Noninfectious conjunctivitis

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Noninfectious conjunctivitis is an inflammation of the conjunctiva caused by mechanical irritation or systemic conditions (e.g., allergy, autoimmune disease). Common symptoms include itching and burning. Clinical history can help to differentiate between the subtypes, e.g., allergic conjunctivitis is associated with allergen exposure, giant papillary conjunctivitis with contact lens use, toxic conjunctivitis with ophthalmic medication use, and keratoconjunctivitis sicca with prolonged screen time. Diagnosis is usually clinical but in cases of diagnostic uncertainty, an ophthalmologist can perform confirmatory studies, including tear osmolarity and conjunctival biopsy. All patients should be started on supportive therapy for conjunctivitis and educated on preventive measures against noninfectious conjunctivitis. If symptoms persist, topical and systemic treatments may be required; these are usually provided in consultation with ophthalmology.

Allergic conjunctivitis is a common cause of conjunctivitis in individuals with a history of atopy.

Epidemiology ^[2]

• Affects up to 40% of the population
• Incidence appears to be increasing.

Pathophysiology ^[2]

IgE-mediated hypersensitivity (type I) to specific allergens (e.g., pollen, cat dander)

Clinical features ^[2][3][4]

• Classic clinical features of conjunctivitis ; ^[2][3]
  • Itching (most characteristic feature)
  • Dry eyes
  • Blurred vision
  • Excessive tearing
  • Typically occurs bilaterally
• Severe or chronic allergic conjunctivitis may manifest with: ^[2][3]
  • Allergic shiners
  • Ptosis
  • Giant papillae of superior tarsal conjunctiva (cobblestone appearance)
  • Corneal ulcer and conjunctival scarring
  • Limbal Horner-Trantas dots
  • Shield ulcer
• Other features of atopy may be present, e.g.: ^[2]
  • Atopic dermatitis of the eyelid
  • Allergic rhinitis
  • Nasal polyps

Diagnostics ^[2]

• Primarily a clinical diagnosis
• To identify allergens or exclude differentials, a specialist may order supportive studies, e.g.:
  • Skin prick test
  • Conjunctival allergen challenge
  • Patch test
  • Total IgE in tears

Treatment ^[2][3]

• Avoid exposure to known allergens; see also “Prevention of noninfectious conjunctivitis.”
• Initiate supportive therapy for conjunctivitis, e.g., artificial tears.
• Optimize management of comorbid conditions (e.g., allergic rhinitis).
• Start pharmacological therapy for allergic conjunctivitis.
• Refer patients with red flag features in conjunctivitis to ophthalmology. ^[2]

Pharmacological therapy for allergic conjunctivitis

• Mild symptoms ^[2][3]
  • Start first-line topical treatments. ^[3]
    • Combined vasoconstrictor/antihistamine, e.g., naphazoline/pheniramine ^[4]
    • Histamine H1 receptor antagonists, e.g., azelastine ^[2]
  • If symptoms remain uncontrolled, consider adding alternatives.
    • Oral antihistamines, e.g., cetirizine (off-label)
    • Topical NSAIDs, e.g., ketorolac ^[4]
• Severe, persistent, or refractory symptoms
  • Consider topical mast-cell stabilizers (e.g., cromolyn sodium ) alone or as a combined mast cell stabilizer/H1 receptor antagonist (e.g., ketotifen ). ^[2][3]
  • Refer to a specialist for management; further treatments include:
    • Corticosteroids (e.g., loteprednol)
    • Calcineurin inhibitors (e.g., cyclosporine, tacrolimus)
    • Allergen-specific immunotherapy ^[3]

Giant papillary conjunctivitis is a form of noninfectious conjunctivitis associated with mechanical irritation.

Etiology ^[3][5]

• Unclear; thought to be a combination of mechanical irritation and immune response to foreign bodies
• Risk factors include:
  • Contact lens use (most common)
  • Ocular sutures
  • Ocular prostheses
  • Corneal foreign bodies

Clinical features ^[3][5]

• Clinical features of conjunctivitis
• Reduced tolerance for contact lens use
• Blurred vision
• Mucoid discharge
• Formation of giant papillae of superior tarsal conjunctiva (cobblestone appearance)
• Eyelid edema
• Ptosis

Diagnostics ^[6]

Diagnosis is clinical.

Treatment ^[3]

• Treat the underlying cause.
  • Advise patients wearing contact lenses to:
    • Change to disposable lenses or, if already using them, change lenses more frequently (daily disposables are recommended).
    • Decrease wear time.
    • Follow contact lens hygiene precautions.
    • Change the contact lens polymer.
    • Consider discontinuing contact lens use.
  • Remove or replace sutures.
  • Clean or replace prostheses.
• Consider topical antiinflammatories or corticosteroids if symptoms persist.

Keratoconjunctivitis sicca is a common disorder in which defects in the production or composition of tears cause conjunctival irritation.

Epidemiology ^[7]

• Very common in the US, especially in individuals > 40 years of age
• ♀ > ♂

Pathophysiology

Irritation and damage to the ocular surface epithelium is caused by underproduction or changes in the composition of lacrimal fluid or by increased evaporation.

