Ocular Immunology & Inflammation, 18(2), 133–138, 2010

Copyright © 2010 Informa Healthcare USA, Inc.

ISSN: 0927-3948 print/ 1744-5078 online
DOI: 10.3109/09273940903494717

Original Article

Endogenous Endophthalmitis: A 10-year Review

of Culture-positive Cases in Northern China
Han Zhang, MD, and Zheli Liu, MD
Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, China

ABSTRACT
Purpose:  The aim of this study was to report the clinical features and treatment outcomes in a series
of patients with endogenous endophthalmitis treated over a 10-year period in a single hospital in
northern China.
Methods:  The authors conducted a retrospective chart review of 19 patients (23 eyes) treated for
culture-proven endogenous endophthalmitis at the First Hospital of China Medical University
between 1998 and 2007.
Results:  Patients were followed up for a mean of 15.9 months (range: 0.5–41 months). The main sys-
temic predisposing risk factors were diabetes mellitus (52.6%), immunosuppressive therapy (36.8%),
and malignancies (31.6%). Fungal isolates were present in 14 eyes (60.9%), gram-positive isolates in
8 eyes (34.8%), and gram-negative isolates in 1 eye (4.3%). All patients received intravenous antibiot-
ics or antifungal agents, and other treatments included injection of intravitreal medication in 7 eyes
(30.4%) and pars plana vitrectomy with injection of intravitreal medication in 14 eyes (60.9%). Final
visual outcomes were obtainable for 21 eyes (one patient died 15 days after diagnosis). Ten (47.6%)
of these 21 eyes achieved a visual acuity of 20/400 or better, and 11 (52.4%) achieved a visual acuity
worse than 20/400, including 5 that were eviscerated. The median visual acuity was counting fingers
(range: 20/25 to no light perception). Eyes with endophthalmitis caused by Candida species tended
to have better visual outcomes than did eyes with bacterial and Aspergillus causes.
Conclusions:  Similar to the findings of previous studies, this study showed that fungi, especially
Candida species, were the most common causative organisms of endogenous endophthalmitis.
Endogenous endophthalmitis is generally associated with poor visual acuity outcomes, particularly
when caused by more virulent species of fungi, such as Aspergillus.
KEYWORDS:  causative organism; endogenous endophthalmitis; predisposing medical conditions; treatment

Endogenous endophthalmitis—a potentially sight-
threatening infection of the eye that usually devel-
ops from the hematogenous spread of organisms
in the intraocular tissue—accounted for 2–15%
of documented cases in a previous large series of
endophthalmitis.1-3 The possible range of infectious
agents is broad and includes gram-positive bacteria,
gram-negative bacteria, and fungi. Most patients with
endogenous endophthalmitis have one or more predis-
posing systemic risk factors, including immunocom-
promised states, debilitating diseases, and a history of
invasive procedures.2-5 Because the diagnosis and treat-
ment of this condition are unfolding, many patients
with endogenous endophthalmitis are misdiagnosed
and the prognosis of these patients is still poor. In this
retrospective study, clinical features and visual out-
comes are reported for patients with culture-proven
endogenous endophthalmitis treated in a single hospi-
tal in northern China for over a 10-year period.

