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.

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.

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.

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.

Neuroprotective Effect of Statins in a Rat Model of Chronic Ocular Hypertension.

Glaucoma is an optic neuropathy in which the degeneration of retinal ganglion cells (RGCs) results in irreversible vison loss. Therefore, neuroprotection of RGCs from glaucomatous afflictions is crucial for glaucoma treatment. In this study, we aimed to investigate the beneficial effects of statins in the protection of RGCs using a rat model. Glaucomatous injury was induced in rats by chronic ocular hypertension (OHT) achieved after performing a circumlimbal suture. The rats were given either statins such as simvastatin and atorvastatin or a solvent weekly for 6 weeks. Retina sections underwent hematoxylin and eosin, Brn3a, or cleaved casepase-3 staining to evaluate RGC survival. In addition, modulation of glial activation was assessed. While the retinas without statin treatment exhibited increased RGC death due to chronic OHT, statins promoted the survival of RGCs and reduced apoptosis. Statins also suppressed chronic OHT-mediated glial activation in the retina. Our results demonstrate that statins exert neuroprotective effects in rat retinas exposed to chronic OHT, which may support the prospect of statins being a glaucoma treatment.

Patterns of Progressive Ganglion Cell-Inner Plexiform Layer Thinning in Glaucoma Detected by OCT.

PURPOSE: To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). DESIGN: Longitudinal, retrospective, observational study. PARTICIPANTS: Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. METHODS: Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. MAIN OUTCOME MEASURES: Spatial characteristics and patterns of progressive GCIPL thinning. RESULTS: Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. CONCLUSIONS: The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression.

Ganglion Cell-Inner Plexiform Layer Change Detected by Optical Coherence Tomography Indicates Progression in Advanced Glaucoma.

PURPOSE: To examine the performance of Guided Progression Analysis (GPA; Carl Zeiss Meditec, Dublin, CA) in spectral-domain optical coherence tomography (OCT) in detecting progressive thinning of ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) in glaucoma. DESIGN: Longitudinal, observational study. PARTICIPANTS: A total of 196 eyes of 123 primary open-angle glaucoma patients (mean follow-up, 5.0 years). METHODS: Macular GCIPL and peripapillary RNFL thicknesses were measured by Cirrus HD-OCT (Zeiss, Dublin, CA), and progressive GCIPL and RNFL thinning were assessed by GPA. The reference standard of glaucoma progression was determined by visual field (VF) progression. Glaucomatous eyes were classified into mild (117 eyes) or moderate to advanced (79 eyes) groups based on VF defects. Ganglion cell-inner plexiform layer and RNFL thinning rates were compared between progressors and nonprogressors. Visual field survival estimates in eyes with and without progressive GCIPL and RNFL thinning were evaluated by Kaplan-Meier survival analysis and compared with the log-rank test. MAIN OUTCOME MEASURES: Progressive GCIPL and RNFL thinning assessed by OCT GPA. RESULTS: Seventy-six eyes (38.8%) and 43 eyes (21.9%) demonstrated progressive GCIPL and RNFL thinning, respectively, and 48 eyes (24.5%) were classified as progressors by reference standard. The rate of change in the average GCIPL thickness was significantly higher in progressors (-1.05±0.98 µm/year for mild glaucoma and -0.66±0.30 µm/year for moderate to advanced glaucoma) than in nonprogressors (-0.47±0.54 µm/year for mild glaucoma and -0.31±0.50 µm/year for moderate to advanced glaucoma), regardless of glaucoma severity (P < 0.05). Eyes with progressive GCIPL thinning had lower VF survival estimates than eyes without, regardless of glaucoma severity. However, the rate of change in the average RNFL thickness did not differ significantly in moderate to advanced glaucoma (P = 0.765; -0.26±0.55 µm/year for progressors and -0.33±0.92 µm/year for nonprogressors), and VF survival estimates did not differ significantly between eyes with and without progressive RNFL thinning in moderate to advanced glaucoma (P = 0.781). CONCLUSIONS: Ganglion cell-inner plexiform layer GPA provides a new approach for evaluating glaucoma progression. It may be more useful for detecting progression in the advanced stages of glaucoma than RNFL GPA.

Subclassification of Primary Angle Closure Using Anterior Segment Optical Coherence Tomography and Ultrasound Biomicroscopic Parameters.

