Viral Conjunctivitis

Adenovirus (Most Common — 65–90% of Cases)

• Epidemic Keratoconjunctivitis (EKC): Adenovirus serotypes 8, 19, and 37 (species D); most severe and contagious form; characterised by subepithelial infiltrates, pseudomembranes, and prolonged course
• Pharyngoconjunctival Fever (PCF): Adenovirus serotypes 3, 4, and 7 (species B); classic triad of pharyngitis, fever, and follicular conjunctivitis; common in children; often associated with communal swimming pools
• Non-specific adenoviral conjunctivitis: Multiple serotypes; milder follicular conjunctivitis without systemic features; self-limiting

Herpesvirus Family

• Herpes Simplex Virus type 1 (HSV-1): Most common herpetic cause; primary infection presents with vesicular lid lesions, follicular conjunctivitis, and preauricular lymphadenopathy; reactivation can cause recurrent keratitis; type 2 (HSV-2) implicated in neonates and sexually active adults
• Varicella Zoster Virus (VZV): Herpes Zoster Ophthalmicus (HZO) results from reactivation in the ophthalmic division (V1) of the trigeminal nerve; Hutchinson’s sign (nasal tip lesions) indicates nasociliary nerve involvement and predicts ocular complications; can produce conjunctivitis, keratitis, uveitis, and optic neuritis
• Epstein-Barr Virus (EBV): Follicular conjunctivitis as part of infectious mononucleosis; associated with periorbital oedema, posterior pole changes, and rare optic neuropathy
• Cytomegalovirus (CMV): Rare cause of follicular conjunctivitis in immunocompetent hosts; primarily causes sight-threatening retinitis in immunocompromised patients (notably HIV/AIDS)

Enterovirus and Picornavirus

• Enterovirus 70 (EV70): Causes acute haemorrhagic conjunctivitis (AHC); explosive onset within 24 hours; hallmark subconjunctival haemorrhages; highly contagious; rare neurological complications (radiculomyelitis)
• Coxsackievirus A24 variant: Second major cause of AHC; similar clinical presentation to EV70; epidemic potential in tropical regions

Other Viral Pathogens

• Molluscum contagiosum (poxvirus): Perilimbal molluscum lesions shed viral particles causing chronic follicular conjunctivitis and punctate keratitis; important in immunocompromised patients and children
• SARS-CoV-2 (COVID-19): Follicular conjunctivitis reported in 1–3% of COVID-19 cases; may be a presenting feature; conjunctiva can serve as entry portal for viral transmission
• Measles virus (Morbillivirus): Catarrhal conjunctivitis with photophobia precedes exanthem; Koplik spots on buccal mucosa are pathognomonic; corneal involvement can cause blindness in malnourished children
• Rubella virus: Mild follicular conjunctivitis as part of rubella infection; congenital rubella causes cataracts and pigmentary retinopathy
• Newcastle disease virus: Rare zoonosis in poultry handlers; self-limiting follicular conjunctivitis with systemic influenza-like illness

