deputy editor this topic last updated: introduction fileadditional risk factors were evaluated in a...

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Bacterial endophthalmitis Author Marlene L Durand, MD Section Editors Stephen B Calderwood, MD Jonathan Trobe, MD Deputy Editor Allyson Bloom, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2015. | This topic last updated: Sep 08, 2015. INTRODUCTION Endophthalmitis refers to bacterial or fungal infection within the eye, including involvement of the vitreous and/or aqueous humors. It is not caused by viruses or parasites; by convention, infections due to these organisms are included in the term "uveitis" (eg, cytomegalovirus [CMV] retinitis, toxoplasma chorioretinitis). Most cases of endophthalmitis are exogenous, resulting from inoculation of organisms from the outside, via trauma, eye surgery, or as an extension of keratitis (corneal infection). In such cases, the aqueous humor may be seeded first before extension into the vitreous. The remaining cases are endogenous, resulting from bacteremic or fungemic seeding of the eye. In endogenous endophthalmitis, organisms usually seed the highly vascular choroid first then extend anteriorly into the vitreous. Most cases of endophthalmitis are due to bacteria and present acutely. Acute bacterial endophthalmitis is a vision- threatening condition and must be managed as an emergency. The clinical outcome depends upon both the virulence of the infecting organism and the speed with which appropriate therapy is initiated. Bacterial endophthalmitis can be divided into six categories: Acute postcataract surgery Chronic pseudophakic Post-intravitreal injection (eg, after anti-vascular endothelial growth factor [VEGF] injections) Bleb related Posttraumatic Endogenous The epidemiology, clinical features, diagnosis, and treatment of bacterial endophthalmitis will be reviewed here. Fungal endophthalmitis is discussed separately. (See"Epidemiology, clinical manifestations, and diagnosis of fungal endophthalmitis" and "Treatment of endogenous endophthalmitis due to Candida species" and "Treatment of exogenous endophthalmitis due to Candida species" and "Treatment of endophthalmitis due to molds" .) ACUTE POSTCATARACT ENDOPHTHALMITIS Acute postcataract endophthalmitis is the most common form of endophthalmitis and, in the United States, is almost always due to bacteria. This complication occurs within six weeks of cataract surgery, with 75 percent of cases presenting in the first postoperative week. Series from the 1990s noted an incidence of endophthalmitis of 0.1 to 0.2 percent of cases [ 1-3 ], whereas a nationwide prospective study in Sweden from 2002 to 2004 found a somewhat lower incidence of 0.05 percent [ 4 ]. Despite the low rate, endophthalmitis represents an important clinical problem since over two million cataract operations are performed annually in the United States. Risk factors The vitreous is much more susceptible than the aqueous humor to infection by exogenously introduced bacteria (figure 1 ) [5 ]. Cataract surgery, which is performed through the anterior chamber, often results in transient bacterial contamination of the aqueous by the patient's conjunctival flora. Several studies have shown that bacteria can be isolated from the anterior chamber at the end of cataract surgery in 7 to 43 percent of cases [6-8 ]. The organism burden in the aqueous is usually low, as demonstrated by quantitative cultures [6 ]. None of the study patients developed endophthalmitis, suggesting that the immune system is usually able to clear a small inoculum of relatively avirulent organisms. If a communication with the vitreous is inadvertently created during surgery (eg, break in the posterior lens capsule), the risk of endophthalmitis is much higher (14 times higher in one report) than in patients without a vitreous communication [4,9 ].

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Bacterial endophthalmitis Author

Marlene L Durand, MD Section Editors

Stephen B Calderwood, MD Jonathan Trobe, MD Deputy Editor

Allyson Bloom, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2015. | This topic last updated: Sep 08, 2015.

INTRODUCTION — Endophthalmitis refers to bacterial or fungal infection within the eye, including involvement of the

vitreous and/or aqueous humors. It is not caused by viruses or parasites; by convention, infections due to these

organisms are included in the term "uveitis" (eg, cytomegalovirus [CMV] retinitis, toxoplasma chorioretinitis). Most

cases of endophthalmitis are exogenous, resulting from inoculation of organisms from the outside, via trauma, eye

surgery, or as an extension of keratitis (corneal infection). In such cases, the aqueous humor may be seeded first

before extension into the vitreous. The remaining cases are endogenous, resulting from bacteremic or fungemic

seeding of the eye. In endogenous endophthalmitis, organisms usually seed the highly vascular choroid first then

extend anteriorly into the vitreous.

Most cases of endophthalmitis are due to bacteria and present acutely. Acute bacterial endophthalmitis is a vision-

threatening condition and must be managed as an emergency. The clinical outcome depends upon both the virulence

of the infecting organism and the speed with which appropriate therapy is initiated.

Bacterial endophthalmitis can be divided into six categories:

●Acute postcataract surgery

●Chronic pseudophakic

●Post-intravitreal injection (eg, after anti-vascular endothelial growth factor [VEGF] injections)

●Bleb related

●Posttraumatic

●Endogenous

The epidemiology, clinical features, diagnosis, and treatment of bacterial endophthalmitis will be reviewed here.

Fungal endophthalmitis is discussed separately. (See"Epidemiology, clinical manifestations, and diagnosis of fungal

endophthalmitis" and "Treatment of endogenous endophthalmitis due to Candida species" and "Treatment of

exogenous endophthalmitis due to Candida species" and "Treatment of endophthalmitis due to molds".)

