Difference between revisions of "Conjunctivitis"

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{{Infobox disease

Latest revision as of 11:50, March 9, 2021


Conjunctivitis


Disease Entity

Disease

Inflammation of the conjunctiva is known as conjunctivitis and is characterized by dilation of the conjunctival vessels, resulting in hyperemia and edema of the conjunctiva, typically with associated discharge. The prevalence of conjunctivitis varies according to the underlying cause, which may be influenced by the patient’s age, as well as the season of the year.

Etiology

For causes of neonatal conjunctivitis, see separate entry “Neonatal conjunctivitis”.

Conjunctivitis can be divided into infectious and noninfectious causes.

  • Noninfectious causes:
    • Allergic: the most frequent cause of conjunctivitis, affecting 15-40% of the population and is observed more frequently in the spring and summer.
    • Toxic:
      • Idoxuridine
      • Brimonidine
      • Apraclonidine
      • Dipivefrin
      • Contact lens solution
    • Secondary to systemic causes:
      • Immune-mediated diseases (e.g. sarcoidosis) and neoplastic processes
  • Infectious causes: viruses and bacteria are the most common infectious causes. In children, infectious conjunctivitis is caused by a similar number of bacterial and viral conjunctivitis cases.
    • Viral: the most common cause of infectious conjunctivitis in the adult population (80%) and is more prevalent in the summer.
      • Acute viral follicular conjunctivitis
      • Chronic viral follicular conjunctivitis
      • Viral blepharoconjunctivitis
    • Bacterial: the second most common cause of infectious conjunctivitis in the adult population; it is observed more frequently from December through April.
      • Acute and subacute bacterial causes include:
        • Neisseria gonorrhoeae
        • Neisseria meningitides
        • Streptococcus pneumoniae
        • Haemophilus influenzae
      • Chronic conjunctivitis:
        • Staphylococcus aureus
        • Moraxella lacunata
      • Less common causes include:
        • Streptococcus
        • Moraxella catarrhalis
        • Corynebacterium diphtheriae
        • Mycobacterium tuberculosis
        • Chlamydia trachomatis
  • Rickettsia
  • Fungus
  • Parasitic conjunctivitis

Risk Factors

Viral conjunctivitis

Direct contact with:

  • Contaminated fingers
  • Medical instruments
  • Swimming pool water
  • Personal items from an infected person

Bacterial conjunctivitis

  • Contact with contaminated fingers, fomites or oculo-genital contact with someone infected
    • Young, sexually active adults below the age of 25 years, have a high risk, especially if they do not use condoms on sexual encounters.
  • Compromised tear production or drainage
  • Disruption of the natural epithelial barrier
  • Abnormality of adnexal structures
  • Trauma
  • Immunosuppressed status

Allergic conjunctivitis

  • History of current or previous non-ocular allergic or atopic conditions (eczema, asthma, urticaria, rhinitis). 

General Pathology

Inflammation of the conjunctiva is known as conjunctivitis and is characterized by dilation of the conjunctival vessels, resulting in hyperemia and edema of the conjunctiva, typically with associated discharge.

The American Academy of Ophthalmology's Pathology Atlas contains virtual microscopy images of tissue samples with the following types of conjunctivitis:

Pathophysiology

The conjunctiva is a thin, transparent, vascular mucous membrane of a non-keratinizing squamous epithelium investing the inner lid surfaces and the anterior sclera, and it is important in maintaining a suitable environment for the cornea and as defense against infection and trauma. Conjunctivitis is the inflammation of the conjunctiva and is characterized by dilation of the conjunctival vessels, resulting in hyperemia and edema of the conjunctiva, typically with associated discharge.

Viral conjunctivitis

Adenoviral conjunctivitis: Viral conjunctivitis secondary to adenoviruses is highly contagious, and the risk of transmission has been estimated to be 10-50%.

Incubation and communicability are estimated to be 5-12 days and 10-14 days, respectively.

Between 65% and 90% of cases of viral conjunctivitis are caused by adenoviruses, and they produce two of the common clinical entities associated with viral conjunctivitis: pharyngoconjunctival fever, and epidemic keratoconjunctivitis.