PURPOSE: To classify eyes with primary angle closure (PAC) in terms of the features visualized using anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM). DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 73 eyes of 73 patients with PAC. METHODS: Participants' eyes that had undergone laser peripheral iridotomy (LPI) were imaged using AS-OCT and UBM under the same lighting conditions. Anterior chamber depth, anterior chamber width, iris cross-sectional area, peripheral iris thickness, iris curvature, lens vault (LV), and angle opening distance 500 µm from the scleral spur (SS) were determined using the AS-OCT image; trabecular-ciliary process angle (TCA), trabecular-ciliary process distance (TCPD), and ciliary body (CB) thickness 1 mm posterior to the SS were estimated on the UBM image using ImageJ software (Wayne Rasband, National Institutes of Health, Rockville, MD). Iris insertion, iris angulation, iris convexity, presence of ciliary sulcus, irido-angle contact, and CB orientation assessed on the UBM image were included. Partitioning around the medoids algorithm was used for cluster analysis based on the parameters obtained using AS-OCT and UBM. Axial length and pupil diameter were incorporated into statistical models. MAIN OUTCOME MEASURES: Clinical and anatomic characteristics were compared between the clusters, as classified using the partitioning around medoids algorithm method. RESULTS: Cluster analysis revealed that 2-group clustering produced the best results. The 2 clusters, which were defined in terms of parameters obtained using AS-OCT and UBM, showed differences in iris curvature (0.16±0.08 vs. 0.11±0.04 mm), TCA (91.0°±13.4° vs. 63.7°±6.2°), TCPD (0.99±0.22 vs. 0.78±0.16 mm), CB orientation (neutral/anterior, 35/13 vs. 0/25), and iris insertion (basal/middle/apical, 37/9/2 vs. 12/11/2). Pre-LPI intraocular pressure (IOP) (18.8±5.4 vs. 16.2±4.5 mmHg; P = 0.037) and percentage of IOP reduction after LPI (22.3%±17.9% vs. 8.3%±19.5%; P < 0.003) showed a significant difference between the 2 clusters. CONCLUSIONS: The most distinct difference between the 2 subgroups in the cluster analysis was TCA, suggesting that the position of the CB is important in subclassifying PAC. By using UBM, clinicians may obtain more clues about the mechanisms of PAC; in turn, they may learn to predict the IOP-lowering effects of LPI.

Statins reduce TGF-beta2-modulation of the extracellular matrix in cultured astrocytes of the human optic nerve head.

Statins are cholesterol lowering drugs and have shown beneficial effects on glaucoma. With regard to the mechanism of statin action on glaucoma, we investigated the effects of statins on transforming growth factor-beta 2 (TGF-ß2)-induced expression of extracellular matrix (ECM) proteins in human astrocytes of the optic nerve head (ONH) lamina cribrosa (LC). By using primary human ONH astrocytes, we found that both simvastatin and lovastatin inhibited TGF-ß2-mediated expression of ECM proteins such as connective tissue growth factor, collagen I, fibronectin, and plasminogen activator inhibitor-1. Suppression of ECM related proteins is due to inhibition of Smad2/3 activation as statins inhibit TGF-ß2-induced Smad2 phosphorylation and Smad2/3 nuclear accumulation. In ONH astrocytes, TGF-ß2 does not induce MAPK activation. In this study we found an anti-fibrotic effect of statins in human astrocytes of the ONH and identified TGF-ß2 as a mediator of statin action, which may support a beneficial role for statins in blocking glaucomatous axonal damage induced by ECM remodeling.

Optical coherence tomography angiography vessel density mapping at various retinal layers in healthy and normal tension glaucoma eyes.

PURPOSE: To investigate peripapillary vessel density at various spatial locations and layers in healthy and normal tension glaucoma eyes using optical coherence tomography angiography (OCTA). METHODS: A commercial OCTA device (AngioPlex; Carl Zeiss Meditec) was used to image microvasculature in a 6 × 6-mm optic disc region. Vessel densities of superficial and deep retinal layers were calculated using an automatic thresholding algorithm. Vessel density maps were plotted by averaging individual angiogram images. The spatial characteristics of vessel densities were analyzed at clock-hour sectors and in five 0.7-mm-thick concentric circles from a diameter of 2.0 to 5.5 mm. Areas under the receiver operating characteristics curves (AUCs) assessed the glaucoma diagnostic ability. RESULTS: Vessel density maps of superficial and deep retinal layers were significantly reduced at the 7 and 11 o'clock positions in glaucomatous eyes. In superficial layer, vessel density significantly decreased as the distance from the optic disc margin increased, except in the innermost circle (2.0-2.7-mm). There were significant differences in AUCs of superficial vessel density between innermost circle and the other outer circles. In the deep layer, the innermost circle showed significantly higher vessel density than the outer circles. Vessel density at 7 o'clock showed the best diagnostic performance (AUCs, 0.898 and 0.789) both in the superficial and deep layers. The innermost circle showed eccentric feature compared to the outer circles in terms of spatial characteristics and diagnostic ability. CONCLUSIONS: Understanding of the spatial characteristics of peripapillary vasculature may be helpful in clinical practice and determining the optimal measurement area of vessel density.

