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Translational Vision Science &... Sep 2023To assess the validity of visual field (VF) results from the Iowa Head-Mounted Display (HMD) Open-Source Perimeter and to test the hypothesis that VF defects and...
PURPOSE
To assess the validity of visual field (VF) results from the Iowa Head-Mounted Display (HMD) Open-Source Perimeter and to test the hypothesis that VF defects and test-retest repeatability are similar between the HMD and Octopus 900 perimeters.
METHODS
We tested 20 healthy and nine glaucoma patients on the HMD and Octopus 900 perimeters using the Open Perimetry Interface platform with size V stimuli, a custom grid spanning the central 26° of the VF, and a ZEST thresholding algorithm. Historical data from the Humphrey Field Analyzer (HFA) were also analyzed. Repeatability was analyzed with the repeatability coefficient (RC), and VF defect detection was determined through side-by-side comparisons.
RESULTS
The pointwise RCs were 2.6 dB and 3.4 dB for the HMD and Octopus 900 perimeters in ocular healthy subjects, respectively. Likewise, the RCs were 4.2 dB and 3.5 dB, respectively, in glaucomatous patients. Limits of agreement between the HMD and Octopus 900 perimeters were ±4.6 dB (mean difference, 0.4 dB) for healthy patients and ±8.9 dB (mean difference, 0.1 dB) for glaucomatous patients. Retrospective analysis showed that pointwise RCs on the HFA2 perimeter were between 3.4 and 3.7 dB for healthy patients and between 3.9 and 4.7 dB for glaucoma patients. VF defects were similar between the HMD and Octopus 900 for glaucoma subjects.
CONCLUSIONS
The Iowa Virtual Reality HMD Open-Source Perimeter is as repeatable as the Octopus 900 perimeter and is a more portable and less expensive alternative than traditional perimeters.
TRANSLATIONAL RELEVANCE
This study demonstrates the validity of the visual field results from the Iowa HMD Open-Source Perimeter which may help expand perimetry access.
Topics: Humans; Iowa; Retrospective Studies; Eye; Visual Field Tests; Glaucoma
PubMed: 37747414
DOI: 10.1167/tvst.12.9.19 -
Scientific Reports Nov 2023Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma... (Meta-Analysis)
Meta-Analysis
Several observational studies have investigated the association between cannabis use and intraocular pressure, but its association with primary open-angle glaucoma (POAG) remains unclear. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) whether cannabis use affects POAG. We used five single-nucleotide polymorphisms (SNPs) associated with lifetime cannabis use (P-value < 5 × 10) from a genome-wide association study (GWAS) (N = 184,765) by the International Cannabis Consortium, 23andMe, and UK Biobank and eleven SNPs associated with cannabis use disorder (P-value < 5 × 10) from a GWAS meta-analysis of (17,068 cases and 357,219 controls of European descent) from Psychiatric Genomics Consortium Substance Use Disorders working group, Lundbeck Foundation Initiative for Integrative Psychiatric Research, and deCode. We associated the selected five SNPs from the GWAS of lifetime cannabis use and the eleven SNPs from the GWAS of cannabis use disorder, with the largest to date GWAS meta-analysis of POAG (16,677 cases and 199,580 controls). MR analysis suggested no evidence for a causal association of lifetime cannabis use and cannabis use disorder with POAG (odds ratio (OR) of outcome per doubling of the odds of exposure (95% confidence interval): 1.04 (0.88; 1.23) for lifetime cannabis use and 0.97 (0.92; 1.03) for cannabis use disorder). Sensitivity analyses to address pleiotropy and weak instrument bias yielded similar estimates to the primary analysis. In conclusion, our results do not support a causal association between cannabis use and POAG.
Topics: Humans; Genome-Wide Association Study; Cannabis; Mendelian Randomization Analysis; Glaucoma, Open-Angle; Marijuana Abuse; Polymorphism, Single Nucleotide
PubMed: 37949880
DOI: 10.1038/s41598-023-45872-z -
Translational Vision Science &... Nov 2023Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum...
PURPOSE
Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. This study investigated the inhibitory effect of PFD on TM fibrosis and evaluated its efficacy in lowering intraocular pressure (IOP).
