Endophthalmitis

Endophthalmitis is an inflammatory condition of the intraocular cavities (ie, the aqueous and/or vitreous humor), usually caused by infection. Noninfectious (sterile) endophthalmitis may result from various causes such as retained native lens material after an operation or from toxic agents. Panophthalmitis is inflammation of all coats of the eye, including intraocular structures.

The two types of endophthalmitis are endogenous (ie, metastatic) and exogenous. Endogenous endophthalmitis results from the hematogenous spread of organisms from a distant source of infection (eg, endocarditis). Exogenous endophthalmitis results from direct inoculation of an organism from the outside as a complication of ocular surgery, foreign bodies, and/or blunt or penetrating ocular trauma.

Under normal circumstances, the blood-ocular barrier provides a natural resistance against invading organisms.

In endogenous endophthalmitis, blood-borne organisms (seen in patients who are bacteremic in situations such as endocarditis) permeate the blood-ocular barrier either by direct invasion (eg, septic emboli) or by changes in vascular endothelium caused by substrates released during infection. Destruction of intraocular tissues may be due to direct invasion by the organism and/or from inflammatory mediators of the immune response.

Endophthalmitis may be as subtle as white nodules on the lens capsule, iris, retina, or choroid. It can also be as ubiquitous as inflammation of all the ocular tissues, leading to a globe full of purulent exudate. In addition, inflammation can spread to involve the orbital soft tissue.

Any surgical procedure that disrupts the integrity of the globe can lead to exogenous endophthalmitis (eg, cataract, glaucoma, retinal, radial keratotomy, intravitreal injections).

Frequency

United States

Endogenous endophthalmitis is rare, occurring in only 2-15% of all cases of endophthalmitis. Average annual incidence is about 5 per 10,000 hospitalized patients. In unilateral cases, the right eye is twice as likely to become infected as the left eye, probably because of its more proximal location to direct arterial blood flow from the right innominate artery to the right carotid artery. Since 1980, candidal infections reported in IV drug users have increased. The number of people at risk may be increasing because of the spread of AIDS, more frequent use of immunosuppressive agents, and more invasive procedures (eg, bone marrow transplantation).

Most cases of exogenous endophthalmitis (about 60%) occur after intraocular surgery. When surgery is implicated in the cause, endophthalmitis usually begins within 1 week after surgery. In the United States, postcataract endophthalmitis is the most common form, with approximately 0.1-0.3% of operations having this complication, which has increased over the last 3 years.[1] Although this is a small percentage, large numbers of cataract operations are performed each year making the chances that physicians may encounter this infection higher. Endophthalmitis occurs in approximately 0.2% of corneal transplantation (keratoplasty) cases in the acute postoperative period and up to 0.7% if later cases are included.[2] Endophthalmitis may also occur after intravitreal injections, although this risk in an analysis of over 10,000 injections is estimated at 0.029% per injection.[3]

A 2016 study analyzed more than 117,000 intravitreal injections and found a similar postinjection infection rate of 0.038%.[4] Posttraumatic endophthalmitis comprises 25%-30% of all endophthalmitis cases and occurs in 45-13% of all penetrating ocular injuries. Incidence of endophthalmitis with perforating injuries in rural settings is higher when compared with nonrural settings.[5] Delay in the repair of a penetrating globe injury is correlated with increased risk of developing endophthalmitis.[6] Incidence of endophthalmitis with retained intraocular foreign bodies is 7-31%. The incidence of endophthalmitis was found to be very low in injuries caused by explosives (eg, bombs or mines), believed to be the result of the high temperature of the metallic foreign body, such that it passes through the eye in a relatively sterile manner.[7]  

Mortality/Morbidity

Decreased vision and permanent loss of vision are common complications of endophthalmitis. Patients may require enucleation to eradicate a blind and painful eye.

Mortality is related to the patient's comorbidities and the underlying medical problem, especially when considering the etiology of hematogenous spread in endogenous infections.

Age

An association appears to exist between the development of endophthalmitis in cataract surgery and age greater than or equal to 85 years.[8]

The prognosis is extremely variable because of the variety of organisms involved. The visual acuity at the time of the diagnosis and the causative agent are most predictive of outcome. Streptococcal infections tend to do worse than coagulase-negative staphylococcal infections.

