The Association Between Regional Macula Vessel Density and Central Visual Field Damage in Advanced Glaucoma Eyes.

PRCIS: Both macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma. PURPOSE: The purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes. METHODS: Macular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD) <-10 dB] were evaluated. Regional and global VF mean sensitivity (MS) was calculated from total deviation plots. Superficial and deep MVD were obtained from 3 × 3 and 6×6 mm 2 OCTA scans using 2 sectoral definitions. Spectral-domain optical coherence tomography macular GCC thickness was obtained simultaneously from the same scan as the MVD measurements. Linear regression models were used to assess the associations ( R2 ). RESULTS: Lower MS was significantly associated with a reduction in superficial MVD and GCC in each region of both scan sizes for both maps. Associations were weaker in the individual sectors of the whole image grid than the Early Treatment Diabetic Retinopathy Study map. Deep-layer MVD was not associated with central MS. Although 6×6 mm 2 and perifoveal vessel density had better associations with central 10-degree MS compared with GCC thickness (eg, R2 from 25.7 to 48.1 µm and 7.8% to 32.5%, respectively), GCC associations were stronger than MVD associations in the central 5-degree MS. CONCLUSIONS: Given a stronger MVD-central 10-degree VF association compared with GCC, as well as stronger GCC-central 5-degree VF association compared with MVD, MVD and GCC are complementary measurements in eyes with advanced glaucoma. A longitudinal analysis is needed to determine the relative utility of the GCC and MVD measurements.

Comparison of the Effects of Latanoprostene Bunod and Timolol on Retinal Blood Vessel Density: A Randomized Clinical Trial.

PURPOSE: To compare the differences in retinal vessel density (VD) between topical administration of latanoprostene bunod (LBN) ophthalmic solution 0.024% and timolol maleate 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and normal subjects. DESIGN: Randomized, single center, crossover clinical trial. METHODS: Eligible subjects were examined during 6 study visits over 12 weeks. All subjects were randomized in a 1:1 ratio to LBN dosed once daily or timolol dosed twice daily in both eyes (OU) for a duration of 4 weeks each, separated by a 2-week washout period. A comprehensive eye examination OU was performed at each visit. Testing was performed with optical coherence tomography and optical coherence tomography angiography (optic nerve and macula), as well as visual field examination, on the study eye at baseline and before and after each treatment. RESULTS: One eye from each of 50 patients was enrolled (10 healthy patients, 26 patients with OHT, and 14 patients with OAG). After administration of LBN there was significantly increased macular VD (0.76% [0.20%-1.33%], P = 0.009) and a trend in increasing peripapillary VD in patients with OAG and patients with OHT. In contrast, after administration of timolol, there were no differences in macular VD, and a decrease in peripapillary VD only was observed in the nasal inferior sector (-0.56% [-1.08% to -0.03%], P = .04) in patients with OAG and patients with OHT. No change in peripapillary or macular VD was observed in the normal subjects (P > .05 for all). CONCLUSIONS: Topical administration of LBN enhanced macular VD in patients with OAG or patients with OHT. In contrast, timolol administration did not have any effect on VD.

Agreement between Compass Fundus Perimeter New Grid and 10-2 Testing Protocols for Detecting Central Visual Field Defects.

