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Clinical Ophthalmology (Auckland, N.Z.) 2024To determine if there was an association between severity of glaucoma and intraocular pressure (IOP) and medication (med) outcomes for patients in the ROMEO...
PURPOSE
To determine if there was an association between severity of glaucoma and intraocular pressure (IOP) and medication (med) outcomes for patients in the ROMEO (etrospective, bservational, ulticenter valuation of MNI) study.
SETTING
Eleven ophthalmology practices in 8 US states.
DESIGN
Post-hoc analysis of all eyes enrolled and treated with ab interno canaloplasty and trabeculotomy in the retrospective, multicenter ROMEO study.
METHODS
Eyes were grouped according to visual field mean deviation (MD): mild (MD better than -6 dB), moderate (MD between -6 and -12 dB), advanced (-12 dB or worse). IOP and med outcomes at 12 months were compared across groups. Least squares regression was used to assess the relationship of MD with month 12 IOP. Outcomes for 1 and last MD deciles were compared as a sensitivity analysis.
RESULTS
One hundred and twenty-seven eyes were available for analysis including 79 mild, 42 moderate, 6 advanced. Most eyes had a reduction in IOP at Month 12 (70%) with most at 18 mmHg or less. Percentage IOP reduction was similar across the groups (mild 16.9%, moderate 18.6%, advanced 18.0%) with mean month 12 IOP between 14 and 16 mmHg. Medications were also reduced in all three groups; -0.8 (mild, P < 0.001), -0.55 (moderate, P < 0.05), and -1.0 (advanced, P = 0.139, ns). Regression analysis revealed no relationship between month 12 IOP and MD. Med reductions were observed for all groups with a reduction of 1 or more medications seen in (%, 95% CI) 69%, 59-79 (mild), 50%, 35-65 (moderate), and 60%, 21-99 (advanced). Secondary interventions tended to have greater incidence with worse MD likely reflecting lower desired IOP targets.
CONCLUSION
Analysis of data from the ROMEO study suggests that similar meaningful IOP and med reductions can be expected across the range of disease severity studied.
PubMed: 38803557
DOI: 10.2147/OPTH.S464233 -
Journal of Ocular Pharmacology and... May 2024Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma....
Emerging data suggest that acetaminophen lowers intraocular pressure (IOP) and has the potential to be repurposed as pharmacotherapy to treat open-angle glaucoma. However, pharmacokinetic data are lacking. This study aims to describe the pharmacokinetics of topical acetaminophen and its metabolite [-arachidonoylaminophenol (AM404)] when administered individually and in combination, and to determine its effect on IOP in the ocular normotensive adult New Zealand White Rabbit (NZWR). A randomized control trial was conducted using topical 1% acetaminophen and 1% AM404. The study was divided into two sub-studies using both paired-eye and two-eye designs. The mean [95% confidence interval of the mean (95% CI)] concentration of acetaminophen detected in the aqueous humor (AH) was 4.09 ppm (3.18-5.00) at 2 h and 0.92 ppm (0.60-1.24) at 4 h after an immediate dose of topical acetaminophen. The integral IOP, defined as the integral of IOP change from baseline over time, was -5.1 mmHg⋅h (95% CI: -10 to 0.41) for control,-7.5 mmHg⋅h (95% CI: -14 to -1.1) for half-hourly acetaminophen, and -4.4 mmHg⋅h (95% CI: -14 to 5.5) for hourly acetaminophen over a 4-h period. When comparing topical acetaminophen with AM404 dosed half-hourly over a 4-h period, the integral IOP was -2.3 mmHg⋅h (95% CI: -5.9 to 1.3) for control,-2.0 mmHg⋅h (95% CI: -5.6 to 1.7) for AM404, -1.7 mmHg⋅h (95% CI: -4.5 to 1.2) for acetaminophen, and -3.2 mmHg⋅h (95% CI: -5.4 to -0.96) for acetaminophen/AM404 combined. Acetaminophen, but not its metabolite AM404, penetrated the multilayered cornea via passive diffusion in a dose-dependent fashion. There was a nonsignificant tendency to cause a lowering of IOP over the 4-h dosing period with higher AH concentrations of acetaminophen. Topical AM404 did not show a significant IOP-lowering effect.
PubMed: 38800944
DOI: 10.1089/jop.2024.0020 -
American Journal of Ophthalmology Case... Sep 2024This case report highlights a possible association between netarsudil use and crystalline keratopathy.
PURPOSE
This case report highlights a possible association between netarsudil use and crystalline keratopathy.
OBSERVATIONS
Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment.
CONCLUSIONS AND IMPORTANCE
Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.
PubMed: 38799226
DOI: 10.1016/j.ajoc.2024.102069 -
BioRxiv : the Preprint Server For... May 2024Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of...
UNLABELLED
Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for nine months after a single dose of only 1500 magnetically-steered hAMSCs, associated with restoration of function to the conventional outflow pathway, as judged by increased outflow facility and TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle three weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically-steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma.
