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Neisseria meningitidis endophthalmitis
Letters to the Editor Postoperative Inflammation Dear Editor: We read with interest the article by the ICL in Treatment of Myopia Study Group.1 The authors have provided us with data regarding postoperative inflammation in patients with an implantable contact lens (ICL) during the first 2 to 3 years. We would be most interested in how patients were recruited into the study, so as to help us select patients if we were to use this type of phakic intraocular lens. We would also like to know the demographics of the patients included. Can the results be generalized to Chinese eyes, for example? Patients included in the study included individuals with relatively mild degrees of myopia. Is there any particular reason why LASIK was not performed on such patients instead of ICL implantation? Or was there any reason why such patients opted for ICL instead of LASIK? The observer assessment of aqueous humor flare and cellular reaction was well standardized; however, it remains a subjective measurement. Whether these measurements were performed by an independent observer or the surgeons themselves may result in unintended systematic or nonsystematic measurement errors. It is important to know who performed the measurements. Use of an independent observer may reduce bias. Objective assessment, such as that by the laser flare and cell meter, would help to eliminate measurement biases. However, such measurements were performed in only 1 center. It would be presumptuous to assume such measurements to be representative of all 12 centers involved. It would be even more informative if objective measurements were used in all 12 centers or in future assessments. We look forward to longer term results from this study. The results do suggest minimal postoperative inflammation in the first 2 to 3 years. Whether this correlates with less cataract formation, less endothelial loss, less chronic inflammation, and less glaucoma in the coming 10 to 20 years or more remains a question that still needs to be addressed and in which we are very much interested. RICKY W. K. LAW, FRCS RANDA T. H. LI, AFRCS, MPH Hong Kong, China Reference 1. ICL in Treatment of Myopia (ITM) Study Group. Postoperative inflammation after implantation of the implantable contact lens. Ophthalmology 2003;110:2335– 41.
Author reply Dear Editor: The basic information regarding study design and demographics is described in detail in a separate publication outlining the overall results of the United States Food and Drug Administration clinical trial.1 Eighty-five percent of the patients in the US trial were Caucasian, so it is difficult to determine whether these results can be generalized to a non-Caucasian population; however, the implantable contact lens (ICL) is being used successfully in Korea, China,
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and South and Central America, where more darkly pigmented eyes are the majority. The average myopia of this population was 10 diopters (D), and only 21% of patients had ⱕ7 D. Although patients with as little as 3 D of myopia were included, at the discretion of the investigators, most of the patients were clearly not optimal candidates for LASIK. Peer-reviewed studies have shown, however, that the ICL is at least as efficacious with regard to uncorrected visual acuity, and at least as predictable and stable as LASIK in the 4- to ⬍8-D myopia range.2 Furthermore, the ICL was demonstrated to be superior to LASIK in the 8- to 12-D myopia range with regard to efficacy, predictability, and stability.3 Although we agree that clinical assessment of aqueous flare and cellular reaction is indeed subjective, we believe that our investigators could very accurately determine when no flare or cells were present. This was the case in 99.8% to 100% of eyes at every visit ⱖ3 months postoperatively. Although we also agree that it would have been desirable to have laser flare and cell measurements at all 12 centers, this very expensive research tool was only available at 1 site. Given the remarkable similarity of our objective flare measurements to that of 4 other peer-reviewed studies of flare with the ICL shown in our article’s Figure 1, we do believe that our single-center results are indeed representative of the postoperative course with the ICL. Although the presence of virtually no postoperative inflammation over a 2- to 3-year period may not correlate with less cataract formation or with glaucoma long term, we do believe that it strongly suggests that chronic inflammation itself or long-term endothelial cell loss due to chronic inflammation will not be a prominent feature of the long-term postoperative ICL course. DONALD R. SANDERS, MD, PHD Elmhurst, Illinois JOHN A. VUKICH, MD Madison, Wisconsin References 1. Sanders DR, Vukich JA, Doney K, et al. U.S. Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia. Ophthalmology 2003;110:255– 66. 2. Sanders DR, Vukich JA. Comparison of the implantable contact lens (ICL) and laser assisted in situ keratomileusis (LASIK) in low myopia. Cornea. In press. 3. Sanders DR, Vukich JA. Comparison of implantable contact lens and laser assisted in situ keratomileusis for moderate to high myopia. Cornea 2003;22:324 –31.
