Intraocular Pressure Reduction Research Articles

Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice

PurposeTo investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express Stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained intraocular pressure (IOP) lowering agent with a reduced ocular surface side effect profile. DesignIn vivo pre-clinical investigation in mice SubjectsC57BL/6J, DBA/2J, FP receptor knockout mice MethodsNormotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 x 109 viral genomes [VGs]) in one eye and the same volume and concentration of ssAAV2-GFP or the same volume of PBS in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. FP receptor knockout mice were injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or PBS. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. IOP was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1 and other treatments including daily topical latanoprost. Main outcome measuresIOP assessment ResultsSubconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 2 post injection (17.4%; 17.1 ± 0.8 vs 14.1 ± 0.8 mmHg, P<0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs 14.8 ± 0.9 mmHg, P<0.001) and steroid-mediated ocular hypertensive mice (19.4%; 18.7 ±0.9 vs 15.1 ± 0.5 mmHg, P<0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild type (15.9%) and FP receptor knockout (15.7%) mice compared to the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost. ConclusionsSubconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular tolerability that also avoids the daily dosing requirements of currently available medications.

Combined Micro-Invasive Glaucoma Surgery (MIGS) with Phacoemulsification in Open Angle Glaucoma: A Systematic Review and Meta-Analysis

The purpose of this study is to compare efficacies and safeties of combined phacoemulsification-Micro-Invasive Glaucoma Surgeries (MIGS) to phacoemulsification only in eyes with open angle glaucoma. Systematic Review and Meta-Analysis. A multi-database literature search was conducted to caputre MIGS articles published prior to April 19th, 2024. Key exclusion criteria were inadequate follow-up, significant loss to follow-up, standalone MIGS surgery, or primary outcomes unreported. MIGS were grouped according to mechanisms of action: 1) Trabecular Meshwork (TM) bypass which improve aqueous drainage into Schlemm's canal (SC), 2) non-GATT Goniotomies which remove TM with varying devices, and 3) GATT which remove TM with a catheter or suture placed into SC. Efficacy was measured by reductions in IOP and medications while safety was compared using incidence of sight-threatening and other adverse events. A total of 95 studies were included, accounting for 9733 eyes followed up at 1-year. The control group had a baseline IOP of 16.9(95%CI 15.9-17.9) mmHg on 1.43(1.19-1.68) medications and a postoperative IOP of 15.2(14.4-15.9) mmHg on 0.80(0.54-1.00) medications. The TM bypass baseline IOP was 18.2(17.6-18.7) mmHg on 1.89(1.78-2.01) medications which lowered to an IOP of 14.8(14.5-15.1) mmHg on 0.80(0.65-0.95) medications at 1-year-postoperation. The non-GATT goniotomy baseline IOP was 20.0(19.2-20.8) mmHg on 2.30(2.09-2.53) medications, and at 1-year followup the IOP was 14.6(14.3-15.0) mmHg on 1.41(1.22-1.62) medications. Lastly, the GATT baseline IOP of 21.8(19.5-24.1) mmHg on 2.90(2.36-3.44) medications was reduced to an IOP of 12.5(10.0-15.0) mmHg on 0.73(0.37-1.09) medications at 1-year-postoperation. All MIGS groups had equal or lower rates of sight-threatening events and secondary glaucoma surgery when compared to control. GATT had the highest hyphema rate at 27.7(13.5-44.5) % followed by non-GATT goniotomy with 15.5(7.8-25.0) %. These were both significantly higher than TM bypass and control groups, with hyphema rates of 3.5(1.6-5.9) % and 4% (only 1 study reporting hyphema rate), respectively. Based on current peer-reviewed articles, there is strong evidence that when compared to phacoemulsification alone, combined phaco-MIGS is beneficial for patients with open angle glaucoma and does not increase the incidence of vision-threatening events. Key limitations of our review stem from heterogeneities in protocol design or outcome reporting, and a limited number of high-quality studies with long-term follow-up.