Received 10 November 2009; accepted 17 November 2009 METHODS

Correspondence: Han Zhang, MD, Department of Ophthalmol-
ogy, The First Affiliated Hospital of China Medical University, We conducted a retrospective chart review of all
Shenyang 110001, China. E-mail: zhanghan73@126.com patients treated for culture-proven endogenous
133
134    H. Zhang and Z. Liu
endophthalmitis at the First Hospital of China Medi-
cal University between January 1998 and December
2007. Patients were included in the study if they had
evidence of endogenous endophthalmitis in either eye,
defined as the presence of iritis and vitritis on ophthal-
mic examination, and one or more of the following:
positive aqueous, vitreous, or blood cultures.5 Patients
with endophthalmitis due to other causes, including
postoperative (defined as less than 1 year after any
eye surgery) corneal ulcer-related, glaucoma filtering
surgery-related, or post-penetrating eye trauma, were
excluded. The study was approved by the institutional
review board of China Medical University.
RESULTS
Twenty-three eyes in 19 patients were included in
the study. A summary of the clinical characteristics
of these patients is provided in Table 1. The average
patient age was 61.5 years (range: 37–85 years). Eleven
(57.9%) of the patients were men, and 8 were women.
Four patients (21.1%) had bilateral endophthalmitis,
9 (47.4%) had right eye involvement, and 6 (31.6%)
had left eye involvement. The average duration of
follow-up was 15.9 months (range: 0.5–41 months).
All patients had at least one potential systemic
risk factor for endogenous endophthalmitis (Table 1).
The most common medical condition was diabetes
mellitus (10 patients, 52.6%). Seven patients (36.8%)
had recently received or were receiving therapy with
immunosuppressive agents: 4 with chemotherapy, 2
with systemic steroids, and 1 with immunosuppres-
sive drugs. Of the 6 (31.6%) patients with a history of
malignancy, 2 had lung cancer, 1 had metastatic colon
cancer, 1 had pancreatic cancer, 1 had acute myelog-
enous leukemia, and 1 had lymphoma. Four (21.1%)
patients had received invasive surgery within 0.5 years
of developing endogenous endophthalmitis: subtotal
gastrectomy in 2 patients, renal transplant in 1 patient,
and pulmonary lobectomy in 1 patient. Three patients
(15.8%) had a history of long-term placement of intra-
venous catheters, 1 (5.3%) had a history of intravenous
drug use, and 1 (5.3%) had chronic obstructive pulmo-
nary disease. Sixteen patients had no previous ocular
history, 2 had received surgery for bilateral primary
acute angle-closure glaucoma, and 1 had received sur-
gery for bilateral age-related cataracts.
Ocular symptoms included decreased vision in 20
(87.0%) of the 23 eyes, eye pain in 16 eyes (69.6%),
redness in 12 eyes (52.2%), and photophobia in 7 eyes
(30.4%). The median time between onset of symptoms
and presentation with endophthalmitis was 12 days
(range: 3–69 days). For fungal cases, the median time
to presentation was longer (median: 19 days; range:
5–69 days) compared with bacterial cases (median: 14
days; range: 3–27 days).
Fungal isolates (14 eyes, 60.9%) were more common
than bacterial isolates, and these included Candida albi-
cans (10 eyes), Aspergillus species (3 eyes), and Candida
tropicalis (1 eye). There were 8 (34.8%) gram-positive
isolates, including Staphylococcus aureus (5 eyes),
Streptococcus species (2 eyes), and Staphylococcus epi-
dermidis (1 eye). There was only 1 (4.3%) gram-negative
isolate: Klebsiella pneumoniae. The microbiologic diag-
nosis was based on aqueous or vitreous cultures in
15 eyes (65.2%), and 7 patients (36.8%) had positive
blood cultures. Four of these blood culture-positive
cases showed fungemia, and 3 showed bacteremia. In
patients 6 (right eye) and 11, both blood and vitreous
cultures were positive and grew the same organisms.
Aside from positive blood cultures and eye specimen
cultures, 6 patients (31.6%) had an additional infec-
tious focus, most frequently a urinary tract infection
(2 patients; 10.5%). None of the cultures had more than
one organism isolated (Tables 1 and 2).
The visual acuity (VA) at presentation was 20/400 or
better in 7 eyes (30.4%), ranging from 20/400 to 20/80.
Sixteen eyes (69.6%) had vision worse than 20/400,
ranging from 20/800 to no light perception (Table 2).
Seven (30.4%) of 23 eyes were treated initially
with intravitreal injection of therapeutic agents, and
12 eyes (52.2%) were treated initially with pars plana
vitrectomy and injection of intravitreal therapeutic
agents (Table 2). Generally, surgical intervention was
indicated for patients infected with especially virulent
organisms, a VA of 20/400 or less, or severe vitreous
involvement. Eyes with VA better than 20/400 were
treated with intravitreal injection alone. Four patients
(patients 1, 6 [left eye], 9, and 19) declined the recom-
mended vitrectomy because of poor general health sta-
tus and were treated instead with intravitreal injection
of therapeutic agents. Two of the 7 eyes initially treated
with intravitreal injection eventually underwent sec-
ondary treatment with pars plana vitrectomy. All
patients received intravenous antibiotic or antifungal
agents, and 3 patients (4 eyes; patients 10, 11, and 13)
were treated with systemic antibiotic or antifungal
agents only, i.e., they underwent neither intravitreous
treatment nor vitrectomy. Of these 3 patients, 2 cases
were due to Aspergillus species and 1 case (2 eyes) was
due to Staphylococcus aureus. Both fungal cases (patients
10 and 11) presented with panophthalmitis (proptosis
and restricted motiliti) and required evisceration. The
other patient (patient 13) rejected further ophthalmic
therapy and died 15 days after diagnosis. The initial
VA for these eyes was light perception and no light
perception, respectively.
Final VA outcomes were available for 21 eyes
(defined as the last VA recorded in the medical record
Ocular Immunology & Inflammation
 Endogenous Endophthalmitis in Northern China    135