Neisseria meningitidis Endophthalmitis Dear Editor: Kerkhoff et al1 report a case of Neisseria meningitidis endophthalmitis in a patient without meningitis. Their case highlights the need to suspect uncommon organisms in cases of endogenous endophthalmitis. I recently treated a patient with N. meningitidis endophthalmitis without men-
Letters to the Editor ingitis—thus bringing to 5 the total number of such known cases. My patient was a 16-year-old male with a 1-week history of migratory arthralgias that was preceded by a cough and fever of 24 hours’ duration. In addition, he had a purpuric rash on his distal extremities and testicular swelling. Two days before presentation to me he started noticing redness and pain in the eye and had progressive loss of vision. On examination, his visual acuity was hand movements. He had moderate conjunctival chemosis and injection, and there was severe anterior chamber and vitreous inflammation. Suspecting an endogenous endophthalmitis, I proceeded to perform a vitreous and aqueous tap and injected ceftazidime and vancomycin into the vitreous cavity. The patient was also admitted to the hospital and started on IV antibiotics. Definitive identification of the organism was made on the vitreous fluid 5 days after the culture was obtained. Management of my patient would not have changed had I known the organism any sooner, as the appropriate antibiotics were already started. The patient went on to have retinal detachments requiring multiple surgeries and resulting in a hypotonous eye with very poor vision. I am uncertain about the chain of events in Kerkhoff et al’s patient, who was initially being treated with steroids for a presumed uveitis. They list many laboratory results before stating that an aqueous tap was performed. Was the aqueous tap performed only after all other results came back negative? Otherwise, it is not clear why an aqueous tap would have been performed for a presumed HLA-B27 uveitis. In addition, their article allows for the presumption that the antibiotics were started only after the definitive culture results came back. A clarification of the clinical timeline would be helpful. In my opinion, the main advantage of the polymerase chain reaction (PCR) technique described by Kerkhoff et al is to allow for identification of the organism in case the cultures do not yield anything. This is particularly important when the organism is difficult to grow, as with N. meningitidis. Perhaps it can also allow for fewer false-negative results when the sample volume is very low, or when only the anterior chamber is sampled. Fortunately, the patient described by Kerkhoff et al went on to have a good visual result, contrary to my and others’ experience in cases of N. meningitidis endophthalmitis without meningitis. What is not clear from their article is that there was an early detection of the organism by the PCR technique that contributed to that outcome. DAVID N. ZACKS, MD, PHD Ann Arbor, Michigan Reference 1. Kerkhoff FT, van der Zee A, Bergmans AMC, Rothova A. Polymerase chain reaction detection of Neisseria meningitidis in the intraocular fluid of a patient with endogenous endophthalmitis but without associated meningitis. Ophthalmology 2003;110:2134 – 6.
Membrane Peeling and Indocyanine Green Dear Editor: Sheidow et al1 have recently reported their results of macular hole surgery with and without both internal limiting membrane (ILM) peeling and use of indocyanine green dye (ICG). The aim of macular hole surgery is to improve vision. Indocyanine green dye is widely accepted to facilitate ILM peeling.2,3 However, concerns have been expressed about potential retinal toxicity from ICG manifesting as suboptimal visual recovery.4 The authors reported that ICG-enhanced ILM peeling in a group of 35 patients was associated with a 97.1% rate of first operation hole closure; it is, however, concerning that only 51.4% of these patients achieved a postoperative acuity of 20/50 or better. Of patients in their similar and contemporaneous group of 44 patients undergoing macular hole surgery with ILM peeling but no ICG, 70.4% regained 20/50 or better postoperative acuity. These data and the fact that 56.7% of the 97 control group patients whose macular hole procedure involved neither ILM manipulation nor ICG use ultimately achieved an acuity of 20/50 or better (even though a second procedure was performed in 15%) might be interpreted to support these toxicity-related concerns. It should be stated that without randomization and/or larger sample sizes, the statistical significance of these concerning and clinically significant acuity differences remain unclear. The concentration