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Low ocular perfusion pressure (OPP) has been proposed as an important risk factor for glaucoma development and progression, but controversy still exists between studies. Therefore, we conducted a systematic review and meta-analysis to analyze the association between OPP and open-angle glaucoma (OAG). Studies were identified by searching PubMed and EMBASE databases. The pooled absolute and standardised mean difference in OPP between OAG patients and controls were evaluated using the random-effects model. Meta-regression analysis was conducted to investigate the factors associated with OPP difference between OAG patients and controls. A total of 43 studies were identified including 3,009 OAG patients, 369 patients with ocular hypertension, and 29,502 controls. The pooled absolute mean difference in OPP between OAG patients and controls was −2.52 mmHg (95% CI −4.06 to −0.98), meaning significantly lower OPP in OAG patients ( P  = 0.001). Subgroup analyses showed that OAG patients with baseline IOP > 21 mmHg ( P  = 0.019) and ocular hypertension patients also had significantly lower OPP than controls ( P  < 0.001), but such difference in OPP was not significant between OAG patients with baseline IOP of ≤21 mmHg and controls ( P  = 0.996). In conclusion, although no causal relationship was proven in the present study, our findings suggest that in patients with high baseline IOP, who already have a higher risk of glaucoma, low OPP might be another risk factor.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide. Although deep learning methods have been proposed to diagnose POAG, it remains challenging to develop a robust and explainable algorithm to automatically facilitate the downstream diagnostic tasks. In this study, we present an automated classification algorithm, GlaucomaNet, to identify POAG using variable fundus photographs from different populations and settings. GlaucomaNet consists of two convolutional neural networks to simulate the human grading process: learning the discriminative features and fusing the features for grading. We evaluated GlaucomaNet on two datasets: Ocular Hypertension Treatment Study (OHTS) participants and the Large-scale Attention-based Glaucoma (LAG) dataset. GlaucomaNet achieved the highest AUC of 0.904 and 0.997 for POAG diagnosis on OHTS and LAG datasets. An ensemble of network architectures further improved diagnostic accuracy. By simulating the human grading process, GlaucomaNet demonstrated high accuracy with increased transparency in POAG diagnosis (comprehensiveness scores of 97% and 36%). These methods also address two well-known challenges in the field: the need for increased image data diversity and relying heavily on perimetry for POAG diagnosis. These results highlight the potential of deep learning to assist and enhance clinical POAG diagnosis. GlaucomaNet is publicly available on https://github.com/bionlplab/GlaucomaNet .

Background Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown. Methods A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca 2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina. Results We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner. Conclusions These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.

Glaucoma is one of the leading causes of blindness worldwide. This review discusses the clinical features, genetics, molecular biology, and cell biology of glaucoma. The authors present a typical case of glaucoma, together with the ocular findings. This review discusses the clinical features, genetics, molecular biology, and cell biology of glaucoma. The authors present a typical case of glaucoma, together with the ocular findings. Glaucoma is a chronic, degenerative optic neuropathy that can be distinguished from most other forms of acquired optic neuropathy by the characteristic appearance of the optic nerve. In glaucoma, the neuroretinal rim of the optic nerve becomes progressively thinner, thereby enlarging the optic-nerve cup. This phenomenon is referred to as optic-nerve cupping. Its cause is the loss of retinal ganglion cell axons, along with supporting glia and vasculature. The remaining neuroretinal rim retains its normal pink color. In other optic neuropathies, the optic-nerve tissue loses its pink color and cupping does not develop. A rare exception is arteritic anterior ischemic . . .

Understanding the molecular mechanism of glaucoma and development of neuroprotectants is significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma. Here, we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (SO) blocks the pupil or migrates into the anterior chamber following vitreoretinal surgery. We observed significant intraocular pressure (IOP) elevation after intracameral injection of SO, and that SO removal allows IOP to return quickly to normal. This simple, inducible and reversible mouse ocular hypertension model shows dynamic changes of visual function that correlate with progressive retinal ganglion cell (RGC) loss and axon degeneration. It may be applicable with only minor modifications to a range of animal species in which it will generate stable, robust IOP elevation and significant neurodegeneration that will facilitate selection of neuroprotectants and investigating the pathogenesis of ocular hypertension-induced glaucoma.

Aims To evaluate the mid-term efficacy and safety of the GTS-400-iStent combined with phacoemulsification in patients with cataract and open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods Prospective, non-comparative, uncontrolled, interventional case series study. Subjects underwent phacoemulsification and two GTS-400 implantation. Efficacy outcomes: intraocular pressure (IOP) and antiglaucoma medications. Safety outcomes: complications, best-corrected visual acuity and endothelial cell count (ECC). Follow-up was 1 year. Results 20 patients were enrolled (mean age: 75.1±8.6 years). Mean medicated baseline IOP was 19.95±3.71 mm Hg and 26±3.11 mm Hg without medication. Mean final IOP was 16.75±2.24, determining a final IOP decrease of 35.68% (9.42±3 mm Hg; p<0.001), from baseline washout IOP. Mean number of medications fell from 1.3±0.66 to 0.3±0.57 (P<0.001). 75% of patients were off medications at one year. Mean ECC decreased from 2289.64±393.5 cells/mm2 to 1986.95±520.58 cells/mm2. Conclusions Combined cataract surgery with implantation of GTS-400-iStent seems to be an effective and safe procedure.

