Common infections of the eye

IIDN1 Volume 7, Number 5, May 1988

Editor

Paul D. Hoeprich, MD Division of Infectious and Immunologic Diseases University of California, Davis Medical Center

Associate Editors

Ruth M. Lawrence, MD

Larry K. Pickering, MD

Charles W. Stratton, MD

Division of Infectious Diseases Texas Tech University Health Sciences Center

Program in Infectious Diseases and Clinical Microbiology The University of Texas Medical School at Houston

Department of Pathology Vanderbilt University Medical Center

C o m m o n Infections of the Eye Charles W. Stratton Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennesee

Common Infections of the Eye Charles W. Stratton ADP-Ribosylation by Bacterial Toxins: The First 100 Years Paul D. Hoeprich CASE REPORT Joseph Koo

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The differential diagnosis of ocular infections is a challenging problem for the clinician. Fortunately, serious infections of the eye are relatively uncommon due to the ocular defense mechanisms. These mechanisms include tears, providing a washout effect and containing secretory IgA and lysozyme; the eyelids, assisting the washout effect of the tears; and the conjunctivas, containing large numbers of inflammatory cells (lymphocytes, plasma cells, and neutrophils) as well as antibodies such as IgA. A logical approach for the differential diagnosis of ocular infections is to consider the various ocular structures and surrounding tissues. Lids Chronic blepharitis is a common ocular problem that is manifest as inflammation of the eyelids. Two important causes are staphylococcal and seborrheic dermatitis. Staphylococcus aureus may be cultured from the lid margins in approximately onethird of persons with normal lids. Failure to wash away the normal seb-

orrheic secretions may result in secondary infection by staphylococci. This occurs primarily in children and elderly persons who fail to wash around the eyes. Patients have inflammation along the anterior portion of the lid that is associated with crusting of the eyelashes and the presence of collarettes (fibrinous scales) surrounding individual cilia. The patient may also have ulcers of the lids and/or margins of the cornea; lost, broken, or misdirected eyelashes; and conjunctivitis and irritation of the inferior third of the cornea. Plugging and secondary infection of a sebaceous (meibomian) gland of the eyelid by staphylococci may result in acute cellulitis and formation of abscesses known as hordeola (styes) or a granulomatous subacute reaction (painless and noninflammed) known as a chalazion. The treatment of chronic staphylococcal blepharitis consists of cleansing the eyelids wtih warm compresses and scrubbing the eyelid with baby shampoo using a moistened cotton swab or wash cloth. Appropriate topical antimicrobics, such as

0278-2316 IDINDN 7(5)33-40, 1988

34 Infectious Diseases Newsletter 7(5) May 1988 ocular preparations of gentamicin or bacitracin, are necessary in some cases. Application of bacitracin ophthalmic ointment for up to 1 month after eradication of the infection may be needed to prevent recurrences. In addition, bacitracin ointment or pseudomonic acid ointment applied in the nares, and the use of Phisohex with handwashing, may be useful to prevent recurrences. A hordeolum may need hot packs plus incision and drainage. Antistaphylococcal antimicrobics are used systemically if there is cellulitis of the surrounding tissues. Chalazia most often need no treatment; however, they may be treated by injection of a few tenths of a milliliter of a glucosteroid or by excision. Patients with seborrheic blepharoconjunctivitis are usually older adults whose disease process is more chronic (measured in years rather than months) than staphylococcal blepharitis. These patients present with oily, greasy crusts around the anterior portion of the eyelid and have only mild to moderate inflammation. Edema of the lids and corneal involvement are not a problem unless there is a mixed seborrheic and staphylococcal blepharoconjunctivitis. Patients with seborrheic blepharitis often have involvement of their meibomian glands (excessive secretions and meibomianitis) as well as other forms of seborrheic dermatitis. Treatment of seborrheic blepharitis consists of keeping the lids clean using warm compresses and scrubs with shampoos containing selenium sulfide. In patients who have severe seborrheic blepharoconjunctivitis with meibomianitis, peroral tetracycline may be useful. The use of topical glucosteroids is controversial and should be limited to no more than 1-2 weeks. If staphylococcal infection is

mixed with seborrheic blepharitis, antistaphylococcal antimicrobics may be needed.

