Transcript Ultrastructure of the Vitreomacular Interface in Full-Thickness

Current Characteristics of Infectious
Keratitis at a Tertiary Referral Center
in South Korea
2008 ASCRS
Poster No. P-139
Sang Beom Han, MD, Tae Hyoung LIm, MD, Won Ryang Wee,
MD,PhD, Jin Hak Lee, MD,PhD, Mee Kum Kim, MD,PhD
Department of Ophthalmology
Seoul National University College of Medicine
Seoul National University Hospital, Korea
Financial Disclosure
 None of the authors has a financial
interest in any material or method in
the study.
Introduction
 The profiles of infectious keratitis vary according to age,
climate, geographic factors, socioeconomic status, and
patient’s general condition.
 The level of ophthalmologic center (primary, secondary, and
tertiary referral center) could also be one of important
factors which determine the clinical features of infectious
keratitis.
 The clinical manifestation of the disease has changed with
time.
–
For example, due to widespread use of contact lens,
 Contact lens wear has emerged to be the main risk factor
 The proportion of youngster in age distribution has increased.
Introduction
 Understanding the recent trend of infectious keratitis,
including predisposing factors, microbiological profile,
clinical manifestation, and response to treatment is
essential in the treatment of the disease.
 The current trend in South Korea has not yet been reported.
Purpose
 To identify risk factors and causative agents,
and to investigate demographic and clinical
features of infectious keratitis at a tertiary
referral center in South Korea.
Materials & Methods
 Review of medical records of 56 patients with cultureproven bacterial or fungal keratitis
– at Seoul National University Hospital.
– from January 1, 2003 to December 31, 2007.
– The diagnosis of bacterial or fungal keratitis was made when
there was acute corneal epithelial defect and suppurative
corneal infiltrate associated with identified causative bacteria
or fungus.
 Data such as demographics, predisposing factors,
microbiological profile, sensitivity to antibiotics, and
healing time were collected and analyzed.
Materials & Methods
 Healing was defined as complete disappearance of
epithelial defect and inactivation of stromal infiltrate
accompanied with absence of anterior chamber
reaction in medically controlled cases.
 Healing time was defined as the term from when the
patient first received treatment with antibiotics or
antifungal agents after diagnosed as infectious
keratitis in our or another facility to the point of
epithelial closure.
 Cases which led to therapeutic penetrating
keratoplasty(PKP) or evisceration were regarded as
treatment failure, and were excluded from the analysis
of healing time.
Materials & Methods
 All patients were divided into two groups according to the
outcome.
– Cases with healing ≤ 4 weeks were included in the better
outcome group (Group 1).
– Poor outcome was defined when healing time was longer than 4
weeks, or surgical intervention such as therapeutic PKP or
evisceration was needed (Group 2).
– The time point of four weeks was set based on the finding that
the median healing time was 4 weeks, and 24 of 45 (53%)
medically controlled cases showed healing time of four weeks or
less.
– Twenty-five (45%) patients were included in the better
outcome group (Group 1), 28 (50%) were in the poorer
outcome group (Group 2), and the remaining three (5.4%)
were lost during following-up.
Materials & Methods
 The possible effect of age, prior empirical treatment,
diabetes mellitus(DM), hypertension, and the sizes of
epithelial defect and stromal infiltration on the outcome was
investigated using Pearson’s chi-square test and Fisher’s
exact test.
 Resistance to antibiotics was investigated.
Results
 The number of patients with culture-proven
infectious keratitis has been increasing every year
Results - Demographics
 33 male (59%) and 23 female (41%)
 The average age was 46.9±27.7 years, and 33 patients
(59%) were 50 years or older.
 the peak at 0th decade was mainly due to the outbreak of
secondary bacterial keratitis after epidemic
keratoconjunctivitis in neonatal intensive care unit (NICU).
Results
– Predisposing Factors
 Ocular surface disease was the most common predisposing factor,
followed by corneal trauma and contact lens wear.
 The proportion of patients who were 50 years or older tends to be
higher in corneal trauma than in ocular surface disease and contact
lens wear.
Predisposing
Younger than 50 yr
50 yr or older (n=33)
Total
factors
(n=23)
Corneal Trauma
2
6
8 (14%)
Ocular surface
16
10
26 (46%)
6
5
11 (20%)
Contact lens wear
5
0
5 (9%)
None
0
17
17 (30%)
Total
23 (41%)
33 (59%)
56 (100%)
disease
(Ocular surface
surgery)
All patients with history of ocular surface surgery are also included in the group with
history of ocular surface disease.
Results
– Microbiological profiles
 49 cases were infection with single organism, while two or
more organisms were identified in 7 cases.
 In cases infection with single organism
– Gram (+) bacteria were most common; 25 patients (51%)
 Staphylococcus species were the most frequently found Gram
(+)bacteria with 15 cases(30%)
 S. aureus was found in 9 of those cases, including six
outbreak cases in NICU in which MRSA was identified.
– Fungus were cultured in 12 patients. (25%)
 Seven of them (14%) were Candida species, followed by
Aspergillus species, and Fusarium species.
– Gram (-) bacteria was found in 11 patients (22%).
 Pseudomonas aeruginosa and Serratia marcescens were found
in three cases, respectively.
