Demodex species
Demodex folliculorum and Demodex brevis inhabit normal superficial hair and eyelash follicles and deeper sebaceous and meibomian glands, respectively, with an increased incidence in facial glands being associated with rosacea (Fig 5-9). Eyelash colonization increases with age and may be associated with blepharoconjunctivitis. (See Fungal and Parasitic Infections of the Eyelid Margin later in the chapter.)
Figure 5-9 Demodex. (Wet mount ×100.) (Courtesy of Elmer Y. Tu, MD.)
Fly larvae
Myiasis occurs when maggots invade and feed on the living or dead tissues of humans or animals. Ophthalmomyiasis (maggot infestation of the eye) can refer to external or internal infestation and involve almost any ocular tissue. Most myiasis occurs when a female fly lands on the host and deposits eggs or larvae. The larvae of some fly species can penetrate through healthy skin and migrate long distances to infest the eye. Extensive larval infestation of a compromised external eye can result in total destruction of orbital contents.
Cox FEG, Wakelin D, Gillespie SH, Despommier DD, eds. Parasitology. In: Collier L, Balows A, Sussman M, eds. Topley & Wilson’s Microbiology and Microbial Infections. 10th ed. Vol 5. London: Hodder Arnold; 2005.
Tu EY. Acanthamoeba and other parasitic corneal infections. In: Krachmer JH, Mannis MJ, Holland EJ. Cornea. 3rd ed. Vol 1. Philadelphia: Elsevier/Mosby; 2011:1023–1032.
Prions
Prions are altered proteins that cause transmissible lethal encephalopathies, including CreutzfeldtJakob disease, scrapie in sheep, bovine spongiform encephalitis, and kuru. Transmission of Creutzfeldt-Jakob disease following corneal transplantation has been reported.
Prusiner SB. Shattuck Lecture: neurodegenerative diseases and prions. N Engl J Med. 2001;344(20):1516–1526.
Microbial and Parasitic Infections of the Eyelid Margin and
Conjunctiva
Staphylococcal Blepharitis
Staphylococcal bacteria on the anterior eyelid margin can cause blepharitis, part of a spectrum consisting of anterior and posterior forms that usually overlap considerably. These conditions are not purely infectious, since antimicrobial therapy is rarely curative due to a significant inflammatory component that may predispose to bacterial overgrowth and perpetuate a local immune deviation. This disorder is discussed in detail in Chapter 3.
Fungal and Parasitic Infections of the Eyelid Margin
Demodex is a genus of mites that are normal commensal acarian parasites of humans (see “Demodex species” earlier in the chapter). Their presence is suggested on slit-lamp biomicroscopy as waxy “sleeves” around eyelashes or as cylinders extending from sebaceous glands of the eyelid margin (Fig 5-10). The role of these parasites in the pathogenesis of blepharitis is unclear, but some patients may experience an inflammatory response with infestation. The infestation may respond to dilute tea tree oil applied to the base of the eyelashes. Other organisms that survive on lipids of eyelid glands, such as Malassezia furfur, have also been incriminated in certain types of blepharitis.
Figure 5-10 Demodex-associated sleeves. (Courtesy of Elmer Y. Tu, MD.)
A focal granuloma or dermatitis affecting the eyelid or conjunctiva can be caused by very rare infections, including
blastomycosis sporotrichosis rhinosporidiosis cryptococcosis leishmaniasis ophthalmomyiasis
Lice infestation of the eyelids and eyelashes, also known as phthiriasis palpebrum, is an uncommon form of conjunctivitis or blepharitis affecting adolescents and young adults and is caused by the pubic louse and its ova. In rare instances, pediculosis involves the ocular region by localized
extension of head or body lice (Pediculus humanus capitis or Pediculus humanus corporis, respectively). Mechanical removal of the lice and nits (eggs) can be performed with jewelers forceps, but pubic hairs are usually treated with a pediculicide. Any ointment can smother the lice and should be applied twice daily for at least 10 days, because the incubation period (of the nits) is 7–10 days. Periodic reexamination is recommended over 10–14 days to detect recurrence and remove any new nits. Bed linen, clothing, and any items of close contact should be washed and dried at the highest temperature setting (at least 50°C).
