Sector-specific Association of Intraocular Pressure Dynamics in Dark-room Prone Testing and Visual Field Defect Progression in Glaucoma.

PURPOSE: To investigate sectoral differences in the relationship between intraocular pressure (IOP) dynamics during dark-room prone testing (DRPT) and visual field (VF) defect progression in primary open-angle glaucoma (POAG) patients. DESIGN: Retrospective, longitudinal study. PARTICIPANTS: This retrospective study included 116 eyes of 84 POAG patients who underwent DRPT and had at least 5 reliable VF tests conducted over a more than 2-year follow-up period. We excluded eyes with mean deviation worse than -20 dB or a history of intraocular surgery or laser treatment. METHODS: Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 or 30-2 program. During DRPT, IOP was measured in the sitting position, and after 60 minutes in the prone position in a dark room, IOP was measured again. The relationship between IOP change during DRPT, IOP after DRPT, and TD slope in each quadrant was analyzed with a linear mixed-effects model, adjusting for other potential confounding factors. MAIN OUTCOME MEASURES: Total deviation slope in each quadrant, IOP change during DRPT, and IOP after DRPT. RESULTS: Intraocular pressure after DRPT and IOP change during DRPT were 18.16 ± 3.42 mmHg and 4.92 ± 3.12 mmHg, respectively. Superior TD slope was significantly associated with both IOP after DRPT (ß = -0.28, P = 0.003) and IOP change during DRPT (ß = -0.21, P = 0.029), while central (ß = -0.05, P = 0.595; ß = -0.05; P = 0.622) and inferior (ß = 0.05, P = 0.611; ß = 0.01, P = 0.938) TD slopes were not. CONCLUSION: Dark-room prone testing might be a useful test to predict the risk of superior VF defect progression in eyes with POAG. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Relationship Between Artificial Intelligence-Assisted OCT Angiography-Derived Foveal Avascular Zone Parameters and Visual-Field Defect Progression in Eyes with Open-Angle Glaucoma.

Purpose: To investigate clinical factors associated with foveal avascular zone (FAZ) parameters obtained using OCT angiography (OCTA) with assistance from a previously developed artificial intelligence (AI) platform in eyes with open-angle glaucoma (OAG). Design: Retrospective longitudinal. Participants: This study followed up 885 eyes of 558 patients with OAG for ≥ 2 years; all eyes underwent ≥ 5 Humphrey visual-field (VF) tests and had 3.0 × 3.0 mm macular OCTA scans available. Methods: Average total deviation (TD) in the superior, superocentral, inferocentral, and inferior sectors of the Humphrey 24-2 program was calculated. We collected 3.0 × 3.0 mm macular OCTA images from each patient and used a previously developed AI platform with these images to obtain FAZ parameters, including FAZ area, FAZ circularity index (CI), and FAZ perimeter. Multivariable linear mixed-effects models were used to analyze the relationship between FAZ parameters, TD or TD slope in each quadrant, and systemic factors, adjusting for potential confounding factors, including axial length. Main Outcome Measures: Ophthalmic and systemic variables, FAZ parameters, and TD or TD slope in each quadrant. Results: The multivariable model showed that FAZ parameters were correlated with both TD and TD slope in the inferocentral quadrant (ß = -0.244 - 0.168, P < 0.001). Both upper-half and lower-half FAZ parameters were better associated with TD-inferocentral and TD-inferocentral slope than TD-superocentral or TD-superocentral slope in terms of ß size and statistical significance, indicating that there was no evident vertical anatomical correspondence between TD in the central quadrant and FAZ parameters. Foveal avascular zone area enlargement was associated with female gender (ß = 0.242, P = 0.003). Loss of FAZ circularity was associated with both aging and comorbid sleep apnea syndrome (SAS) (yes: 1, no: 0) (ß = -0.188, P < 0.001; ß = -0.261, P = 0.031, respectively). Foveal avascular zone perimeter elongation was associated with aging and female gender (ß = 0.084, P = 0.040; ß = 0.168, P = 0.042, respectively). Conclusions: Artificial intelligence-assisted OCTA-measured FAZ enlargement and irregular shape might be good markers of ocular hypoperfusion and associated inferocentral VF defect progression in eyes with OAG. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Effect of ß-Blocker Eye Drops on Pulse Rate, Ocular Blood Flow, and Glaucoma Progression: A Retrospective Longitudinal Study.

