Conjunctivitis

Conjunctivitis (pink eye) is a very common inflammation of the conjunctiva (the mucus membrane that lines the inside of the eyelids and the sclera). It is most commonly caused by viruses or bacteria but can also have noninfectious (e.g., allergic) causes. It is also commonly associated with corneal inflammation (then referred to as keratoconjunctivitis). Conjunctivitis is the most common cause of ocular hyperemia. Other classic features are burning, foreign body sensation, excessive tearing, and photophobia. Additionally, in infectious conjunctivitis, general signs of viral or bacterial infection (e.g., fever) may be seen, while itching is particularly common in allergic conjunctivitis. Dry eye is a hallmark feature of keratoconjunctivitis sicca. In most cases, local pharmacologic therapy with antiinfective, antiinflammatory and/or antiallergic agents is sufficient. However, bacterial conjunctivitis can lead to blindness in newborns; therefore, strict and rapid treatment and prevention is vital. Surgical intervention is only rarely useful or necessary (e.g., correction of eyelids). An important differential diagnosis of conjunctivitis is subconjunctival hemorrhage, which is a collection of blood between the conjunctiva and the sclera that typically appears as a focal, red region on the surface of the eye.

• Conjunctival injection: conjunctival hyperemia with dilatation of blood vessels → ocular hyperemia and reddening
• Discharge and crust formation
• Chemosis: edema of eyelids and/or conjunctiva
• Burning or foreign-body sensation
• Photophobia
• Itching (most intense in seasonal allergic conjunctivitis)

• Epidemiology
  • Most common type of conjunctivitis
  • Incidence rises during the late fall and early spring
• Etiology: adenoviruses (most common), herpes simplex virus (HSV), varicella-zoster virus (VZV), picornavirus, molluscum contagiosum, HIV (highly contagious), measles, zika
  • Epidemic keratoconjunctivitis (“pinkeye”)
    • Pathogen: specific adenovirus subtypes
    • Transmission: direct contact, fecal-oral route, or contaminated water (e.g., swimming pools)
  • Pharyngoconjunctival fever (PCF)
    • Pathogen: adenovirus 3
    • Transmission: direct contact, fecal-oral route, or contaminated water
  • Herpes simplex conjunctivitis
    • Pathogen: usually HSV-1 in children (most common) and adults (HSV-2 infection may occur in neonates)
    • Transmission: close personal contact with inoculation into conjunctiva
• Clinical features
  • See “Clinical features” above.
  • Epidemic keratoconjunctivitis
    • Sudden onset, acute course (lasts 7–21 days)
    • Subconjunctival and petechial hemorrhage
    • Eyelid ecchymosis
    • Multifocal epithelial punctate keratitis → anterior stromal keratitis
      • During acute phase: diffuse epithelial keratitis (in some cases with epithelial defect)
      • After ∼ 1 week: focal epithelial keratitis
      • After ∼ 2 weeks: subepithelial infiltrates
    • Unilateral preauricular lymphadenopathy
    • Increased lacrimation
    • Severe cases
      • Membrane or pseudomembrane formation → conjunctival scarring
      • Anterior uveitis
      • Vision loss (rare)
  • Pharyngoconjunctival fever: fever, pharyngitis, acute follicular conjunctivitis (unilateral or bilateral), tender preauricular lymphadenopathy
  • Herpes simplex conjunctivitis
    • Vesicular blepharitis
    • Dendritic epithelial keratitis of cornea or conjunctiva
    • Endothelialitis, trabeculitis, or uveitis
• Diagnosis
  • Clinical diagnosis and history of upper respiratory infection, if present
  • Conjunctival smear and cultures, viral isolation, or PCR if symptoms are recurrent/chronic
• Treatment
  • Adenovirus: usually supportive (application of cold and moist compresses, artificial tears)
  • Herpes simplex: topical antiviral (e.g., ganciclovir)
  • Topical antibiotics if bacterial superinfection is suspected
• Prognosis: usually self-limiting
• Prevention: disinfect hands and instruments, avoid sharing towels, shaking hands, or touching eyes

Patient education regarding proper hygiene is essential to prevent an outbreak!

References: ^[1][2][3]

General

• Etiology: Staphylococcus aureus (most common in adults); , Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas, Haemophilus, and Moraxella catarrhalis
• Clinical features: See “Clinical features” above.
• Diagnosis
  • Clinical diagnosis
  • Conjunctival scrapings and culture (or PCR) required if persistent or severe disease (i.e., multiple or large corneal lesions), if the diagnosis is uncertain, and in newborn conjunctivitis
• Treatment: Topical broad-spectrum antibiotics (e.g., erythromycin or trimethoprim-polymyxin B)
  • Special recommendations in newborn conjunctivitis
  • Neisserial and chlamydial infections require systemic treatment
• Prevention
  • Proper hygiene
  • Treatment of pregnant women and prophylaxis in newborns
  • Public health programs (e.g., mass treatment)

