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Saudi Journal of Ophthalmology (2012) 26, 181189

Ophthalmic Pathology Update

Endophthalmitis: A review of recent trends


Janice R. Safneck, MD, FRCPC

Abstract
Endophthalmitis is a feared complication of trauma, surgical procedures and septicemia. Although uncommon, its potential for
significant visual loss is well recognized. Especially over the past decade, complicated surgeries and medical techniques have
increased and seriously ill patients are being sustained in ever increasing numbers. New pathogens are being recognized and
known ones reclassified thanks to advances in molecular analysis. Continuously evolving PCR methodologies also add a new
dimension to the diagnosis of infectious endophthalmitis. As well, medical literature is now truly international, encompassing studies from around the world that expand our understanding of ocular infectious disease. This report reviews some of these changes
as they relate to endophthalmitis and particularly to the spectrum of organisms involved.
Keywords: Endophthalmitis, Intraocular infection, Exogenous endophthalmitis, Endogenous endophthalmitis, Fungal endophthalmitis, Bacterial endophthalmitis
2012 Saudi Ophthalmological Society, King Saud University. All rights reserved.
http://dx.doi.org/10.1016/j.sjopt.2012.02.011

Introduction
Endophthalmitis, defined as inflammation of one or more
coats of the eye and adjacent cavities, is an uncommon
potentially sight-threatening condition that varies geographically in incidence and in cause. It may be categorized by clinical course (acute versus chronic), by etiology (infectious
versus non-infectious), by the route the causative agent enters the globe (exogenous versus endogenous) and by the
organism(s) involved (bacteria, fungi, parasites and rarely,
viruses1). Certain organisms tend to be associated with particular clinical settings, means of intraocular access and types
of inflammation (acute, chronic non-granulomatous, chronic
granulomatous or mixed cellular response).
Studies looking at the overall incidence of endophthalmitis
yield differing results. For example, a recent British report
analyzing acute endophthalmitis trends between 1991 and
2004, found that of 120 cases, 59% were exogenous and
41% endogenous in origin.2 In comparison, another series

from India of 955 patients presenting during a 10-year period


found 92.6% exogenous endophthalmitis and only 7.4%
endogenous endophthalmitis.3 Factors influencing variation
between multiple reported studies include the period in time
analyzed, prevalence of predisposing illnesses, geographic
factors in organism incidence, urban versus rural settings,
ethnicity, outpatient versus inpatient populations especially
those in tertiary care centers, and the small size of many
reported series.

Exogenous endophthalmitis
Exogenous endophthalmitis refers to infections resulting
from breach of the globe exterior through surgery or trauma,
or by fulminant progression of inflammatory processes such
as keratitis or scleritis.
Most postoperative endophthalmitis develops after cataract surgery as millions of these procedures are performed
annually worldwide. Both acute endophthalmitis (generally
arising 2448 h to a week post surgery) and chronic forms

Received 29 January 2012; accepted 26 February 2012; available online 3 March 2012.
Departments of Pathology and Ophthalmology, University of Manitoba, Winnipeg, Manitoba, Canada
Address: Department of Pathology, MS-459A, 820 Sherbrook St., Winnipeg, Manitoba, Canada R3A 1R9. Tel.: +1 204 787 1997, mobile: +1 204 791
1787; fax: +1 204 787 4942.
e-mail address: safneck@cc.umanitoba.ca
Peer review under responsibility
of Saudi Ophthalmological Society,
King Saud University