METHODS
Human TM cells were isolated, cultured, and characterized. Cell Counting Kit-8 was used to evaluate the proliferation and toxicity of different concentrations of PFD on normal or fibrotic TM cells. TM cells were treated with transforming growth factor beta-2 (TGF-β2) in the absence or presence of PFD. Western blotting and immunofluorescence analyses were used to analyze changes in the TM cell cytoskeleton and extracellular matrix (ECM) proteins, including alpha-smooth muscle actin (α-SMA), F-actin, collagen IV (COL IV), and fibronectin (FN). An ocular hypertension (OHT) mouse model was induced with Ad-TGF-β2C226/228S and then treated with PFD or latanoprost (LT) eye drops to confirm the efficacy of PFD in lowering IOP.
RESULTS
PFD inhibited the proliferation of fibrotic TM cells in a dose-dependent manner and inhibited TGF-β2-induced overexpression of α-SMA, COL IV, and FN in TM cells. PFD stabilized F-actin. In vivo, PFD eye drops reduced the IOP of the OHT models and showed no significant difference compared with LT eye drops.
CONCLUSIONS
PFD inhibited TGF-β2-induced TM cell fibrosis by rearranging the disordered cytoskeleton and decreasing ECM deposition, thereby enhancing the aqueous outflow from the TM outflow pathway and lowering IOP, which provides a potential new approach to treating glaucoma.
TRANSLATIONAL RELEVANCE
Our work with pirfenidone provides a new approach to treat glaucoma.
Topics: Animals; Humans; Mice; Actins; Cells, Cultured; Fibrosis; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Ophthalmic Solutions; Trabecular Meshwork; Transforming Growth Factor beta2
PubMed: 37975842
DOI: 10.1167/tvst.12.11.21 -
Scientific Reports Nov 2023Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test...
Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test whether chronic HIF activation and the attendant metabolic reprogramming can initiate glaucoma-associated pathology independently of ocular hypertension. HIF-1α stabilization was induced in mice for 2 and 4 weeks by inhibiting prolyl hydroxylases using the small molecule Roxadustat. HIF-1α stabilization and the expression of its downstream bioenergetic targets were investigated in the retina by immunofluorescence, capillary electrophoresis, and biochemical enzyme activity assays. Roxadustat dosing resulted in significant stabilization of HIF-1α in the retina by 4 weeks, and upregulation in glycolysis-associated proteins (GLUT3, PDK-1) and enzyme activity in both neurons and glia. Accordingly, succinate dehydrogenase, mitochondrial marker MTCO1, and citrate synthase activity were significantly decreased at 4 weeks, while mitophagy was significantly increased. TUNEL assay showed significant apoptosis of cells in the retina, and PERG amplitude was significantly decreased with 4 weeks of HIF-1α stabilization. A significant increase in AMPK activation and glial hypertrophy, concomitant with decreases in retinal ganglion cell function and inner retina cell death suggests that chronic HIF-1α stabilization alone is detrimental to retina metabolic homeostasis and cellular survival.
Topics: Animals; Mice; Apoptosis; Glaucoma; Hypoxia-Inducible Factor 1, alpha Subunit; Mitophagy; Ocular Hypertension; Respiration; Retina; Retinal Ganglion Cells
PubMed: 37996657
DOI: 10.1038/s41598-023-47942-8 -
Expert Reviews in Molecular Medicine Apr 2024Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and... (Review)
Review
Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.
Topics: Humans; Glaucoma; Uveitis; Eye; Blindness; Genetic Therapy
PubMed: 38618935
DOI: 10.1017/erm.2024.4 -
MiR-93-5p inhibits retinal neurons apoptosis by regulating PDCD4 in acute ocular hypertension model.Life Science Alliance Sep 2023The present study focused on the effect of miR-93-5p on apoptosis of retinal neurons in acute ocular hypertension (AOH) model by regulating PDCD4 and explored its...
