Viral Conjunctivitis

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Practice Essentials

Viral conjunctivitis, or pinkeye, is a common, self-limiting condition that is typically caused by adenovirus. Other viruses that can be responsible for conjunctival infection include herpes simplex virus (HSV), varicella-zoster virus (VZV), picornavirus (enterovirus 70, Coxsackie A24), poxvirus (molluscum contagiosum, vaccinia), and human immunodeficiency virus (HIV).

Viral conjunctivitis is highly contagious, usually for 10-12 days from onset as long as the eyes are red. Patients should avoid touching their eyes, shaking hands, and sharing towels, among other activities. Transmission may occur through accidental inoculation of viral particles from the patient's hands or by contact with infected upper respiratory droplets, fomites, or contaminated swimming pools. The infection usually resolves spontaneously within 2-4 weeks.

Signs and symptoms

Signs and symptoms of viral conjunctivitis may include the following:

See Clinical Presentation for more details.

Diagnosis

Generally, a diagnosis of viral conjunctivitis is made on the clinical features alone. Lab tests are typically not necessary, but they may be helpful in some cases. Specimens can be obtained by culture and smear if inflammation is severe, in chronic or recurrent infections, with atypical conjunctival reactions, and in patients who fail to respond to treatment. Giemsa staining of conjunctival scrapings may aid in characterizing the inflammatory response.

See Workup for more details.

Management

Treatment of adenoviral conjunctivitis is supportive. Patients should be instructed to use cold compresses and lubricants, such as artificial tears, for comfort. Topical vasoconstrictors and antihistamines may be used for severe itching but generally are not indicated. For patients who may be susceptible, a topical astringent or antibiotic may be used to prevent bacterial superinfection.

Virus-specific treatments

Patients with conjunctivitis caused by HSV usually are treated with topical antiviral agents, including idoxuridine solution and ointment, vidarabine ointment, and trifluridine solution.

Treatment of VZV eye disease includes oral acyclovir to terminate viral replication.

For conjunctivitis associated with molluscum contagiosum, disease will persist until the skin lesion is treated. Removal of the central core of the lesion or inducement of bleeding within the lesion usually is enough to cure the infection.

Prevention

Preventing transmission of viral conjunctivitis is important. Both patient and provider should wash hands thoroughly and often, keep hands away from the infected eye, and avoid sharing towels, linens, and cosmetics. Infected patients should be advised to stay home from school and work. Those who wear contact lenses should be instructed to discontinue lens wear until signs and symptoms have resolved.

See Treatment and Medication for more details.

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Viral conjunctivitis. Image courtesy of Wikimedia Commons.

Background

Viruses are a common cause of conjunctivitis in patients of all ages. A variety of viruses can be responsible for conjunctival infection; however, adenovirus is by far the most common cause, and herpes simplex virus (HSV) is the most problematic. Less common causes include varicella-zoster virus (VZV), picornavirus (enterovirus 70, Coxsackie A24), poxvirus (molluscum contagiosum, vaccinia), and human immunodeficiency virus (HIV). Rarely, conjunctivitis is seen during systemic infection with influenza virus, Epstein-Barr virus, paramyxovirus (measles, mumps, Newcastle), or rubella. (See Etiology.)[1]

Viral conjunctivitis, although usually benign and self-limited, tends to follow a longer course than acute bacterial conjunctivitis, lasting for approximately 2-4 weeks. Viral infection is characterized commonly by an acute follicular conjunctival reaction and preauricular adenopathy. (See History and Physical Examination.)

See the following for more information:

Etiology

Adenoviral conjunctivitis is the most common cause of viral conjunctivitis. Particular subtypes of adenoviral conjunctivitis include epidemic keratoconjunctivitis (pink eye) and pharyngoconjunctival fever.

