Modulation of TRPV4-mediated TNF-α expression in Müller glia and subsequent RGC apoptosis by statins.

In addition to regulating cholesterol synthesis, statins have neuroprotective effects. Apoptosis of retinal ganglion cells (RGCs) causes a gradual loss of visual function in glaucoma. This study aimed to investigate the neuroprotective effect of statins on the RGC apoptosis induced by activated Müller glia. Primary Müller cells and RGCs were cultured from the retina of C57BL6 mice. Müller cells were activated with GSK101, a transient receptor potential vanilloid 4 (TRPV4) agonist, and tumor necrosis factor-alpha (TNF-α) released to the medium was measured using an enzyme-linked immunosorbent assay. Cells were pretreated with simvastatin or lovastatin before GSK101. RGCs were treated with conditioned media from Müller glia cultures, and apoptosis was determined using flow cytometry. TRPV4 activation through GSK101 treatment induced gliosis of Müller cells, and the conditioned media from activated Müller cells was potent to induce RGC apoptosis. Statins suppress both gliosis in Müller cells and subsequent RGC apoptosis. TNF-α release to the media was increased in GSK101-treated Müller cells, and TNF-α in the conditioned media was the critical factor causing RGC apoptosis. The increase in TRPV4-mediated TNF-α expression occurred through the nuclear factor kappa-light chain enhancer of activated B cell pathway activation, which was inhibited by statins. Herein, we showed that statins can modulate gliosis and TNF-α expression in Müller cells, protecting RGCs. These data further support the neuroprotective effect of statins, promoting them as a potential treatment for glaucoma.

Progressive Changes in the Anterior Segment and Their Impact on the Anterior Chamber Angle in Primary Angle Closure Disease.

PURPOSE: To investigate longitudinal changes in the anterior segment (AS) using serial optical coherence tomography (OCT) images and determine the impact of these changes on the anterior chamber angle (ACA) in eyes with primary angle closure disease (PACD) treated with laser peripheral iridotomy (LPI). DESIGN: Retrospective clinical cohort study. METHODS: This study included 103 patients with PACD who underwent LPI and were followed up by a mean 6.7 ± 1.7 AS-OCT examinations for a mean 6.5 ± 2.9 years. Temporal changes in AS-OCT parameters, including anterior chamber depth (ACD), angle opening distance (AOD750), angle recess area (ARA750), iris thickness (IT750), lens vault (LV), and pupil diameter (PD), were analyzed by multivariate linear mixed effects models (LMEMs). RESULTS: Multivariate LMEMs showed that decrease in AOD750 was not significant (-1.59 µm/y, P = .222); however, ARA750 decreased over time (-2.3 × 103 µm2/y, P = .033) and SSA showed marginal significance (-0.20°/y, P = .098), and LV increased significantly (11.6 µm/y, P < .001) after LPI. Mean LV change was negatively associated with AOD750, ARA750, and SSA, whereas PD was negatively associated with ARA750 (P < .001 each). PD decreased with aging (-13.7 µm/y, P = .036), accompanied by thinning of IT750 (-1.7 µm/y, P = .063). CONCLUSIONS: LV tends to increase with aging, which contributes to the shallowing of the anterior chamber and narrowing of ACA in PACD eyes treated with LPI. In the meantime, pupillary constriction and subsequent peripheral iris thinning associated with aging could possibly offset the effect of ACA narrowing.

Topographic comparison of the retinal microvascular changes between patients with compressive and glaucomatous optic neuropathies.

We investigated the difference in optical coherence tomography angiography characteristics between the patients with compressive optic neuropathy (CON, n = 26) and glaucomatous optic neuropathy (GON, n = 26), who were matched for the severity of visual field defect. The peripapillary retinal nerve fiber layer (pRNFL) thickness in the nasal and temporal sectors was thinner in the CON group, whereas the inferior pRNFL thickness was thinner in the GON group. Accordingly, the CON group had lower peripapillary vessel density (pVD) in the nasal and temporal sectors, and the GON group in the inferior sector. In the macular area, the CON group had a thinner macular ganglion cell-inner plexiform layer in the superior and nasal sectors, whereas the GON group in the inferior sector. However, the CON group did not have a lower macular VD than the GON group in any sector, whereas the GON group exhibited lower superficial capillary plexus VD in the superior, inferior, and temporal sectors. Comparison of the structure-vasculature correlation revealed a significant difference in the nasal and temporal peripapillary areas and superior and nasal macular sectors; a decrease in VD was greater in the GON group than in the CON group when the comparable structural change occurred.

