Primary Open-angle Glaucoma Eyes Research Articles

Correlation between Structural and Functional Changes in Glaucoma Patients Using Optical Coherence Tomography and Pattern Electroretinogram

AbstractBackground: To study the correlation between peripapillary retinal nerve fiber layer (RNFL) thickness measured with Optical Coherence Tomography (OCT) and pattern electroretin-ogram (pERG) parameters in primary open-angle glaucoma (POAG) patients.Aim of Study: To study the correlation between peripap-illary RNFL thickness measured with OCT and pERG param-eters in POAG patients.Patients and Methods: Fifty eyes of 50 patients diagnosed with POAG and 15 eyes of 15 normal subjects as control group, were enrolled in a prospective comparative study. The eyes in the POAG group were further subdivided into mild, moderate, and severe subgroups. All eyes had visual field testing using 24-2 Humphery standard automated perimetry, peripapillary RNFL average thickness using the 3.4mm circular scan of the Heidelberg OCT spectralis and pERG using CSO RetiMax device in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines.Results: There were significant differences in the visual field mean deviation (VF MD), peripapillary RNFL average thickness & some pERG measured parameters (N95 latency & P50-N95 latency) between normal and POAG eyes as were as among the three subgroups of POAG. Significant correlation was found between peripapillary RNFL average thickness and N95 amplitude (p<0.001), P50-N95 amplitude (p=0.002), N95 latency (p=0.034) & P50-N95 latency (p=0.045). We found significant correlation between peripapillary RNFL average thickness and N95 amplitude (p=0.001), P50-N95 amplitude (p=0.017) in POAG patients.Conclusion: Peripapillary RNFL average thickness is significantly correlated with pERG N95 amplitude & P50- N95 amplitude. In combination with OCT, pERG can be used to objectively assess functional loss in glaucoma.

The clinical features in patients with newly diagnosed pseudoexfoliative glaucoma in Serbia.

To evaluate the clinical characteristics of newly diagnosed pseudoexfoliative glaucoma and compare them with those pertaining to newly diagnosed primary open-angle glaucoma as well as pseudoexfoliation syndrome. This case-control study involved 306 participants, including patients with newly diagnosed pseudoexfoliative glaucoma, age- and sex-matched normal controls, patients with newly diagnosed primary open-angle glaucoma, and subjects with pseudoexfoliation syndrome. The study was conducted at the Glaucoma Department of Clinic for Eye Diseases, Clinical Center of Serbia, as the referral center for glaucoma in Serbia. The mean age in the pseudoexfoliative glaucoma, primary open-angle glaucoma, pseudoexfoliation syndrome, and normal control groups was 73.61 ± 8.46, 65.50 ± 8.97, 74.81 ± 6.80, and 73.58 ± 9.34 years, respectively (pseudoexfoliative glaucoma vs primary open-angle glaucoma, p < 0.001). Unilateral pseudoexfoliative glaucoma was diagnosed in 35 patients (42.2%). The intraocular pressure was higher in the eyes affected by pseudoexfoliative glaucoma (32.0 ± 9.5 mmHg) than that in the primary open-angle glaucoma eyes (28.8 ± 5.9 mmHg) (p < 0.001). In pseudoexfoliative glaucoma and primary open-angle glaucoma eyes, glaucoma severity was determined via the vertical cup-to-disk ratio (C/D) 0.65 (0.45-1.0) versus 0.60 (0.45-1.0), p = 0.048 and visual field mean deviation -5.68 (-1.58 to -30.9) versus -4.70 (-1.39 to -31.0), p = 0.045. Alzheimer's was the only systemic disease associated with pseudoexfoliative glaucoma in the study sample, with an odds ratio of 0.021 (95% confidence interval = 0.00-21.52, p = 0.022). At the time of diagnosis, pseudoexfoliative glaucoma exhibits different clinical features compared with primary open-angle glaucoma. Higher intraocular pressure, narrow or occludable angle, increased trabecular pigmentation, phacodonesis, and poorer pupillary dilatation emerged as the factors associated with pseudoexfoliative glaucoma.