Optic disc and peripapillary retinal nerve fiber layer characteristics associated with glaucomatous optic disc in young myopia.

PURPOSE: To explore optic disc and peripapillary retinal nerve fiber layer (RNFL) features associated with glaucomatous optic disc (GOD) in young myopia. METHODS: Presence of GOD, optic disc tilt, and disc torsion were determined using fundus photographs. If the measured disc tilt ratio was >1.3, the optic disc was classified as tilted. Optic disc torsion was defined as a >15° deviation in the long axis of the optic disc from the vertical meridian. The average and four quadrants RNFL thicknesses were assessed using spectral domain optical coherence tomography (SD-OCT). Logistic regression analyses were performed to identify factors associated with the presence of GOD. RESULTS: Nine hundred and sixty myopic subjects were recruited from four refractive surgery clinic databases. The mean age was 26.6 ± 5.7 years and spherical equivalent (SE) was -5.5 ± 2.5 diopters. Among 960 eyes, 26 (2.7%) received GOD group classification. Among 934 normal eyes, 290 (31.0%) had titled optic discs. Eighteen eyes (69.2%) in the GOD group had tilted optic discs. When compared to normal eyes, the GOD group had significantly higher tilt ratios (1.4 ± 0.2 vs. 1.2 ± 0.1, p < 0.001) and less SE (-7.8 ± 2.7 vs. -5.4 ± 2.5 diopters, p < 0.001). Greater tilt ratio (odds ratio (OR) = 4.9, p < 0.001), less SE (OR = 0.708, p < 0.001), and thinner average RNFL (OR = 0.910, p = 0.001) were significantly associated with GOD. Among 934 normal eyes, 366 (39.2%) displayed disc torsion, while among 26 glaucomatous eyes, eight (30.8%) displayed disc torsion. CONCLUSIONS: Optic disc tilt was found in approximately one-third of young myopic eyes and was independently associated with the presence of GOD.

Glaucoma Structural and Functional Progression in American and Korean Cohorts.

PURPOSE: To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Three hundred thirteen eyes from 189 glaucoma and glaucoma suspects, followed up for an average of 38 months. METHODS: All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had 5 or more reliable visits. MAIN OUTCOME MEASUREMENTS: The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and disease severity, disease subtype (high- vs. normal-tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. RESULTS: The Korean cohort predominantly demonstrated normal-tension glaucoma, whereas the American cohort predominantly demonstrated high-tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thicker mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean, -0.71 µm/year vs. -0.24 µm/year; P < 0.01). There were no detectable differences in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. CONCLUSIONS: Ethnicity, baseline disease severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies.

Progression of primary open angle glaucoma in asymmetrically myopic eyes.

PURPOSE: To compare progression of primary open angle glaucoma (POAG) in asymmetrically myopic eyes within the same subject and evaluate whether the degree of myopia is related to glaucoma progression. METHODS: POAG patients with asymmetric myopia (axial length [AXL] ≥24 mm in both eyes, and the AXL difference between the right and left eyes to be ≥0.5 mm) were included. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer (RNFL) photographs or by serial visual field (VF) data. The progression rates of VF mean deviation (dB/year) and spectral domain optical coherence tomography measured RNFL thickness (µm/year) were compared between the more myopic eye (MME) and the less myopic eye (LME) within the same subject. RESULTS: A total of 55 patients (mean follow up period; 4.5 ± 1.0 years) were included. The mean AXL demonstrated a significant difference between MME and LME (26.3 ± 1.7 vs. 25.6 ± 1.7 mm; p = 0.036). The mean baseline VF MD (-3.8 ± 5.4 vs. -2.6 ± 4.7 dB; p = 0.21) and average RNFL thickness (77.5 ± 10.6 vs. 79.9 ± 12.3 µm; p = 0.36) did not differ between the MME and LME. Among the 55 patients, optic disc/RNFL photographic progression was noted in the MME in 15 patients, in the LME in 19 patients, and in both eyes in seven patients. VF progression was noted in the MME in seven patients, in the LME in seven patients, and in both eyes in four patients. The VF MD progression rates were -0.25 ± 0.34 dB/year in MME and -0.26 ± 0.34 dB/year in LME cases (p = 0.91). The mean progression rate of the average RNFL thickness also did not differ between the MME and LME (-0.59 ± 0.67 vs. -0.66 ± 0.72 µm/year, p = 0.68). CONCLUSIONS: The degree of myopia was not associated with glaucoma progression when assessing the same patient using either the VF or optic disc/RNFL criteria in asymmetrically myopic patients.

