Comparison of Glaucoma Progression Detection by Optical Coherence Tomography and Visual Field

on behalf of; the Advanced Imaging for Glaucoma Study Group

doi:10.1016/j.ajo.2017.09.020

Comparison of Glaucoma Progression Detection by Optical Coherence Tomography and Visual Field

on behalf of, the Advanced Imaging for Glaucoma Study Group

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). Design Validity assessment. Methods We analyzed subjects with more than 4 semi-annual follow-up visits (every 6 months) in the multicenter Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. Results The analysis included 356 glaucoma suspect/preperimetric glaucoma (GS/PPG) eyes and 153 perimetric glaucoma (PG) eyes. Follow-up length was 54.1 ± 16.2 months for GS/PPG eyes and 56.7 ± 16.0 for PG eyes. Progression was detected in 62.1% of PG eyes and 59.8% of GS/PPG eyes by OCT, significantly (P <.001) more than the detection rate of 41.8% and 27.3% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate than VF in mild PG (63.1% vs. 38.7%, P <.001), but not in moderate and advanced PG. The rate of NFL thinning slowed dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The Kaplan-Meier time-to-event analyses showed that OCT detected progression earlier than VF in both PG and GS/PPG groups. Conclusions OCT is more sensitive than VF for the detection of progression in early glaucoma. While the utility of NFL declines in advanced glaucoma, GCC remains a sensitive progression detector from early to advanced stages.

Original language	English (US)
Pages (from-to)	63-74
Number of pages	12
Journal	American Journal of Ophthalmology
Volume	184
DOIs	https://doi.org/10.1016/j.ajo.2017.09.020
State	Published - Dec 2017

ASJC Scopus subject areas

Ophthalmology

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10.1016/j.ajo.2017.09.020

Cite this

@article{6c2c12c0cf8c48d78c652e939f436659,

title = "Comparison of Glaucoma Progression Detection by Optical Coherence Tomography and Visual Field",

abstract = "Purpose To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). Design Validity assessment. Methods We analyzed subjects with more than 4 semi-annual follow-up visits (every 6 months) in the multicenter Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. Results The analysis included 356 glaucoma suspect/preperimetric glaucoma (GS/PPG) eyes and 153 perimetric glaucoma (PG) eyes. Follow-up length was 54.1 ± 16.2 months for GS/PPG eyes and 56.7 ± 16.0 for PG eyes. Progression was detected in 62.1% of PG eyes and 59.8% of GS/PPG eyes by OCT, significantly (P <.001) more than the detection rate of 41.8% and 27.3% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate than VF in mild PG (63.1% vs. 38.7%, P <.001), but not in moderate and advanced PG. The rate of NFL thinning slowed dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The Kaplan-Meier time-to-event analyses showed that OCT detected progression earlier than VF in both PG and GS/PPG groups. Conclusions OCT is more sensitive than VF for the detection of progression in early glaucoma. While the utility of NFL declines in advanced glaucoma, GCC remains a sensitive progression detector from early to advanced stages.",

author = "{on behalf of} and {the Advanced Imaging for Glaucoma Study Group} and Xinbo Zhang and Anna Dastiridou and Francis, {Brian A.} and Ou Tan and Rohit Varma and Greenfield, {David S.} and Schuman, {Joel S.} and David Huang",

