Marlene L. Durand MD
Essentials of Diagnosis
The eyelids contain meibomian glands (Figure 8-1) that secrete sebum, an oily substance that helps lubricate and protect the corneal surface. Inflammation of these glands may produce a localized swelling in the lid (hordeolum and chalazion) or redness and irritation of the lid margins (blepharitis).
A hordeolum is an acute infection of a sebaceous gland of the upper or lower lid characterized by a red, painful swelling. The swelling may be within the lid (internal hordeolum) or at the lid margin (external hordeolum or stye). The usual cause is Staphylococcus aureus. Treatment is with warm compresses and topical erythromycin or bacitracin ointment (see Box 8-1).
A chalazion is a firm, nontender, chronic mass within the lid. It is a sterile granulomatous reaction to either an internal hordeolum or to inspissated sebum within a meibomian gland. It is best seen on the inner surface of the lid, where the overlying conjunctiva may be reddened. Treatment is with either excision or with intralesional injection of steroids.
Blepharitis is an inflammation of the lid margins. It is usually bilateral and chronic and is caused by dysfunction of the meibomian glands. Superinfection with S aureus seems to play a role. There is often associated rosacea or seborrheic dermatitis. The lid margins are red and irritated, often with skin scales clinging to the eyelashes. Symptoms are burning and itching of the lids. Treatment includes daily gentle lid scrubs with a baby shampoo to remove scales and application of topical bacitracin ointment at night. Tetracycline therapy may help if there is associated rosacea.
Chemosis: edema of the conjunctiva
Endophthalmitis: infection of the vitreous
Epiphora: excessive tearing
Follicles: foci of lymphoid hyperplasia seen on the inner surface of the lids in viral or chlamydial conjunctivitis
Hypopyon: layer of white blood cells in the anterior chamber
Keratitis: infection of the cornea
Limbus: junction of the cornea and sclera
Meibomian glands: sebaceous glands of the lids
Uveitis: inflammation of the choroid, ciliary body, or iris; retinitis is often included in this term
Preseptal cellulitis, sometimes called periorbital cellulitis, is an infection of the skin of the lids, anterior to the tarsal plate or “septum” (Figure 8-2). It is more common in children than in adults. The patient has tender, swollen, red lids but no eye pain, no change in vision or limitation of ocular movement, and no proptosis. Preseptal cellulitis must be distinguished from orbital cellulitis (see below). Common causes include S aureus, (group A) Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. Treatment should be with oral or intravenous (IV) antibiotics directed against these pathogens (eg, cefuroxime). Parenteral antibiotics are usually used in children as initial therapy, because some children with preseptal cellulitis are also bacteremic.
Figure 8-1. The meibomian glands of the eyelids. (Adapted from Last RJ: Eugene Wolff's Anatomy of the Eye and Orbit. W.B. Saunders, 1976.)
THE TEAR FILM
The tear film lubricates and nourishes the corneal surface and helps to focus light. It is composed of three layers. The outer lipid layer, produced by the meibomian glands, helps prevent evaporation of the middle aqueous layer. Chronic meibomitis, as occurs in chronic blepharitis, may decrease this lipid layer, allowing excessive evaporation of the aqueous layer, corneal dryness, and subsequent corneal defects. The middle aqueous layer is the largest layer and is produced by the lacrimal gland. The inner layer is composed of mucin produced by goblet cells in the conjunctiva. Destruction of these goblet cells, as occurs in Stevens-Johnson syndrome, leads to severe dryness and corneal damage.
BOX 8-1 Typical Microbiology and Suggested Empiric Antibiotic Therapy for Infections of the Ocular Adnexa (Lid, Lacrimal System, and Orbital Soft Tissue)
LACRIMAL SYSTEM INFECTIONS
Essentials of Diagnosis
The lacrimal system produces and drains the aqueous middle layer of the tear film. Tears are produced by the lacrimal gland, located in the upper outer portion of the globe. They flow medially across the surface of the eye and drain via canaliculi into the lacrimal sac and the nose (Figure 8-3).
Figure 8-2. Schematic diagram of a sagittal section of the eyelids and anterior eye. The tarsal plate or septum is the connective tissue “skeleton” of the lids.
Acute dacryocystitis is the most common infection of the lacrimal system, and results from obstruction of the lacrimal sac and subsequent infection. Patients present with a unilateral acute, red, painful swelling near the bridge of the nose, just below the medial canthus. There is often a history of chronic epiphora (excessive tearing). The most common pathogens are S aureus, streptococci including S pneumoniae, and H influenzae. Treatment is with systemic antibiotics (eg, cefuroxime); incision and drainage may be necessary.