PURPOSE: To evaluate the agreement between Compass New Grid (NG) and 10-2 test protocols for detecting early glaucomatous defects in the central 10 degrees of the visual field (CVFD). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 123 eyes of 14 healthy individuals, 17 glaucoma suspects, and 32 glaucoma patients were enrolled. METHODS: Subjects performed NG and 10-2 Compass automated perimetry testing within 1 week. For both test protocols, total deviation (TD) and pattern deviation (PD) plot CVFDs were defined by 3 contiguous points with probabilities of <5%, <2%, <2% or <5%, <1%, <1%. Cohen's Kappa statistic was used to assess agreement between NG and 10-2 for identifying CVFDs. The Spectralis GMPE Hood Glaucoma Report (investigational software version) macula deviation analysis obtained within 1 year was used for calculating sensitivities and specificities of test protocols. MAIN OUTCOME MEASURES: Protocols' agreement, sensitivity, and specificity. RESULTS: Fair to moderate agreement was observed between NG and 10-2 protocols for detecting presence of superior CVFDs on TD (k = 0.57) and PD (k = 0.26) plots and for detecting inferior CVFDs on TD (0.49) and PD (0.27) plots. With the use of OCT macula deviation maps, specificity for detecting CVFD was consistently higher with NG than 10-2 tests for TD plots of the superior hemifield (0.82 and 0.65), inferior hemifield (0.92 and 0.84), and PD plots of the superior hemifield (0.81 and 0.36) and inferior hemifield (0.86 and 0.52). Sensitivity of NG was consistently lower than TD plots of the superior hemifield (0.48 and 0.72), inferior hemifield (0.28 and 0.46), and PD plots of the superior hemifield (0.48 and 0.78) and inferior hemifield (0.20 and 0.52). By using pattern standard deviation (PSD) criterion, the mean PSD values for 10-2 and NG VF tests were 1.61 (95% confidence interval [CI], 1.26-1.96) and 1.81 (95% CI, 1.45-2.17) (P < 0.001), respectively. CONCLUSIONS: Although the Compass NG detected fewer CVFDs than the 10-2 test protocol, it did detect CVFDs that were not observed in the Compass 24-2 test in patients with early glaucoma. Therefore, NG may be particularly useful in clinical situations when higher specificity is desired or PSD criterion is used.

Superficial and Deep Macula Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PRECIS: Macular superficial capillary plexus (SCP) vessel density is more informative than deep capillary plexus (DCP) vessel density for the detection of glaucoma. PURPOSE: The purpose of this study was to characterize optical coherence tomography angiography macular SCP and projection-resolved DCP vessel densities and compare their diagnostic accuracies with ganglion cell complex (GCC) thickness in healthy, glaucoma suspect, and glaucoma eyes. MATERIALS AND METHODS: Sixty-eight eyes of 44 healthy subjects, 26 eyes of 16 preperimetric glaucoma suspects, and 161 eyes of 124 glaucoma patients from the Diagnostics Innovations in Glaucoma Study with good quality high-density 6×6 mm2 macula optical coherence tomography angiography images were included. The diagnostic accuracy of SCP vessel density, projection-resolved DCP vessel density and GCC thickness were compared among groups. RESULTS: Mean whole image vessel density (wiVD; % of area occupied by vessels containing flowing blood) in the SCP layer was highest in healthy eyes (49.7%), followed by glaucoma suspect eyes (46.0%), and glaucoma eyes (40.9%) (P<0.001). Mean wiVD in the DCP layer was similar in healthy (50.6%), glaucoma suspect (47.3%), and glaucoma eyes (45.7%) (P=0.925). Diagnostic accuracy of both GCC thickness and SCP wiVD was significantly higher than DCP wiVD for classifying healthy and glaucoma eyes [adjusted area under the receiver operating characteristic curve (95% confidence interval): GCC=0.86 (0.72, 0.94), SCP=0.80 (0.66, 0.91) and DCP=0.44 (0.30, 0.57)] (P<0.001). CONCLUSIONS: SCP vessel densities have better diagnostic accuracy for detecting glaucoma than DCP vessel densities. Although the diagnostic accuracy of the macula SCP is relatively modest, it is more informative than the DCP.

Impact of Pupil Dilation on Optical Coherence Tomography Angiography Retinal Microvasculature in Healthy Eyes.

PRéCIS:: Small but significant decreases in optical coherence tomography angiography (OCTA)-measured circumpapillary capillary density (cpCD) were observed in healthy eyes dilated with 2.5% phenylephrine/0.5% tropicamide. Although likely clinically insignificant, ophthalmologists should consider these changes when interpreting OCTA results from dilated eyes. PURPOSE: The purpose of this study was to investigate the effect of pupil dilation using 2.5% phenylephrine and 0.5% tropicamide on quantitative assessment of retinal microvasculature using OCTA. METHODS: OptoVue AngioVue high density (HD) and non-HD OCTA macula and optic nerve head (ONH) images were obtained at 15-minute intervals predilation and postdilation in 26 healthy participants (mean age: 40.0; 95% confidence interval=33.9, 46.1 y). Superficial macular vessel density (VD) was measured in the whole image VD and the parafoveal region VD. ONH capillary density was measured in the whole image capillary density and the cpCD region. Differences between predilation and postdilation densities were assessed using linear mixed effects models to account for within-patient correlation. RESULTS: Instillation of dilating drops resulted in a small but statistically significant reduction in non-HD ONH whole image capillary density of 0.6%, from a mean of 45.2% (95% confidence interval=41.9%, 48.4%) to 44.6% (41.4%, 47.8%) (P=0.046). A similar reduction in non-HD ONH cpCD of 0.8% also was observed, from a mean of 49.3% (45.3%, 53.3%) to 48.5% (44.5%, 52.4%) (P=0.025). No postdilation decreases in macular VD or HD ONH capillary density were observed. CONCLUSIONS: Pupil dilation using topical 2.5% phenylephrine and 0.5% tropicamide results in a small but statistically significant reduction in non-HD ONH whole image and cpCD in healthy eyes. The observed reduction likely is not clinically significant because the observed reduction was within the previously reported range of measurement variability. Further studies should consider investigating these effects in nonhealthy eyes with glaucoma and media opacities, as well as older individuals.

