Ocular Hypertension Research Articles

Therapeutic Potential of Cannabinoids in Glaucoma – Hit or Myth? - A Review

Introduction: Glaucoma is a leading cause of irreversible blindness, characterized by elevated intraocular pressure (IOP) that damages the optic nerve. Current treatments mainly focus on reducing IOP, but some patients do not respond adequately to conventional therapies. Cannabinoids, particularly Δ9-tetrahydrocannabinol (Δ9-THC), have been investigated as potential adjunctive treatments for glaucoma. Studies have shown varying effects of cannabinoids on IOP regulation, though their precise mechanisms remain unclear. Aim of Study: This study aims to evaluate the therapeutic potential of cannabinoids in the treatment of glaucoma by examining their effects on IOP, their mechanisms of action, and the risks and benefits associated with their use. Material and methods: A comprehensive literature review of studies on the therapeutic potential of cannabinoids in glaucoma was conducted using the PubMed database. Results and Conclusions: Cannabinoids, especially Δ9-THC, have demonstrated the ability to reduce IOP in both healthy individuals and glaucoma patients. However, the effect is typically short-lived, lasting only 3-4 hours. The efficacy of cannabinoids in reducing IOP is influenced by the method of administration (oral, intravenous, inhalation) and the delivery system used for topical application. Despite some promising results, the use of cannabinoids as a mainstream glaucoma treatment is limited by factors such as the short duration of action, the potential for addiction, and the occurrence of adverse effects like tachycardia, hypotension, and cognitive impairment. Although cannabinoids offer a unique approach to glaucoma management, further research is necessary to address these limitations and determine their long-term therapeutic viability.

Goniosynechialysis for Chronic Angle-closure Glaucoma after Extracapsular Cataract Extraction: A Case Report

Purpose: We present a case of goniosynechiolysis in the treatment of chronic angle-closure glaucoma with persistent peripheral anterior synechia (PAS) after extracapsular cataract extraction (ECCE) for phacomorphic glaucoma that remained uncontrolled using topical glaucoma medications.Case summary: A 59-year-old woman presented with right eye pain and visual loss that started 3 days ago. Examination revealed an intraocular pressure (IOP) of 46 mmHg, a narrow central anterior chamber, and peripheral iridocorneal touch, indicative of phacomorphic glaucoma. Although ECCE was performed, PAS was not adequately resolved. Initially, visual acuity, IOP, and visual field were controlled with a single topical glaucoma medication. However, progressive retinal nerve fiber layer thinning and uncontrolled IOP, despite maximal medical therapy. Therefore, goniosynechiolysis was performed at 24 months after ECCE. The procedure reduced IOP from 25 mmHg to 13 mmHg without complications, such as hyphema, cyclodialysis, and fibrin formation.Conclusions: Goniosynechiolysis can be a safe and effective intervention for chronic angle-closure glaucoma with persistent PAS and elevated IOP.

Efficacy and Safety of a Fixed-Dose Combination of Brinzolamide 1%/Timolol 0.5% vs. Dorzolamide 2%/Timolol 0.5% in Indian Patients With Primary Open-Angle Glaucoma or Ocular Hypertension: A Randomized Phase 3 Study

Efficacy and Safety of a Fixed-Dose Combination of Brinzolamide 1%/Timolol 0.5% vs. Dorzolamide 2%/Timolol 0.5% in Indian Patients With Primary Open-Angle Glaucoma or Ocular Hypertension: A Randomized Phase 3 Study

Synapses and dendritic spines are eliminated in the primary visual cortex of mice subjected to chronic intraocular pressure elevation

Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease. Glaucoma directly impairs retinal ganglion cells and their axons, leading to axonal transport dysfuntion, subsequently causing secondary damage to anterior or posterior ends of the visual system. Accordingly, recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway. However, the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear. In this study, we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye. We found that, after 4 weeks of chronic ocular hypertension, the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye. This was accompanied by glial cell activation and increased expression of inflammatory factors. After 8 weeks of ocular hypertension, we observed a reduction in the number of excitatory and inhibitory synapses, dendritic spines, and activation of glial cells in the primary visual cortex contralateral to the affected eye. These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex, providing new insights into the pathogenesis of glaucoma.

