- To review the various viruses that are capable of causing conjunctivitis
- To review recent literature on diagnosis and treatment of viral conjunctivitis
- To review P-values
A 34 year old female with no past medical or ocular history presents to the eye clinic with a red left eye which has been present for the last 48 hours. Approximately 4-5 days ago, she began having symptoms of a cold and this was later followed by the red eye. The eye is not painful or itchy and she reports no visual symptoms. She says most of the discharge is watery, although this morning she did feel her lids “crusted together”.
On exam, best-corrected visual acuity is 20/20 bilaterally. A tender left pre-auricular node is palpable. External exam of the left eye is shown below. On slit lamp exam multiple follicles are seen on the inferior conjunctiva. There is no fluorescein staining. Posterior segment exam is normal.
What is the most likely diagnosis?
• Allergic conjunctivitis
INCORRECT - although allergic conjunctivitis can appear similar, it is often characterized by profound itchiness. In addition, the recent upper respiratory tract infection and lack of information on allergies makes this less likely.
INCORRECT - enterovirus is a cause of viral conjunctivitis, specifically acute hemorrhagic conjunctivitis which is characterized by acute and severe conjunctivitis often with subconjunctival hemorrhages. The lack of subconjunctival hemorrhages makes this less likely. (In addition), acute hemorrhagic conjunctivitis is more likely to be seen in developing countries.
• Bacterial conjunctivitis
INCORRECT - the lack of purulent discharge makes bacterial conjunctivitis less likely, although differentiating viral vs. bacterial conjunctivitis is often difficult in the clinical setting.
Conjunctivitis is an extremely common condition caused by infection or inflammation of the conjunctiva.2 As a whole, conjunctivitis is the most frequent ocular disorder encountered in ophthalmic clinics with viral causes accounting for roughly 62% of all such cases. Viral conjunctivitis is most commonly caused by adenoviral species, however a broad range of viral species may cause the disease. It commonly affects younger age groups, although individuals of all ages are susceptible to it. It exhibits no sexual predilection.
The conjunctiva is a clear mucous membrane covering the sclera and the inner surfaces of the eyelids. Histologically, it consists of a stratified columnar epithelium with an underlying stroma. The epithelium consists of 2-5 layers of cells, with the superficial layers containing mucuus-secreting goblet cells that aid in the function of the tear film. Underneath the epithelium is the stroma, which is divided into an adenoid (superficial) and fibrous (deep) layer.
The conjunctiva is generally divided into the palpebral (tarsal) conjunctiva lining the eyelids, the bulbar conjunctiva covering the sclera, and the forniceal conjunctiva at the junction between the bulbar and palpebral sections. The bulbar conjunctiva is bound to the underling sclera by Tenon’s capsule, a thin membrane surrounding the eye.
The conjunctiva receives its vascular supply from anterior and posterior conjunctival arteries which originate from the anterior ciliary and palpebral arteries, respectively. The anterior conjunctival arteries are branches of the anterior ciliary arteries before they pierce the sclera, and supply an area of about 4mm around the limbus. The posterior conjunctival arteries, branches of the palpebral arteries, supply most of the conjunctiva except for the area around the limbus. The arteries anastamose and create an extensive vascular plexus. The venous supply is similar in that anterior conjunctival veins drain to the anterior ciliary vein and then ophthalmic vein, while posterior conjunctival veins drain to the lid.
A broad variety of viral agents may be the cause of conjunctivitis. While some species (e.g. adenovirus) directly infect the conjunctiva, other species cause conjunctivitis in association with a systemic viral infection. We will briefly discuss the various etiologies.