Rate of Retinal Nerve Fiber Layer Thinning in Glaucomatous Eyes With Optic Disc and Parapapillary Deep-Layer Microvasculature Loss.

PRCIS: Microvasculature dropout in the parapapillary choroidal layer was a more important biomarker of glaucomatous nerve fiber layer thinning when it presented with deep-layer microvasculature of the optic disc rather than when it presents by itself. PURPOSE: To characterize open angle glaucoma eyes with optic nerve head deep-layer microvasculature dropout (MvD-D) and parapapillary choroidal layer microvasculature dropout (MvD-P) and compare their retinal nerve fiber layer (RNFL) thinning rate. MATERIAL AND METHODS: This study included 122 open angle glaucoma eyes that underwent ≥5 serial spectral-domain optical coherence tomography scans during a mean follow-up of 5.4 years. Swept-source optical coherence tomography angiography was used to evaluate MvD-P and MvD-D. Subjects were classified into 3 groups according to the presence of MvD-P and MvD-D: (1) no dropout (n=37); (2) solely MvD-P (n=40), and (3) both MvD-P and MvD-D (n=45). The RNFL thinning rate was compared among the 3 groups, and the associated factors were assessed by Cox proportional hazard analysis. RESULTS: RNFL thinning rates were highest in the group with both MvD-P and MvD-D, followed by the group with solely MvD-P and finally by the no dropout group (-0.24 vs. -0.65 vs. -1.20 µm/y, P <0.001). Thinner central corneal thickness [hazard ratio (HR)0.990, P =0.003], presence of disc hemorrhage (HR=1.802, P =0.035), and coexistence of MvD-P and MvD-D (HR=2.941, P <0.001) were the factors associated with RNFL thinning. CONCLUSIONS: The coexistence of MvD-P and MvD-D was associated with faster RNFL thinning than MvD-P alone or no dropout, which suggested that observing the optic disc deep microvasculature along with parapapillary choroidal layer using Swept-source optical coherence tomography angiography may be clinically relevant in monitoring glaucoma progression.

Association Between Optic Disc Perfusion Determined by Swept-Source Optical Coherence Tomography Angiography and Visual Field Progression in Glaucoma.

PRCIS: Reduced optic disc vessel density determined by swept-source optical coherence tomography angiography (SS-OCTA) was associated with visual field (VF) deterioration in glaucomatous eyes, which suggested that this parameter can be a potential biomarker that correlates well with functional deterioration. PURPOSE: The purpose of this study was to identify the association between optic disc perfusion evaluated by SS-OCTA and VF progression in primary open angle glaucoma (POAG) eyes. METHODS: A total of 266 POAG eyes of 266 patients (5.4 y of mean follow-up) were included. Optic nerve head SS-OCTA was performed to evaluate the optic disc vessel density (dVD), parapapillary choroidal vessel density (pcVD), choroidal microvascular dropout (cMvD), and optic disc microvascular dropout (dMvD). VF progression was defined using Early Manifest Glaucoma Trial criteria. Factors associated with VF worsening were assessed by Cox proportional hazard analysis. RESULTS: Eighty (30.1%) out of the 266 POAG eyes showed VF progression. The progression group showed a significantly higher proportion of disc hemorrhage, cMvD, and dMvD but lower dVD and pcVD than the stable group (all P <0.05). Considering the strong association between the parameters [dMvD vs. dVD ( r = -0.757, P =0.010], cMvD vs. pcVD ( r = -0.745, P =0.012), dMvD vs. cMvD ( r = 0.802, P <0.001], dVD vs. pcVD ( r = 0.862, P <0.001), CMvD vs. dVD ( r = -0.698, P =0.031), and dMvD vs. pcVD ( r = -0.688, P =0.034)], 6 models with different combinations of covariates compensating for multicollinearity were developed. Younger age, presence of disc hemorrhage, and lower dVD were consistently associated with progression in all models that included these parameters. CONCLUSIONS: Optic disc perfusion, represented as dVD, may be a useful biomarker that correlates well with functional deterioration in POAG eyes.