ACUTE POSTCATARACT ENDOPHTHALMITIS — Acute postcataract endophthalmitis is the most common form of

endophthalmitis and, in the United States, is almost always due to bacteria. This complication occurs within six weeks

of cataract surgery, with 75 percent of cases presenting in the first postoperative week.

Series from the 1990s noted an incidence of endophthalmitis of 0.1 to 0.2 percent of cases [1-3], whereas a

nationwide prospective study in Sweden from 2002 to 2004 found a somewhat lower incidence of 0.05 percent [4].

Despite the low rate, endophthalmitis represents an important clinical problem since over two million cataract

operations are performed annually in the United States.

Risk factors — The vitreous is much more susceptible than the aqueous humor to infection by exogenously

introduced bacteria (figure 1) [5]. Cataract surgery, which is performed through the anterior chamber, often results in

transient bacterial contamination of the aqueous by the patient's conjunctival flora.

Several studies have shown that bacteria can be isolated from the anterior chamber at the end of cataract surgery in 7

to 43 percent of cases [6-8]. The organism burden in the aqueous is usually low, as demonstrated by quantitative

cultures [6]. None of the study patients developed endophthalmitis, suggesting that the immune system is usually able

to clear a small inoculum of relatively avirulent organisms.

If a communication with the vitreous is inadvertently created during surgery (eg, break in the posterior lens capsule),

the risk of endophthalmitis is much higher (14 times higher in one report) than in patients without a vitreous

communication [4,9].

Additional risk factors were evaluated in a retrospective case-control series of 57 patients with postcataract

endophthalmitis and 220 controls [10]. Implantation of an intraocular lens without a heparinized surface,

immunosuppressive therapy, and wound abnormality were risk factors for infection by logistic regression analysis.

Risk factors noted in other studies include diabetes [2], wound dehiscence or leak [11], age ≥85 [4], and lens implants

made of polypropylene (Prolene) instead of polymethyl methacrylate [12].

Advances in surgery, such as phacoemulsification and foldable synthetic intraocular lenses, have allowed incisions so

small that they are considered self-sealing. These "sutureless" incisions are now primarily made through the cornea

("clear cornea incision"), which may increase the risk of postoperative endophthalmitis [13-16]. There is evidence that

clear corneal incisions gape intermittently during the first few days after cataract surgery. This may allow external

colonizing flora to enter the eye and account for the increased risk of endophthalmitis [17,18].

Symptoms and signs — The onset of symptoms occurs within one week of surgery in 75 percent of cases. Patients

usually give a 12 to 24 hour history of decreasing vision and eye "ache" (they may deny eye "pain"). Patients feel

otherwise well and are afebrile.

On physical examination, findings are confined to the affected eye. The lids often appear normal, although they may

be swollen. The conjunctiva may be injected or edematous (conjunctival chemosis), although these findings can also

represent residual postoperative changes. Visual acuity is decreased, and a hypopyon (layering of white blood cells in

the anterior chamber) is often present (picture 1). The view of the retina is usually hazy, and, in 80 percent of patients,

no retinal vessels can be seen [15]. Slit lamp examination reveals intraocular white blood cells and protein (called

"cells" and "flare," respectively, by ophthalmologists).

Differential diagnosis — The major entity in the differential diagnosis of endophthalmitis is sterile postoperative

inflammation. This can result from various causes, including a reaction to retained native lens fragments, extensive iris

manipulation, or prolonged and complicated surgery [5].

The sterile inflammation can mimic early endophthalmitis, although the manifestations are typically greatest on the first

postoperative day, whereas bacterial endophthalmitis usually develops on day two or later. However, timing of the

onset of symptoms or findings cannot be relied upon to differentiate these entities. Sterile inflammation must be a

diagnosis of exclusion.

Laboratory findings — Laboratory findings are usually normal. Only one-third of patients with endophthalmitis have a

white blood cell count greater than 10,000/microL[19]. The erythrocyte sedimentation rate is usually normal. An

ultrasound of the eye ("B-scan") usually shows increased echogenicity of the vitreous due to intraocular inflammation.

This test can be helpful when the view of the vitreous is obscured by abnormalities in the anterior segment.

Diagnosis — Endophthalmitis is a clinical diagnosis that is confirmed by positive aqueous or vitreous culture.

However, a negative culture does not exclude the diagnosis.

The ophthalmologist can aspirate the aqueous (0.1 mL sample) and/or vitreous (0.2 to 0.3 mL) with a needle in the

office or perform a pars plana vitrectomy in the operating room. A vitrectomy entails the use of a vitrector, an

instrument inserted into the vitreous that simultaneously cuts and aspirates some of the 4 mL of gel-like vitreous into a

canister. During this process, another catheter irrigates the vitreous with saline. By the end of the case, the vitrectomy

canister contains 50 to 100 mL of dilute vitreous washings (figure 2).

Vitrectomy has the highest yield for a positive culture (90 percent of specimens), whereas only 75 percent of vitreous

aspirate specimens are positive [19]. An aqueous aspirate has the lowest yield for a positive culture. In cases with

positive vitreous cultures, simultaneous aqueous cultures are positive in only 40 percent [19].

Aspirates should be cultured on blood agar, chocolate agar, anaerobic media, meat broth, and Sabouraud agar. One

drop should be placed on a slide for Gram stain. Gram stain is positive in approximately 45 percent of cases [19].

