Epidemic Keratoconjunctivitis (EKC)

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Background

Epidemic keratoconjunctivitis (EKC) is a viral conjunctivitis caused by a group of adenoviruses. This family of adenoviruses contains different serotypes that can also cause pharyngoconjunctival fever and nonspecific follicular conjunctivitis. EKC is highly contagious and has a tendency to occur in epidemics. It has been reported worldwide. (See Etiology and Epidemiology.)

It is one of the most common causes of acute conjunctivitis, with characteristic clinical features such as sudden onset of acute follicular conjunctivitis, with watery discharge, hyperemia, chemosis, and ipsilateral preauricular lymphadenopathy. (Follicular conjunctivitis is seen in the image below.)



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Follicular conjunctivitis and subconjunctival hemorrhage.

Membranes and pseudomembranes can occur, with a distinguishing corneal involvement that ranges from diffuse, fine, superficial keratitis to epithelial defects to subepithelial opacities. Diagnosis is mainly clinical. Treatment is mostly symptomatic (cold compresses and artificial tears). Antiviral (cidofovir ) and cyclosporine eye drops were tried in some patients but without definite benefit.[1, 2] In cases with severe membranous conjunctivitis, mild topical corticosteroids can be used. (See History and Physical Examination.)

EKC is a self-limiting disease. It tends to resolve spontaneously within 1-3 weeks without significant complications. (See History.)

In 20-50% of cases, corneal opacities can persist for a few weeks to months (rarely up to 2 y). This phenomenon can significantly decrease visual acuity and cause glare symptoms. Excimer laser phototherapeutic keratectomy (PTK), along with low-dose mitomycin, can be used to remove subepithelial opacities.[3]

In rare cases, conjunctival scarring and symblepharon can occur secondary to membranous conjunctivitis. (See Physical Examination.)

See the following for more information:

Patient Education

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

Etiology

More than 50 serotypes have been isolated, and at least 19 documented serotypes cause epidemic keratoconjunctivitis (EKC). The most commonly associated serotypes include adenovirus 8, 19, and 37, and, less frequently, serotypes 2-5, 7, 9, 10, 11, 14, 16, 21, and 29. Because of low natural immunity against adenovirus in the general population (eg, adenovirus type 8 antibodies are found in < 5% of the general population in the United States), every individual is considered to be susceptible to infection.

EKC epidemics tend to occur in closed institutions (eg, schools, hospitals, camps, nursing homes, workplaces). Direct contact with eye secretions is the major mode of transmission. Other possible methods of transmission are air droplets and possibly swimming pools. Adenovirus can be recovered from the eye and throat for as long as 14 days after the onset of clinical symptoms.

The role of the medical profession in spreading the disease is well documented in the literature. Many epidemics have been initiated in ophthalmology outpatient clinics by direct contact with contaminated diagnostic instruments. Reasons behind the infectious transmission of EKC in hospitals and clinics include the fact that: (1) the virus (adenovirus type 19) remains viable for 5 weeks; (2) the virus is resistant to standard disinfectants, such as 70% isopropyl alcohol and ammonia; and (3) the virus sheds from the eye 3 days before and 14 days after symptom onset.

EKC in East Asia and other parts of the world is endemic and does not appear to be transmitted through medical intervention. Viruses were isolated from more than 50% of cases of viral conjunctivitis; adenovirus constituted 94% of them.

Epidemiology

The actual prevalence and incidence of epidemic keratoconjunctivitis (EKC) in the United States are unknown, because most cases are seen by general practitioners and optometrists. This infection does not have to be reported to any medical authority in the United States. The prevalence and incidence of EKC are also unknown internationally.

No sex predilection exists.

The infection is more common in adults, but all age groups can be affected.

History

Epidemic keratoconjunctivitis infection may be preceded by flulike symptoms, including fever, malaise, respiratory symptoms, nausea, vomiting, diarrhea, and myalgia.

Often, a recent history of an eye examination or exposure within the family or at work is present.

The incubation period is 2-14 days, and the person may remain infectious for 10-14 days after symptoms develop.

The ocular symptoms are mainly sudden onset of irritation, soreness, red eye, photophobia, foreign body sensation, and excessive tearing.

In more severe cases, patients can present with ocular and periorbital pain and decreased visual acuity.

Symptoms tend to last for 7-21 days. The fellow eye tends to be involved in more than 50% of the cases within 7 days of onset. The signs and symptoms are typically less severe in the fellow eye.

