Chapter 21. Conjunctivitis in the Older Child

Conjunctivitis, commonly referred to as “red eye” or “pink eye,” is a nonspecific term used to describe an inflammation of the conjunctiva, which can be caused by a wide range of conditions. The conjunctivae are the mucous membranes extending from the eyelid margin to the corneal limbus, forming the posterior layer of the eyelids and the anterior layer of the eyeball. Conjunctivitis may result from primary involvement of the conjunctival tissue or may occur as a secondary manifestation of other ocular or systemic conditions that produce conjunctival inflammation.

Conjunctivitis is prevalent worldwide. It is the most common ocular infection in childhood, usually affecting children younger than 6 years, with a peak incidence between 12 and 36 months.1 Infectious causes of conjunctivitis may be sporadic or related to epidemic outbreaks. In most cases, conjunctivitis is benign and self-limited.

The conjunctiva is a loose connective tissue that covers the surface of the eye (bulbar conjunctiva) and forms the inner layer of the eyelids (palpebral conjunctiva). It is adherent to the underlying sclera at the limbus (corneal margin). It also contains numerous goblet cells, which secrete the mucinous layer of the tear film. Conjunctivitis is characterized by dilatation of the superficial conjunctival blood vessels, resulting in hyperemia and edema of the conjunctiva, with discharge. Fluid may accumulate beneath the loosely attached bulbar conjunctiva, causing it to swell away from the globe, making eye closure difficult (a phenomenon known as chemosis).

Patient History

The diversity of etiologies for conjunctivitis makes a detailed patient history the most important step in the differential diagnosis of conjunctivitis. The patient history should include the chief complaint such as itching, burning, tearing, discharge, pain, foreign body sensation, and photophobia. It should also include questions about the onset and course of the disease, whether it is acute or chronic and progressive or stationary. The ocular history should include questions about previous episodes, prior exposure to infected individuals, history of trauma or contact lens wear, and the use of topical legend (i.e., prescription) or over-the-counter medications or cosmetics. The general health history should include descriptions of recent upper respiratory tract infections, autoimmune disorders, atopy, skin conditions, and sexually transmitted infections. Finally, the social history such as environmental exposure and the family history of ocular diseases may contribute to the diagnosis of “red eye.”

The signs and symptoms of conjunctivitis, including redness, tearing or discharge, and foreign body sensation, are similar regardless of the cause. Pain and photophobia are not symptoms of conjunctivitis; if present, they may indicate other entities, including corneal abrasion, keratitis, uveitis, or acute angle-closure glaucoma. Decreased vision is not typical in patients with conjunctivitis. Occasionally, extensive discharge may blur the visual axis intermittently, but, in general, a report of decreased acuity should prompt a search for more serious disorders.

Physical Examination

The ocular examination in a patient with conjunctivitis should include examination of the skin of the lids and the face, looking for any associated skin conditions, edema, ecchymosis, and discoloration. Certain signs and symptoms are important to consider in differentiating among the various causes of conjunctivitis. The character of the discharge may provide some diagnostic help. Serous or watery discharge usually is associated with viral or allergic etiologies. Mucopurulent discharge suggests a viral or chlamydial infection, whereas purulent discharge suggests a bacterial etiology. Close inspection of the conjunctiva may reveal follicles, suggestive of viral or chlamydial infections, or papillae, suggestive of bacterial or allergic processes. Follicles are elevations encircled by blood vessels, whereas papillae have a central vascular core.

It is also important to look for clues on physical examination, which suggest other causes of a “red eye.” In general, the redness of conjunctivitis spares the limbus. If the limbus is involved, other diagnoses must be considered, including keratitis (inflammation of the cornea) and uveitis (intraocular inflammation). A comprehensive eye examination with dilation of the pupils should be performed in those patients with conjunctival hyperemia, accompanied by proptosis, optic nerve dysfunction, decreased visual acuity, diplopia, or evidence of anterior chamber inflammation.2

Manifestations of Common Causes of Conjunctivitis

The etiologies of conjunctivitis can be classified as infectious and noninfectious. Noninfectious causes may be primary in origin, e.g., allergic conjunctivitis, or secondary to other systemic diseases. Infectious conjunctivitis can be bacterial or viral in origin.