Reduced Macular Vessel Density and Capillary Perfusion in Glaucoma Detected Using OCT Angiography

ABSTRACTAims: To evaluate retinal vasculature changes in primary open-angle glaucoma (POAG) and whether the functional visual loss correlates with parameters obtained using optical coherence tomography angiography (OCTA).Materials and methods: OCT and OCTA images were collected from 116 POAG eyes and 40 normal eyes in a prospective, cross-sectional observational study. Glaucomatous eyes were further divided into three groups according to a Glaucoma Staging System. Measurements of macular vessel density, ganglion cell complex (GCC), and disk retinal nerve fiber layer (RNFL) thickness were compared among groups.Results: The macular vessel density, GCC, and RNFL are significantly reduced in POAG compared to normal eyes that also corresponds to the severity of glaucoma (Kruskal–Wallis test with Dunnett’s correction; p < 0.0001). Visual field mean deviation correlates significantly with macular vessel density (p = 0.0028, r = 0.3), GCC (p < 0.0001, r = 0.6), and RNFL (p = 0.008, r = 0.36) in POAG. There are significant correlations between GCC and RNFL (p < 0.0001, r = 0.76) as well as macular vessel density (p < 0.0001, r = 0.48). Increased age also correlates with reduced macular vessel density in both normal (p = 0.0002, r = 0.49) and glaucomatous eyes (p < 0.0001, r = 0.48), but a greater proportionate reduction of vessel density is seen in glaucomatous eyes.Conclusion: Reduced macular vessel density occurs in POAG despite of age-related changes, which also correlates with reductions in RNFL and GCC measurements. OCTA can detect microstructural defects and offers potential to facilitate diagnosis of glaucoma.

Measurement of Structural Parameters of the Lamina Cribrosa in Primary Open-Angle Glaucoma and Chronic Primary Angle-Closure Glaucoma by Optical Coherence Tomography and Its Correlations with Ocular Parameters

Purpose: To measure lamina cribrosa thickness (LCT) and anterior lamina cribrosa surface depth (ALCSD) in primary open-angle glaucoma (POAG), chronic primary angle-closure glaucoma (CPACG), and control patients using spectral-domain optical coherence tomography (SD-OCT) and examine its association with relevant ocular parameters. Methods: In this cross-sectional study, 61 healthy volunteers (61 eyes), 65 POAG patients (65 eyes), and 55 CPACG patients (55 eyes) were recruited to obtain radial B-scans of the optic nerve head by way of enhanced depth imaging using Heidelberg SD-OCT. The obtained LCT and ALCSD were compared among the control, POAG, and CPACG groups. In addition, we evaluated the relationships of mean lamina cribrosa (LC) parameters with visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, intraocular pressure (IOP), and axial length. Results: The mean LCT of CPACG eyes was greater than that of POAG eyes (p = 0.003), but less than that of normal eyes (p < 0.001). The mean ALCSD of POAG and CPACG eyes was greater than that of normal control eyes (both p < 0.001). However, the mean ALCSD showed no significant difference between the POAG and CPACG groups (p = 0.073). Among all eyes, lower MD and thinner RNFL thickness were associated with a deeper and thinner LC (all p < 0.001). Conclusion: LCT is thinner in POAG compared to CPACG eyes. This is compatible with less deformation and compression of the LC in CPACG eyes, implying that the mechanisms of glaucomatous damage are different between POAG and CPACG eyes. Furthermore, VF MD and RNFL thickness were related to LCT and ALCSD in all patients.

Peripapillary Perfused Capillary Density in Exfoliation Syndrome and Exfoliation Glaucoma versus POAG and Healthy Controls: An OCTA Study.

To compare the peripapillary perfused capillary density (PCD) among eyes with exfoliation syndrome (XFS), exfoliation glaucoma (XFG), primary open-angle glaucoma (POAG), and controls. Observational, cross-sectional study. Optical coherence tomography angiography (OCTA) images (4.5×4.5 mm) of the optic nerve head were obtained using a commercial spectral domain OCTA system (AngioVue Avanti RTVue-XR, OptoVue, Fremont, CA). Two concentric circles with 1.95-mm (inner) and 3.45-mm (outer) diameters were placed manually, producing an annulus of width 0.75 mm centered at the optic disc. PCD was calculated as the ratio of pixels associated with capillaries to the pixels in the annulus after large blood vessel removal. Continuous variables were assessed by analysis of variance and Tukey honest significant difference (HSD) test. Multiple linear regression analysis was performed to adjust for confounding factors. Forty-three XFG eyes, 31 POAG eyes matched for visual field mean deviation, 33 XFS eyes, and 45 control eyes were analyzed. PCD demonstrated a progressive decrease from controls to XFS to POAG to XFG. Pairwise comparisons revealed significant differences in PCD between each pair of groups (all P<0.01) except for PCD between XFS and POAG (P = 0.08). A multivariable model adjusting for age and stage showed a more significant decrease in PCD in XFG compared with POAG (P = 0.001). PCD was more significantly decreased in XFG compared with POAG eyes and in XFS compared with control eyes. OCTA provides the first quantitative evidence of the microvascular disturbance that accompanies XFS.

Linear discriminant score for differentiating early primary open angle glaucoma from glaucoma suspects.