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182
(presenting 46 weeks or more post surgery) may occur.
Other procedures associated with varying risks of endophthalmitis include corneal surgeries (penetrating keratoplasty,
keratoprosthesis insertion, refractive corneal surgeries), vitreous procedures (intravitreal injections, vitrectomies), glaucoma surgical treatments (blebs, glaucoma valve
placements), procedures to correct retinal detachment
including scleral buckling, and other miscellaneous ocular
surgeries, even strabismus correction. Most cases are sporadic but occasionally are clustered, suggesting contaminated materials/solutions or problems with instrument
sterilization likely are responsible.4,5 In these situations, unusual bacterial pathogens may be found.
Several recent studies from different parts of the world
(India, China, Sweden, Norway, United Kingdom, USA) provide
post cataract surgery endophthalmitis incidence figures ranging from 0.02% to 0.11% and post penetrating keratoplasty
endophthalmitis from 0.108% to 0.5%.612 Studies from the
Bascom Palmer Institute in Florida covering 3 separate time
periods (19841994, 19952001, 20022009) show a decrease
in post cataract surgery endophthalmitis from 0.08% to 0.05%
to 0.025% in the most recent series.10,11,13 The change was
attributed to progressive improvements in microsurgical and
aseptic techniques. The effect of utilizing clear corneal instead
of scleral incisions has raised fears of increased infection;
however, Lalwani et al.s study14 also from Bascom Palmer,
found similar clinical and microbiologic data although the mean
time to presentation was increased.
Predominant symptoms include decreased vision and pain
while inability to visualize the fundus, pupillary fibrin membrane
and hypopyon are the most common findings.15 Generally
studies have found coagulase negative Staphylococcus is the
top pathogen,68,14 comprising in some series more than 60%
of isolates. Enterococci and streptococci were also frequent
in a study from Sweden6. However, in 2 reports from India,
the incidence of Gram positive and Gram negative bacteria
was approximately equal and more cases of Pseudomonas
aeruginosa endophthalmitis were identified.9,16 Although less
common than bacterial cases, fungal endophthalmitis can
occur post cataract surgery,17,18 and is more frequent in Indian
series where detection of Aspergillus sp. eclipses Candida sp.18
The majority present acutely but latency periods of more
than 200 days have also been reported.18
In chronic endophthalmitis, a pale intracapsular plaque,
fibrinous reaction in the anterior chamber and uveitis may
be seen. Histopathological examination of explanted intraocular lens implants (IOLs) has revealed the presence of bacteria
in relation to lens capsule and/or on the IOL surface, accompanied by inflammatory cells including lymphocytes, plasma
cells and neutrophils.19 Less commonly, fungi (especially
Candida sp.) may be identified.20 Cultures, scanning and/or
transmission electron microscopy or DNA analysis21,22 have
found evidence of Staphylococcus sp. (especially S. epidermidis), Propionibacterium acnes, filamentous bacteria (including
Actinomyces and Nocardia sp.) or mixed bacterial population.19,21,2325 The bacteria are usually a part of conjunctival
flora (although occasional reported organisms such as Enterococcus faecalis are not), and are capable of producing acute
endophthalmitis as well as chronic infections. They adhere
to IOLs and create microcolonies through biofilm formation
that consists of microbes, glycocalyx and surface. Glycocalyx
is a complex mixture of bacterial exopolysaccharides and
locally available cellular materials such as proteins and nucleic

J.R. Safneck
acids that together act as a glue.26 In biofilm, organisms are
well protected from host inflammatory responses, both
physically and through multiple genetic changes that alter
antigenicity. However, as the organisms multiply, those
that are shed outside the biofilm may revert to the original
form, rendering them vulnerable to attack. Organisms in the
biofilm are thus difficult to eradicate and may persist as a
nidus of infection despite apparent response to antibiotic
treatments, resulting in relapsing endophthalmitis.22

