Intraocular Pressure Reduction Research Articles

Swiss Multicenter Ab Interno XEN45 Gel Stent Study: 2-Year Real-World Data.

The aim of this study was to investigate the 2-year postoperative efficacy of the XEN45 Gel Stent by evaluating the reduction of intraocular pressure (IOP) and the need for eye pressure-lowering medications in a multicenter setting in Switzerland. Patients with various types of glaucoma who received a XEN45 Gel Stent with or without combined phacoemulsification cataract surgery at five hospitals in Switzerland were retrospectively enrolled. Pre- and postoperative IOP, the number of antiglaucoma medications, and the need of subsequent interventions to control IOP were assessed. The success rate was defined as a ≥ 20% reduction of IOP 2years postoperatively without the need for subsequent glaucoma surgery. A total of 345 eyes were included: 44.3% with primary open-angle, 42.0% pseudoexfoliation, and 13.7% with other types of glaucoma. Of these, 206 patients were followed for 2years. Preoperatively, the mean IOP was 26.3 ± 8.9mmHg and the mean number of antiglaucoma medications administered was 3.0 ± 1.3. Two years postoperatively, the success rate was 66.0% (95% confidence interval 59.3-72.1%), the IOP had dropped by 43.8% to 14.8 ± 5.7mmHg, and the number of medications was reduced by a mean of 2.0 ± 1.7 per day. Postoperative complications and the need for interventions remained low. The XEN45 Gel Stent successfully reduced IOP and the number of antiglaucoma drugs in most patients at 2years postoperatively.

Effect of a fixed combination of ripasudil and brimonidine on aqueous humor dynamics in mice

Ripasudil–brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ripasudil induces transient vasodilation, brimonidine transient vasoconstriction. Investigating effects on IOP, aqueous dynamics, and EVP in mice eyes by microneedle and constant-pressure perfusion methods, and on cytoskeletal and fibrotic proteins changes in HTM cells by a gel contraction assay and immunocytochemistry. Ripasudil, K-232, and brimonidine droplets significantly reduced IOP at 30 min, with K-232 sustaining the effect at 60 min. For EVP, only K-232 exhibited reduced EVP until 60 min after instillation. In vitro, ripasudil inhibited gel contractility and TGFβ2-induced fibrotic changes, whereas brimonidine did not. K-232 significantly lowered IOPs in mice by combining the effects of ripasudil and brimonidine. Brimonidine alone also showed IOP reductions with enhanced outflow facility, and the drug did not interfere with the effects of ripasudil on the trabecular meshwork outflow; K-232 and ripasudil alone both significantly lowered the EVP and enhanced outflow facility, demonstrating that K-232 efficiently reduces IOPs.

Comparing Outcomes of Tube Versus Trabeculectomy Among Patients with Angle-closure Glaucoma

PurposeCompare outcomes of tube shunt surgery (Tube) and trabeculectomy with Mitomycin C (Trab-MMC) in patients with angle-closure glaucoma (ACG). DesignRetrospective, nonrandomized comparative study. SubjectsA total of 80 eyes from 80 patients with ACG who underwent either Tube (N = 50) or Trab-MMC (N = 30) between January 2015 and January 2022 at Massachusetts Eye and Ear. MethodsReviewed and analyzed 390 visits from patient charts. Main outcome measuresKaplan-Meier (KM) success rates, Intraocular pressure (IOP), medication burden, best-corrected visual acuity (BCVA), adjusted hazard ratios (HRs), and complications. ResultsBaseline demographics were similar between both groups, except for a higher proportion of patients with pseudophakia and prior incisional ocular surgery in the Tube group. The Trab-MMC procedure had significantly higher Kaplan-Meier complete success (CS) rates than the Tube procedure, but similar qualified success (QS) rates. Under QS, the cumulative probability of survival was 87% in the Tube group and 83% in the Trab-MMC group at year 1 (P=0.77), and 75% in the Tube group and 58% in the Trab-MMC group at year 2 (P=0.14). Under CS, the cumulative probability of survival was 13% in the Tube group and 59% in the Trab-MMC group at year 1 (P<0.001), and 11% in the Tube group and 41% in the Trab-MMC group at year 2 (P<0.001). Both Tube and Trab-MMC procedures resulted in significant patterns of IOP and medication reduction from baseline up to 2 years with mean IOP reduced to 12.6 ± 5.9 mmHg on 2.8 ± 1.4 medications after Tube, and 12.1 ± 6.6 mmHg on 2.4 ± 1.7 medications after Trab-MMC. Patients who underwent Trab-MMC required less IOP-lowering medications at every follow-up visit up to year 1, but a similar number at year 2. No significant differences were found in IOP reduction, BCVA, or complication rates between groups.” ConclusionWe demonstrate that Trab-MMC confers similar IOP reduction and QS rates to Tube placement in ACG patients. Trab-MMC, however, demonstrated greater medication burden reduction up to 1 year, and more favorable CS rates up to 2 years, while still maintaining similar complication rates to Tube.