General Viral Mechanism

1. Viral entry and receptor binding: Viruses breach the conjunctival mucosal barrier and adhere to specific epithelial cell receptors. Adenovirus binds to the coxsackievirus-adenovirus receptor (CAR) and integrins (αvβ3, αvβ5) on the conjunctival epithelium; HSV-1 uses heparan sulphate proteoglycans and herpesvirus entry mediator (HVEM)
2. Intracellular replication: Following receptor-mediated endocytosis, viral DNA/RNA is delivered to the nucleus or cytoplasm where viral replication occurs. Adenovirus replicates within the nucleus, forming characteristic intranuclear inclusion bodies; HSV replicates in the nucleus and is transported along axons to sensory ganglia (trigeminal ganglion for HSV-1)
3. Cell lysis and viral shedding: Productive lytic infection destroys conjunctival epithelial cells, releasing virions into the tear film. This lytic phase corresponds to the highly contagious period of acute disease, during which viral shedding may persist for 10–14 days after symptom onset
4. Innate immune activation: Pattern recognition receptors (Toll-like receptors TLR-3, TLR-7, TLR-9 and cytosolic RIG-I/MDA5) on conjunctival epithelial cells and resident dendritic cells detect viral nucleic acids, triggering interferon (IFN-α, IFN-β) and pro-inflammatory cytokine production (IL-1β, IL-6, IL-8, TNF-α)
5. Dendritic cell migration and lymphadenopathy: Antigen-presenting dendritic cells migrate from the conjunctival stroma via lymphatic channels to the preauricular and submandibular lymph nodes, initiating the adaptive immune response. Preauricular lymphadenopathy — a hallmark clinical sign — reflects this immune priming
6. Adaptive immune response and follicle formation: Antigen-specific T lymphocytes and B lymphocytes are recruited to the conjunctival substantia propria, forming organised lymphoid aggregates (follicles) visible as pale, dome-shaped elevations on the palpebral conjunctiva. Follicular reaction is the histological signature of viral (and chlamydial) conjunctivitis
7. Subepithelial infiltrates (EKC-specific): In epidemic keratoconjunctivitis, adenoviral antigens persist in the anterior corneal stroma, triggering a delayed-type hypersensitivity (Type IV) immune reaction 1–3 weeks after the acute phase. T-cell–mediated inflammation produces the characteristic nummular subepithelial infiltrates (SEIs) that cause photophobia, glare, and reduced visual acuity and may persist for months to years

HSV-Specific Pathogenesis

After primary HSV conjunctivitis, the virus establishes latency in the trigeminal ganglion. Reactivation — triggered by UV exposure, fever, stress, or immunosuppression — leads to anterograde axonal transport of virus to the corneal epithelium or eyelid, producing recurrent dendritic or geographic ulcers. Repeated episodes cause progressive stromal scarring, neovascularisation, and corneal opacity. Immune-mediated stromal keratitis, rather than direct viral cytopathic effect, is responsible for the majority of HSV-induced corneal morbidity.

By Clinical Syndrome

• Epidemic Keratoconjunctivitis (EKC): Adenovirus types 8, 19, 37; most severe adenoviral form; bilateral involvement common; subepithelial infiltrates, pseudomembranes, and chemosis; contagious for up to 14 days; outbreaks in healthcare settings and schools
• Pharyngoconjunctival Fever (PCF): Adenovirus types 3, 4, 7; triad of follicular conjunctivitis, pharyngitis, and fever; most common in children; associated with contaminated swimming pools; self-limiting within 1–2 weeks
• Acute Haemorrhagic Conjunctivitis (AHC): Enterovirus 70 / Coxsackievirus A24; explosive onset within 8–48 hours; characteristic subconjunctival haemorrhages; epidemic potential; rare neurological sequelae
• Herpetic (HSV) Conjunctivitis: HSV-1 primary or recurrent; vesicular lid lesions pathognomonic; concurrent dendritic corneal ulcer; antiviral therapy required; avoid topical steroids without antiviral cover
• Herpes Zoster Ophthalmicus (HZO): VZV reactivation in ophthalmic division of V cranial nerve; dermatomal vesicular rash; Hutchinson’s sign; risk of keratitis, uveitis, episcleritis, and cranial nerve palsies; urgent systemic antiviral therapy
• Molluscum-associated Conjunctivitis: Chronic follicular conjunctivitis from periocular molluscum nodules; requires treatment of primary skin lesions; consider immunodeficiency in disseminated cases
• Non-specific Viral Conjunctivitis: Multiple adenovirus and other respiratory virus serotypes; mild, self-limiting; often concurrent with upper respiratory tract infection

