Predictive Factors for the Rate of Visual Field Progression in the Advanced Imaging for Glaucoma Study.
ABSTRACT: PURPOSE:To investigate predictive factors associated with the rate of visual field (VF) loss in open-angle glaucoma. DESIGN:Prospective multicenter cohort study. METHODS:Perimetric glaucoma patients of the Advanced Imaging for Glaucoma study were selected for analysis if they had 9 completed visits. Confirmed rapid significant progression (CRSP) of VF was defined as a significant (P < 0.05) negative VF index (VFI) slope of -1%/year or a mean deviation slope of -0.5 dB/year, confirmed at 2 consecutive follow-up visits. Slow progression was defined as VFI slope greater than -0.5%/year or a mean deviation slope of -0.25 dB/year. Fourier-domain optical coherence tomography (FD-OCT) measured optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thicknesses. Logistic regression was used to identify baseline predictors for CRSP and slow progression. Linear regression was used to identify baseline predictors for the VFI and mean deviation slope. RESULTS:Eyes (n = 150) of 103 participants were included. Slow progression was observed in 80 eyes (53.3%) and CRSP in 23 eyes (15.3%). Larger NFL and GCC baseline focal loss volume (FLV), thinner central corneal thickness, and lower VFI were significant (P < 0.05) baseline predictors of more rapid progression on univariate analysis. The predictor with the highest odds ratio (OR) was NFL-FLV, which was also the most significant non-VF predictor in the multivariate analysis. Eyes with NFL-FLV >8.5% had an OR of 2.67 for CRSP and 0.42 for slow progression. Disc hemorrhage during the follow-up was also important, with an OR of 2.61 for CRSP and 0.23 for slow progression for each occurrence. CONCLUSIONS:Focal loss measured by FD-OCT or VF along with CCT are strong baseline predictors for the rate of glaucoma progression.
Project description:To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma.Multicenter cohort study.Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters.A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI.Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model.
Project description:To predict the development of glaucomatous visual field (VF) defects using Fourier-domain optical coherence tomography (FD OCT) measurements at baseline visit.Multicenter longitudinal observational study. Glaucoma suspects and preperimetric glaucoma participants in the Advanced Imaging for Glaucoma Study.The optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) were imaged with FD OCT. VF was assessed every 6 months. Conversion to perimetric glaucoma was defined by VF pattern standard deviation (PSD) or glaucoma hemifield test (GHT) outside normal limits on 3 consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. Predictive accuracy was measured by the area under the receiver operating characteristic curve (AUC).Of 513 eyes (309 participants), 55 eyes (46 participants) experienced VF conversion during 41 ± 23 months of follow-up. Significant (P < .05, Cox regression) FD OCT risk factors included all GCC, NFL, and disc variables, except for horizontal cup-to-disc ratio. GCC focal loss volume (FLV) was the best single predictor of conversion (AUC = 0.753, P < .001 for test against AUC = 0.5). Those with borderline or abnormal GCC-FLV had a 4-fold increase in conversion risk after 6 years (Kaplan-Meier). Optimal prediction of conversion was obtained using the glaucoma composite conversion index (GCCI) based on a multivariate Cox regression model that included GCC-FLV, inferior NFL quadrant thickness, age, and VF PSD. GCCI significantly improved predictive accuracy (AUC = 0.783) over any single variable (P = .04).Reductions in NFL and GCC thickness can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma patients.
Project description:To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF).Validity assessment.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.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.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.
Project description:To construct an optical coherence tomography (OCT) nerve fiber layer (NFL) parameter that has maximal correlation and agreement with visual field (VF) mean deviation (MD). The NFL_MD parameter in dB scale was calculated from the peripapillary NFL thickness profile nonlinear transformation and VF area-weighted averaging. From the Advanced Imaging for Glaucoma study, 245 normal, 420 pre-perimetric glaucoma (PPG), and 289 perimetric glaucoma (PG) eyes were selected. NFL_MD had significantly higher correlation (Pearson R: 0.68 vs 0.55, p?<?0.001) with VF_MD than the overall NFL thickness. NFL_MD also had significantly higher sensitivity in detecting PPG (0.14 vs 0.08) and PG (0.60 vs 0.43) at the 99% specificity level. NFL_MD had better reproducibility than VF_MD (0.35 vs 0.69?dB, p?<?0.001). The differences between NFL_MD and VF_MD were -0.34?±?1.71?dB, -0.01?±?2.08?dB and 3.54?±?3.18?dB and 7.17?±?2.68?dB for PPG, early PG, moderate PG, and severe PG subgroups, respectively. In summary, OCT-based NFL_MD has better correlation with VF_MD and greater diagnostic sensitivity than the average NFL thickness. It has better reproducibility than VF_MD, which may be advantageous in detecting progression. It agrees well with VF_MD in early glaucoma but underestimates damage in moderate~advanced stages.
Project description:Purpose:To detect visual field (VF) progression by analyzing spatial pattern changes. Methods:We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results:In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7%), and increased nasal steps (16.4%), altitudinal loss (15.9%), superior-peripheral defect (12.1%), paracentral/central defects (10.5%), and near total loss (10.4%). In the clinical validation cohort of 397 eyes with 27.5% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P < 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions:The archetype method can inform clinicians of VF progression patterns.
