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Use of Higher Medication Concentrations in the Treatment of Acanthamoeba Keratitis

Use of Higher Medication Concentrations in the Treatment of Acanthamoeba Keratitis Acanthamoeba keratitis is a notoriously difficult therapeutic challenge.1 We have elected to treat the most severe cases by increasing the concentration of a standard topical medication, chlorhexidine, in addition to increasing the frequency of application. Our previous clinical experience comparing a multiple-drug approach to monotherapy with variable concentrations and frequencies suggests that aggressive monotherapy is the most successful strategy. The standard ophthalmic concentration for topical chlorhexidine, or polyhexamethylene biguanine, is 0.02%. By increasing this to either 0.04% or 0.06%, a higher concentration of the drug will be delivered to the tissue and the pathogen. Data from Hay et al,2 Seal,3 and our own experiments suggest that higher drug levels in the tissue should be more effective.4 In the past 30 months, we have treated approximately 58 patients with acanthamoeba keratitis. Most of these cases were not very severe and were treated successfully with chlorhexidine at a concentration of 0.02% or 0.04%. This was typically applied hourly while awake and every 2 hours at night. We have usually chosen to limit therapy to a single drug and vary the concentration and frequency instead of adding additional medications. During this same interval, we treated 8 patients with very severe disease invading the deep stroma for whom this approach was not successful. After an average of 4 to 8 weeks without improvement, we increased the concentration to 0.06% and maintained it for 2 months. One patient failed this therapy as well and required enucleation whereas 7 patients were successfully treated. Most patients with very severe disease were also treated with oral ketoconazole at a dosage of 200 mg/d and low-dose topical steroids. Chlorhexidine at 0.06% may have some toxic effects on corneal keratocytes, epithelium, and limbal epithelial stem cells, although this has not been clinically apparent. Nevertheless, the higher concentration of chlorhexidine is probably only justified when the lower concentrations fail. When this therapy fails, higher concentrations are justifiable since the risk of vision loss in these cases is very high. Correspondence: Dr Mathers, Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Blvd, Portland, OR 97201 (mathersw@ohsu.edu). Financial Disclosure: None. References 1. Illingworth CDCook SD Acanthamoeba keratitis. Surv Ophthalmol 1998;42493- 508PubMedGoogle ScholarCrossref 2. Hay JKirkness CMSeal DWright P Drug resistance and Acanthamoeba keratitis: the quest for alternative antiprotozoal chemotherapy. Eye 1994;8555- 563PubMedGoogle ScholarCrossref 3. Seal DV Acanthamoeba keratitis update-incidence, molecular epidemiology and new drugs for treatment. Eye 2003;17893- 905PubMedGoogle ScholarCrossref 4. Syam PPNarendran Rvan der Hoek J Persistent acanthamoeba keratitis in a non-contact lens wearer following exposure to bird seed dust. Br J Ophthalmol 2005;89388- 389PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Use of Higher Medication Concentrations in the Treatment of Acanthamoeba Keratitis

Mathers, William
Archives of Ophthalmology , Volume 124 (6) – Jun 1, 2006
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Use of Higher Medication Concentrations in the Treatment of Acanthamoeba Keratitis

Abstract

Acanthamoeba keratitis is a notoriously difficult therapeutic challenge.1 We have elected to treat the most severe cases by increasing the concentration of a standard topical medication, chlorhexidine, in addition to increasing the frequency of application. Our previous clinical experience comparing a multiple-drug approach to monotherapy with variable concentrations and frequencies suggests that aggressive monotherapy is the most successful strategy. The standard ophthalmic concentration for...
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References (5)

Publisher
American Medical Association
Copyright
Copyright © 2006 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.124.6.923
Publisher site
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Abstract

Acanthamoeba keratitis is a notoriously difficult therapeutic challenge.1 We have elected to treat the most severe cases by increasing the concentration of a standard topical medication, chlorhexidine, in addition to increasing the frequency of application. Our previous clinical experience comparing a multiple-drug approach to monotherapy with variable concentrations and frequencies suggests that aggressive monotherapy is the most successful strategy. The standard ophthalmic concentration for topical chlorhexidine, or polyhexamethylene biguanine, is 0.02%. By increasing this to either 0.04% or 0.06%, a higher concentration of the drug will be delivered to the tissue and the pathogen. Data from Hay et al,2 Seal,3 and our own experiments suggest that higher drug levels in the tissue should be more effective.4 In the past 30 months, we have treated approximately 58 patients with acanthamoeba keratitis. Most of these cases were not very severe and were treated successfully with chlorhexidine at a concentration of 0.02% or 0.04%. This was typically applied hourly while awake and every 2 hours at night. We have usually chosen to limit therapy to a single drug and vary the concentration and frequency instead of adding additional medications. During this same interval, we treated 8 patients with very severe disease invading the deep stroma for whom this approach was not successful. After an average of 4 to 8 weeks without improvement, we increased the concentration to 0.06% and maintained it for 2 months. One patient failed this therapy as well and required enucleation whereas 7 patients were successfully treated. Most patients with very severe disease were also treated with oral ketoconazole at a dosage of 200 mg/d and low-dose topical steroids. Chlorhexidine at 0.06% may have some toxic effects on corneal keratocytes, epithelium, and limbal epithelial stem cells, although this has not been clinically apparent. Nevertheless, the higher concentration of chlorhexidine is probably only justified when the lower concentrations fail. When this therapy fails, higher concentrations are justifiable since the risk of vision loss in these cases is very high. Correspondence: Dr Mathers, Casey Eye Institute, Oregon Health and Science University, 3375 SW Terwilliger Blvd, Portland, OR 97201 (mathersw@ohsu.edu). Financial Disclosure: None. References 1. Illingworth CDCook SD Acanthamoeba keratitis. Surv Ophthalmol 1998;42493- 508PubMedGoogle ScholarCrossref 2. Hay JKirkness CMSeal DWright P Drug resistance and Acanthamoeba keratitis: the quest for alternative antiprotozoal chemotherapy. Eye 1994;8555- 563PubMedGoogle ScholarCrossref 3. Seal DV Acanthamoeba keratitis update-incidence, molecular epidemiology and new drugs for treatment. Eye 2003;17893- 905PubMedGoogle ScholarCrossref 4. Syam PPNarendran Rvan der Hoek J Persistent acanthamoeba keratitis in a non-contact lens wearer following exposure to bird seed dust. Br J Ophthalmol 2005;89388- 389PubMedGoogle ScholarCrossref

Journal

Archives of Ophthalmology – American Medical Association

Published: Jun 1, 2006

Keywords: acanthamoeba keratitis

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