INTRODUCTION: Our study was conducted to determine factors associated with the effectiveness of a ß-blocker eye drop add-on in altering pulse rate (PR) in glaucoma patients. METHODS: This retrospective study examined 236 eyes of 138 patients who received a ß-blocker eye drop add-on during follow-up. Patients were included if at least one PR measurement was available both before and after the add-on was started. We collected data on ophthalmic parameters: longitudinal PR; longitudinal choroidal blood flow, represented by laser speckle flowgraphy-measured mean blur rate (MBR); and diacron-reactive oxygen metabolites (d-ROMs). We used a multivariable linear mixed-effects model to investigate the effectiveness of the ß-blocker eye drop add-on in altering PR and examined factors contributing to a larger PR alteration after the add-on was started by analyzing the effect on PR of the interaction term between the add-on and clinical factors. We used the k-means method to classify the patients. RESULTS: The ß-blocker eye drop add-on reduced PR (- 7.61 bpm, P < 0.001). Female gender, higher PR when the add-on was started, lower central corneal thickness, and a higher d-ROM level were associated with greater reduction in PR (P < 0.05). In a cluster of patients with these clinical features, choroidal MBR increased by + 3.42% when we adjusted for change over time; MD slope, which represents the speed of glaucoma progression, improved by + 0.64 dB/year (P < 0.05). CONCLUSIONS: We identified a glaucoma subgroup in which PR decreased, choroidal blood flow increased, and glaucoma progression slowed after a ß-blocker eye drop add-on was started.

Factors associated with intrachoroidal cavitation and sinkhole formation in eyes with glaucomatous visual-field defects.

PURPOSE: To investigate factors associated with intrachoroidal cavitation (ICC) and sinkhole formation in eyes with glaucomatous visual-field defects. METHODS: This retrospective, cross-sectional study enrolled a total of 2808 eyes of 1482 patients who were diagnosed/treated for glaucoma and underwent swept-source optical coherence tomography (OCT). We first determined the prevalence of ICCs and sinkholes and their locations. Next, we selected one eye from each patient and compared the clinical characteristics of eyes with and without ICCs. Finally, in eyes with ICCs, we compared the clinical characteristics of eyes with and without sinkholes. Blood flow (BF), represented by laser speckle flowgraphy-measured tissue-area mean blur rate (MBR), was measured in the temporal optic nerve head (ONH), temporal peripapillary chorioretinal atrophy (PPA) zone, and in the ICC zone. ICC area and angle were analyzed in OCT en-face images. Mean deviation and total deviation in the central area (TD-central) were measured with Humphrey visual-field testing. RESULTS: A total of 86 eyes (3.1%) had ICCs and 52 eyes (1.9%) had sinkholes. ICC eyes had a lower spherical equivalent and longer axial length (AL) than non-ICC eyes (P < 0.05). Patients with eyes with sinkholes were more elderly and had worse best-corrected visual acuity, worse TD-central, a larger ICC, and lower tissue-area MBR in the temporal ONH, temporal PPA zone, and ICC zone (P < 0.05). CONCLUSION: In eyes with glaucoma, AL elongation might be linked to ICC formation. Sinkhole formation might be associated with ICC enlargement, impaired ocular BF, and impaired retinal structure and function involving the central area.

The association between intraocular pressure dynamics during dark-room prone testing and intraocular pressure over a relatively long-term follow-up period in primary open-glaucoma patients.

