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Translational Vision Science &... Dec 2023This study investigated the effects of dexamethasone (Dex) on human trabecular meshwork (TM) cells, a model of glucocorticoid-induced glaucoma, and evaluated the impact...
PURPOSE
This study investigated the effects of dexamethasone (Dex) on human trabecular meshwork (TM) cells, a model of glucocorticoid-induced glaucoma, and evaluated the impact of ripasudil (Rip) as a co-delivery or sequential dosing strategy.
METHODS
In vitro experiments were conducted to assess the effects of Dex and Rip on TM cells. Confocal microscopy was used to evaluate the impact of Dex and Rip on F-actin staining signals. Contractility of the TM cells upon Dex and Rip treatment mimicking co-delivery and sequential delivery was quantified using collagen gel contraction assay. Transepithelial electrical resistance (TEER) values and fluorescein isothiocyanate (FITC)-dextran permeability were also measured to assess the impact of Dex and Rip on TM cells.
RESULTS
Dex and Rip did not exhibit cytotoxicity at the maximum tested concentration (20 µM). Dex-treated TM cells exhibited higher F-actin staining signals compared to controls, which were reduced when co-treated with Rip. Rip inhibited Dex-induced collagen gel contraction activity in both co-delivery and sequential treatments. Dex resulted in increased TEER values as the dose increased, whereas TEER values were maintained when co-treated with Rip.
CONCLUSIONS
Co-delivery of Rip has the potential to prevent glaucoma symptoms when patients are treated with Dex. This study highlights the importance of identifying strategies to reduce the side effects of prolonged use of glucocorticoids, such as Dex, in the treatment of various diseases.
TRANSLATIONAL RELEVANCE
This study demonstrates the potential of co-delivering ripasudil with dexamethasone to mitigate glucocorticoid-induced ocular hypertension and a secondary glaucoma that resembles primary open-angle glaucoma, providing insights for the development of novel preventive strategies in clinical care.
Topics: Humans; Glucocorticoids; Dexamethasone; Trabecular Meshwork; rho-Associated Kinases; Glaucoma, Open-Angle; Actins; Glaucoma; Collagen; Phenotype
PubMed: 38051267
DOI: 10.1167/tvst.12.12.4 -
Translational Vision Science &... Nov 2023Glaucoma is an eye-brain axis disorder characterized by loss of retinal ganglion cells (RGCs). Although the role of intraocular pressure (IOP) elevation in glaucoma has...
PURPOSE
Glaucoma is an eye-brain axis disorder characterized by loss of retinal ganglion cells (RGCs). Although the role of intraocular pressure (IOP) elevation in glaucoma has been established, the reduction of oxidative stress and inflammation has emerged as a promising target for neuronal tissue-supporting glaucoma management. Therefore, we evaluated the effect of a proprietary spearmint extract (SPE) on RGC density, activity, and neuronal health markers in a rat model of hypertensive glaucoma.
METHODS
Animals were divided in four groups: untreated healthy control and three glaucomatous groups receiving orally administered vehicle, SPE-low dose, or SPE-high dose for 28 days. Ocular hypertension was induced through intracameral injection of methylcellulose at day 15. At day 29, rats underwent electroretinogram (ERG) recordings, and retinas were analyzed for RGC density and markers of neural trophism, oxidative stress, and inflammation.
RESULTS
SPE exerted dose-dependent response benefits on all markers except for IOP elevation. SPE significantly improved RGC-related ERG responses, cell density, neurotrophins, oxidative stress, and inflammation markers. Also, in SPE-high rats, most of the parameters were not statistically different from those of healthy controls.
CONCLUSIONS
SPE, a plant-based, polyphenolic extract, could be an effective nutritional support for neuronal tissues.
TRANSLATIONAL RELEVANCE
These results suggest that SPE not only may be a complementary approach in support to hypotensive treatments for the management of glaucoma but may also serve as nutritional support in other ocular conditions where antioxidant, anti-inflammatory, and neuroprotective mechanism are often disrupted.
Topics: Animals; Rats; Mentha spicata; Glaucoma; Ocular Hypertension; Retina; Inflammation
PubMed: 37917085
DOI: 10.1167/tvst.12.11.6 -
Cornea Oct 2023The aim of the study is to investigate US-based ophthalmologists' preferred corneal transplant techniques and postoperative steroid regimen. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The aim of the study is to investigate US-based ophthalmologists' preferred corneal transplant techniques and postoperative steroid regimen.