Glaucoma is a neurodegenerative disease affecting retinal ganglion cells (RGCs), with a multifactorial genesis that includes inflammation and vascular dysfunction. Emerging evidence suggests that glucagon-like peptide 1 receptor agonist (GLP-1RAs) may serve as promising neuroprotective agents in glaucoma. In this study, we investigated the neuroprotective potential of the GLP-1RA semaglutide (SEM) in a rat model of ocular hypertension (OHT) induced by paramagnetic bead injections in Brown Norwegian rats. Rats were divided into four cohorts, two normotensive (NT) cohorts, and two OHT cohorts, treated with either SEM or saline (HBSS), which served as control. Systemic SEM or HBSS administration was initiated simultaneously with OHT induction. We observed that SEM administration seemed to delay the increase in intraocular pressure (IOP) associated with OHT. Although SEM administration did not improve RGC survival, it significantly improved astrocytic fractal dimension value and lacunarity. In conclusion, our findings suggest that GLP-1RAs may exert neuroprotective effects by delaying IOP elevation and preventing OHT-induced reactive astrocyte and vascular remodeling. These findings highlight the potential of GLP-1RAs for retinal neuroprotection, but further studies are needed to elucidate their applicability in glaucoma.

To evaluate the relationship between the displacement of the lamina cribrosa (LC) and prelaminar tissue with corneal hysteresis (CH) using spectral-domain coherence tomography (SD-OCT) after reducing intraocular pressure (IOP) with medical treatment. Sixty-one eyes of 61 patients with ocular hypertension or primary open-angle glaucoma who were going to start with treatment were imaged by means of 12 cross-sectional scans of the optic nerve using enhanced depth imaging SD-OCT before and after 1 week of treatment. We used the 'follow-up' mode to make sure that all the measurements were performed in the same location. We also measured the CH using an Ocular Response Analyzer, and we related it to the magnitude of displacement of LC and prelaminar tissue and the thickness of both structures. There was a significant variation of LC thickness from 132.66±37.40 to 160.09±41.13 µm (p<0001). LC distance was significantly reduced from 258.53±145 µm before treatment to 239.86±135 µm after it. No significant changes were found in the thickness and movement of prelaminar tissue before and after treatment. The only factors related with LC displacement were CH (R =0.48) and age (R =0.42). A significant increase in LC thickness and a reduction in the posterior displacement of LC but not in the prelaminar tissue were demonstrated after IOP reduction with medical treatment. The factors most related with LC displacement were age and CH.

Ocular hypertension is a significant risk factor for vision loss in glaucoma due to the death of retinal ganglion cells (RGCs). This study investigated the effects of the antiapoptotic peptides peptain-1 and peptain-3a on RGC death in vitro in rat primary RGCs and in mouse models of ocular hypertension. Apoptosis was induced in primary rat RGCs by trophic factor deprivation for 48 h in the presence or absence of peptains. The effects of intravitreally injected peptains on RGC death were investigated in mice subjected to retinal ischemic/reperfusion (I/R) injury and elevated intraocular pressure (IOP). I/R injury was induced in mice by elevating the IOP to 120 mm Hg for 1 h, followed by rapid reperfusion. Ocular hypertension was induced in mice by injecting microbeads (MB) or silicone oil (SO) into the anterior chamber of the eye. Retinal flatmounts were immunostained with RGC and activated glial markers. Effects on anterograde axonal transport were determined by intravitreal injection of cholera toxin-B. Peptain-1 and peptain-3a inhibited neurotrophic factor deprivation-mediated RGC apoptosis by 29% and 35%, respectively. I/R injury caused 52% RGC loss, but peptain-1 and peptain-3a restricted RGC loss to 13% and 16%, respectively. MB and SO injections resulted in 31% and 36% loss in RGCs following 6 weeks and 4 weeks of IOP elevation, respectively. Peptain-1 and peptain-3a inhibited RGC death; the loss was only 4% and 12% in MB-injected eyes and 16% and 15% in SO-injected eyes, respectively. Anterograde transport was defective in eyes with ocular hypertension, but this defect was substantially ameliorated in peptain-injected eyes. Peptains suppressed ocular hypertension-mediated retinal glial activation. In summary, our results showed that peptains block RGC somal and axonal damage and neuroinflammation in animal models of glaucoma. We propose that peptains have the potential to be developed as therapeutics against neurodegeneration in glaucoma.

Neuroinflammation is a significant contributor to the pathology of glaucoma. Targeting key-mediators in this process is a realistic option to slow disease progression. Galectin-3 is a β-galactoside binding lectin that has been associated with inflammation in both systemic and central nervous system diseases. Elevated Galectin-3 has recently been detected in multiple animal models of glaucoma and inhibiting Galectin-3 using an intravitreal injection of TD139 (a Galectin-3 small molecule inhibitor) is neuroprotective. We queried whether this neuroprotective effect was translatable to another animal model and species. TD139 was intravitreally injected, in a rat ocular hypertensive model of glaucoma, 3 days after the induction of ocular hypertension (at peak intraocular pressure). Retinal ganglion cell survival and glial morphological markers were quantified. The degeneration of retinal ganglion cells was prevented by TD139 injection, but gross glial markers remained unaffected. These data confirm that the intravitreal injection of TD139 is neuroprotective in a rat ocular hypertensive model of glaucoma, while suggesting that the inhibition of Galectin-3 is not sufficient to alter the gross inflammatory outcome.