Asia-Pacific Journal of Ophthalmology
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Volume 1, Number 4, July/August 2012
Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to Detect Visual Field Progression in Treated Glaucoma Patients To the Editor: etermining visual field progression is pertinent to glaucoma management. Although a number of software packages have been commercially available for evaluation of visual field progression, they are different in the algorithms (trend vs event) and the patterns (global vs local) of analysis. Clinicians often face with the difficulty in interpreting visual field progression when the analysis of one approach is not in line with the others. De Moraes and colleagues conducted an informative study investigating the agreement among 3 commercially available software packages including PROGRESSOR (pointwise linear regression) (Medisoft, Ltd, Leeds, UK), GPAYtrend analysis of visual field index (Carl Zeiss Meditec, Dublin, Calif), and GPAYEarly Manifest Glaucoma Trial criteria (Carl Zeiss Meditec) for detection of visual field progression. They analyzed 130 glaucoma patients followed up for a mean of 7.3 T 1.8 years with at least 8 visual fields and found a moderate agreement among the 3 methods. The authors suggested that the differences between GPA-EMGT criteria and PROGRESSOR were in part related to the different abilities between these methods to detect more rapidly progressing eyes. The rates of global change of visual sensitivity were j0.67 and j0.30 dB/y in progressing eyes detected by PROGRESSOR alone and GPA-EMGT criteria alone, respectively. However, would this difference reflect the defining criteria of progression in PROGRESSOR (a loss of 91.0 dB/y for 2 adjacent locations)? If progression is defined with a loss of greater than 0.5 dB/y for 2 adjacent locations, would the global rates of change differ between PROGRESSOR and GPA-EMGT criteria? Can the authors speculate why eyes with progression detected by both GPA-EMGT criteria and PROGRESSOR had the fastest rate of visual field loss? As correctly pointed out by the authors, understanding the differences in the detection rates among different progression analysis algorithms is relevant and important to select an optimal method to detect glaucoma progression.
D
Christopher Leung, MD, MBChB Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong
Hong Kong Eye Hospital Kowloon, Hong Kong People’s Republic of China
Re: Manuscript Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to Detect Visual Field Progression in Treated Glaucoma Patients To the Editor: e read with interest the comments by Dr Leung regarding our recent article entitled ‘‘Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to Detect Visual Field Progression in Treated Glaucoma Patients.’’1 Dr Leung emphasized that clinicians are often challenged when interpreting visual field progression results when there is disagreement between methods. This is important not only in clinical management, but also when interpreting the results of clinical trials as each one of them used a different progression criterion, thus preventing any direct, objective comparison among their results.2Y6 Despite using different criteria, numerous studies have tried to compare the performance of these criteria to detect visual field progression in different sample populations.7Y10 Given the growing interest of detecting progression using trend analysis, in particular using the PROGRESSOR software (Medisoft, Ltd, Leeds, UK),11Y13 we aimed to perform a comparative study similarly to the ones cited above.7Y10 In agreement with previous studies comparing different forms of event-based techniques,7Y10 we reported certain features that clinicians and researchers should be aware of when facing potential disagreement between methods. Both event- and trend-based methods to detect visual field progression lack a gold standard. In the case of trend analysis, particularly using PROGRESSOR or any method that uses ordinary least squares linear regression, there are many combinations of parameters one can use to define progression. This can be done by setting different slopes, their statistical significance (> level), and spatial distribution of points. Our group has recently validated one such method that revealed the best performance in terms of arbitrarily defined sensitivities and specificities.14 The trend analysis criterion in which a progressing eye had at least 2 adjacent test locations in the same hemifield progressing at j1.0 dB/y at P G 0.01 revealed the best performance. We also found that using
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Letter to the Editor
a single point meeting the aforementioned criteria resulted in greater sensitivity at the expense of very high false-positive rates. As Dr Leung hypothesized, we found a significant difference in global rates of change (dB/y) between the criterion that used a single progressing point versus all other criteria that required at least 2 progressing points. This would very likely also occur if different slopes with different > levels were chosen, that is, less negative pointwise slopes would result in slower global rates of visual field change. It is important to note that the same permutation could also be done with the GPA criteria: if instead of at least 3 points progressing significantly on 3 consecutive visual field test we used less stringent definitions (eg, 1 or 2 points on 2 consecutive examinations), all comparisons would likely be different than we reported. In fact, eyes with progression detected by both GPA-EMGT criteria and PROGRESSOR had the fastest rate of visual field loss1 because they all had more stringent progression criteria (at least 3 points) than eyes that met each criterion alone. Notably, we acknowledged the points above in the discussion section of our article: ‘‘It is important to note that there are different ways of defining progression using GPA2 and PROGRESSOR, and our findings are applicable only for the criteria defined herein. For instance, changing the number and location of progressing points using GPA2 and PROGRESSOR could have led to different rates of agreement. There is a large number of combinations for these analyses, which we avoided doing. Also, all eyes in our study had a large sequence of VF tests to optimize the performance of both event- and trend-based methods. It is known that in eyes with smaller number of tests event analysis may show higher detection rates. Therefore, generalization of our findings is not advised. In addition, the agreement and performance of each method depend on specific predefined criteria that involve number of progressing points, slopes, and statistical significance, and such details should always be taken into account.’’