note = "Funding Information: In glaucoma management, it is believed that structural tests can better identify progression in the early stages of the disease, whereas VF examinations are more useful in the later stages. 6,12,34,37,46 Recent studies have focused on the comparison between progression identified with NFL or optic disc OCT imaging and visual fields. 12,37,47 Abe and associates suggested that in patients with different glaucoma stages, monitoring NFL with spectral-domain OCT gives a higher chance of detection of disease progression in early stages, whereas VF testing is more relevant in later stages. 37 In another study, Banegas and associates supported the role of progression detection using OCT NFL in preperimetric and early glaucoma, while they recommended the use of VF testing and optic disc photography for advanced glaucoma monitoring. 12 The findings of the present study are largely in agreement with the above-mentioned studies, with NFL trend analysis showing good progression detection in early-to-moderate glaucoma and VF being more useful in identifying progression in moderate-to-late stages. However, this study also provides novel evidence to support OCT imaging of the macula (specifically GCC) as a useful tool even in the later stages of glaucoma, with similar ability to detect progression as VF. This is important in that our study included the disease continuum from glaucoma suspects to advanced glaucoma patients and directly compared VF testing with both NFL and GCC trend analyses. The study supports the use of OCT imaging to monitor glaucoma from early to late stages. A number of studies have already recognized that NFL reaches a minimum residual thickness plateau in late glaucoma. 5,6,48 Compared to peripapillary NFL, 37 macular GCC appears to deplete later in the course of glaucoma. 13,37,49 The reason for this difference may be regional. The overall NFL cross-sectional area sampled by the peripapillary circular scan is dominated by the arcuate bundles, which are damaged early in the course of glaucoma. In contrast, the macular region is relatively spared in most cases of early glaucoma, with the papillomacular bundle usually depleted much later in the disease process. In our study, when the PG group was stratified according to disease severity, it became apparent that there was a significant difference between GCC and NFL in the moderate and advanced PG groups. In these later stages of glaucoma, GCC thinning continued while NFL thinning nearly halted ( Table 6 ). As a consequence, GCC was more useful at detecting progression in these later stages ( Table 5 ). This finding is in agreement with the study by Sung and associates, 13 in which the authors studied overall macular thickness (without separate layer segmentation) in a cohort of advanced glaucoma eyes and recognized that it was superior in progression detection compared to optic disc or retinal NFL thickness. They concluded that it may be more reliably associated with VF progression than other OCT parameters. This was further investigated in another cohort of advanced glaucoma patients in which the macular ganglion cell–inner plexiform layer thickness was able to detect progression, further supporting the fact that structural change can be identified even in very advanced glaucoma eyes. 49 By looking at GCC and NFL together, we found that OCT parameters detected progression at higher rates than VF in both the GS/PPG group and the PG group. Stratified analysis in the PG group showed that OCT also had a higher detection rate in all severity groups, including advanced PG. Kaplan-Meier analysis showed that OCT is also able to detect progression in a shorter period of time (with the same visit frequency) in both the PG and GS/PPG groups. OCT parameters also had better specificity, with values close to the 5% cutoff for the significance of linear regression. In contrast, VF trend analyses detected a significantly higher number of false-positives in the permutated series in the PG group. This may have been caused by the MD and VFI distribution deviating from the normal distribution assumed in ordinary least-square linear regression. The residual distribution of VF test error is known to be severely skewed toward the negative in areas of significant damage. 50 VF event analysis has a well-characterized low false-positive rate of 2.6%, 8 but had relatively low detection rates in this study. Overall, OCT may be a more reliable test for glaucoma progression because it has good detection rate and acceptable specificity over a wide range of glaucoma severity. The reason that OCT outperformed VF in detecting progression in most disease stages stems from OCT's greater measurement precision, as shown by our analysis of residuals ( Table 6 ). Many studies have already highlighted the predictive role of OCT NFL thinning on the future visual outcome. Faster rates of retinal NFL thinning were associated with increased risk of visual field loss in glaucoma suspects. 51 In another prospective study, progressive retinal NFL thinning was again predictive of functional decline as measured with visual fields in glaucoma patients. 52 In addition, previous reports from the AIG Study have already suggested that both NFL and GCC thinning can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma 31 and that focal GCC and NFL loss as measured by Fourier-domain OCT can strongly predict faster VF progression in established glaucoma. 33 Therefore, there is evidence to support that thinning of the NFL or GCC on OCT can predict future vision loss. However, we are not advocating relying on OCT alone or ignoring VF in the monitoring of glaucoma. Poor agreement between structural and functional measurements for tracking glaucoma has been noted in many previous publications, but this may relate to the variation of how different patients progress. 53 In the current study, if VF was not used, progression would go undetected in many cases of PG—approximately 6% in moderate PG and 11% in advanced PG. Therefore, OCT and VF were both found to be necessary for tracking progression in perimetric glaucoma and it is crucial that both be used in clinical practice. Between the 2 VF trend progression detection methods, MD trend detected more progression than VFI trend in GS/PPG, but they had exactly the same detection rates in PG, and surprisingly they only overlapped moderately ( Figure 2 ). VFI has been shown to exhibit a ceiling effect in early glaucoma and overestimation of remaining visual field. 