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Bleb-Associated Endophthalmitis: Author Reply
Letters to the Editor Bleb-Associated Endophthalmitis
Author reply
Dear Editor: In their retrospective case series examining the treatment outcomes of patients with bleb-associated endophthalmitis (BAE), Busbee et al suggest that patients with BAE should undergo primary vitrectomy combined with intravitreal administration of antibiotics, rather than an initial vitreous tap and intravitreal administration of antibiotics.1 The authors base this conclusion on the statistically significant difference in the risk of blindness (defined as a visual acuity of no light perception) identified between the vitrectomy and vitreous tap groups in their study. In our opinion, this conclusion is invalid, as the two groups are not comparable at baseline because there are unequal therapeutic delays. The time between the onset of symptoms and initial treatment was significantly shorter among patients undergoing primary vitrectomy (mean, 1.3 days) than among those undergoing an initial vitreous tap and injection of intravitreal antibiotics alone (mean, 3.5 days) (P ⫽ 0.001). The importance of the shorter therapeutic delay in the vitrectomy group becomes clear when the marked virulence of the most common bacterial pathogens (especially streptococcal species) in BAE is considered.2,3 An experimental model of endophthalmitis in the rabbit eye has clearly demonstrated that administration of intravitreal antiobiotics within 24 hours from onset of endophthalmitis is associated with a linear dose–response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor.4 By contrast, treatment after 48 hours from onset with the same intravitreal antibiotic treatment may have no significant effect on bacterial counts. We believe that stronger evidence is required before concluding that primary vitrectomy with administration of intravitreal antibiotics is associated with better visual outcomes than an initial vitreous tap and intravitreal antibiotics for the treatment of BAE.
Dear Editor: We appreciate Sharma et al’s contribution to the ongoing discussion relating to the optimal treatment for patients with bleb-associated endophthalmitis. Our goal in the compilation and presentation of our 68 patients was to provide additional information on this rare entity. We do not feel that any definitive statement, either positive or negative, can be made on a study consisting of level IV evidence-based medicine. A higher level of evidencebased study, such as a prospective randomized trial (level I or II) or even an uncontrolled nonrandomized clinical trial (level III), would be more desirable for any entity. Because the low incidence of bleb-associated endophthalmitis makes it difficult to perform a sound clinical trial, we must evaluate this entity within the parameters of the best available data. Our article is the largest published series of patients with bleb-associated endophthalmitis. However, we also acknowledge this study’s inevitable limitations, which we summarized on pages 1501 to 1502. A definitive treatment recommendation cannot be advocated from our data. We believe our recommendations are stated with appropriate qualifications that prompt vitrectomy “is suggested by this study” and that “patients treated with prompt PPV [pars plana vitrectomy] may achieve better visual outcome.” Sharma et al assert that our conclusions are invalid because of the shorter interval between onset of symptoms and initial treatment in the vitrectomy group. However, they also recognize the deleterious effect of organism virulence, which we analyzed in our study. Interestingly, in our series there was a larger proportion of “more virulent” organisms (i.e., streptococcal species, Staphylococcus aureus, enterococcal species, Serratia species, Pseduomonas species) in the vitrectomy group than in the tap/inject group (75% vs. 53%, respectively). The evidence that Sharma et al cite in support of the importance of prompt treatment is a rabbit model of Pseudomonas endophthalmitis. Our group and others1,2 observed Pseudomonas species in ⬍5% of cases of bleb-associated endophthalmitis. We feel that the extrapolation of data obtained from an animal model and a clinically uncommon pathogen must be made with caution. Numerous factors (e.g., time, organism virulence) contribute to visual outcome in cases of bleb-associated endophthalmitis. Which of these factors is most important? We recognize that our study cannot appropriately answer that question, and that a sufficiently powered multivariate analysis of all factors would be ideal. Conversely, we do not believe that examining one factor alone invalidates the significance of the results. We agree with Sharma et al that prompt treatment is likely to be helpful in preserving vision, and we believe that our findings suggest that primary vitrectomy may be superior to tap/inject in the treatment of bleb-associated endophthalmitis. Larger studies or a meta-
TARUN SHARMA, FRCSED SIMON D. M. CHEN, MRCOPHTH JOHN F. SALMON, MD Oxford, United Kingdom References 1. Busbee BG, Recchia FM, Kaiser R, et al. Bleb-associated endophthalmitis: clinical characteristics and visual outcomes. Ophthalmology 2004;111:1495–503. 2. Song A, Scott IU, Flynn HW Jr, Budenz DL. Delayed-onset bleb-associated endophthalmitis: clinical features and visual acuity outcomes. Ophthalmology 2002;109:985–91. 3. Ciulla TA, Beck AD, Topping TM, Baker AS. Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma filtering surgery. Ophthalmology 1997;104:986 –95. 4. Davey PG, Barza M, Stuart M. Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to “late” treatment of infections. J Infect Dis 1987;155:518 –23.