  • Pharyngoconjunctival fever is characterized by abrupt onset of high fever, pharyngitis, and bilateral conjunctivitis, and by periauricular lymph node enlargement.
  • Epidemic keratoconjunctivitis is more severe and presents with watery discharge, hyperemia, chemosis, and ipsilateral periauricular lymphadenopathy. Lymphadenopathy is observed in up to 50% of viral conjunctivitis cases and is more prevalent in viral conjunctivitis compared with bacterial conjunctivitis.
  • Acute hemorrhagic conjunctivitis
  • Acute follicular conjunctivitis


Herpes virus conjunctivitis:  Herpes simplex virus (HSV) comprises 1.3-4.8% of all cases of acute conjunctivitis and conjunctivitis caused by the virus is usually unilateral.

Primary HSV-l infection in humans occurs as a non-specific upper respiratory tract infection. HSV spreads from infected skin and mucosal epithelium via sensory nerve axons to establish latent infection in associated sensory CN V and its ganglia. Latent infection of the trigeminal ganglion occurs in the absence of recognized primary infection, and reactivation of the virus may follow any of the three branches.

Bacterial conjunctivitis

Bacterial conjunctivitis can be contracted directly from infected individuals, by an abnormal proliferation of the native conjunctival flora, or from the spread of infection from the organisms colonizing the patient's nasal and sinus mucosa. Bacteria infiltrate the conjunctival epithelial layer and sometimes the substantia propia as well.

Direct infection and inflammation of the conjunctival surface, bystander effects on adjacent tissues such as the cornea, and the host's acute inflammatory response and long-term reparative response all contribute to the pathology.

In children, the disease is often caused by H. influenzae , S. pneumoniae , and Moraxella catarrhalis.

The most common pathogens for bacterial conjunctivitis in adults are Staphylococcal species, followed by Streptococcus pneumoniae and Haemophilus influenzae.

The course of the disease usually lasts 7-10 days.

  • Hyperacute bacterial conjunctivitis is often caused by Neisseria gonorrhoeae. When the infection does not respond to standard antibiotic therapy in sexually active patients, Chlamydia trachomatis should be suspected.
  • Chronic bacterial conjunctivitis is commonly caused Staphylococcus aureus, Moraxella lacunata, and enteric bacteria.

Allergic conjunctivitis

Allergic conjunctivitis is an inflammation of the ocular surface in response to a transient allergen (e.g. pollen in seasonal allergic conjunctivitis), or a persistent allergen (e.g. house dust mite in peren­nial allergic conjunctivitis). 

Seasonal allergic conjunctivitis (SAC) is a type I hypersensitivity response with conjunctival activated mast cells as a direct result of allergen cross-linking of surface IgE receptors resulting in degranulation and release of histamine, leukotrienes, proteases, prostaglandins, cytokines, and chemokines. All these substances induce vascular leakage, resulting in further cellular infiltration of eosinophils and neu­trophils and edema but little or no T-cell infiltration is observed.

In perennial allergic conjunctivitis (PAC), the conjunctival tissue is infiltrated by eosinophils, neutrophils, and a small number of T cells, probably recruited as a result of the release of chemokines that attract these cells to the site of inflammation during the persistent, allergen-driven inflammatory response.

Diagnosis

History

Viral conjunctivitis

Adenoviral conjunctivitis:  

Viral conjunctivitis secondary to adenoviruses is highly contagious, and the risk of transmission has been estimated to be 10-50%. Patients commonly report contact with an individual with a red eye, or they may have a history of recent symptoms of an upper respiratory tract infection.

Incubation and communicability are estimated to be 5-14 days for both clinical forms.

Herpes Virus conjunctivitis:

  • When primary ocular HSV infection occurs, the patient typically manifests unilateral, thin, and watery discharge and sometimes accompanying vesicular eyelid lesions.
  • In a small percentage of patients, there is a history of external ocular HSV infection that may lead to the diagnosis.