Adenoviruses are the most common cause of viral conjunctivitis. They are medium-sized, nonenveloped, icosadhedral viruses composed of a nucleocapsid and double stranded DNA genome. They are responsible for many infections in addition to conjunctivitis including upper and lower respiratory tract disease, gastroenteritis, and hemorrhagic cystitis.3 Generally they are divided into 6 species (A-F) making up a total of 51 serotypes. Only a few of the serotypes are responsible for most cases of conjunctivitis, notably serotypes 8, 19 and 37.4
Adenoviruses are extremely contagious and may be spread by direct or indirect contact with ocular or upper respiratory tract secretions.5 Public spaces, in particularly eye clinics, are a major source of spread and even pools and hot tubs have been shown to be sources for virus transmission.6 It usually has an incubation between 2 days to 2 weeks following exposure, during which it is probably not contagious (studies suggest viral particles are not detectable in the conjunctiva prior to symptom onset).5 Following symptom onset, the condition is often contagious for 2 weeks or longer.
Most cases of adenoviral conjunctivitis are benign. Generally, three patterns of disease are seen with adenoviral conjunctivitis, although differentiating patterns in a clinical setting is often irrelevant. These include:
1) Epidemic keratoconjunctivitis: epidemic keratoconjunctivitis (EKC) is especially contagious and most frequently caused by serotypes 8, 19 and 37 (other possible serotypes being 2-5, 7, 10, 11, 21, 22, 29, and 342). It typically involves the cornea to some degree along with conjunctivitis, and often occurs in epidemics, especially in crowded living conditions (e.g. schools, military bases, ophthalmic practices3).
2) Pharyngoconjunctival fever: pharyngoconjunctival fever is a common pattern of adenoviral conjunctivitis seen that is characterized by a mild follicular reaction on the inferior tarsal conjunctiva in association with a systemic viral syndrome. It most commonly affects children and is caused by serotypes 3 and 7.2
3) Nonspecific follicular conjunctivitis: may be caused by multiple serotypes including 1-11, 15-17, 19, 20, and 22.2
Acute hemorrhagic conjunctivitis
Acute hemorrhagic conjunctivitis describes a severe but often self-limited conjunctivitis of viral origin that often occurs in epidemics in developing countries or communities of low socioeconomic status. It is caused primarily by enterovirus type 70 or coxsackie virus type A24 (both species of picornavirus) and is also very contagious. Children and young adults are often affected. The disease is characterized by a conjunctivitis that is more severe than adenoviral conjunctivitis and often accompanied by subconjunctival hemorrhages. It often has no long-term sequelae, but the viruses can cause neurological and systemic disease.7 No treatment is often indicated, however studies have shown interferon to reduce interhousehold spread.8
Herpes simplex virus
A full discussion of ocular herpes simplex is beyond the scope of this module. However, it should be noted that both herpes simplex virus (HSV) 1 and less commonly HSV 2 can cause conjunctivitis during primary or recurrent infection. Primary ocular HSV infection is common in infants and children and usually associated with a follicular conjunctivitis.
Herpes zoster virus
Similarly, a full discussion of herpes zoster and the eye is beyond the scope of this module. However, herpes zoster infection may cause conjunctivitis during both primary (i.e. chicken pox) and reactivation (i.e. zoster) infection, and may occur with or without skin lesions. Primary infection is contracted through direct contact with skin lesions or respiratory secretions (may be airborne), and in addition to the characteristic rash (vesicular rash on body and head that becomes itchy with raw pockmarks) may be associated with a mild conjunctivitis or episcleritis.9 There may also be pox (focal areas of necrosis) on the corneal stroma or conjunctiva. Recurrent zoster (or simplex) may occur following stress, fever, trauma, hormonal changes, reduced cell-mediated immunity or exposure to sunlight.10 11 Herpes zoster ophthalmicus may in addition to corneal findings be associated with conjunctival hyperaemia, petechial hemorrhages, a papillary or follicular conjunctivitis, and rarely a pseudomembrane.12 One study estimated that up to 25% of zoster cases occur along the ophthalmic branch of V1.11
