PRINCIPLES OF THERAPY

In modern endophthalmitis therapy, intravitreal antimicrobial

injections are the mainstay of treatment.64 Pars plana vitrectomy
has an important role in management of several clinical
presentations and stages of the disease. Subconjunctival antibiotic
injection and topical antibiotic injection were previously considered
major routes for antibiotic administration, but now has a less
important role.65 Corticosteroid therapy is important in improving
the final outcome, but there is debate over the proper routes of
administration.

ANTIMICROBIAL THERAPY

Choice of Antimicrobial Agent

Because endophthalmitis therapy must be initiated emergently, the

identity of the organism is unlikely to be known at the time
antimicrobial agents must be chosen. The vast majority of
endophthalmitis infections are gram-positive in origin. 2,66,67 As
noted, the clinical setting often determines which organisms are
more likely to be present. Because it is almost impossible initially
to rule out gram-negative organisms as the cause of most
infections on clinical examination, broad-spectrum antibiotic
coverage usually is chosen.38 In practice, this usually means
empiric treatment with two separate antimicrobial agents as the
initial choice.

Desirable characteristics for antimicrobial agents for treatment of

bacterial endophthalmitis include the following:68

1. Broad spectrum of coverage. Gram-positive organisms

including methicillin-resistant staphylococci and Bacillus as
well as gram-negative organisms must be covered.
2. Bactericidal properties. A bactericidal drug is preferable
because the eye is an immune-privileged site.
3. Excellent therapeutic ratio (activity/toxicity) after
intravitreal injection. The therapeutic window is the dose
range between the lowest potentially efficacious dose and
the upper limits established by tissue toxicity in the host. In
evaluation of drugs for intraocular injection, the usual
parameters studied for indications of toxicity are
electroretinographic testing, histologic sectioning, and
electron microscopic studies. Toxicity may be increased by
repeated injections of certain antibiotics, a phenomenon
that has not been extensively studied at this time.69–71
4. Excellent therapeutic ratio after systemic administration.
Medications administered orally or parenterally typically
have poor penetration from the bloodstream into the
eye.68,72,73 There are several blood–eye barriers that reduce
the ability of the antimicrobial to achieve access to
intraocular structures. The concentration of antimicrobial in
 the aqueous humor is typically higher than that in the
vitreous cavity. Intravitreal antimicrobial levels do not reach
or exceed the minimum inhibitory concentration (MIC) in
the vitreous cavity for many of the target organisms after
systemic administration. Lipid-soluble compounds penetrate
into the eye better than the hydrophilic antibiotics such as
aminoglycosides. . Inflammation may break down blood–
eye barriers allowing increased penetration.68,74–76
Aminoglycosides and amphotericin have significant systemic
toxicity, limiting their effectiveness.77 Combinations of
antibiotics such as vancomycin and aminoglycosides may
improve coverage, but have additive toxicities.
5. Pharmacodynamics. The most favorable pharmacokinetic
parameters are for a drug to access the eye readily from
the bloodstream but to be retained within the eye for long
periods of time after intraocular injection. This combination
of characteristics is rarely, if ever, seen.

The highest possible initial dose is chosen whenever possible so

that the drug remains above the MIC for the longest period of
time. Drugs with longer half-lives are also preferred because the
effective dose of drug is thought to be eliminated from the drug by
the expiration of five half-lives. The upper limit of drug
concentration is defined by the toxicity, usually in the form of
retinal deterioration. If other characteristics are equivalent, then
choice of the drug exceeding the MIC by the greatest degree is
preferable. Some authors have suggested that concentrations of
10 to 30 times the MIC are necessary to effectively treat infections
elsewhere in the body.

Intraocular Injections

The standard of care for most cases of endophthalmitis is

intraocular injection of antimicrobial agents. Antibiotics injected
into the vitreous cavity are eliminated from the eye by either an
anterior or posterior route. β-Lactam antimicrobials were removed
posteriorly, whereas the aminoglycosides exit through the anterior
(trabecular meshwork) route.78,79 The removal of the vitreous
shortens the half-life of antimicrobials, whereas lens removal also
can shorten the half-life of those using an anterior route of
elimination. Inflammation breaks down blood–retinal barriers and
also decreases the half-life of anteriorly eliminated drugs.80–83

Although some controversy exists, there is a short half-life of most

injected antimicrobials, so that effective duration of action of many
antibiotics may be somewhere between 36 and 72 hours. Toxicity
has been demonstrated in the form of retinal vascular shutdown by
intravitreal aminoglycosides84–87 and retinal necrosis in the case of
other antibiotics.70,71 Combinations of antimicrobials such as
vancomycin and amikacin may increase their toxicities.70,71 The
antimicrobials usually chosen for intraocular injections at this time
are the following agents:

1. Vancomycin. Vancomycin is considered the antibiotic of

choice for gram-positive coverage. One study of 246 gram-
positive endophthalmitis isolates demonstrated all to be
susceptible to vancomycin.88 Vancomycin inhibits cell wall
assembly and RNA synthesis, and damages protoplasts. The
spectrum of coverage is entirely gram-positive but includes
all the staphylococcal species, streptococci, P. acnes, and
Bacillus organisms. Although some vitreous sampling after
intraocular injections in human infected eyes has
demonstrated persistent therapeutic levels for 3 to 4 days
after initial injection,89–91 in animal studies the half-life
suggests that therapeutic concentrations should be
maintained for only about 48 hours after intravitreal
injection.80,92
2. Cephalosporins. Cephalosporins are synthetic penicillins that
damage bacterial cell walls. Both cefazolin and ceftazidime
have been extensively studied for intraocular injection and
seem relatively safe when 2.25 mg are injected
intravitreally.93 First-generation cephalosporins are weak
against enterococcus and methicillin-resistant
staphylococcal organisms. Ceftazidime is a third-generation
agent often used for enhanced gram-negative coverage.
One study of 37 gram-negative isolates from cases of
endophthalmitis found 80% to be susceptible to
ceftazidime.88 As with vancomycin, the effective dosage
lasts only 2 to 3 days after injection.68
3. Aminoglycosides. Aminoglycosides have been popular with
ophthalmologists for treatment because of their gram-
positive and -negative coverage. They inhibit protein
synthesis but after intraocular injection may produce retinal
vascular infarction. This complication has been noted both
with gentamicin and amikacin.22,84–87 The half-life of
amikacin in inflamed vitrectomized eyes is approximately 8
hours.82 Because toxicity limits total injected dose, the
concentration of antimicrobials remains above the MIC for
only 24 to 36 hours after intraocular injection.
4. Antifungal Agents. Until recently amphotericin was
considered the gold standard for treatment of intraocular
fungal infection by intraocular injection. The usual
recommended dose is 5 μg/mL. The half-life is long,
reportedly as much as 9 days. However, the half-life is
decreased by inflammation and vitreous removal.81

Systemic Antimicrobials

Systemic antimicrobials were once considered crucial for the

treatment of endophthalmitis, but now their efficacy is debated.
Because inflammation breaks down the blood–eye barriers, greater
penetration into inflamed eyes occurs after systemic
administration.68,72,74–76 Vitrectomy enhances the penetration of
some medications (cefazolin,75 vancomycin,76 and ceftazidime68,74)
into the eye. Repeat intravenous dosing likewise contributes to
progressive increase in intraocular concentrations.68,72,74–76

Antimicrobials may be administered either orally or intravenously.

Although studies have demonstrated response in staphylococcus
endophthalmitis and other more virulent organisms to intravenous
antibiotics only,94 the EVS did not demonstrate any improvement in
visual outcome in patients given intravenous therapy along with
intraocular therapy as compared to patients given intraocular
therapy only.2 However, in that study the intravenous antibiotic
given for gram-positive coverage was amikacin, which has very
poor penetration into the vitreous cavity after intravenous injection
and would not be expected to provide a significant effect.73 Newer
data indicates that fluoroquinolones, particularly fourth-generation
agents, may have improved intraocular penetration due to their
ability to cross the blood–eye barriers.95,96 Most antimicrobials are
more likely to be able to achieve intravitreal levels if the eye is
inflamed because of a breakdown of the blood–ocular barrier.
Specific antimicrobials often considered for systemic therapy
include vancomycin, fluoroquinolones, and cephalosporins.

1. Vancomycin. Vancomycin is a large molecule must be an

administered intravenously. After a single intravenous dose
variable but small intraocular concentrations have been
found in noninflamed human eyes. In inflamed eyes after
repeated dosing in animal models, there is modest
penetration in the vitreous cavity sufficient to be above the
MIC for target organisms.76 High intravenous doses run the
risk of systemic toxicity that may be additive with
intravenous aminoglycosides.
2. Cephalosporins. Penetration of cefazolin into inflamed
vitrectomized eyes can be achieved after repeated
intravenous doses. Levels above MICs for gram-positive
pathogens for endophthalmitis have been demonstrated. 75
Ceftazidime has an even greater penetration particularly
into inflamed eyes.74,75 It has better Pseudomonas coverage
than cefazolin does, but it is not as good as for some gram-
positive organisms.
3. Quinolones. The fourth-generation quinolones have been
recently suggested for their potential effectiveness to
prevent and treat endophthalmitis. Fluoroquinolones have
both gram-positive and gram-negative coverage. Inhibition
of DNA synthesis is their usual mode of action. Ciprofloxacin
was initially promoted for its penetration into the eye after
oral administration but a number of ocular pathogens have
developed resistance to it.97–99 The fourth-generation
quinolones, gatifloxacin, and moxifloxacin, have good levels
of penetration and require two alterations to their genetic
 mechanism in order to produce resistance. Because of this
mechanism, it is hoped that resistance will prove to be a
less important issue. Penetration of gatifloxacin in
noninflamed eyes undergoing vitreous surgery
demonstrated that two doses of oral medication delivered
12 hours apart produced significant intraocular
concentrations as a percentage of serum levels. The
vitreous ratio to serum concentration was 26.17% and the
ratio of aqueous concentration to vitreous was 21.01%. For
most of the pathogens producing intraocular disease, the
levels achieved were above the MIC 90.96,100 Initial studies
suggest that the fourth-generation quinolones cover the
bacterial resistance that developed to the second- and
third-generation agents. Moxifloxacin may be the most
potent fluoroquinolone for gram-positive bacteria, whereas
moxifloxacin and gatifloxacin may be equivalent for gram-
negative organisms.101
4. Antifungal Agents. Amphotericin B has been the time-
honored medication for intravenous administration for
antifungal therapy. Recent reports have demonstrated good
results for vitrectomy and fluconazole.102 Recent studies of
voriconazole have demonstrated intraocular penetration
sufficient to suggest possible efficacy.103

Subconjunctival Injections

Frequent subconjunctival injections were previously advocated as a

mainstay of therapy, but the entry of antimicrobials into the eye
after subconjunctival injection is marginal.104–108 Vitreous levels of
antimicrobial after subconjunctival injection rarely reached
therapeutic levels and are essentially insignificant by comparison
to the concentration produced by intravitreal injections.
Subconjunctival injections may release antimicrobial onto the
surface of the eye and therefore may be useful for any external
aspect of the infection such as bleb infection or wound infection.

