- Email: [email protected]
Treatment for Fungal Endophthalmitis Resulting From Keratitis
We also collected extra spectral-domain (SD) OCT images from some of the subjects. Although the number of cases was not sufficient to reach any conclusion, the development and complete extinction of outer foveolar defects also were noted in the SD OCT examination. Our observation also is in line with previous studies using SD OCT, which documented the disappearance of outer foveolar defects and the restoration of the inner segment and outer segment junctions in 9 of 28 cases after 6 months.3 However, we also agree that there may be tiny outer foveolar defects that may not be detected by Stratus OCT, but could be detected by SD OCT. The transverse resolutions of Stratus OCT and SD OCT are reported as 20 and 10 m, respectively.4,5 Thus, with SD OCT it is possible that the mean period for the disappearance of the defects is longer than the 6 months of our study. In Figure 2, we intended to show a schematic drawing of the MH sealing process. Each illustration is consistent with time-based changes of the fovea on OCTs from different patients. Dr Oh’s comment regarding the process of resolution of outer foveolar defects in Figure 1 is not actually different from the description in the legend of Figure 2 and in the Discussion. There have been many reports about MH development, but research on MH sealing has been hindered by certain limitations so far. In this regard, this study suggests meaningful observations. However, the sealing mechanism hypothesis provided in this study is based on the inference of the authors. This requires further investigation to be proven. We expect that further studies on the MH sealing process may shed light on the development of more efficient means to induce MH sealing. SE WOONG KANG YUN TAEK KIM SONG EE CHUNG
Seoul, Korea
REFERENCES
1. Kang SW, Lim JW, Chung SE, Yi CH. Outer foveolar defect after surgery for idiopathic macular hole. Am J Ophthalmol 2010;150(4):551–557. 2. Funata M, Wendel RT, de la Cruz Z, Green WR. Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade. Retina 1992;12(4):289 –298. 3. Sano M, Shimoda Y, Hashimoto H, Kishi S. Restored photoreceptor outer segment and visual recovery after macular hole closure. Am J Ophthalmol 2009;147(2):313–318. 4. Duker JS, Paunescu LA, Fujimoto JG. Future of optical coherence tomography: ultrahigh-resolution versus standardresolution OCT. In: Arevalo JF, editor. Retinal Angiography and Optical Coherence Tomography, 3rd ed. New York: Springer, 2009:431-437. 5. Coscas G. Appendix: commercially available spectral-domain OCT equipment. In: Coscas G, editor. OCT in AMD. Heidelberg: Springer Medizin Verlag, 2009. p. 380 –389.
VOL. 151, NO. 1
Treatment for Fungal Endophthalmitis Resulting From Keratitis EDITOR: WE READ WITH GREAT INTEREST THE ARTICLE BY SHEN
and associates describing intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis.1 The authors proposed that intracameral voriconazole injection may be an effective treatment for fungal endophthalmitis contiguously spreading from keratitis. We appreciate this report by authors, which provided us with valuable information on new, challenging treatment methods for endophthalmitis spreading from fungal keratitis. Although the study was simple and concise, we have some concerns regarding the study they presented. The final visual outcomes ranged from hand movements to no light perception in Patients 1, 2, and 5. We are concerned to know whether the authors ruled out possible posterior segment involvement by using ocular echography in these patients. Ocular echography is a useful instrument to evaluate posterior segment in endophthalmitis,2 especially in eyes with opaque media such as fungal keratitis. Similar to classification of bacterial endogenous endophthalmitis reported by Greenwald and associates, most cases of fungal endophthalmitis resulting from keratitis are the types of anterior focal or diffuse forms with or without posterior focal endophthalmitis.3 In such types of fungal endophthalmitis, intracameral voriconazole injection may be an effective treatment; moreover, repeated injections of intracameral voriconazole also may prevent organisms from spreading to the vitreous cavity. However, in fungal keratitis with posterior diffuse or panophthalmitis, intracameral voriconazole injection may be ineffective because of a low concentration of intravitreal voriconazole. Therefore, intravitreal voriconazole with or without pars plana vitrectomy should be performed in severe cases with posterior diffuse involvement. The authors should clarify whether the poor visual outcomes are related to posterior segment involvement. First, in the Methods, the authors should provide the results of vitreous cultures and lens status for the patients. Intraocular specimens were obtained only from aqueous humor; however, results of vitreous cultures may indicate whether intravitreal antibiotics should be administered, especially in mildly anterior focal vitreous inflammation. Second, the lens also plays an important role for preventing organisms from invading the posterior segment. Therefore, the authors should illustrate whether eyes with aphakia and pseudophakia have a higher incidence of posterior segment involvement and poor visual outcomes than those with phakia. In the Discussion, we would like to point out a minor error in the authors’ assumption of the normal volume of the anterior chamber. In fact, the normal volume of the anterior chamber in humans is 0.2 mL,4,5 rather than 0.5
CORRESPONDENCE
185
mL, as reported in this study. Therefore, the injected dose of 100 g/0.1 mL should result in an anterior chamber concentration of 333 g/mL or more after aqueous tapping for cultures. The peak levels achieved in the anterior chamber thus were more than 300 times the minimum inhibitory concentration of voriconazole to Candida and Aspergillus species. Final visual outcomes are related to posterior segment involvement in patients with endophthalmitis. If the authors provide more supplementary data such as echographic findings, results of vitreous cultures, and lens status, this study is a valuable reference for clinical practices.