If a vitrectomy is performed, 3 mL of the vitreous washings should be aspirated from the canister, centrifuged, and the

pellet smeared on a slide for Gram stain. The remainder of the canister contents should be vacuum filtered through a

0.45 micron filter; the filter paper should then be cut up and placed on the media listed above.

It is not yet clear what role molecular diagnostic techniques, such as polymerase chain reaction (PCR), will have in the

diagnosis of bacterial endophthalmitis. These methods may amplify bacteria that are conjunctival contaminants and

lead to false-positive results. The value of PCR was evaluated in a study that used eubacterial primers to examine

aqueous and vitreous samples from endophthalmitis cases and noninfectious controls [20]. PCR was positive in all 20

culture-positive cases, but also in one of the 20 controls. The use of PCR to diagnose endophthalmitis is being

evaluated in a large multicenter European study [21].

Bacteriology — Since coagulase-negative staphylococci are the predominant organisms colonizing the surface of the

eye, and since most cases of postcataract endophthalmitis are due to the patient's own conjunctival flora [22], it is not

surprising that coagulase-negative staphylococci are the major pathogens in postcataract endophthalmitis. The best

microbiologic data have been provided by the Endophthalmitis Vitrectomy Study (EVS), a multicenter, National

Institutes of Health (NIH)-sponsored prospective study of 420 patients with postcataract endophthalmitis [23]. Thirty-

one percent of patients had negative or equivocal cultures. Organisms isolated in the confirmed culture-positive group

included:

●Coagulase-negative staphylococci – 70 percent

●Staphylococcus aureus – 10 percent

●Streptococci – 9 percent

●Other gram-positive organisms – 5 percent

●Gram-negative organisms – 6 percent

Treatment — Acute endophthalmitis is a medical emergency. The most important component of treatment of

postcataract endophthalmitis is direct injection of antibiotics into the vitreous. Vitrectomy is important in severe cases.

The role of adjunctive systemic antibiotics is unknown.

Intravitreal antibiotics — The ophthalmologist first obtains a vitreous sample for culture and then injects antibiotics

into the vitreous. Intravitreal antibiotics can be injected either as an office procedure (vitreous aspiration and antibiotic

injection, also called "tap and inject") or in the operating room following vitrectomy (a debridement procedure of the

vitreous).

The empiric intravitreal antibiotics used are vancomycin 1 mg plus either ceftazidime 2.25 mg or amikacin 0.4 mg.

Each agent is diluted in 0.1 mL of sterile water or saline. Ceftazidime is usually preferred over amikacin because of

the small risk of macular infarction with injected aminoglycosides. Antibiotic concentrations in the vitreous decline

rapidly following injection, so most last only 24 to 48 hours. Thus, one injection of antibiotics may not maintain levels in

the vitreous long enough to kill all bacteria. A repeat injection of vancomycin or ceftazidime may be indicated after 48

hours if there is persistent or worsening intraocular inflammation; a second injection of amikacin is avoided given

concerns for retinal toxicity. The choice of antibiotic for repeat intravitreal injection is based on the culture result.

Vitrectomy — Vitrectomy is an important component of treatment in eyes with severe infection. Vitrectomy debrides

the inflamed vitreous, similar to incision and drainage of an abscess. Vitrectomy leads to better visual outcomes in

patients who present with severe vision loss. Whether vitrectomy should also be used in less severe cases is unclear.

Similarly, the role of adjunctive oral or intravenous antibiotics in treating exogenous endophthalmitis is unclear.

The Endophthalmitis Vitrectomy Study was a multicenter trial that evaluated the role of vitrectomy and the value of

adjunctive systemic antibiotics in treating postcataract endophthalmitis [19]. This study changed the practice of

treating postcataract endophthalmitis. However, flaws in study design led to controversy regarding the interpretation of

some of the results. Four hundred and twenty patients with postcataract endophthalmitis were randomly assigned to

four treatment arms (2x2 design): vitrectomy versus vitreous "tap" (aspirate or biopsy) and systemic antibiotics versus

none [19]. The systemic antibiotics used were intravenous ceftazidime and amikacin. All patients received intravitreal

antibiotics and all patients assigned to the vitrectomy group received a vitrectomy in the operating room under local

anesthesia.

It is important to note that the vitreous "tap" group in the EVS was not homogeneous. Although a vitreous "tap" is

understood by ophthalmologists to mean needle aspiration of the vitreous (an office procedure using topical

anesthesia), the "tap" group included patients who received the usual needle aspiration of the vitreous, but also those

who received a vitreous biopsy. Two-thirds of the patients had a vitreous "biopsy," which was really a "mini-vitrectomy"

and was performed with a vitrector in the operating room [24,25]. The EVS authors concluded that there was no

difference in visual outcome between the vitrectomy and "tap" groups, except in patients who presented with the worst

vision (light perception only). In these patients, vitrectomy was superior and significantly decreased the chance of

severe visual loss compared with vitreous "tap" (20 versus 47 percent). In patients who presented with hand motion or

better vision, the authors concluded that vitreous "tap" was sufficient. However, objections have been raised to this

conclusion, since the comparison was really vitrectomy versus mini-vitrectomy in the majority of patients. The question

remains whether patients who present with hand motion or better vision, especially those who present with a rapidly

worsening course, might also benefit from vitrectomy (plus intravitreal antibiotics) rather than intravitreal antibiotics

alone.