Viral conjunctivitis is highly contagious, usually for 10-12 days from onset as long as the eyes are red. Patients should avoid touching their eyes, shaking hands, and sharing towels, among other activities. Transmission may occur through accidental inoculation of viral particles from the patient's hands or by contact with infected upper respiratory droplets, fomites, or contaminated swimming pools.

Primary ocular herpes simplex infection is common in children and usually is associated with a follicular conjunctivitis. Infection usually is caused by HSV type I, although HSV type II may be a cause, especially in neonates. Recurrent infection, typically seen in adults, usually is associated with corneal involvement.

VZV can affect the conjunctiva during primary infection (chickenpox) or secondary infection (zoster). Infection can be caused by direct contact with VZV or zoster skin lesions or by inhalation of infectious respiratory secretions.

Picornaviruses cause an acute hemorrhagic conjunctivitis that is clinically similar to adenoviral conjunctivitis but is more severe and hemorrhagic. Infection is highly contagious and occurs in epidemics.

Molluscum contagiosum may produce a chronic follicular conjunctivitis that occurs secondary to shedding of viral particles into the conjunctival sac from an irritative eyelid lesion.

Vaccinia virus has become a rare cause of conjunctivitis because, with the elimination of smallpox, the vaccination rarely is administered. Infection occurs through accidental inoculation of viral particles from the patient's hands.

HIV is the etiologic agent of acquired immunodeficiency syndrome (AIDS). Ocular abnormalities in patients with AIDS primarily affect the posterior segment, but anterior segment findings have been reported. When conjunctivitis occurs in a patient with AIDS, it tends to follow a more severe and prolonged course than in patients without AIDS. In general, patients with AIDS may develop a transient, nonspecific conjunctivitis, characterized by irritation, hyperemia, and tearing, that requires no specific treatment. Microsporidia has been isolated from the cornea and conjunctiva of several patients with AIDS and keratoconjunctivitis. In these patients, symptoms included foreign body sensation, blurred vision, and photophobia; most cases resolved without antimicrobial therapy.

Epidemiology

US and international occurrence

Viral conjunctivitis is a common ocular disease in the United States and worldwide. Because it is so common, and because many cases are not brought to medical attention, accurate statistics on the frequency of the disease are unavailable. Viral infection frequently occurs in epidemics within families, schools, offices, and military organizations.

Sex predilection

Viral conjunctivitis can occur equally in men and women.

Age predilection

Viral conjunctivitis can affect all age groups, depending on the specific viral etiology. Usually, adenovirus affects patients aged 20-40 years. HSV and primary VZV infection usually affect young children and infants. Herpes zoster ophthalmicus results from reactivation of latent VZV infection and may present in any age group. Typically, the picornaviruses affect children and young adults in the lower socioeconomic classes.[2]

Prognosis

Most cases of viral conjunctivitis are acute, benign, and self-limited, although chronic infections have been reported. Long-term ocular sequelae are uncommon. The infection usually resolves spontaneously within 2-4 weeks. Subepithelial infiltrates may last for several months, and, if in the visual axis, they may cause decreased vision or glare.

Morbidity

Complications include the following: punctate keratitis with subepithelial infiltrates, bacterial superinfection, corneal ulceration with keratoconjunctivitis, and chronic infection.

Epithelial keratitis may accompany viral conjunctivitis. Punctate epithelial erosions that stain with fluorescein are commonly associated with viral keratitis. Rarely, these changes are sufficiently distinctive morphologically to allow identification of a specific type of virus as the etiologic agent. If the conjunctivitis persists or is severe, disturbances in the anterior stroma beneath the epithelial abnormalities may occur. In general, the stromal or subepithelial abnormalities are transient and resolve despite persistence of epithelial keratitis. However, in cases of adenoviral infection, the stromal abnormalities may persist for months to years, long after the epithelial changes have resolved. In such cases, these subepithelial infiltrates are considered to be immunologic in origin, the result of antigen-antibody reaction. If they are in the pupillary axis, they may cause decreased vision and/or glare.