15 Although our results showed MD trend to be more sensitive than VFI trend in GS/PPG, we also showed that VFI trend detected progression in a significant number of eyes missed by MD in the PG group. Therefore the 2 VF trend analyses may be complementary. Between the VF trend progression detection methods and event progression method, trend analyses had greater detection rates in all stages of glaucoma by either MD or VFI. However, they only moderately overlap and both contributed independently toward progression detection. Therefore the use of both trend and event analyses is recommended, in addition to OCT parameters, in the monitoring of glaucoma progression. We investigated several variations in the methods used to detect progression with OCT parameters. The default analysis in this paper averaged measurements from 3 sets of OCT scans at each visit, accounted for the rate of normal age-related thinning in NFL and GCC, 42 and compensated for the effect of OCT signal strength variation on NFL measurements. 41 This differs from the standard clinical practice, where 1 OCT scan is made at each visit, and no compensation for signal strength or aging changes is made in the linear regression analysis software on the commercial RTVue OCT system software. Our analysis found that accounting for the change over time in NFL and GCC owing to normal aging had significant effects on detecting progression; therefore it is desirable to adjust for aging effect when using the trend of NFL and GCC to define progression. This finding agreed with a previous investigation by Medeiros and associates. 47 Adjusting for SSI slightly improved detection. Using results from only 1 OCT scan per visit (instead of the default of averaging results from 3 scans) slightly decreased the rate of detecting significant progression, but still gave better results than VF in GS/PPG and early PG groups. We conclude that the commercial OCT software provides good progression detection, when analyzing time series of only 1 OCT scan per visit, with better performance than VF monitoring in the early glaucoma patients and glaucoma suspects. However, it is worthwhile to add signal strength compensation and aging adjustment to the commercial OCT glaucoma progression analysis software. Certain limitations should be considered when looking at the results of the present study. First, we can only use surrogate methods to indirectly determine false-positive rate for progression detection. The ideal method to assess specificity is to acquire many measurements over a short period of time. 8,54 Unfortunately, this type of data was not available in the AIG Study. Another limitation is that there were very few patients with end-stage glaucoma in the study. Our advanced glaucoma group had only 15 eyes and the MD was −14.4 ± 1.9 dB (range −12 to −19 dB). Thus the performance of GCC in monitoring end-stage glaucoma was not adequately studied. It is possible that GCC also reaches a floor thickness and poorly reflects disease severity in the very advanced glaucoma stage. The floor effect is a consideration in all methods of detecting glaucoma progression, including VF. In very advanced glaucoma, standard 24-2 VF becomes insensitive to further progression, and changes to more central test pattern (ie, to 10-2) and large stimulus sizes become advisable. Thus the monitoring of glaucoma progression in very advanced stages remains a challenge that could benefit from new solutions. 55 In this study we did not require that changes be confirmed on subsequent testing, in order to increase sensitivity. 56 This does not affect our conclusions, since the same methodology was applied to both VF and OCT trend analysis. However, in clinical practice it is still advisable to confirm findings before making significant clinical decisions concerning disease management. In summary, OCT has higher sensitivity for progression detection than VF, both in perimetric glaucoma eyes and in preperimetric glaucoma and early perimetric glaucoma eyes. OCT is able to detect progression within a shorter follow-up time in early glaucoma. Therefore clinicians could rely more heavily on OCT to monitor progression in the early stages of the disease. However, a number of patients seem to progress by either functional or structural tests, or some by both, in all glaucoma stages. Using OCT and VF together for disease monitoring is advisable, as this can track disease progression more frequently than using either method alone. Interestingly, in moderate and advanced glaucoma (with good evidence down to MD of −15 dB), OCT continues to be useful in progression monitoring, with GCC trend analysis being more useful than NFL trend analysis. This can also be especially useful in clinical practice, to overcome difficulties that some advanced glaucoma patients encounter when undertaking VF, since OCT is an objective test and does not depend on patient response. Obtaining 1 OCT scan per visit appears to be adequate for progression monitoring, though averaging more scans per visit could modestly improve the rate of progression detection. Adjusting for aging and signal strength effects could also improve the accuracy of progression rate calculations, and we recommend these improvements to the commercial software for OCT trend analysis. Funding/Support: Supported by NIH grants R01 EY013516, R01 EY023285 (Bethesda, Maryland, USA), P30 EY010572, an unrestricted grant from Research to Prevent Blindness (New York, New York, USA) and the Champalimaud Foundation (Lisbon, Portugal). Financial Disclosures: Ou Tan and David Huang have significant financial interests in Optovue, Inc (Fremont, California, USA), a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by Oregon Health & Science University. David S. Greenfield receives research support from Optovue, Inc, Carl Zeiss Meditec, Inc, and Heidelberg Engineering (Carlsbad, California, USA). Rohit Varma has received research grants, honoraria, and/or travel support from Carl Zeiss Meditec, Inc, Heidelberg Engineering, and Optovue, Inc. The following authors have no financial disclosures: Xinbo Zhang, Anna Dastiridou, and Brian A. Francis. All authors attest that they meet the current ICMJE criteria for authorship. Advanced Imaging for Glaucoma Study Group: A listing of members of the Advanced Imaging for Glaucoma Study Group and additional financial disclosure information for group members is included in an Appendix (Supplemental Material available at AJO.com ). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = dec,