PURPOSE: To investigate the relationship between the dynamics of intraocular pressure (IOP) during dark-room prone testing (DRPT) and IOP over a relatively long-term follow-up period. METHODS: This retrospective study enrolled 84 eyes of 51 primary open-angle glaucoma patients who underwent DRPT for whom at least three IOP measurements made using Goldmann applanation tonometry were available over a maximum follow-up period of two years. We excluded eyes with a history of intraocular surgery or laser treatment and those with changes in topical anti-glaucoma medication during the follow-up period. In DRPT, IOP was measured in the sitting position, and after 60 min in the prone position in a dark room, IOP was measured again. In this study, IOP fluctuation refers to the standard deviation (SD) of IOP, and IOP max indicates the maximum value of IOP during the follow-up. The relationship between these parameters was analyzed with a linear mixed-effects model, adjusting for clinical parameters including age, gender, and axial length. RESULTS: IOP increased after DRPT with a mean of 6.13 ± 3.55 mmHg. IOP max was significantly associated with IOP after DRPT (ß = 0.38; p < 0.001). IOP fluctuation was significantly associated with IOP change in DRPT (ß = 0.29; p = 0.007). CONCLUSION: Our findings suggest that short-term and relatively long-term IOP dynamics are associated. Long-term IOP dynamics can be predicted by DRPT to some extent.

The effect of a brinzolamide/brimonidine fixed combination on optic nerve head blood flow in rabbits.

PURPOSE: The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits. METHODS: A crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day's first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point. RESULTS: There were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P < 0.01). CONCLUSION: BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF.

A ginger extract improves ocular blood flow in rats with endothelin-induced retinal blood flow dysfunction.

The aim of this study was to investigate the effect of a ginger extract on optic nerve head blood flow (ONH BF) under endothelin-1 (ET-1) stimulation. Using laser speckle flowgraphy, we measured ONH BF in brown Norway rats. To establish the ONH BF impairment profile under ET-1 stimulation, we administered an intravitreal injection of ET-1 under anesthesia. We then gave the ginger extract sublingually to assess its effect on ONH BF in both normal and ET-1-induced ischemic conditions. Post ET-1 injection, there were no significant changes in parameters including intraocular pressure or systemic factors. ONH BF showed a dose-dependent decline after ET-1 injection, with a significant reduction after a 2.50 pmol ET-1 dose. Sublingual administration of the ginger extract significantly improved ONH BF in both normal and ET-1-stimulated rats. This suggests that our newly developed supplement for improving ONH BF has a potential role in retinal ischemic diseases, including glaucoma.

Predictive potential of optical coherence tomography parameters for the prognosis of decreased visual acuity after trabeculectomy in open-angle glaucoma patients with good vision.

BACKGROUND: Trabeculectomy (trab) is the most effective surgical procedure for lowering IOP and preventing glaucoma progression. However, decline in best-corrected visual acuity (BCVA) is one of the most serious postoperative complications of trab. Here, we investigated methods to predict decreased BCVA after trab in glaucoma patients with good preoperative BCVA. METHODS: This study included 35 eyes of 35 open-angle glaucoma (OAG) patients (male / female: 21 / 14, age: 64.0 ± 9.7 years old, preoperative intraocular pressure: 15.9 ± 5.4 mmHg, mean deviation: -18.1 ± 5.6 dB) with preoperative BCVA of 0.7 or better who underwent trab and were observed for more than 12 months. As a preoperative analysis, we measured temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell complex thickness in a central strip between the disc and fovea (csGCCT), an area that corresponds to the location of the papillomacular bundle (PMB) in swept-source optical coherence tomography (OCT). We defined BCVA decline as a loss of more than 3 lines of BCVA after 12 months. Measurement parameters were compared between the BCVA-decline group and the non-BCVA-decline group. RESULTS: BCVA decline was detected in 11 cases (31.4%) 12 months after trab. There was a statistically significant difference in axial length (P = 0.049). A single logistic analysis showed that the BCVA-decline group had significantly lower cpRNFLT than the non-BCVA-decline group (27.7 ± 8.0 µm vs. 45.1 ± 5.3 µm, P < 0.001, cut-off value: 33.4 µm), as well as lower csGCCT (72.4 ± 7.7 µm vs. 87.5 ± 5.1 µm, P = 0.002, cut-off value: 82.3 µm). Multivariable logistic analysis showed that the BCVA-decline group had significantly lower temporal quadrant cpRNFLT (P < 0.001) and lower middle csGCCT (P < 0.001) compared to the non-BCVA-decline group. CONCLUSIONS: Lower temporal quadrant cpRNFLT and middle csGCCT, OCT scan areas that correspond to the location of the PMB, might be biomarkers that predict BCVA decline after trab in OAG patients with good vision.

