining makes corneal pathology less likely
• Slit lamp examination: Essential for anterior segment evaluation—assess depth of anterior chamber (narrow chamber increases angle-closure risk), iris color/pattern, lens clarity, and posterior segment involvement; magnification allows visualization of keratic precipitates, hypopyon, and ciliary injection
• Intraocular pressure measurement (tonometry): Pneumotonometry, applanation, or rebound tonometry; IOP <21 mmHg is normal, 21-25 mmHg is borderline, >25 mmHg is elevated; acute elevation >40 mmHg is diagnostic of acute angle-closure; baseline comparison important in glaucoma
• Gonioscopy: Examination of anterior chamber angle to assess angle width and drainage structures; narrow angles (Grade I-II) increase acute closure risk; essential in patients with angle-closure glaucoma or at risk
• Dilated fundus examination: After excluding angle-closure risk (by gonioscopy or Van Herick test), pharmacologic dilation allows posterior segment visualization to assess for posterior uveitis, retinitis, optic neuritis, or other posterior involvement
• Phenylephrine blanching test: Apply 2.5% phenylephrine to conjunctiva; blanching suggests conjunctival/episcleral injection (conjunctivitis, episcleritis, superficial inflammation), while persistence of redness suggests deeper scleral involvement or angle-closure glaucoma
• Culture and sensitivity (bacterial conjunctivitis): Indicated if purulent discharge present, particularly in neonates, contact lens wearers, or immunocompromised patients; helps guide therapy if empiric treatment fails
• PCR for viral pathogens: Not routinely recommended but may help in institutional outbreak investigation; clinical diagnosis of adenoviral conjunctivitis usually sufficient
• Imaging considerations: CT or ultrasound B-scan may be needed if posterior scleritis suspected or if inability to visualize posterior segment due to corneal edema or cataract

Bacterial Conjunctivitis—First-Line

• Topical antibiotics: Fluoroquinolone drops (ciprofloxacin 0.3% or moxifloxacin 0.5%) QID × 7 days is preferred due to

Emergencies — vision lost in hours to days

• Acute angle-closure glaucoma: sustained pressure produces optic nerve head ischemia and permanent field loss; late signs are a fixed atonic pupil from iris sphincter necrosis, glaukomflecken (anterior subcapsular lens opacities), and peripheral anterior synechiae that make the closure chronic. Retinal vascular occlusion can follow. Definitive prevention of recurrence is laser peripheral iridotomy, including prophylaxis of the fellow eye (AAO Primary Angle Closure Disease Preferred Practice Pattern).
• Corneal ulcer → perforation: bacterial or fungal stromal invasion with collagenase-mediated melt; the signals are a dense infiltrate, hypopyon, and a positive Seidel test (fluorescein streaming from the wound). Perforation risks endophthalmitis and permanent central scarring.
• Gonococcal conjunctivitis: penetrates intact epithelium and can perforate within days; copious hyperacute purulence in a sexually active adult or a 2–5-day-old neonate demands same-day ophthalmology involvement and systemic ceftriaxone (CDC STI Treatment Guidelines).

Complications of the underlying disease

• Uveitis: posterior synechiae bind iris to lens → iris bombé → secondary angle-closure glaucoma; also cystoid macular edema, cataract, and band keratopathy in chronic JIA-associated disease.
• Scleritis: necrotizing disease causes scleral thinning with uveal show (scleromalacia perforans), and posterior scleritis causes exudative retinal detachment. It also flags active systemic vasculitis, which carries its own mortality.
• Adenoviral keratoconjunctivitis: subepithelial infiltrates cause glare and blur for months; pseudomembranes can scar into symblepharon.

Complications of treatment

• Topical corticosteroids: steroid-response IOP rise, posterior subcapsular cataract, and catastrophic worsening of undiagnosed HSV (dendritic → geographic ulcer) or fungal keratitis. Never start steroids without slit-lamp confirmation.
• Topical anesthetics: repeated use is epithelial-toxic and produces a neurotrophic non-healing ulcer — diagnostic use only, never a prescription.
• Patching a contact-lens abrasion: creates a warm closed culture chamber for Pseudomonas; contraindicated.
• Systemic acetazolamide: metabolic acidosis, hypokalemia, nephrolithiasis, and caution in sulfonamide hypersensitivity.

• Consensual photophobia localizes the problem: pain in the affected eye when light is shone in the other eye implicates iris/ciliary body (uveitis) or cornea, never simple conjunctivitis, because the stimulus is sphincter constriction, not surface irritation.
• Fixed mid-dilated pupil + hazy cornea + halos + vomiting = acute angle closure. The single best next step is tonometry (with slit-lamp exam), not imaging and not an antiemetic. Medical lowering of IOP is temporizing; laser peripheral iridotomy is definitive per AAO.
• Contact lens wearer + red painful eye = microbial keratitis until proven otherwise. Remove the lens, culture the lens/case/cornea, start topical fluoroquinolone or fortified antibiotics, and refer same day. Do not patch and do not give steroids.
• Fluorescein dendrite with terminal bulbs = HSV epithelial keratitis → topical/oral antivirals. The classic distractor is prescribing a steroid, which converts it to a geographic ulcer.
• The phenylephrine test is the episcleritis-versus-scleritis discriminator: blanching redness with mild discomfort is episcleritis (self-limited); non-blanching violaceous redness with boring pain that wakes the patient is scleritis → systemic NSAIDs or steroids plus a workup for rheumatoid arthritis and ANCA-associated vasculitis.
• The one association examiners love: HLA-B27 and recurrent unilateral non-granulomatous anterior uveitis — ask about low back pain with morning stiffness, urethritis, or bloody diarrhea.
• Neonatal conjunctivitis is a timing question: chemical within the first day, gonococcal at days 2–5, chlamydial at days 5–14. Erythromycin ointment prophylaxis (recommended by the USPSTF and AAP) prevents gonococcal ophthalmia but not chlamydial disease, and chlamydial conjunctivitis needs oral therapy because of afebrile staccato-cough pneumonia.
• Painless, sharply demarcated blood with normal vision = subconjunctival hemorrhage: reassure, check blood pressure and anticoagulation, and resist ordering antibiotics.