Molluscum contagiosum is a viral infection caused by a poxvirus that produces benign, self-limiting papular eruptions of the skin and mucous membrane.13 It is most commonly seen in children and immunocompromised individuals (e.g. AIDS, systemic steroids, etc.). Ocular lesions are not uncommon, and typically involve the eyelid. Such lesions can produce a follicular conjunctivitis or keratoconjunctivitis, thought to be secondary to toxicity or hypersensitivity to viral proteins shed from the lesion onto the tear film.13 Associated findings may include a punctuate keratopathy or epithelial/subepithelial infiltrates.14 15 Conjunctivitis can often be chronic in such cases. Rarely, molluscum may produce conjunctival lesions.13
Molluscum contagiosum often runs a benign and self-limiting course. In cases associated with chronic anterior segment involvement such as conjunctivitis or keratoconjunctivitis, removal of the cutaneous lesion should be considered as it usually improves the condition.15 Options include resection, curettage, cryotherapy, or cautery. The lesions often recur. In patients with HIV infection, treatment with highly active anti-retroviral therapy (HAART) often results in complete regression of the lesions as well.16
Human immunodeficiency virus
Human immunodeficiency virus (HIV), the agent responsible for AIDS, often has ocular manifestations which can occasionally involve the anterior segment. Firstly, conjunctivitis (e.g. viral) is often more severe and prolonged in patients with HIV due to reduced immune clearance of the virus. Also, many patients with HIV will have occasional transient nonspecific conjunctivitis with irritation, hyperaemia and tearing. Such cases often do not come to medical attention and if so, do not require treatment. Finally, patients with HIV and especially those with low CD4 counts can have conjunctival or cornea infection from microsporidia, an opportunistic fungal/protozoan species. Such infections often resolve with proper antimicrobial treatment. It should also be noted that many patients with HIV display abnormal conjunctival vasculature secondary to “conjunctival microvasculopathy” that may make the eye appear red.
Multiple other systemic viral infections can have an associated mild conjunctivitis. Examples include:
- Measles: measles (aka rubeola) is a respiratory tract infection caused by a paramyxovirus. The classic symptoms are cough, coryza (runny nose) and conjunctivitis, with other symptoms/signs including fever, Koplik’s spots (inside the mouth) and a maculopapular, erythematous rash starting on the head and becoming generalized. In its early stages, it may cause photophobia, conjunctivitis, and iritis. Because of the widespread vaccination programs with the MMR vaccine, the disease is much less common but small cluster still occur. Treatment is supportive with monitoring for complications.7
- Mumps: mumps, another infection significantly decreased in incidence since MMR vaccination, is an infection caused by the mumps virus that causes inflammation of salivary (often parotid) and other glands. It often begins with prodromal symptoms of myalgias, anorexia, malaise, headache and fever that may occur with dacroadenitis before parotitis becomes evident. Commonly an acute conjunctivitis with mucoid discharge or episcleritis is present. Patients may have photophobia and tearing. Treatment is supportive.
- Rubella: rubella (“German measles”) is an infection caused by the rubella virus that is also rarely seen in developed countries since MMR vaccination. It is characterized by an often mild disease with an erythematous rash starting on the head and spreading inferiorly. It often causes mild follicular conjunctivitis appearing 2-3 days before the rash and lasting a few days. Recognition of rubella is especially important in women of child-bearing age as infections during pregnancy can cause severe neonatal problems (i.e. congenital rubella syndrome).
- Influenza: influenza virus is occasionally associated with a mild conjunctivitis17
Adenoviral conjunctivitis typically presents with an acute red eye. In its mild form, the conjunctivitis is diffuse and the ocular redness resolves over a few days. It is common to have a tender preauricular node on the affected side. Occasionally the disease may be severe with hemorrhagic conjunctivitis and possibly a fibrin pseudomembrane on the conjunctival surface.15 In severe infections there may also be diffuse epithelial keratitis with a swollen cornea and even iritis. In the latter case the patient will often have severe pain. The acute punctate keratitis lasts for about 7-10 days, after which it recedes. Subepithelial infiltrates may develop during this time, appearing as tiny semi-transparent snowballs in the superficial corneal stroma.15 The infiltrates can cause visual blurring and can wax and wane for weeks to months. If subepithelial infiltrates last for more than 3 months it is likely they will last for years causing discomfort and decreased vision.15
Adenoviral conjunctivitis is (or eventually is) bilateral in most (~75%) of cases.7