TABLE 1  Clinical summary

Culture-positive Other i­ nfectious
Pt Eye Age Gender Risk factors Organism specimens focus
1 OD 65 M DM, subtotal gastrectomy Candida albicans Vitreous
2 OS 63 M Lymphoma, chemotherapy Candida albicans Aqueous, vitreous
3 OD 63 F Subtotal gastrectomy, IV Candida albicans Vitreous
4 OU 67 M DM, systemic steroids Candida albicans Blood
5 OS 60 F Lung cancer, chemotherapy Candida albicans Vitreous UTI
6 OU 69 F DM Candida albicans Vitreous (OD), blood Brain abscess
7 OU 43 M IVDU Candida albicans Vitreous (OU)
8 OS 55 M Pulmonary lobectomy, IV Candida tropicalis Aqueous, vitreous
9 OS 85 F Metastatic colon cancer, Aspergillus species Blood, catheter
­chemotherapy, IV
10 OD 48 M DM, renal TX, IT Aspergillus species Vitreous
11 OS 84 F DM, COPD Aspergillus species Vitreous, blood
12 OD 61 M DM Staphylococcus aureus Vitreous UTI
13 OU 59 M DM Staphylococcus aureus Blood Carbuncle
14 OS 37 F AML, chemotherapy Staphylococcus aureus Vitreous
15 OD 73 M DM, lung cancer Staphylococcus aureus Blood
16 OD 70 M Pancreas cancer Staphylococcus epidermidis Vitreous
17 OD 57 F Systemic steroids Streptococcus pneumoniae Vitreous
18 OD 57 M DM Grop B Streptococcus Vitreous Infectious
­endocarditis
19 OD 52 F DM Klebsiella pneumoniae Blood Liver abscess
Note. AML, acute myelogenous leukemia; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; IT,
­immunosuppressive therapy; IV, intravenous catheter; IVDU, intravenous drug abuse; OD, right eye; OS, left eye; Pt, patient; TX,
transplant; UTI, urinary tract infection.