Antifibrotic effects of pirfenidone on Tenon's fibroblasts in glaucomatous eyes: comparison with mitomycin C and 5-fluorouracil.

PURPOSE: The purpose of this study was to evaluate the antifibrotic effects of pirfenidone (PFD) on primary cultured human Tenon's fibroblasts (HTFs) from primary open-angle glaucoma (POAG) eyes, compared to mitomicin C (MMC) and 5-fluorouracil (5-FU). MATERIALS AND METHODS: Samples of human Tenon's capsule were obtained during respective surgeries from three groups of patients: patients with cataract (CAT group), patients with POAG who underwent glaucoma filtration surgery (GFS) (POAG1 group), and patients with POAG who underwent GFS due to failed bleb of previous GFS (POAG2 group). Cell toxicity, cell migration, and the expression level of α-smooth muscle actin (α-SMA) protein were evaluated in primary cultured HTFs from the three patient groups after treatment (PFD, MMC, or 5-FU). RESULTS: Overall, cell viability after PFD treatment was higher compared to MMC treatment (82.3 ± 5.1 % vs 56.7 ± 3.8 %; p = 0.001) and comparable to 5-FU treatment (82.3 ± 5.1 % vs 85.7 ± 10.7 %, p = 0.214) at the same concentration (0.4 mg/ml). Both 0.3 mg/ml PFD and 0.1 mg/ml MMC inhibited cell migration compared to control (without treatment) cells (p = 0.014 and 0.005, respectively), while 0.2 mg/ml 5-FU showed the highest degree of cell migration among the three agents in the POAG1 group (PFD vs MMC vs 5-FU; 29.5 ± 2.1 % vs 34.5 ± 0.7 % vs 76.0 ± 8.5 %, PFD vs MMC; p = 1.000, PFD vs 5-FU; p = 0.008, MMC vs 5-FU; p = 0.011). PFD (0.1 or 0.3 mg/ml) and MMC (0.05 and 0.1 mg/ml) treatment significantly reduced the protein expression level of α-SMA in the POAG 1 group (all p < 0.05), and the α-SMA protein level following treatment with 0.3 mg/ml PFD was lower than that of 0.1 mg/ml MMC (p = 0.040). CONCLUSION: PFD showed less cytotoxicity compared to MMC. PFD and MMC inhibited cell migration and reduced α-SMA protein expression levels, while 5-FU showed neither inhibition of cell migration nor reduction in α-SMA expression level. These findings indicate PFD as a potential adjunctive antifibrotic agent to prevent bleb failure during GFS.

Lamina cribrosa depth according to the level of axial length in normal and glaucomatous eyes.