Patient Education

To allay patient anxiety, it is helpful to inform patients that their symptoms may worsen during the first 4-7 days after onset before they begin to improve and may not resolve for 2-4 weeks. The contagiousness of the infection also should be emphasized. Proper isolation from the workplace or school is advisable to prevent epidemics.

Patients with conjunctivitis who wear contact lenses should be instructed to discontinue lens wear until signs and symptoms have resolved.

For patient education information, see the Eye and Vision Center and the Skin, Hair, and Nails Center, as well as Pinkeye, How to Instill Your Eyedrops, and Molluscum Contagiosum.

History

While the manifestations of various types of bacterial conjunctivitis are fairly homogenous, those of viral conjunctivitis can vary from one disease process to another. History should focus on eliciting information that will aid in differentiating the various etiologic agents of viral infection.

Inquire about timing, onset, and duration of systemic and ocular symptoms; severity and frequency of symptoms; appropriate risk factors; and personal and environmental exposures.

Patients with adenoviral conjunctivitis may give a history of recent exposure to an individual with red eye at home, school, or work, or they may have a history of recent symptoms of an upper respiratory tract infection. The eye infection may be unilateral or bilateral.

Patients may report ocular itching, foreign body sensation, tearing, redness, discharge, eyelids sticking (worse in the morning), and photophobia (with corneal involvement, as in epidemic keratoconjunctivitis).

Systemic manifestations are rare, except in cases of pharyngoconjunctival fever.

Primary ocular HSV infection predominantly affects young children and infants, but it may occur in individuals of all ages. Patients usually present with a red, irritated, watery eye. Often, concomitant eyelid skin involvement with multiple vesicular lesions is present.

VZV is characterized by a generalized vesicular eruption, fever, and constitutional symptoms. Ocular infection usually is unilateral and presents as small, papular lesions that erupt along the lid margin or at the limbus and may be accompanied by a mild follicular conjunctivitis.

Herpes zoster ophthalmicus represents reactivation of latent VZV infection of the trigeminal ganglion. It is characterized by a prodrome of fever, malaise, nausea, vomiting, and severe pain and skin lesions along the ophthalmic division of the trigeminal nerve. Conjunctival involvement includes hyperemia, follicular or papillary conjunctivitis, and a serous or mucopurulent discharge.

Acute hemorrhagic conjunctivitis has been reported in epidemics in association with 2 major picornaviruses: enterovirus 70 and Coxsackievirus A24. It mostly affects children and young adults in the lower socioeconomic classes. Patients experience a rapid onset of watery discharge, foreign body sensation, burning, and photophobia within 24 hours of exposure.

Molluscum contagiosum can produce a chronic follicular conjunctivitis in association with an irritative eyelid lesion. The lesion usually is a small, elevated, pearly, umbilicated nodule near the lid margin. Multiple lesions may be present, especially in patients who are HIV positive.

Other viruses are less frequent causes of conjunctivitis. In these cases, conjunctivitis usually occurs in association with a systemic illness and includes infections caused by influenza virus, Epstein-Barr virus, paramyxovirus (measles, mumps, Newcastle), rubella, or HIV.

Physical Examination

Typical signs of adenoviral conjunctivitis include preauricular adenopathy, epiphora, hyperemia, chemosis, subconjunctival hemorrhage, follicular conjunctival reaction, and occasionally a pseudomembranous or cicatricial conjunctival reaction. The cornea often demonstrates a punctate epitheliopathy. The eyelids often are edematous and ecchymotic. In severe cases, there can be a corneal epithelial defect. It typically begins in one eye and progresses to the fellow eye over a few days.

With HSV infection, vesicles may be present on the eyelid or face, the eyelids may be swollen, and an ulcerative blepharitis may be present.

Corneal involvement in HSV manifests as a dendritic keratitis with typical features of linear branching and dendritic figures.

Small, papular lesions that erupt along the lid margin or at the limbus are present with varicella conjunctivitis. These lesions may resolve without sequelae, or they may become pustular and form painful, reactive conjunctival ulcers.