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Letters to the Editor analysis of results from multiple centers may be helpful in providing more definitive treatment recommendations. BRANDON G. BUSBEE, MD Nashville, Tennessee
glaucoma patients with ambulatory vision treated with laser cyclotherapy. It may be too early to consider expansion of its indications beyond what we are practicing. JANE C. C. YEUNG, MRSCED Hong Kong, China
References References 1. Song A, Scott IU, Flynn HW Jr, Budenz DL. Delayed-onset bleb-associated endophthalmitis: clinical features and visual acuity outcomes. Ophthalmology 2002;109:985–91. 2. Ciulla TA, Beck AD, Topping TM, Baker AS. Blebitis, early endophthalmitis, and late endophthalmitis after glaucomafiltering surgery. Ophthalmology 1997;104:986 –95.
Transscleral Laser Cyclotherapy Dear Editor: I read with interest Wilensky and Kammer’s article on long-term visual outcome of transscleral laser cyclotherapy in eyes with ambulatory vision.1 The laser cycloablative procedure has been used mainly for eyes with advanced glaucoma with low visual potential, pain relief, and eyes with multiple failed filter operations because of its potential risk of irreversible visual loss.2 Based on the visual outcome of patients in their retrospective series, the authors suggested that the indications for laser cyclotherapy should be expanded beyond those included in the American Academy of Ophthalmology policy statement.2 Before drawing such a conclusion, it would be useful if the authors could provide some of the interesting information that was not reported in their study. Of the 21 patients they recruited, it is noticed that the prelaser intraocular pressures (IOPs) of 3 were ⬍21 mmHg. What was the indication for laser cycloablation in these cases? About 81% of their patients required additional treatment. It would be interesting to know when additional treatment was carried out in their study. The authors claimed that their patients had advanced glaucoma because they had been operated before the laser treatment. However, the cup-to-disc ratio is a more useful indicator of the stage of glaucoma, but this was not reported. I wish to know whether the authors treated a group of glaucoma patients with ambulatory vision as well as advanced optic disc cupping or ambulatory vision with early optic disc cupping only. Although the majority of patients had their IOP finally controlled after laser cyclotherapy, I need to know the mean number of antiglaucoma medications before and after laser treatment to assess the IOP outcome of the laser cyclotherapy. The authors encountered no hypotony in their series and reported only one case of bullous keratopathy. Can the authors tell us the power of their study to detect important problems such as phthisis if it occurs infrequently—say, 5% of the time? One percent of the time? Egbert et al3 and Lai et al4 found that a substantial number of patients developed an atonic pupil after laser cyclophotocoagulation. I wish to know if this and or other complications were noticed in the authors’ study. This study reported only the visual outcome of a group of
1. Wilensky JT, Kammer J. Long-term visual outcome of transscleral laser cyclotherapy in eyes with ambulatory vision. Ophthalmology 2004;111:1389 –92. 2. Pastor SA, Singh K, Lee DA, et al. Cyclophotocoagulation: a report by the American Academy of Ophthalmology. Ophthalmology 2001;108:2130 – 8. 3. Egbert PR, Fiadoyor DL, Budenz DL, et al. Diode laser transscleral cyclophotocoagulation as a primary surgical treatment for primary open-angle glaucoma. Arch Ophthalmol 2001;119:345–50. 4. Lai JS, Tham CC, Chan JC, Lam DS. Diode laser transscleral cyclophotocoagulation in the treatment of chronic angle-closure glaucoma: a preliminary study. J Glaucoma 2003;12: 360 – 4.