Bacterial Conjunctivitis

Bacterial conjunctivitis (Figure 21–1) can be classified as hyperacute, acute, or chronic. It occurs when an organism is able to overcome the host's resistance, or following trauma. Most common bacterial pathogens can cause conjunctivitis. These pathogens include Haemophilus species (nontypable H. influenzae), Streptococcus pneumoniae, and Moraxella species. S. pneumoniae and Haemophilus infections occur more frequently in children.3–5

Symptoms of bacterial conjunctivitis typically include unilateral or bilateral conjunctival injection, purulent discharge, and matting of the eyelids. More severe forms of bacterial conjunctivitis, as indicated by copious purulent discharge, suggest infection by more virulent organisms. These include Neisseria gonorrhoeae, Neisseria meningitidis, or Pseudomonas aeruginosa.

Acute or mucopurulent bacterial conjunctivitis is caused by a number of microbial agents, primarily Staphylococcus aureus, S. pneumoniae, and Haemophilus species. It is a common infectious condition that can affect all ages and races and both genders. This condition is usually self-limiting and generally lasts for <3 weeks. Atypical unencapsulated strains of S.pneumoniae are responsible for large outbreak of conjunctivitis in college campuses.6

Hyperacute or purulent bacterial conjunctivitis is commonly caused by N. gonorrhoeae, microorganisms that can penetrate an intact corneal epithelium, or, less frequently, by N. meningitidis. Infection by N. gonorrhoeae is seen most often in neonates who acquire the disease via passage through an infected birth canal; this topic is discussed in Chapter 20.7 However, this infection can also be contracted through sexual activity and may indicate that a child has been sexually active or has been sexually abused. This organism is highly virulent and may lead to corneal ulceration and perforation. Hyperacute bacterial conjunctivitis is most commonly acquired by autoinoculation from infected genitalia and most often seen in neonates, adolescents, and young adults. It appears to be more common during warmer months of the year.8,9 A less common cause of bacterial conjunctivitis is P. aeruginosa, especially in hospitalized infants, which may lead to a rapidly progressive invasive infection with corneal perforation.10,11

When symptoms of bacterial conjunctivitis last longer than 4 weeks, it can be considered chronic. The most common cause of chronic bacterial conjunctivitis is S. aureus. Chronic bacterial conjunctivitis is frequently associated with continuous inoculation of bacteria associated with blepharitis (inflammation of the eyelids, particularly at the lid margins).12

An unusual cause of conjunctivitis is Lyme disease, which is caused by Borreliaburgdorferi. Conjunctivitis usually occurs early in the disease, is mild and transient, and may be followed by other ocular manifestations of Lyme disease including keratitis, vitritis, uveitis, neuroretinitis, optic atrophy, and Bell's palsy.13

Parinaud oculoglandular syndrome is an entity characterized by unilateral granulomatous conjunctivitis, ipsilateral tenderness, and enlargement of the preauricular lymph nodes. It is often caused by Bartonella henselae14 and less commonly by Francisella tularensis12,15 but may also be associated with other infections.

The conjunctivitis–otitis media syndrome, a distinctive clinical entity, is characterized by purulent conjunctivitis associated with acute otitis media. It was initially described by Coffey16 in 1966 and further characterized by Bodor17 in 1982. It begins with low-grade fevers and mild upper respiratory symptoms, followed several days later by eye discharge and pain, with the development of ear pain in some cases. Sometimes otitis media may be the initial presentation with subsequent development of purulent conjunctivitis. Nontypable strains of H. influenzae are responsible for more than 70% of cases of conjunctivitis–otitis syndrome.18,19 The remaining cases are usually caused by either S. pneumoniae or Moraxella species.

Viral Conjunctivitis

Adenoviruses, the most common viral cause of conjunctivitis, account for 20% of all cases of conjunctivitis.20 Other viral causes of conjunctivitis include herpes simplex virus (HSV), varicella zoster virus, and enteroviruses including coxsackievirus.

Adenoviral Conjunctivitis

Adenoviral conjunctivitis is extremely contagious; transmission typically is by direct contact with infected persons or contaminated objects or instruments such as tonometers used widely in eye clinics.21 Adenovirus conjunctivitis (Figure 21–2) is characterized by acute onset of unilateral and then bilateral, bulbar, and palpebral conjunctival hyperemia and by the formation of follicles on the palpebral conjunctiva. Petechial hemorrhages are commonly present, particularly in the bulbar conjunctiva. Follicular conjunctivitis is the most common type of adenoviral conjunctivitis. Associated findings include watery discharge, rhinitis, and preauricular lymphadenopathy usually more prominent on the side of the initially affected eye.

Depending on the stage of development, conjunctival pseudomembranes may be found on the superior or inferior tarsal conjunctiva. Lid edema may also be present.

Adenovirus infections tend to be more common in the fall and winter. Patients often have symptoms of an upper respiratory infection and may have had recent contact with another person with either a red eye or an upper respiratory tract infection.

