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Purpose To characterize longitudinal changes in macular microvasculature as quantified from optical coherence tomography angiography (OCTA) metrics in primary open-angle glaucoma (POAG) eyes with and without high myopia. Methods In total, 63 and 61 POAG eyes with and without high myopia, respectively, underwent swept-source OCTA imaging in at least four follow-up visits at an ophthalmic center, with a scanning protocol of 3- × 3-mm centered at the fovea. The foveal avascular zone (FAZ) area, FAZ circularity, and vessel density (VD) in both the superficial (SCP) and deep capillary plexuses (DCP) were measured. The rate of change in macular OCTA metrics over time was estimated using linear mixed-effects models in both groups of POAG eyes. Results The mean follow-up time and number of visits were 27.72 ± 8.57 months and 8.5 (8 to 13) times, and 30.95 ± 10.19 months and 10 (8‒13) times in POAG eyes with and without high myopia, respectively. VD in the DCP reduced significantly more quickly in POAG eyes with high myopia than in those without high myopia (−5.14%/year vs. −3.71%/year, P = 0.008). Moreover, lower baseline VD in the DCP was significantly associated with faster VD reduction in POAG with high myopia eyes (P < 0.001). Conversely, the VD reduction rate in the SCP, FAZ area, and FAZ circularity in both the SCP and DCP were similar in both groups (all Ps > 0.05). Conclusions VD in DCP reduced significantly more quickly in POAG eyes with high myopia over time. Density in the DCP reduced more quickly when baseline VD was low.

Purpose The purpose of this study was to investigate the difference in pulsatile trabecular meshwork (TM) motion between normal and eyes with POAG using phase-sensitive optical coherence tomography (PhS-OCT). Methods In this cross-sectional study, eight healthy subjects (16 eyes) and nine patients with POAG (18 eyes) were enrolled. A laboratory-based prototype PhS-OCT system was used to measure pulsatile TM motion. PhS-OCT images were analyzed to obtain parameters of pulsatile TM motion (i.e. maximum velocity [MV] and cumulative displacement [CDisp]). Outflow facility and ocular pulse amplitude were measured using pneumotonography. Detection sensitivity was compared among various parameters by calculating the area under the receiver operating characteristic curves (AUCs). Results A pulsatile TM motion waveform synchronous with digital pulse was observed using PhS-OCT in both healthy and POAG eyes. The mean MV in eyes with glaucoma was significantly lower than healthy eyes (P < 0.001). The mean CDisp in POAG eyes was also significantly lower than healthy eyes (P < 0.001). CDisp showed a significant correlation (r = 0.46; P = 0.0088) with ocular pulse amplitude in the study. Compared with the outflow facility, both the MV and CDisp were found to have a better discrimination of glaucoma (P < 0.001 and P = 0.0074, respectively). Conclusions Pulsatile TM motion was reduced in patients with POAG compared to healthy subjects. The underlying mechanism may be due to the altered tissue stiffness or other biomechanical properties of the TM in POAG eyes. Our evidence suggests that the measurement of pulsatile TM motion with PhS-OCT may help in characterizing outflow pathway abnormalities.

Purpose To explore the microRNA (miRNA) profile and its putative role in glaucomatous optic neuropathy by using next-generation sequencing. Methods Aqueous humor (AH) samples were collected from 19 primary open-angle glaucoma (POAG) eyes and 17 cataract eyes before surgery. Next-generation sequencing was performed for RNA samples extracted from 18 AH samples, and the bioinformatics approach was applied for samples with adequate clean data output. The other 18 samples were used for quantitative PCR validation of sequencing results. Results In total, 12 (six POAG and six cataract controls) samples with sufficient clean data output after sequencing were used for further data analysis. Four hundred sixty-six and 480 mature miRNAs were detected in the POAG and cataract control groups, respectively. Among them, 164 miRNAs were detected in all POAG samples, and 96 miRNAs were detected in all cataract control samples. Furthermore, 88 miRNAs were identified as differently expressed between POAG and cataract control eyes. In addition, 16 miRNAs were differently expressed between POAG eyes with severe visual field damage and eyes with moderate visual field damage. This differential expression was predicted to regulate thiamine metabolism, purine metabolism, and transcriptional misregulation. Relative expression patterns of hsa-miR-184, hsa-miR-486-5p, and hsa-miR-93-5p were confirmed by quantitative PCR. Conclusions This study comprehensively demonstrated the miRNA expression profile in the AH of POAG eyes, especially the differential expression of miRNA in eyes with varying degrees of visual field damage, which, together with the underlying miRNA-related pathways, indicate new targets for the pathogenesis and progression of POAG.