Change of Choroidal Microvasculature Dropout After Trabeculectomy as Assessed by Optical Coherence Tomography Angiography.

PRCIS: Reduction in the angular circumference of choroidal microvascular dropout (CMvD AC) was found in POAG patients after trabeculectomy. Greater percentage of IOP reduction was significantly associated with decreased CMvD AC. PURPOSE: The purpose of this study was to investigate the change of choroidal microvasculature dropout (CMvD) after trabeculectomy and its associated factors in primary open angle glaucoma (POAG) eyes using optical coherence tomography angiography. METHODS: Fifty eyes of 50 POAG participants who had preoperative CMvD and underwent trabeculectomy were prospectively enrolled. Angular circumference (AC) of CMvD was determined from choroidal layer images by optical coherence tomography angiography preoperatively and at postoperative 1 year. The cutoff for significant AC of CMvD decrease was determined by the Bland-Altman method, and accordingly, patients were divided into 2, decreased and stable/increased CMvD AC groups. Changes in intraocular pressure (IOP) and CMvD AC were compared between the groups preoperatively and at postoperative 1 year. Factors associated with CMvD AC decrease were assessed by linear regression analysis. RESULTS: The cutoff for significant CMvD AC decrease was 3.58 degrees; accordingly, 26 eyes (52.0%) were categorized as decreased CMvD AC group. No significant intergroup differences in baseline characteristics were found. However, the decreased CMvD AC group presented significantly lower IOP (10.7±3.7 vs. 12.9±2.6 mm Hg, P =0.022), lower CMvD AC (32.03±33.95% vs. 53.44±39.33%, P =0.044), and higher parapapillary choroidal vessel density ( P =0.014) compared with the increased/stable CMvD AC group at postoperative 1 year. The greater percentage of IOP reduction was significantly associated with decreased CMvD AC ( P =0.046). CONCLUSIONS: CMvD AC reduction associated with IOP lowering was found after trabeculectomy. The long-term clinical relevance of postoperative CMvD reduction should be further investigated.

Optical Coherence Tomography Angiography of the Retinal Circulation Following Trabeculectomy for Glaucoma.

PRCIS: Despite successful trabeculectomy, eyes with similar levels of peripapillary and macular vessel densities but with worse preoperative visual field mean deviations may experience functional and vascular decline after surgery. PURPOSE: To evaluate the retinal microcirculation change after trabeculectomy according to glaucoma severity using optical coherence tomography angiography (OCTA). METHODS: We enrolled 59 eyes of primary open angle glaucoma patients who underwent trabeculectomy. The eyes were categorized into 3 groups by preoperative visual field (VF) mean deviation (MD), group 1: MD>-12.0 dB, group 2: MD -12.0 to -20.0 dB, and group 3: MD <-20.0 dB. OCTA was performed preoperatively and 1 year after trabeculectomy. The differences in the radial peripapillary capillary vessel density (pVD) and macular VD between preoperative and postoperative assessment were analyzed and compared in each group. Factors associated with the VD change after trabeculecomy were determined using linear regression analysis. RESULTS: Mean postoperative IOP and IOP reduction did not differ among the 3 groups after trabeculectomy. Preoperative pVD (37.2 vs. 36.6%, P =1.00) and macular VD (39.0 vs. 38.4%, P =1.00) did not differ between groups 1 and 2. Group 1 and 3 showed no changes in VD parameters after trabeculectomy (all, P >0.05). However, group 2 showed statistically significant decreases in pVD (36.6 vs. 32.9%, P <0.001) and macular VD (38.4 vs. 36.0%, P =0.010) after trabeculectomy. The reduction of pVD was associated with a decrease of IOP (Coefficient (ß); 0.14, P =0.032) and VF MD (ß; 0.15, P =0.0116) in group 2, respectively. CONCLUSION: Following successful trabeculectomy surgery for uncontrolled glaucoma with similar IOP reduction, glaucoma eyes with advanced visual field loss showed reduced pVD and macular VD measured by OCT-A. These findings may be relevant to disease progression.