TABLE 2  Treatment and visual outcome

Systemic treatment Intravitreous agents
Pt Organism Initial vision (duration, weeks) (number of injections) Vitrectomy Final vision
1 Candida albicans HM AMP, fluconazole (2) AMP (1) No Evisceration
2 Candida albicans CF AMP, fluconazole (2) AMP (1) Yes 20/400
3 Candida albicans 20/400 AMP, fluconazole (2) AMP (1) Yes 20/60
4 Candida albicans OD: 2/200 AMP, fluconazole (6) OD: AMP (1) Yes 20/60
OS: 20/300 OS: AMP (2) Yes 20/80
5 Candida albicans 20/400 fluconazole (6) AMP (1) Yes 20/200
6 Candida albicans OD: CF AMP, fluconazole (8) OD: AMP (1) Yes 20/400a
OS: HM OS: AMP (2) No Evisceration
7 Candida albicans OD: 20/400 AMP, fluconazole (3.5) OD: AMP (1) Yes 20/200
OS: 20/80 OS: AMP (2) Yes 20/25
8 Candida tropicalis CF fluconazole (2) AMP (1) Yes Evisceration
9 Aspergillus species LP AMP (6.5) AMP (3) No NLPa
10 Aspergillus species NLP AMP (5) None No Eviscerationa
11 Aspergillus species LP AMP (7.5) None No Evisceration
12 Staphylococcus aureus 20/800 CIP, vancomycin (3.5) Vancomycin (1) Yes 20/200
13 Staphylococcus aureus OD: LP CFZ (2) OU: none OU: no OU: unknownb
OS: NLP
14 Staphylococcus aureus 20/200 CFZ, vancomycin (2) Vancomycin (1) Yes HM
15 Staphylococcus aureus CF CFZ, vancomycin (4) Vancomycin (1) Yes CF
16 Staphylococcus epidermidis 20/80 CFZ (2) Vancomycin (1) No 20/40
17 Streptococcus pneumoniae HM Penicillin G, vancomycin (2) Vancomycin (1) Yes LP
18 Grop B Streptococcus 1/200 CFZ, vancomycin (4) Vancomycin (1) Yes HM
19 Klebsiella pneumoniae LP CFZ (5.5) CFZ (2) No LPa
a
Died within 3 months of diagnosis.
b
Died 15 days after diagnosis.
Note. (See Table 1) AMP, amphotericin B; CF, counting fingers; CFZ, ceftazidime; CIP, ciprofloxacin; LP, light perception; NM, hand motion;
NLP, no light perception; OU,both eyes.

© 2010 Informa Healthcare USA, Inc.