Overexpression of the inwardly rectifying potassium channel Kir4.1 or Kir4.1 Tyr9 Asp in Müller cells exerts neuroprotective effects in an experimental glaucoma model

Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells, which is involved in retinal ganglion cell apoptosis in glaucoma. Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma. In this study, we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation. Following this, we treated Müller glial cells in vitro and in vivo with the mGluR I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr9Asp overexpression. We found that both Kir4.1 and Kir4.1 Tyr9Asp overexpression inhibited activation of Müller glial cells. Subsequently, we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr9Asp in the eye, and observed similar results in Müller cells in vivo as those seen in vitro. Both Kir4.1 and Kir4.1 Tyr9Asp overexpression inhibited Müller cell activation, regulated the balance of Bax/Bcl-2, and reduced the mRNA and protein levels of pro-inflammatory factors, including interleukin-1β and tumor necrosis factor-α. Furthermore, we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr9Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia. In this co-culture system, we observed elevated adenosine triphosphate concentrations in activated Müller cells, increased levels of translocator protein (a marker of microglial activation), and elevated interleukin-1β mRNA and protein levels in microglia induced by activated Müller cells. These changes could be reversed by Kir4.1 and Kir4.1 Tyr9Asp overexpression in Müller cells. Kir4.1 overexpression, but not Kir4.1 Tyr9Asp overexpression, reduced the number of proliferative and migratory microglia induced by activated Müller cells. Collectively, these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma. Kir4.1 and Kir4.1 Tyr9Asp overexpression attenuated Müller cell activation, reduced ATP/P2X receptor-mediated interactions between glial cells, inhibited microglial activation, and decreased the synthesis and release of pro-inflammatory factors, consequently ameliorating retinal ganglion cell apoptosis in glaucoma.

Abstract 4135239: Pausing Under Pressure: Ocular Hypertension as an Atypical Cause of Heart Block

A 67-year-old male with a history of hypertension presented to the emergency department with abnormal cardiac monitor results. Prior to this, he was diagnosed with primary open-angle glaucoma by ophthalmology and underwent left-sided aqueous tube shunt placement, which was complicated by hypotony requiring revision and holding of all topical glaucoma medications. Concurrently, he was noted to have an irregular heart rhythm during a routine physical. In office ECG showed normal sinus rhythm, but subsequent 14-day continuous ECG monitor showed sinus bradycardia with nadir heart rate of 21 beats-per-minute and 114 ventricular pauses (longest 4.8 seconds) primarily due to second-degree atrioventricular (AV) block, Mobitz type 1, but also periods of high-grade AV block. He was sent to the emergency department for expedited pacemaker evaluation. On further review, heart block and ventricular pauses occurred exclusively over a 12-hour period that temporally coincided with a hospitalization for acute ocular hypertension following shunt revision. His intraocular pressure peaked at 56 mmHg (normal range 10-21 mmHg), then normalized to 21 mmHg after acetazolamide and anterior chamber paracentesis. Bradycardia resolved following ophthalmic intervention. Bradyarrhythmias were attributed to excess vagal tone from acute ocular hypertension via an atypical but recognized cause of the oculocardiac reflex, and pacemaker placement was avoided. The oculocardiac reflex is a reflex bradycardia involving the trigeminal and vagus nerves. Cardiac effects are consistent with other vagally-mediated bradyarrhythmias, including sinus bradycardia, AV block, and even asystole. This reflex occurs commonly during traction on extraocular muscles during strabismus surgery, but can be seen in other orbital and ocular stimuli. To our knowledge, this is the first documented case of ocular hypertension leading to atrioventricular block through this mechanism. This case illustrates the importance of (1) clinical context of abnormal events during extended cardiac monitoring, (2) understanding the oculocardiac reflex as a cause of bradyarrhythmias, and (3) ruling out reversible medical causes of dysrhythmias prior to permanent device implantation.