The Impact of Baseline Intraocular Pressure on Initial Treatment Response in the LiGHT Trial: Selective Laser Trabeculoplasty versus Medication

The Laser in Glaucoma and Ocular Hypertension Trial demonstrated the efficacy and safety of selective laser trabeculoplasty (SLT) compared with topical hypotensive medication as first-line therapy for ocular hypertension and open-angle glaucoma. This substudy explored the impact of pretreatment (baseline) intraocular pressure (IOP) on treatment response. Post hoc analysis of randomized control trial data. A total of 1146 eyes from 662 patients were included in this analysis: 559 eyes in the SLT group and 587 in the medication group. Intraocular pressure reduction at 8 weeks after treatment with either SLT or prostaglandin analog (PGA) eye drops was assessed at different levels of baseline IOP, and the groups were compared. Differences in absolute and percentage IOP lowering between SLT and PGA groups were tested with a linear mixed-effects model. Differences in the probability of achieving ≥ 20% IOP lowering between SLT and PGA groups, at different levels of baseline IOP, were estimated using a logistic mixed-effects model. Intraocular pressure-lowering response to SLT versus PGA eye drops. Mean IOP was not significantly different between the groups at baseline or 8 weeks after treatment initiation. Both treatments showed greater IOP lowering at higher baseline IOP and less IOP lowering at lower baseline IOP. Selective laser trabeculoplasty tended to achieve more IOP lowering than PGA drops at higher baseline IOP. Prostaglandin analog drops performed better at lower baseline IOP, and the difference compared with SLT, in terms of percentage IOP reduction, was significant at baseline IOP of ≤ 17 mmHg. A significant difference was found in the relationship between baseline IOP and probability of ≥ 20% IOP lowering between the two treatments (P= 0.01), with SLT being more successful than PGA at baseline IOP of more than 22.5 mmHg. We confirm previous reports of greater IOP lowering with higher baseline IOP for both SLT and PGA drops. In treatment-naïve eyes, at higher baseline IOP, SLT was more successful at achieving ≥ 20% IOP lowering than PGA drops. At lower baseline IOP, a statistically greater percentage, but not absolute, IOP lowering was seen with PGA drops compared with SLT, although the clinical significance of this is uncertain. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcomes and Baseline Predictors of Failure in Primary Standalone Xen45 Gel Stent versus Trabeculectomy for Glaucoma

PurposeTo compare safety, effectiveness and baseline predictors of failure in standalone primary Xen45 gel stent (Xen) vs trabeculectomy (Trab) in glaucoma. DesignRetrospective study SubjectsSubjects that underwent primary Xen or Trab augmented by mitomycin-C with at least 12 months follow-up. MethodsMultinational observational study of eyes in the Fight Glaucoma Blindness international registry Main outcome measuresThe primary outcome was success at 12 months defined by IOP reduction ≥ 20% from baseline and ≤ threshold IOPs of 15mmHg, 18mmHg and 21mmHg with (qualified) or without (complete) medications and without secondary glaucoma surgery. Multivariable mixed effects cox regression models were used to identify risk factors for failure in each cohort. Results701 eyes (Xen, 308; Trab, 393) of 596 subjects were included with baseline IOP being significantly higher (22.4 vs 19.9 mmHg, p < 0.001) and baseline medications significantly lower in the Xen vs the Trab group (2.9 vs 3.4, p <0.001). Baseline visual field (VF) mean deviation (MD) was less severe in the Xen group (-9.47 vs -13.04 dB, p < 0.001). The proportion of complete surgical success was significantly lower in the Xen vs Trab group across the three upper IOP limits at 12 months; 32% vs 52% at 15mmHg, 37% vs 54% at 18mmHg, and 39% vs 55% at 21mmHg (p < 0.001). The incidence of post-operative numerical and symptomatic hypotony was lower in the Xen vs Trab group. In the Xen cohort, a higher failure rate was associated with Asian ethnicity (HR, 1.97; 95% CI, 1.03-3.79) and use of oral acetazolamide at baseline (HR, 1.74; 1.13-2.70), while a lower failure rate was associated with diagnosis of ocular hypertension/open angle glaucoma suspect (HR, 0.52; 0.28-0.94) and secondary open angle glaucoma (HR, 0.45; 0.25-0.8). Exposure to prostaglandin analogue was associated with greater failure in the Trab group (HR, 2.66; 1.18-6.01). ConclusionsThere was significantly greater complete success at 12 months across all complete success definitions for Trab compared to Xen, while the rate of post-operative hypotony was significantly lower in Xen group. Asian ethnicity and use of oral acetazolamide at baseline were associated with greater failure in Xen, while exposure to prostaglandin analogue was associated with greater failure in Trab patients. Such baseline predictors of success and failure may help guide patient selection for subconjunctival minimally invasive glaucoma surgery in patients undergoing surgical intervention.