Other less common forms of adenoviral conjunctivitis include epidemic keratoconjunctivitis and pharyngoconjunctival fever. Epidemic keratoconjunctivitis is caused by adenoviral serotypes 8, 19, and 37.22 Patients usually complain of severe discomfort, photophobia resulting from keratitis, and watery discharge. This form is very contagious and often occurs in epidemic outbreaks. Physical findings include injection, chemosis, follicular reaction, corneal superficial punctate defects, and eyelid edema. Corneal subepithelial infiltrates may begin to form after 2 weeks in the disease process and, if present, may last for as long as 2 years.

The third form of adenoviral conjunctivitis, the pharyngoconjunctival fever, is caused by adenoviral serotypes 3 and 7.22 In addition to the conjunctival injection and chemosis, patients usually present with fever, pharyngitis, and preauricular lymphadenopathy. Symptoms may last for 2 weeks or more. Summertime epidemics of pharyngoconjunctival fever, linked to swimming in infected pools, have been reported.5

Herpetic Conjunctivitis

Infection with a member of the Herpesvirus genus (e.g., herpes simplex, varicella zoster, or Epstein–Barr virus) can result in acute conjunctivitis. HSV conjunctivitis (Figure 21–3) may occur as either a primary or a secondary infection. Most ocular infections occur as result of HSV-1, except in neonates, in whom HSV-2 is more predominant. Transmission occurs by direct contact with another person who has an active lesion or by autoinoculation of the eye from skin lesions. Signs include a follicular conjunctival reaction, watery discharge, and preauricular lymphadenopathy. Other findings suggestive of herpes simplex infection include skin or lid vesicles, gingivostomatitis, and keratitis. Fifty percent of patients with herpes zoster ophthalmicus (involving the ophthalmic division of the trigeminal nerve) show involvement of the ocular structures, of which conjunctivitis is the most common manifestation.

Bulbar or palpebral conjunctivitis may occur during primary varicella zoster infection (chickenpox). The recurrence of varicella zoster infection in the distribution of the ophthalmic division of trigeminal nerve (cranial nerve V) is known as herpes zoster ophthalmicus. It involves the ocular structures, and conjunctivitis is a common manifestation of this disease. Signs and symptoms are similar to HSV infection and include conjunctival injection, follicular conjunctival reaction, vesicles, and watery discharge. Patients may also complain of pain in the cranial nerve V1 distribution.

Causes of conjunctival inflammation in children include infectious conjunctivitis (e.g., viral, bacterial, and chlamydial), allergic conjunctivitis, blepharoconjunctivitis, trauma, foreign body, chemical reaction, and nasolacrimal duct obstruction.2,23 The “red eye” can be the first manifestation of serious systemic disorders (Table 21–1).

Allergic conjunctivitis is mainly a hypersensitivity type I reaction mediated by IgE antibodies and involves mast cell degranulation and release of inflammatory mediators, which are responsible for the signs and symptoms present in patients with allergic conjunctivitis. This form of conjunctivitis is characterized by itching, tearing, redness, chemosis, and eyelid edema. Both eyes are usually involved, and symptoms may present seasonally. A history of other atopic diseases is frequently associated with allergic conjunctivitis.

Mechanical conjunctivitis can result from irritation of the conjunctival surface by eyelashes, sutures, and foreign bodies such as contact lenses. Conjunctivitis may also result from trauma following a direct injury that results in abrasions or lacerations. Finally, toxic conjunctivitis may occur following the administration of drugs or exposure to noxious chemicals and from overuse of eye drops, especially sulfonamide derivatives.

In addition to history taking, a detailed physical examination should be performed on patients with conjunctivitis. Testing of visual acuity, examination of the fundus, tonometry and biomicroscopic examination often aid in making the diagnosis and excluding other causes of conjunctivitis.

Most primary-care physicians treat conjunctivitis presumptively as bacterial in origin and do not order any diagnostic tests.24,25 Conjunctival cultures and smears are helpful and should be considered in cases of treatment failure and for immunocompromised patients. Identification of the etiologic agent and determination of antibiotic sensitivities are essential for proper management, especially in cases of hyperacute, chronic, and recurrent conjunctivitis. If possible, cultures should be obtained prior to beginning treatment, which can help guide the selection of the initial treatment. Tympanocentesis, if indicated, may be helpful in cases of conjunctivitis–otitis syndrome because the culture of the ear exudate usually yields the causative organism.18,19