invasion and replication of fungal filaments into the vitreous may occur in postkeratitis fungal endophthalmitis, which is mainly diagnosed based on positive results from culture of vitreous samples. Injection of intravitreal voriconazole with or without vitrectomy should be performed in case of suspected vitreous invasion. The role of the lens in preventing fungi from invading the posterior segment could not be determined in this study. First, patients in the current series all had phakic eyes. Second, the small number of cases was insufficient for statistical analysis. It has been shown that the depth and volume of the anterior chamber diminishes with age. Male subjects have larger anterior chamber dimensions than female subjects.3 The volume of the anterior chamber is approximately 0.3 mL in the phakic eye and probably increases to approximately 0.5 mL in the pseudophakic eye.4,5 An in vitro study has shown that no corneal endothelial toxicity could be detected after 30 days of treatment with 250 g/mL of voriconazole. Even concentrations of up to 1 mg/mL had no influence on corneal endothelial cells and primary human trabecular meshwork cells when administered for 24 hours.6 With the normal volume of the aqueous humor in the phakic eye assumed to be 0.3 mL, the injected dose of 100 g/0.1 mL in the anterior chamber resulted in an initial aqueous concentration of 250 g/mL. The peak levels achieved in the anterior chamber thus were more than 250 times the minimum inhibitory concentration of voriconazole to Candida and Aspergillus species. Moreover, no endothelial toxicity occurred with such a concentration of voriconazole.
KUAN-JEN CHEN CHI-CHIN SUN CHING-HSI HSIAO HSIN-YUAN TAN LUNG-KUN YEH
Taoyuan, Taiwan
REFERENCES
1. Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. Am J Ophthalmol 2010;149(6):916 – 921. 2. Dacey MP, Valencia M, Lee MB, et al. Echographic findings in infectious endophthalmitis. Arch Ophthalmol 1994;112(10): 1325–1333. 3. Greenwald MJ, Wohl LG, Sell CH. Metastatic bacterial endophthalmitis: a contemporary reappraisal. Surv Ophthalmol 1986;31(2):81–101. 4. Fontana ST, Brubaker RF. Volume and depth of the anterior chamber in the normal aging human eye. Arch Ophthalmol 1980;98(10):1803–1808. 5. Johnson SB, Coakes RL, Brubaker RF. A simple photogrammetric method of measuring anterior chamber volume. Am J Ophthalmol 1978;85(4):469 – 474.
YING-CHENG SHEN CHUN-YUAN WANG
Taichung, Taiwan
REFERENCES
1. Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. Am J Ophthalmol 2010;149(6):916 – 921. 2. Dacey MP, Valencia M, Lee MB, et al. Echographic findings in infectious endophthalmitis. Arch Ophthalmol 1994;112(10): 1325–1333. 3. Fontana ST, Brubaker RF. Volume and depth of the anterior chamber in the normal aging human eye. Arch Ophthalmol 1980;98(10):1803–1808. 4. Murphy CC, Nicholson S, Quah SA, Batterbury M, Neal T, Kaye SB. Pharmacokinetics of vancomycin following intracameral bolus injection in patients undergoing phacoemulsification cataract surgery. Br J Ophthalmol 2007;91:1350 –1353. 5. Schoenwald RD. Ocular pharmacokinetics. In: Zimmerman TJ, ed. Textbook of Ocular Pharmacology. Philadelphia: Lippincott-Raven, 1997:119 –138. 6. Kernt M, Kampik A. Intracameral voriconazole: in vivo safety for human ocular cells. Toxicology 2009;258(2–3):84 –93.