Physical Examination

Ipsilateral preauricular lymphadenopathy is one of the classic findings of epidemic keratoconjunctivitis (EKC).

Decreased visual acuity is rarely present; it is usually present only if there is corneal involvement.

Other clinical signs include the following:

In severe cases, membranous and pseudomembranous conjunctivitis can be seen in one third of cases, which can lead to conjunctival scarring and symblepharon (seen in the image below).



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Symblepharon secondary to epidemic keratoconjunctivitis.

Corneal involvement

One of the distinguishing features of EKC is corneal involvement, which is usually mild and transient.

Corneal involvement has been well documented 3-4 days after symptom onset in the form of diffuse, fine epithelial keratitis that stains with fluorescein and rose bengal. This keratitis can persist for 2-3 weeks. In rare cases, a frank corneal epithelial defect may occur.

One week after the onset, focal epithelial keratitis may develop. This is characterized by central ulceration and irregular borders with gray-white dots. These epithelial changes are related to active viral infection. These lesions persist for 1-2 weeks.

About 2 weeks after onset, subepithelial infiltrates can appear beneath the focal epithelial lesions, persisting for weeks to years. They resolve spontaneously, usually without scarring. These infiltrates are immunologic in nature.

In rare cases, disciform keratitis or anterior uveitis can occur.

There is no change in corneal sensation.

Approach Considerations

A diagnosis of epidemic keratoconjunctivitis (EKC) is routinely based on the characteristic clinical features. Conjunctival cytologic studies and viral cultures are among the means of identifying and confirming the presence of epidemic keratoconjunctivitis.

Diagnostic methods

A simple way to diagnose EKC is by conjunctival cytology with Giemsa stain to look for intranuclear inclusions and lymphocytes.

To confirm the diagnosis, viral culture is the criterion standard. Use a human epithelial cell line and a Chlamydia transport media.

Other available diagnostic methods include fluorescent antibody techniques, Adenoclone or enzyme immune assay, complement fixation, and polymerase chain reaction (PCR) assay.[4]

Approach Considerations

Supportive management of epidemic keratoconjunctivitis includes the following:

Depending on the severity of the signs and symptoms, patients should be followed up in several days to weeks.

Any patient on topical corticosteroids should be observed routinely to monitor for adverse effects, including elevated intraocular pressure and cataract formation.

Surgery is extremely rare and reserved for severe cases with cicatricial conjunctivitis secondary to symblepharon.

If surgery is necessary, it is mainly in the form of fornix reconstruction and entropion repair.

See the following for more information:

Corticosteroid, Antiviral, and Immunosuppressive Therapies

Use topical corticosteroid therapy for severe membranous conjunctivitis or a marked reduction in visual acuity from late subepithelial opacities.

Taper this treatment slowly over a period of weeks to months to avoid recurrence of the corneal opacities.

Research has been ongoing for topical agents that have antiviral activity. Cidofovir has been shown to reduce the viral replication cycle and also to be effective as a prophylactic agent. Cidofovir may prove to be one of the most useful topical antiviral agents in the treatment of and prophylaxis for epidemic keratoconjunctivitis (EKC), which constitutes a professional hazard for all eye care professionals.[1, 2]

Topical 0.03% tacrolimus is a treatment option for subepithelial infiltrates.[5]

Povidone iodine can be used to reduce the duration of conjunctivitis.[6]

Prevention of Epidemic Keratoconjunctivitis

To avoiding spreading epidemic keratoconjunctivitis (EKC), patients should be very careful not to touch others and not to share tissues, towels, or handkerchiefs and to wash their hands frequently as long as the eye is red.

Eye care professionals need to be extremely cautious regarding spreading of this infection to themselves or other patients. They should wash their hands immediately after examining any patient with a red eye. Anything the patient might have touched (especially the examination chair, slit lamp, and occluder) should be disinfected by office personnel immediately after the patient leaves the room.

Every effort needs to be made not to spread infections from one patient to another patient. A “red eye room” is a very good idea to try and limit potential spread. After any patient with a possible EKC infection is seen, the room needs to be disinfected. Physicians should wash their hands thoroughly after seeing any patient with a red eye. As a routine, they should wash their hands before seeing all patients.

In summary, prevention measures include the following:

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The topical steroids dexamethasone, fluorometholone, prednisolone ophthalmic, and rimexolone 1% are used in the treatment of epidemic keratoconjunctivitis.