Bacterial conjunctivitis[1]

  • Conjunctivitis with hyperacute (<24 hours) onset of severe severity and very rapid progression. Symptoms include massive exudation, severe chemosis, eyelid edema, marked conjunctival hyperemia, and if left untreated, corneal infiltrates, melting, and perforation. It has an incubation period and communicability of 1-7 days and is commonly caused by:
    • Neisseria gonorrhoeae
    • Neisseria meningitidis
  • Conjunctivitis with acute or subacute onset (hours-days) of moderate to severe severity are commonly caused by:
    • Haemophilus influenzae biotype III (previously known as Haemophilus aegyptius)
    • Haemophilus influenzae
    • Streptococcus pneumoniae
    • Streptococcus viridans
    • Staphylococcus aureus
  • Chronic bacterial conjunctivitis is used to describe any conjunctivitis lasting more than 4 weeks. It has an incubation period of 2-7 days.

Allergic conjunctivitis

All clinical forms of allergic conjunctivitis present with symp­toms such as redness, watering, discharge, and discomfort or eye pain, and most importantly, ocular itching which is unusual in non-allergic eye condi­tions. Visual disturbance is usually minimal except in the more severe disorders and patients may also complain of swelling of the lids.

Many patients with allergic conjunctivitis will have a history of current or previous non-ocular allergic or atopic conditions (eczema, asthma, urticaria, rhinitis).

Physical examination

Viral conjunctivitis

Conjunctivitis caused by adenoviruses:

  • Pharyngoconjunctival fever presents by abrupt onset of high fever, pharyngitis, subconjunctival hemorrhage, bilateral conjunctivitis, and by preauricular lymph node enlargement.
  • Epidemic keratoconjunctivitis is more severe and presents with watery discharge, conjunctival membranes or pseudo membranes, hyperemia, chemosis, and ipsilateral preauricular lymphadenopathy. Can involve both epithelial and subepithelial corneal infiltrates.
  • Can affect the cornea, look for subepithelial infiltrates.
  • Lymphadenopathy is observed in up to 50% of viral conjunctivitis cases and is more prevalent in viral conjunctivitis compared with bacterial conjunctivitis.


Herpes Virus conjunctivitis

  • The eyelids often are edematous and ecchymotic. Watery discharge and preauricular lymphadenopathy may be present. Usually unilateral.
  • Cutaneous or eyelid margin vesicles, or ulcers on the bulbar conjunctiva
  • The cornea often demonstrates a punctate epitheliopathy. In severe cases, there can be a corneal epithelial defect (Dendritic epithelial keratitis). It typically begins in one eye and progresses to the fellow eye over a few days.
  • It is important to note that herpes virus conjunctivitis does not form conjunctival membranes or pseudo membranes.
    • Herpes zoster virus can involve ocular tissue, especially if the first and second branches of the trigeminal nerve are involved. Eyelids (45.8%) are the most common site of ocular involvement, followed by the conjunctiva. Corneal complication and uveitis may be present in 38.2% and 19.1% of cases, respectively. Severe forms include those presenting with the Hutchinson sign (vesicles at the tip of the nose, which has a high correlation with corneal involvement).

Bacterial conjunctivitis

  • Signs and symptoms include red eye, purulent or mucopurulent discharge, and chemosis and presents with severe copious purulent discharge and decreased vision. There is often accompanying eyelid swelling and eye pain on palpation. When conjunctivitis is caused by Neisseria gonorrhoeae, it carries a high risk for keratitis, endophthalmitis, corneal perforation, and systemic infection.
  • Bilateral mattering of the eyelids and adherence of the eyelids and lack of itching are strong positive predictors of bacterial conjunctivitis.
  • Severe purulent discharge should always be cultured.
  • The possibility of bacterial keratitis is high in contact lens wearers, who should be treated with topical antibiotics and referred to an ophthalmologist.  A patient wearing contact lenses should be asked to immediately remove them.