Evaluation of the macula, retinal nerve fiber layer and choroid thickness in premature ovarian failure using spectral-domain optical coherence tomography.

The aim of our study is to describe the basal findings at the first diagnosis of the disease in patients with premature ovarian failure (POF) and to draw attention to the early changes in the macula, optic nerve head and choroid. In a prospective case-control study, 90 patients with POF and 90 control patients were evaluated. All participants underwent the same ophthalmic examination, including visual acuity, intraocular preasure measurement, anterior and posterior segment evaluation, macular and coroidal thickening, and retinal nerve fiber layer (RNFL) measurements with the same device (Spectral Domain OCT, software version 5.6.3.0, Heidelberg, Germany). The median age was 30.00 (28.00-31.00) in the control group and 29.00 (27.00-31.00) in the POF group (p = 0.249). The median thickness of the temporal outer macular region was statistically significantly thinner in the POF group (295.00 (289.00-303.25)) compared to the control group (306.00 (290.75-328.00)) (p < 0.001). There was a statistically significant decrease in all choroidal regions (p < 0.001), including the central, nasal 500, nasal 1500, temporal 500, and temporal 1500 regions in the POF group according to the control group. An increase in intraocular pressure in the postmenopausal period has been reported, suggesting a link between the postmenopausal decline in sex hormones and glaucoma. Our study is the first to monitor changes in choroidal, retinal thickness and RNFL in POF images showing early menopausal symptoms.

Short-term intraocular pressure changes after intravitreal aflibercept 2 mg, aflibercept 8 mg and faricimab: a prospective, comparative study

Background/aimsIntravitreal injection (IVT) of anti-vascular endothelial growth factor agents is the standard of care for several retinal diseases but can cause intraocular pressure (IOP) elevations. This study investigates short-term postinjection...

Risk of Age-Related Macular Degeneration in Patients with Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome (UPEXS)

Objective: To investigate any relationships between exfoliation syndrome or exfoliation glaucoma and age-related macular degeneration utilizing the Utah population database. Design: This was a retrospective, case–control cohort study. Subjects, Participants, and/or Controls: We identified 3405 patients diagnosed with exfoliation syndrome (XFS) or exfoliation glaucoma (XFG) during a dilated eye exam within the UHealth system from 1996 to 2021, whose dry or wet age-related macular degeneration (AMD) status was assessed. A population-based control pool of 257,714 UHealth patients with no XFS/XFG diagnosis and a dilated eye exam history from 1996 to 2021 was compiled, with its patients randomly selected and individually matched 3:1 to cases based on sex and age at index diagnosis of their respective case. Methods: A covariate analysis was performed of characteristics and risk factors associated with XFS/XFG, which included race/ethnicity, residence location, partner/marital status, and family history of XFS/XFG, obesity, tobacco use, alcohol use, osteoporosis/vitamin D deficiency, primary/essential hypertension, ocular hypertension, and cataract surgery. Main Outcome Measure: We studied the trends of non-exudative (dry) or exudative (wet) AMD in a large Utah population study of XFS/XFG patients and controls. Results: Of 3396 XFS/XFG patients, as well as 10,179 individually matched 3:1 control patients, 64% were female and the average age of XFS onset was 74.3 yrs. In a univariate model, we observed a very modest increased risk of wet AMD in XFS/XFG patients (odds ratio, OR = 1.14, 95% confidence interval (CI) 0.99–1.32), which did not achieve statistical significance (p = 0.07). After adjusting for the main effects of potential confounders, there was no greater presentation of AMD in XFS/XFG patients when compared with controls (dry AMD: OR = 0.94, 95% CI 0.85–1.05, p = 031; wet AMD: OR = 0.98, 95% CI 0.83–1.14, p = 0.76). In XFS/XFG patients compared to controls, the risk of having cataract surgery was elevated (OR = 2.39, 95% CI 2.18–2.62). However, after accounting for an interaction with AMD, XFS/XFG patients who underwent cataract surgery did not exhibit an increased risk of either dry or wet AMD (dry AMD: OR = 0.91, 95% CI 0.80–1.03; wet AMD: OR = 0.89, 95% CI 0.75–1.07). The risk of AMD in XFS/XFG patients vs. controls showed no association with osteoporosis/vitamin D deficiency for dry (OR 0.78 95% CI 0.66–0.92 p = 0.004) or wet AMD (OR = 0.72 95% CI 0.56–0.92 p = 0.01), while we found a borderline positive association with both dry and wet AMD if they had osteoporosis/vitamin D deficiency. Conclusion: Using the Utah Population Database, we found that a cataract surgery history significantly impacts the association between AMD and XFS, and that vitamin D deficiency/osteoporosis is a significant confounder of the association. However, no direct association between XFS and AMD was found in this study.