The outcome of endogenous endophthalmitis is generally worse than exogenous endophthalmitis due to the profile of the organisms typically involved with this form (ie, more virulent organisms, compromised host, delay in diagnosis).

Patients in the traumatic subgroup, especially those caused by Bacillus infection, typically have a poor visual outcome.

In the endophthalmitis vitrectomy study group, 74% of patients had visual recovery of 20/100 or better.[9]

The prognosis appears to also be related to the patient's underlying health conditions, with one study demonstrating worsened outcomes among diabetic patients.

History should be focused toward practices or procedures that would increase risk of endogenous or exogenous endophthalmitis (eg, intravenous drug use, other risks for sepsis or endocarditis, recent invasive ophthalmologic procedure). See discussion below in Causes.

Bacterial endophthalmitis usually presents acutely with pain, redness, lid swelling, and decreased visual acuity. Also, some bacteria (eg, Propionibacterium acnes) may cause chronic inflammation with mild symptoms. This organism is typical skin flora and usually is inoculated at the time of intraocular surgery.

Fungal endophthalmitis may present with an indolent course over days to weeks. Symptoms are often blurred vision, pain, and decreased visual acuity. A history of penetrating injury with a plant substance or soil-contaminated foreign body may often be elicited.

Individuals with candidal infection may present with high fever, followed several days later by ocular symptoms. Persistent fever of unknown origin (FUO) may be associated with an occult retinochoroidal fungal infiltrate.

History of ocular surgery, ocular trauma, hammering steel with steel, working with baling wire, or working in an industrial setting may be elicited.

In cases of postsurgical endophthalmitis, infection most often occurs approximately 1 week after surgery but may occur months or years later as in the case of P acnes.

Symptoms may include the following:

• Visual symptoms in any hospitalized patient or patient taking immunosuppressive therapy

• Visual loss

• Eye pain and irritation

• Headache

• Photophobia

• Ocular discharge

• Intense ocular and periocular inflammation

• Injected eye

Physical findings correlate with structures involved and degree of infection or inflammation. A thorough eye examination should be performed to include acuity, external examination, funduscopic examination, and slit lamp examination. Seek signs of uveitis and other findings as described below. Emergent referral to an ophthalmologist for further evaluation, including more exhaustive physical examination, is indicated if endophthalmitis is seriously considered.

• Eyelid swelling and erythema

• Injected conjunctiva and sclera

• Hypopyon (layering of inflammatory cells and exudate [pus] in the anterior chamber)

• Vitreitis

• Chemosis

• Reduced or absent red reflex

• Proptosis (a late finding in panophthalmitis)

• Papillitis

• Cotton-wool spots

• Corneal edema and infection

• White lesions in the choroid and retina

• Chronic uveitis

• Vitreal mass and debris

• Purulent discharge

• Fever

• Cells and flare in the anterior chamber on slit lamp examination

• Note: Absence of pain and hypopyon do not rule out endophthalmitis, particularly in the chronic indolent form of P acnes infection.

In cases of endogenous endophthalmitis, the emergency physician needs to further evaluate the patient for the underlying source of infection. The intraocular inflammation in fungal endophthalmitis tends to occur in clumps within the aqueous and/or vitreous, whereas intraocular inflammation is typically diffuse in bacterial endophthalmitis.[2]

In most clinical series, gram-positive organisms are the most common causative organisms of endophthalmitis. The most common organisms are coagulase-negative Staphylococcus epidermidis, Staphylococcus aureus, and Streptococcus species. Gram-negative organisms like Pseudomonas, Escherichia coli, and Enterococcus are observed in penetrating injuries. However, when endogenous endophthalmitis is considered alone, the percentage of bacterial organisms drops markedly because of a greater proportion of fungal infections.[10] It is very rare for endophthalmitis to be caused by viral infections. Classically, viruses are responsible for uveitis.

