Epidemic keratoconjunctivitis (EKC) is a highly contagious viral conjunctivitis caused by a group of viruses known as adenoviruses. Adenovirus serotypes 8, 19 and 37 are often associated with EKC. Family of adenoviruses contain different serotypes that can also cause pharyngoconjunctival fever, non-specific sporadic follicular conjunctivitis and chronic papillary conjunctivitis. In addition to infections of ocular (pertaining to eye) surface, adenovirus (mainly those responsible for paryngoconjunctival fever) is responsible for causing infectious diseases of the gastrointestinal tract and respiratory system. EKC is reported worldwide and has a tendency to occur in epidemics.
More than half of cases may show symptoms, though milder, in other eye.
It is one of the most common causes of acute conjunctivitis, with clinical features such as sudden onset of acute follicular conjunctivitis, watering of eyes, chemosis (swelling of conjunctiva), redness and ipsilateral (same side) pre-auricular (in front of ear) lymphadenopathy.
Development of keratitis (corneal inflammation) distinguishes EKC from other forms of conjunctivitis and it usually arises after fourth day of initial onset of symptoms. Corneal involvement ranges from diffuse, fine superficial keratitis to epithelial defects to sub-epithelial infiltrates. Sub-epithelial infiltrates can persist for years, which may cause glare and reduction in visual acuity.
Epidemic kerato-conjunctivitis may also develop membranous or pseudo-membranous conjunctivitis in severe cases, which may lead to scarring of conjunctiva and symblepharon (adhesion between eyelid and eyeball) formation.
EKC is usually a self-limiting disease and it tends to resolve spontaneously within 1-3 weeks without leaving any significant complications. Diagnosis of the disease process is clinical and the treatment is mostly symptomatic. Antiviral and cyclosporine eye drops were tried in some patients, but there was no definite benefit of these. Mild topical steroids may be used in cases with severe membranous conjunctivitis. Excimer laser photo-therapeutic keratectomy (PTK), along with low-dose mitomycin C (MMC), may be used to remove sub-epithelial opacities.
Kanski,Jack J. Clinical Ophthalmology, A Systematic Approach .Third Edition.UK. Butterworth Heinemann, 1994.
Symptoms of EKC may begin following an eye examination and spread in a clinic, exposure within the family or at work.
The incubation period of the disease is 2-14 days, and the person may remain infectious for 10-14 days after the onset of symptoms.
EKC may be preceded by systemic features such as:
- Body fatigue.
- Lymphadenopathy (swollen lymph nodes, specifically pre-auricular)
- Respiratory symptoms.
- General malaise.
Ocular features of EKC:
Symptoms tend to last for 7-21 days. More than half the cases show involvement of fellow eye within 7 days of onset. The signs and symptoms are less severe in the fellow eye.
In more severe cases, patient may present with ocular and peri-orbital pain and diminution of vision.
Ocular symptoms are mainly:
- Redness of eyes.
- Foreign body sensation.
- Epiphora (watering of eyes).
- Chemosis (swelling of conjunctiva).
- Photophobia (increased light sensitivity).
- Sub-conjunctival haemorrhage (haemorrhage below conjunctiva).
- Blurring or diminution of vision.
- Swelling of lids.
- Pseudomembranes on conjunctiva.
EKC is caused by adenoviruses and more than 50 serotypes have been isolated. There are at-least 19 documented serotypes which causes EKC. Most commonly associated serotypes include adenovirus 8, 19 and 37. Less commonly, EKC may be caused by serotypes 2 to 5, 7, 9, 10, 11, 14, 16, 21 and 29.
Because of prevalence of low natural immunity against adenovirus being present in general population, every individual is considered to be susceptible to infection.
EKC is more common in adults, but it can infect all age groups.
Adenovirus can be recovered from eye and throat even up to 14 days, after the onset of clinical symptoms.
EKC epidemics usually take place in closed institutions like schools, camps, nursing homes, hospitals or places of work.
Possible modes of transmission are:
- Direct contact with eye secretions: Direct contact with eye secretions is a major mode of transmission.
- Spread by air droplets.
- Possible exposure through swimming pools.