Ganglion Cell Complex Thickness and Macular Vessel Density Loss in Primary Open-Angle Glaucoma.

PURPOSE: To characterize the change rate of ganglion cell complex (GCC) thickness and macular vessel density in healthy, preperimetric glaucoma and primary open-angle glaucoma (POAG) eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: One hundred thirty-nine eyes (23 healthy eyes, 36 preperimetric glaucoma eyes, and 80 POAG eyes) of 94 patients who had at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was 2.0 years for healthy eyes, 2.6 years for preperimetric glaucoma eyes, and 2.6 years for POAG eyes. METHODS: OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the same 3×3-mm2 GCC scan slab were evaluated. The dynamic range-based normalized rates of vessel density and thickness change were calculated and compared within each diagnostic group. The association between the rates of thickness and vessel density change and potential factors were evaluated. MAIN OUTCOME MEASURES: The rates of GCC thinning and macular vessel density loss. RESULTS: Significant rates of GCC thinning and macular vessel density decrease were detectable in all diagnostic groups (all P < 0.05). In healthy eyes and preperimetric glaucoma eyes, the normalized rates of GCC thinning and macular vessel density decrease were comparable (all P > 0.1). In contrast, the normalized rate (mean, 95% confidence interval) of macular vessel density decrease in the POAG eyes (-7.12 [-8.36, -5.88]%/year) was significantly faster than GCC thinning (-2.13 [-3.35, -0.90]%/year; P < 0.001). In the POAG group, more than two thirds of the eyes showed faster macular vessel density decrease than GCC thinning; faster macular vessel density decrease rate was associated significantly with worse glaucoma severity (P = 0.037). The association between GCC thinning rate and glaucoma severity was not significant (P = 0.586). Intraocular pressure during follow-up significantly affected the rate of GCC thinning in all groups (all P < 0.05) but showed no association with the rate of macular vessel density decrease. CONCLUSIONS: Both GCC thinning and macular vessel density decrease were detectable over time in all diagnostic groups. In POAG eyes, macular vessel density decrease was faster than GCC thinning and was associated with severity of disease. Macular vessel density is useful for evaluating glaucoma progression, particularly in more advanced disease.

Diagnostic Ability of Optical Coherence Tomography Angiography Macula Vessel Density for the Diagnosis of Glaucoma Using Difference Scan Sizes.

PRéCIS:: There is diagnostic information in the outer region of optical coherence tomography angiography (OCT-A) macula scans not available in the inner region, and this information is especially useful in the early stages of glaucoma. PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of 3×3 and 6×6 mm macula OCT-A scans for classifying healthy, mild glaucoma, and moderate to severe glaucoma eyes. METHODS: Participants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with good quality 3×3 and 6×6 mm OCT-A images of the macula acquired on the same day were included in this cross-sectional study. The area under the receiver operating characteristic (AUC) curves were calculated to assess the diagnostic accuracy of vessel density (VD) of both scan sizes for differentiating between 3 diagnostic groups. RESULTS: Two hundred seventy-nine eyes (89 healthy, 127 with mild glaucoma, and 63 with moderate to severe glaucoma) from 190 subjects were included in this study. The VD of the outer area of the 6×6 mm scan size had higher diagnostic accuracy compared with the VD of the inner area of the 3×3 mm scan when differentiating between healthy and mild glaucoma (3×3 mm AUC=0.71 and 6×6 mm AUC=0.79, P=0.032). The VD of the outer area of the 6×6 mm scans had only similar diagnostic accuracy compared with the inner area of the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes (AUC=0.90 for 3×3 mm and 0.92 for 6×6 mm, P=0.279). The VD of the inner area of the 6×6 mm scan size had similar diagnostic accuracy to the corresponding area of the 3×3 mm scan in both diagnostic categories. CONCLUSION: The diagnostic accuracy of VD using the 6×6 mm macula OCT-A scan was better than the 3×3 mm scan when differentiating between healthy and mild glaucoma eyes, and similar to the 3×3 mm scan when differentiating between healthy and moderate to severe glaucoma eyes.