Efficacy and safety of first-line or second-line selective laser trabeculoplasty for normal-tension glaucoma: a multicentre cohort study

Background/aimsThis study aimed to investigate and compare the efficacy and safety of first-line and second-line selective laser trabeculoplasty (SLT) in Japanese patients with normal-tension glaucoma (NTG).Methods100 patients with NTG were...

A digoxin derivative that potently reduces intraocular pressure: efficacy and mechanism of action in different animal models.

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human α2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the α2 isoform of Na,K-ATPase, which is expressed strongly in nonpigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive nonhuman primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 h) and extended (7-10 days) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. 1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. 2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicate that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.NEW & NOTEWORTHY When applied topically, a cyclobutyl derivative of digoxin (DcB) potently reduces intraocular pressure in an ocular hypertensive nonhuman primate model (Macaca fascicularis), associated with increased aqueous humor (AH) flow rate (AFR). The mechanism of action of DcB involves increased AH outflow facility as detected in enucleated perfused porcine eyes and, in parallel, increased (AH) inflow as detected in isolated porcine ciliary epithelium. DcB might have potential as a drug for the treatment of open-angle human glaucoma.

The Efficacy of Fibrin Sealant in Sutureless Deep Sclerectomy - Preliminary Outcomes.

Deep sclerectomy with fibrin adhesive can constitute a safe alternative to the classic procedure using sutures, providing non-allergenic, non-toxic and secure adhesion with no sign of aqueous humor outflow obstruction postoperatively. To evaluate short- and medium-term postoperative results of deep sclerectomy (DS) with a fibrin sealant. This prospective, noncomparative, interventional case-series involves 12 eyes of 12 patients with uncontrolled open-angle glaucoma (OAG) who underwent DS with Esnoper (Clip or V2000) implant between February 2021 and March 2022. A novel method of wound closure (sclera, Tenon´s fascia and conjunctiva) employing fibrin glue was used instead of classic sutures. Surgical outcomes assessed include: intraocular pressure (IOP) and glaucoma therapy (GT) reduction, best-corrected visual acuity (BCVA) changes and number of complications registered peri- and postoperatively. All measurements were performed preoperatively, as well as at 1 day, at 1 and 2 weeks, and at 1, 2, 3, 6, 9 and 12 months after surgery. The mean IOP decreased from 24.0±9.1mmHg to 13.8±6.3mmHg at one year postoperatively (P<0.001). Kaplan-Meier survival analysis revealed complete and qualified success rates of 83.3% and 91.7%. The mean GT decreased from 3.2±1.1 to 0.8±1.3 drugs 12 months after surgery (P<0.001). Nd:YAG goniopunture was performed in 2 eyes at 1 and 12 months postoperatively. No significant BCVA changes were registered. Perioperatively, we noted a trabeculo-descemet microperforation in one eye, transient hypotony in 5 eyes and mild hyphema in 2 eyes. Fibrin adhesive provided an effective closure in sutureless DS in the patients included in our study. This modification of classical DS may simplify the surgical technique, ensure secure wound adaptation, optimize healing, and lower the risk of inflammation and fibrosis postoperatively.