Purpose:To determine the diagnostic accuracy of a linear discriminant function (LDF) based on macular ganglion cell complex (GCC), optic nerve head (ONH) and retinal nerve fibre layer (RNFL) for differentiating early primary open-angle glaucoma (POAG) from glaucoma suspects.Methods:In this cross-sectional study, data from consecutive 127 glaucoma suspects and 74 early POAG eyes were analysed. Each patient underwent detailed ocular examination, standard automated perimetry, GCC and ONH and RNFL analysis. After adjusting for age, gender and signal strength using the analysis of covariance; Benjamin–Hochberg multiple testing correction was performed to detect truly significant parameters to calculate the LDF. Subsequently, diagnostic accuracy of GCC and ONH and RNFL were determined. The obtained LDF score was evaluated for diagnostic accuracy in another test set of 32 suspect and 19 glaucomatous eyes. Data were analysed with the R-3.2.1 (R Core Team 2015), analysis of variance, t-test, Chi-square test and receiver operating curve.Results:Among all GCC parameters, infero temporal had the best discriminating power and average RNFL thickness and vertical CDR among ONH and RNFL parameters. LDF scores for GCC had AUROC of 0.809 for a cut-off value 0.07, while scores for ONH and RNFL had AUROC of 0.903 for a cut-off value − 0.24. Analysis on combined parametric space resulted in avg RNFL thickness, vertical CDR, min GCC + IPL and superior GCC + IPL as key parameters. LDF scores obtained had AUROC of 0.924 for a cut-off value 0.1. The LDF was applied to a test set with an accuracy of 84.31%.Conclusion:The LDF had a better accuracy than individual GCC and ONH and RNFL parameters and can be used for diagnosis of glaucoma.

Choroidal Microvascular Dropout in Primary Angle Closure Glaucoma

To determine the prevalence and factors associated with the presence of choroidal microvascular dropout (CMvD) in primary angle-closure glaucoma (PACG) eyes compared to primary open-angle glaucoma (POAG) eyes. Cross-sectional study. Thirty-six POAG eyes (36 patients) and 28 PACG eyes (28 patients) underwent optical coherence tomography angiography (OCTA). Presence of CMvD was evaluated on choroidal OCTA slabs. Visual field (VF) defects in the glaucoma eyes were classified into initial nasal defect (IND), initial parafoveal scotoma (IPFS), and combined nasal and parafoveal defect, and the association between type of VF defect and CMvD was evaluated. CMvD was detected in 21 POAG (58.3%) and 10 PACG (35.7%) eyes (P= .07). CMvD in POAG eyes was associated with pretreatment intraocular pressure (odds ratio [OR]= 0.91/mm Hg higher intraocular pressure, P= .06), VF mean deviation (MD, OR=0.75/dB higher MD, P= .007), retinal nerve fiber layer thickness (OR= 0.92/μm increase in thickness, P= .02), and peripapillary vessel density (OR= 0.80/unit increase in density, P= .01). CMvD in PACG eyes was associated only with VF MD (OR= 0.90/dB higher MD, P= .05). When analyzed in the entire cohort of glaucoma patients (64 eyes), CMvD was significantly associated with POAG (OR > 3.5, P < .05) after accounting for glaucoma severity. CMvD was seen in 6 of 7 eyes with IPFS and 1 of 13 with IND in the POAG group (P < .05) and 1 of 2 eyes with IPFS and 0 of 10 with IND in the PACG group (P < .05). Prevalence of CMvD was significantly lower in PACG compared to POAG. As in POAG, CMvD in PACG was associated with advanced VF damage and with IPFS on VF.

Ab interno gel implant in patients with primary open angle glaucoma and pseudoexfoliation glaucoma

PurposeTo compare efficacy and safety results of an ab interno gel implant in patients with pseudoexfoliation glaucoma (PXG) and primary open angle glaucoma (POAG).MethodsRetrospective analysis of the medical records of 110 consecutive eyes with open angle glaucoma who had received a XEN45 gel implant between March 2014 and June 2015. Intraocular pressure course, number of glaucoma medications, the need for additional intervention (including needling) and complications were evaluated until 12 months postoperatively.ResultsData of 67 eyes with POAG and 43 eyes with PXG were analyzed. At 12 months postoperatively, the mean IOP had significantly decreased by 54.0% from preoperatively 31.85 ± 8.5 mmHg to 13.99 ± 2.6 mmHg in the POAG group, (p = 0.000; Wilcoxon test), and by 55.2% from 31.63 ± 9.0 mmHg to 13.28 ± 3.1 mmHg in the PXG group (p = 0.000; Wilcoxon test). The mean number of anti-glaucoma medications had significantly decreased from 3.25 ± 0.8 at baseline to 0.3 ± 0.7 medications at 12 months postoperatively in POAG eyes (p = 0.000; Wilcoxon test), and from 3.05 ± 1.0 to 0.3 ± 0.6 medications in PXG eyes (p = 0.000; Wilcoxon test). Hypotony (IOP ≤ 6 mmHg) was observed in 2 POAG eyes (3.0%) and in 5 PXG eyes (11.7%) at 1 month but normalized in all eyes at 12 months postoperatively. Severe complications were not observed. No statistically significant differences were found between PXG eyes and POAG eyes.ConclusionOur data indicate that the XEN45 gel implant provides significant and comparable reduction in IOP and anti-glaucoma medication during the one-year follow-up period in POAG as well as PXG eyes. This suggests that it may be a noteworthy alternative to traditional filtering procedures in patients with POAG and PXG respectively.