The EVS demonstrated that vitrectomy sterilizes the vitreous more quickly than intravitreal antibiotics alone.

Approximately 10 percent of each group had a second procedure and vitreous culture during the first week due to

persistent inflammation. Of these patients, vitreous cultures were persistently positive more often in the "tap" group

than the vitrectomy group (71 versus 13 percent), even though both groups had received the same intravitreal

antibiotics [24]. Therefore, a vitrectomy should be considered for patients with endophthalmitis who received only an

initial "tap and inject" on presentation but are failing to improve by 48 hours (or 24 hours in severe cases), since these

patients may have persistent infection.

A subsequent US study attempted to survey ophthalmologists who had treated 1213 endophthalmitis cases in five

states between 2003 and 2004 (cases identified by Medicare claims) but received responses for only 719 cases (59

percent) and included only 615 cases (51 percent) [26]. The study concluded that vitrectomy offered no benefit, but its

retrospective nature and poor survey response rate confound interpretation of the data.

Adjunctive systemic antibiotics — Systemic antibiotics alone are not effective in treating bacterial endophthalmitis.

Whether systemic antibiotics provide any benefit as adjunctive therapy to intravitreal antibiotics is unknown. Systemic

antibiotics that cross the blood-eye barrier may prolong intravitreal antibiotic concentrations achieved following

intravitreal antibiotic injection. This may be helpful in killing bacteria in the vitreous. However, there are no studies that

have adequately evaluated this. The EVS concluded that adjunctive systemic antibiotics did not improve visual

outcome and were not necessary to treat postcataract endophthalmitis [19]. However, staphylococci accounted for 80

percent of the study isolates [23], but the systemic antibiotics used in the study (amikacin plus ceftazidime) have poor

activity against staphylococci. In addition, amikacin does not cross the blood-eye barrier, so it is ineffective in treating

endophthalmitis. It has been suggested that more effective systemic antibiotics (eg, a regimen that included

intravenous vancomycin) might have demonstrated a benefit [27].

Since the EVS, only retrospective reviews of adjunctive systemic antibiotics have been published. A study from

western Australia that reviewed 213 cases of postcataract endophthalmitis from 1980 to 2000 found that patients who

received various adjunctive oral antibiotics had better visual outcomes compared with those who did not receive

adjunctive antibiotics [25]. However, it is difficult to draw any conclusions from this study given the lack of a uniform

antibiotic regimen and the retrospective study design. Another study reviewed 72 cases of postcataract

endophthalmitis between 2000 and 2009 treated with intravitreal injection of antibiotics (excluding patients treated with

initial vitrectomy in addition to intravitreal antibiotics) [27]. All patients received an oral fluoroquinolone for 10 days

after intravitreal injection of antibiotics; ciprofloxacin was used between 2000 and 2004 (in 48 patients)

and moxifloxacin was used between 2005 and 2009 (in 24 patients). There were no significant differences in patient or

surgical characteristics between the two groups. After controlling for potentially confounding factors such as

ciprofloxacin resistance, moxifloxacin use was significantly associated with a good visual outcome (20/40 or better;

adjusted odds ratio 4.07, 95% CI 1.11-14.9).

Approach to therapy — We recommend the following approach to therapy for patients with postcataract bacterial

endophthalmitis:

●Cultures of the vitreous should be obtained by needle aspiration or vitrectomy as soon as endophthalmitis is

suspected.

●Antibiotics should be injected into the vitreous as soon as endophthalmitis is suspected and vitreous cultures

are obtained. Intravitreal antibiotics are the most important component of endophthalmitis therapy. Empiric

intravitreal antibiotics are usually given when the etiology is unknown, and these include vancomycin 1 mg plus

either ceftazidime 2.25 mg or amikacin 0.4 mg. Ceftazidime is favored over amikacin because of toxicity

concerns.

●Vitrectomy should be performed for eyes with severe vision loss on presentation (light perception vision only or

worse) and should be considered for cases that fail to improve after 24 to 48 hours. Vitreous aspiration ("tap and

inject") may be used initially for other cases. Intravitreal antibiotics are injected at the end of the vitrectomy as

above.

●The intraocular lens implant does not need to be removed, except in cases of chronic endophthalmitis or those

due to fungi. (See 'Chronic pseudophakic endophthalmitis' below and "Treatment of exogenous endophthalmitis

due to Candida species" and "Treatment of endophthalmitis due to molds".)

●The value of adjunctive systemic antibiotics in treating postcataract endophthalmitis is unknown. We

recommend adjunctive systemic antibiotics for severe cases (see 'Adjunctive systemic

antibiotics' above). Moxifloxacin (400 mg orally once daily) achieves excellent vitreous levels [28] and, as noted

above, a retrospective study using 10 days of therapy suggested some benefit [27]. Oral linezolid (600 mg twice

daily) can be used as adjunctive therapy in staphylococcal endophthalmitis, but it has been inadequately studied

for this indication. Linezolid achieves therapeutic intraocular levels [29] and has excellent coverage of gram-

positive bacteria. Whether intravenous antibiotics are indicated as adjunctive therapy in fulminant postcataract

endophthalmitis cases has not been studied. In practice, few ophthalmologists use them.