Surgical outcomes including visual improvement after glaucoma surgery in patients with neovascular glaucoma

PurposeThis study aimed to evaluate the prognostic factors affecting surgical outcomes, including visual acuity (VA) improvement, after glaucoma surgery in patients with neovascular glaucoma (NVG). MethodsThe medical records of 116 patients (116 eyes) with NVG who had undergone trabeculectomy or Ahmed glaucoma valve implantation were reviewed retrospectively. The primary outcome measure was surgical success at 6 postoperative months, defined as sufficient intraocular pressure (IOP) reduction (IOP ≤21 mmHg, ≥20% reduction, regardless of topical medication use) without additional glaucoma surgery, hypotony, or progression to no light perception. Success was categorized as complete or qualified based on whether an improvement in VA was observed in addition to the abovementioned definition. ResultsThe complete and qualified success rates at 6 months were 44.6% and 92.2%, respectively. Age (p = 0.001), preoperative best-corrected VA (p = 0.031), duration of decreased VA (p = 0.001), closed-angle status (p = 0.013), and etiology (p = 0.007) differed significantly between the groups with and without complete success. Multivariate analysis revealed that age (odds ratio [OR] 1.05; p = 0.026), duration of decreased VA (OR 1.05; p = 0.016), and 360° closed-angle status (OR 3.27; p = 0.031) were risk factors for surgical failure according to the complete success criteria, but not the qualified success criteria. ConclusionsPatients with NVG showed improved visual prognosis and successful IOP reduction after glaucoma surgery at a relatively younger age if the duration of visual loss was not prolonged and the angle status was not completely closed.

PRESERFLO™ Microshunt: 1-Year Results of a 25-Gauge vs. 27-Gauge Needle Tract.

Background: The purpose of this study was to evaluate the effectiveness and safety of the PreserFlo™ microshunt (PMS) using a 25-Gauge vs. 27-Gauge needle tract. Methods: This is a prospective postoperative examination of 60 glaucoma eyes that received a PMS. The main outcome measures were intraocular pressure (IOP), glaucoma drug score (GDS), Kaplan-Meier success rates, complications, and secondary intervention rates. Two subgroups were formed for data comparison: 27-Gauge (27G), and 25-Gauge (25G). Success was defined as IOP < 18 mmHg together with ≥20% IOP reduction with medication allowed (qualified success = QS18) or not (full success = FS18). Results: IOP and GDS were reduced from baseline to the 1-year study visit as follows: All eyes from 23.4 ± 8.6 mmHg (3.1 ± 0.9) to 15.1 ± 5.9 mmHg (0.8 ± 1.1); 25G from 24.2 ± 7.3 mmHg (3.0 ± 0.8) to 12.7 ± 2.7 mmHg (0.5 ± 0.8); and 27G from 23.1 ± 9.2 mmHg (3.1 ± 1.0) to 16.2 ± 6.7 mmHg (0.9 ± 1.2). IOP at one year was lower in the 25G group compared to the 27G group (p = 0.035). Bleb needling was required in eight (13.3%) eyes and open bleb revisions in three (5.0%). Transient hypotony occurred in 21% and choroidal effusion in 8% of all eyes. Choroidal effusions were more frequent in the 25G group (21%) compared to the 27G group (2%, p = 0.031). One-year success rates were significantly higher in the 25G group compared to the 27G group for both QS18 (25G: 67.9% vs. 27G: 35.7%, p = 0.002) and FS18 (25G: 63.6% vs. 27G: 29.2%, p = 0.007). Conclusions: The PreserFlo microshunt is an effective and safe glaucoma surgery with a low rate of bleb revisions or needlings. We show that the 25G needle tract might be more efficient for IOP control at the cost of increased IOP-related complications compared to 27G.

