Introduction

While problems with the cornea can cause permanent visual loss, and a leukocoria can indicate the possible presence of a cataract or retinoblastoma, which can be visually devastating or even life threatening, the conjunctiva often causes relatively little concern. However, the conjunctiva is one of the most important structures that helps to maintain the health and wellbeing of the eye. Without this extremely thin covering of the anterior portion of the globe, the eye would be exposed to an extremely harsh environment. Although most cases of routine conjunctivitis will resolve spontaneously over 10–14 days, with or without treatment, the physician should be alert to the case which can potentially cause serious and permanent vision problems. These serious conditions, although rare, that are thought of as ‘only pink eye’ can cause a lifetime of vision problems in the patient. This chapter will look at the anatomy, physiology, pathophysiology, and treatment of the conjunctiva and conjunctival disorders to help the primary care provider in maintaining the health of the child’s eye.

The conjunctiva is a thin, translucent mucous membrane that is vascularized and serves as both a barrier and as a reservoir of immunologic components to protect the eye (69). The only portion of the anterior segment of the eye that is not covered by the conjunctiva is the cornea. The conjunctiva has two anatomical components: the tarsal conjunctiva and the bulbar conjunctiva. The tarsal conjunctiva starts on the lids at the mucocutaneous junction, referred to by ophthalmologists as the ‘gray line’. It is firmly attached to the inside portion of the eyelid, creating the mucosal surface of the lid. The bulbar conjunctiva starts approximately 1 mm from the limbus, the area where the sclera and cornea meet, and is loosely attached to the globe, except at the limbus where it is tightly attached to the episclera. The tarsal and bulbar conjunctivae then meet in the superior, temporal, and inferior portions of the globe, forming a sac called the fornix of the eye. The superior fornix extends up approximately 25 mm from the open eyelid margin, while the inferior fornix extends down approximately 9–10 mm from the eyelid margin.1 The tarsal and bulbar conjunctivae join laterally to create the lateral boundary of the fornix, but

medially, the conjunctiva ends at the caruncle, which contains skin as well as conjunctival components. Tenon’s capsule, also known as the fascia bulbi, is a thin tissue which covers the globe from the optic nerve to the limbus, separating it from the orbital fat. The bulbar conjunctiva sits on Tenon’s capsule, and is fused with this tissue at the limbus at the episclera.

The conjunctiva is composed of nonkeratinized, stratified columnar epithelium which sits on top of the substantia propria, a highly vascularized connective tissue. These tissues then meet at the limbus and the columnar epithelium then transitions to stratified squamous epithelium and joins the corneal epithelium. The conjunctiva is highly populated with cells that produce the aqueous, mucin, and outer lipid layers of the tear film. The conjunctival goblet cells produce the mucopolysaccharides that form the protective mucous layer of the tear film. These cells also produce immunoglobulin A (IgA), which forms the immunologic barrier. Goblet cells are found in greater quantities in the young, and decrease as we age, accounting for the increased occurrence of dry eyes in the elderly. They are distributed throughout the conjunctiva, but with a great preponderance in the inferonasal portion of the conjunctiva. The aqueous portion of the tear film is produced by the lacrimal glands and accessory lacrimal glands. The ducts of these glands open onto the surface of the conjunctiva, and along with keeping the eye moist and comfortable, bring a vast array of immunologic factors which protect the eye from foreign substances.

The conjunctival fornices prevent a contact lens from slipping off of the cornea and becoming dislocated behind the eye of the wearer. If a contact lens remains on the globe, it will be located in either the superior or inferior fornix. The substantia propria contains abundant mast cells, plasma cells and neutrophils, which, although possibly linked to allergy and anaphylaxis, also play a significant role in immunologic protection, as well as wound healing.2

Conjunctivitis

Conjunctivitis literally means an inflammation of the conjunctiva. When this membrane becomes inflamed, it is commonly referred to as ‘pink eye’ or ‘red eye’.3 The etiology of the inflammatory process is complicated (70). The inflammation can result from both an infectious and noninfectious etiology and proper diagnosis of the etiology is imperative in order to deliver effective treatment.4–7 Outbreaks of conjunctivitis are seasonal in nature; they occur most frequently when children are in close contact with each other in the winter, and tend to decrease during warm

weather, when close contact decreases. This is evident in the number of prescriptions written for ocular antibiotics. However, conjunctivitis does occur year round. The etiology of the inflammation also somewhat follows the age of the patient, with a bacterial etiology occurring most frequently in younger, preschool age children, and a viral etiology occurring most frequently in older children and adults.8 However, there have been reported outbreaks of bacterial conjunctivitis occurring in older children as well as adults.9,10 Table 5 presents the various etiologies of conjunctivitis seen in the pediatric population.

Determining the etiology of conjunctivitis is not always easy. Cultures are rarely, if ever, obtained, and a significant number of cases are diagnosed by telephone triage. The most important information to elicit from either telephone triage or the office visit is an accurate history of the child’s signs and symptoms (Table 6).