METHODS
Ophthalmologists attending the 2021 Cornea and Eye Banking Forum and/or Cornea Subspecialty Day were surveyed in person.
RESULTS
Ninety-two ophthalmologists with a median of 13 years (range of 1-35; mean of 14.5; ±9.05 mean ± SD) of experience as attending clinicians were surveyed. One hundred percent of the surgeons performed penetrating keratoplasty, which was followed by 96.7% for Descemet stripping endothelial keratoplasty, 90.2% for Descemet membrane endothelial keratoplasty, and 72.8% for deep anterior lamellar keratoplasty. Prednisolone 1% for postoperative care was the preferred choice across all surveyed keratoplasty techniques and postsurgery time intervals. All surgeons reported steroid administration frequency of 4 times a day in the first month and once a day after 12 months postkeratoplasty. To manage ocular hypertension after corneal transplantation, the leading approach was adding a glaucoma medication (44.6%), and beta-adrenergic antagonists were ranked as the most preferred choice by 59 (66.3%) of the respondents. For graft rejection after corneal transplantation, topical steroids (79.8%) were the initial treatment of choice with hourly administration being the most common frequency prescribed (87.4%). Most surgeons either agreed or strongly agreed (78.4%) that a randomized clinical trial evaluating the safety and efficacy of different steroid regimens after corneal transplantation would influence their clinical decision making.
CONCLUSIONS
Prednisolone remains the predominantly used steroid across different keratoplasties. Steroid regimens are similar for non-high-risk penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, and deep anterior lamellar keratoplasty. To treat graft rejection, surgeons tend to initially add a glaucoma medication than to reduce the potency or frequency of the steroid.
Topics: Humans; Corneal Transplantation; Keratoplasty, Penetrating; Prednisolone; Glaucoma; Surveys and Questionnaires; Steroids; Descemet Stripping Endothelial Keratoplasty; Corneal Diseases
PubMed: 36633636
DOI: 10.1097/ICO.0000000000003174 -
Graefe's Archive For Clinical and... Oct 2023To compare the efficacy and safety of the PRESERFLO™ MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG) after one year.
PURPOSE
To compare the efficacy and safety of the PRESERFLO™ MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG) after one year.
PATIENTS AND METHODS
Institutional prospective interventional cohort study comparing eyes with POAG, which had received the PRESERFLO™ MicroShunt versus trabeculectomy. The MicroShunt group was matched with the trabeculectomy group for age, known duration of disease, and number and classes of intraocular pressure (IOP) lowering medications to have similar conjunctival conditions. The study is part of the Dresden Glaucoma and Treatment Study, using a uniform study design, with the same inclusion and exclusion criteria, follow-ups and standardized definitions of success and failure for both procedures.
PRIMARY OUTCOME MEASURES
mean diurnal IOP (mdIOP, mean of 6 measurements), peak IOP, and IOP fluctuations.
SECONDARY OUTCOME MEASURES
success rates, number of IOP lowering medications, visual acuity, visual fields, complications, surgical interventions, and adverse events.
RESULTS
Sixty eyes of 60 patients, 30 in each group, were analyzed after 1-year follow-ups. Median [Q25, Q75] mdIOP (mmHg) dropped from 16.2 [13.8-21.5] to 10.5 [8.9-13.5] in the MicroShunt and from 17.6 [15.6-24.0] to 11.1 [9.5-12.3] in the trabeculectomy group, both without glaucoma medications. Reduction of mdIOP (P = .596), peak IOP (P = .702), and IOP fluctuations (P = .528) was not statistically significantly different between groups. The rate of interventions was statistically significantly higher in the trabeculectomy group, especially in the early postoperative period (P = .018). None of the patients experienced severe adverse events.
CONCLUSION
Both procedures are equally effective and safe in lowering mdIOP, peak IOP and IOP fluctuations in patients with POAG, one year after surgery.
CLINICAL TRIAL REGISTRATION
NCT02959242.
