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Seo, Wee, Lee, and Kim: Risk Factors Affecting Efficacy of Intracameral Amphotericin Injection in Deep Keratomycosis
Original Article

J Korean Ophthalmol Soc 2007;48(9):1202-1211.

Published online: 30 August 2007

DOI: https://doi.org/10.3341/jkos.2007.48.9.1202

Risk Factors Affecting Efficacy of Intracameral Amphotericin Injection in Deep Keratomycosis

Je Hyun Seo, M.D.1, 2, Won-Ryang Wee, M.D., Ph.D.1, 2, Jin Hak Lee, M.D., Ph.D.1, 3, Mee Kum Kim, M.D., Ph.D.1, 2

1Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea

2Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, Korea

3Department of ophthalmology, Seoul National University Bundang Hospita, Seoul, Korea

Address Reprint requests to Mee Kum Kim, M.D., Department of Ophthalmology, Seoul National University College of Medicine, #28 Yeongeon-dong, Jongno-gu, Seoul 110-744, Korea, Tel: 82-2-2072-2665, Fax: 82-2-741-3187, E-mail: kmk9@snu.ac.kr

Received 21 June 2006       Accepted 29 May 2007

Copyright © 2007 Korean Ophthalmological Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To investigate the clinical efficacy of intracameral amphotericin injection and to evaluate risk factors affecting primary treatment success in fungal infection invading the anterior segment of the eye

Methods

Twenty-six eyes of 26 patients diagnosed with fungal infection in the anterior segment were studied. The initial treatment regimen was a topical 0.15% amphotericin application and itraconazole oral administration after culture. Amphotericin (5 ug/0.1 ml, 0.1 cc) was repeatedly injected intracamerally when the infection intensified. Penetrating keratoplasty was conducted for eyes unresponsive to intracameral amphotericin injection. The relative risk ratios of ulcer size, infiltration depth, culture positivity, and hypopyon were compared in each treatment group to evaluate the treatment response.

Results

Of patients with fungal infection, 30.7% were cured with intracameral amphotericin injection, while 30.7% needed penetrating keratoplasty. Intracameral amphotericin injection was needed in the presence of large corneal ulcers (>14 mm2), hypopyon, positive fungal culture, use of steroid eye drops, and deep infiltration at initial examination. Large ulcer size (>14 mm2) was the main risk factor for needing penetrating keratoplasty. Of the eyes Candida infection, 66.5% needed evisceration.

Conclusions

Large ulcer size and the isolation of Candida were poor prognostic factors related to the efficacy of intracameral amphotericin injection.

Keywords: Candida, Fungal infection, Intracameral amphotericin injection, Prognostic indicator, Ulcer size

References

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Figure 1.
Depths and gradings of infiltration in enrolled cases.
jkos-48-1202f1.tif
Table 1.
Infiltration grading and severity index
Infiltration grading Location
Grade 1 Epithelial layer
Grade 2 Stromal layer
Grade 3 Descement's membrane
Grade 4 Retrocorneal plaque, perforation
Grade 5 Fungus ball in anterior chamber, on iris and lens
Severity index
Mean value of scoring treatment modality-related infection control
Score defined as Group A: 1, Group B: 2, Group C: 4, Evisceration: 8
Ex) fungal infection culture proven as two fungi A, they were treated IC amphotericin and evisceration, then (2 +8)/2, SI is 5.
Relative severity index.
Divided by the largest value of severity index
Infiltration grading defined as infiltration layer at initial examination, increased grade means deep infiltration. It is matched with described in Figure 1.
Table 2.
Summary of cases
Case No. Sex Age Fungus Infiltration depth Hypopyon Ulcerarea (mm2) Injectionrate Treatment Group Result
1 M 57 N 2 N 0.78 0 A P
2 M 70 N 3 N 1.1 0 A P
3 F 52 N 2 N 1.6 0 A P
4 F 70 N 3 N 3.12 0 A P
5 F 49 N 2 N 3.4 0 A P
6 M 60 N 1 N 4.35 0 A P
7 F 69 N 2 Y 6.7 0 A P
8
 M
 40
 Aspergillus
 1
 N
 9.36
 0
 A
 P
9∗‡ M 5 Aspergillus Acremonium 5 N 0 10 B I
10∗ M 20 N 4 Y 0.4 8 B I
11† M 62 N 5 Y 1.33 5 B I
12† M 55 Asperigillus 3 Y 2.1 3 B I
13† F 63 N 4 N 3 4 B I
14∗ M 64 N 4 Y 3.12 4 B I
15† M 55 N 4 Y 9.32 5 B I
16†
 F
 62
 N
 4
 N
 24
 3
 B
 I
17† F 23 Asperigillus 4 N 1.33 5 C T
18† F 51 N 3 Y 1.4 1 C T
19†‡ M 43 Candida 5 Y 3.5 4 C E
20† M 71 Acemonium. 5 Y 16.77 7 C T
21† M 59 Rhizopus Asperigillus 4 Y 17.8 1 C T
22† M 73 Alternaria 5 Y 19.24 5 C T
23∗ F 62 Candida 4 Y 27.9 7 C T
24†
 F
 53
 Acremonium Fusarium
 4
 Y
 30.4
 4
 C
 T
25† M 76 Candida 5 Y 30 2 - E
26 M 67 Fusarium 5 Y 32 0 - E

Y: Yes, N: Negative, not identified.