Effectiveness of pars plana Ahmed® valve implantation in patients with refractory glaucoma

PurposeTo evaluate the success rate and complications of the Ahmed FP7 valve implanted via Pars Plana in a group of vitrectomized patients with refractory glaucoma and anterior segment abnormalities from January 2018 to June 2023. MethodsQuasi-experimental, prospective study. Eleven eyes with refractory glaucoma were included. Participants underwent a comprehensive ophthalmic examination, including assessment of intraocular pressure (IOP) reduction, visual acuity, characterization of glaucoma type, and number of antiglaucoma medications. ResultsThe mean baseline IOP was 37.3 ± 11 mmHg, which decreased to 13.5 ± 3.0 mmHg after one year. The qualified success rate was 63.7%, while the complete success rate was 36.3%. The most common diagnosis was neovascular glaucoma in 36.4% of cases. The most frequent postoperative complications were choroidal detachment and hypotony. ConclusionsOur data suggest that implantation of the Ahmed FP7 valve via pars plana is an effective and safe option for patients with refractory secondary glaucoma.

The Effects of the STREAMLINE™ Surgical System versus Endoscopic Cyclophotocoagulation in Primary and Secondary Glaucoma

Introduction: Glaucoma is an optic neuropathy that is the second most common cause of blindness worldwide and affects over three million Americans. Currently, the only known modifiable risk factor to prevent glaucomatous damage is to decrease the intraocular pressure (IOP). The STREAMLINE™ Surgical System (SSS) is a microinvasive glaucoma (MIGs) device that can create a goniotomy and dilates the drainage system of the eye to reduce IOP. Question &amp; Significance: This study aims to compare the effects on intraocular pressure of patients that had cataract surgery combined the SSS, endoscopic cyclophotocoagulation (ECP), or ECP with SSS in patients with primary and secondary glaucoma’s for 6 months post operatively. Methods: This is a retrospective chart review of patients that had cataract surgery with either ECP, SSS, or SSS + ECP from April 1st, 2022 through April 1st, 2023. Primary endpoints were mean IOP reductions and medication reliance at 6 months compared to baseline. Secondary outcomes were best corrected visual acuity (BCVA), number of patients with  20% decrease in IOP, number of patients with a decrease in IOP lower medications, and significant complications after treatment. Results: Comparing 6-month post-operative mean IOPs in these treatment groups, a significant reduction was noted only in the ECP group at the 6-month visit (p&lt;0.003). No statistically significant reduction was found in either the SSS (p=0.333) or SSS+ECP (p=0.134) groups. The percent of patients having a  20% decrease in IOP from baseline were 52%, 10%, and 38% for ECP, SSS, and SSS+ECP groups, respectively. Conclusions: In the SSS only group, we found a significantly smaller proportion of patients able to achieve the  20% IOP reduction at only 10% of patients compared to other previous studies. This difference is likely due no medication washout in our study. This study did find similar decrease in IOP lowering medications.