Topics: Humans; Trabeculectomy; Glaucoma, Open-Angle; Prospective Studies; Cohort Studies; Glaucoma; Intraocular Pressure; Treatment Outcome; Retrospective Studies
PubMed: 37133501
DOI: 10.1007/s00417-023-06075-4 -
Graefe's Archive For Clinical and... Mar 2024To evaluate the efficacy of XEN-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma.
PURPOSE
To evaluate the efficacy of XEN-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma.
METHODS
Retrospective analysis of 25 eyes receiving XEN gel stent for medically uncontrolled uveitic glaucoma from February 2019 to February 2023 with recording of intraocular pressure (IOP) values, ocular hypotensive medication, requirement for revision or secondary surgery and complications. Prerequisites for XEN implantation were a clear cornea, an open iridocorneal angle and an unscarred, mobile conjunctiva at the implantation site. Minimum follow-up required for inclusion was 3 months. The primary outcome measure was IOP compared to baseline. Complete and qualified success were defined as final IOP of ≤ 18 mmHg without or with topical antiglaucomatous treatment, respectively. Failure was defined as IOP > 18 mmHg on two consecutive visits, IOP reduction < 20%, persisting complications from hypotony and open conjunctival bleb revision. Further glaucoma surgical intervention was defined as complete failure.
RESULTS
Mean preoperative IOP was 35.3 ± 10.9 mmHg on 2.9 ± 0.9 topical antiglaucomatous agents. 19 of 25 patients (76%) received additional oral acetazolamide. 19 eyes were pseudophakic, 5 eyes phakic and 1 aphakic. Early postoperatively, mean IOP reduced to 7.7 ± 3.0 mmHg (75.8% reduction). At final follow-up (mean 17.7 months) mean IOP was 12.0 ± 3.8 mmHg (62.5% reduction) on 0.2 ± 0.6 medications. Six eyes (24%) required bleb revision at mean 28 weeks and therefore were categorized as failure. One eye failed despite bleb revision and restart of topical ocular hypotensive medication. Three other eyes (12%) had IOP spikes with uveitis flare-ups. Transient hypotony complications occurred in 32%. At final follow-up, 18 eyes (72%) achieved complete success and one eye (4%) qualified success.
CONCLUSION
The XEN gel stent effectively reduced IOP in uncontrolled uveitic glaucoma, with 72% complete success. Bleb revision was required in 24%. IOP spikes occurred in 12% despite functioning blebs. Further follow-up is needed to determine long-term outcomes.
Topics: Humans; Retrospective Studies; Glaucoma; Intraocular Pressure; Tonometry, Ocular; Conjunctiva; Antihypertensive Agents
PubMed: 37855957
DOI: 10.1007/s00417-023-06254-3 -
Current Eye Research Mar 2024Coronavirus disease 2019 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and...
PURPOSE
Coronavirus disease 2019 is a disease caused by the novel severe acute respiratory syndrome coronavirus 2. The double-positive of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 have a higher risk of being infected by severe acute respiratory syndrome coronavirus 2. The susceptibility of coronavirus disease 2019 in patients with chronic diseases, especially in different tissues of ocular hypertension eyes like glaucoma, is not yet known.
METHODS
An ocular hypertension model was established by laser photocoagulation in rhesus monkeys. The expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in three ocular hypertension eyes and the three control eyes were analyzed using immunofluorescence.
RESULTS
No difference was observed between ocular hypertension and control eyes in the expression of angiotensin-converting enzyme 2 and transmembrane protease serine type 2 in the conjunctival epithelium, corneal epithelium, and ciliary muscle. In ocular hypertension eyes and control eyes, angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression were both observed in the retina. Angiotensin-converting enzyme 2 staining of retinal ganglion cells was found to be significantly higher in ocular hypertension eyes than in control eyes. However, there was no difference in angiotensin-converting enzyme 2 and transmembrane protease serine type 2 expression in retinal vessels and choroidal vessels between ocular hypertension and control eyes. In our study, the expression and distribution of angiotensin-converting enzyme 2 and TMPREE2 in human retina were similar to that of non-human primates as expected.
CONCLUSION
Our study confirmed that angiotensin-converting enzyme 2 and transmembrane protease serine type 2 were expressed widely in rhesus monkey eyes. When compared with controls eyes, the expression of angiotensin-converting enzyme 2 was higher in the retinal ganglion cells in ocular hypertension eyes, suggesting that high ocular pressure may affect the patients' ocular susceptibility to severe acute respiratory syndrome coronavirus 2 infection.