* 2012 Asia Pacific Academy of Ophthalmology
Copyright © 2012 by Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
251
Letter to the Editor
Given the numerous combinations of event- and trend-based approaches we could have used in our study, we had to stick with the ones more widely used and that have been shown to have better sensitivity and specificity using a predefined gold standard. Therefore, our article brought attention to how different visual progression criteria can reveal disparities and how they can be primarily explained by how stringent one defines progression. This highlights that a gold-standard to define glaucoma progression is warranted and we are glad Dr. Leung helped expand the discussion on this topic. Carlos Gustavo De Moraes, MD *† Jeffrey M. Liebmann, MD *† Robert Ritch, MD *‡ *Department of Ophthalmology, New York University School of Medicine, New York, New York †Einhorn Clinical Research Center, New York Eye and Ear Infirmary, New York, New York ‡Department of Ophthalmology, New York Medical College, Valhalla, New York
REFERENCES 1. De Moraes CG, Ghobraiel S, Ritch R, et al. Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to detect visual field progression in treated glaucoma patients. Asia Pac J Ophthalmol. 2012;1:135Y139.
252
Asia-Pacific Journal of Ophthalmology 2. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714Y720. 3. Leske MC, Heijl A, Hyman L, et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114:1965Y1972. 4. AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:490Y491. 5. Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors. Ophthalmology. 2009;116:200Y207. 6. Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol. 1998;126:487Y497. 7. Vesti E, Johnson CA, Chauhan BC. Comparison of different methods for detecting glaucomatous visual field progression. Invest Ophthalmol Vis Sci. 2003;44:3873Y3879. 8. Nouri-Mahdavi K, Caprioli J, Coleman AL, et al. Pointwise linear regression for evaluation of visual field outcomes and
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Volume 1, Number 4, July/August 2012 comparison with the Advanced Glaucoma Intervention Study methods. Arch Ophthalmol. 2005;123:193Y199.
9. Heijl A, Bengtsson B, Chauhan BC, et al. A comparison of visual field progression criteria of 3 major glaucoma trials in Early Manifest Glaucoma Trial patients. Ophthalmology. 2008;115:1557Y1565. 10. Iester M, Capris E, De Feo F, et al. Agreement to detect glaucomatous visual field progression by using three different methods: a multicentre study. Br J Ophthalmol. 2011;95:1276Y1283. 11. Fitzke FW, Hitchings RA, Poinoosawmy D, et al. Analysis of visual field progression in glaucoma. Br J Ophthalmol. 1996;80:40Y48. 12. Grewal DS, Sehi M, Greenfield DS; Advanced Imaging in Glaucoma Study Group. Comparing rates of retinal nerve fibre layer loss with GDxECC using different methods of visual-field progression. Br J Ophthalmol. 2011;95:1122Y1127. 13. De Moraes CG, Juthani VJ, Liebmann JM, et al. Risk factors for visual field progression in treated glaucoma. Arch Ophthalmol. 2011;129:562Y568. 14. De Moraes CG, Liebmann CA, Susanna R Jr, et al. Examination of the performance of different pointwise linear regression progression criteria to detect glaucomatous visual field change [published online ahead of print]. Clin Exp Ophthalmol. 2011 Sep 8. doi: 10.1111/j.1442-9071.2011.02680.x. [Epub ahead of print].