Author reply Dear Editor: We thank Dr Yeung for her interest in our article. Because of the American Academy of Ophthalmology’s policy statement, our goal was to demonstrate that patients with ambulatory vision could be treated with laser cyclotherapy with preservation of that vision in most cases. It was not a study to demonstrate the general efficacy of laser cyclotherapy, so we did not tabulate information on the number of medications, the time of additional therapy, etc. As we stated in the article, these were all patients with advanced glaucoma. They were all uncontrolled with maximum tolerated medical therapy, and almost all had advanced cupping (0.8 or greater). We disagree with Dr Yeung about the value of the cup-to-disc ratio as an indicator of the stage of glaucoma. We believe that visual fields (particularly Goldmann kinetic perimetry) allow better differentiation of disease stage among these eyes with advanced cupping. Because of the advanced stage of glaucoma in these eyes, the target pressure for many of these patients was ⱕ15 mmHg, which accounts for the fact that some patients were treated with an IOP of ⬍21 mmHg. Because almost all of these patients had had prior cataract surgery and a majority also had had filtering surgery, most of them did not have normal pupils before the laser treatment. In our experience with other phakic patients, we have not frequently encountered atonic pupils or progression of cataracts, an issue of concern that has also been raised. After our article’s publication, a number of glaucoma colleagues in conversations at meetings have indicated to us that they also are safely using laser cyclotherapy to treat eyes with better vision. We hope that they will share their results and help convince Dr Yeung and others that they too
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Author reply
Dear Editor: In their retrospective case series examining the treatment outcomes of patients with bleb-associated endophthalmitis (BAE), Busbee et al suggest that patients with BAE should undergo primary vitrectomy combined with intravitreal administration of antibiotics, rather than an initial vitreous tap and intravitreal administration of antibiotics.1 The authors base this conclusion on the statistically significant difference in the risk of blindness (defined as a visual acuity of no light perception) identified between the vitrectomy and vitreous tap groups in their study. In our opinion, this conclusion is invalid, as the two groups are not comparable at baseline because there are unequal therapeutic delays. The time between the onset of symptoms and initial treatment was significantly shorter among patients undergoing primary vitrectomy (mean, 1.3 days) than among those undergoing an initial vitreous tap and injection of intravitreal antibiotics alone (mean, 3.5 days) (P ⫽ 0.001). The importance of the shorter therapeutic delay in the vitrectomy group becomes clear when the marked virulence of the most common bacterial pathogens (especially streptococcal species) in BAE is considered.2,3 An experimental model of endophthalmitis in the rabbit eye has clearly demonstrated that administration of intravitreal antiobiotics within 24 hours from onset of endophthalmitis is associated with a linear dose–response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor.4 By contrast, treatment after 48 hours from onset with the same intravitreal antibiotic treatment may have no significant effect on bacterial counts. We believe that stronger evidence is required before concluding that primary vitrectomy with administration of intravitreal antibiotics is associated with better visual outcomes than an initial vitreous tap and intravitreal antibiotics for the treatment of BAE.