Reduced intradisc vessel density is associated with optic disc hemorrhage in eyes with primary open-angle glaucoma.

We sought to investigate the association between optic nerve head (ONH)/choroidal microvasculature perfusion and optic disc hemorrhage (ODH) in eyes with primary open-angle glaucoma (POAG) using swept-source optical coherence tomography angiography (SS-OCTA). A total of 266 POAG eyes (59 with a single instance of ODH, 40 with a history of recurrent ODH, and 167 eyes without ODH) with a mean follow-up of 5.4 years were included. Intradisc vessel density (VD), parapapillary choroidal VD, optic disc microvascular dropout (MvD), and choroidal microvascular dropout (CMvD), were evaluated on a 3 × 3 mm SS-OCTA image of ONH and compared between eyes with and without ODH. Recurrent ODH was defined as occurrence 1 year after first ODH detection during the total follow-up period. Logistic regression analyses were performed to investigate factors associated with ODH. The prevalence of CMvD, optic disc MvD, and ß-parapapillary atrophy were not different among the no ODH, single ODH, and recurrent ODH groups. Eyes with ODH had lower intradisc VDs than those without ODH (P = 0.021), but no difference was found in intradisc VDs between the single and recurrent ODH groups (P = 0.977). Better VF MD at baseline (odds ratio [OR], 1.150; 95% confidence interval [CI], 1.055-1.254; P = 0.002) and lower intradisc VD (OR, 0.863; 95% CI, 0.812-0.918; P < 0.001) were associated with ODH occurrence. Among POAG eyes, those with ODH had lower intradisc VDs than those without ODH. POAG eyes in an earlier disease stage or those with lower intradisc VDs should be monitored for the possibility of ODH occurrence.

Structural and vascular changes in glaucoma with single-hemifield defect: predictors of opposite hemifield visual field progression.

PURPOSE: To investigate longitudinal changes in optic nerve head (ONH) superficial vessel density (VD), macular VD, circumpapillary retinal nerve fiber layer (RNFL) thickness, and macular ganglion cell-inner plexiform layer (GCIPL) thickness, and their associations with future VF defects in unaffected hemifields of primary open angle glaucoma (POAG) eyes with baseline VF defect confined to a single hemifield. METHODS: This retrospective observational study included 61 POAG eyes with VF defect confined to a single hemifield monitored over a mean follow-up time of 2.7 years. Development of VF defect in opposite hemifield was defined based the Early Manifest Glaucoma Trail criteria. Each eye was classified into either "conversion" or "no conversion" groups according to development of VF defect in the unaffected hemifield. The rates of longitudinal changes in VD and structure parameters in each hemiretina were compared between the two groups. A Cox proportional hazard model was used to identify potential risk factors for VF conversion in the unaffected hemifield. RESULTS: Among 61 eyes, 17 eyes (27.9%) were classified as "conversion" and 44 eyes (72.1%) were classified as "non-conversion" groups. The conversion group exhibited significantly greater rates of both VD and structural changes in both hemiretinas. In Cox proportional hazard model, greater rate of change in GCIPL thickness, ONH superficial VD, and macular VD of both hemiretinas and greater rate of change in RNFL thickness of the unaffected hemiretina were identified as risk factors for VF conversion in the unaffected hemifield. CONCLUSIONS: Monitoring progressive changes in VD and structural parameters effectively predict future VF defect in the opposite hemifields of POAG eyes with single-hemifield defects.

Assessment of Iridotrabecular Contact and Its Association With Intraocular Pressure After Phacoemulsification in Primary Angle Closure.