Three-year clinical outcome of XEN45 Gel Stent implantation versus trabeculectomy in patients with open angle glaucoma

ObjectiveTo reliably compare the three-year clinical outcome and safety of XEN45 Gel Stent implantation (XEN) vs. trabeculectomy (TRAB) in patients with glaucoma.Subject/methodsWe conducted a retrospective cohort study with patients with primary open angle or pseudoexfoliation glaucoma with uncontrolled intraocular pressure (IOP) undergoing XEN or TRAB at the Innsbruck University Clinic of Ophthalmology and Optometry, Austria and analysed changes in IOP, numbers of IOP-lowering medications, and complete surgical success (i.e., IOP ≤ 18 mmHg, ≥20% IOP reduction and not requiring IOP-lowering medication) up to 36 months postoperatively.ResultsBetween 2013 and 2019, we performed XEN Gel Stent implantation in 58 eyes and trabeculectomy in 84 eyes. From baseline to 36 months, mean IOP decreased from 23.4 to 13.8 mmHg (mean reduction 35%, 95% confidence interval 23–48%, p < 0.001) in the XEN group and from 25.1 to 11.2 mmHg (mean reduction 50%, 41–60%, p < 0.001) in the TRAB group. TRAB provided higher IOP reduction than XEN Gel Stent implantation at 12, 24, and 36 months (all p < 0.05). In XEN versus TRAB, IOP-lowering medication was required by 98.3% vs. 97.6% before surgery (p = 0.781), differed significantly at month 12 (43.2% vs. 2.0%, p < 0.001)but not at month 24 or 36. Complete surgical success was achieved in 40.0% vs. 62.8% at month 24 (adjusted odds ratio 2.70; 1.04–7.00, p = 0.040) and 27.3% vs. 56.8% at month 36 (4.36; 1.25–15.18, p = 0.021).ConclusionCompared to XEN, TRAB was associated with lower intraocular pressure, less IOP-lowering medication, and higher probability of achieving complete surgical success over a 36-month follow-up period.

Effects of reduction in intraocular pressure after trabeculotomy on axial length and intraocular lens selection.

To investigate the relationship between intraocular pressure (IOP) and axial length (AL) and to compare the refractive predicted error in patients who have undergone cataract surgery alone or in combination with trabeculotomy. Hospital. Single-center, retrospective, case-control. The medical records of patients who had undergone cataract surgery alone or in combination with trabeculotomy using the Tanito microhook were retrospectively reviewed. Patients were grouped into cataract surgery alone (CAT) or cataract surgery combined with trabeculotomy (LOT) groups. Demographic data, preoperative and postoperative IOP and AL, and surgically induced astigmatism (SIA) were analyzed before and 1 month postoperatively to evaluate the interplay between IOP, AL, and refractive outcomes. 52 eyes (52 patients) underwent LOT, and 67 eyes (67 patients) underwent CAT. The mean IOP at baseline did not differ between the groups; the change in IOP (dIOP) was significantly higher in the LOT group than in the CAT group. The mean AL at baseline and the change in AL (dAL) were 24.0 ± 1.2 mm and 0.16 ± 0.11 mm, respectively, in the LOT group, and 23.8 ± 1.1 mm and 0.11 ± 0.070 mm, respectively, in the CAT group. The difference in dAL was also significant. In the LOT group, dIOP and dAL were significantly correlated. The mean SIA vectors did not significantly differ between the groups. AL decreased because of the reduction in IOP after cataract surgery combined with trabeculotomy. Consequently, the refractive target error was greater, and the postoperative refractive outcome showed a tendency toward hyperopia.