Efficacy and safety of intravitreal conbercept and triamcinolone acetonide for wet age-related macular degeneration in China: a meta-analysis.

Several studies have investigated the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wet age-related macular degeneration (wAMD), but the results are controversial. Therefore, this meta-analysis aims to evaluate the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wAMD. A total of seven databases were searched for literature on the treatment of wAMD with Conbercept, with the search period from database inception to May 2024. Patients in the experimental group received Conbercept treatment, while patients in the control group received Triamcinolone acetonide treatment. The observed indicators included central macular thickness, incidence of adverse reactions, clinical efficacy, and best-corrected visual acuity. Relative risk (RR) and mean difference (MD) were used as effect measures. A total of 12 studies with 864 patients were included in the meta-analysis. The results showed that the experimental group had a significantly better central macular thickness (MD = - 42.68, 95% CI = - 55.04 ~ - 30.32, P < 0.001), clinical response rate (RR = 1.25, 95% CI = 1.12 ~ 1.39, P < 0.001), and best-corrected visual acuity (MD = 0.16, 95% CI = 0.12 ~ 0.20, P < 0.001) compared to the control group. In terms of adverse events, the overall incidence of adverse events was lower in the experimental group (RR = 0.26, 95% CI = 0.14 ~ 0.51, P < 0.001) compared to the control group. Specifically, the incidence of intraocular pressure elevation (RR = 0.33, 95% CI = 0.12 ~ 0.94, P = 0.04) and intraocular inflammation (RR = 0.17, 95% CI = 0.03 ~ 0.97, P = 0.05) was lower in the experimental group compared to the control group, but there was no significant difference in the incidence of subconjunctival hemorrhage (RR = 0.7, 95% CI = 0.14 ~ 3.5, P = 0.66) and corneal edema (RR = 0.2, 95% CI = 0.04 ~ 1.12, P = 0.07). Conbercept demonstrated superior efficacy in treating wAMD compared to triamcinolone acetonide, with a lower incidence of adverse reactions. However, the current meta-analysis included a limited number of studies, with only two studies evaluating best-corrected visual acuity (BCVA). Further high-quality randomized controlled trials (RCTs) are warranted to validate these findings.

Continuous intraocular pressure variations following positional transitions in normal subjects and open angle glaucoma patients using a contact lens sensor system.