Clinical Comparison Table

Epidemiological Risk Factors

• Close contact with infected individuals: Adenovirus is transmitted via direct contact, fomites, and respiratory droplets; incubation period 2–14 days; contagious for up to 14 days after symptom onset
• Healthcare and institutional settings: Healthcare workers are at elevated risk due to frequent patient contact; nosocomial EKC outbreaks reported in ophthalmology clinics, emergency departments, and ICUs — inadequate equipment sterilisation (tonometer tips, slit lamp chin rests) is a documented vector
• Communal swimming pools: PCF (adenovirus 3, 4) outbreaks associated with inadequately chlorinated pool water; virus survives in pool environments
• Schools and childcare centres: Paediatric populations with high transmission rates due to close contact, hand-to-eye behaviour, and incomplete immune memory
• Seasonal and geographic factors: Adenoviral conjunctivitis shows summer-autumn peak in temperate climates; AHC caused by EV70 and CVA24 has epidemic potential in tropical and subtropical regions (Asia, Africa, Latin America)

Host Risk Factors

• Immunocompromised states: HIV/AIDS (CMV retinitis, severe HSV/VZV disease), systemic corticosteroid use, chemotherapy, haematological malignancy — atypical and severe viral ocular disease
• Prior HSV infection: History of oral herpes labialis or prior HSV keratitis significantly increases risk of ocular HSV reactivation; UV exposure, emotional stress, fever, and immunosuppression are common triggers
• Age: Neonates at risk of severe HSV-2 ocular disease from perinatal transmission; elderly at increased risk of HZO from declining VZV cell-mediated immunity
• Contact lens wear: Contact lens-associated tear film disruption and epithelial microtrauma may facilitate adenoviral adherence; extended wear increases susceptibility to ocular surface infection
• Atopic disease: Atopic individuals may have exaggerated conjunctival inflammatory responses and are at greater risk of corneal complications in viral conjunctivitis
• Previous ocular surgery: Post-LASIK or penetrating keratoplasty patients are at risk of HSV reactivation triggered by surgical trauma or immunosuppressive topical therapy
• Poor hand hygiene: Primary transmission route for adenoviral and enteroviral conjunctivitis; inadequate handwashing after touching infected secretions or contaminated surfaces

External Examination

• Preauricular lymphadenopathy: Tender, enlarged preauricular lymph node on the affected side — a hallmark finding that strongly favours viral (or chlamydial) aetiology over bacterial; may involve submandibular nodes in severe disease
• Eyelid oedema: Palpebral oedema and erythema; may be unilateral initially; vesicular lid lesions are pathognomonic of HSV; dermatomal vesicular crusting extending to the forehead and nasal tip occurs in HZO
• Watery / serous discharge: Copious clear-to-slightly mucoid discharge; contrasts with the mucopurulent or purulent discharge of bacterial conjunctivitis; excessive lacrimation is common

Slit Lamp Findings

• Follicular conjunctival reaction: Pale, avascular, dome-shaped elevations (0.5–2 mm) on the palpebral conjunctiva and/or fornices; composed of lymphocytic aggregates with germinal centres; most prominent on the inferior palpebral conjunctiva; follicles have no central vascular core (distinguishing from papillae)
• Diffuse conjunctival hyperaemia: Conjunctival injection affecting bulbar and palpebral conjunctiva; more diffuse and less intense than gonococcal bacterial conjunctivitis; ciliary injection absent unless cornea is involved
• Chemosis: Conjunctival oedema most prominent in EKC and AHC; may cause significant patient discomfort
• Pseudomembranes and true membranes: Fibrinous exudates adherent to the tarsal conjunctiva in severe EKC; pseudomembranes peel away cleanly without bleeding; true membranes (rarer) bleed on removal and indicate more severe inflammation; risk of conjunctival scarring and symblepharon if untreated
• Subconjunctival haemorrhages: Characteristic of acute haemorrhagic conjunctivitis (EV70, CVA24); petechial to sheet-like haemorrhages in the bulbar conjunctiva
• Corneal changes — Punctate Epithelial Erosions (PEEs): Fine, diffuse punctate fluorescein-staining defects in the epithelium during the acute phase of EKC; represent areas of direct viral cytopathic effect
• Subepithelial infiltrates (SEIs): Pathognomonic of EKC; nummular (coin-shaped), grey-white, subepithelial opacities in the anterior stroma; appear 1–3 weeks after acute onset as direct viral phase resolves; represent delayed hypersensitivity immune deposits; can persist for months to years; cause glare, photophobia, and reduced visual acuity when central
• Dendritic corneal ulcer (HSV): Linear branching epithelial defect with terminal bulbs; stains with fluorescein (active ulcer) and rose bengal/lissamine green (devitalised cells at edges — lissamine green not routinely used in Singapore; may be used by practitioners in other regional settings); pathognomonic of HSV epithelial keratitis
• Punctate keratitis: Fine superficial corneal staining associated with molluscum-related conjunctivitis and HZO

