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Purpose: To investigate the relationship between progression assessed by the visual field guided progression analysis (GPA) and rates of structural and functional change in glaucoma eyes., Methods: This was a longitudinal observational study of 135 eyes of 97 patients with glaucoma followed for an average of 3.5 ± 0.9 years. All patients had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) analysis with spectral domain optical coherence tomography (SDOCT), with an average of 6.8 ± 2.3 visits. A control group of healthy eyes followed longitudinally was used to estimate age-related change. Visual field progression was assessed using the Humphrey Field Analyzer GPA. Estimates of retinal ganglion cell counts from SAP and SDOCT were used to obtain a combined index of glaucomatous damage (RGC index) according to a previously described algorithm. Progression by SDOCT and the retinal ganglion cell (RGC) index were defined as statistically significant (P < 0.05) slopes of change that were also faster than age-related change estimated from healthy eyes., Results: From the 135 eyes, 15 (11%) progressed by GPA, 21 (16%) progressed by SDOCT, and 31 (23%) progressed by the RGC index. Twenty-one eyes showed progression by the RGC index that was missed by the GPA. These eyes had an average rate of change in estimated RGC counts of - 28,910 cells/year, ranging from two to nine times faster than expected age-related losses., Conclusion: Many glaucomatous eyes that are not found to be progressing by GPA may actually have fast rates of change as detected by a combined index of structure and function.

Purpose: To investigate macular ganglion cell-inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs., Methods: 112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs., Result: 47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect., Conclusion: The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect.