To evaluate the efficacy of a novel contact lens sensor system (CLS) in detecting continuous intraocular pressure (IOP) variations following positional transitions, and to explore these IOP variation patterns among normal subjects, untreated glaucoma patients, and untreated ocular hypertension (OHT) subjects. This prospective comparative study included 20 normal subjects, 14 high tension glaucoma (HTG) patients, 16 normal tension glaucoma (NTG) patients, and 14 OHT subjects. Participants wore the CLS for continuous IOP monitoring while undergoing sequential body position changes: from sitting to supine to a 10° head-down tilt (HDT), with each position maintained for ten minutes. Continuous IOP parameters, including mean, peak, and fluctuation (peak minus valley) in each position, as well as increment (peak minus starting value), interval (time to arrive peak), and velocity (increment divided by interval) after two position transitions, were compared among different positions and groups, respectively. Normal subjects, HTG and NTG patients exhibited higher CLS IOP mean and peak in supine/HDT positions compared to sitting (P < 0.05), but the mean or peak in HDT did not significantly differ from that in supine (P > 0.2). In OHT, all IOP parameters showed no significant difference among various positions (P > 0.1), except for velocity. Comparisons among groups revealed that during the transition from sitting to supine, HTG demonstrated higher IOP increment than other three groups and higher velocity than normal subjects (P < 0.05). NTG patients exhibited no significant differences in IOP increment, interval and velocity, compared to normal subjects (P > 0.05). The CLS proved effective in continuously recording IOP responses following positional changes in normal and glaucomatous eyes. Transitioning from sitting to supine resulted in increased IOP among normal subjects, HTG and NTG patients, but not in OHT. Compared to normal subjects, this IOP increase was more pronounced and rapid in HTG, but comparable in NTG. WHAT IS KNOWN : Positional transitions can induce IOP variations, which differ among normal subjects and glaucoma patients, and potentially relate to glaucomatous neuropathy. However, prior findings are constrained by the discontinuity of traditional tonometry. This study utilized a novel contact lens sensor system (CLS) to continuously monitor IOP during positional transitions in normal subjects and untreated glaucoma/OHT subjects. Continuous IOP outcomes revealed that normal subjects, HTG patients, and NTG patients exhibited an increase in IOP when transitioning from sitting to supine, whereas OHT did not. Compared to normal subjects, this increase in IOP was more pronounced and rapid in HTG patients, but similar in NTG.

The impact of different forms of exercise on intraocular pressure, blood flow, and the risk for primary open angle glaucoma.

Primary open angle glaucoma (POAG) is a chronic disease characterized by progressive optic nerve damage and irreversible loss of vision, often diagnosed at late stages. Elevated intraocular pressure (IOP) is the major risk factor for its onset and progression while older age, myopia, genetic factors, blood pressure (BP), and reduced ocular blood flow (OBF) have also been linked to the disease. Different forms of exercise are known to have significant, but variable, effects on IOP, BP, ocular perfusion pressure (OPP), OBF and oxygen metabolism, and ultimately the risk for development and progression of POAG. While population-based studies lack agreement regarding the relationship between exercise and POAG status, data suggests that resistance training causes a short-term increase in IOP, BP, and OPP. Conversely, aerobic exercise has been shown to cause a short-term decrease in IOP and increase in BP and OPP. Research also suggests that following an exercise program over an extended period may lead to a long-term decrease in IOP, however its cessation results in a prompt return to baseline levels. Data suggests normal vascular autoregulation ensures minimal change in OBF following extended exercise unless OPP rises ∼70% above baseline. Although exercise may alter IOP, BP, and OBF, both acutely and chronically, it is currently uncertain if physical activity significantly alters risk for the onset and progression of POAG.

Optimal Timing for Intraocular Pressure Measurement Following Phacoemulsification Cataract Surgery: A Systematic Review and a Meta-Analysis

Post-operative increases in intraocular pressure (IOP) are a frequent complication following phacoemulsification cataract surgery. Assessment of IOP is an essential element in post-operative checks. Despite this, guidance regarding the optimal timing remains vague. The purpose of this meta-analysis was to determine the current status of evidence that may help guide best practice regarding the optimal time following phacoemulsification cataract surgery to measure IOP. A comprehensive literature search was performed on MEDLINE and EMBASE. In two stages, independent reviewers screened articles that reported IOP measurements following uncomplicated cataract surgery. Risk of Bias Assessment was conducted following data extraction. The meta-analysis incorporated 57 randomized clinical studies involving a total of 6318 participants and 7089 eyes. Post-operative hour one had a significant decrease in IOP from baseline, while hour two had a non-significant increase. Post-operative hours four, six, and eight were the only timepoints to have a significant increase in IOP. Finally, post-operative day one had no significant change in IOP, while day two had a non-significant decrease. These results suggest that the optimal time to measure IOP is within the first 4–8 h following phacoemulsification cataract extraction. Taking measurements too soon or too late could result in missed IOP spikes.