Assessment of the correction of neuroretinal changes using 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate in the modeling of POAG

Introduction: Elevated intraocular pressure (IOP) has been identified as a major risk factor for the progression of primary open-angle glaucoma (POAG). However, the continued progression of POAG in some patients, despite the successful IOP reduction, indicates that IOP-independent mechanisms contribute to the development of optical neuropathy. Thus, it is relevant to further determine the molecular mechanisms of retinal ganglion cells (RGCs) death in order to develop therapeutic approaches independent of IOP in order to stop the progression of the disease. The aim: to research the correction possibility of experimental POAG induced by intracameral (i.c.)administration of hyaluronic acid using 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate. Materials and Methods: The study of the correction of neuroretinal changes on a model of POAG was carried out on Wistar rats. In order to correct POAG, 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate (EHMP-NAT) was used at doses of 27.5 mg/kg intramuscularly (i.m.) and 0.5 mg/kg instillationally. Further, the effectiveness of the combination of timolol eye drops with i.m. EHMP-NAT was studied. The effectiveness of the studied agents was evaluated on the 67th day of the experiment using ophthalmoscopic semi-quantitative assessment of the fundus condition, ocular tonometry, estimation of oxidative stress markers and markers involved in retinal apoptosis pathway using enzyme-linked immunosorbent assay (ELISA). Results: On the model of POAG, it was shown that 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyltaurinate with the laboratory code EHMP-NAT has a pronounced neuro-, retinoprotectiveaction based on the data of ophthalmoscopy, semi-quantitative assessment of the fundus condition, ocular tonometry, estimation of oxidative stress markers (GSH, CAT, SOD) and markers involved in retinal apoptosis (BAX, BCL-2, Caspase-3). On the 67th day of the experiment, the results of a comprehensive analysis revealed that the combination of EHMP-NAT 27.5 mg/kg i.m. + timolol 0.04 mg/kg instillationally has a more pronounced protective effect than EHMP-NAT 27.5 mg/kg i.m. in monotherapy in the POAG model. Conclusion: The data obtained indicate the need for the combined use of drugs with a hypotensive effect to normalize IOP with neuroretinoprotective agents in the correction of POAG.

Assessing the Impact of PRESERFLO MicroShunt on Intraocular Pressure in Porcine Eyes Ex Vivo Using Infusion Pump System.

To evaluate the effectiveness of the PRESERFLO MicroShunt (PFM) in reducing intraocular pressure (IOP) ex vivo in porcine eyes using an infusion pump system and to simulate various IOP conditions, In this study, porcine eyes received increasing flows between 2 and 20 μL/min. IOP measurements were taken under conditions with and without the PFM [PFM (+) and PFM (-), respectively]. In the PFM (-) group, IOP increased from 7.4 mmHg to 46.3 mmHg as the flow rate increased from 2 μL/min to 20 μL/min. The rate of IOP reduction (%ΔIOP) rose with increasing flow rates, although the absolute IOP values achieved with the PFM insertion also increased. The correlation between IOPs in the PFM (-) conditions and the %ΔIOP was modeled as %ΔIOP = 22.4 Ln [PFM(-) IOP] - 41.7. According to this equation, IOP reduction by PFM insertion is 0% at IOPs of 6.4 mmHg or lower. IOP reductions of 10%, 20%, 30%, and 40% were observed when the pre-insertion IOPs were 10.1, 15.7, 24.6, and 38.4 mmHg, respectively. Achievable post-insertion IOP levels of ≤21 mmHg, ≤18 mmHg, ≤15 mmHg, and ≤12 mmHg corresponded to the initial IOPs of 33 mmHg, 26 mmHg, 20 mmHg, and 14.8 mmHg, respectively. In conclusion, the PFM effectively reduced IOP within a specific range of IOP values in an ex vivo experimental system. In clinical situations, the PFM is unlikely to be effective at low IOP levels. At higher levels, the PFM reduces IOP, but it may be insufficient to achieve the target IOP.

Evaluation of the Effectiveness of Using a Fixed Combination of Dorzolamide 2.0 % and Timolol 0.5 % in Primary Open-­Angle Glaucoma