Table 5 Types of conjunctivitis

Bacterial conjunctivitis

DEFINITION/OVERVIEW

Acute conjunctivitis is the most common ocular infection in childhood, usually affecting children less than 6 years of age. The belief that most causes of conjunctivitis in children are viral in etiology is not supported by the literature. The literature, from the early 1980s through 2007, shows that the most common

form of acute conjunctivitis in the pediatric population is bacterial in nature.4,11–14 If the

child is under 1 year of age, the presence of a congenital dacryostenosis causing a purulent discharge must be excluded from the diagnosis of acute bacterial conjunctivitis. Bacterial conjunctivitis can occur in three forms: acute, hyperacute, and chronic.

ETIOLOGY

The eye has a number of different defense mechanisms that help to protect it from a bacterial infection. These include the presence of normal, nonpathogenic colonies of bacteria on the conjunctiva – which help prevent the establishment of invading pathologic organisms, the presence of immunologic agents secreted in the normal tear film, and physical shearing forces of the natural blink. These all provide a defense mechanism for the eye. When any of these protective mechanisms are compromised, an acute bacterial infection can result. The organisms that have been shown in all of the published papers from 1981 through

2007 are Staphylococcus aureus, Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis.3,11–16

CLINICAL PRESENTATION

The signs and symptoms of bacterial conjunctivitis are listed in Table 6. The history might reveal that the child has been rubbing their eyes and showing ocular irritation over the past 12–24 hours. The patient will usually present with conjunctival injection of the bulbar and tarsal conjunctival vessels (71). The conjunctival injection might also involve the episcleral vessels. There might be mild discomfort or irritation, but frank pain is atypical and should lead the primary care provider away from the diagnosis of routine bacterial conjunctivitis and towards the differential diagnosis of a more serious etiology for the red eye. There might also be a mild amount of photophobia present, but any significant degree of photophobia is not consistent with the diagnosis of acute bacterial conjunctivitis. Special mention should be made of conjunctivitis in a contact lens wearer. Concerns about

Pseudomonas aeruginosa should be at the forefront of the differential diagnosis of conjunctivitis in this population (72). A contact lens wearer with signs of conjunctivitis and pain or decreased vision should be referred to an ophthalmologist promptly.

The hallmark of acute bacterial conjunctivitis is the presence of purulent or mucopurulent discharge from the eye with

matting of the lashes. The matting will usually be seen after the child awakens in the morning, or after an extended nap. Visual acuity is not altered except possibly briefly with the purulent discharge obscuring the vision. This should clear with blinking. If the child is seen in the office, attempts to obtain a visual acuity measurement should be made, especially in the older child who can cooperate. Lymphadenopathy is usually not present except possibly during the late stages of the disease when the symptoms are spontaneously starting to clear without treatment in 7–10 days. The presence of lymphadenopathy with either preauricular or submandibular involvement should lead the primary care provider towards the diagnosis of a viral etiology for the conjunctivitis. Both membranous as well as pseudomembranous conjunctivitis can be seen (73). The difference between membranous and pseudomembranous conjunctivitis is the way the membrane peels off of the conjunctiva. In pseudomembranous conjunctivitis, the membrane is easily removed and causes no bleeding, where in membranous conjunctivitis, peeling of the membrane causes bleeding and discomfort, and is much more difficult to accomplish. Membranous conjunctivitis can be caused by bacterial conjunctivitis with an etiology of β-hemolytic streptococci, pneumococci, Corynebacterium diptheriae, and Neisseria gonorrhoeae. Pseudomembranous conjunctivitis can be seen in all

of the causes of membranous conjunctivitis as well as ocular cicatricial pemphigoid, superior limbic keratoconjunctivitis, and chlamydial conjunctivitis in newborns. Viral conjunctivitis with an etiology of adenovirus, herpes simplex virus and ocular vaccinia, as well as ligneous conjunctivitis, Stevens–Johnson syndrome, and chemical and thermal burns can all cause membrane formation.

Although bacterial conjunctivitis is very often a bilateral disease, with one eye usually showing more involvement than the fellow eye, it can also occur as a unilateral condition. It can be seen in the pediatric population associated with another acute infection, acute otitis media (AOM) in what is known as the conjunctivitis–otitis media syndrome.14–16 Conjunctivitis–otitis media syndrome can be seen in as high as 35% of children who have conjunctivitis, and is indicative of a bacterial etiology.

The natural history of bacterial conjunctivitis will lead to the return of the normal bacterial flora and eradication of the offending organism. However, if there is a large pathologic organism load and disruption of any of the natural defense mechanisms of the cornea (i.e. breakdown of the intact corneal epithelium from continual rubbing secondary to irritation), a corneal infection (keratitis) or corneal ulcer formation can occur. A corneal ulcer has the potential to interfere with normal vision by causing a corneal scar to form following healing of the ulcer. The healing ulcer causes disruption of the regular alignment of

73

73 Pseudomembrane.

the corneal fibrils, and thus opacification of the clear cornea. If this scar is in the visual axis, permanent visual damage can occur.