136    H. Zhang and Z. Liu
after initial treatment). The final VA improved in 10
eyes (47.6%) after treatment. The median final VA was
“counting fingers” (range: 20/25 to no light percep-
tion), and 10 eyes (47.6%) achieved a final VA of 20/400
or better. Of 14 eyes that underwent vitrectomy, 9 eyes
(64.3%) achieved a VA of 20/400 or better. Eleven
(52.4%) eyes achieved a VA of worse than 20/400,
including 5 eyes that were eviscerated (Table 2). Of the
eyes with bacterial endophthalmitis, 5 (71.4%) of 7 had
final VAs worse than 20/400. Eyes with endophthalmi-
tis caused by Aspergillus species fared the worst; all 3
had no light perception or were eviscerated. Eyes with
endophthalmitis caused by Candida species had a trend
toward better visual outcomes than did the eyes with
bacterial-caused endophthalmitis; 8 (72.7%) of the 11
eyes achieved final VAs of 20/400 or better.
DISCUSSION
Endogenous endophthalmitis, defined as the infection
of intraocular tissue resulting from the hematogenous
spread of organisms to the eye, is both a diagnostic
and treatment challenge for ophthalmologists. Most
patients with endogenous endophthalmitis have one
or more predisposing systemic risk factors, although
cases have been reported in otherwise healthy, immu-
nocompetent persons.6,7 Endogenous endophthalmitis
is associated with many systemic risk factors, includ-
ing chronic immune-compromising illnesses (diabetes
mellitus and renal failure), indwelling or long-term
intravenous catheters, immunosuppressive diseases
and therapy (malignancies, human immunodeficiency
virus infection, and chemotherapeutic agents), recent
invasive surgery, endocarditis, gastrointestinal proce-
dures, hepatobiliary tract infections, and intravenous
drug abuse.2-5, 8-11 We found a similar pattern of systemic
risk factors in our series, the main risk factors being
diabetes mellitus (52.6%), immunosuppressive therapy
(36.8%), and malignancies (31.6%). All patients had at
least one potential systemic risk factor for endogenous
endophthalmitis.
The diagnosis of endogenous endophthalmitis
requires a detailed ophthalmic examination performed
by an ophthalmologist familiar with the disease, and
repeated examinations are often required [12]. Previ-
ously published studies have reported rates of incor-
rect initial diagnosis for Candida endophthalmitis
approaching 50%.4, 5 Jackson’s review found that the
initial misdiagnosis rate ranged between 16% and
63% for endogenous bacterial endophthalmitis.3 In
the current study, the initial diagnosis was incorrect
in 5 patients (patients 1, 2, 6, 8, and 16) who presented
initially to physicians outside our hospital. The ocular
findings for these patients were similar at initial pre-
sentation, masquerading as noninfectious uveitis. All
patients had a significant number of anterior cham-
ber cells without a hypopyon and vitritis varying
from mild to severe. In 5 eyes (patients 1, 2, 6 [both
eyes], and 8), dense vitritis precluded a view of the
posterior pole. These patients were treated with anti-
inflammatory agents, including corticosteroids, for
noninfectious uveitis until the lack of improvement
prompted referral to our hospital. Of these 5 cases,
4 were caused by Candida species (5 eyes), and 1 was
caused by Staphylococcus epidermidis. These findings
underscore the need for ophthalmologists to maintain
a high suspicion for endogenous endophthalmitis in
patients with intraocular inflammation and significant
medical comorbidities and the importance of repeated
ophthalmologic examinations.
Similar to previous studies,2, 5, 11 the present study
isolated an obvious predominance of fungal pathogens
(57.9% of patients, 60.9% of eyes). Candida species
were the most common causative organism isolated,
accounting for 78.6% of all fungal isolates; Aspergillus
species accounted for the remainder of the isolates.
Several studies have shown that diabetes mellitus is a
predisposing systemic condition for the development
of Candida endophthalmitis,2, 3 because the growth of
Candida species requires a high glucose concentra-
tion.13 In the vitreous of patients with diabetes mel-
litus, the glucose concentration is even higher than
in the blood,14, 15 and this increased concentration of
glucose may play a role in the growth of these organ-
isms. The present study also showed that diabetes
mellitus was the most frequent risk factor for Candida
endophthalmitis (37.5% of 8 patients). History of gas-
trointestinal surgery and hyperalimentation seem to be
other risk factors for Candida endophthalmitis. Both of
the patients with a history of gastrointestinal surgery
(patients 1 and 3) in the current study had Candida-
related endophthalmitis.
In 2 previous studies of Candida endophthalmitis,
82.3% of eyes achieved a final VA of 20/200 or better,16
and 76% of eyes achieved a VA of 20/400 or better.17
Our series yielded similar results: 8 eyes (72.7%)
infected with Candida species achieved a final VA of
20/400 or better. In contrast, patients with endogenous
endophthalmitis secondary to Aspergillus species had