Dexamethasone (Maxidex, Ozurdex)

Clinical Context:  Dexamethasone is used for various allergic and inflammatory diseases. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Fluorometholone (FML, Flarex, FML Forte)

Clinical Context:  This agent suppresses the migration of polymorphonuclear leukocytes and reverses capillary permeability.

Prednisolone ophthalmic (Pred Forte, Omnipred, Pred Mild)

Clinical Context:  Prednisolone ophthalmic decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Rimexolone 1% (Vexol)

Clinical Context:  Rimexolone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Topical corticosteroids are a group of anti-inflammatory agents that cause inhibition of the inflammatory response by potentiation of epinephrine vasoconstriction, stabilization of lysosomal membranes, decrease in macrophage movement, prevention of kinin release, interference with lymphocytes and neutrophil function, and inhibition of prostaglandin synthesis through inhibition of phospholipase enzyme.

Artificial tears (Soothe, Bion Tears, Murine Tears, Systane)

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

Class Summary

These agents are used for symptomatic relief.

Tacrolimus ointment (Protopic)

Clinical Context:  Tacrolimus is a treatment option for subepithelial infiltrates in keratoconjunctivitis. Suppresses cellular immunity; mechanism unclear; inhibits T-cell activation by binding to intracellular protein FKBP-12 and complexes with calcineurin-dependent proteins to inhibit calcineurin phosphatase activity.

Class Summary

Agents with immunosuppressant properties can inhibit autoimmune inflammatory responses.

Povidone-iodine (Betadine Ophthalmic Prep)

Clinical Context:  Povidone-iodine is an antibacterial agent with broad antibacterial and antiviral activity. No bacteria are known to be resistant to povidone-iodine. Povidone-iodine is far less expensive and less toxic than agents currently used to prevent conjunctivitis. Used to reduce the duration of conjunctivitis.

Class Summary

Antiseptics are broad-spectrum germicidal agents.

Author

Ahmed Bawazeer, MBChB, FRCSC, Professor and Chairman of Ophthalmology, Department of Ophthalmology, Division of Uveitis and Cornea, King Abdulaziz University, Saudi Arabia

Disclosure: Nothing to disclose.

Coauthor(s)

William G Hodge, MD, PhD, FRCSC, Professor and Chair, Ophthalmologist in Chief, Ivey Eye Institute, Schulich School of Medicine and Dentistry, University of Western Ontario

Disclosure: Nothing to disclose.

Specialty Editors

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

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: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Aerie, Bausch & Lomb, Bio-Tissue, Shire, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue.

Chief Editor

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

Disclosure: Nothing to disclose.

References

  1. Romanowski EG, Yates KA, Gordon YJ. Antiviral prophylaxis with twice daily topical cidofovir protects against challenge in the adenovirus type 5/New Zealand rabbit ocular model. Antiviral Res. 2001 Dec. 52(3):275-80. [View Abstract]
  2. Hillenkamp J, Reinhard T, Ross RS, Bohringer D, Cartsburg O, Roggendorf M, et al. The effects of cidofovir 1% with and without cyclosporin a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study. Ophthalmology. 2002 May. 109(5):845-50. [View Abstract]
  3. Yamazaki ES, Ferraz CA, Hazarbassanov RM, Allemann N, Campos M. Phototherapeutic keratectomy for the treatment of corneal opacities after epidemic keratoconjunctivitis. Am J Ophthalmol. 2011 Jan. 151(1):35-43.e1. [View Abstract]
  4. Sambursky R, Tauber S, Schirra F, Kozich K, Davidson R, Cohen EJ. The RPS adeno detector for diagnosing adenoviral conjunctivitis. Ophthalmology. 2006 Oct. 113(10):1758-64. [View Abstract]
  5. Levinger E, Trivizki O, Shachar Y, Levinger S, Verssano D. Topical 0.03% tacrolimus for subepithelial infiltrates secondary to adenoviral keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol. 2014 May. 252(5):811-6. [View Abstract]
  6. Özen Tunay Z, Ozdemir O, Petricli IS. Povidone iodine in the treatment of adenoviral conjunctivitis in infants. Cutan Ocul Toxicol. 2015 Mar. 34(1):12-5. [View Abstract]

Follicular conjunctivitis and subconjunctival hemorrhage.

Symblepharon secondary to epidemic keratoconjunctivitis.

Follicular conjunctivitis and subconjunctival hemorrhage.

Symblepharon secondary to epidemic keratoconjunctivitis.