Bacterial Conjunctivitis in Children and Adults
PATHOGENESIS Bacterial conjunctivitis is less common than viral conjunctivitis in adults and is characterized by bacterial overgrowth and infiltration of the conjunctival epithelial layer and sometimes the substantia propria. The source of infection is either direct contact with an infected individual’s secretions (usually through eye–hand contact) or the spread of infection from the organisms colonizing the patient’s own nasal and sinus mucosa. In an adult with unilateral bacterial conjunctivitis, the nasolacrimal system should be examined. Nasolacrimal duct obstruction, dacryocystitis, and canaliculitis may lead to unilateral bacterial conjunctivitis.
Though usually self-limited, bacterial conjunctivitis can occasionally be severe and sightthreatening when caused by virulent bacterial species such as N gonorrhoeae or S pyogenes. In rare cases, it may presage life-threatening systemic disease, as with conjunctivitis caused by Neisseria meningitidis. Direct infection and inflammation of the conjunctival surface, bystander effects on adjacent tissues such as the cornea, and the host’s acute inflammatory response and long-term reparative response all contribute to the pathology.
CLINICAL PRESENTATION AND MANAGEMENT Bacterial conjunctivitis should be suspected in patients with conjunctival inflammation and a purulent discharge. The rapidity of onset and severity of conjunctival inflammation and discharge are suggestive of the possible causative organism. Table 5-3 shows the clinical classification of bacterial conjunctivitis based on these parameters.
Table 5-3
Acute purulent conjunctivitis
Acute purulent conjunctivitis, a form of bacterial conjunctivitis, is a self-limited infection of the conjunctiva characterized by an acute inflammatory response with purulent discharge of less than 3 weeks’ duration (definition of acute). Cases may occur spontaneously or in epidemics. The most common etiologic pathogens are S pneumoniae, Streptococcus viridans, S aureus, and H influenzae, with the relative frequency of each determined in part by the patient’s age and geographic location.
S pneumoniae conjunctivitis is characterized by a moderate purulent discharge, eyelid edema, chemosis, conjunctival hemorrhages, and occasional inflammatory membranes on the tarsal conjunctiva. Corneal ulceration occurs in rare instances.
H influenzae conjunctivitis occurs in young children, sometimes in association with otitis media,
and in adults, particularly those chronically colonized with H influenzae (eg, smokers or patients with chronic bronchopulmonary disease). Acute purulent conjunctivitis caused by H influenzae biotype III (previously called H aegyptius) resembles that caused by S pneumoniae; however, conjunctival membranes do not develop, and peripheral corneal epithelial ulcers and stromal infiltrates occur more commonly. H influenzae preseptal cellulitis may be associated with fulminant Haemophilus meningitis, in which up to 20% of patients who recover have long-term neurologic sequelae. The incidence of infection has been reduced by a vigorous program of vaccination against Hib.
S aureus may produce an acute blepharoconjunctivitis. The discharge tends to be somewhat less purulent than that seen in pneumococcal conjunctivitis, and the associated signs are generally less severe.
Gram-stained smears and culture of the conjunctiva are usually not necessary in uncomplicated, largely self-limited cases of suspected bacterial conjunctivitis but should be performed in the following situations:
certain compromised hosts, such as neonates or debilitated or immunocompromised individuals, to assess the risk of local and systemic complications
severe cases of purulent conjunctivitis, to differentiate it from hyperpurulent conjunctivitis, which generally requires systemic therapy
cases unresponsive to initial therapy
MANAGEMENT Most cases of acute bacterial conjunctivitis resolve in 2 to 7 days without treatment. Some prospective studies suggest that delaying treatment until day 3 or 4 would significantly reduce the unnecessary use of antibiotics and would not affect outcomes. Initiating treatment at this time only for persistent or worsening signs would generally shorten the course and improve symptoms. If the conjunctivitis is improving on day 4, then antibiotics may not be necessary at all, as these studies also indicate that initiation of antibiotics after day 4 provides limited benefit. Cases likely to represent a viral conjunctivitis should not be routinely treated with empiric antibiotics.