ONE SENTENCE SUMMARY
A novel magnetic cell therapy provided effective intraocular pressure control in a mouse model of glaucoma, motivating future translational studies.
PubMed: 38798683
DOI: 10.1101/2024.05.13.593917 -
International Ophthalmology May 2024The multifunctional profibrotic cytokine transforming growth factor-beta2 (TGF-β2) is implicated in the pathophysiology of primary open angle glaucoma. Paeoniflorin...
BACKGROUND
The multifunctional profibrotic cytokine transforming growth factor-beta2 (TGF-β2) is implicated in the pathophysiology of primary open angle glaucoma. Paeoniflorin (PAE) is a monoterpene glycoside with multiple pharmacological efficacies, such as antioxidant, anti-fibrotic, and anti-inflammatory properties. Studies have demonstrated that paeoniflorin protects human corneal epithelial cells, retinal pigment epithelial cells, and retinal microglia from damage. Here, the biological role of PAE in TGF-β2-dependent remodeling of the extracellular matrix (ECM) within the trabecular meshwork (TM) microenvironment.
METHODS
Primary or transformed (GTM3) human TM (HTM) cells conditioned in serum-free media were incubated with TGF-β2 (5 ng/mL). PAE (300 μM) was added to serum-starved confluent cultures of HTM cells for 2 h, followed by incubation with TGF-β2 for 22 h. SB-431542, a TGF-β receptor inhibitor (10 μM), was used as a positive control. The levels of intracellular ROS were evaluated by CellROX green dye. Western blotting was used to measure the levels of TGF-β2/Smad2/3 signaling-related molecules. Collagen 1α1, collagen 4α1, and connective tissue growth factor (CTGF) expression was evaluated by RT-qPCR. Immunofluorescence assay was conducted to measure collagen I/IV expression in HTM cells. Phalloidin staining assay was conducted for evaluating F-actin stress fiber formation in the cells.
RESULTS
PAE attenuated TGF-β2-induced oxidative stress and suppressed TGF-β2-induced Smad2/3 signaling in primary or transformed HTM cells. Additionally, PAE repressed TGF-β2-induced upregulation of collagen 1α1, collagen 4α1, and CTGF expression and reduced TGF-β2-mediated collagen I/IV expression and of F-actin stress fiber formation in primary or transformed HTM cells.
CONCLUSION
PAE alleviates TGF-β2-induced ECM deposition and oxidative stress in HTM cells through inactivation of Smad2/3 signaling.
Topics: Humans; Oxidative Stress; Monoterpenes; Transforming Growth Factor beta2; Glucosides; Extracellular Matrix; Trabecular Meshwork; Cells, Cultured; Signal Transduction; Blotting, Western
PubMed: 38795168
DOI: 10.1007/s10792-024-02917-0 -
Bioengineering (Basel, Switzerland) Apr 2024This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma...
This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma (POAG) patients with and without axial myopia. Forty-one POAG patients (19 without myopia, 9 with axial myopia and 13 glaucoma with no intervention) participated. Swept-source optical coherence tomography (OCT) videos of the ONH were obtained before and after IOP-lowering treatment (medical or surgical) achieving a minimum IOP drop of 3 mmHg. A demons registration-based algorithm measured local pulsatile displacement maps within the ONH. Results demonstrated a significant 14% decrease in pulsatile tissue displacement in the non-myopic glaucoma cohort after intervention ( = 0.03). However, glaucoma patients with axial myopia exhibited no statistically significant change. There were no significant changes in the pulsatile ONH deformation in the control group. These findings suggest a potential link between IOP reduction and reduced pulsatile displacement within the ONH in POAG patients without myopia, offering new insights into the disease's pathophysiology and warranting further investigation into underlying mechanisms and clinical implications.
PubMed: 38790278
DOI: 10.3390/bioengineering11050411 -
The British Journal of Ophthalmology May 2024To evaluate efficacy and safety outcomes of the Xen 45 gel stent implant over 24 months of follow-up.
OBJECTIVE
To evaluate efficacy and safety outcomes of the Xen 45 gel stent implant over 24 months of follow-up.
METHODS
A retrospective analysis of prospectively collected data from the Fight Glaucoma Blindness observational registry. Complete success (CS) was defined as intraocular pressure (IOP) reduction ≥20% from preoperative and an IOP ≤18 mm Hg and ≥6 mm Hg with no secondary procedure at 2 years and without IOP-lowering medications. Qualified success (QS) was defined similarly, allowing the use of IOP-lowering medications.
RESULTS
The Xen 45 gel stent implant was implanted in 646 eyes of 515 patients. Preoperative IOP was 21.4±7.6 (mean±SD) mm Hg on 2.7±1.3 IOP-lowering medication and mean deviation was -10.2±8.4 dB. After 24-month follow-up, IOP was 16.8±7.3 mm Hg (mean reduction of 21.7%) on 1.2±1.4 IOP-lowering medications. CS and QS rates at 24 months were 26% and 48%, respectively. CS and QS were higher in the Xen stand-alone group (33% and 52%, respectively) than in the Xen+cataract group (16% and 42%, respectively). Bleb needling was performed in 28.4% of cases, and 18% underwent a secondary procedure.