The present study focused on the effect of miR-93-5p on apoptosis of retinal neurons in acute ocular hypertension (AOH) model by regulating PDCD4 and explored its related mechanism. We detected that miR-93-5p expression was decreased and PDCD4 expression was increased in the AOH retina by qRT-PCR. Therefore, we explored the role of miR-93-5p and PDCD4. MiR-93-5p overexpression inhibited the apoptosis of retinal neurons and the expression of PDCD4 in vivo and in vitro. Inhibiting the expression of PDCD4 via transfected interfering RNA decreased the apoptosis of retinal cells and increased the expression of PI3K/Akt pathway-related proteins in vitro. However, the addition of PI3K protein inhibitor LY294002 reversed this effect, leading to a decrease of PI3K/Akt pathway protein expression and an increase of apoptosis-related protein Bax/Bcl-2 expression ratio. Finally, up-regulating miR-93-5p or down-regulating PDCD4 increased the expression of PI3K/Akt pathway protein in vivo. In conclusion, under the condition of AOH injury, miR-93-5p-inhibiting PDCD4 expression reduced the apoptosis of retinal neurons by activating PI3K/Akt pathway.
Topics: Humans; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Ocular Hypertension; Apoptosis; Retinal Neurons; MicroRNAs; RNA-Binding Proteins; Apoptosis Regulatory Proteins
PubMed: 37308277
DOI: 10.26508/lsa.202201732 -
PloS One 2023Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in...
PURPOSE
Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients.
METHODS
The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool.
RESULTS
Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude.
CONCLUSION
There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.
Topics: Humans; Middle Aged; Cytidine Diphosphate Choline; Glaucoma, Open-Angle; Intraocular Pressure; Glaucoma; Retinal Ganglion Cells; Blindness
PubMed: 37768938
DOI: 10.1371/journal.pone.0291836 -
Investigative Ophthalmology & Visual... Jul 2023This study investigated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on fibrosis after glaucoma filtering surgery with clinical data and an in vitro model...
PURPOSE
This study investigated the effect of dipeptidyl peptidase-4 inhibitors (DPP-4is) on fibrosis after glaucoma filtering surgery with clinical data and an in vitro model that used transforming growth factor-β (TGF-β) to induce human Tenon's fibroblast (HTF) fibrosis.
METHODS
The medical records of 41 eyes of 35 patients with diabetes with neovascular glaucoma (NVG) who received initial trabeculectomy were retrospectively reviewed. The surgical success rate was compared between cases that received (n = 23) and did not receive (n = 18) DPP-4i treatment for diabetes. The antifibrotic effects of linagliptin (a DPP-4i) were evaluated with quantitative real-time PCR for fibrosis markers (α-smooth muscle actin, collagen Iα, and fibronectin), a scratch assay, and a collagen gel contraction assay of primary cultured HTFs treated with TGF-β1 and linagliptin. Western blotting analysis was performed to evaluate the levels of phosphorylated Smad2 and Smad3 in the presence of linagliptin.
RESULTS
The Kaplan-Meier curve for bleb survival was higher in patients who received DPP-4is (P = 0.017, log-rank test). The in vitro experiments demonstrated that treatment with linagliptin attenuated the elevated levels of fibrosis markers induced by TGF-β1 in HTFs. Linagliptin treatment also prevented the migration and gel contraction of HTFs. Linagliptin inhibited the phosphorylation of Smad2 and Smad3, which is the canonical pathway of TGF-β signaling.
CONCLUSIONS
The current study indicates the potential effect of DPP-4is for maintaining bleb function after glaucoma filtering surgery in patients with diabetes with NVG. Our results demonstrate that linagliptin attenuates fibrotic change in HTFs by inhibiting TGF-β/Smad signaling.
Topics: Humans; Transforming Growth Factor beta1; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin; Retrospective Studies; Glaucoma; Fibrosis; Fibroblasts; Trabeculectomy; Transforming Growth Factor beta; Signal Transduction; Collagen; Cells, Cultured
PubMed: 37405760
DOI: 10.1167/iovs.64.10.2 -
BMC Ophthalmology Sep 2023This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma. (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.
METHODS
Eligible studies reporting an association between H. pylori infection and Glaucoma were identified through an extensive search of the Excerpta Medica (EMBASE), Web of Science, Scopus, and PubMed databases and an assessment of the reference list of the top articles until October 2022. Analysis was performed with random effects model using Stata 16.