Conjunctivas Acute Viral Conjunctivitis is most commonly caused by adenoviruses. The manifestations take three forms: pharyngoconjunctival fever, epidemic keratoconjunctivitis (EKC), and nonspecific follicular conjunctivitis. Pharyngoconjunctival fever is characterized by acute follicular conjunctivitis (avascular, opaque, yellowish, or white excretions on the lower tarsal surface) accompanied by an upper respiratory tract infection, regional (anterior cervical) lymphadenopathy, and fever. It occurs most commonly in children and is a self-limited disease lasting 1-2 weeks. It usually begins in one eye and spreads to the other. Epidemic keratoconjunctivitis is a more severe ocular infection with acute IFbllicular conjunctivitis accompanied by a "foreign body" sensation, tender preauricular lymphadenopathy, and diffuse superficial keratitis. In approximately one-third of patients, pseudomembranes form, and may be followed by corneal opacities causing a decrease in vision. These opacities often last for 6-12 months and require topical steroids. Corneal involvement is only seen in EKC, a disease that usually occurs in the 20-40-year age group and is highly contagious. Swimming pools and health clubs are notorious for outbreaks of EKC. Finally, adenovirus may cause a nonspecific, follicular conjunctivitis with only mild redness, pain, and tearing without any upper respiratory tract or corneal involvement. This is the most commonly seen adenoviral ocular infection and is mild and self-

limited. The lay term for this infection is "pink eye." The diagnosis of adenoviral infections of the eye is primarily based on clinical findings, although a rapid direct immunofluorescence test has been developed. Cytological smears (Gram-stain and Giemsa stain) may be useful because bacterial infection may be excluded by the presence of mononulear cells and the absence of bacteria. In addition, the absence of eosinophils is a useful finding to exclude allergic conjunctivitis or the hypersensitivity reaction to neomycin ophthalmic ointment, a complication of the use of this agent. Treatment for adenoviral conjunctivitis is mainly supportive. Compresses and topical agents such as artificial tears may make the patient more comfortable. The routine use of glucosteroids is discouraged. The corneal infiltrates, although responsive to topical glucosteroids, often recur after discontinuation of therapy. Moreover, glucosteroids may destroy the corneal matrix by collagenolytic effect and cause perloration. Other adverse effects of topical glucosteroids include reversible glaucoma and nonreversible cataracts. When glucosteroids are used, patients should be followed closely by an ophthalmologist. None of the currently available ophthalmic antiviral agents is useful for adenoviral infections. Acute bacterial conjunctivitis may vary from a mild to a severe ocular inflammation process. The conjunctival inflammation is usually accompanied by a purulent discharge; such a discharge is an indication tbr Gram stain and culture. If there is a fulminating, purulent discharge that drips out of the eye that is associated with marked redness and swelling of the conjunctiva, gonococcal conjunctivitis should be suspected. Conversely,

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35 Infectious Diseases Newsletter 7(5)

May 1988 mild hyperemia with minimal secretions (lids stuck together on awakening) is most often seen with S. aureus conjunctivitis secondary to chronic blepharitis. Acute bacterial conjunctivitis is caused most often by Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. It usually resolves within a week with topical antimicrobic therapy. Ophthalmic preparations may contain various antimicrobics including gentamicin, neomycin, polymyxin B, chloramphenicol, and bacitracin. One should remember that gentamicin is ineffective against Streptococcus spp. Neomycin is often toxic to the corneal epithelium; hypersensitivity reactions may occur and may mimic the original conjunctivitis. Chlamydial conjunctivitis (inclusion conjunctivitis) must be strongly suspected in a patient with follicular conjunctivitis that lasts longer than 3 weeks. It is most often seen in sexually active adults. The initial infection is indistinguishable from viral conjunctivitis. However, it is not self-limited and is resistant to topical antimicrobics. If conjunctival scrapings are stained with commercially available monoclonal immunofluorescence stains, a specific diagnosis may be made. Treatment is peroral tetracycline for 3-6 weeks; sexual partners should also be treated. Cornea Acute viral infections of the cornea are most commonly caused by the herpes simplex viruses (HSV). The primary ocular infection of HSV is a nonspecific keratoconjunctivitis and blepharitis that usually occurs in children between 6 months and 5 years of age. Most cases are subclinical. The likelihood of subsequent recurrent herpes infection is about 25%. Recurrent attacks occur primarily in adults and are characterized by branching epithelial defects of the cornea known as dendrites. Dendrites may be single or multiple, and multiple dendrites may produce an ulcer. Corneal infection by HSV is often as-