Sensitive HPLC Method to Support Pre-formulation Studies and to Determine Critical Quality Attributes of Therapeutic Contact Lenses Containing Dorzolamide Hydrochloride

Background: Dorzolamide hydrochloride (DRZ) is a carbonic anhydrase inhibitor used to treat glaucoma and ocular hypertension. Drug-eluting contact lenses, such as Acuvue Theravision ™ with Ketotifen, offer improved drug delivery and reduced side effects compared to eye drops. Drug-loaded nanoparticle-loaded contact lenses can sustain drug release and enhance comfort for extended wear. Objective: High buffer concentration and low pH increase the risk of damage to silica-bonded columns. Therapeutic contact lenses face challenges related to critical lens parameters, including the estimation of drug incorporation and release due to interference of lens matrix leaching. There is currently no analytical method available for estimating DRZ in contact lenses. Method: The HPLC method, which was developed and validated using ICH Q2 (R1) criteria, used a C18 column (250 mm × 4.6 mm, 5 μm) as a stationary phase and methanol:water (70:30 v/v) as the mobile phase. The detecting wavelength was 253 nm. Moreover, to support the efficiency of the developed method, the marketed formulation of DRZ eye drops, drug purity, and loading in contact lenses were analysed. The method was also employed to determine the Critical Quality Attributes (CQAs) of therapeutic contact lenses and drug release and drug leaching during the sterilization process. Result: The developed HPLC method shows Rt for DRZ at 2.881 minutes with good linearity (r2 &gt; 0.998) between 2-32μg/mL, precision (RSD &lt; 2%), accuracy (Recovery &gt; 99.5%), sensitivity, and specificity for quantifying DRZ in marketed formulations and therapeutic contact lenses. The developed method is devoid of any buffer or modifier in the mobile phase, making it safer for the stationary phase. This method mitigates the interference of lens matrix leaching, which induces an overestimation of DRZ. All the result for therapeutic contact lenses was found to be closely aligned with theoretically expected results, confirming the reliability of the developed HPLC method for therapeutic contact lenses. Conclusion: This method is specific, accurate, and precise for quantifying DRZ in commercial formulations and newly developed therapeutic contact lenses. It effectively evaluates the critical quality attributes of these lenses, demonstrating their reliability for assessing their performance and ensuring quality in therapeutic applications.

Preclinical and Clinical Pharmacokinetics of a New Preservative-Free Bimatoprost 0.01% Ophthalmic Gel to Treat Glaucoma and Ocular Hypertension.

Purpose: Pharmacokinetic evaluation of ocular penetration and systemic accumulation of preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel). Methods: In a preclinical study, pigmented rabbits received a single ocular administration of PFB 0.01% gel (N = 15) or preserved bimatoprost 0.01% or 0.03% ophthalmic solution [PB 0.01% (N = 15) or PB 0.03% (N = 15)]. The aqueous humor, iris, and ciliary body were analyzed for bimatoprost+bimatoprost free acid. In a Phase 1, randomized, open-label clinical study, healthy participants received PFB 0.01% gel (N = 20) or PB 0.01% (N = 20) daily in each eye (Days 1-15). Bimatoprost levels in human plasma were analyzed on Days 1 and 15. All serological analyses used validated methods. Adverse events were collected throughout and ocular assessments were performed on Days 1 and 15. Results: In the preclinical study, Cmax (bimatoprost+bimatoprost free acid) for PFB 0.01% gel, PB 0.01%, and PB 0.03% was 50.2, 26.3, and 59.9 ng/mL; AUC0.5-8 h was 134.0 ng·h/mL, 67.0 ng·h/mL, and 148.0 ng·h/mL. In the clinical study, systemic exposure to bimatoprost (AUC0-last) on Days 1 and 15 was lower for PFB 0.01% gel (0.5248 and 0.5645 ng·min/mL) than PB 0.01% (0.8461 and 0.7551 ng·min/mL), with no systemic accumulation of bimatoprost in either group. There were no clinically important differences between groups in ocular or systemic tolerability in the clinical study and no serious adverse events. Conclusions: PFB 0.01% gel showed improved ocular penetration compared with PB 0.01%. Systemic absorption was comparable, with a favorable clinical safety profile, supporting PFB 0.01% gel as a potential treatment for glaucoma and ocular hypertension.