Conjunctival scrapings, if needed, are usually performed by a specialist. They provide a detailed examination of conjunctival epithelial cells and identification of intracellular inclusions and may also reveal the nature of the inflammatory cell response. Cell cultures can be used to diagnose viral conjunctivitis (i.e., HSV and adenovirus), but they are time consuming and not very practical in an outpatient setting. However, polymerase chain reaction using the proper primers shows an increased sensitivity over cell culture for the detection of adenoviruses in conjunctival swabs and provides results in a short time compared to cell cultures.26

Clinicians nearly always treat acute conjunctivitis empirically with topical antimicrobial therapy. If the disease is mild or the patient has associated signs of upper respiratory infection, cultures are rarely obtained either because of expense or because culture results are reported days later. Social factors, including the need for children to attend day care or school and parents to go to work, the parents’ desire to seek early treatment in response to their own beliefs, and advice from others that this is a contagious disease, contribute to the decision to prescribe antibiotics for children with acute infective conjunctivitis.24,25

Bacterial Conjunctivitis

Ideally, the causative organism of bacterial conjunctivitis should be identified and effective antimicrobial treatment against the offending organism should be initiated. In the absence of a microbiological diagnosis, the etiologic agent should be considered in the context of the patient's age, environment, and related ocular findings, and the empiric treatment should be based on clinical evaluation.

Most cases of bacterial conjunctivitis are self-limited, but treatment with effective antibiotics can decrease the duration of the infection, alleviate the patient's symptoms, and reduce the chances of its recurrence compared with placebo. In randomized trials, subgroups of patients with culture-positive bacterial conjunctivitis have increased microbiological cure when treated with topical antibiotics compared with placebo.27–29 Treatment usually consists of a broad-spectrum topical antibiotic administered four to eight times daily, depending on the type. This empirical approach is highly effective, with no major adverse consequences.24 The available topical antibiotics have a broad spectrum of activity, including gram-positive as well as gram-negative bacteria. Topical antibiotic therapy with polymyxin–bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva.30,31 Commonly used topical antibiotics are summarized in Table 21–2.

Current Clinical Laboratory Standard Institute breakpoints for susceptibility to topical antibiotics are not available, and the appropriate formulation of combination antibiotics for in vitro testing has not been determined. Thus, evaluating antibiotic pharmacokinetics in tears may better predict efficacy for some topical antibiotics; these kinetics are usually affected by frequent tearing in children, leading to an overestimation of the concentrations in tears of younger children. Topical ointments probably deliver more sustained concentrations of antibiotic to the conjunctiva, but they are poorly tolerated in toddlers and difficult for most parents. Alternatively, a short course of an oral beta-lactam antibiotic may possibly eradicate the conjunctival infection. In a randomized trial of oral cefixime and topical polymyxin–bacitracin, bacteriologic failure occurred in 62% for children receiving oral cefixime (orally, once daily for 3 days) and in 82% for children receiving topical polymyxin–bacitracin (topically, four times daily for 7 days); however, clinical cure rates among the 80 patients were virtually 100%, regardless of treatment group.32 However, In cases of conjunctivitis–otitis syndrome, therapy with an appropriate oral antibiotic for the otitis media is sufficient for the cure of conjunctivitis without the addition of topical therapy.33

Hyperacute conjunctivitis may involve the cornea and may cause peripheral ulceration, ultimately leading to perforation if left untreated. It requires aggressive treatment and immediate referral to an ophthalmologist. Systemic treatment against gonorrhea should be instituted immediately. Current treatment recommendation is a single dose of ceftriaxone, 50 mg/kg, intramuscularly, up to a maximum of 1g.34 Frequent saline lavage is also indicated until the purulence resolves. All children beyond the neonatal period diagnosed with gonococcal conjunctivitis should be investigated for sexual abuse.

Antimicrobial resistance is evolving rapidly especially for H. influenzae and S. pneumoniae, the two most common causative organisms of bacterial conjunctivitis in children. Nontypable strains of H. influenzae are also responsible for more than half of the cases of conjunctivitis–otitis syndrome. The rate of beta-lactamase producing H. influenzae isolated from children with acute conjunctivitis has increased from 16% in the nasopharynx during the mid-1980s, compared with rates from conjunctivitis of 44% in the late 1980s, to 69% in the late 1990s.35,36

On the other hand, penicillin resistance rates among S. pneumoniae isolates has been reported as high as 60% from conjunctival cultures.35,36 The introduction of the heptavalent pneumococcal conjugate vaccine (PCV-7) has led to the “serotype replacement” phenomenon already described for acute otitis media and nasopharyngeal carriage promoting invasive pneumococcal disease caused by the nonvaccine serotypes. One study showed that PCV-7 would cover only 44% of S. pneumoniae strains isolated from conjunctival specimens and reported high penicillin resistance rates among the vaccine isolates causing conjunctivitis.36 The penicillin resistance rate is also high among nontypable strains of S. pneumoniae, which are a major cause of conjunctivitis outbreaks and a common cause of sporadic acute conjunctivitis.6,36