Association of Macular and Circumpapillary Microvasculature with Visual Field Sensitivity in Advanced Glaucoma.

PURPOSE: To evaluate the association between optical coherence tomography angiography (OCTA) macular and circumpapillary vessel density and visual field mean deviation (MD) in advanced primary open angle glaucoma. DESIGN: Cross-sectional study. METHODS: Macula (superficial layer) and optic nerve head (ONH) with capillary density (CD) and without vessel density (VD) automated removal of large vessels OCTA of 34 eyes (34 patients, MD < -10 dB) were investigated as macula whole image VD (wiVD), parafoveal VD (pfVD), ONH wiVD, wiCD, circumpapillary VD, and cpCD. Spectral domain OCT circumpapillary retinal nerve fiber layer, macular ganglion cell complex, and ganglion cell inner plexiform layer were also analyzed. RESULTS: Macular and ONH VD decreased significantly with worsening MD. Each 1-dB decrease in MD was associated with a reduction of 0.43% and 0.46% for macular wiVD and pfVD with R2 of 0.28 and 0.27, respectively (all P < .01). The association between MD and VD was strongest for measures of ONH with large vessels removed, wiCD, and cpCD, followed by wiVD and circumpapillary VD with R2 of 0.26, 0.22, 0.17, 0.14, and a VD reduction of 0.43%, 0.51%, 0.33%, and 0.40%, respectively (all P < .02). There was a reduction of 1.19 µm in Avanti parafoveal ganglion cell complex, 1.13 µm in Spectralis ganglion cell inner plexiform layer, and 1.01 µm in Spectralis circumpapillary retinal nerve fiber layer, with R2 of 0.19 (P = .006), 0.23 (P = .002), and 0.24 (P = .002), respectively. CONCLUSIONS: ONH and macula OCTA VD and thickness are associated with the severity of visual field damage in advanced primary open angle glaucoma.

Measurement Floors and Dynamic Ranges of OCT and OCT Angiography in Glaucoma.

PURPOSE: To determine if OCT angiography (OCTA)-derived vessel density measurements can extend the available dynamic range for detecting glaucoma compared with spectral-domain (SD) OCT-derived thickness measurements. DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 509 eyes from 38 healthy participants, 63 glaucoma suspects, and 193 glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study. METHODS: Relative vessel density and tissue thickness measurement floors of perifoveal vessel density (pfVD), circumpapillary capillary density (cpCD), circumpapillary retinal nerve fiber (cpRNFL) thickness, ganglion cell complex (GCC) thickness, and visual field (VF) mean deviation (MD) were investigated and compared with a previously reported linear change point model (CPM) and locally weighted scatterplot smoothing curves. MAIN OUTCOME MEASURES: Estimated vessel density and tissue thickness measurement floors and corresponding dynamic ranges. RESULTS: Visual field MD ranged from -30.1 to 2.8 decibels (dB). No measurement floor was found for pfVD, which continued to decrease constantly until very advanced disease. A true floor (i.e., slope of approximately 0 after observed CPM change point) was detected for cpRNFL thickness only. The post-CPM estimated floors were 49.5±2.6 µm for cpRNFL thickness, 70.7±1.0 µm for GCC thickness, and 31.2±1.1% for cpCD. Perifoveal vessel density reached the post-CPM estimated floor later in the disease (VF MD, -25.8±3.8 dB) than cpCD (VF MD, -19.3±2.4 dB), cpRNFL thickness (VF MD, -17.5±3.3 dB), and GCC thickness (VF MD, -13.9±1.8 dB; P < 0.001). The number of available measurement steps from normal values to the CPM estimated floor was greatest for cpRNFL thickness (8.9), followed by GCC thickness (7.4), cpCD (4.5), and pfVD (3.8). CONCLUSIONS: In late-stage glaucoma, particularly when VF MD is worse than -14 dB, OCTA-measured pfVD is a promising tool for monitoring progression because it does not have a detectable measurement floor. However, the number of steps within the dynamic range of a parameter also needs to be considered. Although thickness parameters reached the floor earlier than OCTA-measured pfVD, there are more such steps with thickness than OCTA parameters.