Neisserial conjunctivitis

• Etiology
  • Pathogen: Neisseria gonorrhoeae
  • Route of infection (highly contagious)
    • Young, sexually active adults: direct contact to contaminated secretions (e.g., from the genitalia to the hand to the eye)
    • Newborns: perinatally; presents 2–5 days after birth
• Clinical features
  • See “Clinical features” above; hyperacute conjunctivitis with marked eye swelling and profuse purulent discharge
  • Also preauricular lymphadenopathy
• Diagnosis: gram stain shows intracellular gram negative diplococci
• Treatment: IV or IM ceftriaxone plus oral azithromycin with saline irrigation (topical antibiotics may also be considered)
• Prevention: (in newborns): erythromycin ophthalmic ointment ^[4]

N. gonorrhoeae infection is an ocular emergency that can lead to keratitis, perforation, and blindness without prompt treatment!

Trachoma (granular conjunctivitis)

• Etiology
  • Infection with Chlamydia trachomatis type A–C
  • Route of infection: direct (human-to-human contact with eyes or nose) or indirect (flies or towels) contact
  • Incubation period: 5–12 days
• Epidemiology
  • A common infectious cause of blindness worldwide ^[5]
  • Endemic primarily in developing countries; Africa is the most affected continent.
  • Predominantly affects young children and women
• Clinical features: See “Clinical features” above.
  • Often a chronic infection
  • Can be divided into two stages, which may occur simultaneously:
    • Active phase; : conjunctival follicles (with eventual involution forming Herbert pits), inflamed upper tarsal conjunctiva
    • Cicatricial phase : chronic/recurring inflammation in both eyes → conjunctival scarring → progressive conjunctival shrinkage → corneal ulcers and opacities, superficial neovascularization with cellular infiltration (corneal pannus), entropion, trichiasis
• Diagnosis: clinical diagnosis
• Treatment/Prevention
  • Antibiotics
    • Drug of choice: single oral dose azithromycin
    • Alternative: topical tetracycline (for six weeks)
  • Surgical intervention (eyelid correction in trichiasis)
  • Hygienic measures (particularly facial cleanliness) and environmental improvement (e.g., supply of clean water)
• Prognosis: good (if treated early)

Chlamydia trachomatis serotypes A, B, and C are most common in Africa and can cause Blindness and Chronic infection.

The WHO introduced the SAFE strategy for trachoma elimination: Surgery, Antibiotics, Facial cleanliness, Environmental improvement.

Inclusion conjunctivitis (paratrachoma)

• Epidemiology: more common in industrialized countries
• Etiology
  • Pathogen: Chlamydia trachomatis types D–K
  • Route of infection: sexually; , perinatally, or via swimming pools
• Clinical features: See “Clinical features” above.
  • Conjunctival follicles
  • Papillary hypertrophy
  • Corneal pannus
  • Preauricular lymphadenopathy
• Treatment/prevention: : oral azithromycin, erythromycin, or doxycycline

References:^[6][7][8]

Gonococcal conjunctivitis is an emergency. Suspect and treat for gonococcal infection in newborns with conjunctivitis unless another cause of infection is found.

References:^[9][10]

Ocular cicatricial pemphigoid (OCP)

• Etiology: autoimmune
• Epidemiology: predominantly affects older women
• Pathology: subepithelial blistering with subsequent scarring
• Symptoms/Clinical features
  • Paroxysmal, chronic course, often with unilateral onset
  • General signs and symptoms of conjunctivitis
  • Progressive scarring of the conjunctiva: subepithelial fibrosis → fornix shortening → symblepharon → ankyloblepharon with immobilization of the globe
  • Extraocular features: oral lesions (e.g., gingivitis), skin lesions on head, neck or upper trunk
• Diagnostics: biopsy → histologic staining (immunofluorescent staining of antibodies)
• Treatment
  • Systemic immunosuppression
    • Mild to moderate disease: e.g., dapsone or methotrexate
    • Severe disease: cyclophosphamide + prednisone
  • Symptomatic: moisturizing eye drops
  • Surgical therapy: e.g., correction of symblephara
• Prognosis
  • Usually chronic progression (∼ 10–30 years from symptom onset to end stage) with periods of remission and exacerbation
  • Individual progression on or off treatment is unpredictable (long term follow-up is vital)