CONCLUSIONS
The Xen 45 gel stent implant offers acceptable long-term efficacy for the treatment of open-angle glaucoma. However, there is a significant rate of reoperation and needling, and outcomes are less effective if combined with cataract surgery.
PubMed: 38789132
DOI: 10.1136/bjo-2023-325077 -
Experimental Eye Research Jul 2024Transforming growth factor-β2 (TGF-β2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and...
Transforming growth factor-β2 (TGF-β2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-β2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-β2-induced cell migration, and mitigated TGF-β2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-β2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-β2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-β2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-β2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-β2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.
Topics: Humans; Trabecular Meshwork; Transforming Growth Factor beta2; STAT3 Transcription Factor; Signal Transduction; Janus Kinase 2; Proto-Oncogene Proteins c-akt; Cells, Cultured; Silybin; Phosphatidylinositol 3-Kinases; Cell Proliferation; Cell Movement; Blotting, Western; Fibrosis; Silymarin; Antioxidants; Glaucoma, Open-Angle
PubMed: 38789021
DOI: 10.1016/j.exer.2024.109939 -
Journal of Glaucoma May 20243D-angle parameters and cutoff values for detecting angle closure were proposed. The 3D parameters demonstrated excellent diagnostic performance. Certain horizontal 2D...
PRCIS
3D-angle parameters and cutoff values for detecting angle closure were proposed. The 3D parameters demonstrated excellent diagnostic performance. Certain horizontal 2D parameters (i.e.,TISA-750, AOD-750, and AOD-500) can attain similar performance to their high-performing 3D counterparts.
PURPOSE
To investigate the diagnostic performance of single horizontal 2-dimensional (2D) versus 3-dimensional (3D) angle parameters from swept-source anterior segment optical coherence tomography (CASIA2) in detecting angle closure.
METHODS
The cross-sectional study included 118 phakic subjects (59 open-angle, 59 closed-angle). Angle opening distance (AOD), angle recess area (ARA), trabecular-iris space area (TISA) at 250, 500, and 750 μm from scleral spur were measured in 360° radial-scan images. The 3D information of each measurement was analyzed in two patterns: (1) average 3D parameter - the averaged value from 360-degree angle values, and (2) estimate 3D parameter - the estimation of surface area of circumferential angle inlet (using AOD) or circumferential angle volume (using ARA and TISA). The areas under receiver operating curve (AUCs) of eighteen 3D parameters were compared with 2D horizontal parameters.
RESULTS
Among 3D parameters, AOD-500 estimate 3D gave the highest AUC (AUC 0.950, cut-off 6.09 mm2), followed by AOD-750 estimate 3D (AUC 0.948, cut-off 8.26 mm2). 3D parameters significantly increased the AUC of ARA-250 and TISA-250 (all P<0.02) compared to the 2D parameters. No significant improvement in AUC was demonstrated for AOD-250 and all parameters at 500 and 750 μm. No significant difference in AUC was found among the six maximum AUC parameters which were AOD-750 horizontal 2D, AOD-500 estimate 3D, TISA-750 horizontal 2D, AOD-500 horizontal 2D, AOD-750 estimate 3D and TISA-750 average 3D.
CONCLUSIONS
The 3D-angle parameters had high performance in detecting angle closure. However, comparing a horizontal measurement to 3D parameters, the AUC improvement was mostly insignificant.
PubMed: 38780278
DOI: 10.1097/IJG.0000000000002442 -
Cureus Apr 2024This prospective observational study investigates the impact of cataract surgery on anterior segment parameters in nonglaucomatous and primary open-angle glaucoma...
This prospective observational study investigates the impact of cataract surgery on anterior segment parameters in nonglaucomatous and primary open-angle glaucoma (POAG) eyes, utilizing anterior segment optical coherence tomography (AS-OCT). The study involved 42 Caucasian patients, divided into a control group and a POAG group. Comprehensive ophthalmic examinations were performed along with AS-OCT imaging and biometry preoperatively, as well as on one day, one week, and one month following cataract surgery. The results showed significant post-operative changes in anterior chamber depth (ACD) and angle width in both groups, suggesting that cataract surgery may influence the structural parameters associated with glaucoma risk and management. Specifically, a marked increase in ACD and improvement in angle-opening distances were observed, highlighting the potential of cataract extraction to alter intraocular fluid dynamics favorably. Despite these changes, the study noted an initial spike in increased intraocular pressure (IOP) in POAG patients immediately post-operative, which stabilized during follow-up. For the control group, IOP showed gradually reducing IOP values in the follow-up visits. The findings underscore the role of advanced imaging technologies in understanding glaucoma's pathophysiology and the potential benefits of cataract surgery in glaucoma patients. The study advocates for further research with a larger, more diverse patient population and extended follow-up to explore the long-term implications of cataract surgery on glaucoma dynamics, emphasizing the importance of personalized management and treatment strategies particularly for glaucoma patients.
PubMed: 38779247
DOI: 10.7759/cureus.58703