of ICG employed by the authors was 4.2 mg/ml, with what seems to be the minimum achievable dye contact time. We have performed full-thickness macular hole surgery with ICG-enhanced ILM peeling on 23 patients with 19 stage 2 or 3 holes and 4 stage 4 holes, all of ⬍12 months’ duration. There were 13 males and 10 females, and the mean age was 66 years (range, 55–77). In each case, a solution of ICG diluted in balanced salt solution to a concentration of 0.5 mg/ml and the minimum achievable contact time was employed. This is approximately 12% of the dye concentration employed by Sheidow et al. Internal limiting membrane peeling was achieved in all cases. Prophylactic clear lens cataract extraction was performed in 65.3% (15/23), no phacoemulsification was performed in 21.7% (5/23), and 13.0% (3/23) were pseudophakic. Follow-up was for at least 3 months in all cases. Our primary surgery hole closure rate was 100%, and 69.6% (16/23) achieved a postoperative acuity of 20/40 or better. (Snellen acuity charts routinely employed in the United Kingdom do not include a line between 20/60 and 20/40; this clearly compromises comparison on the basis of either lines of improvement or the proportion of patients achieving 20/50 or better acuity.) We are not aware of any reports suggesting retinal toxicity from ICG when it is used at a concentration of 0.5 mg/ml. Our experience is one of good anatomical and visual results from macular hole surgery with this dye concentration. There are, however, data to suggest that higher dye concentrations and or longer dye contact may be associated with worse acuity outcomes in macular hole surgery. None of these data regarding potential ICG use or toxicity have
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Author reply Dear Editor: The basic information regarding study design and demographics is described in detail in a separate publication outlining the overall results of the United States Food and Drug Administration clinical trial.1 Eighty-five percent of the patients in the US trial were Caucasian, so it is difficult to determine whether these results can be generalized to a non-Caucasian population; however, the implantable contact lens (ICL) is being used successfully in Korea, China,
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and South and Central America, where more darkly pigmented eyes are the majority. The average myopia of this population was 10 diopters (D), and only 21% of patients had ⱕ7 D. Although patients with as little as 3 D of myopia were included, at the discretion of the investigators, most of the patients were clearly not optimal candidates for LASIK. Peer-reviewed studies have shown, however, that the ICL is at least as efficacious with regard to uncorrected visual acuity, and at least as predictable and stable as LASIK in the 4- to ⬍8-D myopia range.2 Furthermore, the ICL was demonstrated to be superior to LASIK in the 8- to 12-D myopia range with regard to efficacy, predictability, and stability.3 Although we agree that clinical assessment of aqueous flare and cellular reaction is indeed subjective, we believe that our investigators could very accurately determine when no flare or cells were present. This was the case in 99.8% to 100% of eyes at every visit ⱖ3 months postoperatively. Although we also agree that it would have been desirable to have laser flare and cell measurements at all 12 centers, this very expensive research tool was only available at 1 site. Given the remarkable similarity of our objective flare measurements to that of 4 other peer-reviewed studies of flare with the ICL shown in our article’s Figure 1, we do believe that our single-center results are indeed representative of the postoperative course with the ICL. Although the presence of virtually no postoperative inflammation over a 2- to 3-year period may not correlate with less cataract formation or with glaucoma long term, we do believe that it strongly suggests that chronic inflammation itself or long-term endothelial cell loss due to chronic inflammation will not be a prominent feature of the long-term postoperative ICL course. DONALD R. SANDERS, MD, PHD Elmhurst, Illinois JOHN A. VUKICH, MD Madison, Wisconsin References 1. Sanders DR, Vukich JA, Doney K, et al. U.S. Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia. Ophthalmology 2003;110:255– 66. 2. Sanders DR, Vukich JA. Comparison of the implantable contact lens (ICL) and laser assisted in situ keratomileusis (LASIK) in low myopia. Cornea. In press. 3. Sanders DR, Vukich JA. Comparison of implantable contact lens and laser assisted in situ keratomileusis for moderate to high myopia. Cornea 2003;22:324 –31.