Allergic conjunctivitis

• Epidemiology: common in young adults
• Pathophysiology: :IgE-mediated hypersensitivity (type I) against specific allergens (e.g., cat dander)
• Subtypes and key features
  • Seasonal allergic conjunctivitis (SAC)
    • Seasonal
    • Less acute onset and severe than the other types
  • Perennial allergic conjunctivitis (PAC)
    • Seasonal or occurs all year round
    • Similar features to SAC
  • Giant papillary conjunctivitis (GPC)
    • Chronic mechanical irritation (often by contact lenses) in combination with exposure to allergens
    • Giant papillae at the tarsal conjunctiva of the upper lid
  • Atopic keratoconjunctivitis (AKC)
    • Associated with atopic dermatitis of the eyelids
    • Papillary reaction in the inferior tarsal conjunctiva
  • Vernal keratoconjunctivitis (VKC)
    • ♂ > ♀, especially with atopic disease
    • Seasonal
    • Forms
      • Palpebral: giant papillae
      • Limbal : Horner-Trantas dots , Shield ulcer
    • Frequently associated with blepharospasm, conjunctival scarring, and corneal damage
• Clinical features
  • Bilateral symptoms
  • General signs and symptoms of conjunctivitis
  • Itching
  • Excessive tearing (in SAC, PAC, and VKC)
  • Ptosis (mainly in VKC, sometimes in GPC)
  • Sneezing (in SAC and PAC)
• Treatment
  • Avoid chronic irritation (contact lenses, allergens)
  • Local
    • Cold compresses
    • Artificial tears
    • NSAIDs (e.g., ketorolac)
    • Antihistamines and mast-cell stabilizers; (e.g., ketotifen)
    • Corticosteroids (e.g., fluorometholone): second-line treatment for SAC
    • Calcineurin inhibitors (e.g., cyclosporine) for VKC and AKC
  • Systemic: oral antihistamines (e.g., cetirizine)

Keratoconjunctivitis sicca (dry eye disease)

• Definition: disease of the eye surface caused by underproduction or changes in the composition of lacrimal fluid or by increased evaporation
• Epidemiology
  • Very common in the US, especially > 40 years
  • ♀ > ♂
• Etiology
  • Environmental factors
  • Often associated with blepharitis (inflammation of the edge of the lid)
  • Primary and secondary Sjögren's syndrome
  • Disorders of the lid positioning or ↓ blink rate (e.g., cranial nerve lesions V or VII)
  • Medication: systemic or local
  • Vitamin A deficiency
  • Contact lenses
• Clinical features
  • General signs and symptoms of conjunctivitis
  • Dry eyes; (paradoxically, excessive tearing is also possible )
  • Blurred vision
  • Entropion or ectropion
• Diagnosis
  • Primarily a clinical diagnosis
  • Slit-lamp examination
    • Conjunctival injection (usually symmetric and bilateral)
    • Punctate epithelial erosions (superficial punctate keratitis)
    • Epithelial filaments on the corneal surface (filamentary keratitis)
  • Also see “Sjögren's syndrome.”
• Treatment
  • Avoid triggers (e.g., dry air) or change environment (e.g., use of humidifiers)
  • Patient education on eyelid hygiene
  • Medical therapy
    • Artificial tears and ocular lubricants
    • If symptoms persist despite above therapy
      • Topical corticosteroids and/or cyclosporine
      • Topical or systemic Omega-3 supplementation
      • Topical or systemic tetracyclines (for meibomitis or rosacea)
      • Moisture chamber spectacles
  • Surgical (if symptoms persist despite above medical therapy)
    • Punctal occlusion (after inflammation controlled)
    • Correction of eyelid abnormalities.

References:^[11][12]

Subconjunctival hemorrhage (SCH) ^[13][14]

• Definition: collection of blood between the conjunctiva and the sclera secondary to bleeding from conjunctival or episcleral capillaries
• Etiology
  • Transiently increased venous pressure (the most common cause of spontaneous SCH): Valsalva maneuver, coughing, vomiting
  • Traumatic eye injury: blunt ocular trauma, contact lens use (more common in adults < 40 years)
  • Hypertension (most common cause in elderly individuals)
  • Diabetes mellitus
  • Coagulopathy
  • Antiplatelet and anticoagulation therapy
  • Vaginal delivery is a common cause of SCH in neonates
  • Ocular surgery
  • Tumors of the conjunctiva (e.g., cavernous hemangioma, lymphangioma)
  • Fat emboli (e.g., in the context of long-bone fractures)
• Clinical features
  • Painless red focal region on the surface of the eye
  • Signs and symptoms of traumatic eye injury:
    • Changes in visual acuity, photophobia, eye pain, foreign body sensation
    • Bullous SCH: elevated hemorrhage indicates underlying severe intraocular injury e.g., scleral laceration
• Diagnosis
  • Usually based on eye exam and absence of other symptoms
  • In patients with a history of blunt trauma
    • Slit lamp exam to rule out conjunctival lacerations, abrasions, and foreign bodies
    • CT to rule out intraocular or intraorbital injury
      • Eye globe rupture (open globe injury, closed globe injury)
      • Orbital fractures
      • Retrobulbar hemorrhage
  • Recurrent SCH: rule out underlying conditions
    • Blood pressure measurement
    • Coagulation studies to rule out bleeding diathesis or overmedication
  • A suspicious or unlikely history of trauma in infants aged 1–12 months who present with SCH should raise concern for child abuse
• Treatment
  • Spontaneous SCH
    • Reassurance
    • Usually resolves spontaneously within 2 to 3 weeks
  • Traumatic SCH with conjunctival injury
    • Antibiotic ointment (erythromycin)
    • Removal of superficial foreign bodies (via slit lamp or saline irrigation)
    • Emergency ophthalmologic consultation
    • See “Traumatic eye injuries” for more details.

The differential diagnoses listed here are not exhaustive.