PURPOSE: To investigate the association between the quantitative assessment of iridotrabecular contact (ITC), measured by swept-source anterior segment optical coherence tomography (SS AS-OCT), and intraocular pressure (IOP) control after phacoemulsification in patients with primary angle closure disease (PACD). DESIGN: Retrospective, clinical cohort study. METHODS: Preoperative and postoperative anterior chamber angle parameters were measured using SS AS-OCT. IOP was measured preoperatively and until 6 months postoperatively. Percent IOP reduction and fluctuation after surgery were calculated, and their relationships with SS AS-OCT parameters were assessed by correlation analyses and locally weighted scatterplot smoothing (LOWESS) regression with change-point analysis. RESULTS: A total of 51 eyes of 51 PACD patients were included. Preoperative ITC index and area (r = 0.626, r = 0.551), as well as changes in ITC index and area (r = 0.632, r = 0.543) after surgery, were significantly correlated with postoperative IOP reduction, after adjusting for age and gender (all P <.001). Higher postoperative ITC index (r = 0.405, P = .005) and ITC area (r = 0.460, P = 0.001) were associated with greater postoperative IOP fluctuations. Change points on LOWESS curves were observed for preoperative ITC index (33.0%) and change in ITC index (27.0%) and percent IOP reductions were significantly correlated with them above (ß = 0.386, ß = 0.664, all P < .001) but not below the change points. CONCLUSIONS: Quantitative assessment of circumferential ITC can predict postoperative IOP control after phacoemulsification, and thus it may be used as a reference for determining lens extraction in PACD eyes.

Comparison of surgical outcomes with and without Ologen collagen matrix augmentation during XEN gel stent implantation.

BACKGROUND: To compare the surgical outcomes and postoperative complications with and without Ologen collagen matrix augmentation during XEN gel stent implantation. METHODS: We retrospectively analyzed patients who underwent XEN gel stent implantation with an ab externo technique. The amount of intraocular pressure (IOP) reduction, percentage of postoperative complications and additional management, and surgical success defined as IOP reduction greater than 20% compared with the preoperative IOP measurement were compared between Ologen-augmented and non-augmented groups. Groups of patients who underwent XEN gel stent implantation alone and combined with phacoemulsification were analyzed separately. RESULTS: A total 103 eyes of 103 participants were included. Of those, 72 eyes underwent standalone XEN gel stent implantation: 42 eyes with Ologen augmentation (Oloxen group) and 30 eyes without Ologen augmentation (Xen group). Thirty-one eyes underwent XEN gel stent implantation with phacoemulsification: 19 eyes with Ologen augmentation (Phaco-Oloxen group) and 12 eyes without Ologen augmentation (PhacoXen group). The surgical success rate at six months postoperatively was not different between the Oloxen and Xen groups (56.4% vs 43.3%, P > 0.05) or between the Phaco-Oloxen group and PhacoXen group (57.9% vs 41.7%, P > 0.05). The prevalence of postoperative hypotony, 5-fluorouracil injections, use of anti-glaucoma medications, bleb needling, and additional glaucoma surgeries was not different between the Oloxen and Xen groups or between the Phaco-Oloxen and PhacoXen groups when assessed six months postoperatively. CONCLUSIONS: All groups showed significant IOP reduction after XEN gel stent implantation, but there was no significant difference between the Ologen collagen matrix augmented and non-augmented groups in surgical outcomes.

Development of Cumulative Order-Preserving Image Transformation Based Variational Autoencoder for Anterior Segment Optical Coherence Tomography Images.