Factors Associated With Visual Acuity Decline in Glaucoma Patients With Loss of Ganglion Cell Complex Thickness.

Purpose: To investigate the association between ocular/systemic factors and visual acuity decline in glaucoma patients with loss of ganglion cell complex thickness (GCCT). Methods: In 515 eyes of 515 patients with open-angle glaucoma (mean age, 62.6 ± 12.8 years; mean deviation, -10.95 ± 9.07 dB), we used swept-source optical coherence tomography to measure macular GCCT in sectors classified as corresponding to circumpapillary retinal nerve fiber layer clock-hour sectors from 7 o'clock (inferotemporal) to 11 o'clock (superotemporal). We calculated Spearman's rank correlation coefficient between each sector and best-corrected visual acuity (BCVA), determined cutoff values for BCVA decline (<20/25), and used multivariable linear regression models to determine the correlation between BCVA and biological antioxidant potential (BAP), corneal hysteresis (CH), and temporal-tissue optic nerve head blood flow (represented by temporal mean blur rate, or MBR-T). Results: Macular GCCT corresponding to the 9 o'clock sector had the highest correlation with BCVA (Rs = -0.454; P < 0.001) and a cutoff of 76.17 µm (area under the receiver operating characteristic curve = 0.891; P < 0.001). Subjects below this cutoff (N = 173) showed significant correlations between BCVA and age, BAP, CH, and MBR-T (ß = 0.192, P = 0.033; ß = -0.186, P = 0.028; ß = -0.217, P = 0.011; and ß = -0.222, P = 0.010, respectively). Conclusions: Multiple factors are involved in BCVA decline in patients with glaucoma with decreased macular GCCT. This suggests that evaluating BCVA may require assessing multiple factors. Translational Relevance: Multiple factors contribute to BCVA decline.

The Relationship Between Kiritsu-Meijin-Derived Autonomic Function Parameters and Visual-Field Defects in Eyes with Open-Angle Glaucoma.

PURPOSE: This retrospective cross-sectional study aimed to investigate the association between autonomic parameters measured using the Kiritsu-Meijin device and visual-field defects in patients with open-angle glaucoma. METHODS: A total of 79 eyes of 42 patients with open-angle glaucoma were enrolled in this study. Kiritsu-Meijin testing comprised three phases: sitting, standing, and sitting again (2 min, 2 min, and 1 min, respectively). Continuous electrocardiograms were recorded for five minutes. Autonomic parameters were extracted from the resulting data and analyzed, including activity, balance, reaction, switchover, and recovery; these are five representative parameters derived from Kiritsu-Meijin testing. Correlations between these parameters and mean deviation from Humphrey visual field testing were determined. Additionally, we used a linear mixed-effects model to observe sectoral differences in the relationship between total deviation and the Kiritsu-Meijin parameters. In this study, we focused on superior, central, and inferior total deviations. RESULTS: Significant positive correlations were observed between activity, balance, and recovery and mean deviation values (ß = 0.29-0.38, p < .05). The ß value between activity and inferior total deviation was higher than that between activity and superior total deviation (ß = 0.22, p < .05). Balance did not show any sectoral differences (p > .05). Recovery was more strongly associated with central to inferior total deviation than superior total deviation (ß = 0.17-0.25, p < .05). CONCLUSION: Our findings suggest that in patients with open-angle glaucoma, lower activity and recovery are associated with more severe central and/or inferior visual field defects in the superior quadrant. These results imply that measurements of autonomic function made with the Kiritsu-Meijin device may have clinical utility in the management of glaucoma.

Vasoreactivity of the optic nerve head, nailfold, and facial skin in response to cold provocation in normal-tension glaucoma patients.