Circumpapillary structure-function relationships with microperimetry and spectral domain optical coherence tomography in glaucoma: a pilot study.

PurposeTo compare the relationships between circumpapillary microperimetry (MP)-sensitivity measurements and various circumpapillary retinal thickness parameters in healthy and primary open-angle glaucoma (POAG) eyes.MethodsIn 14 eyes of 14 healthy subjects and 22 early–moderate POAG eyes of 22 patients, circumpapillary optical coherence tomography thickness measurements (RS-3000 Advance OCT, NIDEK) of the retinal nerve fiber layer (cpRNFL), total retina (cpTR), and ganglion cell complex (cpGCC) and outer retina (cpOR) and circumpapillary MP-sensitivity measurements (MP-3 microperimeter, NIDEK) were made in 12 sectors of identical circumpapillary circles. The structure-function relationship was investigated in each sector.ResultsStatistically significant correlations with circumpapillary MP-sensitivity values were found for cpRNFL in five sectors, cpTR in nine sectors, cpGCC in nine sectors, and cpOR in three sectors. The structure-function relationship was strong (r=0.4–0.69) in three sectors for cpRNFL, in six for cpTR, in four for cpGCC, and in one for cpOR. The relationship was very strong (r>0.7) in one sector for cpRNFL, cpTR, and cpGCC, and in no sectors for cpOR. The very strong relationships all occurred in sector 5 (inferotemporal sector).ConclusionIn our pilot study, the circumpapillary structure-function relationship was more extensive for cpTR thickness and cpGCC thickness than for cpRNFL thickness, which suggests that the former parameters may require greater attention in structure-function research into glaucoma.

Macula Vessel Density and Thickness in Early Primary Open-Angle Glaucoma

To characterize and compare the ganglion cell complex (GCC) thickness and macula vessel density in preperimetric and early primary open-angle glaucoma (POAG) eyes. Cross-sectional study. Fifty-seven healthy, 68 preperimetric, and 162 early POAG eyes enrolled in the Diagnostic Innovations in Glaucoma Study. Optical coherence tomography angiography (OCT-A)-based superficial macula vessel density and OCT-based GCC thickness were evaluated simultaneously. Percent loss from normal of GCC thickness and macula vessel density was compared. Area under the receiver operating characteristic curve was used to describe the diagnostic utility. Both GCC thickness and vessel density were significantly lower in preperimetric and early POAG eyes compared to healthy eyes. Compared to the preperimetric POAG group, the early POAG group showed larger GCC thickness percent loss (whole image 4.72% vs 9.86%; all P < .01) but similar vessel density percent loss (whole image 4.97% vs 6.93%; all P > .05). In preperimetric POAG, GCC thickness and vessel density percent losses were similar (all P > .1). In contrast, in early POAG, GCC thickness percent loss was larger than that of vessel density (all P ≤ .001). To discriminate preperimetric or early glaucoma eyes from healthy eyes, GCC thickness and macula vessel density showed similar diagnostic accuracy (all P > .05). Both GCC thinning and macula vessel density dropout were detectable in preperimetric and early POAG eyes. GCC loss was greater than maculavessel density loss in early perimetric POAG. However, OCT-A and OCT measurements showed similar efficiency to detect early glaucoma.

Peripapillary microvasculature in the retinal nerve fiber layer in glaucoma by optical coherence tomography angiography: focal structural and functional correlations and diagnostic performance.