Purpose: To develop a variational autoencoder (VAE) suitable for analysis of the latent structure of anterior segment optical coherence tomography (AS-OCT) images and to investigate possibilities of latent structure analysis of the AS-OCT images. Methods: We retrospectively collected clinical data and AS-OCT images from 2111 eyes of 1261 participants from the ongoing Asan Glaucoma Progression Study. A specifically modified VAE was used to extract six symmetrical and one asymmetrical latent variable. A total of 1692 eyes of 1007 patients were used for training the model. Conventional measurements and latent variables were compared between 74 primary angle closure (PAC) and 51 primary angle closure glaucoma (PACG) eyes from validation set (419 eyes of 254 patients) that were not used for training. Results: Among the symmetrical latent variables, the first three and the last demonstrated easily recognized features, anterior chamber area in η1, curvature of the cornea in η2, the pupil size in η3 and corneal thickness in η6, whereas η4 and η5 were more complex aggregating complex interactions of multiple structures. Compared with PAC eyes, there was no difference in any of the conventional measurements in PACG eyes. However, values of η4 were significantly different between the two groups, being smaller in the PACG group (P = 0.015). Conclusions: VAE is a useful framework for analysis of the latent structure of AS-OCT. Latent structure analysis could be useful in capturing features not readily evident with conventional measures. Translational Relevance: This study suggested that a deep learning-based latent space model can be applied for the analysis of AS-OCT images to find latent characteristics of the anterior segment of the eye.

Progression detection capabilities of circumpapillary and macular vessel density in advanced glaucomatous eyes.

This study investigated the progression detection capabilities of circumpapillary and macular vessel density (cpVD and mVD) in advanced primary open angle glaucoma (POAG) eyes using the rates of change in VD (trend-based analysis) and variability limits derived from healthy eyes. (event-based analysis) This study included 75 POAG eyes [visual field (VF) mean deviation < - 10 decibels, mean follow-up; 2.3 years] and 33 healthy eyes. Of 75 POAG eyes, 17 (22.7 %) and 58 eyes (77.3 %) were classified into the VF progression and stable groups, respectively. The VF progression group showed significantly faster VD loss than the stable group. (cpVD; - 1.76 vs. - 0.84 %/year, mVD; - 1.10 vs. - 0.47 %/year, P < 0.05) However, the rates of change in circumpapillary retinal nerve fiber layer and macular ganglion cell complex thickness were similar between the groups. (cpRNFLT; - 0.67 vs. - 0.53 [Formula: see text]m/year, GCCT; - 0.48 vs. - 0.12 [Formula: see text]m/year, P > 0.05) Event-based analysis showed stronger agreement between VD and VF progression (cpVD; kappa value (k) = 0.630, mVD; k = 0.667, P < 0.05) than that between structure and VF progression. (cpRNFLT; k = 0.111, GCCT; k = 0.194, P > 0.05). In conclusion, VD loss showed better progression detection capabilities than structural loss in advanced POAG eyes. Detection of cpVD and mVD loss may be useful for detecting progression in the advanced stages of POAG to complement other reference standard strategies.

Effect of Optic Disc Tilt on the Measurement of Peripapillary Vessel Density Using Optical Coherence Tomography Angiography.

PRCIS: Eyes with tilted disc (TD) had significantly lower peripapillary vessel density (pVD) and lower long-term measurement reproducibility in optical coherence tomography angiography (OCTA). After adjusting for confounding factors, disc tilt still contributed to the reduction of pVD in most sectors. PURPOSE: The purpose of this study was to investigate the effect of optic disc tilt on the measurement of sectoral pVD by OCTA and on the long-term measurement reproducibility. MATERIALS AND METHODS: This retrospective observational case-control study included 70 healthy eyes. Average and 8-sector pVDs and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were obtained from OCTA at 2 visits at 1-year intervals. The disc tilt was quantified by ovality ratio (the longest/shortest disc diameter) on fundus photography, with a TD defined as an ovality ratio ≥1.3. pVD and pRNFL thickness of each sector were compared in the TD and nontilted disc (NTD) groups. Long-term reproducibility was assessed by the intraclass correlation coefficients (ICCs) for both groups. Factors associated with pVD were evaluated by univariable and multivariable linear regression analyses. RESULTS: Thirty-five eyes each had TD and NTD. Average pVD was lower in the TD than in the NTD group (47.0%±3.5% vs. 51.7%±2.8%, P <0.001), as were pVDs in all 8 sectors. The long-term reproducibilities of average and sectoral pVD measurements were lower in the TD (ICC: 0.46-0.83) than in the NTD (ICC: 0.67-0.96) group. Disc tilt was significantly associated with pVD in average and all sectors except for nasal inferior sector after adjusting for axial length, pRNFL thickness, and signal strength index of OCTA image. CONCLUSION: OCTA-measured pVD and the long-term reproducibility were lower in eyes with TD than NTD. These findings should be considered when interpreting OCTA-measured pVD.