- Iatrogenic (spread by treating people in clinics).
Objects that come into contact with eyes (such as cosmetics) should not be shared or allowed to come in contact with others.
Many epidemics of EKC started in ophthalmology out-patient clinics by direct contact with contaminated diagnostic instruments.
Reasons for infectious transmission of EKC in hospitals and clinics include:
- Virus is resistant to standard disinfectants (70% isopropyl alcohol and ammonia).
- Virus sheds from eye 3 days before and 14 days after the onset of symptoms. Therefore, this fact should be taken into consideration for allowing a patient to return to work or school.
- Adenovirus serotype 19 remains viable for 5 weeks.
Adenovirus is the main causative agent being isolated from patients suffering from viral conjunctivitis.
Diagnosis of epidemic keratoconjunctivitis usually depends upon the characteristic clinical features.
Viral cultures and conjunctival cytological studies are the means of identifying and confirming epidemic keratoconjunctivitis.
Epidemic keratoconjunctivitis infection is preceded by flu-like general symptoms.
Ocular presentation is like features of any conjunctivitis with associated keratitis.
Ipsilateral pre-auricular lymphadenopathy is one of the classic features of epidemic keratoconjunctivitis.
Decreased visual acuity is rarely present except in cases with corneal involvement.
Slit-lamp examination by an eye specialist is required for diagnosis.
- Swelling of eyelids.
- Erythema (redness) of eyelids.
- Conjunctival hyperaemia (redness of conjunctiva).
- Chemosis (conjunctival swelling).
- Follicular reaction, mainly in lower palpebral (eyelid) conjunctiva (earliest and most common sign).
- Papillary hypertrophy.
- Subconjunctival and petechial (small red or purple spot caused by bleeding) haemorrhage.
- Membranous or pseudo-membranous conjunctivitis.
- Conjunctival scarring.
- Symblepharon formation which may restrict eye movement.
One of the distinguishing features of EKC from other viral conjunctivitis is involvement of cornea, which is usually mild and transient.
There is no change in sensation of cornea.
- Diffuse, fine epithelial keratitis: Diffuse, fine epithelial keratitis develops 3-4 days after the onset of symptoms and it may persist for 2-3 weeks. Keratitis stains with fluorescein and rose Bengal stain. Keratitis may lead to frank corneal epithelial defect.
- Focal epithelial keratitis: Focal epithelial keratitis may develop one week after the onset of symptoms and it may persist for 1-2 weeks. This is characterised by central ulceration and irregular borders with grey-white dots. These epithelial changes are related to active viral disease.
- Sub-epithelial infiltrates: Sub-epithelial infiltrates beneath focal epithelial lesions may develop about 2 weeks after the onset of symptoms and may persist for weeks to years. These are immunologic in nature and may resolve spontaneously, usually without scarring. Transient mild anterior uveitis may accompany this.
- Disciform keratitis: Disciform keratitis may develop rarely.
- Anterior uveitis: Transient mild anterior uveitis may occur rarely.
Following tests may be used for diagnosis of EKC:
- Polymerase chain reaction assay (PCR assay):
- Fluorescent antibody test:
- Complement fixation test:
- Giemsa cytology: Giemsa cytology is microscopic examination of stained conjunctival scrapings for intranuclear inclusions and lymphocytes.
- Cell culture:
- Enzyme immune assays:
- AdenoPlus test: AdenoPlus test, an enhanced device for Rapid Pathogen Screening (RPS), is an antigen-based immunoassay. This test detects the presence of adenoviral particles and thus allows patient a speedier return to school or work when the virus is no longer detectable. Ability to confirm adenoviral infection may allow the study and use of novel therapies for the disease.
PCR test is more sensitive test, and therefore, use of AdenoPlus test should be limited to diagnostically challenging patients.
EKC should be differentiated from conditions such as:
- Adult inclusion conjunctivitis.
- Herpes simplex infection.
- Allergic conjunctivitis.
- Acute haemorrhagic conjunctivitis.
- Bacterial conjunctivitis.
- Viral conjunctivitis.
- Complications of contact lens use.
Management should be carried out under medical supervision.