Primary Open-Angle Glaucoma Polygenic Risk Score and Risk of Disease Onset

Primary open-angle glaucoma (POAG) is a heritable disease. A polygenic risk score (PRS) threshold may be used to identify individuals at low risk of disease onset. To assess the utility of a POAG PRS to identify ocular hypertensive individuals at low risk of disease onset. This is a post hoc analysis of the Ocular Hypertension Treatment Study (OHTS), a multicenter randomized clinical trial across 22 centers in the US conducted among 1636 participants with ocular hypertension from February 1994 to April 2019 with available genetic data. Of the 1636 original participants, 1077 had available genetic data; after excluding 67 for missing data, data quality concerns, or ancestry other than European or African, 1010 were included in the present analysis. Data for this report were analyzed from November 2023 to June 2024. From 1994-2002, participants were randomized to receive topical intraocular pressure (IOP)-lowering medications. From 2002 onwards, all participants were given topical IOP-lowering medications. Twenty-year conversion rates by POAG PRS threshold, baseline randomization status, and OHTS clinical risk tertile. Among the 1010 participants in this study, 563 (65.8%) were female, and the mean (SD) age was 55.9 (9.4) years. In a mixed-effects logistic regression model adjusted for OHTS risk factors for conversion to POAG and randomization status, a PRS under the 48th percentile was associated with a 1.49 times higher likelihood of disease-free status after 20 years of follow-up (95% CI, 1.04-2.15; P = .03; unadjusted hazard ratio [HR], 1.64; 95% CI, 1.13-2.38; P = .009), compared with high polygenic risk. When we stratified the trial cohort into nongenetic OHTS clinical risk tertiles, the largest differences in survival probability at 20 years based on PRS threshold was observed in eyes in the highest tertile, initial observation group (20-year conversion rate: 61.1% in the high polygenic risk group vs 23.8% in the low polygenic risk group; 95% CI, -63.0 to -11.6; P = .01), with randomization to early treatment partially mitigating the effect of high genetic risk (20-year conversion rate: 37.3% in the high polygenic risk group vs 24.1% in the low polygenic risk group; 95% CI, -35.6 to 9.3%; P = .32). These findings support considering use of a POAG PRS threshold to identify individuals at low risk of disease onset, with those below the PRS threshold more likely to have lower conversion rates over 20 years. Among those considered at highest risk based on the OHTS clinical risk model, early treatment may partially offset the association with high genetic risk but provide limited benefit for those with low genetic risk. ClinicalTrials.gov Identifier: NCT00000125.

Self-assembled latanoprost loaded soluplus nanomicelles as an ophthalmic drug delivery system for the management of glaucoma

Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability.

A small disc size, a big challenge: effect of optic disc size on the correlation between peripapillary choroidal thickness, peripapillary retinal nerve fiber layer, and ganglion cell layer.

We aimed to analyze the effect of optic disc size on the correlation between the peripapillary choroid (PPC), peripapillary retinal nerve fiber layer (RNFL), and macular ganglion cell inner plexiform layer (MGCIPL) thicknesses in subjects with ocular hypertension (OHT) and primary open angle glaucoma (POAG). This study included 61 eyes with a disc area (DA) of ≤ 1.63 mm2, 92 eyes with a DA of 1.63-2.42 mm2, and 59 eyes with a DA of ≥ 2.42 mm2 in small disc, regular disc, and large disc groups, respectively. The swept-source optical coherence tomography scans of the PPC, RNFL, and MGCIPL were analyzed according to disc size. The three groups did not significantly differ in RNFL or MGCIPL measurements, but the PPC measurement was statistically significantly higher in the small disc group and statistically significantly thinner in the large disc group. Most of the correlations observed between the RNFL and MGCIPL measurements and eye characteristics in the regular disc group were not detected in the small and large disc groups. While the RNFL and MGCIPL were well correlated in all disc size groups, the PPC did not correlate with the RNFL or MGCIPL in any of the groups. Overall, the RNFL and MGCIPL measurements were consistent across all three disc sizes. While the PPC was thicker in small discs than in larger discs, it was not correlated with the RNFL or MGCIPL.

