Conjunctivitis

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Original article contributed by:

Martha Cecilia López Montero, MD

All contributors:

S. Grace Prakalapakorn, MD, MPH and Martha Cecilia López Montero, MD

Assigned editor:

S. Grace Prakalapakorn, MD, MPH

Review:

Assigned status Update Pending

 by S. Grace Prakalapakorn, MD, MPH on December 4, 2020.

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Conjunctivitis

DiseasesDB

3067

ICD-10

H10.9

Disease Entity

Disease

Inflammation or infection of the conjunctiva is known as conjunctivitis and is characterized by dilatation 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.

• Viral conjunctivitis is the most common cause of infectious conjunctivitis both overall and in the adult population and is more prevalent in summer.
• Bacterial conjunctivitis is the second most common cause and is responsible for the majority (50%-75%) of cases in children; it is observed more frequently from December through April.
• Allergic conjunctivitis is the most frequent cause, affecting 15% to 40% of the population and is observed more frequently in spring and summer

Etiology

Conjunctivitis can be divided into infectious and noninfectious causes. Viruses and bacteria are the most common infectious causes.

1. Bacterial causes:
   • Acute and subacute bacterial causes includes:
     • Neiseria gonorrhoeae
     • Neiseria meningitides
     • Streptococo pneumonia
     • Heamophilus influenza
   • Chronic conjunctivitis:
     • Staphylococus aureus
     • Moraxella lacunata
   • Less common causes includes:
     • Streptococus
     • Moraxella catarrhalis
     • Corynebacterium diphteriae
     • Mycobacterium tuberculosis
2. Chlamydia trachomatis
3. Viral conjunctivitis:
   • Acute viral follicular conjunctivitis
   • Chronic viral follicular conjunctivitis
   • Viral blepharoconjunctivitis
4. Rickettsia
5. Fungus
6. Parasitic conjunctivitis
7. Allergic causes
8. Toxic
   • Idoxuridine
   • Brimonidine
   • Apraclonidine
   • Dipivefrin
   • Contact lens solution
9. Secondary to systemic causes
   • Immune-mediated diseases and neoplastic processes.

Risk Factors

Bacterial conjunctivitis

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

Viral conjunctivitis

Direct contact with:

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

Allergic conjunctivitis

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

General Pathology

Inflammation or infection of the conjunctiva is known as conjunctivitis and is characterized by dilatation 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:

• Chronic Follicular Conjunctivitis
• Granulomatous Conjunctivitis
• Papillary 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. When Inflammation or infection of the conjunctiva occurs is known as conjunctivitis and is characterized by dilatation of the conjunctival vessels, resulting in hyperemia and edema of the conjunctiva, typically with associated discharge

Bacterial conjunctivitis:

Sometimes, bacterial conjunctivitis can be contracted directly of infected individuals, or by an abnormal proliferation of the native conjunctival flora, or can result from the spread of infection from the organisms colonizing the patient's own 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

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

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

The course of the disease usually lasts 7 to 10 day.

• Hyperacute bacterial is often caused by Neisseria gonorrhoeae. When Conjunctivitis not responding to standard antibiotic therapy in sexually active patients a chlamydial infection should be suspected.
• Chronic bacterial is commonly caused Staphylococcus aureus, Moraxellalacunata, and enteric bacteria

Viral conjunctivitis

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

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

Between 65% and 90% of cases of viral conjunctivitis are caused by adenoviruses, and they produce 2 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 lymphadenopathy. 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:  Herpes simplex virus comprises 1.3% to 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 nonspecific 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 it´s 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 3 branches.

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

Bacterial conjunctivitis

• Hyperacute bacterial conjunctivitis has a period of incubation and communicability estimated to be 1 to 7 days.
• Chronic bacterial conjunctivitis is used to describe any conjunctivitis lasting more than 4 weeks. It has an incubation period from 2 to 7 days.

Viral conjunctivitis

Adenoviral conjunctivitis:  

Viral conjunctivitis secondary to adenoviruses is highly contagious, and the risk of transmission has been estimated to be 10% to 50%. Patients commonly refer contact with an individual with 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 to14 days for both clinical forms.