Cornea-related endophthalmitis
The majority of endophthalmitis is bacterial27,28 and
mainly due to Streptococcus sp. and Staphylococcus sp. In
one series, Gram negative organisms caused approximately
a quarter of infections.27 Fungal (Candida sp.) endophthalmitis also has been reported2831 and may be increasing: cases
have been linked to donor-to-host spread and correlate with
longer donor cornea storage times.29 Recently, more limited
transplantation such as Descemet stripping automated endothelial keratoplasty (DSAEK) is gaining favor. So far, there
have been limited reports of endophthalmitis post DSAEK,
with Mycobacterium abscessus,32 Streptococcus pneumoniae33 and Candida parapsilosis34 the pathogens involved.
In comparison, endophthalmitis secondary to keratitis is
predominantly bacterial, in both American and Indian
series.3,33,36 P. aeruginosa followed by Staphylococcus and
Streptococcus sp. are common causes with filamentous fungi
particularly Aspergillus sp.36 and Fusarium sp.37 making up to
40% of pathogens in one study.36 Contributing factors include dry eye, corneal perforation, systemic immune dysfunction and both topical and oral steroid use.35 Acanthamoeba
is well known for its ability to produce vision-threatening
keratitis that can be difficult to treat. However, it is highly
unusual for keratitis to progress to Acanthamoeba endophthalmitis38,39 even though in Kitzmann et al.s series40 this
occurred in 1 of 31 Acanthamoeba infected corneas.

Endophthalmitis associated with vitreous procedures


Both infectious and non-infectious endophthalmitis have
been documented after intravitreal injections administering
triamcinolone or anti-vascular endothelial growth factor
agents (anti-VEGF). Risk is low but has increased as more
injections are performed. Endophthalmitis incidence varies
widely. Deriving meaningful conclusions from published data
requires careful assessment since most series are retrospective with non-uniform injection protocols of varying therapeutic agents. Some large recently published/cited examples
include McCannels meta-analysis of 105,531 anti-VEGF
injections with 54 instances of endophthalmitis (0.049%), 26
of which were culture positive with Streptococcus sp. most
commonly isolated (31%)41; Jagers meta-analysis of all kinds
of intravitreal injections with 24 cases of endophthalmitis per
14,866 injections, most frequently due to Staphylococcus
sp.42; and Murrays series of 34, 278 injections with 9 cases
of endophthalmitis (0.03%), 5 of which were culture positive,
predominantly Streptococcus.43 A subset of this latter group
performed with standardized protocols, sterile techniques
and patient follow-up had just one case of endophthalmitis
(Staphylococcus epidermidis) in 10,142 injections.43 Other
organisms reported include Hemophilus influenzae and

183

Endophthalmitis: A review of recent trends


Mycobacterium chelonae abscessus.44 Differentiation between infectious and non-infectious endophthalmitis is often
a challenge. Irigoyen et al.45 found commonly cited factors
for distinction, i.e., lack of pain, conjunctival injection and earlier presentation, were not always helpful; in her study, they
applied reasonably well to infectious endophthalmitis post
anti-VEGF injection but were only rarely apparent in bacterial
endophthalmitis following triamcinolone injections. Her
group also noted 12 patients who had poor visual outcomes
although this may have been at least in part due to underlying conditions. Since all endophthalmitis cases in the series
presented within the first 48 h, vigilance from 24 to 72 h post
injection was recommended.
Concerns have been raised that increasing use of sutureless 25-gauge vitrectomy would lead to an increased incidence of exogenous endophthalmitis over that found with
20-gauge pars plana vitrectomy. Study results have been
conflicting and a recent meta-analysis of 6 large series found
interinstitutional differences in surgical practices and the
population base made drawing conclusion difficult.46 However, diabetes mellitus is recognized as a risk factor for exogenous endophthalmitis in all types of vitrectomy.

Glaucoma surgery endophthalmitis


Glaucoma related surgeries, blebs and implants (Molteno, Baerveldt and Ahmed), also may be associated with
infectious endophthalmitis (Fig. 1). A large study of Ahmed
glaucoma valves (542 eyes in 505 patients) from Riyadh
found endophthalmitis developed in 9 eyes (1.7%).47 Combining these findings with a review of reports from 1991
to 2003 yielded 27 instances of endophthalmitis in 1427
cases with an occurrence rate of 1.9%. Endophthalmitis
developed 63330 days post valve insertion. Both acute