sociated with uveitis, which in turn may produce secondary glaucoma. In addition, herpetic keratitis may produce corneal edema that may be chronic; it is thought to represent a delayed hypersensitivity reaction, and it may have a pronounced adverse effect on vision. The diagnosis of acute herpetic keratitis may be made by the characteristic dendritic pattern and/or by cultures of corneal scrapings. Treatment consists of gentle mechanical debridement of the corneal epithelium coupled with frequent use of antiviral agents. The drugs of choice are vidarabine 3% ointment used 5 times a day, or trifluorothymidine 1% drops used every 2 h while the patient is awake. Neither agent penetrates the eye well enough to affect the course of herpetic uveitis, a situation requiring parenteral acyclovir. Post-herpetic corneal scarring may be a chronic problem requiring corneal transplantation for rehabilitation of vision. Acute bacterial infections of the cornea are usually secondary to trauma or surgery, or are superimposed on debilitating processes such as diabetes mellitus, dry eyes, or nutritional or hygienic deficiencies. Bacteria of all kinds are potential causes; any inflammatory infiltrate in the cornea requires prompt scraping and culturing to identify the responsible agent. Until the results of cultures are known, an ophthalmic topical solution containing a number of antimicrobics may be used to provide broad coverage. Concentrated solutions of antimicrobics prepared as eyedrops by the opthalmologist from materials for parenteral use are preferable to commercial eyedrops of low concentration. Penicillins should not be used because they are highly sensitizing in the conjunctival sac. Parenteral antimicrobics are of no use unless endophthalmitis is present. Bacterial corneal infections are frequently caused by S. aureus; Pseudomonas aeruginosa may produce a particularly virulent infection because of pseudomonal proteases that may © 1988 Elsevier Science Publishing Co., Inc. 0278-2316/88/$0.00 + 2.20

liquefy corneal proteoglycans rapidly. Fungal infections of the cornea occur rarely and mostly in warm climates and in association with minor trauma to the cornea outdoors or involving plants. Fusarium solani is the most common pathogen. Natamycin, a polyene that is nontoxic when administered topically, has been useful. Fungal infection of the cornea may also be a problem for patients who have received antibacterial therapy for long periods. Aspergillus spp. and Candida spp. are usually responsible for infections in these patients. Treatment may be difficult and often involves extensive debridement. Acanthamoeba keratitis is a newly recognized infection of the cornea that is associated with wearing contact lenses. The infection is a chronically progressive ulcerative keratitis that may result in blindness. The clinical appearance of a 360 ° ring infiltrate or abscess is a specific diagnostic sign that should alert the clinician to the possibility of amebic infection. Acanthamoeba spp. are among the most common protozoa found in soil and fresh water (including tap water, as the cyst form is resistant to chlorine); a number of different species may cause infection of the cornea. Acanthamoeba infection should be considered in the differential diagnosis of any chronically progressive ulcerative keratitis. Severe ocular pain is a prominent feature as is recurrent epithelial breakdown. If amebic keratitis is suspected, the laboratory diagnosis may be made by histological examination of keratoplasty specimens. Calcofluor white, a chemoflorescent dye used to detect fungi, will also reveal cysts of Acanthamoeba spp. in corneal scrapings. Finally, cultures can be set up in most clinical laboratories as the organisms grow readily on non-nutrient agar with an overlay of either living or killed bacteria (e.g., E. coli) as a food source. Plates are kept at room temperature for 1 week and examined daily with a dissecting microscope to detect the

36 Infectious Diseases Newsletter 7(5) May 1988 random meanderings of the motile amebae over the agar surface; the amebae are refractile structures at the ends of trails. Treatment is difficult; corneal transplantation may be needed and, in some cases, enucleation has been necessary. The best therapeutic regimen currently available appears to be topical dibrompropamidine (0.15%) ointment, propamidine isethionate (0.1%) eye drops (Brolene®), and neomycin. The propamidine drugs are analogues of stilbamidine and are available only through the Division of Parasitic Diseases at the Centers for Disease Control (404-454-4428 or 404-454-4240).