Endogenous endophthalmitis

Individuals at risk for developing endogenous endophthalmitis usually have comorbidities that predispose them to infection.[10] These include conditions such as diabetes mellitus, chronic renal failure, cardiac valvular disorders, systemic lupus erythematosus, AIDS, leukemia, gastrointestinal malignancies, neutropenia, lymphoma, alcoholic hepatitis, and bone marrow transplantation.

Invasive procedures, which may result in bacteremia, such as hemodialysis, bladder catheterization, gastrointestinal endoscopy, total parenteral nutrition, chemotherapy, and dental procedures, also can lead to endophthalmitis.

Recent nonocular trauma or surgery, prosthetic heart valves, immunosuppression, and intravenous drug abuse may predispose to endogenous endophthalmitis.[11]

Sources for endophthalmitis include meningitis, endocarditis, urinary tract infection, and wound infection. Additionally, pharyngitis, pulmonary infection, septic arthritis, pyelonephritis, and intra-abdominal abscess also have been implicated as sources of infection.

Fungal organisms can occur in up to 50% of all cases of endogenous endophthalmitis.[10] Candida albicans is by far the most frequent cause (75-80% of fungal cases). Aspergillosis is the second most common cause of fungal endophthalmitis, especially in IV drug users. Less frequent are other candidal species and Torulopsis, Sporotrichum, Cryptococcus, Coccidioides, and Mucor species.

The single most commonly involved gram positive organism is S. aureus, which often is implicated with skin infections or chronic systemic disease, such as diabetes mellitus or renal failure. Streptococcal species including Streptococcus pneumoniae, Streptococcus viridans, and group A streptococci also are common. Other streptococcal species, eg, group B in newborns with meningitis or group G in elderly patients with wound infections or malignancies, also have been isolated. Bacillus cereus has been implicated in intravenous drug abuse and intravenous injections. Clostridium species have been implicated in association with bowel carcinomas.

Gram-negative bacteria are other bacterial etiologies. E coli is the most common among the gram-negative bacteria. Haemophilus influenzae, Neisseria meningitidis, Klebsiella pneumoniae, Serratia species, and Pseudomonas aeruginosa also can cause endogenous endophthalmitis.

Nocardia asteroides, Actinomyces species, and Mycobacterium tuberculosis are acid-fast bacteria that may cause endogenous endophthalmitis.

Exogenous endophthalmitis

Organisms that reside at the conjunctiva, eyelid, or eyelashes and are introduced at the time of surgery usually cause postoperative endophthalmitis.

Most cases of exogenous endophthalmitis develop postoperatively or after trauma to the eye. In fact, postoperative endophthalmitis is the most common cause of the disease. Of these cases, gram-positive organisms account for almost 90% of cases, of which the majority are coagulase-negative Staphylococcus from the natural conjunctival flora.[12]

The single most common cause of exogenous endophthalmitis is S epidermidis, which is a normal flora of the skin and conjunctiva. Other common gram-positive bacteria are S aureus and streptococcal species.

The most common gram-negative organisms associated with postoperative endophthalmitis are P aeruginosa and Proteus and Haemophilus species.

Although very rare, many different fungi have caused postoperative endophthalmitis, including Candida, Aspergillus, and Penicillium species. Postoperatively, fungal endophthalmitis is most common after keratoplasty (corneal transplantation), with up to 31% of cases due to fungi, mostly Candida.[2]

The rates of endophthalmitis postoperatively after cataract surgery appear to be declining in the last decade.[13, 14]

The use of intracameral antibiotics is associated with a decreased occurrence of postoperative endophthalmitis.[15]

Traumatic endophthalmitis

Bacteria or fungi are introduced at the time of injury. Endophthalmitis can occur in up to 13% of cases of penetrating injury to the globe. Since penetrating trauma usually occurs in a nonsterile environment, most objects that strike the eye are contaminated with multiple infectious agents.