Topics: Animals; Humans; SARS-CoV-2; COVID-19; Angiotensin-Converting Enzyme 2; Peptide Hydrolases; Peptidyl-Dipeptidase A; Ocular Hypertension; Glaucoma; Serine; Serine Endopeptidases
PubMed: 38212998
DOI: 10.1080/02713683.2023.2291749 -
Biomedicine & Pharmacotherapy =... Jun 2024Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline....
Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline. Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADP) and glutathione (GSH) are two redox reducers in neuronal and glial metabolism. However, therapeutic strategies targeting NAD/NADP or GSH do not exert ideal effects, and the underlying mechanisms are still poorly understood. We assessed morphological changes in retinal ganglion cells (RGCs), the affected neurons in glaucoma, and Müller cells, the major glial cells in the retina, as well as the levels of phosphorylated p38 (p-p38) and Caspase-3 in glaucoma patients. We constructed a modified chronic ocular hypertensive rat model and an oxygen-glucose deprivation (OGD) cell model. After applying NADPH and N-acetylcysteine (NAC), a precursor to cysteine, the rate-limiting substrate in GSH biosynthesis, to cells, apoptosis, axonal damage and peroxidation were reduced in the RGCs of the NAC group and p-p38 levels were decreased in the RGCs of the NADPH group, while in stimulated Müller cells cultured individually or cocultured with RGCs, gliosis and p38/MAPK, rather than JNK/MAPK, activation were inhibited. The results were more synergistic in the rat model, where either NADPH or NAC showed crossover effects on inhibiting peroxidation and p38/MAPK pathway activation. Moreover, the combination of NADPH and NAC ameliorated RGC electrophysiological function and prevented Müller cell gliosis to the greatest extent. These data illustrated conjoined mechanisms in glaucomatous RGC injury and Müller cell gliosis and suggested that NADPH and NAC collaborate as a neuroprotective and anti-inflammatory combination treatment for glaucoma and other underlying human neurodegenerative diseases.
Topics: Animals; NADP; p38 Mitogen-Activated Protein Kinases; Ocular Hypertension; Acetylcysteine; Rats; Male; Retinal Ganglion Cells; Rats, Sprague-Dawley; Glaucoma; Neuroinflammatory Diseases; Humans; Ependymoglial Cells; Disease Models, Animal; MAP Kinase Signaling System; Apoptosis; Chronic Disease; Neuroprotective Agents; Cells, Cultured; Lipid Peroxidation
PubMed: 38735082
DOI: 10.1016/j.biopha.2024.116711 -
Journal of Glaucoma Nov 2023In this case-control study of the Japanese population, including 3207 glaucoma cases, alcohol consumption patterns such as frequency and quantity showed a positive...
PRCIS
In this case-control study of the Japanese population, including 3207 glaucoma cases, alcohol consumption patterns such as frequency and quantity showed a positive association with glaucoma prevalence.
PURPOSE
To examine the association between alcohol consumption patterns and glaucoma.
SUBJECTS AND METHODS
This case-control study evaluated 3207 cases with glaucoma and 3207 matched controls. Patients over 40 years of age were included from 1,693,611 patients admitted to 34 hospitals in Japan. Detailed alcohol consumption patterns (drinking frequency, average daily drinks, and total lifetime drinks) were obtained, as well as various confounding factors, including smoking history and lifestyle-related comorbidities. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for glaucoma prevalence.
RESULTS
Drinking frequency showed an association with glaucoma for "a few days/week" (OR, 1.19; 95% CI, 1.03-1.38) and "almost every day/week" (OR, 1.40; 95% CI, 1.18-1.66). Average daily drinks showed an association for ">0-2 drinks/day" (OR, 1.16; 95% CI, 1.03-1.32). Total lifetime drinks showed an association for ">60-90 drink-year" (OR, 1.23; 95% CI, 1.01-1.49) and ">90 drink-year" (OR, 1.23; 95% CI, 1.05-1.44). As alcohol consumption levels differed considerably between men and women, additional analyses were conducted separately for men and women. Among men, drinking frequency of "a few days/week" and "almost every day/week," average daily drinks of ">0-2 drinks/day" and ">2-4 drinks/day," and total lifetime drinks of ">60-90 drink-year" and ">90 drink-year" had an association with glaucoma. Conversely, among women, neither drinking frequency, average daily drinks, nor total lifetime drinks were associated.