●If the eye is not improving by 48 hours after the initial intravitreal antibiotic injection (ie, unchanged or

worsening intraocular inflammation based on the ophthalmologist's examination), there are two things one

should consider: a second injection of intravitreal antibiotics and vitrectomy (if this has not already been

performed). In fulminant cases, these should be considered at 24 rather than 48 hours. For this second injection

of intravitreal antibiotics, either intravitrealvancomycin and/or ceftazidime should be given, based on culture

results. A second injection of amikacin is avoided, if possible, due to toxicity concerns. A repeat culture of the

vitreous should also be obtained. In rare cases, a third injection of intravitreal antibiotics may be indicated 24 to

48 hours after the second injection, especially if repeat vitreous cultures are positive.

Visual outcome — About half of eyes with postcataract endophthalmitis will eventually recover 20/40 vision, whereas

10 percent will lose useful vision (5/200 or worse) [19]. The outcome of postcataract endophthalmitis depends on the

virulence of the pathogen: the worst outcomes are seen in cases due to streptococci of any type and the best

outcomes occur in cases due to coagulase-negative staphylococci or cases that are culture negative [19].

CHRONIC PSEUDOPHAKIC ENDOPHTHALMITIS — Chronic pseudophakic-related endophthalmitis is a rare

complication of cataract surgery. During cataract surgery, most of the opacified native lens (cataract) is removed,

leaving behind some residual native lens and the posterior portion of the lens capsule. An artificial intraocular lens

(IOL) is placed in front of this in the posterior chamber, the space between the lens and iris. "Pseudophakic" refers to

the intraocular lens. Chronic pseudophakic endophthalmitis is usually caused by Propionibacterium acnes. A few

cases have been caused by coagulase-negative staphylococci and diphtheroids. This infection is characterized by

low-grade intraocular inflammation that may persist for months. It is often misdiagnosed as noninfectious iritis and

typically improves with topical corticosteroid therapy but flares each time corticosteroids are stopped. It may be

months before the correct diagnosis is made.

Symptoms include decreased vision in nearly all patients and eye pain (usually mild) in approximately half of patients.

Eye examination with a slit lamp reveals white blood cells in the anterior chamber and, in nearly all patients, a

characteristic white plaque in the posterior lens capsule. A hypopyon and white blood cells in the anterior vitreous

(anterior vitritis) are also seen in some patients.

For years, this process was thought to be a reaction to the remaining native lens tissue and was called toxic lens

syndrome or phacoanaphylactic endophthalmitis. That the inflammation typically decreased with topical corticosteroid

therapy added support to this misdiagnosis. Vitreous culture was negative or grew only P. acnes, initially thought to be

a contaminant. Subsequent Gram stain and electron microscopy studies of the removed lens capsule showed small

gram-positive rods, consistent with P. acnes, adherent to the capsular remnants [30].

Diagnosis is often difficult and is based on clinical suspicion supported by cultures of the aqueous or posterior lens

capsule. However, cultures of the aqueous are often negative, even in cases where subsequent electron microscopy

of the removed lens or lens capsule demonstrates organisms [31]. Anaerobic cultures should be included if possible.

The highest yield for culture is usually by sampling the white plaque in the posterior lens capsule, but this can only be

obtained by surgery (removal of the intraocular lens and posterior lens capsule). Aspirate of the aqueous can be

performed in an outpatient ophthalmology procedure room using a topical anesthetic.

Treatment requires at least vitrectomy and intravitreal vancomycin, although 50 percent of cases recur with this

treatment alone [32,33]. Removing part of the lens capsule (partial capsulectomy), in addition to vitrectomy and

intravitreal vancomycin, reduced the recurrence rate in one study to 14 percent [33]. However, in another study, this

treatment was associated with a 44 percent recurrence rate [34]. Exchanging the IOL for a new one improved

outcomes considerably. The combination of total capsulectomy, IOL exchange or removal, vitrectomy, and intravitreal

antibiotics cured all cases in both studies. This was true whether this treatment was used as initial therapy or as

treatment of recurrence after other therapy had failed. Systemic antimicrobial therapy is not indicated.

POST-INTRAVITREAL INJECTION ENDOPHTHALMITIS — Neovascular, or "wet" macular degeneration, accounts

for about 10 percent of cases of macular degeneration. Regular (usually monthly) injections of anti-vascular

endothelial growth factor (VEGF) medications into the vitreous are often used to treat wet macular degeneration. Each

injection carries a risk of endophthalmitis similar to that of cataract surgery. A study using a Medicare database of

41,000 injections found the rate of postinjection endophthalmitis to be 0.09 percent per injection [35]. Since these

injections are usually repeated monthly for many months, there is a substantial cumulative risk of postinjection

endophthalmitis over time. In many centers, post-VEGF injection endophthalmitis is seen more often than postcataract

endophthalmitis.

The bacteriology of postinjection endophthalmitis is similar to that of postcataract endophthalmitis, except that the

proportion of cases due to viridans streptococci is much higher (30 percent versus 9 percent) [36]

(see 'Bacteriology' above). This may be due to the fact that these injections occur in an office setting rather than the

operating room. Masks are usually not worn, and patient and medical personnel often converse before and during the

procedure. Speaking transmits oral flora bacteria into the air, and these organisms can contaminate the ocular

surface; wearing a mask or avoiding talking reduces the risk of contamination [37]. In a multicenter study from France

involving over 300,000 intravitreal injections, all ophthalmologists wore surgical gowns and hats, sterile gloves, and

face masks, and the endophthalmitis rate was 0.021 percent [38]. Only 43 percent of cases were culture-positive, and

of those, coagulase-negative staphylococci caused 78 percent and streptococci only 4 percent.