Published data showed that ciprofloxacin, ofloxacin, and tetracycline are the most active drugs in vitro against both pathogens (H. influenzae and S. pneumoniae). Gentamicin, tobramycin, polymyxin B–trimethoprim, and polymyxin B–neomycin have intermediate activity.35

Failure of treatment should always raise the possibility of resistant organisms. In this case, conjunctival cultures should be obtained, treatment should be switched and more potent antibiotics should be used. Topical quinolones are approved by the food and drug administration for use in children to treat conjunctivitis. Their concentrations in tears remain above the minimum inhibitory concentrations described for H. influenzae and S. pneumoniae.37 They can be used safely if first-line agents fail to cure the symptoms of conjunctivitis.

Viral Conjunctivitis

Viral conjunctivitis is usually self-limited and not routinely treated with antibiotics. Topical antiviral drugs are not indicated in adenoviral conjunctivitis.31 The use of topical steroids in the management of this infection remains controversial. Their use is usually limited to complicated cases to reduce inflammatory reaction and prevent scarring. Corticosteroids may also prolong the disease course and may cause serious side effects such as glaucoma. Supportive therapy, including eye washing, lubricants, and cold compresses, may provide some relief, and the use of topical antibiotic is unnecessary.

The treatment of herpes simplex conjunctivitis includes topical antiviral agents such as trifluridine, which may be as effective as supportive measures.38 Oral antiviral therapy may be used in case of complicated infections and keratitis. Topical steroids are specifically contraindicated for treating herpes simplex conjunctivitis because they may exacerbate the infection by depressing local immunity.

The treatment of herpes zoster conjunctivitis (i.e., conjunctivitis caused by reactivation of varicella zoster) includes the use of systemic antiviral therapy. This therapy should be started within 72 hours of the beginning of the symptoms to be most effective in reducing viral shedding and postherpetic neuralgia. Topical antibiotics may be used to reduce the risk of secondary bacterial infection. In contrast with herpes simplex conjunctivitis, topical steroids do not aggravate herpes zoster infections and decrease the inflammatory response.39 They may be used in case of keratitis and uveitis.

Once the primary-care physician has diagnosed conjunctivitis and initiated proper treatment, the patient requires follow-up visits, depending on the severity of the condition, the etiology considered, and the potential for ocular complications. The primary-care physician should be aware of and able to exclude other possible and serious causes of conjunctivitis that may warrant referral for a subspecialist. The patient should be referred to a subspecialist in certain cases including but not limited to

1. gonococcal conjunctivitis because of the potential complications;

2. progression of the disease despite adequate treatment;

3. lack of improvement of the symptoms despite alteration of therapy;

4. development of complications during treatment;

5. recurrent or chronic conjunctivitis;

6. monitoring of ocular pressure in case of use of topical steroids;

7. decrease in visual acuity and presence of photophobia, proptosis, or diplopia;

8. conjunctivitis diagnosed as part of other systemic disorders.

Although conjunctivitis is a benign and curable disease, it may have serious complications usually related to its etiology and dependent on associated systemic and ocular disorders.

Acute forms of bacterial conjunctivitis can lead to adhesion of the eyelids to the eyeballs (symblepharon) and/or conjunctival scarring. Hyperacute forms of bacterial conjunctivitis should be monitored closely for the development of bacterial keratitis and the potential corneal perforation and visual loss. Toxic and irritative conjunctivitis, especially when the cause is unknown, has the potential to become chronic. Topical antibiotics may cause irritation of the inflamed conjunctiva and some patients may develop an allergic reaction to the instilled solution, requiring the discontinuation of the drug. If there is no improvement in the symptoms of conjunctivitis in 7–10 days, the patient should be referred to an ophthalmologist.

Primary infectious conjunctivitis occurs sporadically as a result of exposure to pathogens from direct hand-to-eye contact, exposure to airborne pathogens, or sexual transmission.

Viral conjunctivitis is highly contagious. Replicating adenovirus is present in 95% of patients 10 days after the appearance of symptoms.40 It has been recovered from nonporous surfaces for up to 49 days,21 hence the potential transmission through sharing towels or other objects, through close contact with other persons including indirect contact (e.g., in a swimming pool), and through improperly disinfected instruments in eye clinics. Preventing the spread of infectious conjunctivitis involves, in addition to patient education, adequate infection control practices including hand washing before and after the examination, the use of protection barrier (gloves), and proper techniques for disinfection or sterilization of all equipment.