Dear Editor: We appreciate Sharma et al’s contribution to the ongoing discussion relating to the optimal treatment for patients with bleb-associated endophthalmitis. Our goal in the compilation and presentation of our 68 patients was to provide additional information on this rare entity. We do not feel that any definitive statement, either positive or negative, can be made on a study consisting of level IV evidence-based medicine. A higher level of evidencebased study, such as a prospective randomized trial (level I or II) or even an uncontrolled nonrandomized clinical trial (level III), would be more desirable for any entity. Because the low incidence of bleb-associated endophthalmitis makes it difficult to perform a sound clinical trial, we must evaluate this entity within the parameters of the best available data. Our article is the largest published series of patients with bleb-associated endophthalmitis. However, we also acknowledge this study’s inevitable limitations, which we summarized on pages 1501 to 1502. A definitive treatment recommendation cannot be advocated from our data. We believe our recommendations are stated with appropriate qualifications that prompt vitrectomy “is suggested by this study” and that “patients treated with prompt PPV [pars plana vitrectomy] may achieve better visual outcome.” Sharma et al assert that our conclusions are invalid because of the shorter interval between onset of symptoms and initial treatment in the vitrectomy group. However, they also recognize the deleterious effect of organism virulence, which we analyzed in our study. Interestingly, in our series there was a larger proportion of “more virulent” organisms (i.e., streptococcal species, Staphylococcus aureus, enterococcal species, Serratia species, Pseduomonas species) in the vitrectomy group than in the tap/inject group (75% vs. 53%, respectively). The evidence that Sharma et al cite in support of the importance of prompt treatment is a rabbit model of Pseudomonas endophthalmitis. Our group and others1,2 observed Pseudomonas species in ⬍5% of cases of bleb-associated endophthalmitis. We feel that the extrapolation of data obtained from an animal model and a clinically uncommon pathogen must be made with caution. Numerous factors (e.g., time, organism virulence) contribute to visual outcome in cases of bleb-associated endophthalmitis. Which of these factors is most important? We recognize that our study cannot appropriately answer that question, and that a sufficiently powered multivariate analysis of all factors would be ideal. Conversely, we do not believe that examining one factor alone invalidates the significance of the results. We agree with Sharma et al that prompt treatment is likely to be helpful in preserving vision, and we believe that our findings suggest that primary vitrectomy may be superior to tap/inject in the treatment of bleb-associated endophthalmitis. Larger studies or a meta-
TARUN SHARMA, FRCSED SIMON D. M. CHEN, MRCOPHTH JOHN F. SALMON, MD Oxford, United Kingdom References 1. Busbee BG, Recchia FM, Kaiser R, et al. Bleb-associated endophthalmitis: clinical characteristics and visual outcomes. Ophthalmology 2004;111:1495–503. 2. Song A, Scott IU, Flynn HW Jr, Budenz DL. Delayed-onset bleb-associated endophthalmitis: clinical features and visual acuity outcomes. Ophthalmology 2002;109:985–91. 3. Ciulla TA, Beck AD, Topping TM, Baker AS. Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma filtering surgery. Ophthalmology 1997;104:986 –95. 4. Davey PG, Barza M, Stuart M. Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to “late” treatment of infections. J Infect Dis 1987;155:518 –23.
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Letters to the Editor analysis of results from multiple centers may be helpful in providing more definitive treatment recommendations. BRANDON G. BUSBEE, MD Nashville, Tennessee
glaucoma patients with ambulatory vision treated with laser cyclotherapy. It may be too early to consider expansion of its indications beyond what we are practicing. JANE C. C. YEUNG, MRSCED Hong Kong, China
References References 1. Song A, Scott IU, Flynn HW Jr, Budenz DL. Delayed-onset bleb-associated endophthalmitis: clinical features and visual acuity outcomes. Ophthalmology 2002;109:985–91. 2. Ciulla TA, Beck AD, Topping TM, Baker AS. Blebitis, early endophthalmitis, and late endophthalmitis after glaucomafiltering surgery. Ophthalmology 1997;104:986 –95.