Needle goniotomy decreases early intraocular pressure spike compared with phacoemulsification alone

PurposeTo evaluate the effect of needle goniotomy during phacoemulsification cataract surgery on early IOP spikes in patients with glaucoma compared with phacoemulsification alone. DesignRetrospective case control series MethodsCataract surgeries with concurrent goniotomy for glaucoma (n = 46) were compared with controls (n = 115) with and without glaucoma. IOP was measured prior to surgery and monitored through six months postoperatively. Between-group differences in IOP and postoperative IOP reduction were tested with ANOVA and Welch's 2-sided t-tests. Demographic, clinical, and intraoperative variables were also analyzed for significant association with postoperative IOP using univariate analysis. The incidence of IOP spike was evaluated according to two criteria: IOP > 30 mmHg or IOP > 10 mmHg above baseline. ResultsPhaco-goniotomy significantly lowered IOP at postoperative day one and month six. Following goniotomy, IOP was reduced on average 28 % (95 % CI [21, 36]) at month six compared with baseline, a mean reduction of -6.3 mmHg (95 % CI [-8.6, -4.0]), and a significantly greater reduction than in glaucoma controls (1 %, 95 % CI [-9, 7] and -0.3 mmHg, 95 % CI [-1.7, 1.1], p < 0.05). The average month six IOP following phaco-goniotomy was 12.9 mmHg (95 % CI [11.6, 14.1]), significantly lower than for glaucoma controls (15.6 mmHg, 95 % CI [14.0, 17.3], p < 0.05). The incidence of early IOP spike was significantly higher in glaucoma controls (23.1 %) than in the phaco-goniotomy cohort (6.0 %) (OR = 4.5, p < 0.05). There were no associations between CDE, ultrasound and aspiration time, or irrigation volumes on postoperative IOP. We showed that preoperative IOP was the only significant contributor to postoperative IOP reduction after phaco-goniotomy. ConclusionIncidence of early postoperative IOP elevation after phacoemulsification alone was 4.5 times higher than after phaco-goniotomy. Needle goniotomy may be a consideration for IOP lowering in glaucomatous eyes having cataract surgery.

Minimally invasive micro sclerostomy (MIMS) procedure in the treatment of open-angle glaucoma

BackgroundTo evaluate the safety and efficacy of the Minimally Invasive Micro Sclerotomy (MIMS) procedure in the management of uncontrolled open-angle glaucoma.MethodsA prospective, open-label, single-arm clinical evaluation with intra-subject comparisons performed at the Ophthalmologic Center after S.V. Malayan, Yerevan, Armenia. Included were adults with primary open-angle glaucoma (OAG) (N = 114) or exfoliative glaucoma (N = 6) who were uncontrolled (IOP > 21) on tolerated topical medication. Mild (N = 7), moderate (N = 66) and severe (n = 47) cases were prospectively included without preselection. Following subconjunctival Mitomycin C, an ab-interno MIMS procedure was performed alone (N = 100) or combined with phacoemulsification (N = 20). Patients were followed for 52 weeks. Procedure-related complications and adverse events were recorded. Success criteria were defined as -5 < IOP ≤ 21mmHg OR a reduction in IOP of ≥ 20% from baseline with (qualified success) or without (complete success) hypotensive medications.ResultsMean patient age was 69 ± 10.1 years. The mean duration of the procedure was 2:01 ± 0:41 min:sec. Scleral drainage channels were achieved in all cases. No device malfunctions, intraoperative complications, or serious adverse events were reported. Iris plugging of the sclerostomy site and early spikes in IOP were the most common adverse events. The only reason for failure was final IOP > 21 mmHg on tolerated medication. At 52 weeks (n = 93), mean IOP decreased by 38% from baseline (P < 0.001), from 27.9 ± 3.7 to 17.5 ± 5.3 mmHg, a difference of 10.5 mmHg (95% CI: -11.7, -9.3). One-year qualified success was documented in 82.1% (95% CI: 72.9%,89.2%) of the patients and complete success, in 70.5% (60.3-79.4%). 60% (95 CI:49.4%,69.9%) of the patients achieved maximum IOP level of 14 mmHg or at least 30% reduction in IOP.ConclusionsMIMS procedure is a relatively simple, short and safe minimally invasive bleb-forming procedure. Its efficacy, as found in this short-term evaluation, lends it suitable for mild and moderate uncontrolled open-angle glaucoma patients.Trial registrationClinicalTrials.gov ID: NCT04503590 2019-05-29.