and chronic forms occurred and children are much more


likely to be affected than adults. Conjunctival erosion
overlying the valve tube was common. Most frequent organisms were Haemophilus influenzae and Streptococcus sp.
and less commonly, P. aeruginosa.47 Similarly, both acute
and delayed onset endophthalmitis may develop with filtering blebs, reported to occur in 0.29.6% of cases. In a recent series of 71 eyes from 68 patients, one quarter of
patients had a bleb leak and 83% were culture positive, predominantly for Streptococcus sp., a variety of Gram negative organisms (Moraxella sp., P. aeruginosa, H. influenzae,
Serratia sp.) and coagulase negative Staphylococcus. Thirteen percent (9 eyes) had polymicrobial infections and the
same percentage ultimately was eviscerated/enucleated.48
More virulent organisms than seen in post cataract surgery
endophthalmitis and poor visual outcomes have been noted
in other studies as well.48

Exogenous endophthalmitis secondary to trauma


Posttraumatic endophthalmitis has an overall frequency of
<118.9% in recently reported series.4954 Intraocular culture
results post-trauma do not necessarily correlate with the
presence of endophthalmitis.53 Onset may be acute or delayed but the most virulent organisms can destroy an eye in
hours. Risk factors for infection differ in various series and
comparison can be challenging as series are usually retrospective and treatment practices not consistent; outcomes
also vary widely with trauma and endophthalmitis related
damage together impairing successful recovery. Amongst
the best results reported were visual acuity of 20/200 or better in 67% of patients55 Longer time between injury and
examination, poorer visual acuity at presentation, virulence
of organisms, and the presence of an intraocular foreign

Figure 1. Mycobacterial endophthalmitis post Ahmed valve insertion (A). Abundant inflammation was seen especially at the tube insertion site (B,
hematoxylin and eosin, 40). Acid fast bacilli are noted in suppurative inflammation without giant cells or granulomas (C, ZN 600).

184
body (IOFB) were often reported as significant for endophthalmitis development.50,53,56,57
In both adult and pediatric series of posttraumatic
endophthalmitis from around the world, Staphylococcus
and Streptococcus sp. are the most frequent pathogens
55,58,59
P. aeruginosa and B. cereus also are frequently identified51,60 but their prevalence varies with geographic location.
Bacillus sp. infections are noteworthy for the rapid
destruction they can cause, with visual loss and often loss
of the eye in hours to a few days after injury (Fig. 2). In two
retrospective series, only 15 of 31 and 8 of 22 patients with
Bacillus sp. endophthalmitis ultimately had visual acuity better than 20/400.61,63 Bacillus sp. have been reported as
responsible for 1546% of post-traumatic endophthalmitis
but are only rarely isolated from post-surgical endophthalmitis cases.62 B. cereus is most commonly found in America62
while in an Indian study,61 a variety of species were isolated
and some infections were caused by a mixture of Bacillus
sp. Bacillus organisms are spore-forming Gram positive rods,
ubiquitous in soil, water and dust. Initial reports suggested
that these bacteria were particularly associated with metal
object lacerations but a variety of trauma causes have been
reported. Virulence is attributable to bacterial toxins hemolysins, lipases, enterotoxins and proteases acting together.63 As well, wild-type motile strains are more virulent
than non-motile ones as they can cause not only posterior
disease but also anterior segment destruction.64 Experimental studies have demonstrated that decline in retinal function
and neutrophilic infiltration of vitreous can occur as fast as 4 h
post-infection,65 suggesting that therapeutic interventions
must be initiated rapidly if vision is to be saved.
In two recent studies from Saudi Arabia56 and India,66 fungi made up 3.8% and 7.3% of post-traumatic endophthalmitis
respectively. Gupta et al noted filamentous fungi especially
Aspergillus sp. and Fusarium sp. were usually isolated.66
The incidence of endophthalmitis associated with IOFBs
varies but they generally increase the risk of endophthalmitis
over that associated with open globe injury alone. Bhagat
et al.57 in their extensive literature review of post-traumatic
endophthalmitis noted a range of 3.130% without an IOFB