Association Between Lamina Cribrosa Defects and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

Importance: Certain features of the lamina cribrosa may be associated with increased risk of glaucoma progression. Objectives: To compare the rates of retinal nerve fiber layer (RNFL) thinning in patients with open-angle glaucoma with or without lamina cribrosa (LC) defects and to evaluate factors associated with the rate of glaucoma progression in eyes with LC defects. Design, Setting, and Participants: This longitudinal cohort study designed in September 2017 and conducted at a tertiary glaucoma center in California included 51 eyes of 43 patients with LC defects and 83 eyes of 68 patients without LC defects followed up for a mean (SD) of 3.5 (0.8) years from April 2012 to May 2017. Main Outcomes and Measures: Focal LC defects were detected using swept-source optical coherence tomographic images. All participants underwent visual field testing and spectral-domain optical coherence tomography for RNFL thickness measurements every 6 months. Univariate and multivariable random-effects models were used to compare the rate of local and global RNFL loss. Results: The mean (95% CI) age at baseline for individuals with LC defects was 69.5 (65.4 to 73.6) years, and for those without LC defects, it was 69.6 (67.2-72.0) years; 18 individuals (41%) with LC defects and 35 individuals (51%) without LC defects were men; 6 individuals (14%) with LC defects and 17 individuals (25%) without were African American. The mean (95% CI) rate of global RNFL loss in eyes with LC defects was 2-fold faster than that in eyes without LC defects (-0.91 [-1.20 to -0.62] vs -0.48 [-0.65 to -0.31] µm/y; difference, -0.43 [-0.76 to -0.09] µm/y; P = .01). The rate of RNFL thinning was faster in the LC defect sectors than that in the unaffected sectors (difference, -0.90 [95% CI, -1.68 to -0.12] µm/y, P = .02). Thinner corneal thickness was the only factor that was associated with a faster rate of RNFL loss in eyes with LC defects (ß2 = -0.09 [95% CI, -0.14 to -0.04], P = .001). No association was found between mean intraocular pressure during follow-up and the mean rate of RNFL thinning in eyes with LC defects (ß2, -0.05 [95% CI, -0.17 to 0.06], P = .36). Conclusions and Relevance: These data suggest that LC defects are an independent risk factor for RNFL thinning and that glaucoma progression may correspond topographically to the LC defect location. Thinner corneal thickness in eyes with LC defects was associated with faster further glaucoma progression. In the management of open-angle glaucoma, LC findings may inform the likelihood and rate of glaucoma progression.

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

PURPOSE: To characterize and compare the ganglion cell complex (GCC) thickness and macula vessel density in preperimetric and early primary open-angle glaucoma (POAG) eyes. DESIGN: Cross-sectional study. METHODS: 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. RESULTS: 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). CONCLUSIONS: Both GCC thinning and macula vessel density dropout were detectable in preperimetric and early POAG eyes. GCC loss was greater than macula vessel density loss in early perimetric POAG. However, OCT-A and OCT measurements showed similar efficiency to detect early glaucoma.

New ex vivo model of corneal endothelial phacoemulsification injury and rescue therapy with mesenchymal stromal cell secretome.