poor visual outcomes. None of the patients with posi-
tive mold cultures regained useful vision. This finding
is similar to the findings of previous studies in which
0–25% of cases had a final VA of 20/200 or better [9,
17]. Eyes with Aspergillus infection had extensive reti-
nal necrosis and choroidal damage histopathologically,
whereas eyes with Candida infection had only small
foci of retinal damage.13 These differences may explain
the relatively better visual prognosis in Candida cases
than in Aspergillus cases.
Ocular Immunology & Inflammation
 Endogenous Endophthalmitis in Northern China    137
Bacterial pathogens were isolated in 9 eyes (39.1%)
in our series: 88.9% were gram-positive isolates (Staph-
ylococcus aureus, Streptococcus species, and Staphylococ-
cus epidermidis), and only 11.1% were gram-negative
isolates (Klebsiella pneumoniae). Our findings agree with
those of some previous studies,3, 4 which showed that
gram-positive organisms are responsible for most cases
of endogenous bacterial endophthalmitis. In contrast,
some studies from Singapore and Taiwan10,18 showed
that almost 70% of organisms isolated from patients
with endogenous bacterial endophthalmitis were
gram-negative (approximately 60% were ­Klebsiella
­pneumoniae). One possible explanation for the relatively
high frequency of gram-negative organism involvement
in endogenous bacterial endophthalmitis in the reports
is the microbe’s relation with hepatobiliary infections.
In these studies, liver abscess was the major source of
infection, and Klebsiella is frequently implicated in liver
abscesses.10, 18 However, urinary tract infection was the
most frequent infection in the current study, and only
1 patient (patient 19) had a liver abscess infected with
Klebsiella pneumoniae.
Although visual outcomes associated with endog-
enous bacterial endophthalmitis have improved since
the 1930s, when a mere 2.8% of patients regained
useful vision,19 current visual outcomes are still poor,
with only 34% of affected eyes achieving a final VA of
“counting fingers” or better.10 Our results for the bacte-
rial cases were comparable to results from previous
studies with a final VA of 20/400 or better in 2 eyes
(28.6%).
The treatment of endogenous endophthalmitis
should include both ocular and systemic therapy. Intra-
venous antibiotics or antifungal agents are considered
mandatory treatment for both the eyes and the source
of infection. However, most antibiotics and antifun-
gal agents have a poor penetration capacity into the
vitreous cavity when administered intravenously or
orally.20 In established endophthalmitis, these routes
of administration are unable to provide sufficient anti-
biotic concentrations in the avascular vitreous cavity.
Therefore, intravitreal injections are the treatment of
choice for endogenous endophthalmitis. In fungal
endophthalmitis, intravitreal injections are the only
local delivery method, because antifungals are rarely
effective topically and subconjunctival injections can
be toxic.
Since the first reported successful treatment of
Candida endophthalmitis with parenteral amphoteri-
cin B in 1960,21 this drug has become the treatment
of choice for intraocular fungal infections. However,
the poor penetration of intravenously administered
amphotericin B into the vitreous,22 its serious systemic
side effects,23 and its confirmed retinal toxicity follow-
ing intravitreal injection of recommended concentra-
© 2010 Informa Healthcare USA, Inc.
tions24 render this drug undesirable. Several clinical
and experimental results confirm the good intraocular
penetration of fluconazole.25-28 In the current study, all
11 patients with fungal endophthalmitis were treated
with intravenous fluconazole as primary systemic
therapy, and 12 eyes (85.7%) were treated with intra-
vitreal amphotericin B.
Surgical intervention is generally recommended for
patients infected with especially virulent organisms,
with a VA of 20/400 or less, or with severe vitreous
involvement.29 Early vitrectomy with antibiotic injec-
tion can save eyes with endogenous endophthalmitis as
well as restore vision.30 In our series, 60.9% of patients
underwent vitrectomy, 64.3% of whom achieved a VA
of 20/400 or better.
In summary, the clinical course and microbiologi-
cal profile of pathogens in patients with endogenous
endophthalmitis in our series were similar to those
reported in previous studies. Fungi, especially Candida
species, are the most common causative organisms of
endophthalmitis. The most common predisposing
medical conditions are diabetes mellitus, immunosup-
pressive therapy, and malignancies. Visual outcomes
are poor and are largely influenced by the ­causative
organism, with Aspergillus and gram-negative
­infections having the worst prognosis. Close monitor-
ing of immunocompromised patients with systemic
infections may enable early diagnosis and treatment
and improve prognosis.
Declaration of interest: The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of the paper.
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