J.R. Safneck
and 1.360% with an IOFB.57 Degree of risk is dependent
on size and composition of the foreign body including any
contaminating materials such as soil, the speed with which
it enters the globe, its path within the eye, the length of time
between injury and foreign body removal, and the immune
system of the affected individual in addition to treatment
undertaken. Most endophthalmitis associated with IOFBs is
bacterial, and Bacillus sp. are particularly of concern in this
setting. In addition, vision-threatening sterile reactive
endophthalmitis also can develop from IOFBs, in particular
with metallic IOFBs, especially copper.57

Endogenous endophthalmitis
Endogenous or metastatic endophthalmitis is typically the
result of hematogenous spread. It is highly unusual for individuals with endogenous endophthalmitis to have no risk factors for systemic infection67 although it has been reported.68
Patients generally have a history of chronic illness (diabetes,
HIV, malignancy, intravenous drug use), transplantation,
immunosuppressive therapy, and/or catheterization. Bacteria
and fungi are the most common pathogens, the former typically Staphylococcus sp., Streptococcus sp. and Klebsiella
pneumoniae, the latter generally Candida sp. or Aspergillus
sp. A variety of organisms, including agents that are little
known and/or otherwise of limited virulence have been
increasingly found.69 Even protozoa such as Microsporidia70
and amoebae71 may be pathogens, including in patients with
no history of HIV infection. In culture proven endogenous
endophthalmitis, fungi typically exceed bacteria as isolates,7274 62% versus 38% as illustrated by one recent
study75 but in some but not all East Asian populations, bacteria are more frequent.76
The vast majority of affected individuals are adults with
pediatric endogenous endophthalmitis representing between 0.1% and 4% of cases, incidence dependent on cohort
location with higher rates in India than in America.77 Patients
may have overt systemic sepsis, or the initiating focus of
infection may be occult, consisting of either multiorgan

Figure 2. Bacillus sp. post-traumatic endophthalmitis (A) leading to evisceration 48 h after penetrating injury with metallic shards. Numerous organisms
were seen in the inflammatory debris (B, Gram stain, 1000).

Endophthalmitis: A review of recent trends


subclinical involvement or a localized clandestine nidus of
pathogens, possibly with only transient bacteremia/fungemia
as an explanation for the infective endophthalmitis.78,79 Both
these scenarios can present diagnostic perils. Patients without obvious systemic infection may have their endophthalmitis misdiagnosed,75,80,81 or have it thought to be a strictly
ocular process, leaving unrecognized possibly devastating
disease elsewhere (for example, endocarditis). Seriously ill
patients may neglect or be unable to mention eye symptoms
and medical staff may be so focused on other pressing issues
that endophthalmitis is overlooked until vision is permanently
compromised.
Some literature reports suggest endogenous endophthalmitis is increasing, perhaps because of expanded transplantation, more complicated surgeries and the ability to keep
serious ill patients alive longer. Consequently, it has been
recommended that ophthalmic screening should be routine
in high risk situations such as intravenous drug use, long term
antibiotics, immunosuppressive therapy, primary or secondary immunodeficiency, prolonged central line use, debilitated
patients and premature infants.82 On the other hand, even in
the setting of culture-proven sepsis, endogenous endophthalmitis is unusual. Lingappan et al.83 found no cases of
endophthalmitis in the routine screening of patients with
fungemia. Feman et al.84 observed that of 82 patients with
systemic fungal disease, only 2 patients developed endophthalmitis and Dozier et al.85 noted that of 211 patients with
positive fungal cultures at a tertiary care center, less than
1% had ocular involvement.
These apparently conflicting findings illustrate that endogenous endophthalmitis is a complex subject. In part, this relates to the patient population studied, their risk factors, to
the organism(s) involved and to the early administration of
antibiotic/antifungal agents in bacteremic/fungemic patients.
Candida sp. are the most commonly reported causes of
endogenous endophthalmitis,67,86,87 perhaps not surprisingly
as yeasts including Candida make up 25% of blood stream
infection acquired in American hospitals.88 However, while
historically the rate of intraocular Candida sp. infections
was between 9% and 45%,67 current rates are around 12%
likely due to the early identification of Candida and prompt
administration of antifungal agents in septic patients.84,89
Two recent series are illustrative of this point. In a Scandina-