BLEB-RELATED ENDOPHTHALMITIS — A filtering bleb is used to treat severe glaucoma that has failed medical

management. It is a surgically created defect in the sclera, covered only by conjunctiva, which allows excess aqueous

humor to leak out of the anterior chamber and be absorbed into the systemic circulation. It is usually placed in the

superior portion of the eye and, when the upper lid is raised, it may be seen as a small bump in the sclera. A bleb can

also rarely occur as a complication of other types of eye surgery.

A bleb may become infected (blebitis) (picture 2), and bacteria may enter the eye, resulting in endophthalmitis. The

onset of endophthalmitis is usually abrupt and typically occurs months to years following surgery. In a retrospective

study of late-onset bleb-related endophthalmitis, infection developed suddenly an average of two years

postoperatively (range one month to eight years) [39].

The incidence of endophthalmitis after bleb surgery in various studies depends on the duration of follow-up and

ranges from 0.06 to 13.2 percent [2,40,41]. One study used a Kaplan-Meier method to calculate incidence following

bleb surgery, based on retrospective data on 239 eyes in 198 patients. The probability of developing endophthalmitis

was 1.3 percent per patient-year, with a five-year probability of 7.5 percent [42].

Patients with bleb-related endophthalmitis present with sudden onset of eye pain and decreased vision. The eye is

often red with purulence over the bleb, although bleb-related endophthalmitis may occur without any signs of blebitis.

The clinical diagnosis of endophthalmitis is confirmed by vitreous cultures, although vitreous cultures were negative in

45 percent of cases in one study [43]. Cultures of the infected bleb should also be obtained. Most studies of late-onset

endophthalmitis report that 50 percent of culture-positive cases are due to streptococci (viridans streptococci or S.

pneumoniae). Haemophilus influenzae and Moraxella catarrhalis are other major pathogens [43,44]. In contrast, one

study found that streptococci caused only about 20 percent of cases, whereas S. aureus and Staphylococcus

epidermidis caused approximately 30 percent each [39]. Cases of late-onset endophthalmitis due to Enterococcus

faecalis or gram-negative bacilli other than H. influenzae or M. catarrhalis (eg, Serratia) have been reported [43],

although these cases are unusual. Early onset bleb-related endophthalmitis, developing within four to six weeks of

surgery, is uncommon, and all four culture-positive cases were caused by S. epidermidis in one study [43].

The outcome of bleb-related endophthalmitis is typically poor, with only 13 percent of 32 patients in one study

achieving 20/40 or better visual acuity [44]. Almost one-half of patients in this study were left with minimal

vision (5/200 or worse), including 10 patients (31 percent) who lost all vision in the infected eye.

No prospective study has determined optimal therapy. Although the Endophthalmitis Vitrectomy Study (EVS) is often

cited for treatment approaches to all types of endophthalmitis, this study was of postcataract endophthalmitis only. In

addition, there were design flaws in the study and results should be interpreted with caution even for postcataract

endophthalmitis. (See 'Treatment' above.)

For treatment of bleb-related endophthalmitis, the author recommends a three-pronged approach:

●Vitrectomy, rather than vitreous aspirate, based on the likelihood that infection will be caused by bacteria (eg,

streptococci) known to cause fulminant infections in the eye.

●Intravitreal vancomycin (1 mg) plus either ceftazidime (2.25 mg) or amikacin (0.4 mg). Intravitreal antibiotics

may be repeated after 48 hours if marked vitreous inflammation persists, although repeat injections of

aminoglycosides should be avoided due to concern for toxicity (macular infarction). Injection of corticosteroids

may also be considered in cases with marked vitritis, although the possible benefit is uncertain.

●The role of adjunctive systemic antibiotics in exogenous endophthalmitis is unknown (see 'Approach to

therapy' above). In bleb-related endophthalmitis, however, most patients have severe infection and we

recommend adding oral moxifloxacin 400 mg daily for 7 to 10 days. The value of adjunctive intravenous (IV)

antibiotics has not been evaluated and ophthalmologists rarely use them, but IV antibiotics should be considered

for fulminant cases.

POSTTRAUMATIC ENDOPHTHALMITIS — Endophthalmitis occurs after penetrating trauma to the globe of the eye

in 3 to 10 percent of cases [45,46]. Endophthalmitis is much more likely to occur after lacerating injury with a metal

object than after injury from glass or blunt trauma. The risk of endophthalmitis is also increased by the presence of

retained intraocular foreign bodies, delay in repair of more than 24 hours [47], and disruption of the lens [47-49].

Bacillus cereus is one of the major pathogens in most studies and causes a fulminant endophthalmitis [50]. B.

cereus endophthalmitis is characterized by abrupt onset of symptoms 12 to 24 hours after eye injury, and a ring

corneal infiltrate. Most eyes lose all vision even with prompt treatment. Other causes of posttraumatic endophthalmitis

include coagulase-negative staphylococci, streptococci, and gram-negative bacilli such

as Klebsiella and Pseudomonas and molds [51,52].