Project description:BACKGROUND:To investigate structural and functional correlations in glaucoma patients using enhanced depth imaging spectral-domain optical coherence tomography (EDI OCT)-derived parameters. METHODS:We prospectively enrolled healthy participants and glaucomatous patients with a wide range of disease stages. All participants underwent visual field (VF) testing (SITA - Standard 24-2; Carl Zeiss Meditec, Dublin, CA) and EDI OCT imaging (Spectralis; Heidelberg Engineering Co., Heidelberg, Germany). The following optic nerve head parameters were measured on serial vertical EDI OCT B-scans by two experienced examiners masked to patients clinical data: lamina cribrosa (LC) thickness and area, prelaminar neural tissue thickness and area, anterior LC depth, Bruch's membrane opening (BMO) and average, superior, and inferior BMO-minimum rim width (BMO-MRW). Only good quality images were considered, and whenever both eyes were eligible, one was randomly selected for analysis. Scatter plots were constructed to investigate correlations between each anatomic parameter and patient's VF status (based on VF index [VFI] values). RESULTS:A total of 73 eyes of 73 patients were included. All EDI OCT parameters evaluated differed significantly between glaucomatous and control eyes (P???0.045). A secondary analysis, in which glaucomatous patients were divided according to VF mean deviation index values into 3 groups (mild [G1; >?-?6?dB], moderate [G2; -?6 to -?12?dB] and advanced [G3; <-?12?dB] glaucoma), revealed that average BMO-MRW was the EDI OCT parameter that presented more significant differences between the different stages of glaucoma. Significant structure-function correlations were found between VFI values and prelaminar neural tissue area (R2?=?0.20, P?=?0.017), average BMO-MRW (R2?=?0.35, P???0.001), superior BMO-MRW (R2?=?0.21, P?=?0.012), and inferior BMO-MRW (R2?=?0.27, P?=?0.002). No significant correlations were found for LC area and anterior LC depth (P???0.452). CONCLUSIONS:Evaluating the distribution pattern and structure-function correlations of different laminar and prelaminar EDI OCT-derived parameters in glaucomatous patients, we found better results for neural tissue-based indexes (compared to LC-derived parameters). The diagnostic utility of each parameter deserves further investigations.
Project description:PURPOSE:To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN:Retrospective longitudinal cohort study. PARTICIPANTS:Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831?240 VFs, a subset of 90?713 VFs from 13?156 eyes of 8499 patients met the inclusion criteria. METHODS:Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's ? coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES:Agreement and discordance between algorithms. RESULTS:Individual algorithms showed poor to moderate agreement with each other when compared directly (? range, 0.12-0.52). Based on at least 4 algorithms, 11.7% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P < 0.01) and older age at first available VF (P < 0.01). A greater number of VFs (P < 0.01), more years of follow-up (P < 0.01), and eye care institution (P = 0.03) also were associated with discordance. CONCLUSIONS:This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.
Project description:The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals.This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ? -2 diopter (D), and axial length ? 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch's membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis.The mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it.In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself.
Project description:BACKGROUND/OBJECTIVES:To investigate the correlation between obstructive sleep apnea (OSA) severity and the structural and functional progression in patients with glaucoma. SUBJECTS/METHODS:This retrospective comparative cohort study included subjects from the polysomnography database in Chang Gung Memorial Hospital between June 1, 2009, and June 1, 2017, by identifying patients who had received diagnoses of primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), or glaucoma suspect. Patients with follow-up time of <3 years and/or <3 consecutive reliable optical coherence tomography (OCT) or visual field (VF) tests were excluded. Progression of overall peripapillary retinal nerve fiber layer (RNFL) thickness on OCT scans and VF mean deviation (MD) or VF index (VFI) were determined through linear regression trend analysis. RESULTS:Thirty-two patients were included. There was a trend to higher percentage of progression on RNFL thickness and VF in higher OSAS severity. After stratifying patients to no OSA/mild OSA (group 1) and moderate/severe OSA (group 2), group 2 exhibited a significantly higher percentage of RNFL thickness progression than did group 1 (64.7% vs 26.7%, P?=?0.042). Multivariate Cox regression analysis showed that severe OSA had an 8.448-fold higher risk of RNFL thickness progression after age, sex, diabetes mellitus, hypertension, hyperlipidemia, and body mass index adjustment (95% confidence interval, 1.464-48.752, P?=?0.017). CONCLUSIONS:Severe OSA is significantly correlated with a higher risk of structural deterioration in patients with glaucoma.
Project description:PurposeTo evaluate a progression-detecting algorithm for a new automated matched alternation flicker (AMAF) in glaucoma patients.MethodsOpen-angle glaucoma patients with a baseline mean deviation of visual field (VF) test>-6?dB were included in this longitudinal and retrospective study. Functional progression was detected by two VF progression criteria and structural progression by both AMAF and conventional comparison methods using optic disc and retinal nerve fiber layer (RNFL) photography. Progression-detecting performances of AMAF and the conventional method were evaluated by an agreement between functional and structural progression criteria. RNFL thickness changes measured by optical coherence tomography (OCT) were compared between progressing and stable eyes determined by each method.ResultsAmong 103 eyes, 47 (45.6%), 21 (20.4%), and 32 (31.1%) eyes were evaluated as glaucoma progression using AMAF, the conventional method, and guided progression analysis (GPA) of the VF test, respectively. The AMAF showed better agreement than the conventional method, using GPA of the VF test (?=0.337; P<0.001 and ?=0.124; P=0.191, respectively). The rates of RNFL thickness decay using OCT were significantly different between the progressing and stable eyes when progression was determined by AMAF (-3.49±2.86??m per year vs -1.83±3.22??m per year; P=0.007) but not by the conventional method (-3.24±2.42??m per year vs -2.42±3.33??m per year; P=0.290).ConclusionsThe AMAF was better than the conventional comparison method in discriminating structural changes during glaucoma progression, and showed a moderate agreement with functional progression criteria.