PURPOSE: To compare the lamina cribrosa (LC) depth of the optic nerve head in normal and glaucomatous eyes over a wide range of axial length (AXL). METHODS: A total of 402 eyes, including 210 normal and 192 glaucomatous eyes, were imaged by spectral domain optical coherence tomography. Normal and glaucomatous eyes were each divided into three subgroups according to the level of AXL; long (> 26 mm), mid-level (23-26 mm), and short (< 23 mm). Visual field mean deviation (VF MD), LC thickness, and LC depth were compared between normal and glaucomatous eyes in each of the AXL subgroups. These parameters were also compared between normal and glaucomatous eyes in the three AXL subgroups. Factors associated with LC depth in each AXL subgroup were evaluated by univariate and multivariate regression analyses. RESULTS: A comparison of the three AXL subgroups in normal eyes showed that the LC was thinnest in the long AXL subgroup (short; 189.7 ± 24.1 µm, mid-level; 179.9 ± 34.3 µm, long; 149.2 ± 36.2 µm, p < 0.001), but LC depth did not differ significantly in the three subgroups (short; 527.1 ± 144.4 µm, mid-level; 578.2 ± 163.5 µm, long; 594.4 ± 187.5 µm, p = 0.144). In glaucomatous eyes, glaucoma severity assessed by VF MD did not differ significantly among the three AXL subgroups (short; -6.99 ± 8.50 dB, mid-level; -6.40 ± 7.64 dB, long; -4.61 ± 5.22 dB, p = 0.168). However, LC depth was greater in the long than in the short AXL subgroup (679.5 ± 192.7 µm and 555.9 ± 134.1 µm, respectively, p = 0.004), although neither subgroup differed significantly in LC depth from the mid-level AXL subgroup (611.8 ± 162.3 µm, p = 0.385, p = 0.090). LC thickness was significantly different between normal and glaucomatous eyes (p < 0.001). LC depth was not different between normal and glaucomatous eyes in both short and mid-level AXL subgroups (p = 0.297, 0.222), but differed in the long AXL subgroup (p = 0.022). The presence of glaucoma was associated with greater LC depth only in the long AXL subgroup (p = 0.012). CONCLUSIONS: LC depth may vary according to the level of AXL in glaucomatous eyes with a similar level of glaucoma severity, with the greatest LC depth found in eyes with long AXL. Those findings suggest that glaucomatous optic disc cupping would manifest differently according to the level of AXL.

Effect of combined cataract surgery and ranibizumab injection in postoperative macular edema in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate whether intravitreal ranibizumab injection at cataract surgery prevents postoperative diabetic macular edema (PME) in patients with stable diabetic retinopathy without significant macular edema. METHODS: Eighty patients with cataract, stable diabetic retinopathy, and no significant macular edema were randomized to a sham group (cataract surgery only) or a group undergoing cataract surgery plus intraoperative ranibizumab injection. Best-corrected visual acuities, central subfield thickness, and total macular volume were assessed at baseline and 1 week, 1, 3, and 6 months postoperatively by spectral domain optical coherence tomography. Clinically meaningful PME (central subfield thickness increase >60 µm relative to baseline) was computed. RESULTS: The groups did not differ in baseline best-corrected visual acuity, central subfield thickness, and total macular volume. Compared with the ranibizumab injection group, the sham group had significantly larger central subfield thickness increases relative to baseline at 1 week and 1 month; larger total macular volume increases at all time points (P = 0.012, P = 0.005, P < 0.001, P < 0.001, P = 0.005, P = 0.017, respectively); higher PME frequency at 1 month (P = 0.019); and poorer best-corrected visual acuity improvement from baseline to 6 months after surgery (P = 0.046). CONCLUSION: In patients with stable diabetic retinopathy without significant macular edema, intravitreal ranibizumab injection at cataract surgery may prevent the postoperative worsening of macular edema and may improve the final visual outcome without affecting safety.

Anterior Chamber Angle and Intraocular Pressure Control After Phacoemulsification in Primary Angle Closure with Different Mechanisms.

PRECIS: Different mechanisms of angle closure represented distinct aspects of intraocular pressure (IOP) control after phacoemulsification. Classification of angle closure mechanisms is necessary for postoperative IOP management and glaucoma progression in primary angle closure eyes. PURPOSE: To investigate the relationship between the anterior chamber angle (ACA) characteristics, measured by swept-source anterior segment optical coherence tomography (SS AS-OCT), and intraocular pressure (IOP) control after phacoemulsification in eyes with primary angle closure disease (PACD) with different angle closure mechanisms. METHODS: PACD eyes were classified into 3 groups according to angle closure mechanisms using preoperative SS AS-OCT images; pupillary block (PB), plateau iris configuration (PIC), exaggerated lens vault (ELV). This retrospective, clinical cohort study included eighty-five eyes of 85 PACD patients: 34 with PB, 23 with PIC, and 28 with ELV. ACA parameters were measured preoperatively and 1 month postoperatively using SS AS-OCT. IOP measurements were performed preoperatively and during six months postoperatively. Postoperative IOP reduction and fluctuation were calculated, and their correlations with SS AS-OCT parameters were analyzed. RESULTS: PIC group showed the lowest postoperative IOP reduction compared to the other groups (P=0.023). Preoperative ACA measurements were significantly associated with postoperative IOP reduction in ELV and PB groups, while postoperative measurements were in PIC group. Preoperative and postoperative change of iridotrabecular contact (ITC) index and area were correlated with postoperative IOP reduction in PB and ELV groups but not in PIC group. Postoperative ITC index (P=0.031) and area (P=0.003) showed significant correlations with postoperative IOP fluctuation only in PIC group. CONCLUSIONS: SS AS-OCT parameters including ITC index and area showed different associations with postoperative IOP control, which should be considered in determination of lens extraction and treatment of PACD eyes.