Efficacy and Safety of Rho Kinase Inhibitors vs. Beta-Blockers in Primary Open-Angle Glaucoma: A Systematic Review with Meta-Analysis.

Background: In order to support the positioning of Rho kinase inhibitors (Rhokis) in the European market for the treatment of glaucoma, scientific evidence comparing the efficacy and safety of Rhokis and beta-blockers (β-βs) in the treatment of open-angle glaucoma after 3 months was assembled through a systematic review and meta-analysis (meta-A) of randomized controlled trials (RCTs). Methods: Relevant articles were searched for on PubMed, EMBASE, and the Cochrane Library. Of the 251 articles found, three met all eligibility criteria. These three articles were assessed for risk of bias. Data were extracted and a random effects meta-A was performed. The studies' methods were homogeneous but there was great heterogeneity within the data (I2 = 92-93%; p < 0.001). Results: All studies had low risk of bias. The meta-A showed statistically better efficacy of β-βs, resulting in an intraocular pressure (IOP) reduction mean difference of 1.73 (1.19-2.27) at 8 a.m., 0.66 (0.19-1.15) at 10 a.m. and 0.49 mmHg (0.001-0.98) at 4 p.m., compared to Rhokis. This difference is not clinically significant as intra-operator variability of IOP measurements varies from ±2 to ±3 mmHg The adverse effects of Rhokis were essentially topical, whereas β-βs mainly caused systemic side effects. Conclusions: This Meta-A showed that Rhokis are clinically non-inferior to beta-blockers in reducing IOP. Rhokis have a better safety profile.

A Randomized, Controlled Comparison of NCX 470, a Nitric Oxide-Donating Bimatoprost, and Latanoprost in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The MONT BLANC Study

PurposeTo compare intraocular pressure (IOP)-lowering efficacy and safety profile of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with glaucoma or ocular hypertension. DesignProspective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial. Methods: Participants691 subjects with open-angle glaucoma or ocular hypertension and unmedicated IOP of IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye. Study Procedures: Subjects were randomized to treatment with NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. To identify the final NCX 470 dose, an interim analysis was performed after at least 30 subjects in each group had completed the Week 2 visit. Enrolled subjects were randomized to this final NCX 470 dose, 0.1%, or latanoprost for 12 weeks. Main outcome measure: We evaluated non-inferiority followed by superiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months. ResultsNCX 470 0.1% was the final dose and 661 subjects were analyzed that received NCX 470 0.1% (n=328) or latanoprost (n=333). At baseline, the mean (SD) IOP at 8AM and 4 PM was 28.3 (2.0) mmHg and 25.5 (2.5) mmHg, respectively, in the NCX 470 0.1% group, and was significantly reduced at all on-treatment time points, with reductions ranging from 8.0-9.7 mmHg (p<0.0001 at each time point). Likewise, mean (SD) baseline IOP at 8AM and 4PM was 28.2 (2.0) mmHg and 25.4 (2.4) mmHg, respectively, in the latanoprost group and was significantly reduced at all on-treatment time points, with reductions ranging from 7.1-9.4 mmHg (p<0.0001 at each time point). At the 3-month visit, mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (p<.05) at 4 of the 6 time points. Noninferiority versus latanoprost was established at all 6 timepoints. The most common adverse event was conjunctival/ocular hyperemia and was more common in the NCX 470 group compared to latanoprost; 8 NCX 470 and 6 latanoprost subjects discontinued due to adverse events. ConclusionThe NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with open-angle glaucoma or ocular hypertension at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.

Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists.

We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.

An Evaluation of the Efficacy and Safety of Timolol Maleate 0.5% Microdrops Administered with the Nanodropper

To examine if 12.5 μl timolol maleate 0.5% microdrops dispensed with the Nanodropper Adaptor provide noninferior intraocular pressure (IOP) reduction compared with conventional 28 μl drops in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. Both eyes of subjects received 1 commercially available drop or both eyes of subjects received 1 microdrop of timolol maleate 0.5%. We measured IOP, resting heart rate (HR), and blood pressure (BP) at baseline and 1, 2, 5, and 8 hours after timolol administration. The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). Adaptor-mediated microdrops and conventional drops of timolol significantly decreased IOP compared with baseline at all timepoints. Noninferiority was established at 3 of 4 timepoints. Heart rate decreases with Nanodropper were approximately 3 beats per minute (bpm) less than with conventional drops. Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. Proprietary or commercial disclosure may be found after the references.

Effect of digital ocular massage on intraocular pressure and Schlemm’s canal dimensions

Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. Using anterior segment optical coherence tomography, the Schlemm’s canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman’s test, p < 0.001). There was significant change in SC area (median 10,063.5 μm2 at baseline to median 10,151.0 μm2 after ocular massage, Wilcoxon test, p = 0.02), and TM thickness (median 149.8 μm at baseline to 144.6 ± 25.3 μm after ocular massage, Wilcoxon test, p = 0.036). One-third of the subjects demonstrated collapse of the SC area (−2 to −52%), while two-thirds showed expansion of the SC area (2 to 168%). There were no significant changes in SC diameter (270.4 ± 84.1 μm vs. 276.5 ± 68.7 μm, paired t-test, p = 0.499), and TM width (733.3 ± 110.1 μm vs. 733.5 ± 111.6 μm, paired t-test, p = 0.988). Eyes with a higher baseline IOP demonstrated a greater IOP reduction (Pearson correlation coefficient r = −0.521, p < 0.001). Eyes with smaller SC area at baseline showed greater SC area expansion (Pearson correlation coefficient = −0.389, p < 0.001). Greater IOP reduction appeared in eyes with greater SC area expansion (Pearson correlation coefficient r = −0.306, p = 0.01). Association between change in IOP and change in TM thickness was not significant (Spearman’s ρ = 0.015, p = 0.902). Simple digital ocular massage is an effective method to lower IOP values, and change in the SC area was significantly associated with IOP changes.

Combined Endoscopic Cyclophotocoagulation and Phacoemulsification Versus Phacoemulsification Alone in the Glaucoma Treatment: A Systematic Review and Meta-Analysis.

The complete safety and efficacy of endoscopic cyclophotocoagulation (ECP) remainunclear in the literature and, to our knowledge, there are no current meta-analyses on phaco-ECP versus phacoemulsification alone to date. Thus, we conducted a systematic review and meta-analysis comparing these two strategies through studies, assessing the effectiveness and safety of outcomes in a population with glaucoma. The protocol for this systematic reviewwas registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023482376). We systematically searched PubMed, Embase, and Web of Science from inception to December 2023. A random-effects model was used for all analyses due to heterogeneity. Review Manager 5.3 (Cochrane Centre, The Cochrane Collaboration, Denmark) was used for statistical analysis. Finally, nine studies were included in this comprehensive review and a total of 5389 eyes were analyzed in our study. In comparison to the ECP and phacoemulsification group, those receiving phacoemulsification alone showed better results in best-corrected visual acuity(MD 0.09; CI 95% 0.03 to 0.16; I²=0%), but worse outcomes in intraocular pressure (IOP) (MD -1.49; 95% CI -2.29 to -0.68; I²=29%) and use medications (MD -0.75; 95% CI -0.94 to -0.56; I²=0%) in the last visit. Complication rates, both general and serious, were significantly different between the groups, indicating the potential impact of combined procedures on patient outcomes. Thus, combining ECP with phacoemulsification for glaucoma treatment showed sustained IOP reduction and decreased medication dependence. However, higher complication rates suggest careful consideration of risks. More extensive research with larger trials and longer follow-ups is needed to validate findings and address limitations, providing valuable insights into this treatment approach.