CONCLUSIONS
Both the frequency and quantity of alcohol consumption were associated with glaucoma. Further research on gender differences is warranted.
Topics: Male; Humans; Female; Adult; Middle Aged; Alcohol Drinking; Japan; Case-Control Studies; Intraocular Pressure; Glaucoma
PubMed: 37748099
DOI: 10.1097/IJG.0000000000002308 -
Archivos de La Sociedad Espanola de... Sep 2023To assess the efficacy and safety of combined phacoemulsification and excimer laser trabeculostomy (ELT) in eyes with cataract and mild controlled glaucoma or ocular...
OBJECTIVES
To assess the efficacy and safety of combined phacoemulsification and excimer laser trabeculostomy (ELT) in eyes with cataract and mild controlled glaucoma or ocular hypertension (OHT).
METHODS
Single-centre analysis of eyes that underwent phacoemulsification and ELT between 2017 and 2021. Change in intraocular pressure (IOP), glaucoma medication requirements, corrected distance visual acuity (CDVA), complications and re-interventions were evaluated. Success was defined as a reduction ≥20% from preoperative IOP, an IOP ≤ 14 mmHg or a reduction in glaucoma medication requirements with an IOP equal or lower than the preoperative IOP.
RESULTS
Mean follow-up was 658 ± 64 days. Mean preoperative IOP was 17.76 ± 4.88 mmHg, it decreased to 15.35 ± 3.10 mmHg at 1 year (n = 37) (p = 0.006) and to 14.00 ± 3.78 at 3 years (n = 8) (p = 0.074). Mean number of glaucoma medication requirements decreased from 2.02 ± 1.0 preoperatively to 1.02 ± 0.96 at 1 year (n = 37) (p < 0.001) and to 1.63 ± 0.92 at 3 years (n = 8) (p = 0.197). Complete success was achieved in 17.7% of eyes and qualified success in 54.8%. Two eyes of 2 patients had early postoperative hyphema. Two eyes of 1 patient underwent filtering surgery 2 months after the procedure, and 2 eyes of 1 patient underwent laser trabeculoplasty 3.8 years after the procedure due to uncontrolled IOP.
CONCLUSIONS
Combined phacoemulsification and ELT is effective and safe in eyes with mild glaucoma or OHT and cataract. It significantly reduced IOP and glaucoma medication requirements 1 year after surgery.
Topics: Humans; Phacoemulsification; Lasers, Excimer; Glaucoma; Ocular Hypertension; Cataract
PubMed: 37364679
DOI: 10.1016/j.oftale.2023.05.012 -
Gene Feb 2024Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle... (Review)
Review
Glaucoma stands as a leading global cause of blindness, affecting millions. It entails optic nerve damage and vision loss, categorized into open-angle and closed-angle glaucoma with subtypes like POAG, ACG, XFG, PCG, PDG, and developmental glaucoma. The pathophysiological and genetic factors behind glaucoma remain partially understood, with past studies linking intraocular pressure (IOP) levels to retinal ganglion cell death. Open-angle glaucoma involves elevated resistance to aqueous outflow via the trabecular meshwork, while angle-closure glaucoma typically sees drainage pathways obstructed by the iris. Genes have been identified for POAG, ACG, XFG, PCG, PDG, and developmental glaucoma, allowing for early-onset detection and the emergence of gene therapy as an effective treatment. Nevertheless, diagnostic and treatment options have their constraints, necessitating large-scale, well-designed studies to deepen our grasp of genetics' role in glaucoma's pathogenesis. This review delves into glaucoma's risk factors, pathophysiology, genetics, diagnosis, and available treatment options, including gene therapy. Additionally, it suggests alternative therapies like yoga and meditation as adjunct treatments for glaucoma prevention. Overall, this review advances our comprehension of the pathophysiology and genetic associations of glaucoma while highlighting the potential of gene therapy as a treatment avenue. Further research is imperative to fully elucidate the genetic mechanisms underpinning glaucoma and to devise effective treatments.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma; Trabecular Meshwork; Optic Nerve; Intraocular Pressure
PubMed: 37952746
DOI: 10.1016/j.gene.2023.147983