Topical Antimicrobials

Topical antimicrobials have the same limitations as do

subconjunctival injections. Attempts are made to overcome this
problem by producing highly concentrated formulations and
administering the drops frequently during the day. Some authors
recommend topical vancomycin (25 mg/mL), aminoglycosides (9 to
14 mg/mL) or ceftazidime (50 mg/mL). Like subconjunctival
injections, these may have some benefit for external aspects of the
infection but the amount of drug delivered to the vitreous cavity is
marginal

SURGICAL PROCEDURES

Two basic procedures are used for initial treatment of

endophthalmitis: a) vitreous tap with injection of intraocular
antibiotics, and b) pars plana vitrectomy.

Tap and Inject

A vitreous tap is usually done through the pars plana because most
cases of endophthalmitis occur in eyes that have a posterior
chamber intraocular lens (PCIOL) in position or that are phakic.
The anterior chamber may be tapped to obtain aqueous culture, or
may be the entrance site for a tap to sample the vitreous cavity in
an aphakic eye. To tap the anterior chamber, topical anesthesia is
usually employed. The eye may be stabilized with a Q-tip or
forceps in one hand and entered with a 30-gauge needle at the
limbus with the operative hand. A tuberculin syringe often is used
for convenience, and as much as 0.2 cc of fluid may be withdrawn.
If there is significant fibrin in the anterior chamber, the small-bore
needle may not be sufficient to achieve a good sample, and an
entry must be made with a 25- or 27-gauge needle. A small
puncture incision with a blade may facilitate use of the larger
gauge needles.

Tap of the vitreous cavity usually is made through the pars plana
3.5 to 4 mm posterior to the limbus. Depending on the amount of
inflammation and the pain tolerance, this may be done with a
conjunctival injection or retrobulbar injection. A topical anesthetic
of choice may be placed in the eye and supplemented if desired
with a pledget of lidocaine placed over the area for injection for a
few moments. A bleb may be raised with subconjunctival lidocaine
2% in the area if the topical anesthesia does not seem to produce
sufficient analgesia. In the case of very inflamed eyes, this may
not be sufficient, and retrobulbar or peribulbar injection of
lidocaine 2% to 4% may be chosen.

Topical povidone iodine 5% is instilled in the conjunctival sac for 1

to 2 minutes prior to the injection. A lid spectrum usually is helpful
to prevent blinking. The eye then is stabilized with forceps or a Q-
tip and a position 3.5 mm posterior to the limbus is identified. A
22- to 27-gauge needle may be used for the initial penetration and
inserted with a slight screwing motion. Once in the eye, it should
be advanced far enough to be clear of the vitreous base and then
suction should be applied. If the medium is clear enough, it is best
to visualize the position of the needle in the vitreous cavity before
suctioning. Suction without clear visualization is dangerous and
should be avoided if possible. The goal should be to obtain 0.2 to
0.3 cc of fluid for gram stain, culture, and sensitivity. Needles as
large as 20 to 22 gauge sometimes are necessary because of the
viscous nature of an inflamed vitreous. The tap should be aborted
if liquid vitreous is not obtained. A single port vitrectomy then may
be used to obtain material for analysis. Once the needle is
withdrawn, pressure is placed over the sclerotomy site with a
cotton tip. Material is submitted immediately to the laboratory.
After the tap has been done, injection is performed often through
the same incision site if possible. Typically, 0.1 cc of each of two
antimicrobials is injected into the vitreous cavity. The usual
antibiotic injections are vancomycin 1 mg in 0.1 cc and either
amikacin 200 γg in 0.1 cc or ceftazidime 2.25 mg in 0.1 cc.

Pars Plana Vitrectomy

Pars plana vitrectomy was adopted early for treatment of

intraocular infection shortly after its introduction and acceptance as
a surgical procedure.109,110 Pars plana vitrectomy allows application
of the principles of incision and drainage of an abscess. This
intervention allows for the removal of the infected organisms,
removal of opacified vitreous and debris, and potentially reduction
of toxins.

Pars plana vitrectomy for infection is performed under local or

general anesthesia, although it may be somewhat difficult to
achieve adequate local anesthesia in a very inflamed eye. Standard
conjunctival cutdowns are performed and an infusion port placed
into the inferotemporal sclera 3.5 mm posterior to the limbus. It is
important to visualize the port inside before turning on infusion.

The anterior chamber may be quite opaque. In these cases pars

plana infusion is put in position but not turned on. Another infusion
is carried through the limbus and the vitrectomy cutting probe
introduced into the anterior chamber to clear debris. It is often
necessary to strip away fibrin membrane from the surface of the
iris and intraocular lens. In some instances iris retractors may be
beneficial if the pupil will not dilate properly. Material obtained
from the anterior chamber is submitted for culture and sensitivity.

Once the vitreous cavity may be examined, the infusion is

identified and turned on so that a light source and cutting probe
may be introduced into the posterior segment. Before turning on
the posterior infusion the vitrectomy probe is hooked up to a small
syringe and an undiluted sample is taken, cutting the opaque
vitreous and sucking the material into the syringe: 0.5 to 1 cc may
be safely removed in this manner and submitted for culture and
stains.

Vitrectomy is carried further into the vitreous cavity using

simultaneous fluid infusion. Once the central cavity is clear, whitish
material on the surface of the retina may be noted. It is important
to be careful not to apply traction either with suction or direct
pulling on areas of necrotic retina. Sometimes white material
represents white cells layered on the surface of the retina which
can be vacuumed free. White material trapped in membrane often
clears within the first few days without being stripped away if the
infection has been adequately treated. In cases of
Propionibacterium acnes there may be small plaque of white
material sequestered in the capsule that is thought to be the nidus
of infection. It is then necessary to remove this plaque in most
eyes in order to cure the infection. Removal of the entire lens
capsule and even removal of the lens and/or IOL exchange is
sometimes necessary to effect a cure in these cases.42–44,111

One sclerotomy is closed and then a stitch put into the second
sclerotomy. Intraocular antibiotics are injected into the eye
through the second sclerotomy before closure.

INDICATIONS.

There are a variety of indications for pars plana vitrectomy in the

treatment of endophthalmitis. The EVS demonstrated that in eyes
with light perception there is a 33% chance of achieving 20/40
vision at the initial intervention with vitrectomy and intraocular
antibiotic injection versus only 11% likelihood if the initial
intervention was a vitreous tap and injection only. For eyes with
hand motion or better vision, there was no difference in visual
outcome between these two initial strategies.2 Subsequent analysis
of the data demonstrated that eyes of patients with diabetes
mellitus had a tendency to fare better with a vitrectomy as an
initial intervention, but the trend did not reach statistical
significance.112 This study was an analysis of a factor identified
retrospectively which was not part of the randomization scheme.

Vitrectomy also may be elected for eyes with acute infections not
responding to the initial strategy of tap and inject. 113 In the EVS,
over 10% of eyes were subjected to additional surgery within a
week of the initial therapeutic intervention. Early secondary
interventions were undertaken in 8% of eyes undergoing initial
vitrectomy and in 14% of eyes treated with tap and inject.
Surgeons should consider a vitrectomy in eyes that do not respond
to initial therapeutic intervention, because it is clear from
laboratory113–117 and clinical studies113,118,119 that a single injection of
antimicrobials does not cure all endophthalmitis. Furthermore, in
animal studies the strategy of initial vitrectomy is more effective in
sterilizing the vitreous cavity as an initial strategy than is an
injection of antibiotics alone.114,115 In the EVS cultures obtained in
33 eyes operated for worsening inflammation were positive 42% of
the time. Eyes initially treated with vitrectomy were positive in
only 13% of the cases, whereas eyes treated with tap and inject
initially were positive 71% of the time.113

In eyes that have apparent cure of the infection some vitreous

opacities may persist for several months interfering with the
patient's ability to see. Only a few of these eyes eventually require
a vitrectomy to clear the media.113
Vitrectomy and intraocular antibiotic injection may be elected as
initial intervention in other circumstances when vision is better
than light perception. In cases with severe bleb infections, for
example, the incidence of virulent organisms is high and the onset
may be rapid. In such instances the suspicion of rapid progression
of a more severe infection may tip the balance toward vitrectomy
as an initial intervention. Vitrectomy also may be elected in
situations where there is an indication for vitreous surgery in
addition to the infection. These might include infection associated
with retained intraocular foreign body or retained lens material.

Chronic indolent cases of endophthalmitis have been demonstrated

to respond better to vitrectomy than initial antibiotic injection. This
is particularly true for Propionibacterium acnes infections that have
a very low rate of cure with injection of antibiotic injection only. 42–
44,111
Fungal cases also may require vitrectomy with an intraocular
injection of amphotericin B.120

COMPLICATIONS.

In most instances, an eye treated with vitrectomy shows as much

or more inflammation the following day than it did at presentation
because of the addition of surgical trauma. Aggressive anti-
inflammatory therapy is often indicated. In the immediate
postoperative period, the cornea is often edematous if the
inflammation has been severe. Persistent epithelial defects occur in
some patients and sometimes require management with a bandage
contact lens.

Intraocular pressure may be elevated in the postoperative period

usually responding to medical management. If there has been
severe inflammation, hypotony may occur, associated with
persistent inflammation, and lead to a downhill course. A leaking
wound site may be suspected, but in general the cause of this
complication is ciliary body shutdown.

In eyes that are phakic at the time of infection and therapy,

cataract often develops in the postoperative period. Usually time is
allowed to pass for the inflammation to clear before cataract
surgery is undertaken. If there is apparent vitreous opacity on
clinical examination or ultrasound, pars plana lensectomy
combined with vitrectomy may be elected.

The most feared complication of endophthalmitis with or without

vitrectomy is retinal detachment. In the EVS, retinal detachment
occurred in 8.3% of the eyes; there was no significant difference in
incidence between eyes treated with initial vitrectomy and those
treated with tap and inject as the first intervention. 121 Retinal
detachment may occur because of breakdown of necrotic retina or
because of traction on the vitreous or vitreous base during
vitrectomy or vitreous tap. Detachments are a major cause of
failure in many series,122 but in the EVS series, 78% of cases were
successfully repaired. There was a correlation of retinal
detachment and poor visual outcome.121

In eyes of the retinal detachment, proliferative retinopathy is a

significant complication. Sympathetic ophthalmia has been reported.
Endophthalmitis is defined by marked inflammation of intraocular
fluids and tissues. When caused by microbial organisms,
endophthalmitis often results in severe visual loss.1,2 In this
chapter, the etiologic categories, management, and prevention
issues for infectious endophthalmitis are reviewed.
Back to Top
CLASSIFICATION
Infectious endophthalmitis is classified by the events leading to the
infection and by the timing of the clinical diagnosis. 1,2 The broad
categories include postoperative endophthalmitis (acute-onset,
chronic or delayed-onset, conjunctival filtering-bleb associated),
posttraumatic endophthalmitis, and endogenous endophthalmitis.
Miscellaneous categories include cases associated with microbial
keratitis,3 intravitreal injections,4 or suture removal.5 These
categories are important in predicting the most frequent causative
organisms and in guiding therapeutic decisions before
microbiologic confirmation of the clinical diagnosis (Table 1).