Infection of the canaliculi causes epiphora, and “pouting puncta” are seen on examination. Actinomyces israelii is the most common pathogen, and applying pressure near the punctum causes the “sulfur granules” characteristic of this organism to be expressed. Treatment includes expressing this material and irrigating through the punctum with penicillin.
Figure 8-3. The lacrimal system. (Adapted from Barza M & Baum J: Ocular infections. Med Clin N Am 1983;67: 131.)
Dacryoadenitis, or infection of the lacrimal gland, is rare. Acute dacryoadenitis causes redness and swelling in the upper outer portion of the orbit. Viral causes include Epstein-Barr virus, mumps, and adenovirus; bacterial causes include S aureus, Streptococcus pneumoniae, and H influenzae. Chronic enlargement of the gland may be caused by tuberculosis or syphilis, but tumors or autoimmune disorders (including sarcoidosis) are more likely causes and should be excluded first.
Essentials of Diagnosis
The bony orbit (eye socket) is shaped like a cone placed horizontally in the skull, point inwards. The medial wall is formed by the paper-thin lateral wall of the ethmoidal sinus, the “lamina papyracea” bone. Because this barrier is so thin, infection in the ethmoidal sinus may spread into the orbit (see Figure 8-4). Hence, ethmoidal sinusitis is the most common cause of orbital infections.
Figure 8-4. Schematic diagram of the five main categories of orbital infection. A, preseptal cellulitis; B, orbital cellulitis; C, subperiosteal abscess; D, orbital abscess; E, cavernous sinus thrombosis. (Adapted from Chandler JR, Langenbrunner DJ, Stevens FR: The pathogenesis of orbital complications in acute sinusitis. Laryngoscope 1970;80:1414.)
Orbital cellulitis is an infection of the orbital soft tissue contents, and usually results from sinusitis. The onset is acute, with symptoms often developing within 24 h. The patient complains of unilateral eye pain and lid swelling. It is more common in children than in adults. Fever and leukocytosis are common. The lids are red, tender, and edematous, and they may be swollen shut. There is chemosis (edema) and injection of the conjunctiva. There is proptosis, but this may not be noted until measured by an ophthalmologist. Visual acuity may be decreased, and there is pain with eye movement. With progression of the infection, there is limitation of extraocular movement. The characteristic findings on computed tomography (CT) are proptosis and stranding in the orbital fat. Evidence of sinusitis on the same side is often seen. Pathogens include S aureus, Streptococcus pneumoniae, anaerobes, and H influenzae, although the frequency of H influenzae infections has markedly decreased since the 1985 introduction of the H influenzae type b vaccine. Treatment includes IV antibiotics (eg, ampicillin-sulbactam or nafcillin plus ceftriaxone) and drainage of any sinus pus. Patients should be closely monitored by both an otolaryngologist and an ophthalmologist. Progression of symptoms despite IV antibiotics should be evaluated by a repeat CT to exclude a drainable orbital abscess.
An orbital abscess is a collection of pus within the orbit. This is most often found in the medial or superior part of the orbit because infection usually begins in the ethmoid or frontal sinus. There is marked limitation of eye movement, and the eye usually looks “down and out” (away from the site of the abscess). Other signs and symptoms are similar to those of orbital cellulitis. On CT scan, a low-density collection within the orbit is seen. Treatment requires immediate drainage of the abscess and IV antibiotics directed against S aureus, streptococci, anaerobes, and H influenzae (eg, nafcillin plus ceftriaxone or ampicillin-sulbactam).
A subperiosteal abscess is a collection of pus between the bony wall and periosteum of the orbit. Because this is usually an extension of infection from the ethmoidal sinuses, the medial wall is most often involved. It is difficult to distinguish a subperiosteal abscess from an orbital abscess on clinical grounds; both produce fever, leukocytosis, lid swelling, redness, warmth, tenderness, chemosis, decreased vision, and marked limitation of extraocular movement. As with orbital abscess, the eye is usually nearly fixed in position looking “down and out.” On CT scan, a subperiosteal collection is seen. The bacteriology and treatment are the same as for orbital abscess: immediate surgical drainage plus IV antibiotics (eg, nafcillin plus ceftriaxone).