The purpose of the work was to evaluate the effectiveness of the drug Domizia Duo® (OTCPharm JSC), which is a fixed combination (dorzolamide 20 mg/ml and timolol 5 mg/ml) in the treatment of patients diagnosed with primary open­angle glaucoma. The multicenter study involved 156 patients (280 eyes) with primary open­angle glaucoma (POAG) (136 patients — 243 eyes), primary angle­closure glaucoma (PACG) (8 patients — 15 eyes), ocular hypertension (12 patients — 22 eyes). 37 doctors from 22 medical institutions took part in the study. Patients aged 55–75 years with first­time POAG stages I–III, PAOG, ocular hypertension, as well as with abnormal intraocular pressure, patients with pseudophakia, if the diagnosis of glaucoma was made before cataract extraction and at least 6 months before the study, were included. According to the study results, intraocular pressure decreased significantly in all groups of patients and at all stages of treatment: primary open­angle glaucoma, primary angle­closure glaucoma, ocular hypertension. In 136 patients (243 eyes) with POAG, a 28 % reduction in IOP was achieved at an initial level of 25 (22–28) mm Hg. In the group of patients with PCOG (8 patients, 15 eyes), a decrease in IOP by 19 % was shown with an initial intraocular pressure of 20.1 (19.1–23.0) mm Hg. The high effectiveness of the drug Domizia Duo® (OTCPharm JSC) was established at all stages of POAG, so at stage I of newly diagnosed POAG, the reduction in IOP was 35.5 % within a month after the start of therapy, at stage II of newly diagnosed POAG by 28 %, at stage III by 44.4 %, in the group of patients with ocular hypertension, the degree of reduction in intraocular pressure was 27 % at an initial level of 26 (23–27) mm Hg. The data obtained from the study prove the high effectiveness of the fixed combination (FC) Domizia Duo® (OTCPharm JSC) against the background of good tolerability in patients with primary open­angle glaucoma (POAG) at stages I–III. The drug was also highly effective not only when prescribed as monotherapy, but also when switching from another drug or adding Domizia Duo® to treatment.

Anterior Chamber Angle and Intraocular Pressure Control After Phacoemulsification in Primary Angle Closure With Different Mechanisms.

Different mechanisms of angle closure represented distinct aspects of intraocular pressure (IOP) control after phacoemulsification. Classification of angle closure mechanisms is necessary for postoperative IOP management and glaucoma progression in primary angle closure eyes. To investigate the relationship between the anterior chamber angle (ACA) characteristics, measured by swept-source anterior segment optical coherence tomography (SS AS-OCT), and intraocular pressure (IOP) control after phacoemulsification in eyes with primary angle closure disease (PACD) with different angle closure mechanisms. PACD eyes were classified into 3 groups according to angle closure mechanisms using preoperative SS AS-OCT images; pupillary block (PB), plateau iris configuration (PIC), exaggerated lens vault (ELV). This retrospective, clinical cohort study included eighty-five eyes of 85 PACD patients: 34 with PB, 23 with PIC, and 28 with ELV. ACA parameters were measured preoperatively and 1 month postoperatively using SS AS-OCT. IOP measurements were performed preoperatively and during 6 months postoperatively. Postoperative IOP reduction and fluctuation were calculated, and their correlations with SS AS-OCT parameters were analyzed. PIC group showed the lowest postoperative IOP reduction compared with the other groups ( P =0.023). Preoperative ACA measurements were significantly associated with postoperative IOP reduction in ELV and PB groups, while postoperative measurements were in PIC group. Preoperative and postoperative change of iridotrabecular contact (ITC) index and area were correlated with postoperative IOP reduction in PB and ELV groups but not in PIC group. Postoperative ITC index ( P =0.031) and area ( P =0.003) showed significant correlations with postoperative IOP fluctuation only in PIC group. SS AS-OCT parameters including ITC index and area showed different associations with postoperative IOP control, which should be considered in determination of lens extraction and treatment of PACD eyes.

Efficacy and safety of the paul glaucoma implant in the treatment of refractory primary congenital glaucoma