PurposeTo quantify peripapillary microvasculature within the retinal nerve fiber layer (RNFL) in primary open-angle glaucoma (POAG) and normal eyes, determine association of perfusion parameters with structural and functional measures, and report diagnostic accuracy of perfusion parameters.Patients and methodsPOAG and normal patients underwent 6×6 mm2 optic nerve head scans (Angioplex optical coherence tomography angiography [OCTA]; Cirrus HD-OCT 5000) and Humphrey Field Analyzer II-i 24-2 visual field (VF) testing. Prototype software performed semiautomatic segmentation to create RNFL en face images and quantified vessel area density (VAD), vessel skeleton density (VSD), and vessel complexity index (VCI) in the optic nerve head globally and focally. Generalized estimating equations models assessed association of OCTA parameters with VF mean deviation (MD) and RNFL thickness.ResultsThirty-eight POAG and 17 normal eyes were studied. Global VAD, VSD, and VCI were reduced in mild POAG vs normal (P<0.02) and moderate-severe vs mild POAG (P<0.04). Stepwise focal reductions across disease stage were demonstrated for OCTA parameters in the inferior hemisphere (P<0.05); reduction in OCTA parameters in mild POAG vs normal was demonstrated in inferior and superior quadrants (P<0.05). Reduced global VF MD was associated with reduced VAD, VSD, and VCI (P=0.0007, 0.0013, <0.0001; R2=0.449, 0.312, 0.399, respectively), and global RNFL thickness was associated with VAD, VSD, and VCI (P<0.0001; R2=0.499, 0.524, 0.542), superior and inferior hemifield MD were associated with corresponding VAD, VSD, and VCI (P≤0.001; R2 from 0.208 to 0.513). RNFL thickness in all quadrants was associated with corresponding OCTA parameters (P<0.05; R2 from 0.213 to 0.394), except temporal VAD and VCI. Area under curves for VAD, VSD, and VCI demonstrated good diagnostic ability (0.868, 0.855, 0.868; P<0.0001).ConclusionGlaucomatous eyes showed stepwise reductions in RNFL microcirculation across severity; focal reductions in the inferior hemisphere and inferior and superior quadrants were most significant. OCTA parameters had stronger associations with structural rather than functional measures of glaucoma.

Optical coherence tomography angiography measured capillary density in the normal and glaucoma eyes

PurposeTo compare the diagnostic ability of optical coherence tomography angiography (OCT-A) derived radial peripapillary capillary (RPC) measured capillary density (CD) and inside the optic nerve head (ONH) CD measurements to differentiate between the normal and primary open angle glaucoma (POAG) eyes. MethodsAngioVue disc OCT-A images were obtained and assessed in 83 eyes of POAG patients and 74 age matched healthy eyes. RPC CD was quantitatively measured in the peripapillary area within 3.45 mm circle diameter around the ONH and inside the ONH in 8 equally divided sectors, using Bar – Selective Combination of Shifted Filter Responses method after the suppressing large vessels. Area under receiver operating characteristic (AUROC) curve was used to assess the diagnostic accuracy of the two scanning regions of CD to differentiate between the normal and POAG eyes. ResultsThe mean peripapillary RPC density (0.12 ± 0.03) and mean ONH CD (0.09 ± 0.03) were significantly lower in POAG eyes when compared to the normal eyes (RPC CD: 0.17 ± 0.05, p < 0.0001 and ONH CD 0.11 ± 0.02, p = 0.01 respectively). The POAG patients showed 29% reduction in the RPC CD and 19% reduction in the ONH CD when compared to the normal eyes. The AUROC for discriminating between healthy and glaucomatous eyes was 0.784 for mean RPC CD and 0.743 for the mean ONH CD. ConclusionsDiagnostic ability of OCT-A derived peripapillary CD and ONH CD was moderate for differentiating between the normal and glaucomatous eyes. Diagnostic ability of even the best peripapillary average and inferotemporal sector for RPC CD and average and superonasal sector for the ONH CD was moderate.

Prospective Evaluation of XEN Gel Implant in Eyes With Pseudoexfoliative Glaucoma

The main purpose of this study was to compare the safety and efficacy of XEN gel implant surgery in patients with pseudoexfoliative glaucoma (PEXG) and primary open-angle glaucoma (POAG). This was a prospective, interventional study in a tertiary glaucoma center. Fifty-seven eyes (43 patients) with POAG and 53 eyes (42 patients) with PEXG with uncontrolled intraocular pressure (IOP) despite medical treatment underwent combined XEN+cataract surgery or standalone XEN surgery. Mean IOP, mean number of medications at 1-year follow-up, needling rates, and incidence of adverse effects (AEs) were analyzed. Complete success, defined as an IOP <16 mm Hg without medications at 1 year, was also analyzed. Combined XEN+cataract surgery was performed in 72% of POAG and 75% of PEXG eyes (P=0.674), the remainder underwent standalone XEN surgery. Patient characteristics were similar between the 2 groups except for higher age for the PEXG patients (78.5±8.5 vs. 71.3± 8.7 y; P<0.001). Mean medicated IOP was 19.8±5.8 (POAG) and 19.7±8.2 (PEXG) at baseline (P=0.98) and 13.9±4.6 (-29.8%) and 13.6±4.3 mm Hg (-31%) at 1 year (P=0.87), respectively (P<0.01). Mean medications dropped from 1.9±1.6 (POAG) and 2.0±1.3 (PEXG) preoperatively to 0.4±0.8 and 0.5±0.8, respectively at 1 year (P<0.001). A total of 42% (POAG) and 63% (PEXG) eyes achieved complete success (P=0.06) at 1 year. Needling was performed in 36.8% (POAG) versus 37.7% (PEXG) (P=0.923). The XEN gel implant as a standalone or combined procedure demonstrated similar efficacy and safety results in PEXG and POAG eyes.