The risk of developing traumatic endophthalmitis by foreign objects carrying soil or vegetable matter is highest in rural settings. Staphylococcal, streptococcal, and Bacillus species usually cause traumatic endophthalmitis.[16] B cereus causes much more infections in the traumatic population than in either of the other two groups, and can cause serious infection.[17] A history of penetrating trauma with intraocular foreign body contaminated with organic matter implicates Bacillus species.[18]

Patients with open globe injuries are at risk of developing endophthalmitis. Specifically, those with pure corneal injuries, intraocular foreign bodies, lens rupture, or needle-related injuries have a higher incidence.[19] Prophylactic intravitreal/intracameral antibiotics were noted to significantly reduce the occurrence of endophthalmitis in open globe injuries.[20]

Patients with larger lacerations, delay in time to repair of open globe, and those with more virulent organisms tend to do worse than patients with traumatic etiology.[21]

Complications of endophthalmitis may include the following:

• Impairment of vision

• Complete loss of vision

• Loss of eye architecture

• Enucleation

The most important laboratory study for endophthalmitis is Gram stain and culture of the aqueous and vitreous obtained by the ophthalmologist.

Real-time polymerase chain reaction (RT-PCR) has improved diagnostic results over traditional culture.[22]

For endogenous endophthalmitis, other laboratory studies that may be performed include the following:

• Complete blood count with differential - Evaluating for signs of infection, elevated white count, left shift

• Erythrocyte sedimentation rate - Evaluating for rheumatic causes, chronic infections, or malignancy. The ESR is often normal in cases of endophthalmitis.

• Blood urea nitrogen - Evaluating for renal failure or patients at increased risk

• Creatinine - Evaluating for renal failure or patients at increased risk

Imaging studies include the following:

• Chest radiograph - Evaluating for source of infection

• Cardiac ultrasound - Evaluating for endocarditis as source of infection

• CT scan/MRI of orbit - May help rule out other entities in the differential diagnosis

• Ocular ultrasound – Helpful when positive findings are seen, such as low-amplitude mobile echoes, vitreous membranes, and thickening of the retina and choroid; however, sensitivity is not high enough to rule out the diagnosis with a negative ultrasound[3, 23]

Other tests include the following:

• Blood cultures - Evaluating for source of infection

• Urine culture - Evaluating for source of infection

• Other cultures depending on clinical signs or symptoms

  • Cerebrospinal fluid - Evaluating for source of infection

  • Throat culture - Evaluating for source of infection

  • Stool - Evaluating for source of infection

  • Indwelling intravascular catheter tip - Evaluating for source of infection

  • A culture of the penetrating object, if available, can be a valuable resource.

  • Vitreous culture obtained by the ophthalmologist

Ophthalmological evaluation includes the following:

• Check visual acuity

• Examine both eyes by slit lamp biomicroscopy

• Intraocular pressure

• Dilated funduscopy

• Possible ultrasonography if fundus not well visualized (This will help determine if a retained intraocular foreign body is present, the density of the vitreitis, and if the retina is attached or not.)

• Routine cultures should include aerobic, anaerobic, and fungal cultures.

Once the diagnosis has been made, or strongly considered, prompt consultation to an ophthalmologist is needed. Treatment depends on the underlying cause of endophthalmitis. Final visual outcome is heavily dependent on timely recognition and treatment. Although multiple different approaches to and advances in treatment have been made, according to recent data, the rate of preservation of visual acuity has not changed significantly since 1995.[24]

Treatment of postoperative endophthalmitis

Pars plana vitrectomy or vitreous aspiration may be performed by an ophthalmologist with administration of intravitreal antibiotics (ie, vancomycin, amikacin, ceftazidime).

Consider systemic antibiotic administration as well as intravitreal steroids.

Patients with postoperative endophthalmitis usually are not admitted to the hospital. However, the decision to admit the patient is determined in consultation with the ophthalmologist.

Treatment of traumatic endophthalmitis

Admit the patient to the hospital.

Treat ruptured globe (if present).

Systemic antibiotics including vancomycin and an aminoglycoside or a third-generation cephalosporin are indicated. Consider clindamycin until Bacillus species can be ruled out if soil contamination is suspected.

Topical fortified antibiotics are used.

Intravitreal antibiotics should be administered.

Consider pars plana vitrectomy.

Tetanus immunization is necessary if immunization record is not current.

Cycloplegic drops (ie, atropine) may be considered.

Treatment of endogenous bacterial endophthalmitis

Admit the patient to the hospital.