PurposeTo evaluate the safety and efficacy of the PAUL Glaucoma Implant (PGI) for managing refractory primary congenital glaucoma (PCG) over a one-year period.Study DesignRetrospective.MethodsA study was conducted using the medical records of thirty eyes of 17 patients who underwent PGI surgery for the treatment of refractory PCG. Primary outcome measures included failure criteria such as intraocular pressure (IOP) > 21 mm Hg, < 20% IOP reduction, necessity for further glaucoma intervention, implant removal, or loss of vision. Secondary outcomes focused on mean IOP, average number of glaucoma medications, best corrected visual acuity (logMAR), and incidence of complications.ResultsThe mean preoperative IOP of 38.8 ± 9.2 mmHg significantly decreased to 16.1 ± 3.3 mmHg at 12 months postoperatively (p < 0.001). The average number of glaucoma medications reduced from 3.6 ± 0.5 preoperatively to 0.9 ± 1.2 at 12 months post-op. Visual acuity remained stable in 24 eyes, decreased in 4, and increased in 2. Early postoperative complications occurred in 13.3% of patients, but no late complications were reported. The cumulative success rate was 86.6%.ConclusionThe PGI appears to be a safe and effective option for managing refractory primary congenital glaucoma, demonstrating significant IOP reduction and decreased dependence on glaucoma medications over a one-year period, with a high success rate and manageable complication profile.

Fabrication of acetazolamide loaded leciplex for intraocular delivery: Optimization by 32 full factorial design, in vitro, ex vivo and in vivo pharmacodynamics

The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ − LP) using a simple one-step fabrication approach followed byoptimization employing a 32 Full Factorial Design. The ACZ – LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ − LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ − LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.

Forskolin is an effective therapeutic small molecule for the treatment of hypertrophic cardiomyopathy through ADCY6/cAMP/PKA pathway

Hypertrophic cardiomyopathy (HCM) arises from a pathogenic variant in the gene responsible for encoding the myocardium-associated protein. Forskolin (FSK), a labdane diterpene isolated from Sphingomonas capillaris, exhibits diverse pharmacological effects, including bronchospasm relief, intraocular pressure reduction, and glaucoma treatment. However, whether FSK could regulate HCM and its associated mechanism remains unclear. Here, we discovered that FSK could mitigate cardiac hypertrophy in two HCM mouse models (Myh6R404Q and Tnnt2R109Q) in vivo. Additionally, FSK could prevent norepinephrine (NE)-induced cardiomyocyte hypertrophy in vitro. It reversed cardiac dysfunction, reduced enlarged cell size, and downregulated the expression of hypertrophy-related genes. We further demonstrated that FSK's mechanism in alleviating HCM relied on the activation of ADCY6. In conclusion, our findings demonstrate that FSK alleviates hypertrophic cardiomyopathy by modulating the ADCY6/cAMP/PKA pathway, suggesting that FSK holds promise as a therapeutic agent for HCM.

Evaluation of the lamina cribrosa after topical latanoprost therapy in primary open-angle glaucoma or ocular hypertension

PurposeTo investigate that the changes of lamina cribrosa (LC) thickness and depth after latanoprost therapy in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. MethodsIn this single-center prospective cross-sectional study, 35 eyes from 35 patients with POAG or OHT (study group) and 26 age- and gender- matched healthy individuals (control group) were included. All participants were examined by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode for LC thickness and depth measurements at the first visit before latanoprost therapy and at visits after 1 (second visit) and 3 (third visit) months of latanoprost therapy. ResultsThe mean LC thickness in both horizontal and vertical scans of the study group were thinner than the control group (p < 0.001, for both). During latanoprost therapy in the study group, the LC thickness values in horizontal scans significantly differed over the three visits, gradually increased (p < 0.05). There was significantly decrease in LC depth in horizontal scans between the first and third visits, and the second and third visits (p = 0.003 and p = 0.008, respectively). The gradual decrease in LC depth in vertical scans was observed at all visits, but the statistically significant difference was between the first and third visits only (p = 0.048). ConclusionPOAG/OHT patients showed more LC thinning compared with healthy individuals. The significant increase in LC thickness and the significant decrease in LC depth were detected after IOP reduction therapy with latanoprost in ocular hypertensive/ glaucomatous eyes.

Evaluation of Intrascleral Lakes after Phaco-Viscocanalostomy using Anterior Segment Optical Coherence Tomography.