In herpes zoster ophthalmicus, look for skin involvement with the appearance of a dermatomal pattern of vesicles. These vesicles may become necrotic, resulting in pitted scarring of the skin. Conjunctival involvement includes hyperemia, follicular or papillary conjunctivitis, and a serous or mucopurulent discharge. Preauricular adenopathy is common. Very early in the process, there may be multiple fine, dendritic corneal lesions, which disappear over a few days without treatment.

Acute hemorrhagic conjunctivitis starts unilaterally but rapidly involves the fellow eye within 1 or 2 days. Signs on examination include a swollen, edematous eyelid and pronounced hemorrhage beneath the bulbar conjunctiva.

Approach Considerations

Generally, a diagnosis of viral conjunctivitis is made on the clinical features alone. Signs of acute viral conjunctivitis include inferior palpebral conjunctival follicles, tender palpable preauricular lymph node, watery discharge, red and edematous eyelids, pinpoint subconjunctival hemorrhages, punctuate keratopathy, and membrane/pseudomembrane. Intraepithelial microcysts may be an early corneal finding, which, when present, is helpful in the diagnosis. Subepithelial corneal infiltrates may develop 1-2 weeks after the onset of the conjunctivitis. HSV infection may demonstrate the classic corneal dendrites.

Conventional laboratory identification can be expensive and time-consuming but may be helpful in certain circumstances.[3, 4, 5, 6]

Culture, Smear, and Stain

Specimens should be obtained for culture and smear if inflammation is severe, in chronic or recurrent infections, with atypical conjunctival reactions, and with failure to respond to treatment.

Giemsa staining of conjunctival scrapings may aid in characterizing the inflammatory response. Polymorphonuclear cells are prevalent in bacterial infections, whereas mononuclear cells and lymphocytes are seen with viruses.

Viral Isolation

Viral isolation methods may be helpful in the diagnosis of acute follicular conjunctivitis, but they are not indicated in chronic conjunctivitis.

Direct immunofluorescence monoclonal antibody staining and enzyme-linked immunosorbent assay (ELISA) are rapid and widely available detection techniques.

Alternative methods include the use of immunoperoxidase, electron microscopy, and polymerase chain reaction (PCR) assay.

Serologic tests are available but generally require 2 serum samples at least 2 weeks apart, which can delay treatment.

Approach Considerations

Treatment of adenoviral conjunctivitis is supportive. No evidence exists that demonstrates the efficacy of antiviral agents.

Symptomatic Treatment

Patients should be instructed to use cold compresses and lubricants, such as artificial tears, for comfort.

Topical vasoconstrictors and antihistamines may be used for severe itching but generally are not indicated, because they are minimally helpful and may cause rebounding of symptoms, as well as local toxicity and hypersensitivity.

Antibiotic and Topical Steroid Treatment

For patients who may be susceptible, a topical astringent or antibiotic may be used to prevent bacterial superinfection.

Topical steroids may be used for pseudomembranes or when subepithelial infiltrates impair vision, although subepithelial infiltrates may recur after discontinuing the steroids. Extreme caution should be taken when using corticosteroids, as they may worsen an underlying HSV infection.

A study by Wilkins et al focused on whether topical steroids improve the comfort of patients compared with hypromellose in acute presumed viral conjunctivitis. It found that the use of a short course of topical dexamethasone for patients with acute follicular conjunctivitis presumed to be viral in origin was not harmful.[7]

Virus-Specific Treatments

Adenoviral infection

An in vitro study using adenovirus 8 and A549 human epithelial cell cultures demonstrated that povidone-iodine at a concentration of 1:10 (0.8%) is highly effective against free adenovirus, less effective against intracellular adenoviral particles in already infected cells, and not significantly cytotoxic for healthy cells. Thus, povidone-iodine 0.8% may represent a potential option to reduce contagiousness in cases of adenoviral infections.[8]

HSV infection

Patients with conjunctivitis caused by HSV usually are treated with topical antiviral agents, including idoxuridine solution and ointment, vidarabine ointment, and trifluridine solution. An ophthalmologist should see any patient with ocular HSV infection.