CAVERNOUS SINUS THROMBOSIS
Cavernous sinus thrombosis is a life-threatening complication of orbital infection and results from bacteria gaining access (via venous drainage of the orbit) to the cavernous sinus. It represents extension of the orbital infection (cellulitis or abscess) backwards. Because the cavernous sinus is a venous plexus that crosses the midline, inflammation in this region produces bilateral signs. Hence, bilateral signs of orbital cellulitis with systemic toxicity are very worrisome for cavernous sinus thrombophlebitis. The patient should be cared for in the intensive care unit; any drainable pus (eg, an orbital abscess or purulent sinusitis) should be drained, and nafcillin plus ceftriaxone should be given in meningeal doses (eg, in adults, 2 g of nafcillin every 4 h and 2 g of ceftriaxone every 12 h in patients with normal renal function).
Essentials of Diagnosis
Conjunctivitis is the most common type of eye infection. It is characterized by an inflamed conjunctiva, with injection and exudate. The conjunctiva is the mucous membrane that lines the inner surface of the lids (palpebral conjunctiva) and the surface of the sclera (bulbar conjunctiva) (see Figure 8-2). It does not cover the cornea, but abuts the corneal epithelium at the limbus (corneal-scleral border).
In general, patients with conjunctivitis complain of discomfort or pruritus, but they do not have deep eye pain unless the cornea is also involved (eg, epidemic keratoconjunctivitis or gonococcal disease). Any patient with a red eye and eye pain should see an ophthalmologist immediately, so that more serious eye conditions can be excluded (eg, acute glaucoma, uveitis, or endophthalmitis). Conjunctivitis may be classified by the speed with which symptoms develop: hyperacute, acute, and chronic (Table 8-1).
Hyperacute conjunctivitis is a medical emergency because it may progress to corneal perforation and visual loss. It is nearly always caused by Neisseria gonorrhoeae; the remaining cases are caused by N meningitidis. It affects neonates and sexually active adults. Patients have copious purulent discharge (which reaccumulates within seconds to minutes of wiping clean), marked chemosis, injection, and mild lid swelling. Bilateral involvement and preauricular adenopathy may occur. The cornea is involved in about two-thirds of patients, causing true eye pain. Without prompt treatment, perforation of the cornea may occur.
The diagnosis of hyperacute conjunctivitis is made by clinical appearance and finding the gram-negative diplococci (“kissing kidney beans”) characteristic of Neisseria spp. on the Gram stain of the exudate. Treatment for gonococcal disease consists of a single 1-g IV or intramuscular injection of ceftriaxone. In highly penicillin-allergic patients, oral ciprofloxacin (500 mg) can be used, although efficacy data are lacking. Saline irrigation or ciprofloxacin eyedrops may be given to clear the exudate. Patients and their sexual partners should be screened for other sexually transmitted diseases and treated for possible coexistent infection by Chlamydia spp.
Meningococcal conjunctivitis is followed by systemic illness in 20% of patients. Blood cultures should be obtained and patients should be examined for signs of meningitis. Treatment is with ceftriaxone (2 g IV once or twice daily) or high-dose IV penicillin.
Acute conjunctivitis may be bacterial or viral; viral is more common. Distinguishing features are given in Table 8-1. In bacterial conjunctivitis, the discharge is purulent; in viral, it is usually watery. In bacterial conjunctivitis, papillae give the inner surface of the lids a velvety appearance. In viral conjunctivitis, follicles (larger than papillae) give the inner surface of the lids a pebbly appearance. Preauricular adenopathy is typical of viral conjunctivitis.
Table 8-1. Clinical clues in the differential diagnosis of conjunctivitis.
Most cases of acute viral conjunctivitis are caused by adenovirus. Pharyngoconjunctival fever is caused by adenovirus types 3 and 7. Sore throat and fever accompany the conjunctivitis. It is easily spread from person to person; transmission in poorly chlorinated swimming pools has been reported.
Epidemic keratoconjunctivitis is usually caused by adenovirus type 8, although other serotypes have been noted. It is highly contagious and may survive on fomites (eg, doorknobs) for ≤2 mo. It has been associated with epidemics arising in ophthalmologists' offices where there has been inadequate disinfection. The name implies involvement of the cornea (“kerato”), and indeed corneal involvement is common, causing eye pain and photophobia. Treatment is supportive, and patients should stay home from work or school for 2 wk. Symptoms may persist for 6 wk.
Acute hemorrhagic conjunctivitis is caused by enterovirus type 70 and coxsackievirus A24 and is characterized by conjunctival hemorrhages and a 5- to 7-d course.
The most common bacteria involved in acute bacterial conjunctivitis are S aureus, Streptococcus pneumoniae, H influenzae (especially in children), and Moraxella catarrhalis. Haemophilus aegyptius has caused epidemic conjunctivitis in tropical countries and may be part of Brazilian purpuric fever.