doi = "10.1016/j.ajo.2017.09.020",

language = "English (US)",

volume = "184",

pages = "63--74",

journal = "American Journal of Ophthalmology",

issn = "0002-9394",

publisher = "Elsevier USA",

}

TY - JOUR

T1 - Comparison of Glaucoma Progression Detection by Optical Coherence Tomography and Visual Field

AU - on behalf of

AU - the Advanced Imaging for Glaucoma Study Group

AU - Zhang, Xinbo

AU - Dastiridou, Anna

AU - Francis, Brian A.

AU - Tan, Ou

AU - Varma, Rohit

AU - Greenfield, David S.

AU - Schuman, Joel S.

AU - Huang, David

N1 - Funding Information: In glaucoma management, it is believed that structural tests can better identify progression in the early stages of the disease, whereas VF examinations are more useful in the later stages. 6,12,34,37,46 Recent studies have focused on the comparison between progression identified with NFL or optic disc OCT imaging and visual fields. 12,37,47 Abe and associates suggested that in patients with different glaucoma stages, monitoring NFL with spectral-domain OCT gives a higher chance of detection of disease progression in early stages, whereas VF testing is more relevant in later stages. 37 In another study, Banegas and associates supported the role of progression detection using OCT NFL in preperimetric and early glaucoma, while they recommended the use of VF testing and optic disc photography for advanced glaucoma monitoring. 12 The findings of the present study are largely in agreement with the above-mentioned studies, with NFL trend analysis showing good progression detection in early-to-moderate glaucoma and VF being more useful in identifying progression in moderate-to-late stages. However, this study also provides novel evidence to support OCT imaging of the macula (specifically GCC) as a useful tool even in the later stages of glaucoma, with similar ability to detect progression as VF. This is important in that our study included the disease continuum from glaucoma suspects to advanced glaucoma patients and directly compared VF testing with both NFL and GCC trend analyses. The study supports the use of OCT imaging to monitor glaucoma from early to late stages. A number of studies have already recognized that NFL reaches a minimum residual thickness plateau in late glaucoma. 5,6,48 Compared to peripapillary NFL, 37 macular GCC appears to deplete later in the course of glaucoma. 13,37,49 The reason for this difference may be regional. The overall NFL cross-sectional area sampled by the peripapillary circular scan is dominated by the arcuate bundles, which are damaged early in the course of glaucoma. In contrast, the macular region is relatively spared in most cases of early glaucoma, with the papillomacular bundle usually depleted much later in the disease process. In our study, when the PG group was stratified according to disease severity, it became apparent that there was a significant difference between GCC and NFL in the moderate and advanced PG groups. In these later stages of glaucoma, GCC thinning continued while NFL thinning nearly halted ( Table 6 ). As a consequence, GCC was more useful at detecting progression in these later stages ( Table 5 ). This finding is in agreement with the study by Sung and associates, 13 in which the authors studied overall macular thickness (without separate layer segmentation) in a cohort of advanced glaucoma eyes and recognized that it was superior in progression detection compared to optic disc or retinal NFL thickness. They concluded that it may be more reliably associated with VF progression than other OCT parameters. This was further investigated in another cohort of advanced glaucoma patients in which the macular ganglion cell–inner plexiform layer thickness was able to detect progression, further supporting the fact that structural change can be identified even in very advanced glaucoma eyes. 49 By looking at GCC and NFL together, we found that OCT parameters detected progression at higher rates than VF in both the GS/PPG group and the PG group. Stratified analysis in the PG group showed that OCT also had a higher detection rate in all severity groups, including advanced PG. Kaplan-Meier analysis showed that OCT is also able to detect progression in a shorter period of time (with the same visit frequency) in both the PG and GS/PPG groups. OCT parameters also had better specificity, with values close to the 5% cutoff for the significance of linear regression. In contrast, VF trend analyses detected a significantly higher number of false-positives in the permutated series in the PG group. This may have been caused by the MD and VFI distribution deviating from the normal distribution assumed in ordinary least-square linear regression. The residual distribution of VF test error is known to be severely skewed toward the negative in areas of significant damage. 