TABLE 1. Classification of Endophthalmitis (Most Frequent

Organisms In Various Clinical Settings)

1. Postoperative.
a. Acute-onset postoperative endophthalmitis:
Coagulase-negative staphylococci, Staphylococcus
aureus, streptococcus species, gram-negative
bacteria.
b. Delayed-onset (chronic) pseudophakic
endophthalmitis (>6 weeks postoperative):
Propionibacterium acnes, coagulase-negative
staphylococci, fungi.
c. Conjunctival filtering bleb-associated
endophthalmitis: Streptococcus species, Hemophilus
influenza, Staphylococcus species
2. Posttraumatic (open globe): Bacillus species, staphylococci.
3. Endogenous: Candida species, S. aureus, gram-negative
bacteria.
4. Miscellaneous.
a. Keratitis: Staphylococcus and pseudomonas species
b. Intravitreal injection (intravitreal triamcinolone,
intravitreal ganciclovir, pneumatic retinopexy, etc):
Coagulase negative staphylococci
 c. Suture removal: both bacteria and fungi

Back to Top
INCIDENCE
Postoperative endophthalmitis is the most frequent category,
accounting for more than 70% of cases. In a nosocomial survey
(1995–2001) of 35,916 intraocular surgical procedures performed
at a university-based hospital, acute-onset endophthalmitis
occurred in 17 cases (0.05%).6 In this survey, the incidence of
acute-onset endophthalmitis (≤6 weeks of surgery) after cataract
surgery was 0.04% and did not appear to be increased by a clear
corneal approach to cataract surgery. Also in this survey, the rates
of endophthalmitis were highest after secondary intraocular lens
implantation (1 of 485 cases; 0.2%) and glaucoma surgery (4 of
1,970 cases; 0.2%), and lowest after pars plana vitrectomy (2 of
7,429 cases; 0.03%). There is an increased incidence of
endophthalmitis in patients with diabetes mellitus, which is
possibly explained by the relative immune compromise in these
patients.7 Endophthalmitis may also occur infrequently in the
setting of a conjunctival filtering bleb,8–11 suture removal,5 wound
dehiscence, or vitreous wick.12 Chronic or delayed-onset
endophthalmitis may be caused by less virulent bacteria (e.g.,
Propionibacterium acnes, Staphy1ococcus epidermidis) or by
fungi.13–16

In reported large clinical series,17–20 endophthalmitis after

penetrating ocular trauma represents approximately 25% of all
cases. In one large study of penetrating ocular trauma,
endophthalmitis occurred in 10.7% of cases with a retained
intraocular foreign body and 5.2% of cases without a retained
intraocular foreign body.20 The National Eye Trauma System
Registry reported an endophthalmitis incidence of 6.9% (34 of 492
cases) after penetrating ocular injuries with retained intraocular
foreign bodies.21 Metallic intraocular foreign bodies were as likely to
be associated with infectious endophthalmitis (7.2%) as
nonmetallic (7.3%) and organic matter (6.3%) foreign bodies.21
Rupture of the crystalline lens capsule is also a reported risk for
endophthalmitis in open globe injuries.22

Compared to the postoperative and posttrauma categories,

endogenous endophthalmitis occurs with less frequency and, when
it occurs, usually presents in debilitated or immunocompromised
patients or in patients with a history of intravenous drug abuse.23–27
In one large series, culture-proven fungal cases were more
frequent than bacterial cases.27

In the miscellaneous category, endophthalmitis after intravitreal

injections can be subdivided into infectious and noninfectious
categories. In a series of over 828 intravitreal triamcinolone
acetonide injections, there were no cases of infectious etiology, but
pseudohypopyon from migration of triamcinolone crystals into the
anterior chamber occurred in 7 patients in this report.28 Pooled
data from 14,866 intravitreal injections in 4382 eyes revealed 38
cases of endophthalmitis.29 Excluding cases reported specifically as
pseudoendophthalmitis (e.g., pseudohypopyon), the prevalence of
endophthalmitis was 0.2% per injection. 29 Noninfectious
endophthalmitis cases after intravitreal triamcinolone are noted in
several reports (Table 2). 30–34

TABLE 2. Noninfectious Endophthalmitis After Intravitreal

Triamcinolone Acetonide Injection for Macular Disease

Study (Date, # Identified/

Findings
Reference #) # Patients
3 out of 4 observed
Sutter et al 4/600* 1 out of 4 given vitreous tap and
(2003, 30) (0.6%) injection
Negative culture (vitreous)
Negative culture (vitreous)
Roth et al
7/104 (6.7%) 6 out of 7 given vitreous tap and
(2003, 31)
injection of intravitreal antibiotics
2 cases with Staphy1ococcus
Nelson et al epidermidis positive cultures treated
9/440 (1.6%)
(2003, 32) with vitreous tap and injection
7 out of 9 observed
Triamcinolone acetonide crystals
Jonas et al
1/454 (0.2%) seen in AC specimens
(2003, 33)
Negative culture (anterior chamber)
No cultures obtained
Moshfeghi et
No patients given intravitreal
al 7/828(0.8%)
antibiotics
(2004, 28)
No infectious endophthalmitis

* Approximation

 
Back to Top
DIAGNOSIS
The diagnostic features of infectious endophthalmitis can be
divided into two aspects: clinical recognition and microbiologic
confirmation. The clinical signs of endophthalmitis vary depending
on the preceding events or surgery, the infecting organism, the
associated inflammation, and the duration of the disease. In acute-
onset postoperative endophthalmitis, when bacteria are the
etiologic agents, the hallmark of the clinical diagnosis is marked
intraocular inflammation with hypopyon (Fig. 1).1,2 Other signs of
acute-onset postoperative bacterial endophthalmitis include fibrin
in the anterior chamber and on the intraocular lens, corneal
edema, marked conjunctival congestion, lid edema, and vitritis.
Retinal periphlebitis is another clinical sign that is diagnostically
helpful in eyes with relatively clear media. 35 Endophthalmitis
caused by fungal organisms generally has less inflammation, a
more indolent course, and less ocular pain. Endogenous candida
cases often manifest as isolated white infiltrates in the formed
vitreous overlying a focal area of chorioretinitis. 24,35

Fig. 1. Acute-onset endophthalmitis

following clear corneal cataract surgery.
The patient shows conjunctival
congestion, prominent fibrin in the pupil,
and hypopyon.

The clinical diagnosis of endophthalmitis is confirmed by obtaining

intraocular (aqueous and vitreous) specimens. A vitreous specimen
is much more likely to yield a positive culture result than a
simultaneously acquired aqueous specimen.36 The vitreous
specimen can be obtained either by needle biopsy or by using an
automated vitrectomy instrument. A needle biopsy, or limited
vitrectomy approach, can be performed in a treatment room, but a
three-port pars plana vitrectomy is usually performed in the
operating room. One report of 138 culture-proven endophthalmitis
cases showed a positive culture result in 34.8% of anterior
chamber specimens, 58.2% of vitreous specimens, and 80% of
vitrectomy fluid specimens.36

The technique for culturing intraocular specimens depends on the

volume of the specimen and the suspected clinical diagnosis. 36,37
Direct inoculation of the intraocular fluid specimen onto culture
media is a traditional approach and remains a very practical
technique. The specific media used for direct inoculation are listed
in Table 3. This approach is especially important when limited
specimens (such as a needle vitreous or aqueous aspiration) are
obtained. These specimens can be inoculated directly onto the
appropriate media, including anaerobic media in cases of
suspected Propionibacteriurn acnes endophthalmitis. Specimens
obtained with automated vitrectomy instruments are diluted by the
infusion fluid but can be processed by two methods. One method
for processing the vitrectomy specimen uses a membrane filter
system in which the vitrectomy specimen is passed through
0.45mm filter paper that concentrates the microorganisms and
particulate matter. This filter paper is then sectioned and
distributed on the appropriate media.

TABLE 3. Culture Media Used for Endophthalmitis Specimens

1. Chocolate agar: An enriched medium for the recovery of

fastidious organisms (i.e., Neisseria gonorrhoeae and
Hemophilus influenzae) from clinical specimens. The
chocolate agar should be used as a general-purpose
 medium and as the medium of choice for the recovery of
common endophthalmitis isolates when only a few drops of
intraocular fluids are available for culture. It must be placed
in a CO2 jar or bag.
2. 5% Sheep blood agar: A general-purpose medium for the
recovery of the most common bacterial and fungal
endophthamitis isolates. It should be placed in the CO2 jar
or bag.
3. Thioglycollate broth: An enriched medium for the recovery
of small numbers of aerobic or anaerobic (including
Propionibacterium acnes) organisms from ocular fluids and
tissues. The broth dilutes out the effects of antibiotics and
other inhibitory susbstances. The broth should be kept a
minimum of five days.
4. Anaerobic blood agar: A general-purpose medium for the
recovery of anaerobic and facultative anaerobic organisms.
This medium should be included for all chronic cases of
endophthalmitis and/or where P. acnes is suspected. The
viridans and B-hemolytic streptococci may grow better and
faster on this plate. This medium is placed in an anaerobic
jar or bag.
5. Sabouraud agar: A selective medium used to promote the
growth of fungi (yeasts and molds) from clinical specimens.
6. Blood culture bottles: Contain specially prepared medium
for the recovery of both aerobic and anaerobic bacteria and
fungi. Intraocular fluids may be inoculated directly into
blood culture bottles. Undiluted fluids should be inoculated
into pediatric bottles and diluted fluids (6–12 mL of
vitrectomy specimen) injected into a set of routine (adult)
bottles. Identification is made after growth is established.

An alternative method involves direct inoculation of the initially

aspirated vitrectomy specimen into standard blood culture bottles
(Fig. 2).37 This latter technique is particularly useful at night or on
the weekend when the microbiology laboratory staff are not
available to assist in the processing of the vitrectomy specimen. In
a retrospective review of 83 cases, this blood culture bottle method
for processing vitrectomy specimens yielded a 91% incidence of
positive culture results.37 This rate of positive culture results from
clinically diagnosed endophthalmitis cases was similar to
simultaneously processed specimens using the membrane filter
system.
 Fig. 2. Blood culture bottles may be
used for vitrectomy specimens at night
or on the weekend when the
microbiology staff are not available.
Left: The bottle is unopened and has
clear media. Right: The inoculated
bottle shows growth of organisms as
manifested by the opaque media.
Immunologic as well as molecular genetic technologies enable
rapid and specific identification of infectious agents. These real-
time techniques have been used in both clinical and experimental
settings, and their future use in this area appears promising.38–40
Molecular genetic technology has made available specific DNA
probes that will interact with the unique DNA sequence for a
particular pathogen.40 Clinical application of PCR techniques
continues to evolve for the more rapid diagnosis of infectious
endophthalmitis.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of marked intraocular cellular

inflammation after ocular surgery includes sterile inflammation
(related to retained lens fragments or vitreous hemorrhage), iris
trauma, pre-existing uveitis, and foreign material introduced
during surgery.1,2 Retained cortical lens remnants are reported to
cause more inflammation than nuclear remnants.41 These retained
lens fragments may occasionally cause a marked inflammatory
reaction with hypopyon, which may clinically resemble infectious
endophthalmitis.42,43 Blood in the anterior chamber or vitreous
cavity may also be confused with endophthalmitis, especially when
the blood is long-standing and associated with anterior segment
trauma during preceding surgery. Similarly, difficult or prolonged
surgery, which often includes vitreous loss or vitreous incarceration
in the cataract incision, may increase postoperative inflammation.