Purpose: To investigate the relationship between corneal hysteresis (CH) and progressive retinal nerve fiber layer (RNFL) loss in a cohort of patients with glaucoma followed prospectively over time., Design: Prospective observational cohort study., Methods: One hundred and eighty-six eyes of 133 patients with glaucoma were followed for an average of 3.8 ± 0.8 years, with a median of 9 visits during follow-up. The CH measurements were acquired using the Ocular Response Analyzer (Reichert Instruments, Depew, New York, USA) and RNFL measurements were obtained at each follow up visit using spectral-domain optical coherence tomography (SDOCT). Random-coefficient models were used to investigate the relationship between baseline CH, central corneal thickness (CCT), average intraocular pressure (IOP), and rates of RNFL loss during follow-up, while adjusting for potentially confounding factors., Results: Average baseline RNFL thickness was 76.4 ± 18.1 μm and average baseline CH was 9.2 ± 1.8 mm Hg. CH had a significant effect on rates of RNFL progression. In the univariable model, including only CH as a predictive factor along with time and their interaction, each 1 mm Hg lower CH was associated with a 0.13 μm/year faster rate of RNFL decline (P = .011). A similar relationship between low CH and faster rates of RNFL loss was found using a multivariable model accounting for age, race, average IOP, and CCT (P = .015)., Conclusions: Lower CH was significantly associated with faster rates of RNFL loss over time. The prospective longitudinal design of this study provides further evidence that CH is an important factor to be considered in the assessment of the risk of progression in patients with glaucoma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the diagnostic accuracies of swept-source optical coherence tomography (OCT) wide-angle and peripapillary retinal nerve fiber layer (RNFL) thickness measurements for glaucoma detection., Design: Cross-sectional case-control study., Methods: In this study we enrolled 144 glaucomatous eyes of 106 subjects and 66 eyes of 42 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Glaucoma was defined by the presence of repeatable abnormal standard automated perimetry results and/or progressive glaucomatous optic disc change on masked grading of stereophotographs. Wide-angle and peripapillary RNFL thicknesses were assessed using swept-source OCT. Peripapillary RNFL thickness was also evaluated using spectral-domain OCT. Areas under the receiver operating characteristic (ROC) curves were calculated to evaluate the ability of the different swept-source OCT and spectral-domain OCT parameters to discriminate between glaucomatous and healthy eyes., Results: Mean (± standard deviation) average spectral-domain OCT wide-angle RNFL thicknesses were 50.5 ± 5.8 μm and 35.0 ± 9.6 μm in healthy and glaucomatous eyes, respectively (P < 0.001). Corresponding values for swept-source OCT peripapillary RNFL thicknesses were 103.5 ± 12.3 μm and 72.9 ± 16.5 μm, respectively (P < 0.001). Areas under the ROC curves of swept-source OCT wide-angle and peripapillary RNFL thickness were 0.88 and 0.89, respectively. Swept-source OCT performed similar to average peripapillary RNFL thickness obtained by spectral-domain OCT (area under the ROC curve of 0.90)., Conclusion: Swept-source OCT wide-angle and peripapillary RNFL thickness measurements performed well for detecting glaucomatous damage. The diagnostic accuracies of the swept-source OCT and spectral-domain OCT RNFL imaging protocols evaluated in this study were similar., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To investigate the relationship between macular ganglion cell-inner plexiform layer (mGCIPL) thickness and estimated macular retinal ganglion cell (RGC) counts in glaucoma., Design: Observational cohort study., Participants: Cross-sectional study of 77 healthy, 154 glaucoma suspect, and 159 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study., Methods: All eyes underwent 24-2 standard automated perimetry (SAP) and optic nerve and macular imaging using high-definition optical coherence tomography (OCT). The total number of RGCs was estimated using a previously described model that uses SAP and OCT circumpapillary retinal nerve fiber layer (cpRNFL) measurements. The number of macular RGCs was estimated from the temporal cpRNFL and SAP test points within the central 10°., Main Outcome Measures: The correlation between mGCIPL thickness and estimates of macular RGC counts., Results: The average estimated macular RGC count in glaucomatous eyes was 306 010 ± 109 449 cells, which was significantly lower than the estimate of 520 678 ± 106 843 cells in healthy eyes (P < 0.001). Glaucomatous eyes had 41% fewer estimated macular RGCs than healthy eyes and suspects had 21% fewer estimated macular RGCs. There was strong correlation between estimated macular RGC counts and mGCIPL thickness (R(2) = 0.67; P < 0.001). Macular RGC counts performed better than average mGCIPL thickness in discriminating healthy and glaucomatous eyes with receiver operating characteristic curve areas of 0.873 and 0.775, respectively (P = 0.015)., Conclusions: The strong association between estimated macular RGC counts and mGCIPL thickness and the better diagnostic performance of the macular RGC counts compared with mGCIPL thickness provides further evidence that estimates of RGC number from cpRNFL thickness and SAP sensitivity can be used to assess neural losses in glaucoma., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate choroidal thickness (CT) in healthy and glaucomatous eyes using Swept Source Optical Coherence Tomography (SS-OCT)., Methods: A cross-sectional observational study of 216 eyes of 140 subjects with glaucoma and 106 eyes of 67 healthy subjects enrolled in the Diagnostic Innovations in Glaucoma Study. CT was assessed from wide-field (12×9 mm) SS-OCT scans. The association between CT and potential confounding variables including age, gender, axial length, intraocular pressure, central corneal thickness and ocular perfusion pressure was examined using univariable and multivariable regression analyses., Results: Overall CT was thinner in glaucomatous eyes with a mean (± standard deviation) of 157.7±48.5 µm in glaucoma compared to 179.9±36.1 µm in healthy eyes (P<0.001). The choroid was thinner in both the peripapillary and macular regions in glaucoma compared to controls. Mean peripapillary CT was 154.1±44.1 µm and 134.0±56.9 µm (P<0.001) and macular CT 199.3±46.1 µm and 176.2±57.5 µm (P<0.001) for healthy and glaucomatous eyes respectively. However, older age (P<0.001) and longer axial length (P<0.001) were also associated with thinner choroid and when differences in age and axial length between glaucomatous and healthy subjects were accounted for, glaucoma was not significantly associated with CT. There was also no association between glaucoma severity and CT., Conclusions: Glaucoma was not associated with CT measured using SS-OCT; however, older age and longer axial length were associated with thinner choroid so should be considered when interpreting CT measurements.