BACKGROUND: The dysfunction of optic nerve head (ONH) hemodynamics has been suggested to be involved in the pathogenesis of normal-tension glaucoma (NTG). The aim of this study was to compare vasoreactivity in the ONH, nailfold, and facial skin in response to cold-water provocation in NTG patients and healthy controls. METHODS: We performed cold-water provocation in 14 eyes of 14 NTG patients and 15 eyes of 15 age-matched control subjects. Laser speckle flowgraphy-derived tissue-area mean blur rate (MT), skin blood flowmetry-derived pulse wave amplitude (PA), nailfold capillaroscopy-derived nailfold capillary diameter, and other clinical parameters were recorded at baseline and 4 and 6 min after the cold stimulus. We compared changes (as percentages) in these variables in the NTG and control subjects with a linear mixed-effects model and evaluated correlations between these changes with Spearman's rank correlation coefficient. RESULTS: The interaction term between the NTG group (reference, control group) and the 4-min protocol step (reference, baseline) significantly affected the changes in MT, nailfold capillary diameter and PA (ß = -9.51%, P = 0.017, ß = -20.32%, P = 0.002; ß = + 18.06%, P = 0.017, respectively). The change in MT was positively correlated with the change in nailfold capillary diameter, and negatively correlated with the change in PA (r = 0.39, P = 0.036; r = -0.40, P = 0.031, respectively). CONCLUSION: NTG patients showed abnormal vasoconstriction in the ONH and nailfold and vasodilation in the facial skin in response to cold-water provocation.

Effects of constitutively active K-Ras on axon regeneration after optic nerve injury.

Visual disturbance after optic nerve injury is a serious problem. Attempts have been made to enhance the intrinsic ability of retinal ganglion cells (RGCs) to regenerate their axons, and the importance of PI3K/Akt and RAF/MEK/ERK signal activation has been suggested. Since these signals are shared with oncogenic signaling cascades, in this study, we focused on a constitutively active form of K-Ras, K-RasV12, to determine if overexpression of this molecule could stimulate axon regeneration. We confirmed that K-RasV12 phosphorylated Akt and ERK in vitro. Intravitreal delivery of AAV2-K-RasV12 increased the number of surviving RGCs and promoted 1.0 mm of axon regeneration one week after optic nerve injury without inducing abnormal proliferative effects in the RGCs. In addition, AAV2-K-RasV12 induced robust RGC axon regeneration, reaching as far as approximately 2.5 mm from the injury site, in eight weeks. Our findings suggest that AAV2-K-RasV12 could provide a good model for speedy and efficient analysis of the mechanism underlying axon regeneration in vivo.

The relationship between choroidal blood flow and glaucoma progression in a Japanese study population.

PURPOSE: To determine whether choroidal blood flow (BF) is related to visual field (VF) defect severity and progression in eyes with open-angle glaucoma (OAG). STUDY DESIGN: Retrospective and longitudinal. METHODS: This study comprised 443 eyes of 285 OAG patients who underwent laser speckle flowgraphy (LSFG), optical coherence tomography, and visual-field (VF) testing at baseline. The patients were then observed for at least 2 years and at least 5 reliable VF tests were performed. In the LSFG images, we set regions of interest at the optic nerve head (ONH) and the parapapillary choroid to obtain ONH-tissue mean blur rate (MBR) and choroidal MBR, respectively. We used univariable and multivariable linear mixed-effects models to determine clinical factors associated with choroidal MBR at baseline. We also used a linear mixed-effects model to determine the contribution of ONH-tissue MBR and choroidal MBR to baseline mean deviation (MD) and to MD slope during follow-up, adjusting for potential confounding factors, including circumpapillary retinal nerve fiber layer thickness. RESULTS: Choroidal MBR was associated with age, MD slope, and ONH-tissue MBR (ß = -0.181, P = 0.001; ß = 0.134, P = 0.002; ß = 0.096, P = 0.049, respectively). ONH-tissue MBR was associated with both MD and MD slope (ß = 0.146, P = 0.004; ß = 0.152, P = 0.009, respectively), whereas choroidal MBR was associated only with MD slope (ß = 0.147, P = 0.005). CONCLUSION: LSFG-derived choroidal MBR might be a useful biomarker to predict VF defect progression in a Japanese population.