Toxic Anterior Segment Syndrome (TASS) is an inflammatory

reaction to noninfectious agents that enter the eye during
intraocular ophthalmic procedures.44–47 The typical clinical picture is
the presence of diffuse corneal edema (“limbus to limbus”) and
marked anterior chamber inflammation detected on the first
postoperative day. Symptoms on the first postoperative day
include variable pain and impaired vision. Additional hallmarks of
the disease include fixed or almost fixed dilated pupil, severe
elevation of intraocular pressure, and iris thinning or atrophy. The
exact cause of TASS is controversial, but the most frequently
implicated cause is the use of improperly cleaned or processed
instruments, which allows denatured residual viscoelastic or
enzyme detergents to enter the patient's eye during cataract
surgery. Treatment consists of topical anti-inflammatory
medications and careful follow-up to rule out the possibility of
endophthalmitis. Similar to postoperative endophthalmitis, TASS is
a rare problem that can have poor visual acuity outcomes because
of persistent corneal edema and chronic intraocular inflammation.
It is often difficult to distinguish TASS from endophthalmitis during
the early postoperative course. In the Endophthalmitis Vitrectomy
Study (EVS), endophthalmitis cases were diagnosed one day after
cataract surgery in 5% of patients, within 2 days in 12% of
patients, within 3 days in 24% of patients, and within 1 week in
61% of patients.48–58 Further, in the EVS, more virulent organisms
(e.g., gram-negative bacteria, Streptococcus species, and
Staphylococcus aureus) were more likely to be diagnosed within 2
days of cataract surgery. These cases may also present with
marked corneal edema as well as severe intraocular inflammation
with varying levels of hypopyon. In the EVS, 31% of patients had a
negative intraocular culture. It is possible that some of these cases
may have had TASS but were clinically diagnosed as having
endophthalmitis. In the EVS, 86% of patients presented with a
hypopyon, but TASS may or may not present with a hypopyon
early in the course of the disease.

In eyes with mild-to-moderate postoperative inflammation without

hypopyon, intensive therapy with topical corticosteroids may be
used initially. The careful sequential observation of such eyes will
allow appropriate diagnostic and treatment approaches to be
employed. Acute-onset postoperative endophthalmitis caused by
more virulent organisms, such as Streptococcus species or gram-
negative bacteria, will usually present with rapidly progressive
clinical signs aiding in the early diagnosis of infectious
endophthalmitis. Endophthalmitis caused by the coagulase-
negative staphylococci may have fewer inflammatory signs and
may have a delayed presentation, often creating difficulty in
distinguishing between an infectious and a noninfectious etiology.
Back to Top
TREATMENT MODALITIES
Antibiotics can be delivered to the eye by several local routes,
including direct intravitreal injection, periocular injection, and
topical administration (Table 4). Endophthalmitis treatment, like
the management of infections elsewhere in the body, requires
selection of safe and effective antimicrobial agents. The antibiotics
selected should cover the broad range of gram-positive and gram-
negative bacteria causing clinical endophthalmitis. In the EVS, the
use of systemic antibiotics did not improve the outcomes of acute-
onset postoperative endophthalmitis in eyes that concurrently
received intravitreal antibiotics.48 However, the effect of recently
available systemic antibiotics with improved intraocular penetration
and broader spectrum, such as fourth-generation fluoroquinolones,
could possibly be of benefit in endophthalmitis treatment or
prevention.81

TABLE 4. Antibiotics Considered for Local Treatment of

Endophthalmitis: Concentration and Dosages of Principal Agents

Agent Intraocular Subconjunctival Topical

Amikacin 0.4 mg 25 mg 20 mg/mL
Ampicillin 0.5 mg 100 mg 50 mg/mL
Ceftazolin 2.25 mg 100 mg 50 mg/mL
Ceftazidime 2.25 mg 100–200 mg 50 mg/mL
Chloramphenicol 1.0 mg 50–100 mg 20 mg/mL
Clindamycin 1.0 mg 15–50 mg 50 mg/mL
Gentamicin 0.1 mg 20 mg 15 mg/mL
Methicillin 2.0 mg 100 mg 100 mg/mL
Tobramycin 0.1 mg 20 mg 15 mg/mL
Vancomycin 1.0 mg 25 mg 25 mg/mL

Compiled from PDR for Ophthalmology, 2005

 
Back to Top
INTRAVITREAL ANTIBIOTICS
Of all the available antimicrobial agents evaluated for intravitreal
injection, only a few are used regularly in clinical practice. In the
EVS, intravitreal vancomycin 1 mg in combination with amikacin
0.4 mg were used for the initial empiric treatment of acute-onset
endophthalmitis.48–58 This combination of intravitreal antibiotics has
been reported to be almost always effective for the broad range of
bacterial organisms. An alternative to the aminoglycosides for
coverage of gram-negative organisms is the use of intravitreal
ceftazidime 2.25 mg, a third-generation cephalosporin.61–67
Outcomes of endophthalmitis treatment are demonstrated in
Tables 5 and 6.14,59–60,64–71,88,105 No single antibiotic is effective
against the broad spectrum of gram-positive and gram-negative
bacteria and fungi.61

TABLE 5. Visual Acuity Outcomes Following Treatment of

Endophthalmitis Caused by Various Gram-Positive Organisms*

Number 20/50 or 20/400 or No Light

Organism (Reference
of Better Better Perception
#)
Patients No. (%) No. (%) No. (%)
Coagulase-negative 24
46 40 (87.0) 1 (2.2)
Staphylococcus (68) (52.1)
Propionibacterium 12
22 16 (72.7) 2 (9.1)
species (14) (54.5)
Staphylococcus 13
27 17 (63.0) 4 (14.8)
aureus (88) (48.2)
Streptococcus
27 2 (7.4) 8 (29.6) 10 (37.0)
pneumoniae (59)
Enterococcus faecalis
29 2 (6.9) 5 (17.2) 4 (13.8)
(60)
Bacillus species (105) 18 1 (5.6) 2 (11.1) 14 (77.8)

*All patients were treated at the Bascom Palmer Eye Institute

TABLE 6. Visual Acuity Outcomes Following Treatment of

Endophthalmitis Caused by Various Gram-Negative Organisms*

Final Visual Final Visual

Organism Number Acuity 20/50 Acuity 20/400 NLP No.
(Reference #) of Eyes or Better No. or Better No. (%)
(%) (%)
Xanthomonas
4 3 (75%) 4 (100%) 0 (0%)
maltophilia (70)
Serratia 5
10 2 (20%) 4 (40%)
marcescens (69) (50%)
Haemophilus 6
16 2 (13%) 5 (31%)
influenza (71) (38%)
Moraxella species 1
10 1 (10%) 7 (70%)
(65,66) (10%)
8
Proteus species§ 16 1 (6%) 5 (31%)
(50%)
Klebsiella
1 0 (0%) 1 (100%) 0 (0%)
oxytoca (67)
Klebsiella 1
5 0 (0%) 2 (40%)
pneumoniae (67) (20%)
Pseudomonas 19
28 0 (0%) 1 (4%)
aeruginosa (64) (68%)

* All patients treated at Bascom Palmer Eye Institute

§ARVO Abstract 2003
NLP = No light perception

Repetitive injections of intravitreal antibiotics cause significant

retinal toxicity in a rabbit model; eyes treated with a second or
third vancomycin/aminoglycoside injection at 48-hour intervals
showed progressive toxicity.72 In view of the low rate of persistent
infection after initial combination therapy, repeat injection of
intravitreal antibiotics are considered only in those cases with
progressive inflammation caused by virulent organisms. 73 Based on
the initial culture report, a single intravitreal antibiotic may be
selected for this repeat injection.
Back to Top
VITRECTOMY
The potential advantages of vitrectomy for infectious
endophthalmitis include the ability to obtain an adequate vitreous
specimen without the theoretically harmful tractional effects of
needle aspiration on formed vitreous. Vitrectomy also debulks the
vitreous cavity, allowing the removal of the majority of infecting
organisms and other inflammatory mediators. Finally, the
vitrectomized eye theoretically should allow improved drug
circulation throughout the vitreous cavity.

Disadvantages of vitrectomy include the requirement for

instrumentation, possibly available only in an operating room
setting, which may be associated with a delay in initiating
treatment. The view of the posterior segment is frequently
obscured by fibrin and inflammatory debris on the surface of the
intraocular lens or in the anterior chamber, making vitrectomy
surgery difficult and potentially hazardous. The view of the
posterior segment can be improved frequently by aspirating or
peeling the inflammatory material from the anterior segment or
surface of the intraocular lens (IOL).74

Another disadvantage of vitrectomy is its effect on reducing the

half-life of injected intravitreal antibiotics.75 Doft and associates
studied the ocular clearance of amphotericin B injected into the
vitreous in a rabbit model of unmodified phakic eyes, Candida-
infected phakic eyes, aphakic eyes, and aphakic vitrectomized
eyes. With the use of high-pressure liquid chromatography to
assess drug level, the half-lives of drug disappearance after a
single amphotericin B 10-mg intravitreal injection were 9.1, 8.6,
4.7, and 4.1 days, respectively. The authors summarized that this
rapid disappearance of amphotericin B from vitrectomized eyes
must be considered in the clinical management of patients with
fungal endophthalmitis.

Vitrectomy for endophthalmitis can be performed using either a

two-port (vitreous cutter and infusion needle or irrigating light
pipe) or three-port technique (sutured infusion cannula,
endoilluminator probe, and vitreous cutter), depending on the
surgeon's preference and the clinical circumstances. A pars plana
vitrectomy (PPV) is often recommended for endophthalmitis cases
with light perception visual acuity and with moderate (red reflex
present and poor view of fundus detail) or severe (no red reflex
visible) vitritis. In such cases, preoperative echography is generally
performed to rule out retinal detachment and to document the
 presence or absence of a posterior vitreous detachment. When
there is a posterior vitreous detachment, the vitrectomy surgeon
can remove more opaque vitreous near the posterior pole and
have greater confidence in avoiding contact with the retina. In
EVS, the goal of the three-port PPV was to remove at least 50% of
the formed vitreous.