Allergic conjunctivitis

Classic ocular signs of allergic inflammation are lid swelling, diffuse conjunctival redness, and mild swelling, which often combine to give a pink rather than red color, and a velvety thickening and redness of the tarsal con­junctiva with the presence of fine excrescences called papillae, which may vary from tiny pinprick size to giant papillae which are >1 mm in diameter and give a cobblestone appearance under the lid. Macroscopic noticeable swelling of the conjunctiva, called ‘chemosis’, is sometimes seen. Other signs, such as der­matitis of the lid skin, inflammation of the lid margin (blepharitis), conjunctival scarring, and involve­ment of the cornea occur only in the most severe disorders. When the limbus becomes inflamed, it might present as a pale-pink coloration in an annular pattern or with characteristic white dots called Horner-Trantas dots.

Clinical presentation of disease subtypes:

  • Seasonal and perennial allergic conjunctivitis – may see lower-lid ecchymoses = allergic shiners
  • Atopic keratoconjunctivitis (AKC)
  • Vernal keratoconjunctivitis (VKC)
  • Giant papillary conjunctivitis (GPC)

Management

General treatment

Bacterial and Viral Conjunctivitis

Avoid spreading:

  • Frequent hand washing
  • Avoid sharing personal care objects such towels, cosmetics, etc
  • Avoid contact with eyes
  • Avoid shaking hands
  • Strict instrument disinfection
  • In hospitalized patients with viral conjunctivitis, isolation is recommended for 10-14 days or as long as the eye looks red


Medical treatment:

  • Cold compresses
  • Artificial tears

Allergic Conjunctivitis

The treatment consists of:

  • Allergen avoidance
  • Immunotherapy via parenteral and oral routes has been shown to be effective in seasonal and perennial allergic conjunctivitis.
  • Non-specific medical therapy:
    • Cold compresses may be all that is required in mild seasonal and perennial allergic conjunctivitis and may reduce the need for pharmacotherapy.
    • The use of topical normal saline or lubricants (artificial tears) will reduce symptoms and may help dilute or flush away allergen and inflammatory mediators. 
    • The use of cotton buds soaked in weak sodium bicarbonate or baby shampoo solution), application of topical antibiotic (and occasionally steroid) ointment, and systemic antibiotic therapy with a long-term low-dose regimen (e.g. doxycycline 100 mg daily for 3–6 months) is indicated to treat ocular symptoms in atopic keratoconjunctivitis. Other cutaneous manifestations should be treated in conjunction with a dermatologist.

Medical therapy

Viral conjunctivitis

Adenoviral conjunctivitis:

  • Although no effective treatment exists, artificial tears, topical antihistamines, or cold compresses may be useful in alleviating some of the symptoms.
  • Topical antibiotics should not be used since they do not protect against secondary infections, and their use may complicate the clinical presentation by causing allergies and toxicity, leading to a delay in diagnosis of other possible ocular diseases. Topical antibiotics can also increase the risk of spreading the infection to the other eye from a contaminated dropper.
  • Complications should be investigated if symptoms do not resolve after 7-10 days because of the risk of complications.


Herpes virus conjunctivitis:

  • Topical and oral antivirals are recommended to shorten the course of the disease.


Acyclovir:

  • 200, 400, 800 mg PO 5x/day for 10 days.
  • 5% dermatologic ointment, 6x/day for 7 days.


Ganciclovir:

  • 0.15% topical ophthalmic gel, 5x/day until epithelium heals; then 3x/day for 7 days
  • Topical corticosteroids should be avoided because they potentiate the virus and may cause harm.


Herpes Zoster conjunctivitis

  • Treatment usually consists of a combination of oral antivirals and topical steroids.