Correlation Between Enlargement of Retinal Nerve Fiber Defect Angle in En Face Imaging and Visual Field Progression.

Purpose: Retinal nerve fiber layer defects (RNFLDs) become enlarged with glaucoma progression. We measured the RNFLD angle and investigated whether it was correlated with deterioration of the visual field in patients with glaucoma. Methods: This study included 84 eyes of 84 patients with open-angle glaucoma (mean deviation [MD] = -6.51 ± 5.91 dB, follow-up period = 2.82 ± 0.74 years) with the RNFLDs, who underwent en face swept-source optical coherence tomography (SS-OCT) wide scans (12 × 9 mm) at least 6 times. The RNFLD angle was measured as the intersection between the RNFLD and a circle centered on the disc with a radius half the distance between the disc and the fovea. Slopes for the RNFLD angle, macular ganglion cell layer thickness (GCCT), and circumpapillary RNFL thickness (cpRNFLT) were compared with the MD slope, as measured with the Humphrey field analyzer 24-2 program. Results: The correlation coefficients with MD slope were -0.67 for the RNFLD angle slope (P < 0.001), 0.15 for the macular GCCT slope (P = 0.163), and 0.04 for the cpRNFLT slope (P = 0.719). The RNFLD angle tended to increase as the number of disc hemorrhage occurrences increased (rs = 0.31, P = 0.004). The RNFLD angle slope also had good predictive power for glaucoma progression (area under the receiver operating characteristic curve = 0.88, 95% confidence interval = 0.81-0.95). Conclusions: We found that the RNFLD angle slope was more closely associated with the MD slope than were other OCT parameters. This suggests that measurement of the RNFLD angle with en face OCT images could be effective in evaluating glaucoma progression. Translational Relevance: Our study provides a method for monitoring glaucoma progression with SS-OCT.

Time-Course Changes in Optic Nerve Head Blood Flow and Retinal Nerve Fiber Layer Thickness in Eyes with Open-angle Glaucoma.

PURPOSE: To determine whether decreased optic nerve head (ONH) blood flow (BF) precedes or follows decreased circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in eyes with open-angle glaucoma (OAG). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: This study followed up 350 eyes of 225 OAG patients for at least 2 years and collected data from each patient from at least 5 examinations obtained with laser speckle flowgraphy (LSFG) and OCT. METHODS: In the superior, temporal, and inferior ONH quadrants, tissue area mean blur rate (MT), representing ONH tissue BF, was measured with LSFG, whereas cpRNFLT was measured with OCT. A multivariate linear mixed-effects model was used to identify potential predictors of faster MT decrease, adjusting for possible confounding factors. Based on these results, each quadrant of each patient was assigned a risk point if the quadrant was the superior or temporal, if patient age was older than the median (61 years), and if patient pulse rate was higher than median (74 beats per minute). The quadrants were then compared with a mixed-effects Cox model for MT and cpRNFLT changes, defined as a difference between the baseline value and the values from the latest 2 consecutive follow-up visits of more than 1.96 × the corresponding coefficient of variation. MAIN OUTCOME MEASURES: Ophthalmic and systemic variables and MT and cpRNFLT in the superior, temporal, and inferior quadrants. RESULTS: The multivariate model showed that MT decrease was faster in older patients with higher pulse rate and slower in inferior quadrants (P < 0.05). Quadrants with 0 risk points showed primary cpRNFLT decrease (P = 0.048), 1-risk point quadrants showed simultaneous cpRNFLT and MT decrease (P = 0.260), and 2-risk point and 3-risk point quadrants showed primary MT decrease (P < 0.001). CONCLUSIONS: Older patients with higher pulse rate are at greater risk of a primary reduction in ONH tissue BF, that is, preceding cpRNFLT decrease, in the superior and temporal quadrants.