A concentrated undiluted vitreous specimen can be obtained at the

beginning of the procedure by manual aspiration into a syringe
attached to the aspiration line of the vitrectomy handpiece. The
intraocular specimens are evaluated using stained smears and
direct cultures.
Back to Top
THE ENDOPHTHALMITIS VITRECTOMY STUDY
The EVS was a multicenter, National Eye Institute (NEI) sponsored
trial that evaluated PPV and systemic antibiotics in acute
postoperative endophthalmitis.48–58 The EVS also evaluated a
variety of clinical and microbiologic factors relating to
endophthalmitis. The study enrolled 420 patients with symptoms
and signs of endophthalmitis occurring within 6 weeks of cataract
extraction or secondary intraocular lens implantation. Patients
were randomized to treatment with PPV or to vitreous tap/biopsy
and to treatment with or without systemic antibiotics. All patients
in the study received intravitreal antibiotic therapy (vancomycin 1
mg and amikacin 0.4 mg), and topical and systemic
corticosteroids. Patients who appeared clinically worse 36 to 60
hours after presentation underwent reinjection of intravitreal
antibiotics. Similarly, patients who were initially randomized to
tap/biopsy and had worsening conditions also underwent
vitrectomy. The main endpoint of the study was best-corrected
visual acuity at 9 to 12 months after presentation. A secondary
endpoint was media clarity.

VISUAL ACUITY RESULTS IN THE EVS

The EVS reported that, among patients who presented with visual
acuity of light perception (LP) only, the visual acuity outcomes
after immediate PPV were better when compared to the tap/biopsy
group.37 In the light perception subgroup of patients, using
vitrectomy was associated with a threefold increase in the
frequency of achieving 20/40 or better acuity (33% vs. 11%),
approximately a twofold chance of achieving 20/100 or better
acuity (56% vs. 30%), and a 50% decrease in the frequency of
worse than 5/200 acuity (20% vs. 47%). There was no difference
in outcomes between immediate PPV and tap/biopsy for patients
with an initial visual acuity of hand motions or better (Figs. 3 and
4). In this subgroup, patients had about the same chance of
achieving 20/40 or better acuity (66% vs. 62%) and 20/100 or
better acuity (86% vs. 84%) and a similar risk for severe visual
loss to worse than 5/200 acuity (5% vs. 3%), whether they had
immediate three-port PPV or vitreous tap/biopsy. However, there
was a possible exception. Diabetic patients with initial visual acuity
of hand motions or better obtained somewhat better visual acuity
outcomes with vitrectomy compared to tap/biopsy. Final visual
acuity of 20/40 or better was obtained in 57% of vitrectomy
patients and 40% of tap biopsy patients. The difference was not
statistically significant. It was suggested that either vitrectomy or
tap/biopsy could be considered reasonable for diabetic patients.49

Fig. 3. Acute-onset endophthalmitis

following cataract surgery. Left:
Conjunctival congestion, hypopyon,
fibrin in anterior chamber, and visual
acuity reduced to hand motions on
postoperative day 6. The patient was treated with a vitreous tap
and ijected with intravitreal antibiotics. Right: The vitreous
specimen showed coagulase-negative staphylococcus. Following
treatment, visual acuity improved to 20/25.

Fig. 4. Acute-onset endophthalmitis

following cataract surgery. Left: Marked
conjunctival congestion, fibrin in the
pupil and anterior chamber, hypopyon,
and visual acuity reduced to light
perception on postoperative day 1. The patient was treated with
pars plana vitrectomy and injected with intravitreal antibiotics.
Right: The vitreous culture isolated Serratia marcescens. The final
visual acuity improved to 20/50 but was limited by cystoid
macular edema.
At 9 to 12 months after presentation, clear media, as judged by a
20/40 view of the fundus by indirect ophthalmoscopy, was
achieved slightly less frequently in the tap/biopsy eyes (83%) than
in the vitrectomized eyes (90%), but this difference was not
statistically significant. In no cases were vitreous opacities judged
to be a principal cause of impaired vision at the final examination.53

The use of systemic antibiotics (amikacin and ceftazidime) did not

improve visual outcomes or media clarity in the EVS, even when
subgroup analysis that considered microbiologic susceptibilities
was performed.48–58 The study concluded that systemic antibiotics
provided no additional benefit to other routes of treatment.

COMPLICATIONS FROM ENDOPHTHALMITIS AND ITS

MANAGEMENT

In the EVS, major adverse events included retinal detachment in

8.3% of patients, phthisis in 3% of patients, significant elevation of
intraocular pressure (30 mm Hg or more) in 1% of patients, and
enucleation or evisceration in 1% of patients. Compared to
vitreous tap/biopsy, vitrectomy was associated with a slightly
lower complication rate. Retinal detachment occurred in 7.8% of
vitrectomy eyes compared to 9.0% of tap/biopsy eyes.78
Enucleation was performed in 3 tap/biopsy eyes but not in
vitrectomy eyes. EVS treatment recommendations were based on
visual outcome, not small differences in complication rates among
treatment modalities.

Macular abnormalities were the most common cause of visual loss

in the EVS. These included macular edema, pigmentary
degeneration, epiretinal membrane, and ischemia. Such
abnormalities were more common with worse presenting visual
acuity, occurring in up to 17% of patients with hand motions or
better acuity and up to 40% of patients presenting with light
perception acuity. In light perception eyes that did not receive
vitrectomy (the subgroup that did most poorly), excess visual loss
was due to anterior segment media opacification (15%) and
phthisis or enucleation (23%). These events were observed much
less frequently (0.7–7%) in the remaining treatment groups.

Two adverse events during or after endophthalmitis treatment may

markedly influence visual acuity outcomes. Antibiotic toxicity and
retinal detachment are significant because further visual loss may
occur in spite of successful treatment of the infections. Macular
infarction after the use of intraocular aminoglycosides (Fig. 5) is a
clinically recognized complication manifesting as a relatively well-
defined area of retinal whitening, often in the macula.76,77 Reported
cases of macular infarction secondary to administration of
intraocular aminoglycosides have been observed after excessive
intraocular doses; other cases were reported after apparent
injection of a recommended safe dose. A localized increase in the
drug concentration in dependent areas of the retina may play a
role in aminoglycoside toxicity. If some of the perifoveal capillaries
are spared, retention of some central vision is possible.

Fig. 5. Macular infarction following

intravitreal amikacin 0.4 mg injection.
Left: The color photograph shows
whitening of the retinal tissue that
involves the macula as well as scattered
intraretinal hemorrhages. Right: The
angiogram shows prominent capillary nonperfusion that involves
the macula. The organism cultured from the vitreous was
Staphylococcus epidermidis. Despite resolution of the infection,
visual acuity was limited to hand motion only because of the
macular infarction.
Retinal detachment may occur before, during, or after
endophthalmitis treatment. The visual prognosis for eyes with
retinal detachment in the setting of endophthalmitis is generally
poor in reported series.78,79 The rates of postvitrectomy retinal
detachment may be reduced by performing only a partial
vitrectomy when the view is compromised by corneal edema.

EARLY AND LATE ADDITIONAL PROCEDURES IN THE EVS

The EVS also evaluated the frequency of additional intervention

following initial treatment.53 Within one week of presentation,
additional procedures were required in 8% of vitrectomized eyes
versus 13% of eyes treated with tap/biopsy. Of 44 eyes (10%
overall) that required repeat procedures, most (9%) underwent
such procedures for worsening inflammation; the remainder
(1.4%, 6 eyes) for other complications after the initial treatment
procedure. As reported by the EVS, these remainder complications
included glaucoma, wound leak, and retinal detachment. EVS eyes
that required additional procedures soon after initial presentation
had a poorer visual outcome, with only 15% of eyes achieving
20/40 or better visual acuity compared to 57% of eyes that did not
require such procedures. The poorer outcome in eyes requiring
secondary procedures could be attributed to the worse early course
in such eyes, rather than to the secondary procedures themselves.

The incidence of late additional surgical procedures was 27%

overall, and did not differ whether or not vitrectomy was
performed or intravenous antibiotics administered. Overall, late
additional procedures included posterior capsulotomy in 9% of
patients, vitrectomy in 7%, retinopexy in 2%, scleral buckling in
1%, and glaucoma procedures in 1%. In about 2% of patients,
vitrectomy for epiretinal membrane was performed. Including early
additional surgical procedures, approximately one-third of EVS
patients required further surgical intervention after initial
treatment.

CLINICAL PRESENTATION AND VISUAL OUTCOME IN THE

EVS

Clinical factors on presentation can be correlated with final visual

outcome in the EVS. The single most important predictor of visual
outcome was presenting visual acuity. Patients with LP visual
acuity at presentation had twice the risk of decreased vision
compared to those with hand motions or better. Overall, 23% of
patients with LP acuity achieved 20/40 or better final acuity,
compared with 64% of patients who had hand motions or better
acuity.48 The data confirmed that early treatment of
endophthalmitis prior to severe visual loss is critical to maximize
visual outcome and that such treatment is more important in
influencing outcome than any other factor, including vitrectomy.
Other clinical factors that independently predicted decreased final
visual acuity were older age, history of diabetes, corneal infiltrate
or ring ulcer, abnormal intraocular pressure, rubeosis, an absent
red reflex, and an open posterior capsule.49
MICROBIOLOGIC FACTORS IN THE EVS

The EVS evaluated the microbiologic spectrum and susceptibilities

of infecting organisms. The findings provided a basis for choosing
initial empiric antibiotic therapy and for evaluating subsequent
changes in microbiologic spectrum in this disease. As observed in
the EVS, the type of organisms and their distribution as well as
visual outcomes by infecting species are shown in Table 7. Because
both gram-positive and gram-negative organisms were
encountered, antibiotic coverage for both types of organisms is
recommended.

TABLE 7. Visual Outcome by Infecting Organism in the

Endophthalmitis Vitrectomy Study*

>20/40 >20/100 <5/200

Infecting Organism N
(%) (%) (%)
Gram-positive, coagulase-
214 58 81 4
negative micrococci
Staphylococcus aureus 30 37 50 37
Streptococcus species 23 13 30 39
Enterococcus species 7 0 14 43
Gram-positives, (excluding
gram (+) coagulase(−) 69 28 59 33
micrococci)
Gram-negatives 18 39 44 28

*Data obtained from: The Endophthalmitis Vitrectomy Study

Group: Microbiologic factors and visual outcome in the
Endophthalmitis Vitrectomy Study. Am J Ophthalmol 122:837,
1996.