Ocular Soft Tissues Periorbital cellulitis is somewhat arbitrarily defined as cellulitic infection that is anterior to the septum of the eyelids. This septum, known as the orbital septum, is a reflection of the periorbita which goes from the orbital rim to the tarsal plates and limits the globe anteriorly; it prevents infections from passing directly through to the orbital tissues. Clinical signs of periorbital cellulitis include circumferential warmth, edema, and erythema. Sensation, orbital pressure, pupillary responses, and fundi are normal. Moderate chemosis and a pustular discharge may be present, but pain on eye motion should be lacking. Other signs should suggest other diagnoses. Marked chemosis, especially along the nasal border, high fever, and restricted or painful movement of the eye indicate the presence of sinusitis. Proptosis, ophthalmoplegia, or impaired vision suggest orbital cellulitis (cellulitis involving orbital tissues behind the orbital septum). Conditions that predispose to periorbital cellulitis include local trauma, animal bites, insect stings, sinusitis, abscessed teeth, impetigo, hordeola, upper respiratory tract infections, and otitis media. Patients with local trauma, bites, or impetigo are usually infected with staphylococci or streptococci. In young patients with otitis media or upper respiratory tract infections, H.

influenzae is often the causative organism. Other causes include pneumococci and Gram-negative bacilli. Complications of periorbital cellulitis are severe (e.g., orbital cellulitis/abscess) and potentially lethal (e.g., cavernous sinus thrombosis). Empiric therapy with parenterally administered, broadly active antibacterial agents is indicated early in the course of periorbital cellulitis. Orbital cellulitis occurs most often following direct extension from the adjacent sinuses. There is a close relationship between the paranasal sinuses and the orbit and its contents. Once the sinuses are fully developed, over half of the orbit consists of thin bony plates limited by a sinus cavity. There are several mechanisms which may allow direct extension of infection from sinuses into orbital tissues: bony dehiscences, destruction of sinus/orbital walls, periosteal dissection by an abscess, entrance through the foramina of the anterior and posterior ethmoid vessels and nerves, or phlebitic spread. Clinical signs that suggest orbital cellulitis are proptosis, ophthalmoplegia, severe pain on movement of the eye, and impaired vision. Ophthalmoplegia indicates third-, fourth-, and sixth-nerve palsies. Computer-assisted tomographic scans are extremely important for appropriate management. Orbital cellulitis or abscesses necessitate surgical intervention in order to decompress the orbit and alleviate increased pressure that may damage the optic nerve. Surgical drainage of orbital abscesses (and/or sinuses) minimizes mechanical complications and provides infected material for Gram stain and culture. The most common pathogens are those seen in sinus infections: staphylococci, streptococci, pneumococci, H. influenzae, and anaerobes. Unusual pathogens include Zygomycetes (diabetic ketoacidosis, immunocompromised hosts), Aspergillus spp (immunocompromised hosts), and Gram-negative enteric bacilli such as E. coli and Klebsiella spp. A potentially lethal complication ~t~ 1988 Elsevier Science Publishing Co~, Inc. 0278-2316/88/$0.00 + 2.20

from orbital cellulitis is cavernous sinus thrombosis. This may occur because the major orbital veins permit a free flow of blood directly into the cavernous sinuses. Clinical signs of cavernous sinus thrombosis include proptosis, marked chemosis and edema of the lid, and papilledema with venous congestion. Reduced sensation and vision indicate inapending loss of consciousness. Bilateral cavernous sinus thrombosis results in swelling and bluing of the uninfected eyelid, but without erythema and warmth. Other infectious complications of orbital celtulitis include osteomyelitis, meningitis, and brain abscess. Common infections of the eye may be quite diverse. However, if the anatomical relationships are kept in mind, the pathogenesis of most of these infections will be readily apparent. Proper diagnostic and therapeutic measures can then be taken.

Bibliography Baum JL: Ocular infection. N Engl J Med 299:28-31, 1978. Cohen EJ, Buchanan HW, Laughrea P, et al: Diagnosis and management of Acanthamoeba keratitis. Am J Ophthalmol 100:389-395, 1985. Guindi GM: Acute orbital cellulitis: A multidisciplinary emergency. Gr J Oral Surg 21:201-207, 1983. Israele V, Nelson J: Periorbital and orbital cellulitis. Pediatr Infect Dis 6:404-410, 1987. Laibson P: Ocular adenoviral infections. Int Ophthalmol Clin 21:49, 1984. Matoba A: Ocular viral infections. Pediatr Infect Dis 3:358-368,1984. McCulley JP: Blepharoconjunctivitis. lnt Ophthalmol Clin 24:65-78, 1984. Pavan-Langston D: Diagnosis and management of herpes simplex ocular infection. Int Ophthalmol Clin 14:19, 1975. Stehr-Green JK, Bailey TM, Brandt FH, et al: Acanthamoeba keratitis in soft contact lens wearers. JAMA 258:57-60, 1987. Thoft RA: Corneal disease. N Engl J Med 298:1239-1241, 1978