Progression in Open-Angle Glaucoma with Myopic Disc and Blood Flow in the Optic Nerve Head and Peripapillary Chorioretinal Atrophy Zone.

PURPOSE: To investigate the effect of blood flow in the temporal optic nerve head (ONH) and peripapillary chorioretinal atrophy (PPA) zone on central visual field (VF) defects and progression in eyes with open-angle glaucoma (OAG) and myopic disc. DESIGN: Retrospective longitudinal medical chart review. PARTICIPANTS: This study comprised 366 eyes of 245 OAG patients with myopic disc, followed for at least 2 years with at least 5 reliable VF tests. OCT and laser speckle flowgraphy (LSFG) were performed at baseline. METHODS: We analyzed the relationship between temporal ONH-tissue mean blur rate (MBR), temporal PPA-tissue MBR, total deviation (TD)-central, and TD-central slope with a linear mixed-effects model. Additionally, we investigated background factors influencing temporal PPA-tissue MBR. Main outcome measures were basic ophthalmic and systemic variables, baseline ONH-tissue MBR, baseline PPA-tissue MBR, baseline TD, and TD slope. RESULTS: Lower temporal ONH-tissue MBR was associated with both worse TD-central and faster TD-central slope (ß = 0.30, P < 0.001; ß = 0.18, P = 0.001, respectively). However, lower temporal PPA-tissue MBR was only associated with faster TD-central slope (ß = 0.15, P = 0.005). Lower ONH-tissue MBR and lower PPA-tissue MBR were significant independent contributors to worse TD-central slope, after adjusting for potential confounding factors (ß = 0.12 to 0.15, P < 0.05). The multivariate analysis showed that lower pulse rate, larger temporal PPA area, and lower circumpapillary retinal nerve fiber layer thickness were associated with lower PPA-tissue MBR (P < 0.05). CONCLUSIONS: Measurement of systemic variables and LSFG analysis might help clinicians to predict central VF defect severity and progression in OAG eyes with myopic disc.

A pyruvate dehydrogenase kinase inhibitor prevents retinal cell death and improves energy metabolism in rat retinas after ischemia/reperfusion injury.

We aimed to assess the neuroprotective effect of a pyruvate dehydrogenase kinase (PDK) inhibitor, Nov3r after ischemia/reperfusion (IR) injury in rats. IR injury was induced by applying 150 mmHg of intraocular pressure for 50 min. Nov3r was orally administered (100 mg/kg) 3 h before and 24 h after IR injury. TUNEL-positive cells increased and immunoreactive RBPMS-positive cells decreased in the rat retinas after IR injury. Administration of Nov3r significantly ameliorated the increase in TUNEL-positive cells and prevented the RBPMS-positive cell decrease. Similarly, the number of IR-induced Iba1-positive microglial cells was significantly reduced with Nov3r treatment. Among metabolic parameters, IR damage induced the elevation of lactate and pyruvate, and the reduction of ATP. Oral administration of Nov3r ameliorated these changes. Our data suggest that the Nov3r had a retinal neuroprotective effect in IR injury in rats. This finding suggests that the regulation of pyruvate dehydrogenase (PDH) activity has potential therapeutic value by enabling metabolic reprograming in diseases associated with ischemic retinal damage, such as diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, ischemic optic neuropathy and glaucoma.

The optic nerve head vasoreactive response to systemic hyperoxia and visual field defect progression in open-angle glaucoma, a pilot study.