Ocular Symptoms

• Ocular irritation / foreign body sensation: Gritty, sandy feeling is universal; more prominent as follicular reaction develops; moderate rather than severe pain (deep pain suggests keratitis or uveitis)
• Watery or mucoid discharge: Profuse tearing; watery discharge distinguishes viral from bacterial; patients may describe constant lacrimation and the inability to keep eyes clear
• Redness: Diffuse ocular redness, typically unilateral at onset; bilateral involvement follows in 1–5 days in most adenoviral cases
• Photophobia: Mild in early adenoviral conjunctivitis; significant photophobia suggests corneal epithelial involvement (PEEs) or subepithelial infiltrates; severe photophobia with ciliary flush warrants corneal and anterior chamber assessment
• Blurred vision: Transient blurring due to excessive tearing and discharge (clears with blinking) in mild disease; persistent or non-clearing blur indicates SEIs involving the visual axis, corneal ulceration, or anterior uveitis
• Eyelid swelling: Palpebral oedema causing a heavy, swollen sensation; prominent in acute phase; vesicular lid lesions cause burning pain in HSV
• Periocular pain and neuralgia: Deep aching or burning periocular pain in HZO; post-herpetic neuralgia (PHN) may persist for months after rash resolution, particularly in elderly patients

Systemic Symptoms

• Upper respiratory tract symptoms (adenovirus): Sore throat, cough, nasal congestion, and mild fever preceding or concurrent with conjunctivitis; mandatory features of PCF (pharyngitis + fever + conjunctivitis triad)
• Fever and malaise: Systemic viral illness commonly accompanies acute adenoviral conjunctivitis; generalised fatigue and myalgia in PCF and EBV-associated conjunctivitis
• Tender preauricular and/or cervical lymphadenopathy: Reported by patients as a lump or tenderness in front of the ear; may be tender to palpation

Adenoviral Complications

• Subepithelial infiltrates (SEIs): Most significant complication of EKC; nummular opacities appear 1–3 weeks after acute onset; persistent central SEIs cause reduced visual acuity, glare, and photophobia; may recur after topical steroid cessation; very rarely cause permanent corneal scarring
• Pseudomembranous conjunctivitis: Fibrinous exudate adherent to the palpebral conjunctiva; if not mechanically removed, can lead to subconjunctival fibrosis and fornix shortening; risk of symblepharon (adhesions between bulbar and palpebral conjunctiva)
• Dry eye and tear film dysfunction: Goblet cell loss and conjunctival scarring following severe EKC may produce permanent aqueous-deficient or mucin-deficient dry eye; symptoms may persist for years after acute infection
• Punctal / canalicular scarring: Rare; obstruction of lacrimal drainage causing chronic epiphora

Herpetic Complications (HSV / HZO)

• HSV epithelial keratitis: Dendritic ulcer may progress to geographic ulcer with inappropriate steroid use; risk of secondary bacterial or fungal superinfection
• HSV stromal keratitis: Immune-mediated necrotising or non-necrotising stromal inflammation; recurrent episodes cause progressive corneal scarring, thinning, neovascularisation, and permanent visual loss; leading cause of corneal blindness from infectious disease in developed countries
• HSV endotheliitis: Direct viral invasion of the corneal endothelium; produces disc-shaped stromal oedema (disciform keratitis); can lead to bullous keratopathy
• Recurrent erosion syndrome: Defective adhesion of regenerated epithelium following herpetic epithelial keratitis; spontaneous epithelial breakdown causing sudden pain on waking
• HZO — uveitis and trabeculitis: Anterior uveitis with sectoral iris atrophy, raised intraocular pressure (trabeculitis), or hyphaema; may lead to glaucoma if untreated
• HZO — cranial nerve palsies: Third, fourth, or sixth nerve involvement causing diplopia; acute retinal necrosis (ARN) in immunocompromised patients
• Post-herpetic neuralgia (PHN): Persistent severe neuropathic pain for >3 months after HZO; more common and severe in elderly patients; can be debilitating
• Corneal perforation: Rare end-stage complication of severe stromal keratitis or neurotrophic ulceration from corneal anaesthesia (especially HZO)