MANAGEMENT/TREATMENT

Table 7 (overleaf) summarizes the modalities available for treatment of bacterial conjunctivitis in 2008, compiled from the package inserts of the various antibiotics. This information will continually change as newer antibiotics are added to the pharmaceutical armamentarium, and bacteria continue to develop resistance to chemotherapeutic agents. The use of the algorithm in Figure 70, especially if telephone triage is used, can help the physician in choosing the most appropriate treatment regimen for the child’s inflamed eye.

A contact lens wearer who shows signs of a bacterial conjunctivitis should be evaluated and may require cultures prior to the initiation of antibiotic therapy. If treatment is started without obtaining cultures, and any patient does not respond to treatment of a significant purulent conjunctivitis, the primary care provider should consult an ophthalmologist, especially if the patient is a contact lens wearer. At this point, cultures and Gram stain of the conjunctiva are often obtained prior to any change in therapy, to ascertain the etiology of the infective organism to prevent the possibility of visually devastating sequelae (74).

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74 Pseudomonas corneal ulcer 6 months postinfection.

Rationale for the treatment of bacterial conjunctivitis

The use of antibiotics, in any circumstance, systemically or topically, must be well thought out, and antibiotics should not be used in a haphazard or ‘shotgun’ approach. Unless the etiology of the disease process, or its sequelae, is bacterial in nature, the use of antibiotics is inappropriate and should be avoided. To treat everything ‘with a pill or drop’ will accelerate the emergence of ‘super bugs’ such as methicillin-resistant Staphylococcus aureus (MRSA), both hospital and community acquired (HA-MRSA, CA-MRSA). The treatment of bacterial conjunctivitis should include the following goals:

•A rapid rate of bacterial kill to minimize the spread of the contagion.

•A high concentration of the antibiotic in the target tissue to exceed the minimum inhibitory concentration (MIC) for the suspected pathogens.

•A broad range of coverage to include all of the known bacterial etiologies of the disease, including staphylococci, streptococci, Haemophilus influenzae, and Moraxella catarrhalis.

•A low incidence of bacterial resistance.

•A low level of ocular toxicity.

•A drop that is comfortable and well tolerated by the pediatric population.

•A convenient dosing schedule to enhance parental compliance.

If any of these points are not met, the treatment of the disease could prove to be worse than this self-limiting disease itself. In addition, treating suspected bacterial conjunctivitis with an antibiotic that meets all of these criteria facilitates rapid identification of a masquerade syndrome; a disease may present as a ‘routine’ case of conjunctivitis, but is actually a process that can cause significant damage to the eye, or even blindness. With the use of an antibiotic that is bacteriocidal and shows minimal resistance to the most common bacteria causing conjunctivitis in the pediatric population, these masquerade syndromes can be rapidly identified, and appropriate therapy can be initiated.

With increasing bacterial resistance, the most logical approach to the choice of an appropriate antibiotic would be to limit the use of newer antibiotics, and use an older antibiotic until failure of treatment is seen. This is

commonly called the ‘Big Gun’ theory, and is very relevant to systemic disease. However, in topical treatment of bacterial conjunctivitis, the use of the ‘Correct Gun’ is much more appropriate and will help to identify a masquerade syndrome much more rapidly. A virtual ‘safety net’ can be achieved by prescribing a bacteriocidal antibiotic which can rapidly eradicate the organism.17 The newer generation fluoroquinolones fit this profile extremely well because of their rapid action on the bacteria.18 The appropriate way to treat bacterial conjunctivitis is therefore to make the diagnosis, select the appropriate antibiotic, treat for a short period of time, and then discontinue the use of the antibiotic; this will not lead to increasing resistance of the bacteria.

Resistance

One of the most frightening things seen in medicine is the emergence of bacteria that have mutated to become resistant to antimicrobial agents. The prolonged use of antibiotics, along with tapering dosage regimens, is the most likely cause of increasing resistance. There are definite correlations between the inappropriate use of antibiotics and patient noncompliance with the emergence of resistant organisms.19 The use of antibiotics in animal feed to help bring livestock to market has also played a role in the development of antibiotic resistance in humans.20 Bacteria have shown a definite increase in resistance to the fluoroquinolones. Although this group shows excellent Gram-negative coverage, Gram-positive organisms are developing increasing resistance to the secondand third-generation fluoroquinolones, especially S. pneumoniae.21 A retrospective study of isolates recovered from bacterial conjunctivitis and keratitis was conducted during the 12-year period from 1990 to 2001 to determine the resistance of methicillin-sensitive S. aureus (MSSA) to ciprofloxacin and levofloxacin.22 There was a definite pattern of increasing resistance, which was statistically significant. In a 15-year study in Sao Paulo, Brazil, from 1985 to 2000, of 4585 conjunctival cultures examined, there was a marked decrease of in vitro activity of gentamycin and tobramycin against

S. pneumoniae and S. aureus.23 Recent findings show that approximately half of the S. epidermidis isolates from the normal human conjunctiva had one or more mutations of topoisomerase II and topoisomerase IV, which is strongly associated with reduced susceptibility to fluoroquinolones.24