VZV infection

Treatment of VZV eye disease includes oral acyclovir, 600-800 mg, 5 times daily for 7-10 days, to terminate viral replication. Topical corticosteroids usually are not indicated for conjunctivitis or keratitis.

Molluscum contagiosum

For conjunctivitis associated with molluscum contagiosum, disease will persist until the skin lesion is treated. Removal of the central core of the lesion or inducement of bleeding within the lesion usually is enough to cure the infection. Occasionally, surgical excision is required.

Considerations for other viral causes

Other viral causes of conjunctivitis generally are self-limited and treated supportively with compresses for comfort and topical antibiotics as necessary to prevent bacterial superinfection.

Treatment of Acute Hemorrhagic Conjunctivitis

Treatment of acute hemorrhagic conjunctivitis is supportive, as in adenoviral infection, and includes bed rest, cold compresses, and analgesics. Antibiotics have no useful role unless bacterial superinfection is present.

Prevention of Viral Conjunctivitis

Prevention of transmission, especially in health care facilities, is extremely important. Careful hand washing before seeing every patient, proper cleansing of instruments, and frequent changing of multiuse ophthalmic drops are vital. Using a single infective examination room, as well as educating the staff and the patient, is important.

Patients should be instructed to take contagion and isolation precautions for at least 2 weeks or as long as their eyes are red and weeping.

Physicians have been sued by patients who believe they acquired viral conjunctivitis in the doctor's office. Every attempt to prevent transmission from patient to patient (not to mention to the doctor) should be made. Suggestions include not having patients with a red eye wait in the general waiting room, having a special examination room for patients with red eye, disinfecting the examination room after seeing any patient with a red eye, not shaking hands with patients with red eye (after explaining the reason to them), touching their eyelids with cotton-tipped applicators and not your fingers, washing the hands immediately after examining the patient (even before writing in the chart), and not giving the chart to the patient to bring to the receptionist.

Viral conjunctivitis is an occupational hazard of eye care physicians. Take all precautions possible not to become a victim.

Follow-up Considerations

Patients with conjunctivitis, especially those treated with medications, require follow-up care. Patients should return in 1-3 weeks or sooner if the condition worsens.

Consultations

An important aspect of treatment is to know the proper time to refer the patient to a specialist.

Patients with hyperacute conjunctivitis or those with corneal involvement, such as ulceration, herpetic keratitis, or suspected orbital cellulitis, should be referred to an ophthalmologist.

An ophthalmologist also should evaluate patients who fail to respond to appropriate therapy.

Medication Summary

Medications used in the treatment of viral conjunctivitis include the following:

Artificial tears (Refresh Tears, Akwa Tears, Bion Tears, Murine Tears)

Clinical Context:  Artificial tears act to stabilize and thicken precorneal tear film and prolong tear film breakup time, which occurs with dry eye states.

Class Summary

These agents are used for symptomatic relief.

Levocabastine

Clinical Context:  Levocabastine is a potent histamine H1-receptor antagonist; it is for ophthalmic use.

Class Summary

These agents are used to treat severe itching.

Prednisolone ophthalmic (AK-Pred, Pred Mild, Omnipred)

Clinical Context:  This agent decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Less potent (eg, prednisolone 0.125%, fluorometholone 0.1%) are usually sufficient to treat subepithelial infiltrates. The steroid must be tapered very slowly, over months.

Class Summary

Corticosteroids may be used for pseudomembranes and decreased vision and/or glare due to subepithelial infiltrates. They have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Extreme caution should be taken when using corticosteroids, as they may worsen an underlying HSV infection.