Neisseria meningitidis Endophthalmitis Dear Editor: Kerkhoff et al1 report a case of Neisseria meningitidis endophthalmitis in a patient without meningitis. Their case highlights the need to suspect uncommon organisms in cases of endogenous endophthalmitis. I recently treated a patient with N. meningitidis endophthalmitis without men-
Letters to the Editor ingitis—thus bringing to 5 the total number of such known cases. My patient was a 16-year-old male with a 1-week history of migratory arthralgias that was preceded by a cough and fever of 24 hours’ duration. In addition, he had a purpuric rash on his distal extremities and testicular swelling. Two days before presentation to me he started noticing redness and pain in the eye and had progressive loss of vision. On examination, his visual acuity was hand movements. He had moderate conjunctival chemosis and injection, and there was severe anterior chamber and vitreous inflammation. Suspecting an endogenous endophthalmitis, I proceeded to perform a vitreous and aqueous tap and injected ceftazidime and vancomycin into the vitreous cavity. The patient was also admitted to the hospital and started on IV antibiotics. Definitive identification of the organism was made on the vitreous fluid 5 days after the culture was obtained. Management of my patient would not have changed had I known the organism any sooner, as the appropriate antibiotics were already started. The patient went on to have retinal detachments requiring multiple surgeries and resulting in a hypotonous eye with very poor vision. I am uncertain about the chain of events in Kerkhoff et al’s patient, who was initially being treated with steroids for a presumed uveitis. They list many laboratory results before stating that an aqueous tap was performed. Was the aqueous tap performed only after all other results came back negative? Otherwise, it is not clear why an aqueous tap would have been performed for a presumed HLA-B27 uveitis. In addition, their article allows for the presumption that the antibiotics were started only after the definitive culture results came back. A clarification of the clinical timeline would be helpful. In my opinion, the main advantage of the polymerase chain reaction (PCR) technique described by Kerkhoff et al is to allow for identification of the organism in case the cultures do not yield anything. This is particularly important when the organism is difficult to grow, as with N. meningitidis. Perhaps it can also allow for fewer false-negative results when the sample volume is very low, or when only the anterior chamber is sampled. Fortunately, the patient described by Kerkhoff et al went on to have a good visual result, contrary to my and others’ experience in cases of N. meningitidis endophthalmitis without meningitis. What is not clear from their article is that there was an early detection of the organism by the PCR technique that contributed to that outcome. DAVID N. ZACKS, MD, PHD Ann Arbor, Michigan Reference 1. Kerkhoff FT, van der Zee A, Bergmans AMC, Rothova A. Polymerase chain reaction detection of Neisseria meningitidis in the intraocular fluid of a patient with endogenous endophthalmitis but without associated meningitis. Ophthalmology 2003;110:2134 – 6.
Membrane Peeling and Indocyanine Green Dear Editor: Sheidow et al1 have recently reported their results of macular hole surgery with and without both internal limiting membrane (ILM) peeling and use of indocyanine green dye (ICG). The aim of macular hole surgery is to improve vision. Indocyanine green dye is widely accepted to facilitate ILM peeling.2,3 However, concerns have been expressed about potential retinal toxicity from ICG manifesting as suboptimal visual recovery.4 The authors reported that ICG-enhanced ILM peeling in a group of 35 patients was associated with a 97.1% rate of first operation hole closure; it is, however, concerning that only 51.4% of these patients achieved a postoperative acuity of 20/50 or better. Of patients in their similar and contemporaneous group of 44 patients undergoing macular hole surgery with ILM peeling but no ICG, 70.4% regained 20/50 or better postoperative acuity. These data and the fact that 56.7% of the 97 control group patients whose macular hole procedure involved neither ILM manipulation nor ICG use ultimately achieved an acuity of 20/50 or better (even though a second procedure was performed in 15%) might be interpreted to support these toxicity-related concerns. It should be stated that without randomization and/or larger sample sizes, the statistical significance of these concerning and clinically significant acuity differences remain unclear. The concentration of ICG employed by the authors was 4.2 mg/ml, with what seems to be the minimum achievable dye contact time. We have performed full-thickness macular hole surgery with ICG-enhanced ILM peeling on 23 patients with 19 stage 2 or 3 holes and 4 stage 4 holes, all of ⬍12 months’ duration. There were 13 males and 10 females, and the mean age was 66 years (range, 55–77). In each case, a solution of ICG diluted in balanced salt solution to a concentration of 0.5 mg/ml and the minimum achievable contact time was employed. This is approximately 12% of the dye concentration employed by Sheidow et al. Internal limiting membrane peeling was achieved in all cases. Prophylactic clear lens cataract extraction was performed in 65.3% (15/23), no phacoemulsification was performed in 21.7% (5/23), and 13.0% (3/23) were pseudophakic. Follow-up was for at least 3 months in all cases. Our primary surgery hole closure rate was 100%, and 69.6% (16/23) achieved a postoperative acuity of 20/40 or better. (Snellen acuity charts routinely employed in the United Kingdom do not include a line between 20/60 and 20/40; this clearly compromises comparison on the basis of either lines of improvement or the proportion of patients achieving 20/50 or better acuity.) We are not aware of any reports suggesting retinal toxicity from ICG when it is used at a concentration of 0.5 mg/ml. Our experience is one of good anatomical and visual results from macular hole surgery with this dye concentration. There are, however, data to suggest that higher dye concentrations and or longer dye contact may be associated with worse acuity outcomes in macular hole surgery. None of these data regarding potential ICG use or toxicity have
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