PURPOSE: To develop a reproducible ex vivo model of corneal endothelial cell injury using phacoemulsification in porcine eyes and to evaluate the effects of mesenchymal stromal cell secretome in this injury model. SETTING: Department of Ophthalmology, University of Illinois at Chicago, Illinois, USA. DESIGN: Experimental study. METHODS: A corneal endothelial injury model was optimized using different powers and durations of ultrasound energy inside ex vivo porcine eyes. Conditioned media from corneal mesenchymal stem cells was collected under serum-free conditions from passages 4 to 6. Immediately after the phacoemulsification injury, the anterior chamber fluid was replaced with unconditioned media or conditioned media and incubated at 37°C for 4 hours. At the end, endothelial cell viability was evaluated using trypan blue staining and analyzed with ImageJ software. RESULTS: Using specific parameters (50% power for 30 seconds), phacoemulsification inside fresh porcine eyes led to a consistent level of endothelial cell injury. Incubation with corneal mesenchymal stromal cell-conditioned media after the injury significantly reduced endothelial cells loss compared with unconditioned media (mean 1.29% ± 0.91% [SD] and 5.33% ± 3.24%, respectively, P < .05). CONCLUSIONS: Phacoemulsification inside fresh porcine eyes provided a reproducible model to study endothelial cell injury. Treatment with corneal mesenchymal stromal cell secretome after injury appeared to significantly enhance the survival of corneal endothelial cells. This might provide a new strategy for preventing corneal endothelial cell loss after phacoemulsification or other endothelial injuries. Further in vivo studies are necessary to determine the therapeutic potential.

Macular and Optic Nerve Head Vessel Density and Progressive Retinal Nerve Fiber Layer Loss in Glaucoma.

PURPOSE: To investigate prospectively the relationship between macular and peripapillary vessel density and progressive retinal nerve fiber layer (RNFL) loss in patients with mild to moderate primary open-angle glaucoma. DESIGN: Prospective, observational study. PARTICIPANTS: One hundred thirty-two eyes of 83 patients with glaucoma followed up for at least 2 years (average: 27.3±3.36 months). METHODS: Measurements of macular whole image vessel density (m-wiVD) and optic nerve head whole image vessel density (onh-wiVD) were acquired at baseline using OCT angiography. RNFL, minimum rim width (MRW), and ganglion cell plus inner plexiform layer (GCIPL) thickness were obtained semiannually using spectral-domain OCT. Random-effects models were used to investigate the relationship between baseline vessel density parameters and rates of RNFL loss after adjusting for the following confounding factors: baseline visual field mean deviation, MRW, GCIPL thickness, central corneal thickness (CCT), and mean intraocular pressure during follow-up and disc hemorrhage, with or without including baseline RNFL. MAIN OUTCOME MEASURES: Effects of m-wiVD and onh-wiVD on rates of RNFL loss over time. RESULTS: Average baseline RNFL thickness was 79.5±14.8 µm, which declined with a mean slope of -1.07 µm/year (95% confidence interval, -1.28 to -0.85). In the univariate model, including only a predictive factor and time and their interaction, each 1% lower m-wiVD and onh-wiVD was associated with a 0.11-µm/year (P < 0.001) and 0.06-µm/year (P = 0.031) faster rate of RNFL decline, respectively. A similar relationship between low m-wiVD and onh-wiVD and faster rates of RNFL loss was found using different multivariate models. The association between vessel density measurements and rate of RNFL loss was weak (r2 = 0.125 and r2 = 0.033 for m-wiVD and onh-wiVD, respectively). Average CCT also was a predictor for faster RNFL decline in both the univariate (0.11 µm/year; P < 0.001) and multivariate models. CONCLUSIONS: Lower baseline macular and optic nerve head (ONH) vessel density are associated with a faster rate of RNFL progression in mild to moderate glaucoma. Assessment of ONH and macular vessel density may add significant information to the evaluation of the risk of glaucoma progression and prediction of rates of disease worsening.

Inter-eye Asymmetry of Optical Coherence Tomography Angiography Vessel Density in Bilateral Glaucoma, Glaucoma Suspect, and Healthy Eyes.

PURPOSE: To investigate inter-eye retinal vessel density asymmetry in healthy, glaucoma suspect, and mild-to-moderate glaucoma subjects, and its potential utility for early detection of glaucomatous damage. DESIGN: Cross-sectional study. METHODS: In 153 subjects including 55 healthy, 32 glaucoma suspect, and 66 glaucoma subjects enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS), vessel density was obtained from optical coherence tomography angiography (OCT-A) macular and optic nerve head scans. Thickness of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (mGCC) was measured with spectral-domain optical coherence tomography (SD-OCT) scans. Inter-eye asymmetry was calculated by taking the absolute value of difference in vessel density and thickness between the right and left eyes. RESULTS: Inter-eye retinal vessel density asymmetry parameters were significantly different among the 3 groups. Glaucoma suspects had significantly higher peripapillary and macular inter-eye vessel density asymmetries compared to healthy groups in univariate (1.1% vs 2.0%, P = .014 and 1.2% vs 2.5%, P = .027, respectively) and multivariate analyses (P = .007 and P = .038, respectively). No significant differences in asymmetry of thickness parameters were found between glaucoma suspect and healthy groups (all P > .718). However, significant differences in asymmetry of thickness parameters between glaucoma suspects and glaucoma patients (P < .01) were found for all parameters. CONCLUSION: Inter-eye vessel density asymmetry can be quantified by OCT-A measurement. Glaucoma suspects have significantly greater vessel density asymmetry than healthy eyes. Longitudinal studies are needed to better characterize the relationship of vessel density asymmetry with the development and progression of glaucoma.