Glaucoma severity and intraocular pressure reduction after cataract surgery in eyes with medically controlled glaucoma.

To investigate the relationship between glaucoma severity and intraocular pressure (IOP) reduction after cataract surgery in patients with medically controlled primary open-angle glaucoma (POAG).Retrospective case series.This study included glaucoma suspects (GS) and POAG patients who underwent cataract surgery and continued to use the same glaucoma medications during the postoperative period of 4 months. The main outcomes were percent and absolute IOP changes calculated using the preoperative IOP and the postoperative IOP at 3 months. Preoperative glaucoma medications, preoperative IOP, demographic information, biometric parameters and variables for glaucoma severity were evaluated as potential predictors of IOP change.The average IOP reduction was 3.3 ± 2.4 mmHg (20.0%) and 2.2 ± 2.5 mmHg (13.1%) from the preoperative mean of 16.0 ± 2.9 mmHg and 15.2 ± 3.3 mmHg in the GS and POAG groups, respectively. Preoperative IOP, preoperative IOP/anterior chamber depth (preoperative IOP/ACD [PD ratio]) and preoperative IOP/retinal nerve fiber layer (RNFL) thickness (preoperative IOP/RNFL [PNFL ratio]) and preoperative IOP score x MD score x number of glaucoma medications (glaucoma index) predicted absolute IOP change in the POAG group, whereas preoperative IOP, PD ratio, PNFL ratio, and axial length (AL) did in the GS group. Preoperative IOP, PD ratio, and PNFL ratio predicted %IOP change in the POAG group, whereas only AL did in the GS group.In medically controlled POAG eyes, structural or functional parameters for glaucoma severity did not independently predict IOP change following phacoemulsification. However, novel severity indices obtained by addition of preoperative IOP and/or glaucoma medications to the structural or functional parameter predicted IOP changes.

Accuracy of peripapillary versus macular vessel density in diagnosis of early to advanced primary open angle glaucoma

To evaluate macular and peripapillary vessel density (mVD, pVD) using optical coherence tomography angiography (OCT-A) in healthy subjects, patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG) patients. In this prospective observational study, OCT-A images were obtained from 60 eyes of 36 healthy, ocular hypertension (OHT), preperimetric glaucoma (PPG), early glaucoma (EG) and moderate and advanced POAG subjects. Superficial mVD was acquired over a 6×6-mm cube centered on the foveal avascular zone and pVD over a 4.5×4.5-mm cube centered on the optic disc. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell complex (GCC) thickness was calculated using spectral-domain OCT. Correlations between vascular, structural and Humphrey VF indices were evaluated (Spearman's rank correlation coefficient). Median pVD and mVD in the PPG eyes were lower than in healthy eyes (51.87% and 47.23% versus 55.70% and 53.61%, respectively; P<0.001 and P=0.003), but higher than in mild glaucoma eyes (46.21% and 41.98%, P<0.001 compared to normal eyes) and moderate to advanced glaucoma eyes (37.45% and 39.89%, P<0.0001 compared to normal eyes). The highest correlations were found between structural parameters and pVD (r=0.87 and 0.86 for pRNFL and GCC, P<0.0001), followed by mVD (r=0.69 for both pRNFL and GCC, P<0.0001). Correlations with mean VF sensitivity were similar for pVD and mVD (r=0.61 and 0.56) and for GCC and pRNFL (r=0.60 and 0.52, P<0.0001 for all). VD measured with OCT-A shows reduction in POAG. Detection of this damage differentiates PPG from normal and perimetric POAG eyes with a high correlation with structural parameters. Peripapillary VD accuracy is higher than mVD in detecting the disease. These results suggest that OCT-A could improve POAG diagnosis and understanding of the pathophysiologic mechanisms behind glaucoma.

Intraocular retinal thickness asymmetry in early stage of primary open angle glaucoma and normal tension glaucoma.