Machine learning-assisted prediction of trabeculectomy outcomes among patients of juvenile glaucoma by using 5-year follow-up data.

To develop machine learning (ML) models, using pre and intraoperative surgical parameters, for predicting trabeculectomy outcomes in the eyes of patients with juvenile-onset primary open-angle glaucoma (JOAG) undergoing primary surgery. The study included 207 JOAG patients from a single center who met the following criteria: diagnosed between 10 and 40 years of age, with an IOP of >22 mmHg in the eyes on two or more occasions, open angle on gonioscopy in both eyes, with glaucomatous optic neuropathy, and requiring a trabeculectomy for IOP control. Only the patients with a minimum 5-year follow-up after surgery were included in the study. A successful surgical outcome was defined as IOP ≤18 mmHg (criterion A) or 50% reduction in IOP from baseline (criterion B) 5 years after trabeculectomy. Feature selection techniques were used to select the most important contributory parameters, and tenfold cross-validation was used to evaluate model performance. The ML models were evaluated, compared, and prioritized based on their accuracy, sensitivity, specificity, Matthew correlation coefficient (MCC) index, and mean area under the receiver operating characteristic curve (AUROC). The prioritized models were further optimized by tuning the hyperparameters, and feature contributions were evaluated. In addition, an unbiased relationship analysis among the parameters was performed for clinical utility. Age at diagnosis, preoperative baseline IOP, duration of preoperative medical treatment, Tenon's thickness, scleral fistulation technique, and intraoperative mitomycin C (MMC) use, were identified as the main contributing parameters for developing efficient models. The three models developed for a consensus-based outcome to predict trabeculectomy success showed an accuracy of >86%, sensitivity of >90%, and specificity of >74%, using tenfold cross-validation. The use of intraoperative MMC and a punch for scleral fistulation compared to the traditional excision with scissors were significantly associated with long-term success of trabeculectomy. Optimizing surgical parameters by using these ML models might reduce surgical failures associated with trabeculectomy and provide more realistic expectations regarding surgical outcomes in young patients.

Intraocular pressure across the lifespan of Tg-MYOCY437H mice

Transgenic C57BL/6 mice expressing human myocilinY437 (Tg-MYOCY437H) are a well-established model for primary open-angle glaucoma (POAG). While the reduced trabecular meshwork (TM) cellularity due to severe endoplasmic reticulum (ER) stress has been characterized as the etiology of this model, there is a limited understanding of how glaucomatous phenotypes evolve over the lifespan of Tg-MyocY437H mice. In this study, we compiled the model's intraocular pressure (IOP) data recorded in our laboratory from 2017 to 2023 and selected representative eyes to measure the outflow facility (Cr), a critical parameter indicating the condition of the conventional TM pathway. We found that Tg-MYOCY437H mice aged 4−12 months exhibited significantly higher IOPs than age-matched C57BL/6 mice. Notably, a decline in IOP was observed in Tg-MYOCY437H mice at 17−24 months of age, a phenomenon not attributable to the gene dosage of mutant myocilin. Measurements of the Cr of Tg-MYOCY437H mice indicated that the age-related IOP reduction was not a result of ongoing TM damage. Instead, Hematoxylin and Eosin staining, immunohistochemistry analysis, and transmission electron microscopic examination revealed that this reduction might be induced by degenerations of the non-pigmented epithelium in the ciliary body of aged Tg-MYOCY437H mice. Overall, our findings provide a comprehensive profile of mutant myocilin-induced ocular changes over the Tg-MYOCY437H mouse lifespan and suggest a specific temporal window of elevated IOP that may be ideal for experimental purposes.