185
vian study of 203 patients with Candidemia, 9 cases of retinitis and 1 of endophthalmitis were detected.88 In a similar
American study of 38 patients with Candidemia, 8 had chorioretinitis but none had endophthalmitis.90 In excess of 150
Candida species are documented human pathogens, yet
Candida albicans remains the most important although others such as C. glabrata, C. tropicalis, C. dubliniensis and C.
krusei are being increasingly detected.91 C. albicans has been
shown in several reports to have a greater risk of progression
from chorioretinitis to endophthalmitis, in keeping with
greater virulence and prevalence,89,90 while the opposite is
true of C. parapsilosis.89 Risk factors for the development
of Candida endogenous fungal endophthalmitis include diabetes, antibiotic use, gastrointestinal surgery, catheters, solid
tumors, intravenous drug use and immunosuppression.78,79,87,9294 Many patients with identified ocular disease
are without ocular symptoms89 or present in a subacute fashion with altered vision, low-grade pain, photophobia and
injection.90 Experimental models of C. albicans endogenous
endophthalmitis have shown the initial lesions appear at the
equator then spread posteriorly, and animals with prior steroid treatment had more fungal pseudohyphae than those
without.95 Histopathologic study of clinical enucleation specimens have demonstrated Candida organisms in vitreous with
associated suppurative non-granulomatous inflammation and
typically minimal if any choroidal or retinal necrosis.93 These
findings are consistent with 7685% of endogenous Candida
endophthalmitis patients having final visual acuities of 20/200
or better.78,96
In studies of endogenous fungal endophthalmitis, Aspergillus sp. have been reported less frequently than Candida
sp., 75% versus 25% in an American study83 but are much
more visually devastating.75,79,97,98 Aspergillus endogenous
endophthalmitis often presents with nonspecific symptoms
but rapidly progressive retinal damage soon occurs (Fig. 3).
Histopathological analysis of enucleated globes has shown
involvement of retinal and choroidal vasculature with retinal
necrosis and predominantly a neutrophilic inflammatory response although chronic granulomatous inflammation may
be found.93,98 Septate fungi with 45 angle branching are
typical of Aspergillus sp. but do not permit definitive diagnosis as some other molds (e.g. Monosporium apiospermum/
Pseudoallescheria boydii) can be morphologically similar.

Figure 3. Bilateral Aspergillus sp. endophthalmitis in a renal transplant patient. Endocarditis was suspected but not confirmed until just prior to death
(A). Globe at autopsy with hazy vitreous and pale thickened retina (B). Microscopy revealed abundant neutrophilic inflammation in vitreous and retina
with fungal hyphae (C, hematoxylin and eosin, 200).