To investigate the intraocular retinal thickness asymmetry of peripapillary retinal nerve fiber layer (pRNFL) and macular layers measured by spectral-domain optical coherence tomography (SD-OCT) in patients with early stage of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG). A total of 117 patients with early stage of glaucoma (54 patients with POAG and 63 patients with NTG) and 32 normal subjects were recruited for the study. The pRNFL thickness, total macular layer (TML) thickness, and isolated inner macular layer (IML) thickness were measured by SD-OCT. Hemisphere TML thickness asymmetry measured by the posterior pole asymmetry scan was evaluated. Thickness differences of pRNFL and IML between superior and inferior quadrants were calculated. Asymmetry indices (AIs) of the pRNFL, TML and isolated IML were also computed. Areas under the receiver-operating characteristic curves (AROCs) were generated to determine the diagnostic capabilities of different parameters. Intraocular pRNFL thickness differences and AIs between the superior and inferior quadrants were significantly different between normal and NTG groups (P=0.009 and P<0.001, respectively). Intraocular pRNFL thickness differences and AIs between the temporal-superior and temporal-inferior sectors were also significantly different between normal and NTG groups (P=0.035 and P<0.001, respectively). The thickness differences and AIs of TML between superior and inferior hemispheres were significantly different between normal and NTG groups (P=0.001 and P=0.001, respectively) and between normal and POAG groups (P=0.032 and P=0.020, respectively). The thickness differences and AIs of macular ganglion cell layer (mGCL) between superior and inferior quadrants were significantly different between normal and NTG groups (P=0.013 and P=0.004, respectively), and between NTG and POAG groups (P=0.015 and P=0.012, respectively). The thickness difference of TML between superior and inferior hemispheres showed the highest diagnostic capability for early NTG eyes (AROC=0.832). Intraocular retinal thickness asymmetry in pRNFL, TML and mGCL are found in early stage of NTG. Hemisphere TML thickness asymmetry is also found in POAG eyes. Asymmetry analysis of retinal thickness can be an adjunctive modality for early detection of glaucoma.

Use of Machine Learning on Contact Lens Sensor–Derived Parameters for the Diagnosis of Primary Open-angle Glaucoma

To test the hypothesis that contact lens sensor (CLS)-based 24-hour profiles of ocular volume changes contain information complementary to intraocular pressure (IOP) to discriminate between primary open-angle glaucoma (POAG) and healthy (H) eyes. Development and evaluation of a diagnostic test with machine learning. Subjects: From 435 subjects (193 healthy and 242 POAG), 136 POAG and 136 age-matched healthy subjects were selected. Subjects with contraindications for CLS wear were excluded. This is a pooled analysis of data from 24 prospective clinical studies and a registry. All subjects underwent 24-hour CLS recording on 1 eye. Statistical and physiological CLS parameters were derived from the signal recorded. CLS parameters frequently associated with the presence of POAG were identified using a random forest modeling approach. Area under the receiver operating characteristic curve (ROC AUC) for feature sets including CLS parameters and Start IOP, as well as a feature set with CLS parameters and Start IOP combined. The CLS parameters feature set discriminated POAG from H eyes with mean ROC AUCs of 0.611, confidence interval (CI) 0.493-0.722. Larger values of a given CLS parameter were in general associated with a diagnosis of POAG. The Start IOP feature set discriminated between POAG and H eyes with a mean ROC AUC of 0.681, CI 0.603-0.765. The combined feature set was the best indicator of POAG with an ROC AUC of 0.759, CI 0.654-0.855. This ROC AUC was statistically higher than for CLS parameters or Start IOP feature sets alone (both P < .0001). CLS recordings contain information complementary to IOP that enable discrimination between H and POAG. The feature set combining CLS parameters and Start IOP provide a better indication of the presence of POAG than each of the feature sets separately. As such, the CLS may be a new biomarker for POAG.

Noninvasive Detection of Mitochondrial Dysfunction in Ocular Hypertension and Primary Open-angle Glaucoma.

