Current Characteristics of Infectious Keratitis at a Tertiary Referral Center in South Korea

1. Current Characteristics of Infectious Keratitis at a Tertiary Referral Center in South Korea 2008 ASCRSPoster 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

2. Financial Disclosure • None of the authors has a financial interest in any material or method in the study.

3. 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.

4. 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.

5. 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.

6. Materials & Methods • Review of medical records of 56 patients with culture-proven 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.

7. 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.

8. 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.

9. 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.

10. Results • The number of patients with culture-proven infectious keratitis has been increasing every year

11. 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).

12. 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. All patients with history of ocular surface surgery are also included in the group with history of ocular surface disease.

13. 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.

14. Results – Microbiological profiles • Seven cases of mixed infection *G(+): Gram positive bacteria G(-):Gram negative bacteria Fungus: fungus

15. Resistance to antibiotics • 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.

16. 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.

17. Outcome • The contribution of factors to the clinical outcome • 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

18. Outcome • The difference in clinical outcome according to causative microorganisms *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.

19. 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.

20. 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.

21. 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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