186
Culture and/or PCR technique are needed for definitive diagnosis. Aspergillus fumigatus is the most common species
found with A. flavus second. However, in some studies, Fusarium sp. outnumber Aspergillus sp.79
Risk factors for endogenous Aspergillus endophthalmitis
include corticosteroid use, intravenous drug use, solid organ
and stem cell transplantation and lung disease, and many patients have more than one underlying contributing condition.69,79,98 Approximately three quarters of cases are
unilateral and one quarter ultimately involve both eyes. More
than half have spread to other organs. Blurred vision, eye
pain and redness are common and in one study, vitritis was
observed in 45 of 73 cases and retinal lesions or chorioretinitis in another 28. Only 2 patients had anterior chamber
involvement.98 This distribution is consonant with vitrectomy
as the most reliable means of organism diagnosis.79,83
Recovery of useful vision has been reported in 010%.75,98
Just over half of the patients have a diagnosis of Aspergillus
endophthalmitis made only after autopsy98 and in cancer patients, filamentous fungal endophthalmitis such as Aspergillus sp. is a marker for high mortality.69,79 Brain, lung and
heart (endocarditis) are other typical sites of involvement at
post-mortem.
Endogenous bacterial endophthalmitis is much less frequent than endogenous fungal endophthalmitis or exogenous bacterial endophthalmitis with an incidence of 2
11%.80 Age ranged from neonates to patients greater than
90 years old with a mean of 5060 years of age depending
on the population/literature assessed.80 Nineteen percent
were bilateral in one study.99 Patients often complain of
blurred vision with ocular pain and most but not all have evidence of systemic illness. Examination reveals hypopyon and
hazy ocular media.80,99 Both Gram positive and Gram negative bacteria have been reported as pathogens with incidences differing around the world. For example, several
reports of East Asian populations76,99101 have clearly documented K. pneumoniae as the predominant endogenous
endophthalmitis cause, with hepatobiliary infections (especially liver abscesses), as the initial disease site and diabetes
mellitus a common co-existing condition.99 Elsewhere in the
world, S. aureus, Group B Streptococcus and S. pneumoniae
have been more frequent.68,80,81 In Caucasians, endocarditis,
skin/joint and urinary tract infections were common organism
sources.80,87,99,102 Other noteworthy pathogens include P.
aeruginosa which is more frequent in individuals younger
than 25 years of age including neonates80 and Neisseria meningitidis which was noted to be decreasing in incidence in the
1980s but still a factor in childhood infections.103 Escherichia
coli has been isolated from endogenous endophthalmitis patients with urinary tract infections80 and from seemingly
healthy individuals who have endogenous bacterial endophthalmitis.68 B. cereus has been associated with intravenous
drug use and, as in trauma-related cases, commonly progressed to evisceration/enucleation.80,103
As with endogenous fungal endophthalmitis, visual outcomes are often poor regardless of the organism involved.68,80,99,104 In Wongs East Asian study, good visual
acuity returned in only 28% of cases.99 Similarly, Jackson in
his British cohort found 81% of affected eyes with light perception or worse.80 More recent cases of K. pneumoniae
have had more patients with visual acuities of at least 10/
200, perhaps due to more clinical experience with the disease. However, overall results are still unsatisfactory with

J.R. Safneck
approximately three-quarters of patients having a visual acuity of 1.101 Statistical analysis has pointed to the virulence of
K. pneumoniae as the most important factor.99 This organism
has been isolated from multiple types of clinical specimens
and may colonize up to 20% of hospitalized patients.100 Animal models of K. pneumoniae endophthalmitis have shown
hypermucoviscosity phenotypes, K1 and K2 capsular phenotypes and aerobactin production as virulence indicators. Recently strains that produce beta-lactamase enzymes
conferring resistance to antibiotics frequently employed in
the treatment of Gram negative endophthalmitis have been
discovered.100 Experimentally, retinal destruction has appeared as soon as 48 h post infection,100 so patients with
posterior infections and cloudy media at presentation are
more likely to do poorly.99 Timely diagnosis and treatment
are essential.

Diagnosis
Aspirate of aqueous and/or vitreous for Gram stain is commonly employed for diagnosis; although helpful when positive for organisms, it is often not very sensitive. In the past,
culture has been the only available means of establishing
organism(s) causing endophthalmitis. As previously mentioned, in endogenous endophthalmitis, vitrectomy cultures
have proven the most reliable with poor concordance noted
between anterior chamber cultures and vitreous isolates.105
Recently, PCR has been found to be an important diagnostic
technique and has been reported to greatly aid in bacterial
and fungal detection.106,107 For example, in one real-time
PCR study, detection of bacteria improved from 47.6% to
95.3%.107 As with cultures, specimen contamination will yield
false positive results and poorly stored specimens can be so
degraded that they are not helpful. Another advantage of
PCR is its rapidity: results can be ready in as little as
90 min,87 a tremendous advantage over cultures, especially
for some slow-growing organisms such as mycobacteria. Further, it can be performed on fixed paraffin embedded histology specimens108,109 to identify organisms not diagnosed
presurgery/autopsy. PCR techniques are important diagnostic tools that hopefully will become more widely available.