To compare the anterior and posterior choroid thickness (ACT and PCT, respectively) in primary open-angle glaucoma (POAG), primary angle-closure disease (PACD), and healthy control subjects.A total of 29 POAG patients (56 eyes), 37 PACD patients (64 eyes), and 34 healthy volunteers (68 eyes) were enrolled in this study; 50 POAG eyes were divided into 25 early/moderate-stage and 25 advanced-stage eyes by visual field loss, while 64 PACD eyes were classified as primary angle-closure suspect (PACS), 8 eyes; primary angle closure (PAC), 18 eyes; and primary angle-closure glaucoma (PACG), 38 eyes. Ultrasound biomicroscopy (UBM) was used to measure the ACT at a distance of 4 mm from the root of iris in all participants. ACT and PCT were measured using UBM and swept-source optical coherence tomography (SS-OCT), respectively. A 4-mm distance from the iris root was self-defined as the anterior choroid that well matched the real anterior choroid.The mean ACT measured by UBM was 0.45 ± 0.057 mm in POAG eyes, 0.38 ± 0.050 mm in PACD eyes, and 0.30 ± 0.050 mm in healthy eyes. Both the POAG and PACD eyes had a thicker anterior choroid than healthy eyes (P0.01). Compared to early/moderate-stage eyes of POAG, advanced-stage eyes had similar ACT (P0.05). PACG eyes had a thinner anterior choroid than PAC/PACS eyes (P0.05). However, no statistically significant difference was noted for POAG, PACD, and normal control eyes' PCT using SS-OCT (P0.05).POAG/PACD eyes had a thicker anterior choroid than the controls. However, there was no significant difference in the PCT among the groups. The anterior choroid might play a role in the pathogenesis of glaucoma, warranting further investigation.

Glaucoma is one of the leading causes of blindness in humans and is characterized by damage to retinal ganglion cells (RGCs) and the optic nerve.1,2 While abnormally high IOP is a widely recognized risk factor,3,4 the molecular pathways linking elevated IOP and RGC loss are complex. Although several inroads toward understanding the mechanisms have recently been made,5–13 much remains to be learned, particularly regarding the responses in chronic injury. Extracellular ATP is a likely candidate to link the elevated IOP in glaucoma to perturbed signaling in the retina and optic nerve. Throughout the body, released ATP conveys information about mechanical strain and accompanies shear stress, swelling, and stretch.14–18 This mechanosensitive release of ATP can initiate a series of physiological and pathological responses including cell death, volume regulation, pain, inflammatory responses, and neuroprotection by activating ionotropic P2X and metabotropic P2Y receptors.19 Evidence is accumulating for an increased release of ATP following IOP elevation in glaucoma. For instance, humans with primary acute angle closure glaucoma (PAACG) displayed a 9-fold rise in the ATP levels in their anterior chamber.20 Bovine eyes released ATP into the vitreal chamber in levels proportional to the magnitude of applied pressure,21 while the damage caused to rat RGCs by acute rises in IOP was related to levels of extracellular ATP.22 Both RGCs and astrocytes release ATP upon mechanical strain, with pannexin hemichannels a likely pathway for release in both cell types.23–25 While these reports indicate that acute increases in IOP and/or mechanical strain lead to release of ATP in the retina, most patients with glaucoma suffer from an elevation in IOP for extended periods. Evidence for a sustained release of ATP associated with a prolonged elevation of IOP would thus have relevance for the most common forms of the disease. We have previously demonstrated that humans with primary chronic angle closure glaucoma (PCACG) have a 14-fold increase in ATP levels in the anterior chamber.26 While this finding supports the theory that a chronic elevation in IOP leads to a sustained elevation in extracellular ATP release, it was not possible to confirm this increase in the human retina as sampling was only justified from the anterior segment in these patients and not in the vitreal chamber. As the pathological changes to the retina and optic nerve head are most directly associated with vision loss, it is important to determine whether elevated extracellular levels of ATP also occur in the posterior eye during a chronic rise in IOP. Given that excessive stimulation of the P2X7 receptor for ATP can both kill RGCs and activate the inflammasome,27,28 the relationship between elevated IOP and extracellular ATP in chronic glaucoma has particular importance. The present study asked whether extracellular ATP was elevated in animal models of chronic glaucoma. As all current animal models of chronic glaucoma are imperfect, we used three different models to ensure the broadest relevance of the findings to the human condition. Specifically, chronic elevation of IOP was monitored in the Tg-MyocY437H mouse, in rat eyes following injection of hypertonic saline into episcleral veins, and in primates after laser photocoagulation of the trabecular meshwork. As ATP measurement from the small extracellular space in the retina is problematic, ATP levels in the vitreous were measured. Levels of the enzyme NTPDase1 were also compared in retinal tissue from rats, mice, and primates with sustained elevation in IOP and control IOP levels as sustained exposure to extracellular ATP increased expression of the ectoATPase NTPDase1 in optic nerve head astrocytes in vitro.