Other Complications

• Secondary bacterial superinfection: Viral conjunctivitis predisposes to bacterial superinfection by disrupting the conjunctival epithelial barrier and impairing mucosal immunity; suspect if discharge becomes mucopurulent or symptoms worsen after initial improvement
• Acute haemorrhagic conjunctivitis (AHC) neurological sequelae: Rare but serious complication of EV70 infection; acute radiculomyelitis presenting 1–5 weeks after conjunctivitis with asymmetric lower-limb motor weakness resembling poliomyelitis; self-limiting but may cause permanent disability
• Measles-associated blindness: Corneal ulceration and perforation in measles conjunctivitis, primarily affecting malnourished children in developing countries; associated with vitamin A deficiency

Systemic Associations by Pathogen

• Adenovirus: Systemic adenoviral disease includes upper and lower respiratory tract infection (pharyngitis, tonsillitis, pneumonia), gastroenteritis, haemorrhagic cystitis, and myocarditis; children with PCF commonly have concurrent pharyngitis, fever, and cervical lymphadenopathy; adenoviral conjunctivitis in neonates carries risk of disseminated adenoviral infection
• Herpes Simplex Virus (HSV): Ocular HSV-1 may coexist with orolabial herpes (herpes labialis); genital HSV-2 can cause neonatal HSV ocular and systemic disease via perinatal transmission; encephalitis (HSV-1) is a rare but life-threatening systemic complication requiring prompt neurological assessment if suspected
• Herpes Zoster / VZV: HZO is a manifestation of varicella-zoster reactivation in the trigeminal ganglion; systemic dissemination (visceral zoster) occurs in immunocompromised patients; VZV vasculopathy can cause stroke; Ramsay Hunt syndrome (HZV in geniculate ganglion) presents with facial palsy, ear pain, and auricular vesicles — may coexist with ophthalmic zoster
• Epstein-Barr Virus (EBV) / Infectious Mononucleosis: Conjunctivitis and periorbital oedema are recognised features; ophthalmic manifestations include papilloedema, cranial nerve palsies, uveitis, and rare optic neuropathy; positive monospot and heterophile antibody test; splenomegaly contraindicates contact sports
• Enterovirus 70 / AHC: Neurological complication of acute radiculomyelitis (acute haemorrhagic conjunctivitis motor paralysis) occurs 2–5 weeks post-conjunctivitis; presents as acute asymmetric flaccid paralysis of lower limbs; associated with EV70 and CVA24 epidemics in South and Southeast Asia
• Measles: Conjunctivitis is an early prodromal feature alongside cough, coryza, and Koplik spots; post-measles encephalitis, pneumonia, and sub-acute sclerosing panencephalitis (SSPE) are serious systemic complications; measles remains a leading cause of childhood blindness globally
• Rubella: Mild conjunctivitis, posterior cervical lymphadenopathy, and maculopapular rash; congenital rubella syndrome causes cataracts, pigmentary retinopathy, cardiac defects, and sensorineural deafness following first-trimester maternal infection
• SARS-CoV-2 (COVID-19): Follicular conjunctivitis may precede respiratory symptoms or occur as isolated ocular manifestation; conjunctival ACE2 receptor expression supports ocular viral entry; systemic COVID-19 can produce retinal microvascular changes, cranial nerve palsies, and Miller Fisher syndrome
• HIV/AIDS: HIV-positive patients are susceptible to CMV retinitis (not conjunctivitis), severe recurrent HSV/VZV ocular disease, and disseminated molluscum contagiosum; ocular involvement may be the first indicator of underlying immunodeficiency