Factors Associated with Deterioration of Primary Angle Closure after Lens Extraction.

The purpose of the study was to explore factors associated with glaucomatous deterioration in eyes with primary angle closure (PAC) after lens extraction, including PAC suspect (PACS), PAC, and PAC glaucoma (PACG). We retrospectively analyzed data of 77 eyes with PACS, PAC, and PACG that underwent lens extraction with more than 2 years postoperative follow-up. Postoperative glaucoma progression was analyzed by either structural (optic disc/retinal nerve fiber layer (RNFL) photographs or optical coherent tomography (OCT)) or functional (visual field (VF)) criterion. Cox proportional hazard analysis (hazard ratio (HR)) was used to determine risk factors for progression using uni-and multivariate analysis. The analysis was conducted in groups with or without glaucomatous optic neuropathy (PACS/PAC vs. PACG). Forty-one eyes with PACS/PAC and 36 eyes with PACG were included. The mean postoperative follow-up period was 3.5 ± 1.4 years. Intraocular pressure (IOP) was reduced postoperatively from 23.1 ± 14.4 to 13.4 ± 2.1 mmHg. In the PACS/PAC group, seven eyes (17.0%) showed structural progression, but none showed progression in VF. Preoperative RNFL thickness was the only risk factor for structural progression (HR = 0.928, p = 0.002) in the PACS/PAC group. In the PACG group, 24 eyes (66.7%) showed structural progression and 12 eyes (33.3%) showed VF progression. Thinner preoperative RNFL thickness (HR = 0.964, p = 0.043) and high postoperative IOP fluctuation (HR = 1.296, p = 0.011) were significantly associated with VF progression; none of the factors were associated with structural progression. Angle closure eyes with thinner baseline RNFL thickness and higher postoperative IOP fluctuation may require careful follow-up for glaucoma progression after lens extraction.

Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation.

We characterized Müller cell gliosis induced by the activation of transient receptor potential vanilloid-type 4 (TRPV4) and assessed whether statins could modulate the gliosis. The human Müller cell line, MIO-M1, was used to analyze the gliosis caused by glaucomatous stimulation. To induce Müller gliosis in MIO-M1 cells, GSK101 was used to activate TRPV4, and Müller gliosis was evaluated by analyzing vimentin, nestin, and glial fibrillary acidic protein (GFAP) expression. The expression level of TNF-α was determined by ELISA. To evaluate the GSK101 activation of the NF-κB pathway, p65 phosphorylation was measured by Western blotting, and the nuclear translocation of p65 and IκBα phosphorylation were assessed by immunostaining. To assess the effect of statins on MIO-M1 gliosis, cells were pretreated for 24 h with statins before GSK101 treatment. Vimentin, nestin, and GFAP expression were upregulated by GSK101, while statins effectively inhibited them. The expression of TNF-α was increased by GSK101. The phosphorylation and nuclear translocation of p65 and IκBα phosphorylation, which occurs prior to p65 activation, were induced. Statins suppressed the GSK101-mediated phosphorylation of IκBα and p65 translocation. Statins can mitigate gliosis in the human Müller cell line. Because TRPV4 activation in Müller cells reflects glaucoma pathophysiology, statins may have the potential to prevent RGC death.

Comparison of Vision-related Quality of Life Between Normal Tension Glaucoma and Primary Open-angle Glaucoma.