* 2012 Asia Pacific Academy of Ophthalmology
Copyright © 2012 by Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
&
Volume 1, Number 4, July/August 2012
Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to Detect Visual Field Progression in Treated Glaucoma Patients To the Editor: etermining visual field progression is pertinent to glaucoma management. Although a number of software packages have been commercially available for evaluation of visual field progression, they are different in the algorithms (trend vs event) and the patterns (global vs local) of analysis. Clinicians often face with the difficulty in interpreting visual field progression when the analysis of one approach is not in line with the others. De Moraes and colleagues conducted an informative study investigating the agreement among 3 commercially available software packages including PROGRESSOR (pointwise linear regression) (Medisoft, Ltd, Leeds, UK), GPAYtrend analysis of visual field index (Carl Zeiss Meditec, Dublin, Calif), and GPAYEarly Manifest Glaucoma Trial criteria (Carl Zeiss Meditec) for detection of visual field progression. They analyzed 130 glaucoma patients followed up for a mean of 7.3 T 1.8 years with at least 8 visual fields and found a moderate agreement among the 3 methods. The authors suggested that the differences between GPA-EMGT criteria and PROGRESSOR were in part related to the different abilities between these methods to detect more rapidly progressing eyes. The rates of global change of visual sensitivity were j0.67 and j0.30 dB/y in progressing eyes detected by PROGRESSOR alone and GPA-EMGT criteria alone, respectively. However, would this difference reflect the defining criteria of progression in PROGRESSOR (a loss of 91.0 dB/y for 2 adjacent locations)? If progression is defined with a loss of greater than 0.5 dB/y for 2 adjacent locations, would the global rates of change differ between PROGRESSOR and GPA-EMGT criteria? Can the authors speculate why eyes with progression detected by both GPA-EMGT criteria and PROGRESSOR had the fastest rate of visual field loss? As correctly pointed out by the authors, understanding the differences in the detection rates among different progression analysis algorithms is relevant and important to select an optimal method to detect glaucoma progression.
D
Christopher Leung, MD, MBChB Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong
Hong Kong Eye Hospital Kowloon, Hong Kong People’s Republic of China
Re: Manuscript Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to Detect Visual Field Progression in Treated Glaucoma Patients To the Editor: e read with interest the comments by Dr Leung regarding our recent article entitled ‘‘Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to Detect Visual Field Progression in Treated Glaucoma Patients.’’1 Dr Leung emphasized that clinicians are often challenged when interpreting visual field progression results when there is disagreement between methods. This is important not only in clinical management, but also when interpreting the results of clinical trials as each one of them used a different progression criterion, thus preventing any direct, objective comparison among their results.2Y6 Despite using different criteria, numerous studies have tried to compare the performance of these criteria to detect visual field progression in different sample populations.7Y10 Given the growing interest of detecting progression using trend analysis, in particular using the PROGRESSOR software (Medisoft, Ltd, Leeds, UK),11Y13 we aimed to perform a comparative study similarly to the ones cited above.7Y10 In agreement with previous studies comparing different forms of event-based techniques,7Y10 we reported certain features that clinicians and researchers should be aware of when facing potential disagreement between methods. Both event- and trend-based methods to detect visual field progression lack a gold standard. In the case of trend analysis, particularly using PROGRESSOR or any method that uses ordinary least squares linear regression, there are many combinations of parameters one can use to define progression. This can be done by setting different slopes, their statistical significance (> level), and spatial distribution of points. Our group has recently validated one such method that revealed the best performance in terms of arbitrarily defined sensitivities and specificities.14 The trend analysis criterion in which a progressing eye had at least 2 adjacent test locations in the same hemifield progressing at j1.0 dB/y at P G 0.01 revealed the best performance. We also found that using
W
Letter to the Editor
a single point meeting the aforementioned criteria resulted in greater sensitivity at the expense of very high false-positive rates. As Dr Leung hypothesized, we found a significant difference in global rates of change (dB/y) between the criterion that used a single progressing point versus all other criteria that required at least 2 progressing points. This would very likely also occur if different slopes with different > levels were chosen, that is, less negative pointwise slopes would result in slower global rates of visual field change. It is important to note that the same permutation could also be done with the GPA criteria: if instead of at least 3 points progressing significantly on 3 consecutive visual field test we used less stringent definitions (eg, 1 or 2 points on 2 consecutive examinations), all comparisons would likely be different than we reported. In fact, eyes with progression detected by both GPA-EMGT criteria and PROGRESSOR had the fastest rate of visual field loss1 because they all had more stringent progression criteria (at least 3 points) than eyes that met each criterion alone. Notably, we acknowledged the points above in the discussion section of our article: ‘‘It is important to note that there are different ways of defining progression using GPA2 and PROGRESSOR, and our findings are applicable only for the criteria defined herein. For instance, changing the number and location of progressing points using GPA2 and PROGRESSOR could have led to different rates of agreement. There is a large number of combinations for these analyses, which we avoided doing. Also, all eyes in our study had a large sequence of VF tests to optimize the performance of both event- and trend-based methods. It is known that in eyes with smaller number of tests event analysis may show higher detection rates. Therefore, generalization of our findings is not advised. In addition, the agreement and performance of each method depend on specific predefined criteria that involve number of progressing points, slopes, and statistical significance, and such details should always be taken into account.’’