Culture of the exudate is usually not required, but should be done in any patient who fails to respond to therapy. Symptoms are self-limited and will last 7–10 d if untreated or 3–5 d if treated. Topical preparations are listed in Table 8-2; bacitracin, erythromycin, or bacitracin/polymyxin ointments are reasonable choices for empiric therapy.
Chronic conjunctivitis is either follicular or nonfollicular. Nonfollicular conjunctivitis is often associated with chronic blepharitis, and S aureus or M lacunatamay be cultured. Rarely, anaerobes have caused chronic conjunctivitis, and patients have responded to amoxicillin plus metronidazole.
Chronic follicular conjunctivitis is nearly always caused by Chlamydia trachomatis. There are two syndromes, depending on the serotype: trachoma (serotypes A–C), and inclusion conjunctivitis (serotypes D–K). Diagnosis for either is by isolation of C trachomatis on tissue culture, demonstration of chlamydial antigen by enzyme immunoassay or fluorescent monoclonal antibody stain (eg, MicroTrak, Chlamydiazyme), or nucleic acid hybridization (Gen-Probe). Giemsa staining, an older technique, is less sensitive.
Table 8-2. Some commercially available antibiotic eyedrops and ointments.
Trachoma is a potentially blinding disease because repeated infections lead to scarring of the cornea and corneal vascularization. It is the most common infectious cause of blindness in the world and is prevalent in parts of Africa, the Middle East, and northern India. Follicles are seen inside the upper lid. Transmission occurs by flies, fomites, or person-to-person contact. Treatment with tetracycline for 3–6 wk or azithromycin is effective, but reinfection is difficult to prevent in endemic areas. Hand washing significantly reduces the frequency of infection.
Inclusion conjunctivitis occurs in ~1 in 300 sexually active adults with genital chlamydial infection. It is a chronic bilateral conjunctivitis with minimal discharge. Follicles are seen inside the lower lids. Unlike trachoma, corneal scarring does not occur. Treatment is with doxycycline, 100 mg orally 2 times/d (or erythromycin 500 mg orally 4 times/d) for 2 wk; sexual partners should also be examined and treated for chlamydial disease.
Inclusion conjunctivitis also occurs in neonates exposed to the infected mother during birth. Because neonates lack conjunctival lymphoid tissue, however, no follicles are seen. Treatment is with oral erythromycin (50 mg/kg/d) for 10–14 d.
KERATITIS (CORNEAL ULCER)
Essentials of Diagnosis
The cornea is only 0.5–1.0 mm thick, but it and the overlying tear film account for 75% of the refractive power of the eye. It has no blood vessels, but has many nerve fibers (hence corneal abrasions are painful). Its barrier to infection is a 5-cell-layer-thick epithelium that is contiguous with the conjunctiva. Microbes may infect this epithelium (epithelial keratitis), the corneal stroma or interstitium (interstitial keratitis), or both (ulcerative keratitis).
In the United States, ~30,000 cases of bacterial corneal ulcers are treated annually. Bacteria usually cause a craterlike ulcer when they infect the cornea (ulcerative keratitis). The patient complains of a red, painful eye; the redness is more intense near the limbus. A flashlight alone may show the defect in the cornea and a focal opacity. There may be a sterile hypopyon (layer of leukocytes in the anterior chamber) (see Figure 8-5).
Figure 8-5. Typical bacterial corneal ulcer with sterile hypopyon. The patient has a red eye owing to conjunctival injection. The corneal ulcer appears white.
A major risk factor for ulcerative keratitis is contact lens wear. Most bacteria (except gonococci) cannot penetrate an intact corneal epithelium. Contact lenses can cause breaks in this epithelium. Soft contact lenses worn overnight carry an especially high risk of keratitis: >10- to 15-fold the risk with daily-wear lenses. Other risk factors for keratitis include corneal abrasions, previous corneal graft, dry eyes, neurotrophic keratitis (absence of normal sensation), and exposure keratitis (eg, in comatose patients in the intensive care unit).
Patients with keratitis must be promptly evaluated by an ophthalmologist. For identification of the bacteria involved, the ophthalmologist will view the cornea with the slit lamp, carefully scrape the ulcer with a Kimura spatula, and directly plate the scrapings onto agar; a swab of the ulcer should be placed in broth.
Although coagulase-negative staphylococci are the most common organisms isolated from corneal ulcers, they may be surface colonizers rather than pathogens. Pathogens include S aureus, Streptococcus pneumoniae, viridans streptococci, and Pseudomonas aeruginosa. P aeruginosa is the most common pathogen in patients who wear contact lenses.