50 VF event analysis has a well-characterized low false-positive rate of 2.6%, 8 but had relatively low detection rates in this study. Overall, OCT may be a more reliable test for glaucoma progression because it has good detection rate and acceptable specificity over a wide range of glaucoma severity. The reason that OCT outperformed VF in detecting progression in most disease stages stems from OCT's greater measurement precision, as shown by our analysis of residuals ( Table 6 ). Many studies have already highlighted the predictive role of OCT NFL thinning on the future visual outcome. Faster rates of retinal NFL thinning were associated with increased risk of visual field loss in glaucoma suspects. 51 In another prospective study, progressive retinal NFL thinning was again predictive of functional decline as measured with visual fields in glaucoma patients. 52 In addition, previous reports from the AIG Study have already suggested that both NFL and GCC thinning can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma 31 and that focal GCC and NFL loss as measured by Fourier-domain OCT can strongly predict faster VF progression in established glaucoma. 33 Therefore, there is evidence to support that thinning of the NFL or GCC on OCT can predict future vision loss. However, we are not advocating relying on OCT alone or ignoring VF in the monitoring of glaucoma. Poor agreement between structural and functional measurements for tracking glaucoma has been noted in many previous publications, but this may relate to the variation of how different patients progress. 53 In the current study, if VF was not used, progression would go undetected in many cases of PG—approximately 6% in moderate PG and 11% in advanced PG. Therefore, OCT and VF were both found to be necessary for tracking progression in perimetric glaucoma and it is crucial that both be used in clinical practice. Between the 2 VF trend progression detection methods, MD trend detected more progression than VFI trend in GS/PPG, but they had exactly the same detection rates in PG, and surprisingly they only overlapped moderately ( Figure 2 ). VFI has been shown to exhibit a ceiling effect in early glaucoma and overestimation of remaining visual field. 15 Although our results showed MD trend to be more sensitive than VFI trend in GS/PPG, we also showed that VFI trend detected progression in a significant number of eyes missed by MD in the PG group. Therefore the 2 VF trend analyses may be complementary. Between the VF trend progression detection methods and event progression method, trend analyses had greater detection rates in all stages of glaucoma by either MD or VFI. However, they only moderately overlap and both contributed independently toward progression detection. Therefore the use of both trend and event analyses is recommended, in addition to OCT parameters, in the monitoring of glaucoma progression. We investigated several variations in the methods used to detect progression with OCT parameters. The default analysis in this paper averaged measurements from 3 sets of OCT scans at each visit, accounted for the rate of normal age-related thinning in NFL and GCC, 42 and compensated for the effect of OCT signal strength variation on NFL measurements. 41 This differs from the standard clinical practice, where 1 OCT scan is made at each visit, and no compensation for signal strength or aging changes is made in the linear regression analysis software on the commercial RTVue OCT system software. Our analysis found that accounting for the change over time in NFL and GCC owing to normal aging had significant effects on detecting progression; therefore it is desirable to adjust for aging effect when using the trend of NFL and GCC to define progression. This finding agreed with a previous investigation by Medeiros and associates. 