Risk factors ^[7]

• Environmental factors: e.g., dry room air, smoke, prolonged screen time
• Eyelid conditions, e.g.:
  • Blepharitis
  • Disorders of the lid positioning (e.g., entropion or ectropion)
  • ↓ Blink rate (e.g., cranial nerve lesions V or VII)
• Medication: systemic or local
• Vitamin A deficiency ^[8]
• Contact lens intolerance
• Local injury: e.g., trauma or resulting from surgery or radiation,
• Associated conditions include:
  • Rosacea
  • Systemic autoimmune diseases (e.g., primary and secondary Sjogren syndrome)
  • Infections (e.g., herpes simplex keratitis, HIV)

Clinical features ^[7]

• Dry eyes
• Burning or itching sensation; see also "Clinical features of conjunctivitis.”
• Blurred vision (does not usually lead to vision loss)
• Slit-lamp examination findings may include:
  • Conjunctival injection (usually symmetric and bilateral)
  • Punctate epithelial erosions (superficial punctate keratitis)
  • Epithelial filaments on the corneal surface (filamentary keratitis)
• Symptoms of connective tissue disorders may also be present.

Dry eye is a chronic disease in which symptoms worsen over the course of the day with prolonged eye strain and exposure to dry environments. ^[7]

Diagnosis ^[7]

• Primarily a clinical diagnosis
• Specialty tests to support the diagnosis may include:
  • Assessment of tear osmolarity
  • Schirmer test
  • Ocular surface dye staining
• Consider testing for autoimmune conditions.

Treatment ^[7]

• Treat underlying systemic causes (e.g., autoimmune conditions).
• Address modifiable risk factors, e.g.:
  • When possible, discontinue medications causing dry eye and switch to an alternative therapy.
  • Avoid triggers, e.g., dry air, cigarette smoke, prolonged screen time.
• Provide supportive therapy for conjunctivitis, including:
  • Artificial tears (during the day)
  • Ocular lubricants (during the night)
• Refer patients with severe and/or persistent symptoms to ophthalmology for further management, including:
  • Moisture chamber spectacles or special contact lenses
  • Pharmacotherapy
    • Topical treatments include lifitegrast, antibiotics, immunomodulators (e.g., corticosteroids, cyclosporine)
    • Oral treatments include antibiotics, secretagogues, and omega-3 supplements. ^[7]
  • Surgery, e.g., punctal occlusion, correction of eyelid abnormalities

Treat dry eye syndrome before certain surgeries (e.g., keratorefractive surgery, cataract), as symptoms can worsen postoperatively. ^[7]

Ocular cicatricial pemphigoid (a subset of benign mucous membrane pemphigoid) is a chronic autoimmune disorder of the conjunctiva. ^[9]

Epidemiology

• Rare condition
• Predominantly seen in women approx. > 50 years of age ^[10]

Pathophysiology

Subepithelial blistering may lead to scarring and, in severe cases, blindness.

Clinical features ^[3]

• Can manifest as a chronic condition with periods of remission and exacerbation
• Early stages: unilateral with general signs and symptoms of conjunctivitis
• Advanced disease
  • Bilateral
  • Progressive scarring of the conjunctiva: subepithelial fibrosis → fornix shortening → symblepharon → ankyloblepharon or immobilization of the globe
  • Vision loss
• Extraocular features of mucous membrane pemphigoid may be present, including:
  • Oral lesions
  • Skin lesions of the head, neck, or upper trunk

Diagnostics ^[3][10]

• Usually a diagnosis of exclusion ^[3]
• Confirmatory test: conjunctival biopsy with immunofluorescent staining of antibodies ^[3]

Ocular cicatricial pemphigoid is a diagnosis of exclusion; as part of the diagnostic process, stop all medications that could be causing toxic conjunctivitis. ^[3]

Management

• Promptly refer to ophthalmology to confirm the diagnosis.
• Initiate supportive treatment for conjunctivitis.
• Specialized treatment may include:
  • Systemic immunosuppression, e.g., dapsone, methotrexate, cyclophosphamide, IVIG ^[9]
  • Surgery for complications (e.g., correction of symblepharon)

Response to treatment is variable and follow-up with a specialist is necessary. ^[3]

Toxic keratoconjunctivitis is caused by exposure to an environmental irritant (e.g., air pollution, chemicals) or medications.

Etiology

• Conjunctivitis medicamentosa: a reaction to topical ophthalmic medications ^[11][12]
• Environmental factors (e.g., air pollution)
• Harsh chemicals (e.g., in swimming pools)
• Contact lenses and/or solutions ^[11]

Glaucoma medications appear to be particularly prone to causing toxic conjunctivitis and scarring (pseudopemphigoid), even when a preservative-free formulation is used. ^[11]

Clinical features ^[11]

• Unilateral or bilateral
• Hyperemia, chemosis, eyelid edema (see also “Clinical features of conjunctivitis”)
• Conjunctival follicles
• Conjunctival scarring and corneal ulceration with chronic exposure

Diagnosis ^[11]

• Primarily a clinical diagnosis based on the history of exposure to an irritant
• Confirmatory studies include :
  • Ocular surface stains (e.g., fluorescein)
  • Conjunctival biopsy

Management

• Discontinue any offending topical medications. ^[11]
• Provide supportive treatment for conjunctivitis.
• Refer to an ophthalmologist for the following:
  • Ocular chemical burn
  • Red flag features in conjunctivitis
  • Persistent or severe symptoms despite supportive therapy
• Educate patients on preventive measures against noninfectious conjunctivitis.