Herpes Virus conjunctivitis:

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

Allergic conjunctivitis

All clinical forms of allergic conjunctivitis present with symp­toms like redness, watering, discharge, and discomfort or sometimes pain of the eyes and, most importantly, with 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 (ezcema, asthma, urticaria, rhinitis).

Physical examination

Bacterial conjunctivitis

Signs and symptoms include red eye, purulent or mucopurulent discharge, and chemosis and presents with a severe copious purulent discharge and decreased vision. There is often accompanying eyelid swelling, eye pain on palpation, and preauricular adenopathy. When conjunctivitis is caused by Neisseria gonorrhoeae carries a high risk for corneal involvement and subsequent corneal perforation.

Bilateral mattering of the eyelids and adherence of the eyelids, lack of itching, and no history of conjunctivitis 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

Viral conjunctivitis

Conjunctivitis caused by adenoviruses:

• Pharyngoconjunctival fever presents 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, conjunctival membranes or pseudo membranes, hyperemia, chemosis, and ipsilateral lymphadenopathy. 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.
• 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 conjunctivitis caused by Herpes virus do 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 Hutchinson sign (vesicles at the tip of the nose, which has high correlations with corneal involvement)

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 certain of the most severe disorders. When the limbus becomes inflamed might presents a pale-pink coloration in an annular pattern or with characteristic white dots called Trantas Dot´s

Clinical presentation of disease subtypes

• Seasonal and perennial allergic conjunctivitis
• Atopic keratoconjunctivitis (AKC)
• Vernal keratoconjunctivitis (VKC)
• Giant papillary conjunctivitis (GPC)

Management

General treatment

Bacterial and Viral Conjunctivitis

Avoid spreading:

• Frecuent 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 to 14 days or as long eye looks red.

Medical treatment:

• Cold compresses
• Artificial tears

Allergic Conjunctivitis

The treatment consists in

• Allergen avoidance
• Immunotherapy, via parenteral and oral routes, has been shown to be effective in SAC and PAC.
• Non-specific medical therapy:
  • Cold compresses may be all that is required in mild SAC and PAC 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 AKC. Other cutaneous manifestations should be treated in conjunction with a dermatologist.

Medical therapy

Bacterial conjunctivitis

• Most cases are self-limiting within 1 to 2 weeks of presentation, but in cases caused by highly virulent bacteria, such as S. pneumoniae, N. gonorrhoeae, and H. influenzae might be beneficial reducing the duration of conjunctivitis.
• There are no significant differences among all broad-spectrum antibiotic eyedrops in achieving clinical cure. Factors that influence antibiotic choice are local availability, patient allergies, resistance patterns, and cost.
• Initial medical therapy dosing schedule for acute non-severe bacterial conjunctivitis is 4 times daily for approximately 5- 7 days of any of the following:
  • Polymixin combination drops
  • Aminoglycosides or fluoroquinolone (ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, or gatifloxacin) drops
  • Bacitracin or ciprofloxacin ointment.
• Topical steroids should be avoided because of the risk of potentially prolonging the course of the disease and potentiating the infection.
• Treatment for hyperacute conjunctivitis secondary to N gonorrhoea consists of 1 gr intramuscular Ceftriaxone, only dose and patient should be instructed on how to lavage the infected eye.
• Concurrent chlamydial infection should be managed with either 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

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 indicated in due they do not protect against secondary infections, and their use may complicate the clinical presentation by causing allergy and toxicity, leading to delay in diagnosis of other possible ocular diseases and they can even 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 to 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:

• 3% ophthalmic ointment 200, 400, 800 mg  5x/day for 10 days.
• 200 mg/5 mL suspensión, 400 mg 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.

Allergic Conjunctivitis

• Topical antihistamines: (Levocabastine, azelastine, and 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 and ketotifen). They 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)
• Ciclosporin

Additional Resources

• Boyd K, Pagan-Duran B. Conjunctivitis (Pink Eye) . American Academy of Ophthalmology. EyeSmart^® Eye health. https://www.aao.org/eye-health/diseases/conjunctivitis-pink-eye. Accessed March 07, 2019.

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. "