This study aimed to investigate the results of combined phacoemulsification and viscocanalostomy (phaco-VC) in a six-month follow-up and its relationship with intrascleral lake (IL) using anterior segment optical coherence tomography (AS-OCT) in patients with primary open-angle glaucoma (POAG). In total, 36 eyes with POAG eligible for phaco-VC were enrolled in this prospective observational study. All patients underwent AS-OCT evaluation and ophthalmologic examination including Goldman tonometry, cup-disc ratio assessment, best corrected visual acuity (BCVA) measurement, and antiglaucoma medication(s) prior to surgery and one, three, and six months after the surgery. The width, length, area, and circumference of the ILs were evaluated using AS-OCT at each follow-up. A total of 36 eyes of 34 patients with POAG were investigated in this study. According to the results, the mean age of the patients was 70.09 8.73 years, and the majority of the cases were male (n = 23; 63.9%). The mean preoperative intraocular pressure (IOP) was 20.11 7.22 mmHg on 2.47 1.1 medications, and the mean postoperative IOP reduced to 11.11 2.58 mmHg on 0.11 medications, which was statistically significant (P 0.001). ILs were detectable in all cases which resulted in a 100% qualified success rate. The reduction in the width, area, and circumference of the IL was significant during the six-month follow-up. The relationship between IOP changes and IL parameters on AS-OCT was not significant. This study evaluated the associations between IL changes and IOP reduction after phaco-VC. A six-month follow-up showed a notable reduction in the IL, but unexpectedly, IOP control did not decline. A reduction in IL diameter, when there is sufficient IOP control, indicates that there may be various IOP lowering mechanisms through VC other than the IL diameters. Further evaluation of VC focusing on long-term changes in IL and Schlemm's canal diameter is necessary to explain the precise mechanisms of lowering the IOP.

Effect of Bromfenac on Reducing Neuroinflammation in an Ischemia-Reperfusion Glaucoma Model.

In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.

Establishing target intraocular pressure in newly diagnosed exfoliation glaucoma patients

ABSTRACT Background This study aimed to determine the appropriate target intraocular pressure (IOP) for patients newly diagnosed with exfoliation glaucoma. Research design and methods The study followed a prospective cohort of newly diagnosed exfoliation patients for three years. The target IOP was defined using three methods to measure visual field deterioration, mean deviation (MD), visual field index (VFI), and guided progression analysis (GPA). Results Over the three years, the mean deviation (MD) values declined by an average of −3.84 (±2.61) dB, while the visual field index (VFI) values dropped by an average of 9.66 (±6.25) %. The untreated IOP at inclusion was 32.52 ± 5.54 mmHg. At the end of the study (due to treatment), it was 17.94 ± 1.82 mmHg, resulting in a reduction of 14.58 mmHg (45% reduction). Based on the MD and VFI methods, the target IOP for the whole cohort was around 14–15 mmHg, while the target IOP based on GPA was around 15 mmHg. For advanced glaucoma cases, the target IOP was around 13 mmHg. Conclusions The study concludes that the traditional reported IOP reduction of 20% and/or IOP 18–20 mmHg may not be sufficient for patients newly diagnosed with exfoliation glaucoma. Instead, the study recommends a target IOP of 14–15 mmHg for these patients. Clinical Trial Registration The study was registered in the www.clinicaltrials.gov website with the number NCT06237764.

Consistent Intraocular Pressure Reduction by Solid Drug Nanoparticles in Fixed Combinations for Glaucoma Therapy.

Efficient topical drug delivery remains a significant challenge in glaucoma management. Although nanoparticle formulations offer considerable promise, their complex preparation processes, co-delivery issues, and batch consistency have hindered their potential. A scalable fabrication strategy is developed here for preparing solid drug nanoparticles (SDNs) with enhanced drug delivery efficiency. Utilizing hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX), uniform fixed combination BM/BX SDNs are fabricated through a continuous process, improving batch-to-batch consistency for combined glaucoma treatment. With trehalose being used as a lyoprotectant, BM/BX SDNs can be stored as dry powder and easily reconstituted in phosphate buffered saline. Importantly, reconstituted BM/BX SDNs form clear, homogenous solutions, and exhibit negligible cytotoxicity and irritation, making them well-suited for topical administration as eyedrops. Ex vivo and in vivo studies demonstrated that topically applied BM/BX SDNs permeate through the cornea significantly (about two fold to three fold) compared to their hydrophilic counterparts, i.e., brimonidine tartrate, and betaxolol hydrogen chloride. Notably, BM/BX SDNs displayed consistent intraocular pressure lowering effects in vivo in both normotensive rats and glaucoma mice. Collectively, this study demonstrates the potential of the scalable fabrication strategy and the resultant BM/BX SDNs for improving glaucoma management through eyedrops.