Clinical Diagnosis

Viral conjunctivitis remains primarily a clinical diagnosis. The diagnostic triad of watery discharge, follicular conjunctival reaction, and preauricular lymphadenopathy in the context of a preceding or concurrent upper respiratory infection is highly characteristic. Accurate clinical differentiation from bacterial and allergic conjunctivitis guides appropriate management and infection control measures.

• History: Assess onset, laterality, discharge character, contact history (infected individual, swimming pools, institutional outbreaks), systemic symptoms (sore throat, fever, rash, vesicular skin lesions), prior herpes episodes, immunocompromised status, contact lens use, and recent travel
• Visual acuity: Reduced VA not clearing with blink warrants urgent corneal assessment and raises concern for SEIs involving the visual axis, keratitis, or anterior uveitis
• External examination: Assess for preauricular lymphadenopathy (palpate pre-tragal region), vesicular or crusted lid lesions (HSV/HZO), dermatomal rash, and Hutchinson’s sign
• Slit lamp biomicroscopy: Examine palpebral conjunctiva for follicles vs. papillae; assess discharge character; evaluate cornea using white light and fluorescein for PEEs, SEIs, dendritic ulcer, or stromal haze; assess anterior chamber for cells and flare (uveitis); evert upper lid to assess superior tarsal plate
• Fluorescein staining: Reveals PEEs (early EKC), geographic or dendritic ulcer (HSV), and SEIs (appear as non-staining subepithelial opacities with overlying corneal thinning on slit beam); rose bengal or lissamine green (optional; not routinely available in Singapore — used by practitioners in other regional contexts) further highlights devitalised cells at dendritic ulcer margins

Laboratory Investigations

• Rapid immunochromatographic assay (RPS Adeno Detector / AdenoPlus): Point-of-care lateral flow test detecting adenoviral antigen from conjunctival swab; sensitivity 85–90%, specificity >96% in the acute phase; reduces unnecessary antibiotic prescription; results available in 10 minutes; most accurate within first 5 days of symptom onset
• Conjunctival swab PCR: Gold standard for viral identification; highly sensitive (>95%) and specific; detects adenovirus, HSV-1/2, VZV, EV70, and other pathogens; indicated when diagnosis is uncertain, disease is severe, immunocompromised patient, outbreak investigation, or medicolegal documentation required; results available within 24–72 hours
• Conjunctival scraping cytology (Giemsa stain): Viral conjunctivitis characterised by mononuclear cells (lymphocytes and monocytes) and absence of bacteria; HSV shows multinucleated giant cells and intranuclear inclusions (Cowdry type A); chlamydial conjunctivitis shows basophilic intracytoplasmic inclusions in epithelial cells; a predominantly neutrophilic response indicates bacterial aetiology
• Viral culture: Historically the gold standard; now largely replaced by PCR due to superior sensitivity and faster turnaround; still used in research settings and outbreak investigations requiring serotyping
• Serology: HSV and VZV IgM/IgG titres occasionally useful in atypical or severe cases; EBV heterophile antibody test (monospot) if infectious mononucleosis suspected; generally not required in routine acute conjunctivitis
• Corneal sensitivity testing: Reduced corneal sensation (cotton wisp or Cochet-Bonnet aesthesiometry) indicates herpetic involvement of the corneal nerves — important finding in HSV and HZO that influences management

Key Differentiating Features

General Prognosis

The prognosis of viral conjunctivitis is largely determined by the causative pathogen. The majority of adenoviral cases are self-limiting and resolve without permanent sequelae, though the prolonged contagious period and discomfort of acute EKC impose significant quality-of-life and occupational burden. Herpetic disease carries a considerably more guarded prognosis due to the risk of recurrence, progressive corneal scarring, and vision loss.

Prognosis by Aetiology