Non-infectious endophthalmitis
This condition has diverse etiologies, and includes systemic autoimmune diseases, local ocular inflammations of unknown cause, endophthalmitis related to lens material and
endophthalmitis attributable to intraocular foreign bodies.
Phacoanaphylactic endophthalmitis (lens induced granulomatous inflammation) is a rare consequence of lens injury
and represents an autoimmune response to lens protein to
which the body is normally tolerant.110 This may occur after
trauma, as a result of inflammation from other causes rupturing the lens capsule, or post surgery such as following extracapsular cataract extraction when residual lens cortex is
present. Histopathologically, a mixed neutrophilic and granulomatous response is centered around the lens, typically in a
zonal pattern: neutrophils associated with degenerating lens
material are surrounded by giant cells and histiocytes which
are in turn encircled by chronic non-granulomatous inflammation. The condition is suspected clinically in only 5% of histologically proven cases and thus is usually a surprise at

187

Endophthalmitis: A review of recent trends


enucleation. However, diagnosis is also possible in vivo on
fine needle aspiration biopsy.111 Seventy percent of cases
are associated with patchy choroidal non-granulomatous
inflammation, 60% with retinal detachment, 50% with retinal
mononuclear cell perivasculitis, 30% with optic atrophy and
37% with sympathetic ophthalmia.110,112
The term phacotoxic endophthalmitis was previously
used to cover a mixed group of conditions related to intraocular lens implant surgery. As the inflammation is centered anteriorly, the term toxic anterior segment syndrome (TASS) is
more appropriate. Causes include reactions to chemicals (irrigation solutions, preservatives, drugs, denatured viscoelastics), IOL materials, instrument sterilization and preparationrelated compounds and bacterial endotoxins.113,114 The latter
are the result of bacterial growth killed by product sterilization
with the heat-resistant endotoxin remaining. In sufficient levels, the endotoxin may produce sterile endophthalmitis.115
Sterile endophthalmitis has been noted as well following intraocular injection, post vitrectomy and after surgery including
glaucoma drainage device implantation. Similar to TASS, the
condition may be multifactorial. Intravitreal triamcinolone acetonide has been associated with pseudoendophthalmitis
caused by triamcinolone crystals migrating into the anterior
chamber; infectious and sterile endophthalmitis have also
been reported in association with this chemical.116
Clinically sterile endophthalmitis and TASS are differentiated from infectious endophthalmitis by the former entities
typically arising within 24 h of surgery, being Gram stain
and culture negative, involving the anterior segment in the
case of TASS, and showing no effect from antibiotics but
improvement with topical and/or oral steroids. However, distinction may be problematic as some infectious cases may
have rapid onset and have initial negative cultures.113

4.

5.

6.

7.

8.
9.

10.

11.

12.

13.

14.

15.

Conclusion
Through an improved understanding of the causes and
epidemiology of endophthalmitis will come further measures
for decreasing the incidence of this dreaded disease. Widespread use of molecular techniques such as real-time PCR
promise to lessen diagnostic times and provide more accurate diagnosis, permitting faster targeted therapies. On the
other hand, the rise of organisms such as methicillin resistant
S. aureus and other super bugs will necessitate constant
vigilance so that the successes achieved so far will not be lost.

16.

Acknowledgements

20.

The author wishes to thank Dr. Lisa Gould and Dr. Stephen
Brodovsky for clinical information pertaining to the case illustrated in Fig. 1.

21.

17.

18.

19.

22.

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