Initial medical therapy for acute nonsevere bacterial conjunctivitis includes the following topical agents: polymyxin B/trimethoprim combination drops, aminoglycosides or fluoroquinolone drops, or bacitracin or ciprofloxacin ointment. The dosing schedule is 4–6 times daily for approximately 5– 7 days unless otherwise indicated. Cases with gram-negative coccobacilli on Gram-stained smears are probably caused by Haemophilus species and should be treated with polymyxin B–trimethoprim. Supplemental oral antibiotics are recommended for patients with acute purulent conjunctivitis associated with pharyngitis, for conjunctivitis-otitis syndrome, and for Haemophilus conjunctivitis in children.
When empiric broad-spectrum antibiotic therapy is prescribed in cases of acute conjunctivitis, the initial treatment should be weighted toward the results of the Gram-stained morphology of the conjunctival smear, if available. Definitive treatment should be based on the culture results, if available, as smear results may sometimes be inconclusive as to the predominant category of organism responsible for the infection. Cultures of the nose or throat may be performed if an associated sinusitis or pharyngitis is present. Even if no overt sinusitis, rhinitis, or pharyngitis is present, nasal or throat swabs should be considered in cases of relapsing conjunctivitis, because organisms persisting in and colonizing the respiratory mucosa may be the source of infection.
Hyperacute gonococcal conjunctivitis
Gonococcal conjunctivitis presents with explosive onset and very rapid progression of severe purulent conjunctivitis: massive exudation; severe chemosis; eyelid edema; marked conjunctival
hyperemia; and, in untreated cases, corneal infiltrates, melting, and perforation. The organism most commonly responsible for hyperpurulent conjunctivitis is N gonorrhoeae (Fig 5-11). Gonococcal conjunctivitis is a sexually transmitted disease resulting from direct genital–eye transmission, genital–hand–ocular contact, or maternal–neonate transmission during vaginal delivery.
Figure 5-11 Peripheral corneal ulceration and perforation occurring several days after onset of hyperacute conjunctivitis caused by N gonorrhoeae.
Gonococcal conjunctivitis is one of the few bacterial diseases associated with preauricular lymphadenopathy and the formation of conjunctival membranes. Keratitis, the principal cause of sight-threatening complications, has been reported to occur in 15%–40% of cases. Corneal involvement may consist of diffuse epithelial haze, epithelial defects, marginal infiltrates, and ulcerative keratitis that can rapidly progress to perforation.
LABORATORY EVALUATION N gonorrhoeae grows well on chocolate agar and Thayer-Martin media.
MANAGEMENT Gonococcal conjunctivitis requires systemic antibiotic therapy, with topical ophthalmic antibiotics used as adjunctive therapy only. Current treatment regimens for gonococcal conjunctivitis reflect the increasing prevalence of penicillin-resistant N gonorrhoeae (PRNG) in the United States. Ceftriaxone, a third-generation cephalosporin, is highly effective against PRNG. Patients with gonococcal conjunctivitis without corneal ulceration may be treated on an outpatient basis with 1 intramuscular (IM) ceftriaxone (1 g) injection; patients with corneal ulceration should be admitted to the hospital and treated with intravenous (IV) ceftriaxone (1 g IV every 12 hours) for 3 consecutive days. Patients with penicillin allergy can be given spectinomycin (2 g IM) or oral fluoroquinolones (ciprofloxacin 500 mg or ofloxacin 400 mg orally twice daily for 5 days).
Erythromycin ointment, bacitracin ointment, gentamicin ointment, and ciprofloxacin solution have been recommended for topical therapy. Treatment of severe cases should include copious, frequent (every 30–60 minutes) irrigation of the conjunctival sac with normal saline to remove inflammatory cells, proteases, and debris that may be toxic to the ocular surface and contribute to corneal melting.
Up to one-third of patients with gonococcal conjunctivitis have been reported to have concurrent chlamydial venereal disease. Because of this frequent association, it is advisable to give patients supplemental oral antibiotics for treatment of chlamydial infection. Treatment regimens for chlamydia are discussed later in this chapter. Patients should be instructed to refer their sex partners for evaluation and treatment.
American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Conjunctivitis. San Francisco: American Academy of Ophthalmology; 2008. Available at: www.aao.org/ppp.
Cortina MS, Tu EY. Antibiotic use in corneal and external eye infections. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2011, module 6.