PURPOSE: To investigate the effect of optic nerve head (ONH) tissue vasoreactivity on glaucoma visual field defect progression. METHODS: This prospective, longitudinal study comprised 28 eyes of 16 patients with open-angle glaucoma. Baseline data were obtained from oxygen inhalation testing, including laser speckle flowgraphy measurements of tissue-area mean blur rate (MT), which represents ONH tissue blood flow, and the mean percentage change in MT (MT-change). Follow-up data were collected for at least 2 years, including at least 5 reliable visual field tests. The average total deviation (TD) was calculated in each sector of the Garway-Heath map; in this study, superior, central and inferior TD corresponded to inferior, temporal and superior MT or MT-change, respectively. MT and MT-change in three sectors per eye were included as explanatory variables in a multivariable linear mixed-effects model, with TD slope set as the response variable. RESULTS: At baseline, lower MT and higher diastolic blood pressure were associated with lower MT-change (p < 0.05). Additionally, MT-change significantly contributed to TD slope in the corresponding sectors (ß = 0.41, p = 0.01). CONCLUSIONS: Weaker ONH tissue vasoreactivity to systemic hyperoxia, assessed with laser speckle flowgraphy, was associated with lower baseline ONH tissue blood flow, higher diastolic blood pressure and rapid visual field defect progression. Laser speckle flowgraphy variables during oxygen provocation testing may represent potentially useful predictive biomarkers of glaucoma progression.

Sectoral Differences in the Association of Optic Nerve Head Blood Flow and Glaucomatous Visual Field Defect Severity and Progression.

Purpose: To investigate sectoral differences in the relationship between optic nerve head tissue blood flow, anatomically corresponding visual field defect severity, and future progression. Methods: This retrospective longitudinal medical chart review comprised 508 eyes of 319 open-angle glaucoma patients (mean deviation: -9.2 ± 7.0 dB), followed for an average of 4.7 ± 1.1 years; an average 11.7 ± 3.7 visual field tests were performed. Average total deviation (TD) was calculated in the superior, central, and inferior sectors of the Humphrey 24-2 program. The optic nerve head was divided to obtain inferior, temporal, and superior tissue-area mean blur rate (MT), derived from laser speckle flowgraphy. At baseline, the correlation between MT and TD was compared in anatomically corresponding sectors. We performed a multivariate analysis to determine the contribution of baseline MT to corresponding TD slope and to determine background factors influencing superior to temporal MT. We used a linear-mixed effect model for the statistical analysis. Results: At baseline, the highest ß coefficients were found between MT-superior and TD-inferior, MT-temporal and TD-central, and between MT-inferior and TD-superior, in that order (ß = 0.38, ß = 0.27, ß = 0.26, respectively). MT-superior and MT-temporal independently contributed to corresponding TD slope (P < 0.05). Male sex, high body mass index, and the prevalence of sleep apnea syndrome were contributing factors to lower superior to temporal MT (P < 0.05). Conclusions: Review of medical history, measurements of systemic variables, and laser speckle flowgraphy parameters might help clinicians to predict visual field defect severity and progression.

Quantitative analysis of the macula with optical coherence tomography angiography in normal Japanese subjects: The Taiwa Study.

This study evaluated age-related changes in the superficial and deep retinal capillary plexus (SCP and DCP, respectively) and in the foveal avascular zone (FAZ). SCP and DCP perfusion density (PD) were measured in optical coherence tomography angiography (OCTA) macular scans of 145 eyes of 145 healthy Japanese subjects, and findings were compared with SCP FAZ and clinical data. We found that age was negatively correlated with SCP and DCP PD (r = -0.17, P = 0.04 and r = -0.20, P = 0.02, respectively) and positively correlated with FAZ area (r = 0.18, P = 0.03). SCP and DCP PD were correlated with each other (r = 0.67, P < 0.001). FAZ area was negatively correlated with SCP PD, DCP PD and central macular thickness (CMT) (r = -0.18, P = 0.03; r = -0.25, P < 0.01; and r = -0.39, P < 0.001, respectively). FAZ was larger and CMT was lower (P = 0.01 and P < 0.001, respectively) in women than men. SCP and DCP PD were positively correlated with estimated glomerular filtration rate (r = 0.17, P = 0.03 and r = 0.24, P < 0.01, respectively). Multiple regression analysis confirmed that age independently affected DCP PD and FAZ (P = 0.02 and P < 0.01, respectively) and that CMT independently affected FAZ area (P < 0.001). Thus, normal subjects showed age-related decreases in macular PD and renal function. FAZ and CMT were related, suggesting that age-related changes in macular thickness also affect capillary vasculature.