Broad-spectrum intravenous antibiotics including vancomycin and an aminoglycoside or third-generation cephalosporin. Consider adding clindamycin in intravenous drug users until Bacillus infection can be ruled out.

Periocular antibiotics are sometimes indicated.

Intravitreal antibiotics are indicated.

Cycloplegic drops (ie, atropine) may be administered.

Topical steroids may be considered.

Vitrectomy may be needed for virulent organisms.

Treatment of candidal endophthalmitis

Admit the patient to the hospital.

Oral fluconazole is indicated.

Amphotericin B intravenous or intravitreal may be considered.

Cycloplegic drops (ie, atropine) may be considered.

Ophthalmologist: Emergent consultation is necessary if this diagnosis is entertained. This is an ophthalmologic emergency, as the patient is in danger of losing his or her vision.

Few randomized controlled trials have been performed to determine the most effective methods to prevent endophthalmitis. Use of appropriate protective eyewear can decrease risk of ocular trauma or globe penetration in certain circumstances.

The emergency department physician should consider transfer to another facility if ophthalmology consultation is not available at his or her institution.

In postoperative endophthalmitis, parenteral therapy is not necessary unless evidence of infection exists outside the globe.

In other forms of endophthalmitis, administer broad-spectrum antibiotics once cultures have been obtained. An ophthalmologist usually administers intravitreal and subconjunctival injections. The following list of systemic antibiotics can be administered in conjunction with injection.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Vancomycin (Vancocin)

Empiric coverage for gram-positive organisms including B cereus. DOC for both intravitreal and systemic administration; excellent gram-positive coverage and has added advantage of providing better coverage against resistant organisms; bactericidal against most organisms and bacteriostatic for enterococci; inhibits cell wall biosynthesis, interfering with cell-membrane permeability and RNA synthesis.

After systemic administration, drug penetrates most tissues including vitreous, especially if the blood-ocular barrier is compromised. Use creatine clearance to adjust dose in patients with renal impairment.

Gentamicin (Gentacidin, Garamycin)

Empiric coverage for gram-negative organisms including P aeruginosa. First choice aminoglycoside for systemic gram-negative coverage; bactericidal inhibitor of protein synthesis (30S ribosomal subunit).

Dosing regimens are numerous; adjust dose based on CrCl.

Ceftazidime (Fortaz, Ceptaz)

Third-generation cephalosporin with broad gram-negative coverage but decreased efficacy to gram-positive organisms; gram-negative coverage includes Enterobacter, Citrobacter, Serratia, Neisseria, Providencia, and Haemophilus species.

Cephalosporins bind to one or more of the penicillin-binding proteins and prevent cell wall synthesis inhibiting bacterial growth.

Ceftriaxone (Rocephin)

Third-generation cephalosporin that crosses blood brain barrier. Active against resistant bacteria including gonococci, H influenzae, and other gram-negative organisms.

Used in suspected hematogenous source for endophthalmitis in combination with vancomycin while cultures are pending. Cephalosporins bind to the penicillin binding protein and prevent cell wall synthesis, which inhibits bacterial growth.

Cefotaxime (Claforan)

Third-generation cephalosporin that has broad gram-negative coverage but lower efficacy for gram-positive organisms. Cephalosporins bind to one or more of the penicillin-binding proteins and prevent cell wall synthesis inhibiting bacterial growth.

Clindamycin (Cleocin)

Use in IV drug abusers or penetrating trauma with soil contamination for suspected B cereus infection. Semisynthetic antibiotic that inhibits bacterial protein synthesis by interfering with peptide bond formation at the 50S ribosomal subunit; has both bacteriostatic and bactericidal activity.

Class Summary

For suspected candidal or Aspergillus infection. Indicated in patients who are immunosuppressed, who have indwelling venous catheters, or who are currently taking broad-spectrum antibiotics.

Amphotericin B (AmBisome)

Fungistatic or fungicidal depending on concentration attained in body fluids; polyene antibiotic produced by a strain of Streptomyces nodosus. Changes permeability of fungal cell membrane by binding to sterols, which causes fungal cell death as intracellular components leak out.