PRCIS: Although there was little difference in overall vision-related quality of life (VRQOL) between patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) after controlling for confounding factors, POAG tended to have poorer VRQOL, especially in social functioning and dependency, than NTG. PURPOSE: The fundamental goal of treatment of patients with glaucoma is to preserve their VRQOL. The aim of this study was to compare VRQOL between patients with NTG and those with POAG. MATERIALS AND METHODS: The self-reported National Eye Institute Visual Function Questionnaire (NEI VFQ-25) survey was performed, including clinical, demographic, and socioeconomic data from 506 Korean patients with NTG and 287 with POAG. The mean deviation of the integrated binocular visual field was calculated using the best location method. The NEI VFQ-25 results were evaluated by Rasch analysis to control item difficulty and variation in individual response ability. Propensity score matching was used to control for various confounding factors affecting VRQOL. RESULTS: Although patients with POAG tended to have worse VRQOL than those with NTG, there was no statistically significant between-group difference in ocular pain, near and distance activities, mental health, role difficulties, ability to drive, and the overall composite score. However, the social functioning (P=0.016) and dependency (P=0.026) were significantly poorer in POAG patients. CONCLUSIONS: Overall VRQOL in patients with NTG and POAG was found to be similar. However, social functioning and dependency were significantly worse in those with POAG. These findings are relevant to supporting glaucoma patients.

Association of Epiretinal Membrane With Pseudoexfoliation Glaucoma and Long-term Factors Affecting Visual Function.

PRCIS: Epiretinal membrane (ERM) tended to deteriorate more in pseudoexfoliation eyes with than without glaucoma. Incremental change in central macular thickness (CMT) induced by ERM deterioration affected longitudinal visual function in pseudoexfoliation glaucoma (PXG) eyes. PURPOSE: The aim was to investigate longitudinal changes in the ERM and their association with glaucoma in patients with pseudoexfoliation syndrome (PXS) and to identify factors associated with the changes in ERM and visual field (VF). PARTICIPANTS: One hundred two eyes with PXG and 32 eyes with nonglaucomatous pseudoexfoliation (ngPX) (mean 8.1±2.6 years of follow-up). METHODS: Two observers independently assessed the presence and staging of ERM (stages 1, 2, and ≥3) on serial macular images of spectral-domain optical coherence tomography. Clinical characteristics were compared in eyes with ERM (+) and (-) in both groups. The relationship between putative factors and changes in ERM was determined using logistic regression analysis. Prognostic factors of VF worsening were assessed by Cox proportional hazard analysis. RESULTS: Of the 102 eyes with PXG, 22 (21.6%) had an ERM at baseline; of the latter, 6 eyes deteriorated (all from stage 1 to 2) and 3 eyes with PXG developed new ERM during follow-up. Of the 32 ngPX eyes, 8 (25%) had an ERM at baseline, with none changing over time. The presence of glaucoma was marginally associated with ERM deterioration (odds ratio: 1.061, P =0.064). Incremental change in CMT was the only factor associated with VF progression (hazard ratio: 1.040, P =0.029) in PXG eyes. CONCLUSIONS: ERM tended to deteriorate more in PXS eyes with than without glaucoma. Incremental change in CMT induced by ERM deterioration affected longitudinal visual function in PXG eyes.

Development of a ß-Variational Autoencoder for Disentangled Latent Space Representation of Anterior Segment Optical Coherence Tomography Images.

PURPOSE: To investigate the feasibility of extracting a low-dimensional latent structure of anterior segment optical coherence tomography (AS-OCT) images by use of a ß-variational autoencoder (ß-VAE). METHODS: We retrospectively collected 2111 AS-OCT images from 2111 eyes of 1261 participants from the ongoing Asan Glaucoma Progression Study. After hyperparameter optimization, the images were analyzed with ß-VAE. RESULTS: The mean participant age was 64.4 years, with mean values of visual field index and mean deviation of 86.4% and -5.33 dB, respectively. After experiments, a latent space size of 6 and ß value of 53 were selected for latent space analysis with ß-VAE. Latent variables were successfully disentangled, showing readily interpretable distinct characteristics, such as the overall depth and area of the anterior chamber (η1), pupil diameter (η2), iris profile (η3 and η4), and corneal curvature (η5). CONCLUSIONS: ß-VAE can successfully be applied for disentangled latent space representation of AS-OCT images, revealing the high possibility of applying unsupervised learning in the medical image analysis. TRANSLATIONAL RELEVANCE: This study demonstrates that a deep learning-based latent space model can be applied for the analysis of AS-OCT images.