REPLY WE APPRECIATE THE INTEREST IN AND COMMENTS ABOUT
our article.1 To evaluate posterior segment in patients with opaque media, ocular echography is a useful instrument.2 In our patients, ocular echographic examination was performed routinely when the retina could not be viewed directly. In Patient 1, a descemetocele and corneal leukoma resulted in poor visual acuity. The visual outcomes in Patients 2 and 5 resulted from advanced glaucoma and retinal detachment, respectively. Most cases of fungal endophthalmitis contiguously spreading from keratitis tend to be more localized with the fungal mass, and inflammation often is confined to the anterior chamber, pupillary space, or anterior vitreous. In such cases, repeated injections of intracameral voriconazole may be an effective treatment. We agree that 186
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JANUARY 2011
Seoul, Korea
REFERENCES
1. Kang SW, Lim JW, Chung SE, Yi CH. Outer foveolar defect after surgery for idiopathic macular hole. Am J Ophthalmol 2010;150(4):551–557. 2. Funata M, Wendel RT, de la Cruz Z, Green WR. Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade. Retina 1992;12(4):289 –298. 3. Sano M, Shimoda Y, Hashimoto H, Kishi S. Restored photoreceptor outer segment and visual recovery after macular hole closure. Am J Ophthalmol 2009;147(2):313–318. 4. Duker JS, Paunescu LA, Fujimoto JG. Future of optical coherence tomography: ultrahigh-resolution versus standardresolution OCT. In: Arevalo JF, editor. Retinal Angiography and Optical Coherence Tomography, 3rd ed. New York: Springer, 2009:431-437. 5. Coscas G. Appendix: commercially available spectral-domain OCT equipment. In: Coscas G, editor. OCT in AMD. Heidelberg: Springer Medizin Verlag, 2009. p. 380 –389.
VOL. 151, NO. 1
Treatment for Fungal Endophthalmitis Resulting From Keratitis EDITOR: WE READ WITH GREAT INTEREST THE ARTICLE BY SHEN
and associates describing intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis.1 The authors proposed that intracameral voriconazole injection may be an effective treatment for fungal endophthalmitis contiguously spreading from keratitis. We appreciate this report by authors, which provided us with valuable information on new, challenging treatment methods for endophthalmitis spreading from fungal keratitis. Although the study was simple and concise, we have some concerns regarding the study they presented. The final visual outcomes ranged from hand movements to no light perception in Patients 1, 2, and 5. We are concerned to know whether the authors ruled out possible posterior segment involvement by using ocular echography in these patients. Ocular echography is a useful instrument to evaluate posterior segment in endophthalmitis,2 especially in eyes with opaque media such as fungal keratitis. Similar to classification of bacterial endogenous endophthalmitis reported by Greenwald and associates, most cases of fungal endophthalmitis resulting from keratitis are the types of anterior focal or diffuse forms with or without posterior focal endophthalmitis.3 In such types of fungal endophthalmitis, intracameral voriconazole injection may be an effective treatment; moreover, repeated injections of intracameral voriconazole also may prevent organisms from spreading to the vitreous cavity. However, in fungal keratitis with posterior diffuse or panophthalmitis, intracameral voriconazole injection may be ineffective because of a low concentration of intravitreal voriconazole. Therefore, intravitreal voriconazole with or without pars plana vitrectomy should be performed in severe cases with posterior diffuse involvement. The authors should clarify whether the poor visual outcomes are related to posterior segment involvement. First, in the Methods, the authors should provide the results of vitreous cultures and lens status for the patients. Intraocular specimens were obtained only from aqueous humor; however, results of vitreous cultures may indicate whether intravitreal antibiotics should be administered, especially in mildly anterior focal vitreous inflammation. Second, the lens also plays an important role for preventing organisms from invading the posterior segment. Therefore, the authors should illustrate whether eyes with aphakia and pseudophakia have a higher incidence of posterior segment involvement and poor visual outcomes than those with phakia. In the Discussion, we would like to point out a minor error in the authors’ assumption of the normal volume of the anterior chamber. In fact, the normal volume of the anterior chamber in humans is 0.2 mL,4,5 rather than 0.5
CORRESPONDENCE
185
mL, as reported in this study. Therefore, the injected dose of 100 g/0.1 mL should result in an anterior chamber concentration of 333 g/mL or more after aqueous tapping for cultures. The peak levels achieved in the anterior chamber thus were more than 300 times the minimum inhibitory concentration of voriconazole to Candida and Aspergillus species. Final visual outcomes are related to posterior segment involvement in patients with endophthalmitis. If the authors provide more supplementary data such as echographic findings, results of vitreous cultures, and lens status, this study is a valuable reference for clinical practices.