Predictive biomarkers of intra-ocular pressure decrease after cataract surgery associated with trabecular washout in patients with pseudo exfoliative glaucoma

To investigate biomarkers of intra-ocular pressure (IOP) decrease after cataract surgery with trabecular washout in pseudo-exfoliative (PEX) glaucoma. A single-center observational prospective study in PEX glaucoma patients undergoing cataract surgery with trabecular washout (Goniowash) was performed from 2018 to 2021. Age, gender, visual acuity, IOP, endothelial cell count, central corneal thickness, medications, were collected over 16-month follow-up. Multivariable binomial regression models were implemented. 54 eyes (35 subjects) were included. Mean preoperative IOP (IOPBL) was 15.9 ± 3.5 mmHg. Postoperative IOP reduction was significant at 1-month and throughout follow-up (p < 0.01, respectively). IOPBL was a predictive biomarker inversely correlated to IOP decrease throughout follow-up (p < 0.001). At 1 and 12 months of follow-up, IOP decrease concerned 31 (57.4%) and 34 (63.0%) eyes with an average IOP decrease of 17.5% (from 17.6 ± 3.1 to 14.3 ± 2.2 mmHg) and 23.0% (from 17.7 ± 2.8 to 13.5 ± 2.6 mmHg), respectively. Performance (AUC) of IOPBL was 0.85 and 0.94 (p < 0.0001, respectively), with IOPBL threshold ≥ 15 mmHg for 82.1% and 96.8% sensitivity, 84.2% and 75.0% specificity, 1.84 and 3.91 IOP decrease odds-ratio, respectively. All PEX glaucoma patients with IOPBL greater than or equal to the average general population IOP were likely to achieve a significant sustainable postoperative IOP decrease.

One-year outcome of goniotomy with Kahook Dual Blade in primary open-angle glaucoma patients

Objectives: The objective is to describe a -year outcome of goniotomy using the Kahook Dual Blade (KDB, New World Medical Inc., Rancho Cucamonga, CA) in patients with primary open-angle glaucoma (POAG) either as a standalone or plus phacoemulsification (phaco). Material and Methods: We reviewed 12 eyes of 9 patients who had goniotomy with KDB either as a standalone or combined with cataract surgery by phaco from April 2017 to July 2018 at Eye Foundation Hospital, Ikeja, Lagos. The patients were followed for a minimum of 12 months. Results: The mean age of the patients was 66.4 ± 8.8 years. The mean pre-operative intraocular pressure (IOP) for all eyes was 18.58 ± 5.42 mmHg. After 12 months of follow-up, the mean IOP was 14.27 ± 5.22 mmHg, representing a drop of 4.31 mmHg (23.2%) from baseline. For the Phaco+KDB group, the mean IOP changed from 19.25 ± 4.56 mmHg to 15.0 ± 6.03 mmHg for the same period, representing a reduction of 4.25 mmHg (22.1%) from baseline, and for the KDB as a standalone, the mean IOP change was 4.25 mmHg (24.6%) from baseline (17.25 ± 7.45 to 13.0 ± 3.83 mmHg). For all eyes, the mean number of topical antiglaucoma medications dropped by 0.88 (36.4%) from 2.42 ± 0.90 to 1.54 ± 1.51, whereas for the Phaco+KDB group, the topical antiglaucoma medications were reduced by 1.17 (46.8%) from 2.50 ± 0.93 to 1.33 ± 1.50. However, there was no change in the number of topical antiglaucoma medications in the KDB group after 12 months of follow-up (2.25 ± 0.96 to 2.25 ± 1.50). Transient hyphema in one and posterior capsular opacity (PCO) were the only recorded post-operative complications. Conclusion: KDB, either as a standalone or with phaco, recorded at least a 20% reduction in IOP after one year of follow-up in these series.