Empiric treatment is begun with a topical quinolone (eg, 0.3% ciprofloxacin or ofloxacin solution) or with cefazolin (50 mg/ml) plus fortified gentamicin or tobramycin (14 mg/ml) eyedrops. Of note, most eyedrops used to treat keratitis must be made up by the hospital pharmacy (the quinolones are exceptions). These are listed in Table 8-3. Antibiotic drops can be tailored to specific therapy when culture results are known. Drops must be given every hour. Patients with advanced ulcers require hospitalization, as drops should be given around the clock. IV antibiotics are needed only for extension into the sclera or for impending perforation.
Table 8-3. Fortified antibiotic eyedrops for treating bacterial keratitis. Except as noted, these are not available commercially.
In interstitial keratitis, the interstitium or stroma of the cornea is involved rather than the surface. On examination, there is no craterlike ulcer, but rather a haze within the cornea. Vision is decreased, and there may be photophobia, but there is usually no pain. Syphilis, Lyme disease, and mycobacteria (tuberculosis, atypical mycobacteria, and leprosy) are the most common bacterial causes; herpes infections are the most common viral causes.
Herpes simplex virus is the most common cause of keratitis in the United States, causing 500,000 cases per year. Most cases are from reactivation of latent infection, acquired during an earlier subclinical primary ocular or orofacial infection. Herpes simplex virus type 1 is the cause of most ocular infections in adults, whereas type 2 is the major cause in neonates.
The hallmark of herpes keratitis is a dendritic (branching) defect of the epithelium. The deeper corneal stroma is not initially involved. Diagnosis may be confirmed by viral culture. Treatment includes débridement of the involved epithelium and frequent eyedrops with a topical antiviral such as trifluridine (Viroptic).
One-third of patients have recurrent episodes within 2 y. Each recurrence carries a greater risk of stromal involvement, which may lead to permanent corneal scarring. Although topical steroids should never be used in the epithelial disease, they are helpful in treating stromal keratitis. Oral acyclovir suppressive therapy (400 mg twice a day) decreases recurrences of both epithelial and stromal disease.
Herpes zoster keratitis occurs in two-thirds of patients with herpes zoster ophthalmicus, the involvement of the ophthalmic division of the trigeminal nerve seen in ~10% of cases of zoster. An epithelial keratitis occurs at the time of the rash and consists of punctate or dendritic lesions. Treatment is with oral acyclovir (800 mg 5 times/d) or valacyclovir (1 g orally 3 times/d) for 10 d (doses assume normal renal function). Stromal keratitis may follow by several weeks. This is thought to be immune mediated and is treated with topical steroids.
Acanthamoeba is an amoeba that lives in fresh water. It is a rare cause of keratitis, but is the most common cause of parasitic keratitis in the United States. Nearly all cases occur in contact lens wearers. Acanthamoeba may contaminate contact lens cases or lenses rinsed with water or homemade lens solutions. Acanthamoeba keratitis is characterized by pain out of proportion to clinical findings and a ring corneal infiltrate. Symptoms may be chronic, with relentless progression, while the patient is mistakenly treated for presumed herpes keratitis.
Diagnosis may be difficult. A calcofluor white stain of corneal scrapings may show the cysts. For culture, corneal scrapings should be transported in Page's saline, then plated on a nonnutrient agar overlain with a lawn of Escherichia coli. The organisms usually grow in 48 h and may be seen by viewing the agar plate under a light microscope.
Treatment is also difficult, and must be continued for weeks to months to prevent recrudescence of disease. The preferred drug is a swimming pool cleaner, the disinfectant Baquacil (polyhexamethylene biguanide). This is applied topically around the clock. Brolene (propamidine 0.1%) has also been used with success; it is available in England but not in the United States.
Onchocerciasis is caused by a filarial parasite, Onchocerca volvulus, that is transmitted by Simulium blackflies. The flies breed in fast-moving streams in savannahs and rain forests in Africa, and hence the disease is called “river blindness.” The worms (microfilariae) infect 20 million Africans and cause 290,000 cases of blindness. Microfilariae that invade the cornea and anterior chamber of the eye cause keratitis and uveitis. Treatment is with ivermectin. A major control program is underway in West Africa.
Fungal infections of the cornea cause < 2% of corneal ulcers in this country, but are very difficult to treat. Infections caused by molds are more common in the southern United States, especially in agricultural workers. On examination, one sees a gray, plaquelike infiltrate with feathery edges and satellite lesions. Fusarium and Aspergillus spp. are the most common molds cultured. Treatment is with topical natamycin or amphotericin.
Essentials of Diagnosis
Endophthalmitis means infection within the eye and specifically the vitreous (see Figure 8-6). The vitreous is a gel-like substance that fills the posterior segment of the eye (volume ~6 ml). It is present at birth and becomes liquified with age. It is not reformed once removed, but may be replaced by saline, oil, etc.