Bacterial conjunctivitis in neonates
N gonorrhoeae causes the most severe neonatal conjunctivitis. (Neonatal is defined as occurring within the first month of life.) In order of decreasing prevalence, the causes of neonatal bacterial conjunctivitis, reflective of the vaginal and nosocomial flora, are as follows:
Chlamydia trachomatis S viridans
S aureus
H influenzae
group D Streptococcus Moraxella catarrhalis
E coli and other gram-negative rods
N gonorrhoeae
Ophthalmia neonatorum is discussed in more detail in BCSC Section 6, Pediatric Ophthalmology and Strabismus.
Neonatal gonococcal conjunctivitis Prenatal screening for maternal gonococcal genital infection and neonatal antibiotic prophylaxis have reduced the overall rate of gonococcal conjunctivitis to 1% in newborns and 2% in infected mothers. In infants with gonococcal conjunctivitis, a bilateral conjunctival discharge typically develops 3–5 days after parturition. The discharge may be serosanguinous during the first several days, with a copious purulent exudate, severe corneal complications, and endophthalmitis developing later (see “Hyperacute gonococcal conjunctivitis” above). Infected infants may also have other localized gonococcal infections, including rhinitis and proctitis. Disseminated gonococcal infection with arthritis, meningitis, pneumonia, and sepsis resulting in death of the infant is a rare complication.
MANAGEMENT Because of the developing resistance of N gonorrhoeae to various antibiotics— including penicillin (PRNG), fluoroquinolones (QRNG), and tetracycline—the currently recommended first-line treatment for neonatal gonococcal conjunctivitis is ceftriaxone. For nondisseminated infections, a single IM or IV ceftriaxone injection (up to 125 mg or a dose of 25–50 mg/kg) or cefotaxime at a single dose of 100 mg/kg IV or IM is recommended. For disseminated infection, treatment should be augmented according to infectious disease consultation. Either of these regimens should be combined with hourly saline irrigation of the conjunctiva until discharge is eliminated. If corneal involvement is suspected, application of topical erythromycin or gentamicin ointment or frequent application of a topical fluoroquinolone should be considered. Topical cycloplegia may also prove beneficial. Systemic treatment is advised for infants born to mothers with active gonorrhea, even in the absence of conjunctivitis.
American Academy of Pediatrics. Gonococcal infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. 2009 Red Book: Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:305–313.
Centers for Disease Control and Prevention; Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines 2006. MMWR Recomm Rep. 2006;55(RR-11):1–94.
Cortina MS, Tu EY. Antibiotic use in corneal and external eye infections. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2011, module 6.
Neonatal chlamydial conjunctivitis Chlamydial conjunctivitis in neonates differs clinically from that in adults in the following ways:
There is no follicular response in newborns.
The amount of mucopurulent discharge is greater in newborns. Pseudomembranes can develop on the tarsal conjunctiva in newborns.
Intracytoplasmic inclusions are seen in a greater percentage of Giemsa-stained conjunctival specimens in newborns.
The infection in newborns is more likely to respond to topical medications.
Both Gram and Giemsa stains of conjunctival scrapings are recommended in neonates with conjunctivitis to identify C trachomatis and N gonorrhoeae, as well as other bacteria, as causative agents. Other Chlamydia-associated infections, such as pneumonitis and otitis media, can accompany inclusion conjunctivitis in the newborn. Therefore, systemic erythromycin (12.5 mg/kg oral or IV 4 times daily for 14 days) is recommended, even though inclusion conjunctivitis in the newborn usually responds to topical erythromycin or sulfacetamide.
Chlamydial conjunctivitis
PATHOGENESIS C trachomatis is a bacterium that causes several different conjunctivitis syndromes; each is associated with different serotypes of C trachomatis:
trachoma: serotypes A–C
adult and neonatal inclusion conjunctivitis: serotypes D–K lymphogranuloma venereum: serotypes L1, L2, and L3
There have been reports of rare cases of keratoconjunctivitis in humans caused by Chlamydia species that typically infect animals, such as Chlamydia psittaci, an agent generally associated with disease in parrots, and the feline pneumonitis agent.