To assess mitochondrial dysfunction in vivo in ocular hypertension (OHT) and primary open-angle glaucoma (POAG) using retinal metabolic analysis. This was an observational, cross-sectional study performed from November 2015 to October 2016 at the New York Eye and Ear Infirmary of Mount Sinai. Thirty-eight eyes with varying stages of POAG, 16 eyes with OHT, and 32 control eyes were imaged on a custom fundus camera modified to measure full retinal thickness fluorescence at a wavelength optimized to detect flavoprotein fluorescence (FPF). Optical coherence tomography was used to measure the retinal ganglion cell-plus layer (RGC+) thickness. Macular FPF and the ratio of macular FPF to RGC+ thickness were the primary outcome variables and were compared among the three groups using an age-adjusted linear regression model. A mixed-effects model was used to assess correlations between FPF variables and clinical characteristics. Both macular FPF and the macular FPF/RGC+ thickness ratio were significantly increased in OHT compared with control eyes (P<0.05 and <0.01, respectively). In POAG eyes, macular FPF was not significantly increased compared with controls (P=0.24). However, the macular FPF/RGC+ thickness ratio in POAG eyes was significantly increased compared with controls (P<0.001). FPF was significantly correlated to age in POAG eyes. Despite lacking clinical evidence of glaucomatous deterioration, OHT eyes displayed significantly elevated macular FPF, suggesting that mitochondrial dysfunction may be detected before structural changes visible on current clinical imaging. Our preliminary results suggest that macular FPF analysis may prove to be a useful tool in assessing and evaluating OHT and POAG eyes.

Diagnostic Ability and Discriminant Values of OCT-Angiography Parameters in Early Glaucoma Diagnosis

Purpose: To evaluate papillary, peripapillary, and macular vasculature with optical coherence tomography angiography in preperimetric (PPG), primary open-angle glaucoma (POAG), and normal eyes, and to assess diagnostic ability and associations among the vasculature and structural damage. Methods: This was an observational, cross-sectional study. Retinal nerve fiber layer (RNFL), ganglion cell complex thickness, whole-image (wiVD), inside disc (idVD), peripapillary (ppVD), and macular vessel densities were obtained. Analysis of variance, post hoc test, and Pearson coefficient were used. The areas under the receiver operating characteristic curve (AUC) and cut-offs were calculated. Results: Thirteen healthy, 39 PPG, and 19 POAG eyes were included. Papillary and peripapillary VD were lower in POAG eyes in all parameters analyzed. wiVD in PPG eyes (52.37 ± 5.04%) was significantly decreased compared to healthy eyes (58.02 ± 2.02%, p < 0.05). AUC ranged from 0.62 to 0.90; the established cut-off values were 56% for wiVD, 55% for idVD, and 62% for ppVD. Pearson’s correlation coefficient showed a direct correlation between the papillary or peripapillary VD and RNFL thickness. Conclusions: Vessel densities in POAG eyes are significantly lower than in healthy eyes, and they show good discriminatory abilities. A diminished microvascular network is associated with RNFL thinning more strongly in POAG than in PPG eyes.

Baseline Lamina Cribrosa Curvature and Subsequent Visual Field Progression Rate in Primary Open-Angle Glaucoma

To investigate the relationship between the degree of posterior bowing of the lamina cribrosa (LC) at baseline and the rate of subsequent visual field (VF) progression in eyes with primary open-angle glaucoma (POAG). Prospective, observational study. One hundred one early-stage (VF mean deviation [MD], -5.0 to -0.01 dB) POAG eyes that met the following conditions: (1) follow-up longer than 3.5 years, (2) more than 5 reliable standard automated perimetry tests, and (3) medically well-controlled intraocular pressure during follow-up. All participants underwent swept-source OCT scanning of the LC at baseline. The area enclosed by a vertical line at the anterior laminar insertion, anterior LC plane, and reference plane of Bruch's membrane opening (BMO) was divided by D (distance between the 2 cross-points made by vertical lines drawn from the anterior laminar insertion to the reference plane of BMO) to approximate the LC depth (LCD). The difference between the LCD and mean anterior laminar insertion depth was defined as the LC curvature index (LCCI). To consider the steepness of the LC curve, the adjusted LCCI (aLCCI) was calculated as LCCI divided by D and multiplied by 100. The mean LCD (mLCD), mean LCCI (mLCCI), and mean aLCCI (maLCCI) were computed by averaging the measurements on 12 radial scans. The subsequent MD slope and associated factors were analyzed. Lamina cribrosa parameters and subsequent MD slope. The participants' mean baseline MD was -3.8 ± 3.4 dB. The mean baseline mLCD, mLCCI, and maLCCI were 419.0 ± 111.2 μm, 76.4 ± 29.0 μm, and 4.8 ± 1.9, respectively. A greater MD slope was associated with a greater baseline maLCCI (P < 0.001). We found a statistically significant breakpoint for the maLCCI (4.12) above which a larger maLCCI showed a steeper MD slope (P < 0.001). Analysis by age revealed that significantly more VF progression with maLCCI changes occurred in the relatively younger group (≤69 years; P= 0.043). The baseline maLCCI showed a significant correlation with the rate of subsequent VF deterioration. This suggests that, in POAG eyes with greater posterior bowing of the LC, the axons of retinal ganglion cells may be more vulnerable to further glaucomatous injury.