PurposeTo investigate the relationship between corneal hysteresis (CH) and progressive retinal nerve fiber layer (RNFL) loss in a cohort of patients with glaucoma followed prospectively over time.DesignProspective observational cohort study.MethodsOne hundred and eighty-six eyes of 133 patients with glaucoma were followed for an average of 3.8 ± 0.8 years, with a median of 9 visits during follow-up. The CH measurements were acquired using the Ocular Response Analyzer (Reichert Instruments, Depew, New York, USA) and RNFL measurements were obtained at each follow up visit using spectral-domain optical coherence tomography (SDOCT). Random-coefficient models were used to investigate the relationship between baseline CH, central corneal thickness (CCT), average intraocular pressure (IOP), and rates of RNFL loss during follow-up, while adjusting for potentially confounding factors.ResultsAverage baseline RNFL thickness was 76.4 ± 18.1 μm and average baseline CH was 9.2 ± 1.8 mm Hg. CH had a significant effect on rates of RNFL progression. In the univariable model, including only CH as a predictive factor along with time and their interaction, each 1 mm Hg lower CH was associated with a 0.13 μm/year faster rate of RNFL decline (P = .011). A similar relationship between low CH and faster rates of RNFL loss was found using a multivariable model accounting for age, race, average IOP, and CCT (P = .015).ConclusionsLower CH was significantly associated with faster rates of RNFL loss over time. The prospective longitudinal design of this study provides further evidence that CH is an important factor to be considered in the assessment of the risk of progression in patients with glaucoma.

PurposeTo estimate the diagnostic accuracy and lead time gained by retinal nerve fiber layer (RNFL) thickness measurements from optical coherence tomography (OCT) for detecting glaucoma before the development of visual field defects.DesignObservational cohort study.ParticipantsThe study group included 75 eyes of 75 patients suspected of having glaucoma. These eyes had normal standard automated perimetry (SAP) at baseline and demonstrated repeatable (3 consecutive) abnormal tests during a median follow-up of 6.3 years. A control group of 75 eyes of 75 healthy subjects matched by age and number of OCT tests during follow-up was included.MethodsThe RNFL thickness measurements were obtained at the time of development of the earliest SAP defect (time 0) and also at times -1, -2, -3, and so forth, corresponding to 1 year, 2 years, 3 years, and so forth, before the development of field loss. The OCT measurements at corresponding intervals were analyzed for controls. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy of OCT.Main outcome measuresAreas and sensitivities of ROC curve at fixed specificities at different times before development of field loss.ResultsAt the date of conversion to the earliest visual field defect (time 0), mean ± standard deviation average RNFL thickness was 75.0±9.8 μm in glaucomatous eyes and 90.6±8.0 μm for controls (P < 0.001). Significant differences were seen up to 8 years before development of visual field defects (86.3±8.2 μm vs. 91.4±7.6 μm, respectively; P = 0.021). The ROC curve areas decreased with increasing times before detection of field defects. At times 0, -4, and -8 years, ROC curve areas were 0.87, 0.77, and 0.65, respectively. At 95% specificity, up to 35% of eyes had abnormal average RNFL thickness 4 years before development of visual field loss and 19% of eyes had abnormal results 8 years before field loss.ConclusionsAssessment of RNFL thickness with OCT was able to detect glaucomatous damage before the appearance of visual field defects on SAP. In many subjects, significantly large lead times were seen when applying OCT as an ancillary diagnostic tool.

Purpose: To investigate the relationship between progression assessed by the visual field guided progression analysis (GPA) and rates of structural and functional change in glaucoma eyes.Methods: This was a longitudinal observational study of 135 eyes of 97 patients with glaucoma followed for an average of 3.5 ± 0.9 years. All patients had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) analysis with spectral domain optical coherence tomography (SDOCT), with an average of 6.8 ± 2.3 visits. A control group of healthy eyes followed longitudinally was used to estimate age-related change. Visual field progression was assessed using the Humphrey Field Analyzer GPA. Estimates of retinal ganglion cell counts from SAP and SDOCT were used to obtain a combined index of glaucomatous damage (RGC index) according to a previously described algorithm. Progression by SDOCT and the retinal ganglion cell (RGC) index were defined as statistically significant (P < 0.05) slopes of change that were also faster than age-related change estimated from healthy eyes.Results: From the 135 eyes, 15 (11%) progressed by GPA, 21 (16%) progressed by SDOCT, and 31 (23%) progressed by the RGC index. Twenty-one eyes showed progression by the RGC index that was missed by the GPA. These eyes had an average rate of change in estimated RGC counts of − 28,910 cells/year, ranging from two to nine times faster than expected age-related losses.Conclusion: Many glaucomatous eyes that are not found to be progressing by GPA may actually have fast rates of change as detected by a combined index of structure and function. [ABSTRACT FROM AUTHOR]