Although the infecting organism type predicted visual outcome and

response to vitrectomy, the presenting visual acuity was a more
powerful, independent predictor of outcome. Presenting visual
acuity appeared to serve as a useful proxy for factors such as the
duration of infection, host response, and degree of ongoing tissue
damage that are determinants of visual prognosis and response to
vitrectomy. Other important EVS observations included:

1. A confirmed culture positivity rate of 69% overall, 82% if

equivocal cultures were included.54
2. A high frequency (approximately 70%) of coagulase-
negative staphylococci in culture positive cases, with a high
 concordance of intraocular isolates with the patients'
periocular skin flora being observed.51
3. A 9% rate of polymicrobial infection (infection with two or
more strains or species in the same eye).54
4. A high rate of susceptibility of infecting organisms (99.4%)
to either of two antimicrobial drug combinations available
for intravitreal administration, vancomycin plus amikacin, or
vancomycin plus ceftazidime.54
5. A statistically significant association between secondary IOL
implantation and infection with organisms other than
coagulase-negative staphylococci, such as S. aureus and
streptococci.54 Such organisms were associated with a much
poorer visual prognosis.
6. Virtually identical visual outcome for culture-negative cases
and cases infected with coagulase-negative staphylococci,
suggesting that many cases of “sterile” endophthalmitis
may actually be infectious in origin.50
7. Topical preoperative surgical preparation with povidone-
iodine had been administered in 85 of 211 (40.3%) EVS
study patients for whom such data were recorded.54
8. Prophylactic antibiotics had been administered in the
cataract infusion fluid at the initial cataract surgery in 10 of
87 (11.5%) patients in which the data were available.54

PITFALLS IN THE APPLICATION OF THE EVS FINDINGS

Measurements of presenting visual acuity were an important factor

in the EVS and its recommendations regarding PPV. According to
the EVS, patients who were unable to perceive hand motions at a
distance of two feet were designated as having LP visual acuity.
Such patients were shown to benefit from immediate PPV.
Improperly designating such patients with actual LP acuity as
having hand motions acuity would result in their inappropriate
exclusion from receiving a potentially beneficial vitrectomy. In the
EVS, discrimination between LP and hand motions acuity required
that the illumination source be placed behind (not in front of) the
patient and that the patient correctly identify four of five
presentations of hand movements at a distance of two feet. A large
proportion of patients in the EVS (70%) required such
discrimination, having presented with either LP or hand motions
acuity.48

The EVS recommendations regarding the use of vitrectomy or

systemic antibiotic therapy in acute-onset postoperative
endophthalmitis may not be applied directly to other forms of
endophthalmitis. The predominant infecting organism in acute-
onset postoperative endophthalmitis, coagulase-negative
staphylococci, accounted for 70% of the culture-positive cases in
the study. Other common forms of endophthalmitis are not
characterized by such a predominance of this organism. Bleb-
related, traumatic, or endogenous endophthalmitis are more likely
to harbor organisms of greater virulence, such as the toxin-
producing Streptococcus or Bacillus species. In such cases, the
benefits of vitrectomy might theoretically be greater because of its
presumed ability to physically remove bacteria and toxins from the
eye.

With respect to systemic antibiotic therapy, only amikacin and

ceftazidime were evaluated in the EVS. The study made no
recommendations regarding systemic antibiotics for
endophthalmitis prophylaxis, or for chronic, traumatic, bleb-
related, fungal, or endogenous endophthalmitis. The EVS was
conducted prior to the availability of the fourth-generation
fluorquinolones81 and linezolid,82 which can be administered
systemically and may have better intravitreal penetration.
Back to Top
TOPICAL ANTIBIOTIC THERAPY
Most studies concerning the efficacy of topically applied antibiotics
pertain to corneal infections. The value of topical therapy for
endophthalmitis is unknown, particularly when intravitreal
antibiotics are administered. Nevertheless, it appears reasonable to
apply such treatment if there is a wound abnormality, bleb
infection, or other external infection of the eye or adnexae.

Significant intraocular levels of antibiotics can be achieved with

frequent administration of highly concentrated solutions. 83 In eyes
with intact corneal epithelium, lipid-soluble antibiotics, such as
chloramphenicol, penetrate better than the less lipid-soluble drugs,
such as the aminoglycosides. This difference is reduced when the
corneal epithelium is damaged. For acute-onset postoperative
endophthalmitis, topical vancomycin (25 mg/ml) in combination
with an aminoglycoside (9 or 14 mg/ml) or ceftazidime (50 mg/ml)
administered hourly is often considered. This regimen can then be
adjusted to the specific organism after culture and sensitivity
results are available. The fourth-generation fluoroquinolones,
available commercially for topical use, can also be considered.
Back to Top
PERIOCULAR ANTIBIOTIC THERAPY
Conflicting data regarding the intravitreal penetration after
periocular antibiotic injection have been reported. Causes for the
variability in these experiments include the inflammatory status of
the eye and, possibly, sampling technique. The physiochemical
properties of the drug may affect transscleral and transcorneal
permeability. Of the currently used antibiotics, the third-generation
cephalosporins (ceftazidime and ceftriaxone) achieve the highest
vitreous levels. Some investigators have reported that
subconjunctival antibiotics were not associated with improved
outcomes when intravitreal antibiotics were used.84,85
Back to Top
CORTICOSTEROID THERAPY
Marked infiltration of the anterior chamber and vitreous cavity by
polymorphonuclear neutrophils often occurs in endophthalmitis
caused by bacteria. These white blood cells are implicated as
mediators of tissue-destructive events by liberating oxygen
metabolites such as superoxide and hydrogen peroxide as well as
proteolytic enzymes (elastase, collagenase, gelatinase).
Theoretically, corticosteroids should reduce this inflammation-
induced ocular damage associated with endophthalmitis.

Corticosteroids can be administered to the eye by several routes

(intravitreal, systemic, periocular, and topical). Clinical studies
have reported mixed results regarding adverse effects when using
intravitreal dexamethasone in conjunction with intraocular
antibiotics. In a prospective randomized clinical trial of 63 bacterial
endophthalmitis cases, intravitreal dexamethasone was shown to
reduce inflammation scores early in the course of treatment but
had no independent influence on the final visual outcome.86 In a
series of endophthalmitis cases caused by gram-negative
organisms, Irvine and associates87 reported no adverse effects
using intravitreal dexamethasone, 400 μg, in conjunction with
intravitreal antibiotics. In this report, visual acuity rates of 20/400
or better in eyes treated with adjunctive intraocular
dexamethasone (70.0%) were compared with eyes not receiving
adjunctive dexamethasone (44.2%). Similarly, Mao and
associates88 reported better visual acuity outcomes (% ≥ 20/400)
after adjunctive treatment with intravitreal dexamethasone, 400
μg (87.5% vs. 52.6%), for S. aureus endophthalmitis.

In addition to intravitreal corticosteroids, periocular corticosteroids

are also commonly used in the treatment of endophthalmitis. The
periocular dosage may include dexamethasone, 12 mg or more,
administered together with periocular antibiotics.1 Topical
corticosteroids are usually started on the first morning after the
initial treatment of endophthalmitis. These drops may be
alternated on an hourly basis with the use of topical antibiotics.

Systemic corticosteroids were used in the EVS in the treatment of

all study patients with postoperative endophthalmitis. In one
study, a combination of topical and systemic corticosteroids gave
better results than no corticosteroids or only topical corticosteroid
administration.89 Because many patients with endophthalmitis also
have diabetes mellitus,7 use caution when administering higher
dosages of systemic corticosteroids.
Back to Top
TISSUE PLASMINOGEN ACTIVATOR
Marked fibrin formation often accompanies endophthalmitis. This
fibrin may sometimes cause pupillary block glaucoma or may form
a scaffold for cellular proliferation with subsequent traction retinal
detachment, cyclitic membrane formation, and/or hypotony. The
use of tissue plasminogen activator (t-PA) for treating more severe
postvitrectomy intraocular fibrin formation was reported for 23
eyes.82 In three of 23 eyes, endophthalmitis was the underlying
cause for the fibrin production. In all three patients, intraocular t-
PA 25 mg resulted in prompt fibrinolysis, although two eyes had
recurrent fibrin formation. No complications were related directly to
the t-PA injection. Only one of these three t-PA–treated patients
achieved 20/400 visual acuity. Although t-PA may have a role in
the treatment of fibrin formation complicating endophthalmitis, it is
rarely used as initial therapy. It is important to note that t-PA
injection itself may be associated with the development of
endophthalmitis.91
Back to Top
CRYSTALLINE LENS MANAGEMENT AND THE IOL
DURING ENDOPHTHALMITIS TREATMENT
An uninvolved crystalline lens can generally be left in place during
endophthalmitis treatment (e.g., in endogenous endophthalmitis).
Successful treatment of culture-positive cases has been reported
using vitrectomy and intravitreal antibiotics while preserving the
uninvolved crystalline lens.92

In most cases of acute-onset postoperative pseudophakic

endophthalmitis, intraocular lens removal is not necessary.2 There
is no evidence that leaving the intraocular lens in place reduces the
chance of sterilizing the eye.93 Removal of the posterior chamber
IOL may be hazardous in inflamed eyes and may predispose to
anterior and posterior segment complications. In selected cases of
fungal endophthalmitis and in cases of P. acnes not responsive to
more conservative therapy, IOL removal can be considered.14–16 If
recurrent infection occurs following PPV, partial capsulotomy, and
intravitreal antibiotics, these cases may require removal of the
entire capsular bag and the intraocular lens to achieve a cure.94
Back to Top
ENDOPHTHALMITIS CATEGORIES
ACUTE-ONSET POSTOPERATIVE ENDOPHTHALMITIS

This category of endophthalmitis occurs within 6 weeks of

intraocular surgery. It can occur from a variety of intraocular
surgical procedures ranging from radial keratotomy to cataract
surgery. Pain is a frequent but inconsistent symptom and was
absent in 25% of EVS patients. The visual loss is generally greater
than that expected during the usual postoperative course.
Organisms most frequently involved are the coagulase-negative
staphylococci, S. aureus, Streptococcus species, and gram-
negative organisms.

DELAYED-ONSET OR CHRONIC POSTOPERATIVE

ENDOPHTHALMITIS

In this endophthalmitis category, patients may present weeks to

months after cataract extraction, often with mild-to-moderate
inflammatory signs and a chronic indolent course.16,94 P. acnes, a
gram-positive, anaerobic pleomorphic rod, is a common causative
organism in this category. The clinical P. acnes syndrome of
delayed-onset pseudophakic endophthalmitis, first described by
Meisler and associates94 in 1986, typically includes granulomatous
inflammation with large keratic precipitates (Fig. 6) and a white
intracapsular plaque that has been shown to be composed of
organisms mixed with residual lens cortex. When infection with this
slow-growing organism is suspected, anaerobic cultures of both the
aqueous and vitreous should be obtained and held at least 2
weeks.

Fig. 6. Delayed-onset pseudophakic

endophthalmitis. Left: This patient
presented with granulomatous uveitis,
vitritis, and a white plaque within the
capsular bag, which is characteristic of
infection caused by Propionibacterium acnes. Right: Marked
granulomatous keratic precipitates are occasionally seen in
endophthalmitis caused by P. acnes.
In a review of 19 patients with delayed-onset pseudophakic
endophthalmitis (defined as those cases diagnosed 6 weeks or
more after cataract surgery and excluding filtering bleb-associated
cases), four different etiologic organisms were isolated.13 These
included Propionibacterium species (63%), Candida parapsilosis
(16%), Staphylococcus epidermidis (16%), and Corynebacterium
species (5%).11 Endophthalmitis due to Mycobacterium chelonae
may also present as delayed-onset or chronic postoperative
endophthalmitis with white opacities in the lens capsule or anterior
vitreous; such cases may be initially misdiagnosed as P. acnes.95

In the initial management of P. acnes pseudophakic

endophthalmitis with a white intracapsular plaque, a PPV and a
central capsulectomy together with intravitreal antibiotics
(intravitreal corticosteroids are optional) is generally
recommended.14–16 Selective removal of the observed white plaque
using the vitrectomy probe assisted by scleral depression may
reduce the frequency of recurrent infection (Figs. 4A and 4B).
Vancomycin 1 mg has been the initial antibiotic of choice because
of its broad spectrum of coverage against gram-positive organisms
and because it can be injected into the remaining capsular bag
after the vitrectomy.14–16 Vancomycin has been recommended over
other antibiotics, but vancomycin's activity is diminished under
anaerobic conditions. Isolates of P. acnes are also sensitive to
methicillin, cefazolin, and clindamycin.