invasion and replication of fungal filaments into the vitreous may occur in postkeratitis fungal endophthalmitis, which is mainly diagnosed based on positive results from culture of vitreous samples. Injection of intravitreal voriconazole with or without vitrectomy should be performed in case of suspected vitreous invasion. The role of the lens in preventing fungi from invading the posterior segment could not be determined in this study. First, patients in the current series all had phakic eyes. Second, the small number of cases was insufficient for statistical analysis. It has been shown that the depth and volume of the anterior chamber diminishes with age. Male subjects have larger anterior chamber dimensions than female subjects.3 The volume of the anterior chamber is approximately 0.3 mL in the phakic eye and probably increases to approximately 0.5 mL in the pseudophakic eye.4,5 An in vitro study has shown that no corneal endothelial toxicity could be detected after 30 days of treatment with 250 g/mL of voriconazole. Even concentrations of up to 1 mg/mL had no influence on corneal endothelial cells and primary human trabecular meshwork cells when administered for 24 hours.6 With the normal volume of the aqueous humor in the phakic eye assumed to be 0.3 mL, the injected dose of 100 g/0.1 mL in the anterior chamber resulted in an initial aqueous concentration of 250 g/mL. The peak levels achieved in the anterior chamber thus were more than 250 times the minimum inhibitory concentration of voriconazole to Candida and Aspergillus species. Moreover, no endothelial toxicity occurred with such a concentration of voriconazole.
KUAN-JEN CHEN CHI-CHIN SUN CHING-HSI HSIAO HSIN-YUAN TAN LUNG-KUN YEH
Taoyuan, Taiwan
REFERENCES
1. Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. Am J Ophthalmol 2010;149(6):916 – 921. 2. Dacey MP, Valencia M, Lee MB, et al. Echographic findings in infectious endophthalmitis. Arch Ophthalmol 1994;112(10): 1325–1333. 3. Greenwald MJ, Wohl LG, Sell CH. Metastatic bacterial endophthalmitis: a contemporary reappraisal. Surv Ophthalmol 1986;31(2):81–101. 4. Fontana ST, Brubaker RF. Volume and depth of the anterior chamber in the normal aging human eye. Arch Ophthalmol 1980;98(10):1803–1808. 5. Johnson SB, Coakes RL, Brubaker RF. A simple photogrammetric method of measuring anterior chamber volume. Am J Ophthalmol 1978;85(4):469 – 474.
YING-CHENG SHEN CHUN-YUAN WANG
Taichung, Taiwan
REFERENCES
1. Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. Am J Ophthalmol 2010;149(6):916 – 921. 2. Dacey MP, Valencia M, Lee MB, et al. Echographic findings in infectious endophthalmitis. Arch Ophthalmol 1994;112(10): 1325–1333. 3. Fontana ST, Brubaker RF. Volume and depth of the anterior chamber in the normal aging human eye. Arch Ophthalmol 1980;98(10):1803–1808. 4. Murphy CC, Nicholson S, Quah SA, Batterbury M, Neal T, Kaye SB. Pharmacokinetics of vancomycin following intracameral bolus injection in patients undergoing phacoemulsification cataract surgery. Br J Ophthalmol 2007;91:1350 –1353. 5. Schoenwald RD. Ocular pharmacokinetics. In: Zimmerman TJ, ed. Textbook of Ocular Pharmacology. Philadelphia: Lippincott-Raven, 1997:119 –138. 6. Kernt M, Kampik A. Intracameral voriconazole: in vivo safety for human ocular cells. Toxicology 2009;258(2–3):84 –93.
REPLY WE APPRECIATE THE INTEREST IN AND COMMENTS ABOUT
our article.1 To evaluate posterior segment in patients with opaque media, ocular echography is a useful instrument.2 In our patients, ocular echographic examination was performed routinely when the retina could not be viewed directly. In Patient 1, a descemetocele and corneal leukoma resulted in poor visual acuity. The visual outcomes in Patients 2 and 5 resulted from advanced glaucoma and retinal detachment, respectively. Most cases of fungal endophthalmitis contiguously spreading from keratitis tend to be more localized with the fungal mass, and inflammation often is confined to the anterior chamber, pupillary space, or anterior vitreous. In such cases, repeated injections of intracameral voriconazole may be an effective treatment. We agree that 186
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JANUARY 2011