47 Adjusting for SSI slightly improved detection. Using results from only 1 OCT scan per visit (instead of the default of averaging results from 3 scans) slightly decreased the rate of detecting significant progression, but still gave better results than VF in GS/PPG and early PG groups. We conclude that the commercial OCT software provides good progression detection, when analyzing time series of only 1 OCT scan per visit, with better performance than VF monitoring in the early glaucoma patients and glaucoma suspects. However, it is worthwhile to add signal strength compensation and aging adjustment to the commercial OCT glaucoma progression analysis software. Certain limitations should be considered when looking at the results of the present study. First, we can only use surrogate methods to indirectly determine false-positive rate for progression detection. The ideal method to assess specificity is to acquire many measurements over a short period of time. 8,54 Unfortunately, this type of data was not available in the AIG Study. Another limitation is that there were very few patients with end-stage glaucoma in the study. Our advanced glaucoma group had only 15 eyes and the MD was −14.4 ± 1.9 dB (range −12 to −19 dB). Thus the performance of GCC in monitoring end-stage glaucoma was not adequately studied. It is possible that GCC also reaches a floor thickness and poorly reflects disease severity in the very advanced glaucoma stage. The floor effect is a consideration in all methods of detecting glaucoma progression, including VF. In very advanced glaucoma, standard 24-2 VF becomes insensitive to further progression, and changes to more central test pattern (ie, to 10-2) and large stimulus sizes become advisable. Thus the monitoring of glaucoma progression in very advanced stages remains a challenge that could benefit from new solutions. 55 In this study we did not require that changes be confirmed on subsequent testing, in order to increase sensitivity. 56 This does not affect our conclusions, since the same methodology was applied to both VF and OCT trend analysis. However, in clinical practice it is still advisable to confirm findings before making significant clinical decisions concerning disease management. In summary, OCT has higher sensitivity for progression detection than VF, both in perimetric glaucoma eyes and in preperimetric glaucoma and early perimetric glaucoma eyes. OCT is able to detect progression within a shorter follow-up time in early glaucoma. Therefore clinicians could rely more heavily on OCT to monitor progression in the early stages of the disease. However, a number of patients seem to progress by either functional or structural tests, or some by both, in all glaucoma stages. Using OCT and VF together for disease monitoring is advisable, as this can track disease progression more frequently than using either method alone. Interestingly, in moderate and advanced glaucoma (with good evidence down to MD of −15 dB), OCT continues to be useful in progression monitoring, with GCC trend analysis being more useful than NFL trend analysis. This can also be especially useful in clinical practice, to overcome difficulties that some advanced glaucoma patients encounter when undertaking VF, since OCT is an objective test and does not depend on patient response. Obtaining 1 OCT scan per visit appears to be adequate for progression monitoring, though averaging more scans per visit could modestly improve the rate of progression detection. Adjusting for aging and signal strength effects could also improve the accuracy of progression rate calculations, and we recommend these improvements to the commercial software for OCT trend analysis. Funding/Support: Supported by NIH grants R01 EY013516, R01 EY023285 (Bethesda, Maryland, USA), P30 EY010572, an unrestricted grant from Research to Prevent Blindness (New York, New York, USA) and the Champalimaud Foundation (Lisbon, Portugal). Financial Disclosures: Ou Tan and David Huang have significant financial interests in Optovue, Inc (Fremont, California, USA), a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by Oregon Health & Science University. David S. Greenfield receives research support from Optovue, Inc, Carl Zeiss Meditec, Inc, and Heidelberg Engineering (Carlsbad, California, USA). Rohit Varma has received research grants, honoraria, and/or travel support from Carl Zeiss Meditec, Inc, Heidelberg Engineering, and Optovue, Inc. The following authors have no financial disclosures: Xinbo Zhang, Anna Dastiridou, and Brian A. Francis. All authors attest that they meet the current ICMJE criteria for authorship. Advanced Imaging for Glaucoma Study Group: A listing of members of the Advanced Imaging for Glaucoma Study Group and additional financial disclosure information for group members is included in an Appendix (Supplemental Material available at AJO.com ). Publisher Copyright: © 2017 Elsevier Inc.