In clinically suspected fungal infections characterized by fluffy

white vitreous infiltrates (Fig. 7), injection of intravitreal
amphotericin B 5 μg should be considered. If the initial treatment
approach does not eliminate the infection, total capsulectomy and
intraocular lens removal or exchange can be considered in this
staged approach.96,97 Voriconazole or miconazole can be considered
for amphotericin B–resistant organisms.98–101

Fig. 7. Delayed-onset endophthalmitis

occurring more than six weeks following
cataract surgery. This patient presented
with a white string of vitreous infiltrates,
which is characteristic of
endophthalmitis caused by Candida
species. Candida parapsilosis was
isolated from the same patient's
vitrectomy specimen.
Other categories of delayed-onset endophthalmitis include cases
associated with suture removal or severe bacterial keratitis, or
exposed glaucoma drainage devices.102 Sutures for scleral fixation
of intraocular lens haptics may erode through the conjunctiva and
allow organisms entry into the eye.103

CONJUNCTIVAL FILTERING BLEB-ASSOCIATED

ENDOPHTHALMITIS

This category of endophthalmitis is similar to acute postoperative

endophthalmitis in that these patients manifest a sudden onset of
pain, visual loss, conjunctival congestion, purulent bleb
involvement, and the typical diagnostic features of acute-onset
endophthalmitis (Fig. 8).10,11,104 Risk factors for this category of
endophthalmitis include a history of conjunctivitis, contaminated
topical glaucoma medications, the use of contact lenses, and
inferior filtering bleb.10,104 The incidence of bleb-related
endophthalmitis after a glaucoma-filtration procedure with
mitomycin C may be higher than for trabeculectomy without
antifibrotic agents.104 The organisms frequently involved in this
type of endophthalmitis include streptococcal species8,71 and
Hemophilus influenzae. Because of the frequency of these virulent
organisms and the generally poor visual acuity outcomes, PPV and
intraocular antibiotics are often considered as the initial approach
for conjunctival filtering bleb-associated endophthalmitis.

Fig. 8. Delayed-onset endophthalmitis

associated with glaucoma filtering blebs.
Organisms invade the bleb initially and
spread to involve intraocular fluids and
tissues. This patient shows characteristic
purulence of the filtering bleb,
conjunctival congestion, hypopyon and
fibrin in the pupil. Streptococcus
pneumoniae was isolated from the
vitreous specimen.
It is important to distinguish between a localized bleb infection
(blebitis) and true endophthalmitis associated with an infected
filtering bleb.11 The former category can be treated with intensive
topical, subconjunctival, and possibly systemic antibiotics while the
latter category can be treated in a manner similar to acute-onset
postoperative endophthalmitis (Fig. 9).

Fig. 9. Bleb-associated endophthalmitis

occurring two years following glaucoma
filtering surgery. Left: Marked purulence
of the bleb, hypopyon, and fibrin in the
pupil. Visual acuity was reduced to hand
motion. The patient was treated with a vitreous tap and injected
with intravitreal antibiotics. Right: Coagulase-negative
staphylococcus was isolated from the vitreous. Final visual acuity
was 20/400 because advanced glaucomatous disease limited
visual recovery.
POSTTRAUMATIC ENDOPHTHALMITIS

The visual outcomes after treatment of posttraumatic

endophthalmitis are generally worse than the other
endophthalmitis categories. In addition to vitreous infiltrates and
hypopyon, other signs of posttraumatic endophthalmitis include
exudate around foreign body and retinal periphlebitis (Fig. 10). In
the National Eye Trauma System21 review of endophthalmitis after
penetrating injuries with retained intraocular foreign bodies, 9 of
22 (40.9%) culture positive cases achieved 20/400 or better visual
acuity. Either Bacillus or staphylococci species were isolated in 21
of these 22 (95%) culture-positive cases. Endophthalmitis was
much less likely to develop in eyes with primary repair within 24
hours of the injury (10/287 or 3.5%) than in eyes with primary
repair more than 24 hours after the injury (22/164 or 13.4%; p <
0.0001). Major reasons for the poor visual acuity outcomes in
these cases are the marked structural damage to the eye resulting
from the initial injury, the delay in the primary wound repair, and
the greater virulence of the organisms commonly associated with
the traumatic endophthalmitis. Bacillus species, most commonly B.
cereus, are cultured from 28% to 46% of eyes with posttraumatic
endophthalmitis.20,21,105 Bacillus species are ubiquitous, aerobic,
gram-positive, spore-forming rods. Endophthalmitis caused by
Bacillus species is characterized by a rapidly progressive course,
ring corneal infiltrates (Fig. 11), and, generally, a poor visual
outcome even with prompt therapy (Fig. 12).105–109

Fig. 10. Posttraumatic endophthalmitis.

Left: Marked purulence around an
intraocular foreign body. Right: Marked
periphlebitis.

Fig. 11. Endophthalmitis caused by

Bacillus cereus and a retained
intraocular foreign body. Note the
prominent conjunctival congestion,
corneal ring infiltrate, and dense
hypopyon. Visual acuity was light
perception. Despite prompt treatment,
enucleation was eventually performed
because of the blind, painful eye.

Fig. 12. Posttraumatic endophthalmitis.

Left: Marked purulence surrounding an
intraretinal foreign body. Bacillus cereus
was isolated from the vitrectomy
specimen. Right: Following successful
vitrectomy, removal of the foreign body, and an injection of
intravitreal antibiotics, visual acuity improved to 20/200 during
follow-up.
A subgroup of trauma-related endophthalmitis is endophthalmitis
associated with retained intraocular foreign bodies. Mieler and
associates110 reported 27 consecutive cases of retained intraocular
foreign bodies managed by prompt removal of the foreign body
using PPV techniques. Positive vitreous cultures were obtained in
seven of the 19 cases in which cultures were performed. Bacillus
species were identified in two of these seven culture-positive
cases. In spite of the positive intraocular cultures, no patient
developed clinical endophthalmitis. In the National Eye Trauma
System data, fewer patients with retained foreign bodies (10 of
287 patients [3.5%]) developed endophthalmitis when the primary
surgical repair was within 24 hours after the injury compared with
patients in whom the primary surgical repair was delayed more
than 24 hours (22 of 164 patients [13.4%]). 21 Signs of infectious
endophthalmitis were described at the primary surgical repair in 31
of 34 patients (91.2%), but 3 of 34 patients (8.8%) developed
signs of infection after the primary repair. These reports speculate
that prompt surgical intervention, use of vitrectomy, and possible
use of prophylactic intravitreal antibiotics in selected high-risk
cases may reduce the incidence of endophthalmitis or reverse early
undiagnosed endophthalmitis in the setting of a retained
intraocular foreign body.

The role of prophylactic intravitreal antibiotics in penetrating ocular

trauma cases is controversial.110 However, given the potential for
severe visual loss in trauma-related endophthalmitis, it seems
prudent to consider their use in selected cases resulting from
material such as vegetable matter, foreign-body injuries incurred
in an outdoor or rural environment, and penetrating ocular injury
from eating utensils.105–112 The combination of vancomycin 1 mg
alone or in conjunction with either an aminoglycoside (amikacin
0.4 mg) or ceftazidime 2.25 mg can be considered when
prophylactic intraocular therapy seems appropriate. In addition,
systemic antibiotics (such as fourth-generation fluoroquinolones)
may be considered.81

ENDOGENOUS ENDOPHTHALMITIS

Endogenous endophthalmitis is caused by fungi more often than

bacteria.27 The most common organism causing endogenous fungal
endophthalmitis is Candida albicans; Aspergillus species is the
second most common fungal cause.22,27 Endogenous
endophthalmitis is more commonly diagnosed in
immunocompromised and debilitated patients or intravenous drug
abusers (Table 8).

TABLE 8. Conditions Possibly Predisposing to Endogenous

Endophthalmitis

Long-term intravenous line placement Malignancy

Parenteral hyperalimentation Diabetes mellitus
Prolonged antibiotic therapy Pregnancy
Systemic corticosteroids Massive Trauma
Immunosuppressive therapy Alcoholism
Abdominal surgery Hepatic insufficiency
Hemodialysis Postpartum
Intravenous drug abuse Prematurity
AIDS Genitourinary manipulation
The typical clinical features of Candida endogenous
endophthalmitis include fluffy yellow or white vitreous opacities
and creamy white chorioretinal infiltrates (Fig. 13). Anterior uveitis
frequently accompanies the posterior segment findings. A large
macular abscess and pseudohypopyon formation (layering of
inflammatory material under the internal limiting membrane of the
retina) is not uncommon in cases of endogenous Aspergillus
infection.25

Fig. 13. Endogenous endophthalmitis

caused by Candida species. The patient,
with no previous ocular surgery,
presents with prominent white vitreous
infiltrates typical of Candida species in a
patient with systemic candidiasis.

The management of endogenous endophthalmitis depends on the

clinical features (fungal vs. bacterial), the specific organism
isolated, and the severity of infection.24–27 Once a diagnosis of
endogenous endophthalmitis is suspected, evidence for other
organ involvement must be sought. This is usually accomplished in
consultation with an infectious disease specialist or internist. The
presumptive clinical diagnosis is made by positive blood or urine
cultures or by focal active infection of nonocular tissues.

The management approach in cases of suspected endogenous

Candida endophthalmitis is generally tailored to the clinical
situation. When chorioretinal infiltrates are present with no or
minimal vitreous involvement, systemic therapy alone is
recommended. With moderate-to-severe vitreous involvement
(Fig. 14) or in cases with a worsening course in spite of systemic
therapy, vitrectomy and intraocular amphotericin B are generally
recommended. Although many antifungal agents are not available
for intravitreal administration, voriconazole and miconazole are
treatment options for amphotericin-resistant fungi (Table 9).

Fig. 14. Endogenous fungal

endophthalmitis. Left: The patient
presents four weeks following surgery
involving the large intestine. A
progressive retinal infiltrate (Candida) is
seen below the optic disc; visual acuity is 20/400. The patient was
treated with pars plana vitrectomy and injected with intravitreal
amphotericin B 5 μg. The patient was treated systemically with
fluconazole 400 mg daily. Right: The culture confirmed Candida
species. Final visual acuity improved to 20/25. The uninvolved
crystalline lens was not removed in this patient.
TABLE 9. Antifungal Agents
I. Polyenes
      Amphotericin B
Action:Bind to membrane sterols and
      Nystatin Ointment
increase permeability
      Natamycin
(Primaricin)
II. Imidazoles
Action:Inhibition of membrane-
      Miconazole
dependent enzymes
      Ketaconazole
III. Triazoles
      Voriconazole Action:Same as imidazoles, but more
      Fluconazole specific binding
      Itraconazole
IV. Pyrimidine synthesis
inhibitors Action:Inhibitor of DNA/RNA synthesis
      5–Fluorocytosine
 

The choice of systemic antifungal agents is based on several

factors.27,114 For example, if there is no evidence of disseminated
disease or if patients are too ill to tolerate the toxicity associated
with systemic amphotericin B, other less toxic systemic oral
antifungal medications can be used. This is usually administered in
conjunction with an infectious disease consultant.