Results
– Microbiological profiles
 Seven cases of mixed infection
Case
1
Microorginisms
Chryseobacterium indologenes (G(-))*, Achromobacter xylosoxidans(G(-)), and Candida
parapsilosis (Fungus)
2
Streptococcus pneumoniae (G(+)) and Pseudomonas alcailigenes (G(-))
3
Streptococcus species (G(+)) and Pantotea agglomerans (G(-))
4
Achromobacter xylosoxidans (G(-)) and Stenotrophomonas maltophilia (G(-))
5
Coagulase-negative Staphylococcus (G(+)) and Corynebacterium species (G(+))
6
Streptococcus species (G(+)) and Corynebacterium species (G(+))
7
Klepsiella pneumoniae (G(-)) and Stenotrophomonas maltophilia (G(-))
*G(+): Gram positive bacteria
G(-):Gram negative bacteria
Fungus: fungus
Resistance to antibiotics
Isolates
All Gram positive
Staphylococcus
Penicillin
Cefazolin
Erythromycin
Gentamicin
Tobramycin
Ofloxacin
Ciproflxacin
Vancomycin
53% (16/30)
86% (6/7)
37% (11/30)
33% (5/15)
-
0% (0/ 17)
0% (0/15)
0% (0/30)
94% (15/16)
-
50% (8/16)
-
-
0% (0/15)
0% (0/15)
0% (0/16)
13% (1/8)
86% (6/7)
11% (1/9)
33% (5/15)
-
0% (0/2)
-
0% (0/9)
-
60% (3/5)
-
44% (8/18)
35% (6/17)
-
11% (2/18)
-
-
-
-
25% (1/4)
0% (0/4)
-
0% (0/4)
-
-
100% (3/3)
-
0% (0/3)
0% (0/2)
-
0% (0/3)
-
spp.
Streptococ cus
spp.
All Gram negative
Pseudomonas
spp.
Serratia spp.
High resistance of Gram (+) bacteria to penicillin, cefazolin and
erythromycin. (although the number of cases in which the sensitivity test to
cefazolin was too small)
High resistance of Gram (-) bacteria to gentamicin and tobramicin.
However, quinolone showed low resistance to both Gram (+) and (-)
bacteria.
Results - Outcome
 45 cases were controlled with medical treatment.
– The average healing time was 5.1 ± 2.8 wk (1 to 12 wk)
 4 patients underwent therapeutic PKP, and four cases
led to evisceration.
 The remaining 3 patients were lost during follow-ups.
 In 17 out of 42patients (40%) whose visual acuity was
measured, the visual acuity improved by 1 line or more.
Outcome
 The contribution of factors to the clinical outcome
Factors
Group 1 (N)
Group 2 (N)
Odds Ratio* (95%
P value
CI†)
Sex (M:F)
15:10
16:12
1.13 (0.38 - 3.37)
0.833§
Extreme age‡ (Yes:No)
14:11
20:8
1.96 (0.63 - 6.13)
0.242§
Diabetes Mellitus
4:21
7:20
1.83 (0.47 - 7.25)
0.503||
Hypertension (Yes:No)
2:23
7:20
4.02 (0.75 - 21.6)
0.143||
Infiltration
4:12
11:1
33.0 (3.18 – 342)
0.001||
4:14
8:5
5.60 (1.16 -27.1)
0.032||
(Yes:No)
(>10:≤10mm2)
Epithelial defect
(>10:≤10mm2)
Significant correlation between the outcome and the size of
infiltration and epithelial defect was found.
*Odds Ratio (Poorer outcome/ Better outcome)
†CI: Confidence interval
‡Extreme age was defined as age yonger than 10 years or older than 60 years.
§ Pearson’s chi-square test
||Fisher’s exact test
Outcome
 The difference in clinical outcome according to
causative microorganisms
Organisms
Group 1
Group 2
Odds Ratio*
P value‡
(95% CI†)
21:4
26:2
0.40 (0.07 - 2.43)
0.404
G(-) : G(+)
3:15
8:9
4.44 (0.93 – 21.2)
0.075
Fungus : G(+)
3:15
9:9
5.00 (1.06 – 23.3)
0.038
Fungus : G(-)
3:3
9:8
0.89 (0.14 – 5.72)
1.000
Single :
Poly-organisms
*Odds Ratio (Poorer prognosis / Better prognosis)
†CI: Confidence interval
‡ Fisher’s exact test
Keratitis caused by Gram(+) bacteria showed significantly better
outcome than that due to fungus, and tended to have better
outcome than that due to Gram(-) bacteria, although the difference
was not statistically significant.
Dicussion
 The age profile showed two peaks in 0s and 60s.
– 6 cases of outbreak in NICU caused bias in age
distribution
– Low proportion of contact lens (CL)-related keratitis
(9%, 5 patients) and low proportion of patients in 20s
and 30s
: most CL-related cases might be have been cured
before referral to tertiary center. (most CL wearers are
youngsters who have more competent immune system
than elderly)
 The resistance to ofloxacin and ciprofloxacin was
shown to be low in spite of the widespread empirical
use, suggesting that monotherapy with topical
quinolones can still be considered as primary
treatment of bacterial keratitis.
Discussion
 The result that Gram (+) bacteria was the most
frequently identified pathogen, and Staphylococcus
species was the most common in them.
 Low proportion of G(-) bacteria might be due to low
incidence of CL-related keratitis.
 Infection with Gram (+) bacteria showed statistically
significant better outcome than that with fungus, and
tended to have better outcome than that with Gram (-)
bacteria, although the result was not statistically
significant.
Discussion
 The severity of corneal inflammation is an important
prognostic factor. Based on the findings that there was
significant correlation between the outcome and the size
of infiltration and epithelial defect, this contention is in
good agreement with previous reports.
 Although this study has a limitation that the size of
study patients were small, and only culture-proven
cases of only one tertiary center were included, we
believe that this study provided updated data of
infectious keratitis in South Korea to some extent.
These data are expected to be useful in upcoming
multi-center study with larger patients group.
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