Because of the fulminant nature of posttraumatic endophthalmitis, we advocate the same aggressive treatment as

described above for bleb-related endophthalmitis. To prevent endophthalmitis after open globe (penetrating) eye

trauma, we recommend two days of systemic prophylactic antibiotics (eg, intravenous vancomycin plus either

intravenous ceftazidime or oral ciprofloxacin) after the penetrating eye injury. A review of 558 cases of open globe

injuries revealed a very low rate (0.9 percent) of endophthalmitis following a protocol that included two days of

prophylactic systemic antibiotics [53].

Molds may cause posttraumatic endophthalmitis, although this is rare in temperate climates. The presentation of mold

endophthalmitis is usually subacute. (See"Epidemiology, clinical manifestations, and diagnosis of fungal

endophthalmitis", section on 'Clinical manifestations'.)

ENDOGENOUS BACTERIAL ENDOPHTHALMITIS — Endogenous bacterial endophthalmitis is rare in the United

States and results from bacterial seeding of the eye during bacteremia. A retrospective review of a 10-year period at a

large acute care hospital and an adjoining eye specialty hospital identified only 28 cases [54].

Sources of bacteremia include endocarditis, urinary tract infections, abdominal abscesses (including liver), meningitis,

indwelling catheters, procedures such as endoscopy that cause transient bacteremia, and illicit injection drug use. In

the United States, endocarditis is a major cause of endogenous endophthalmitis, causing 40 percent of cases in one

series [54]. However, in Taiwan, Singapore, and other East Asian nations, Klebsiella pneumoniae is the major cause

of endophthalmitis associated with liver abscess, accounting for up to 60 percent of cases [55]. (See "Clinical features,

diagnosis, and treatment of Klebsiella pneumoniae infection", section on 'Endophthalmitis'.)

Patients with endogenous bacterial endophthalmitis may present with symptoms of their bacteremia or may only

complain of eye pain and decreased vision. Half of patients in one series reported no systemic symptoms and over

half saw an ophthalmologist first [54]. In another series, fewer than 20 percent of patients had fever on presentation,

and 40 percent had an unremarkable general physical examination [56]. Patients who do not have systemic symptoms

may initially be misdiagnosed as having noninfectious uveitis. Endophthalmitis should be considered in any patient

complaining of decreased vision or eye pain in the setting of possible bacteremia or injection drug use.

The diagnosis of endogenous endophthalmitis is established by clinical findings consistent with endophthalmitis (eg,

vitritis, hypopyon) in the setting of positive blood cultures or by positive vitreous or aqueous cultures in patients

presenting with endophthalmitis but who do not have a history of recent eye trauma or surgery. Blood cultures are

positive in 75 percent of those tested, as are vitreous cultures [54].

The microbiology of endogenous endophthalmitis varies with the patient population. In North America and Europe,

streptococci (S. pneumoniae, S. milleri group, group A, group B) cause 30 to 50 percent of cases, S. aureus causes

25 percent, and gram-negative bacilli cause 30 percent [54,56]. In Asia, gram-negative bacilli, especiallyKlebsiella,

cause the majority of cases of endogenous endophthalmitis [55,57].

The treatment of endogenous endophthalmitis includes intravitreal and systemic antibiotics. The duration of systemic

antibiotics should be determined by the need to treat the underlying source of bacteremia (eg, six weeks in many

cases of endocarditis). Systemic antibiotics alone will not effectively treat endophthalmitis, however, and all patients

with endogenous endophthalmitis require intravitreal antibiotic injection. Vitrectomy plus intravitreal antibiotic injection

is indicated in most cases, rather than intravitreal antibiotic injection alone, because of the virulent nature of most of

the pathogens involved. Vitrectomy debrides the vitreous and leads to better visual outcome in severe cases of

endophthalmitis. If the eye worsens over the next 24 to 48 hours, a second intravitreal antibiotic injection should be

given. A third injection may also be given if there is still no improvement after a similar time interval or if cultures from

the second vitreous sample were positive. The basis for this approach is discussed above. (See 'Intravitreal

antibiotics' above and 'Approach to therapy' above.)

FUNGAL ENDOPHTHALMITIS — Fungal endophthalmitis due to yeasts (eg, Candida albicans) is very different from

that due to molds (eg, Aspergillus or Fusarium). While Candida endophthalmitis is usually treated successfully, mold

endophthalmitis often results in the loss of vision. Fungal endophthalmitis is discussed separately.

(See "Epidemiology, clinical manifestations, and diagnosis of fungal endophthalmitis" and "Treatment of endogenous

endophthalmitis due to Candida species" and"Treatment of exogenous endophthalmitis due to Candida

species" and "Treatment of endophthalmitis due to molds".)

SUMMARY AND RECOMMENDATIONS

●Endophthalmitis refers to bacterial or fungal infection within the eye, including involvement of the

vitreous and/or aqueous humors. Most cases of endophthalmitis are exogenous, resulting from inoculation of

organisms from the outside, via trauma, eye surgery, or as an extension of keratitis (corneal infection). In such

cases, the aqueous humor may be seeded first before extension into the vitreous. The remaining cases are

endogenous, resulting from bacteremic or fungemic seeding of the eye. In endogenous endophthalmitis,

organisms usually seed the highly vascular choroid first then extend anteriorly into the vitreous.

(See 'Introduction' above.)