Progression of Primary Open-Angle Glaucoma in Diabetic and Nondiabetic Patients.

PURPOSE: To compare the rates of visual field (VF) loss and retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG) patients with or without type 2 diabetes mellitus (DM). DESIGN: Cohort study. METHODS: A total of 197 eyes (55 eyes of 32 POAG patients with DM in POAG/DM group and 142 eyes of 111 age-matched POAG patients without DM in POAG/DM- group) were included from the Diagnostic Innovations in Glaucoma Study (DIGS). Type 2 DM participants were defined by self-report of DM history and use of antidiabetic medication. The rates of VF loss and RNFL loss were compared in POAG eyes with and without DM using univariate and multivariable mixed-effects models. RESULTS: The median (interquartile range) follow-up was 5.7 years (4.0, 6.4). The mean rate of global RNFL loss in the POAG/DM group was 2-fold slower than in the POAG/DM- group overall (-0.40 µm/year vs -0.83 µm/year, respectively P = .01). Although a slower rate of VF mean deviation and pattern standard deviation loss was found in the POAG/DM group compared to the POAG/DM- group, the difference was not statistically significant. CONCLUSIONS: POAG patients with treated type 2 DM, who had no detectable diabetic retinopathy, had significantly slower rates of RNFL thinning compared to those without diagnosed DM.

Macular Vessel Density in Glaucomatous Eyes With Focal Lamina Cribrosa Defects.

PURPOSE: To compare optical coherence tomography angiography (OCTA) measured macular vessel density and spectral domain optical coherence tomography (SDOCT) measured macular ganglion cell complex (GCC) thickness in primary open-angle glaucoma eyes with and without focal lamina cribrosa (LC) defects. METHODS: In this cross-sectional, case-control study of patients with primary open-angle glaucoma, 46 eyes of 46 patients with LC defects and 54 eyes of 54 patients without observable LC defects were included. OCTA and SDOCT imaging were performed on the same day by the same operator. Perimetry and swept-source OCT testing used to identify LC defects were conducted within 6 months of OCTA and SDOCT testing. Global and local parafoveal vessel density and macular GCC thickness were compared between study groups. RESULTS: Glaucoma severity was similar between groups (SAP mean deviation=-5.63 and -4.64 dB for eyes with and without LC defects, respectively; P=0.40). Global and local measured parafoveal vessel density was similar between groups (all P≥0.11). GCC focal loss volume was higher in eyes with LC defects than eyes without LC defects (7.2% and 4.97%, respectively; P=0.03). In addition, GCC focal loss volume was topographically related to defect location in LC defect eyes. CONCLUSIONS: Although OCTA macular vessel density was not significantly different between eyes with and without LC defects, focal GCC loss in eyes with LC defects was different. This highlights the importance of not relying solely on vessel density measurements for determining macular changes for diagnosing and detecting glaucomatous progression.

Three Dimensional Stimulus Source for Pattern Electroretinography in Mid- and Far-peripheral Retina.