Trifluridine (Viroptic)

Clinical Context:  Trifluridine is a pyrimidine (thymidine) analogue drug of choice in the United States for topical antiviral therapy for HSV infection. It inhibits viral replication by incorporating into viral deoxyribonucleic acid (DNA) in place of thymidine. If the patient has no response in 7-14 days, consider other treatments.

Acyclovir (Zovirax)

Clinical Context:  This is a prodrug that inhibits viral replication; it is activated by phosphorylation by virus-specific thymidine kinase.

Class Summary

These agents are used for the treatment of HSV infection.

Author

Ingrid U Scott, MD, MPH, Professor, Department of Ophthalmology and Public Health Sciences, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Kevin Luu, MD, Consulting Staff, Pediatric Anesthesia Associates Medical Group, Inc; Consulting Staff, Children's Hospital of Central California

Disclosure: Nothing to disclose.

Specialty Editors

Jerre Freeman, MD, Founder and Chairman, Memphis Eye and Cataract Associates; Clinical Professor, Department of Ophthalmology, University of Tennessee Health Science Center College of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; RPS Ownership interest Other; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting fee Consulting; Tear Science Consulting fee Consulting; Nicox Consulting; Bio-Tissue Honoraria Speaking and teaching

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

References

  1. Ishiko H, Shimada Y, Konno T, Hayashi A, Ohguchi T, Tagawa Y, et al. Novel human adenovirus causing nosocomial epidemic keratoconjunctivitis. J Clin Microbiol. Jun 2008;46(6):2002-8. [View Abstract]
  2. Kuo SC, Shen SC, Chang SW, Huang SC, Hsiao CH. Corneal superinfection in acute viral conjunctivitis in young children. J Pediatr Ophthalmol Strabismus. Nov-Dec 2008;45(6):374-6. [View Abstract]
  3. Park SW, Lee CS, Jang HC, et al. Rapid identification of the coxsackievirus A24 variant by molecular serotyping in an outbreak of acute hemorrhagic conjunctivitis. J Clin Microbiol. Mar 2005;43(3):1069-71. [View Abstract]
  4. Kimura R, Migita H, Kadonosono K, Uchio E. Is it possible to detect the presence of adenovirus in conjunctiva before the onset of conjunctivitis?. Acta Ophthalmol. Feb 2009;87(1):44-7. [View Abstract]
  5. Udeh BL, Schneider JE, Ohsfeldt RL. Cost effectiveness of a point-of-care test for adenoviral conjunctivitis. Am J Med Sci. Sep 2008;336(3):254-64. [View Abstract]
  6. Kaneko H, Maruko I, Iida T, Ohguchi T, Aoki K, Ohno S, et al. The possibility of human adenovirus detection from the conjunctiva in asymptomatic cases during nosocomial infection. Cornea. Jun 2008;27(5):527-30. [View Abstract]
  7. Wilkins MR, Khan S, Bunce C, et al. A randomised placebo-controlled trial of topical steroid in presumed viral conjunctivitis. Br J Ophthalmol. Sep 2011;95(9):1299-303. [View Abstract]
  8. Monnerat N, Bossart W, Thiel MA. [Povidone-iodine for treatment of adenoviral conjunctivitis: an in vitro study]. Klin Monatsbl Augenheilkd. May 2006;223(5):349-52. [View Abstract]
  9. Keller DM. Rapid Tests Diagnose Dry Eye, Adenovirus Conjunctivitis. Medscape Medical News. January 15, 2013. Available at http://www.medscape.com/viewarticle/777710. Accessed January 23, 2013.
  10. Sambursky R, Trattler W, Tauber S, Starr C, Friedberg M, Boland T, et al. Sensitivity and Specificity of the AdenoPlus Test for Diagnosing Adenoviral Conjunctivitis. JAMA Ophthalmol. Jan 1 2013;131(1):17-21. [View Abstract]

Viral conjunctivitis. Image courtesy of Wikimedia Commons.

Viral conjunctivitis. Image courtesy of Wikimedia Commons.