Transscleral Laser Cyclotherapy Dear Editor: I read with interest Wilensky and Kammer’s article on long-term visual outcome of transscleral laser cyclotherapy in eyes with ambulatory vision.1 The laser cycloablative procedure has been used mainly for eyes with advanced glaucoma with low visual potential, pain relief, and eyes with multiple failed filter operations because of its potential risk of irreversible visual loss.2 Based on the visual outcome of patients in their retrospective series, the authors suggested that the indications for laser cyclotherapy should be expanded beyond those included in the American Academy of Ophthalmology policy statement.2 Before drawing such a conclusion, it would be useful if the authors could provide some of the interesting information that was not reported in their study. Of the 21 patients they recruited, it is noticed that the prelaser intraocular pressures (IOPs) of 3 were ⬍21 mmHg. What was the indication for laser cycloablation in these cases? About 81% of their patients required additional treatment. It would be interesting to know when additional treatment was carried out in their study. The authors claimed that their patients had advanced glaucoma because they had been operated before the laser treatment. However, the cup-to-disc ratio is a more useful indicator of the stage of glaucoma, but this was not reported. I wish to know whether the authors treated a group of glaucoma patients with ambulatory vision as well as advanced optic disc cupping or ambulatory vision with early optic disc cupping only. Although the majority of patients had their IOP finally controlled after laser cyclotherapy, I need to know the mean number of antiglaucoma medications before and after laser treatment to assess the IOP outcome of the laser cyclotherapy. The authors encountered no hypotony in their series and reported only one case of bullous keratopathy. Can the authors tell us the power of their study to detect important problems such as phthisis if it occurs infrequently—say, 5% of the time? One percent of the time? Egbert et al3 and Lai et al4 found that a substantial number of patients developed an atonic pupil after laser cyclophotocoagulation. I wish to know if this and or other complications were noticed in the authors’ study. This study reported only the visual outcome of a group of
1. Wilensky JT, Kammer J. Long-term visual outcome of transscleral laser cyclotherapy in eyes with ambulatory vision. Ophthalmology 2004;111:1389 –92. 2. Pastor SA, Singh K, Lee DA, et al. Cyclophotocoagulation: a report by the American Academy of Ophthalmology. Ophthalmology 2001;108:2130 – 8. 3. Egbert PR, Fiadoyor DL, Budenz DL, et al. Diode laser transscleral cyclophotocoagulation as a primary surgical treatment for primary open-angle glaucoma. Arch Ophthalmol 2001;119:345–50. 4. Lai JS, Tham CC, Chan JC, Lam DS. Diode laser transscleral cyclophotocoagulation in the treatment of chronic angle-closure glaucoma: a preliminary study. J Glaucoma 2003;12: 360 – 4.
Author reply Dear Editor: We thank Dr Yeung for her interest in our article. Because of the American Academy of Ophthalmology’s policy statement, our goal was to demonstrate that patients with ambulatory vision could be treated with laser cyclotherapy with preservation of that vision in most cases. It was not a study to demonstrate the general efficacy of laser cyclotherapy, so we did not tabulate information on the number of medications, the time of additional therapy, etc. As we stated in the article, these were all patients with advanced glaucoma. They were all uncontrolled with maximum tolerated medical therapy, and almost all had advanced cupping (0.8 or greater). We disagree with Dr Yeung about the value of the cup-to-disc ratio as an indicator of the stage of glaucoma. We believe that visual fields (particularly Goldmann kinetic perimetry) allow better differentiation of disease stage among these eyes with advanced cupping. Because of the advanced stage of glaucoma in these eyes, the target pressure for many of these patients was ⱕ15 mmHg, which accounts for the fact that some patients were treated with an IOP of ⬍21 mmHg. Because almost all of these patients had had prior cataract surgery and a majority also had had filtering surgery, most of them did not have normal pupils before the laser treatment. In our experience with other phakic patients, we have not frequently encountered atonic pupils or progression of cataracts, an issue of concern that has also been raised. After our article’s publication, a number of glaucoma colleagues in conversations at meetings have indicated to us that they also are safely using laser cyclotherapy to treat eyes with better vision. We hope that they will share their results and help convince Dr Yeung and others that they too
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