LABORATORY EVALUATION As an obligate intracellular pathogen, C trachomatis cannot be easily isolated using standard ophthalmic culture techniques, requiring either direct observation of the intracellular bacterium or cell culture. Direct visualization is possible with a Giemsa stain or direct fluorescent antibody staining. PCR probes are available and increasingly being used in place of other diagnostic methods.
CLINICAL PRESENTATION AND MANAGEMENT Trachoma and adult inclusion conjunctivitis are discussed individually in the following sections.
Trachoma Trachoma is an infectious disease that occurs in communities with poor hygiene and inadequate sanitation. It affects approximately 150 million individuals worldwide and is the leading cause of preventable blindness. Trachoma is currently endemic in the Middle East and in developing regions around the world. In the United States, it occurs sporadically among American Indians and in mountainous areas of the South. Most infections are transmitted from eye to eye. Transmission may also occur by flies and household fomites that also spread other bacteria, causing secondary bacterial infections in patients with trachoma.
Solomon AW, Holland MJ, Alexander ND, et al. Mass treatment with single-dose azithromycin for trachoma. N Engl Journal Med. 2004;351(19):1962–1971.
CLINICAL PRESENTATION The initial symptoms of trachoma include foreign-body sensation, redness,
tearing, and mucopurulent discharge. A severe follicular reaction develops, most prominently in the superior tarsal conjunctiva but sometimes appearing in the superior and inferior fornices, inferior tarsal conjunctiva, semilunar fold, and limbus. In acute trachoma, follicles on the superior tarsus may be obscured by diffuse papillary hypertrophy and inflammatory cell infiltration. Large tarsal follicles in trachoma may become necrotic and eventually heal with significant scarring. Linear or stellate scarring of the superior tarsus (Arlt line) typically occurs (Fig 5-12). Involution and necrosis of follicles may result in limbal depressions known as Herbert pits (Fig 5-13). Corneal findings in trachoma include epithelial keratitis, focal and multifocal peripheral and central stromal infiltrates, and a superficial fibrovascular pannus, which is most prominent in the superior third of the cornea but may extend centrally into the visual axis (Fig 5-14).
Figure 5-12 Linear scarring of the superior tarsal conjunctiva (Arlt line) in a patient with old trachoma. (Courtesy of Vincent P.
deLuise, MD.)
Figure 5-13 Trachoma exhibiting Herbert pits of the superior limbus (round to oval, pigmented areas within pannus). (Courtesy
of Tom Lietman, MD.)
Figure 5-14 Superior corneal micropannus in a patient with adult chlamydial conjunctivitis (trachoma).
Clinical diagnosis of trachoma requires at least 2 of the following clinical features:
conjunctival follicles on the upper tarsal conjunctiva limbal follicles and their sequelae (Herbert pits) typical tarsal conjunctival scarring
vascular pannus most marked on the superior limbus
Severe conjunctival and lacrimal gland duct scarring from chronic trachoma can result in aqueous tear deficiency, tear drainage obstruction, trichiasis, and entropion.
The World Health Organization (WHO) has introduced a simple severity-grading system for trachoma based on the presence or absence of 5 key signs:
1.follicular conjunctival inflammation
2.diffuse conjunctival inflammation
3.tarsal conjunctival scarring
4.aberrant lashes
5.corneal opacification
The WHO grading system was developed for use by trained personnel other than ophthalmologists to assess the prevalence and severity of trachoma in population-based surveys in endemic areas.
Thylefors B, Dawson CR, Jones BR, West SK, Taylor HR. A simple system for the assessment of trachoma and its complications. Bull World Health Organ. 1987;65(4):477–483.
MANAGEMENT Current recommendations for treatment of active trachoma are tetracycline 1% ophthalmic ointment, applied twice daily for 2 months, and oral azithromycin 1000 mg, given as a single dose. Although azithromycin is more effective and easier for patient adherence, cost and availability dictate the best therapy. Topical erythromycin, given at the same frequency as topical tetracycline, and oral tetracycline 1.5–2.0 g daily in divided doses for 3 weeks are also effective. Oral erythromycin is recommended for treatment of the rare tetracycline-resistant cases. Management of the vision-threatening complications of trachoma may include tear substitutes for dry eye and eyelid surgery for entropion or trichiasis.