Endophthalmitis is a medical emergency as it may quickly lead to blindness in the involved eye. Patients complain of eye discomfort (some have no pain) and a rapid decrease of vision. Patients feel otherwise well, are afebrile, and usually have a normal leukocyte count. On examination, the eye is injected and a hypopyon may be apparent. The view of the retina is hazy or obscured by the intraocular inflammation.
There are four major predisposing factors for endophthalmitis: cataract surgery, the presence of a filtering bleb for glaucoma, penetrating eye trauma, and bacteremia.
Figure 8-6. Eye anatomy. Endophthalmitis is an infection involving the vitreous. Uveitis is an inflammation of the uvea, which is made up of the choroid, ciliary body, and iris.
Endophthalmitis after cataract surgery is the most common type of endophthalmitis. It occurs as a complication of only 0.1–0.2% of cataract surgeries, but this is a large number because there are 2 million cataract surgeries performed annually in the United States. Onset of symptoms usually occurs 2–7 d after surgery, although it may occur later. Cultures of the vitreous are positive in ~70% of cases. The major pathogens are coagulase-negative staphylococci (70% of culture-positive cases). S aureus and streptococci each cause ~10%, whereas Gram-negative bacilli cause only 6% of cases.
Patients with severe glaucoma may need a permanent “filtering bleb” created to reduce intraocular pressure. A bleb is a tunnel from the anterior chamber through the sclera, through which excess aqueous humor can leak. Endophthalmitis may occur abruptly months to years after surgery and is usually fulminant. The major pathogens are streptococci (including pneumococci), M catarrhalis, and H influenzae. The visual outcome is usually poor.
Endophthalmitis develops in ~5% of patients who have penetrating eye injuries. The major pathogens are coagulase-negative staphylococci and Bacillus cereus. Bacillus produces a fulminant infection, and the eye is frequently lost. All penetrating eye trauma patients therefore should be given prophylactic antibiotics (eg, vancomycin plus ceftazidime) to prevent this complication.
Endogenous endophthalmitis means that bacteria (or fungi) have seeded the eye from the bloodstream. Endocarditis is the major risk factor, but cases have occurred in patients with urinary tract/kidney infections, abdominal abscesses, cellulitis, and meningitis and even after upper gastrointestinal endoscopy. S aureus and streptococci account for ~50% of cases. Patients should be treated with intravitreal as well as IV antibiotics.
Candidemia is associated with intraocular infection in 5–30% of cases. Most intraocular infections produce chorioretinitis rather than vitreal infection, but endophthalmitis does occasionally occur. Vitrectomy with injection of intraocular amphotericin (10 µg) is indicated, along with prolonged therapy with fluconazole (assuming normal renal function, 400 mg orally every day if the Candida species is sensitive).
For diagnosis of endophthalmitis, an ophthalmologist will either use a syringe to aspirate and culture a sample of vitreous (a bedside procedure) or perform a vitrectomy in the operating room. A vitrectomy uses a cutting instrument (vitrector) to remove most of the vitreous, which is simultaneously replaced by saline. The dilute vitreous washings are filtered, and the filter paper is cut up and plated on agar.
All patients should have antibiotics injected into the vitreous as soon as the vitreous sample is taken (Box 8-2). All patients should receive intravitreal vancomycin (1 mg in 0.1 ml) plus either amikacin (0.4 mg in 0.1 ml) or ceftazidime (2.25 mg in 0.1 ml). Amikacin is chosen because it has the least amount of retinal toxicity of the aminoglycosides, although a rare complication of any intravitreal aminoglycoside is macular infarction and loss of vision.
The role of systemic antibiotics in treating endophthalmitis is controversial. Some antibiotics, such as aminoglycosides, do not penetrate the blood-eye barrier well and do not achieve therapeutic levels in the vitreous. Vancomycin, quinolones, penicillins, third-generation cephalosporins (especially ceftazidime), and fluconazole are among the antimicrobials that can achieve therapeutic levels in inflamed eyes. A recent multicenter randomized trial (the Endophthalmitis Vitrectomy Study) concluded that systemic antibiotics did not affect outcome in postcataract endophthalmitis, although the study was criticized because the antibiotics used (ceftazidime and amikacin) have poor activity against coagulase-negative staphylococci, the major pathogens. Vancomycin plus ceftazidime is the standard empiric IV antibiotic therapy to treat endophthalmitis.