PY - 2017/12

Y1 - 2017/12

N2 - Purpose To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). Design Validity assessment. Methods We analyzed subjects with more than 4 semi-annual follow-up visits (every 6 months) in the multicenter Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. Results The analysis included 356 glaucoma suspect/preperimetric glaucoma (GS/PPG) eyes and 153 perimetric glaucoma (PG) eyes. Follow-up length was 54.1 ± 16.2 months for GS/PPG eyes and 56.7 ± 16.0 for PG eyes. Progression was detected in 62.1% of PG eyes and 59.8% of GS/PPG eyes by OCT, significantly (P <.001) more than the detection rate of 41.8% and 27.3% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate than VF in mild PG (63.1% vs. 38.7%, P <.001), but not in moderate and advanced PG. The rate of NFL thinning slowed dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The Kaplan-Meier time-to-event analyses showed that OCT detected progression earlier than VF in both PG and GS/PPG groups. Conclusions OCT is more sensitive than VF for the detection of progression in early glaucoma. While the utility of NFL declines in advanced glaucoma, GCC remains a sensitive progression detector from early to advanced stages.

AB - Purpose To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). Design Validity assessment. Methods We analyzed subjects with more than 4 semi-annual follow-up visits (every 6 months) in the multicenter Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. Results The analysis included 356 glaucoma suspect/preperimetric glaucoma (GS/PPG) eyes and 153 perimetric glaucoma (PG) eyes. Follow-up length was 54.1 ± 16.2 months for GS/PPG eyes and 56.7 ± 16.0 for PG eyes. Progression was detected in 62.1% of PG eyes and 59.8% of GS/PPG eyes by OCT, significantly (P <.001) more than the detection rate of 41.8% and 27.3% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate than VF in mild PG (63.1% vs. 38.7%, P <.001), but not in moderate and advanced PG. The rate of NFL thinning slowed dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The Kaplan-Meier time-to-event analyses showed that OCT detected progression earlier than VF in both PG and GS/PPG groups. Conclusions OCT is more sensitive than VF for the detection of progression in early glaucoma. While the utility of NFL declines in advanced glaucoma, GCC remains a sensitive progression detector from early to advanced stages.

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DO - 10.1016/j.ajo.2017.09.020

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EP - 74

JO - American Journal of Ophthalmology

JF - American Journal of Ophthalmology

ER -

Comparison of Glaucoma Progression Detection by Optical Coherence Tomography and Visual Field

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