Bacterial conjunctivitis

  • Most cases are self-limited within 1-2 weeks of presentation, but in cases caused by highly virulent bacteria (e.g. S. pneumoniae, N. gonorrhoeae, and H. influenzae) antibiotic eyedrops might be beneficial in reducing the duration of the conjunctivitis.
  • There are no significant differences among the various broad-spectrum antibiotic eyedrops in achieving a clinical cure. Factors that influence antibiotic choice are local availability, patient allergies, resistance patterns, and cost.
  • Initial empiric therapy dosing schedule for acute non-severe bacterial conjunctivitis is 4-6 times daily for approximately 5-7 days of any of the following:
    • Polymyxin B-trimethoprim combination drops
    • Aminoglycosides or fluoroquinolone (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, or gatifloxacin) drops
    • Bacitracin or ciprofloxacin ointment
  • If results of the gram stain/culture show gram-negative coccobaccilli, the causative agent is probably Haemophilus species and should be treated with polymyxin B-trimethoprim, with supplemental oral antibiotics for patients with acute purulent conjunctivitis associated with pharyngitis, for those with conjunctivitis-otitis syndrome, and for children with Haemophilus conjunctivitis.[1]
  • Topical steroids should be avoided because of the risk of potentially prolonging the course of the disease and potentiating the infection. However, Holland et al. showed that these perceived risks are associated with long-term steroid uses that are dissimilar to applications for infective conjunctivitis.[2] They reported that corticosteroids, in combination with broad-spectrum anti-infectives, could be effective for acute conjunctivitis if used for short-term treatment of up to 2 weeks.
  • Treatment for hyperacute conjunctivitis without corneal ulceration secondary to N. gonorrhoeae may be given as an outpatient and consists of 1 g intramuscular ceftriaxone single dose, and the patient should be instructed on how to lavage the infected eye. Patients with hyperacute conjunctivitis with corneal ulceration secondary to N. gonorrhoeae should be admitted to the hospital and treated with 1 g q12h intravenous ceftriaxone for 3 consecutive days. If allergic to penicillin, patients should be given 2 g intramuscular spectinomycin or oral fluoroquinolones (ciprofloxacin 500 mg or ofloxacin 400 mg BID for 5 days).[1]
  • Concurrent chlamydial infection in adults should be managed with one of the following:
    • Azithromycin 1000 mg single dose
    • Doxycycline 100 mg BID for 7 days
    • Tetracycline 250 mg QID for 7 days
    • Erythromycin 500 mg QID for 7 days

Allergic Conjunctivitis

  • Topical antihistamines:
    • Levocabastine
    • Azelastine
    • Emedastine
    • These are commonly prescribed in combination with a sympathomimetic vasoconstrictor (e.g. antazoline– naphazoline).
  • Oral antihistamines
  • Topical mast cell inhibitors:
    • Cromolyn sodium/chlorphenamine
    • Nedocromil sodium
    • Lodoxamide tromethamine
    • Olopatadine
    • Ketotifen
    • These offer a preventive action and are most effective if used before the onset of symptoms where possible (e.g. at the beginning of the pollen season as their onset of action is relatively slow (5–7 days) and stinging upon instillation can occur particularly in the presence of active inflammation, patients should be warned that their eyes may initially feel worse.
  • Surface-acting steroids:
    • Fluorometholone
    • Rimexolone
  • Topical Cyclosporine

Additional Resources

References:

  1. Azari, Amir A., and Neal P. Barney. "Conjunctivitis." Jama 310.16 (2013): 1721. Web.
  2. Hingorani, Melanie, Virginia L. Calder, Leonard Bielory, and Susan Lightman. Allergy. 4th ed. Holgate: Elsevier, 2012. Print.
  3. Infectious Diseases of the External Eye: Microbial and Parasitic Infections: External Disease and Cornea. San Francisco, CA: American Academy of Ophthalmology, 2012. Print.
  4. "Silverman, Michael A., and Barry E. Brenner."Acute Conjunctivitis.": Overview, Clinical Evaluation, Bacterial Conjunctivitis. Web. 15 Jan. 2016
  5. "Ocular Pathology Atlas. American Academy of Ophthalmology Web site. https://www.aao.org/resident-course/pathology-atlas. Published 2016. Accessed December 21, 2016. " 
  1. 1.0 1.1 1.2 Basic and Clinical Science Course 2019-2020: External Disease and Cornea. San Francisco, CA: American Academy of Ophthalmology; 2019.
  2. Holland EJ, Fingeret M, Mah FS. Use of Topical Steroids in Conjunctivitis: A Review of the Evidence. Cornea. 2019;38(8):1062-1067.