The need for a vitrectomy to “debride” the vitreous (vs a vitreous aspirate only) is also controversial. In the Endophthalmitis Vitrectomy Study of postcataract endophthalmitis, patients who presented with severe loss of vision (light perception only) had a better visual outcome with vitrectomy than with vitreous aspirate. This difference was not apparent for patients who presented with a milder loss of vision. There were potentially confounding factors, however (patients in the vitreous aspirate group could have a subsequent vitrectomy and still be counted in the aspirate group).
A reasonable approach to the treatment of endophthalmitis would be intravitreal antibiotics for all patients with endophthalmitis, plus vitrectomy for any patient who presents with poor vision, fulminant eye symptoms and signs, or non-postcataract endophthalmitis. Intravitreal steroid (dexamethasone, 400 µg) may also be helpful. We favor using IV antibiotics for the initial 48 h until culture results are known. Therapy may be stopped then if the eye is improving and cultures are negative or reveal coagulase-negative staphylococci. For more virulent organisms, we favor 5–10 d of systemic therapy. Repeat intraocular injections of vancomycin or ceftazidime (depending on the organism) may be helpful after the first 48 h, because antibiotic levels in the vitreous fall 24–48 h after injection.
BOX 8-2 Typical Microbiology and Suggested Empiric Antibiotic Therapy for Bacterial Endophthalmitis
UVEITIS & RETINITIS
Essentials of Diagnosis
The eye is made up of three coats: (1) the outer coat is composed of sclera plus cornea; (2) the middle coat is composed of the uvea (choroid, ciliary body, and iris); and (3) the inner coat is composed of the retina (see Figure 8-6). Uveitis is an inflammation of the middle, vascular layer. The term usually includes retinitis as well, because the retina is often involved when there is inflammation of the underlying choroid (a part of the uvea). Uveitis affects 1.2 million people and causes 10% of all blindness in the United States.
In anterior uveitis, the iris (iritis) or iris plus ciliary body (iridocyclitis) is involved. The patient has eye pain, photophobia, a red eye, and usually decreased vision. A slit lamp examination shows cells in the anterior chamber; some may coalesce on the back of the cornea (“kps” or keratic precipitates).
Of all anterior uveitis cases, ~10% have a known infectious etiology (eg, herpes simplex or zoster, syphilis, Lyme disease, or mycobacteria). The eye findings will regress when the underlying disease is treated. The remaining ~90% of cases are idiopathic or autoimmune (eg, ankylosing spondylitis, Reiter's disease, or systemic lupus erythematosus).
Unlike anterior uveitis, posterior uveitis usually produces no pain. The main symptom is gradual visual loss. Both choroid and overlying retina are usually involved (chorioretinitis).
Toxoplasma is the leading cause of posterior uveitis in normal hosts (see Chapter 81, “Toxoplasma”). It usually represents reactivation of latent toxoplasma infection. On viewing the retina, new large yellow-white lesions are seen near old black scars. The vitreous often has inflammatory cells, so the view of the retina may be hazy—a “headlight in the fog” appearance. Diagnosis is by clinical appearance. Serology is helpful only if negative (usually excluding the diagnosis), because 50–70% of the general population is seropositive. Treatment is with pyrimethamine (with folinic acid “rescue”), sulfadiazine, and clindamycin. Corticosteroids are also used if there are lesions that threaten the macula.
Although Candida spp. may cause endophthalmitis, they more typically cause chorioretinitis, with fluffy white lesions seen on funduscopic examination. Treatment is with oral fluconazole (400 mg orally every day) if the Candida species is sensitive.
Syphilis may cause almost any retinal appearance, but typically produces a “salt and pepper” retina. Diagnosis is by clinical appearance and serology. Serology must include a fluorescent treponemal antibody test, because ocular syphilis may occur in tertiary syphilis when the nonspecific tests (eg, rapid plasma reagin test or Venereal Disease Research Laboratory test) are often negative. Ocular syphilis may also result from congenital infection. Any patient with ocular syphilis should have a lumbar puncture (to exclude neurosyphilis), as well as a test for human immunodeficiency virus [HIV (there is a higher incidence of ocular syphilis in patients with this viral infection)]. Treatment consists of high-dose IV penicillin (4 million U every 4 h, assuming normal renal function).
Tuberculosis, like syphilis, may cause either an anterior or posterior uveitis. In posterior uveitis, the typical appearance is of bilateral multifocal choroid nodules. Treatment is the same as for other forms of extrapulmonary tuberculosis.