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.

Evaluation of lamina cribrosa in pseudoexfoliation syndrome using spectral-domain optical coherence tomography enhanced depth imaging.

PURPOSE: To evaluate the features of the lamina cribrosa (LC) in pseudoexfoliation glaucoma (PXG) patients using enhanced depth imaging (EDI) of spectral-domain optical coherence tomography (SD OCT). The results were compared with those of patients with primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with PXG (n = 21) and POAG (n = 35) matched for age and visual field mean deviation (VF MD). METHODS: Participants were imaged using SD OCT. Lamina cribrosa thickness (LT) and anterior lamina cribrosa depth (ALD) were determined at 3 areas (mid superior, center, and mid inferior) by 2 examiners using an EDI mode of the optic nerve head. MAIN OUTCOME MEASURES: The LT and ALD were compared between PXG and POAG eyes. RESULTS: Mean ± standard deviation baseline untreated intraocular pressure was not significantly different between the 2 groups (PXG, 18.3 ± 8.2 mmHg; POAG, 15.3 ± 3.4 mmHg; P = 0.310). The mean VF MD was -12.7 ± 9.0 dB in the PXG group versus -11.6 ± 9.1 dB in the POAG group (P = 0.643). When compared with the POAG group, the PXG group demonstrated a significantly thinner LT in all 3 areas and a thinner mean LT (133.4 ± 14.5 µm in the POAG group vs. 121.3 ± 13.0 µm in the PXG group; P<0.001). Anterior lamina cribrosa depth did not demonstrate a significant difference in any of the 3 areas between both groups (mean ALD, 324.3 ± 91.9 µm in the POAG group vs. 358.7 ± 142.7 µm in the PXG group; P = 0.470). Of 21 eyes in the PXG group, 9 eyes demonstrated a unilateral clinical presentation. When we compared the PXG eyes and the apparently normal-looking fellow eyes of those 9 eyes, neither the LT nor ALD demonstrated a significant difference (P = 0.223 and P = 0.079, respectively). CONCLUSIONS: Eyes with PXG demonstrate a thinner LC compared with POAG eyes at similar levels of glaucoma severity. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Detection of glaucomatous progression by spectral-domain optical coherence tomography.

PURPOSE: To compare the rate of change of circumpapillary retinal nerve fiber layer (cRNFL) thickness, macular volume and thickness, and optic nerve head (ONH) parameters assessed using spectral-domain optical coherence tomography (SD-OCT) between eyes with progressing and nonprogressing glaucoma. DESIGN: Longitudinal, observational study. PARTICIPANTS: Two hundred seventy-nine eyes from 162 glaucoma patients followed for an average of 2.2 years. METHODS: Eyes were classified as progressors and nonprogressors according to assessment of optic disc and RNFL photographs and visual field progression analysis. Linear mixed effects models were used to evaluate the overall rate of change of cRNFL thickness, macular volume and thickness, and ONH parameters after adjustment for age, spherical equivalent, signal strength, and baseline SD-OCT measurements. MAIN OUTCOME MEASURES: The rate of change of cRNFL thickness, macular volume, and thickness and ONH parameters. RESULTS: Sixty-three eyes (22.6%) from 52 subjects were identified as progressors. Average, inferior quadrant, and 6- and 7-o'clock sector cRNFL thickness decreased faster in progressors than in nonprogressors (-1.26 vs -0.94, -2.47 vs -1.75, -3.60 vs -2.52, and -2.77 vs -1.51 µm/year, respectively; all P<0.05). The ONH rim area decreased faster, and average and vertical cup-to-disc ratio increased faster in progressors than in nonprogressors (-0.016 vs -0.006 mm(2)/year, and 0.004 vs 0.002 and 0.006 vs 0.004 per year, respectively; all P<0.05). Macular cube volume and the thickness of temporal outer and inferior inner macular sectors decreased faster in progressors than in nonprogressors (-0.068 vs -0.048 mm(3)/year, and -2.27 vs -1.67 and -2.51 vs -1.73 µm/year, respectively; all P<0.05). CONCLUSIONS: Serial measurement of parameters in all 3 areas (cRNFL, macula, and ONH) by SD-OCT may permit identification of progression in glaucomatous eyes. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.