●Most cases of endophthalmitis are due to bacteria and present acutely. Acute bacterial endophthalmitis is a

vision-threatening condition and must be managed as an emergency. The clinical outcome depends both upon

the virulence of the infecting organism and the speed with which appropriate therapy is initiated.

(See'Introduction' above.)

●Bacterial endophthalmitis can be divided into five categories:

•Acute postcataract surgery

•Chronic pseudophakic

•Postinjection (eg, after intravitreal injection of anti-vascular endothelial growth factor [VEGF] medications)

•Bleb related

•Posttraumatic

•Endogenous (see 'Introduction' above)

Acute postcataract endophthalmitis

●Acute postcataract endophthalmitis is the most common form of endophthalmitis and, in the United States, is

almost always due to bacteria. Approximately 95 percent of cases are caused by gram-positive bacteria,

particularly coagulase-negative staphylococci (70 percent). (See 'Diagnosis' above and 'Bacteriology' above.)

●The most important component of treatment is direct injection of antibiotics into the vitreous. For severe cases,

immediate vitrectomy (followed by intravitreal injection of antibiotics) is also essential. Specific recommendations

are reviewed above. (See 'Approach to therapy' above.)

Chronic pseudophakic endophthalmitis

●Chronic pseudophakic-related endophthalmitis is a rare complication of cataract surgery; "pseudophakic" refers

to the intraocular lens. Chronic pseudophakic endophthalmitis is usually caused by Propionibacterium acnes.

Treatment requires at least vitrectomy and intravitreal vancomycin, although 50 percent of cases recur with this

treatment alone. Removal of the residual lens capsule and exchange or removal of the intraocular lens may also

be necessary for cure. Systemic antibiotics are not indicated. (See 'Chronic pseudophakic

endophthalmitis' above.)

Post-intravitreal injection endophthalmitis

●Endophthalmitis may occur after an intravitreal injection of medications to treat "wet" age-related macular

degeneration. The incidence is approximately 0.1 percent per injection; since injections are typically given

monthly for many months, the cumulative risk is substantial. The bacteriology is similar to postcataract

endophthalmitis except that the incidence of viridans streptococci is higher. This may be due to the fact that

these injections are performed in the office setting and masks are not usually worn. Having patient and physician

(and anyone in the room) either wear masks or completely refrain from talking before and during the procedure

may decrease ocular surface contamination with oral flora bacteria, such as viridans streptococci. This in turn

may decrease the rate of postinjection endophthalmitis.

Bleb-related endophthalmitis

●A filtering bleb is a surgically created defect in the sclera that is used to treat severe glaucoma that has failed

medical management. Bleb-related endophthalmitis can be caused by a range of gram-positive and gram-

negative bacteria, but streptococci, Haemophilus influenzae, and Moraxella catarrhalis are major pathogens. For

treatment, we recommend a three-pronged approach that includes vitrectomy, intravitreal vancomycin plus

either ceftazidime or amikacin, and a systemic antibiotic that achieves good intravitreal concentrations and treats

the most likely pathogens (eg, oral moxifloxacin). (See 'Bleb-related endophthalmitis' above.)

Posttraumatic endophthalmitis

●Posttraumatic endophthalmitis occurs after penetrating trauma to the globe of the eye in 3 to 10 percent of

cases. Bacillus cereus is one of the major pathogens in most studies and causes a fulminant endophthalmitis.

Because of the fulminant nature of posttraumatic endophthalmitis, we recommend immediate vitrectomy,

intravitreal vancomycin plus either ceftazidime or amikacin, and a systemic antibiotic that achieves good

intravitreal concentrations. For initial empiric treatment, the systemic antibiotic chosen should cover B. cereus.

To prevent endophthalmitis after eye trauma, we recommend initial systemic prophylactic antibiotics (eg,

intravenous vancomycin plus either intravenous ceftazidime or oral ciprofloxacin for 48 hours).

(See 'Posttraumatic endophthalmitis' above.)

Endogenous endophthalmitis

●Endogenous bacterial endophthalmitis is rare in the United States and results from bacterial seeding of the eye

during bacteremia. In North America and Europe, streptococci (Streptococcus pneumoniae, S. milleri group,

group A, group B) cause 30 to 50 percent of cases, Staphylococcus aureus causes 25 percent, and gram-

negative bacilli cause 30 percent. In Asia, gram-negative bacilli (especially Klebsiella) cause the majority of

cases. (See 'Endogenous bacterial endophthalmitis' above.)

●The treatment of endogenous endophthalmitis includes intravitreal and systemic antibiotics. Systemic

antibiotics alone will not effectively treat endophthalmitis, however, and all patients with endogenous

endophthalmitis require intravitreal antibiotic injection. Vitrectomy plus intravitreal antibiotic injection is indicated

in most cases, rather than intravitreal antibiotic injection alone, because of the virulent nature of most of the

pathogens involved. (See 'Endogenous bacterial endophthalmitis'above.)

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Eye anatomy in cross section

Hypopyon in endophthalmitis

A postoperative eye showing endophthalmitis with conjunctival injection and a hypopyon, the layering

of white blood cells in the anterior chamber. Reproduced with permission from the department of

Ophthalmology and Vision Science, University of Toronto. Graphic 59911 Version 4.0

Vitreous aspirate and vitrectomy

Blebitis

The patient is a 32-year-old man with glaucoma who suffered minor trauma to the eye two days prior. He

now complains of pain, redness, and discharge from the eye