PURPOSE: The pattern electroretinogram (pERG) response reflects, in part, ganglion cell function. However, probing retinal ganglion cell (RGC) function in the mid- and far peripheral retina is difficult with conventional flat-panel pERG stimulus sources. A pattern stimulus source is presented for probing the peripheral retina. Peripheral pERG (ppERG) responses were evaluated versus luminance, reversal rate, and field subtended, and were compared with conventional pERG in healthy eyes. METHODS: Eleven normally-sighted subjects were recruited. A hemispherical surface was used to present a reversing checkerboard pattern to the peripheral retina, from approximately 35° to 85° of visual field, in all directions. Responses to stimuli presented to peripheral field sectors (superior, nasal, inferior, temporal) were also recorded. Conventional pERG responses were recorded on the same day. Amplitudes and implicit times of waveform peaks were evaluated. RESULTS: Robust pERG responses from peripheral retina resemble conventional pERG responses but with shorter implicit times and reduced positive component. Responses to high-luminance patterns include high-frequency components resembling flash ERG oscillatory potentials. Negative response component amplitudes increased with increasing pattern luminance, and decreased with increasing reversal rate. CONCLUSIONS: Peripheral-field pERG responses are robust and repeatable; the unique response properties reflect differences between central and peripheral retina. Field-sector response ratios can be used to probe for sectoral dysfunction associated with disease. TRANSLATIONAL RELEVANCE: The ppERG approach provides direct measurement of proximal retinal function beyond the fields probed by conventional perimetry and pERG, providing access to a relatively under studied part of the retina relevant to early stage glaucoma.

The Ocular Hypotensive Efficacy of Topical Fasudil, a Rho-Associated Protein Kinase Inhibitor, in Patients With End-Stage Glaucoma.

To investigate the effects of topical administration of a selective Rho-associated kinase (ROCK) inhibitor, fasudil 0.5% and 1.2% in glaucomatous patients. In this interventional case series study, 4 eyes of 4 patients with unilateral end-stage primary open-angle glaucoma and no light perception vision were assigned to receive topical fasudil 0.5% (in 3 eyes) or 1.2% (in 1 eye) ophthalmic solution twice daily for 8 weeks. At weeks 1, 2, 3, 4, and 8, intraocular pressure (IOP) and adverse events were evaluated. Baseline mean IOP was 53.5 ± 3.4 mm Hg and mean IOP reductions of the last visit were -8.25 ± 1.2 mm Hg at 2 hours and -8.75 ± 2.2 mm Hg at 4 hours. Mean IOP reductions were clinically and statistically significant with 0.5% and 1.2% fasudil and peak effects occurred 2-4 hours after application (P = 0.0002). The largest IOP reductions were produced by 1.2% fasudil (up to -12 mm Hg). Conjunctival hyperemia was found in 1 patient with 1.2% fasudil. Topical administration of fasudil in end-stage primary open-angle glaucoma patients, caused reduction in IOP and was well tolerated. ROCK inhibitors could be considered as a candidate for glaucoma therapy in future.

Distribution of intraocular pressure, central corneal thickness and vertical cup-to-disc ratio in a healthy Iranian population: the Yazd Eye Study.

PURPOSE: To determine the distribution of intraocular pressure (IOP), central corneal thickness (CCT) and vertical cup-to-disc ratio (VCDR) in the healthy Iranian population. METHODS: This population-based, epidemiologic study evaluated Iranian aged 40-80 years, residing in Yazd, Iran, in 2010-2011. Eligible subjects were selected by cluster random sampling. Each participant underwent an interview and ophthalmologic examination including slit lamp examination, Goldmann applanation tonometry, binocular optic disc evaluation, stereoscopic fundus photography, ultrasonic pachymetry and visual field testing. RESULTS: Of 2320 eligible individuals, 2098 subjects (response rate of 90.4%) participated in the study. One eye from 1159 subjects (total of 2262 normal eyes) were randomly selected for the purpose of the study. Mean age was 53.1 ± 9.6 years. Mean IOP, CCT and VCDR were 14.2 ± 2.5 mmHg, 543 ± 37 µm and 0.32 ± 0.14, respectively. Multiple regression analysis showed a significant correlation between IOP and age (regression coefficient = 0.02 per year, p = 0.015), CCT (regression coefficient = 0.02 per micron, p < 0.001), Spherical equivalent (regression coefficient = -0.15 per dioptre, p = 0.0.024) and smoking (regression coefficient = 0.89 higher for smokers, p = 0.009); it also showed a significant correlation between CCT with spherical equivalent (regression coefficient = 3.6 per dioptre, p = 0.002) and IOP (regression coefficient = 3.6 per mmHG, p < 0.001). There was no significant correlation with VCDR. CONCLUSIONS: Mean IOP, CCT and VCDR were 14.2 ± 2.5 mmHg, 543 ± 35 µm and 0.32 ± 0.14, respectively, in healthy Iranians that is different from other ethnicities. It seems advisable to pay attention to ethnicity for interpretation of each person's variables.