Cytomegalovirus (CMV) is the most common cause of retinitis. Cytomegaloviral retinitis usually occurs in immunosuppressed patients and, until recently, occurred in 20–40% of patients with AIDS. The incidence is now much lower, owing to highly active antiretroviral therapy. The typical appearance is of retinal hemorrhages (red) and exudates (white), giving the retina a “brush-fire” appearance. Unlike toxoplasmosis, CMV does not usually cause inflammation in the vitreous, so the view of the retina is clear. Diagnosis is by clinical appearance of the retina. Serology is helpful only if negative, although patients with advanced AIDS may have falsely negative serologies. Treatment is with ganciclovir or foscarnet. Systemic therapy is favored because direct ganciclovir intraocular injections or implants treat the ocular disease but do not treat the systemic CMV disease. In patients with AIDS, life-long maintenance therapy has been required to prevent recrudescent retinitis. Recently, however, a study of seven patients on potent combination antiretroviral therapy (and with very low HIV viral loads) reported no recrudescence of retinitis when observed for 9–12 mo after maintenance CMV therapy was stopped.
Bajart AM: Lid inflammations. In Albert DM, Jakobiec FA: Principles and Practice of Ophthalmology. Philadelphia, WB Saunders, 1994. (An excellent chapter in a major textbook of ophthalmology.)
Donahue SP, Schwartz G: Preseptal and orbital cellulitis in childhood. Ophthalmology 1998;105:1902.
Jackson K, Baker SR: Periorbital cellulitis. Head Neck Surg 1987;9:227. (A retrospective review of 98 cases of preseptal cellulitis and 39 cases of orbital cellulitis)
Lacrimal System Infections
Lavrich JB, Nelson LB: Disorders of the lacrimal system apparatus. Pediatr Ophthalmol 1993;40:767.
Barone SR, Aiuto LT: Periorbital and orbital cellulitis in the Haemophilus influenzae vaccine era. J Pediatr Ophthalmol Strabismus 1997;34:293. (A review of 134 cases: H influenzae type b was no longer a significant pathogen. Sinusitis was present in 96% of children with orbital cellulitis.)
Chandler JR, Langenbrunner DJ, Stevens ER: The pathogenesis of orbital complications in acute sinusitis. Laryngoscope 1970;80:1414. (The classic paper on the topic.)
Lessner A, Stern GA: Preseptal and orbital cellulitis. Infect Dis Clin North Am 1992;6:933.
Gigliotti F et al: Etiology of acute conjunctivitis in children. J Pediatr 1981;98:531.
Wan WL et al: The clinical characteristics and course of adult gonococcal conjunctivitis. Am J Ophthalmol 1986;102:575.
Durand M, Adamis A, Baker AS: Infections of the eyelid, lacrimal system, conjunctiva, and cornea. In Remington JS, Swartz MN: Current Clinical Topics in Infectious Diseases, vol. 16. Blackwell Science, 1996.
McLeod SD et al: The importance of initial management in the treatment of severe infectious corneal ulcers. Ophthalmology 1995;102:1943. (A retrospective review of 62 patients with corneal ulcers requiring hospitalization. Patients who received inadequate outpatient or inpatient therapy had a higher risk of requiring corneal transplant than those in whom initial therapy was appropriate ([73% vs 20%, respectively].)
O'Brien TP et al: Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy of bacterial keratitis. Arch Ophthalmol 1995;113:1257. (A multicenter trial of 140 patients with culture-positive bacterial keratitis found no difference in efficacy between these two regimens.)
Ciulla TA et al: Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma-filtering surgery. Ophthalmology 1997;104:986.
Duch-Samper AM et al: Endophthalmitis following open-globe injuries. Curr Opin Ophthalmol 1998;9:59.
Endophthalmitis Vitrectomy Study Group: Results of the Endophthalmitis Vitrectomy Study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 1995;113:1479. (A multicentered trial involving 420 patients. For shortcomings of the study, see Letters to Editor: Arch Ophthalmol 1996;114:1025.)
Okada AA, Johnson RP, Liles WC, et al: Endogenous bacterial endophthalmitis: report of a ten-year retrospective study. Ophthalmology 1994;101:832.
Uveitis & Retinitis
Forrester JV: Uveitis: pathogenesis. Lancet 1991;338: 1498.
Holland GN: Acquired immunodeficiency syndrome and ophthalmology: the first decade. Am J Ophthalmol 1992;114:86.
Opremcak EM: Uveitis: A Clinical Manual for Ocular Inflammation. Springer-Verlag, 1995.
Rosenbaum JT: Uveitis: an internist's view. Arch Intern Med 1989;149:1173.
Tural C et al: Long-lasting remission of cytomegalovirus retinitis without maintenance therapy in human immunodeficiency virus-infected patients. J Infect Dis 1998;177:1080.