* 2012 Asia Pacific Academy of Ophthalmology
Copyright © 2012 by Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
251
Letter to the Editor
Given the numerous combinations of event- and trend-based approaches we could have used in our study, we had to stick with the ones more widely used and that have been shown to have better sensitivity and specificity using a predefined gold standard. Therefore, our article brought attention to how different visual progression criteria can reveal disparities and how they can be primarily explained by how stringent one defines progression. This highlights that a gold-standard to define glaucoma progression is warranted and we are glad Dr. Leung helped expand the discussion on this topic. Carlos Gustavo De Moraes, MD *† Jeffrey M. Liebmann, MD *† Robert Ritch, MD *‡ *Department of Ophthalmology, New York University School of Medicine, New York, New York †Einhorn Clinical Research Center, New York Eye and Ear Infirmary, New York, New York ‡Department of Ophthalmology, New York Medical College, Valhalla, New York
REFERENCES 1. De Moraes CG, Ghobraiel S, Ritch R, et al. Comparison of PROGRESSOR Versus Glaucoma Progression Analysis 2 to detect visual field progression in treated glaucoma patients. Asia Pac J Ophthalmol. 2012;1:135Y139.
252
Asia-Pacific Journal of Ophthalmology 2. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714Y720. 3. Leske MC, Heijl A, Hyman L, et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114:1965Y1972. 4. AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:490Y491. 5. Musch DC, Gillespie BW, Lichter PR, et al. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors. Ophthalmology. 2009;116:200Y207. 6. Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol. 1998;126:487Y497. 7. Vesti E, Johnson CA, Chauhan BC. Comparison of different methods for detecting glaucomatous visual field progression. Invest Ophthalmol Vis Sci. 2003;44:3873Y3879. 8. Nouri-Mahdavi K, Caprioli J, Coleman AL, et al. Pointwise linear regression for evaluation of visual field outcomes and
&
Volume 1, Number 4, July/August 2012 comparison with the Advanced Glaucoma Intervention Study methods. Arch Ophthalmol. 2005;123:193Y199.
9. Heijl A, Bengtsson B, Chauhan BC, et al. A comparison of visual field progression criteria of 3 major glaucoma trials in Early Manifest Glaucoma Trial patients. Ophthalmology. 2008;115:1557Y1565. 10. Iester M, Capris E, De Feo F, et al. Agreement to detect glaucomatous visual field progression by using three different methods: a multicentre study. Br J Ophthalmol. 2011;95:1276Y1283. 11. Fitzke FW, Hitchings RA, Poinoosawmy D, et al. Analysis of visual field progression in glaucoma. Br J Ophthalmol. 1996;80:40Y48. 12. Grewal DS, Sehi M, Greenfield DS; Advanced Imaging in Glaucoma Study Group. Comparing rates of retinal nerve fibre layer loss with GDxECC using different methods of visual-field progression. Br J Ophthalmol. 2011;95:1122Y1127. 13. De Moraes CG, Juthani VJ, Liebmann JM, et al. Risk factors for visual field progression in treated glaucoma. Arch Ophthalmol. 2011;129:562Y568. 14. De Moraes CG, Liebmann CA, Susanna R Jr, et al. Examination of the performance of different pointwise linear regression progression criteria to detect glaucomatous visual field change [published online ahead of print]. Clin Exp Ophthalmol. 2011 Sep 8. doi: 10.1111/j.1442-9071.2011.02680.x. [Epub ahead of print].
* 2012 Asia Pacific Academy of Ophthalmology
Copyright © 2012 by Asia Pacific Academy of Ophthalmology. Unauthorized reproduction of this article is prohibited.