EKC is usually a self-limiting disease and it tends to resolve spontaneously within 1-3 weeks without leaving any significant complications. There is no effective treatment for EKC.
Depending upon the severity of signs and symptoms, patients are followed up for several days to weeks.
Goals of pharmacotherapy (treatment with medicines) are to reduce morbidity and to prevent any complications.
Supportive medical management of EKC includes:
- Cold compresses.
- Artificial tears: Artificial tears stabilise and thicken pre-corneal tear film and prolong tear film break-up time (BUT), which occurs with dry eye.
- Topical vasoconstrictor/antihistamine: Topical vasoconstrictor/antihistamine may be used for severe itching. On discontinuation, it may cause rebound (recurrence) of symptoms.
- Topical non-steroidal anti-inflammatory agents (NSAIDs): Topical non-steroidal anti-inflammatory agents (NSAIDS) may be used to reduce inflammation.
- Topical antibiotic: Topical antibiotic may be used to prevent superadded bacterial infection.
- Cycloplegic agents: Cycloplegic agents may be used for severe photophobia.
- Mild topical corticosteroids: Mild topical corticosteroids may be used in severe membranous conjunctivitis or patients with marked reduction in vision due to late sub-epithelial opacities. While corticosteroids do assist in reducing inflammation, they do not have any significant impact on natural course of the disease. Taper this treatment slowly to avoid recurrence of corneal opacities. Any patient on topical corticosteroid should be observed for side effects such as glaucoma (elevated intraocular pressure) and formation of cataract.
- Topical immune-suppressants (e.g.Tacrolimus ointment): Topical immune-suppressants can inhibit autoimmune inflammatory responses. Tacrolimus is a treatment option for sub-epithelial infiltrates in EKC. Tacrolimus suppresses cellular immunity.
- Ophthalmic antiseptics (e.g.Povidone-iodine): Ophthalmic antiseptics are broad-spectrum germicidal agents. Povidone-iodine has broad antibacterial and antiviral activity. Povidone iodine may be used to reduce the duration of disease.
Surgery is extremely rare for EKC and is reserved for severe cases with cicatricial conjunctivitis or symblepharon.
If surgery is necessary, it is mainly in the form of:
- Excimer laser photo-therapeutic keratectomy (PTK): Excimer laser photo-therapeutic keratectomy (PTK), along with low-dose mitomycin, may be used to remove sub-epithelial opacities.
- Membrane or pseudo-membrane removal: Membrane or pseudo-membrane may be peeled off gently and a topical corticosteroid may be prescribed.
- Fornix reconstruction.
- Entropion repair.
Most cases of EKC are acute, benign and self-limiting. Infection usually resolves spontaneously within 2-3 weeks. Sub-epithelial infiltrates may last for months together and may decrease vision if visual axis is involved.
Potential complications of EKC are:
- Punctate keratitis.
- Sub-epithelial infiltrates.
- Superadded bacterial infection.
- Chronic infection.
- Corticosteroid induced protracted clinical course with prolonged corneal opacification.
Epidemic keratoconjunctivitis is a highly contagious disease and since there is no effective treatment, prevention is important to tackle disease. Virus can spread by contact with infected surfaces or objects. A patient can spread disease agents by touching infected eyes and then touching objects. Objects that come into contact with eyes, such as cosmetics, should not be shared. A person may be contagious for two weeks or more after onset of symptoms, and therefore, should avoid return to work or school.
Preventive measures include:
- Patients should not touch others and not to share tissues, towels, pillows or handkerchiefs and should wash hands frequently as long as the eye is red.
- Eye care professionals should wash their hands thoroughly after examining any patient. As a routine, they should wash their hands before seeing all patients.
- Health care workers caring for immune-compromised individuals are precluded from patient contact for up to two weeks to avoid transmission of infection.
- Ophthalmic instruments should be properly cleaned and sterilised.
- A ‘red eye room’ may be created to separate out red eye patients from other patients.
- Patient and their family members should be educated about the features of the disease. Patient should be informed that the symptoms may worsen during first 4-7 days after onset before they begin to improve, and they may not resolve for 2-3 weeks.