P: Primary treatment suceess. I: Needed Inracameral Amphotericin. T:Needed surgical treatment. E: Eviscerated.

∗ : Amphotericin mixed with BSS: success rate 75%,

† : Amphoterin mixed with 5% dextrose: success rate 38%.

‡ : Cataract developed.

Table 3.
Treatment success and failure of subgroup patients with fungal keratitis and significant predictors of disease progression
Table A. Risk factors and calculated chi-square test between Group A and Group B and Group C, respectively
Characteristics at diagnosis Group A
 Group B
 Group C
 p-value∗
N N=8% N=8% N=8 %
Age (yr) 0.84
 ≦55 11 3 27.2 4 36.3 4 36.3
 >55 13 5 38.4 4 30.7 4 30.7
Gender 0.50
Male 14 4 28.5 6 42.8 4 28.5
Female 10 4 40.0 2 20.0 4 40.0
Duration of Sx
 ≦7 6 3 50.0 2 33.3 1 16.6 0.51
 >7 18 5 27.7 6 33.3 7 38.8
Trauma 0.47
 Present 15 4 26.6 6 40.0 5 33.3
 Absent 9 4 44.4 2 22.2 3 33.3
Steroid use 0.30
 Present 4 0 0.0 2 50.0 2 50.0
 Absent 20 8 40.0 6 30.0 6 30.0
Ulcer size (mm2) 0.009
 ≤14 17 8 47.0 7 41.2 3 17.6
 >14 6 0 0.0 1 16.6 5 83.3
Hypopyon 0.03
 Present 11 0 0.0 5 45.4 6 54.5
 Absent 13 8 61.5 3 23.1 2 18.2
Culture result 0.005
 Positive 10 1 10.0 2 20.0 7 70.0
 Negative 14 7 50.0 6 42.9 1 7.1
Infiltration Grade 0.01
 Mean±SD 2.0±0.75 4.1±0.64 4.2±0.70

∗ Chi-square test.

Table B.
Significant risk factors in primary failure with topical amphotericin alone (Group A vs. Group B and C)
Characteristics Risk Ratio∗ 95 % CI p-value
Steroid use
 Present 1.67 1.17-2.38 <0.01
 Absent
Ulcer size (mm2)
 ≤14
 >14 1.80 1.19-2.7 <0.01
Hypopyon
 Present 2.2 1.10-4.39 <0.01
 Absent
Culture result
 Positive 1.8 1.03-3.16 <0.01
 Negative
Infiltration grade Group A Group B&C p-value
 Mean±SD 2.0±0.75 vs. 4.18±0.65 <0.001

∗ : Relative risk ratio.

Table C.
Significant risk factors in treatment failure with intracameral amphotericin (Group B vs. Group C)
Characteristics Ulcer size (mm2) Risk Ratio 95 % CI P-Value
≤14
> 14 2.78 1.01-7.64 <0.01

Group A: 0.15% Topical Amphotericin + 200 mg Itraconazole.

Group B: 0.15% Topical Amphotericin + 200 mg

Itraconazole + Intracameral Amphotericin 5 Μg/0.1ml, 0.1cc.

Group C: 0.15% Topical Amphotericin + 200 mg Itraconazole + Intracameral Amphotericin 5 Μg/0.1 ml, 0.1 cc. + Therapeutic PKP.

Table 4.
Severity index according to the fungus
Fungus genus Total number Group
 Success ∗ Rate (%) Evisce ration Severity † Index RSI ‡
A B C
Aspergillus 5 1 2 2 50 2.6 0.39
Acremonium 3 1 2 33.3 3.3 0.50
Candida 3 1 0 2 6.6 1.0
Fusarium 2 1 0 1 6 0.91
Alterina 1 1 0 4 0.67
Rhizopus 1 1 0 4 0.67

∗ : Success rate of IC amphotericin injection (Group B) according to the identified fungus.

† : Severity index: Mean value of scoring treatment modality related infection control.

Values defined as Group A: 1, Group B: 2, Group C: 4, Evisceration: 8.

‡ : Relative severity index (RSI): Divided by the largest value of severity index.

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