PURPOSE To measure levels of various inflammation-related cytokines in the aqueous humor of patients with acute primary angle-closure (APAC) and senile cataract. METHODS Aqueous humor samples were prospectively collected from 23 eyes (12 eyes with current APAC and 11 eyes with previous APAC) of 23 APAC patients and 15 eyes of 15 cataract patients. The levels of 15 inflammation-related cytokines in the aqueous humor of APAC and cataract subjects were measured by using the multiplex bead immunoassay technique. Data on patient demographics and preoperative intraocular pressure (IOP) were also collected for correlation analysis. RESULTS Compared with the group with previous APAC and the cataract group, the group with current APAC showed clear and significantly elevated concentrations of interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein (MCP)-1, MCP-3, and vascular endothelial growth factor (VEGF) (all P < 0.0167). The group with previous APAC and the cataract group had similar levels of cytokines. Intraocular pressure was positively correlated with IL-8 (P = 0.001), G-CSF (P = 0.002), MCP-3 (P < 0.001), and VEGF (P < 0.001). CONCLUSIONS An early "acute inflammatory" condition occurs in eyes with current APAC. In addition to controlling IOP, anti-inflammatory treatments are necessary for eyes suffering from APAC.

PURPOSE We compared the choroidal thickness of the eyes of patients with acute primary angle-closure (APAC) with fellow eyes in the same patients. METHODS The analysis included 21 participants with unilateral APAC affected eyes and 21 fellow eyes with a diagnosis of primary angle-closure suspect (PACS). Enhanced depth imaging-optical coherence tomography (EDI-OCT) was used to measure the macular and peripapillary retinal and choroidal thickness in both eyes. The average choroidal thickness of the APAC eyes at each location or segment was compared to that of the fellow eyes. RESULTS At all macular locations, the choroidal thickness was greatest at the subfovea for both groups. Comparison of the choroidal thickness between the groups showed that the thickness in the APAC eyes was significantly greater than in the PACS eyes at all locations except at 1 mm, 3 mm superior, 3 mm inferior, and 3 mm temporal from the fovea (P < 0.005). The mean subfoveal choroidal thickness was 349.0 ± 78.1 μm in the APAC eyes and 308.1 ± 70.5 μm in the PACS eyes, with a statistically significant difference (P < 0.005). Multivariable linear regression analysis showed that the subfoveal choroidal thickness was significantly greater in association with the APAC diagnosis and diastolic blood pressure and thinner in association with older subjects. CONCLUSIONS APAC eyes have a higher level of macular choroidal thickness than PACS eyes when the IOP is reduced. However, the source of this difference is unclear and must be investigated further.

We evaluated choroidal thickness in the fellow eyes of patients with acute primary angle-closure (APAC) and compared findings to those of normal controls.The study group comprised 44 fellow eyes defined as primary angle-closure suspect (PACS) of 44 subjects who had experienced APAC and 43 eyes of 43 healthy volunteers. Using enhanced depth imaging optical coherence tomography (EDI-OCT), the peripapillary and macular choroidal thickness of the PACS eyes and the control eyes were measured and compared at each location or segment. Pearson correlation analysis and a multivariable regression model were used to evaluate the relationships between choroidal thickness and related factors.At all the macular locations, the choroidal thickness was thickest at the subfovea. The PACS eyes had a thicker choroid than the control eyes at all macular locations (all P0.05), and it still was significantly thicker after controlling for age, axial length, and sex, except at 3 mm superior from the fovea (P = 0.124). Multivariable linear regression analysis showed that the subfoveal choroidal thickness was significantly thicker in association with the PACS diagnosis, and thinner in association with older subjects and longer axial length eyes. There were no statistically significant differences in the choroidal thickness between the groups at any peripapillary location or segment (P0.05).PACS eyes that had a fellow eye experience of APAC had a thicker macular choroid than the control eyes. The potential role of a thicker choroid as a risk factor for APAC must be investigated further.

To examine the anatomic relationships of retinal blood vessels to the nerve fiber layer.Retinal flat preparations from monkey and cat were stained with methylene blue dye and examined by light microscopy.A focal transition in nerve fiber bundle patterns occurs just above major retinal blood vessels. Bundles abandon a compact form and splay open just as they reach a major blood vessel. Maximum separation of axon fascicles occurs immediately above the blood vessel and the bundles reform after the crossing of the blood vessel is complete. In so doing, nerve fiber bundles temporarily thin and broaden, assuming the shape of an inverted hull. In contrast, at the retinal periphery, minor blood vessels and axon fascicles have no special relationship to each other.At major blood vessel crossings, a focal alteration in nerve fiber bundle anatomy takes place under which local deformability may be enhanced. This adaptation probably lessens the risk of injury to ganglion cell axons from vascular compression. In addition, deflection of the nerve fiber pathway obviates the need for major blood vessels to bend or kink to achieve a crossing, thus avoiding turbulent flow.