When Aspergillus infection is suspected, aggressive local ocular

therapy including vitrectomy and intravitreal amphotericin B is
usually indicated.25 Successful treatment in Aspergillus
endophthalmitis cases can be accomplished, but the occurrence of
a macular abscess may reduce central vision on a permanent basis
(Fig. 15). Because an intraocular Aspergillus infection is frequently
associated with other organ involvement, particularly cardiac valve
vegetation, a comprehensive systemic evaluation is mandatory,
and systemic therapy is indicated in most cases.

Fig. 15. Endogenous fungal

endophthalmitis. Left: Patient with
history of intravenous drug abuse
presents with progressive visual loss in
the right eye. Marked retinochoroidal
infiltrate is identified in the posterior pole. The patient was treated
with pars plana vitrectomy and injected with amphotericin B 5 μg.
Right: Aspergillus species was isolated from the vitreous
specimen. Final visual acuity was 20/200 because of prominent
chorioretinal scarring in the macula following treatment.
Endogenous bacterial endophthalmitis is felt to be less common
than fungal endophthalmitis. In a 10-year retrospective study of 28
bacterial cases at the Massachusetts Eye and Ear Infirmary,26 the
fol1owing organisms were most frequently isolated: S. aureus
25%, Escherichia coli, 18%, and Streptococcus species 30%.
Sources of infection were identified in 90% of cases. Endocarditis
and the gastrointestinal tract were the most common sources.

In a retrospective review of 72 cases of endogenous

endophthalmitis from multiple sources, one report reviewed the
spectrum of causative bacteria and showed B. cereus as the most
frequently reported bacterial agent.23 This high incidence of
endogenous Bacillus endophthalmitis was due to its association
with intravenous drug abuse. This report also showed an increasing
incidence of infections by organisms of low pathogenicity in
immune-compromised hosts. The authors of this series proposed a
classification scheme for endogenous endophthalmitis based on the
location (anterior or posterior segment) and extent (focal or
diffuse) of the primary intraocular infection. Focal and anterior
cases appear to have a better visual prognosis, while posterior
diffuse disease nearly always leads to significant loss of vision. 23

To diagnose endogenous bacterial endophthalmitis, a high index of

suspicion is important. All patients with visual loss and progressive
intraocular inflammation should undergo indirect ophthalmoscopy
looking for evidence of septic foci in the posterior segment. In
some cases, the established intraocular inflammation is the initial
finding leading to the diagnosis of bacterial endocarditis and
sepsis. As with endogenous fungal endophthalmitis, an internist or
infectious disease specialist should be involved in both the
systemic workup and medical therapy. Some patients will present
with a known site of infection. In these cases, the intraocular
organism is almost always the same as that cultured from the
other organ site. These findings will help guide the selection of
appropriate antibiotic therapy for both the systemic and ocular
infection. In cases without a known site of infection other than the
eye, a systemic laboratory workup that includes cultures of blood,
urine, sputum, and other suspicious sites should be obtained.

Systemic antibiotics are often used to treat of endogenous

endophthalmitis. In cases with focal chorioretinitis but without
marked vitreous infiltrates, systemic therapy alone may achieve
involution of the lesions. In eyes that fail to respond to systemic
antibiotic therapy alone, intraocular therapy may be beneficial.
When severe vitritis or marked vitreous infiltrates are present, a
vitrectomy and intraocular antibiotic injection are usually
recommended.114
Back to Top
ENDOPTHTHALMITIS AFTER INTRAVITREAL
INJECTIONS
Endophthalmitis after intravitreal injection (Fig. 16) is an
uncommon complication that has become the focus of attention in
recent years as the use of intravitreal triamcinolone acetonide and
various anti-angiogenesis medications have become available
(Table 2). It is important to distinguish infectious endophthalmitis
from a noninfectious pseudohypopyon caused by triamcinolone
acetonide crystals (Fig. 17). Another modality, pneumatic
retinopexy, is also rarely associated with the development of
endophthalmitis. In the multicenter clinical trial on pneumatic
retinopexy, one patient out of 103 eyes in the pneumatic
retinopexy group developed endophthalmitis. A total of three
endophthalmitis cases have now been reported following
pneumatic retinopexy.115–117 The most common isolate is S.
epidermidis and treatment approaches include standard intravitreal
antibiotic injection as performed in postsurgical endophthalmitis.
Strategies to reduce the risk of endophthalmitis include using a
povidone-iodine ocular preparation (Fig. 18), using a lid speculum
(Fig. 19), and avoiding needle contact with the lid margins and
lashes (Fig. 20).

Fig. 16. Infectious endophthalmitis

following intravitreal triamcinolone
acetonide injection. Left: Marked
conjunctival congestion, hypopyon, and
prominent fibrin in the anterior
chamber. Visual acuity is reduced to hand motion. Right: Higher-
powered view of the anterior chamber shows marked fibrin
strands in the anterior chamber.

Fig. 17. Noninfectious endophthalmitis

after intravitreal triamcinolone acetonide
A pseudohypopyon is created by the
triamcinolone crystals in the anterior
chamber. Notice the quiet conjunctiva,
small, very white hypopyon, and
minimal fibrin. This patient was
examined on the second postinjection
day as part of a routine follow-up
protocol. No treatment was given and the psuedohypopyon
cleared spontaneously.
 Fig. 18. A povidone-iodine preparation is
used to prepare the eye for an
intravitreal injection.

Fig. 19. A lid speculum maintains the lid

position and allows access to the pars
plana region for intravitreal injection.

Fig. 20. In spite of the preparation with

povidone-iodine, it is recommended that
needle contact with the lid margins and
lashes be avoided.

Back to Top
PREVENTION
Eyelid and ocular surface microflora have been implicated as the
source of infection in most cases of postoperative
endophthalmitis.40 Because bacteria can be cultured from the
ocular surface of almost any person, certain risk factors may make
patients more susceptible to infection by their ocular surface
microflora. Risk factors for endophthalmitis include chronic
bacterial blepharitis, active conjunctivitis, infections of the lacrimal
drainage system, tear drainage obstruction, contaminated eye
drops, contact lens wear, a prosthesis in the fellow eye, and active
nonocular infections.118–121 These conditions may lead to an
abnormally elevated population of ocular surface microbes or
colonization of the ocular surface by atypical organisms with
greater virulence than the normal microflora. Intraoperative risk
factors are prolonged surgery (>60 minutes), surgery complicated
by vitreous loss, and contaminated irrigating solutions or
intraocular lenses.121 Postoperative entry of ocular surface
microflora may be facilitated by mechanical wound problems such
as wound leaks or vitreous incarceration in the surgical wound.12
Host factors that lower resistance to infection such as chronic
immunosuppressive therapy and diabetes mellitus have also been
reported to be significant risk factors for postoperative
endophthalmitis.7

To reduce the incidence of postoperative endophthalmitis, each of

the factors implicated in the pathogenesis should be addressed.
First, an attempt should be made to decrease or eliminate eyelid
and conjunctival microflora both preoperatively and
intraoperatively. This goal may be accomplished by using
preoperative topical antibiotics and topical antiseptic agents.
Second, administering subconjunctival antibiotic at the time of
surgery should be considered.

Studies evaluating the effectiveness of preoperative administration

of antibiotics and povidone-iodine have reported a significant
decrease in conjunctival bacterial colony counts. 122–125 Topical
antibiotics were reported to be most effective in decreasing
conjunctival bacterial colony counts when administered 2 hours
before surgery rather than one or more days before surgery. 123 The
combination of topical antibiotics and povidone-iodine was found to
sterilize the conjunctiva in more than 80% of treated patients. 122

Subconjunctival antibiotics are commonly administered after

intraocular surgery. The rationale for subconjunctival antibiotic
administration at the completion of the ocular procedure is to
inhibit growth of bacteria that may gain entry into the eye during
the operative procedure. Studies performed evaluating the
effectiveness of prophylactic subconjunctival antibiotics in reducing
the incidence of postoperative endophthalmitis reported conflicting
results.119–121

Administering antibiotics in the irrigating fluid for cataract surgery

has become a common technique for infection prophylaxis. This
technique carries the risks of antibiotic toxicity, cost, and the
possibility of emergence of resistant bacteria. 126–127 One study
showed a higher risk of postoperative cystoid macular edema with
prophylactic instillation of vancomycin in irrigating fluid.128 At least
10 patients in the EVS developed endophthalmitis in spite of
receiving antibiotics in the irrigating fluid for cataract surgery. The
non–peer-reviewed literature contains reports of extremely low
infection rates, but statistical support has been lacking. Thus, the
risk-to-benefit ratio of this approach is not known. The American
Academy of Ophthalmology (2000) has issued a Policy Statement
discouraging the routine use of antibiotics in the irrigating fluid for
cataract surgery.

The various strategies to prevent postoperative endophthalmitis

are based on current knowledge regarding the pathogenic
mechanisms of postoperative endophthalmitis. Perhaps of greatest
importance, the preoperative ocular examination will help to
identify the high-risk patient as previously described. In these
patients, eyelid and conjunctival cultures can be performed before
performing intraocular surgery. Based on the culture results and
the overall clinical evaluation, preoperative topical antibiotic
treatment may be considered. In patients with eye diseases
requiring chronic administration of topical medications, new sterile
medications should be provided to the patient before and after
intraocular surgery.

On the day of cataract surgery, treating patients with prophylactic

topical antibiotics that have activity against organisms commonly
causing endophthalmitis can be considered. A thorough surgical
prep, which includes lid margins, is performed. Instillation of 5%
povidone-iodine on the conjunctiva followed by irrigation with
saline is part of the surgical prep.129 The eyelids and eyelashes can
be draped out of the surgical field with a plastic eye drape. A dry
surgical field can be maintained when instruments are passed in
and out of the eye. Attention to watertight wound closure is a
priority, particularly in complicated surgical procedures or in
reoperations that tend to have a higher incidence of postoperative
wound leak. Vitreous incarceration in the wound should be
eliminated by anterior vitrectomy techniques. At the conclusion of
surgery, subconjunctival antibiotic injection using a combination of
agents effective against the majority of causative gram-positive
and gram-negative organisms can be considered.
Back to Top
CONCLUSION
Endophthalmitis can be associated with intraocular surgery,
penetrating trauma, or endogenous sources and may cause severe
visual loss. Early recognition, together with appropriate and timely
treatment, may reduce visual loss associated with endophthalmitis.
Identifying and treating high-risk patients before intraocular
surgery and maintaining careful aseptic techniques during
intraocular surgery can reduce the incidence of endophthalmitis.