RESULT
Twenty-four studies were included in the systematic review. This study involved 1602 glaucoma patients and 2800 control individuals. The combined RRs of cohort studies and overall combined ORs of case-control studies showed a significant correlation between H. pylori infection and Glaucoma. Subgroup analysis showed that glaucoma patients had a higher risk of having H. pylori infection if they were residents of Europe countries (Cohort: RR: 1.69; 95% CI: 1.3-2.19) and (Case-Control: RR: 3.71; 95% CI: 2.07-6.64), if they had POAG type (Cohort: RR: 1.76; 95% CI: 1.37-2.27) and (Case-Control: RR: 3.71; 95% CI: 2.934.70), if their diagnostic method of HP was histology (Cohort: RR: 1.95; 95% CI: 1.26-3.01) and (Case-Control: RR: 4.06; 95% CI: 2.28-7.22), and if they were over 60 years old (Cohort: RR: 1.63; 95% CI: 1.33-2.00) and (Case-Control: RR: 2.95; 95% CI: 2.27-3.83).
DISCUSSION
The results of this meta-analysis suggest a statistically significant association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.
Topics: Humans; Middle Aged; Helicobacter Infections; Glaucoma, Open-Angle; Helicobacter pylori; Case-Control Studies; Glaucoma
PubMed: 37697285
DOI: 10.1186/s12886-023-03111-z -
JAMA Network Open Oct 2023Recent studies indicate that alcohol consumption is linked to increased intraocular pressure and higher prevalence of open-angle glaucoma (OAG). However, there is...
IMPORTANCE
Recent studies indicate that alcohol consumption is linked to increased intraocular pressure and higher prevalence of open-angle glaucoma (OAG). However, there is insufficient evidence to establish any correlation between alcohol abstinence and improved outcomes in patients with OAG.
OBJECTIVE
To evaluate the association between alcohol consumption status (and its changes) and risk of incident severe visual impairment (VI) or blindness in patients with newly diagnosed OAG.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, nationwide, population-based cohort study used the Korean National Health Insurance Service's claims and health examination database to enroll patients who were newly diagnosed with OAG between January 1, 2010, and December 31, 2011, and had been alcohol drinkers before their OAG diagnosis. The cohort was followed up until December 2020. The data were analyzed from February to December 2022.
EXPOSURES
The patients were categorized into 2 groups based on their post-OAG diagnosis alcohol consumption status: sustainers and abstainers. The risks of severe VI or blindness were compared using weighted Cox proportional hazards regression models along with inverse probability of treatment weighting.
MAIN OUTCOMES AND MEASURES
Incident severe VI or blindness.
RESULTS
Among 13 643 patients with newly diagnosed OAG (mean [SD] age, 53.7 [11.9] years; 12 066 men [88.4%]) who were drinkers, 2866 (21.0%) quit drinking after the diagnosis. During 91 366 person-years of follow-up, patients abstaining from alcohol after their OAG diagnosis had a lower risk of severe VI or blindness than did those who had sustained drinking (adjusted hazard ratio [AHR] after inverse probability of treatment weighting, 0.63; 95% CI, 0.45-0.87). Among the sustained drinkers, both mild consumption (<105 g/wk; AHR, 1.52; 95% CI, 1.01-2.28) and moderate to heavy consumption (≥105 g/wk; AHR, 1.78; 95% CI, 1.11-2.86) after OAG diagnosis were associated with higher risk of severe VI or blindness relative to abstainers. Frequent drinking (≥4 d/wk) also was associated with a higher risk of severe VI or blindness (AHR, 2.56; 95% CI, 1.52-4.33) compared with abstinence.
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with OAG who were drinkers, abstaining from alcohol after an OAG diagnosis was associated with lower risk of severe VI or blindness. These findings suggest that lifestyle interventions, such as alcohol abstinence, could be essential for patients with newly diagnosed OAG.
Topics: Male; Humans; Middle Aged; Cohort Studies; Glaucoma, Open-Angle; Retrospective Studies; Alcohol Abstinence; Blindness; Vision Disorders
PubMed: 37856121
DOI: 10.1001/jamanetworkopen.2023.38526