Safety and efficacy of the Yamane technique for intraocular three-piece lens implantation in Egyptian patients diagnosed with Marfan syndrome: a retrospective study

BackgroundThis study aimed to investigate the safety and efficacy of the Yamane technique (flanged intrascleral haptic fixation with double-needle technique /FIHFT) for three-piece intraocular lens (IOL) implantation in Egyptian patients diagnosed with Marfan syndrome (MFS) presented with subluxated lenses (ectopia lentis, EL).MethodsThis was a retrospective evaluation of thirty-three patients who were diagnosed with MFS and had subluxated lenses in a total of forty eyes. Seven of these patients had bilateral subluxation. Lensectomy or phacoemulsification was performed with limited anterior vitrectomy, followed by IOL implantation using the FIHFT method. Data was collected from medical records, including preoperative and postoperative corrected distant visual acuity (CDVA) using logarithm of the minimal angle of resolution (log MAR), preoperative and postoperative refractions, intraoperative and postoperative complications, and follow-up periods.ResultsThe mean age of patients in the study was 30.79 years, with a mean follow-up of 23.9 months. Post-surgery, the refractive sphere decreased significantly from -9.1 ± 1.4 diopter (D) to -1.4 ± 0.7 D, and cylinder measurements dropped from -4.5 ± 0.8 D to -1.4 ± 0.6 D. The spherical equivalent (SEQ) also declined from -11.4 ± 1.5 D to -2.1 ± 0.8 D. The CDVA improved from 0.80 ± 0.32 to 0.18 ± 0.10 log MAR (P < 0.001). No intraoperative complications were identified. Postoperative complications included IOL decentration (12.5%), vitreous hemorrhage (7.5%), IOL slippage (5%), IOL tilt (5%), and retinal detachment (RD) (5%). Further surgical procedures were necessary for only four cases (10%), all of which had positive outcomes. IOL tilting and slippage occurring at average ages of 18 and 19 years, respectively. No other complications, such as hypotony, elevated intraocular pressure (IOP), corneal edema, iritis, IOL dislocation, cystoid macular edema (CME) or endophthalmitis, were reported.ConclusionsThe Yamane technique has proven effective and safe for treating subluxated lenses in Egyptian patients with Marfan Syndrome, resulting in improved visual acuity with minimal complications, mostly minor and manageable. Comprehensive fundus examinations before and after surgery are essential for promptly identifying retinal breaks and reducing the risk of retinal detachment. IOL tilting and slippage are more common in younger patients.

Impaired axonal transport at the optic nerve head contributes to neurodegeneration in a novel Cre-inducible mouse model of myocilin glaucoma.

Elevation of intraocular pressure (IOP) due to trabecular meshwork (TM) dysfunction, leading to neurodegeneration, is the pathological hallmark of primary open-angle glaucoma (POAG). Impaired axonal transport is an early and critical feature of glaucomatous neurodegeneration. However, a robust mouse model that replicates these human POAG features accurately has been lacking. We report the development and characterization of a novel Cre-inducible mouse model expressing a DsRed-tagged Y437H mutant of human myocilin (Tg.CreMYOCY437H). A single intravitreal injection of HAd5-Cre induced selective MYOC expression in the TM, causing TM dysfunction, reducing outflow facility, and progressively elevating IOP in Tg.CreMYOCY437H mice. Sustained IOP elevation resulted in significant retinal ganglion cell (RGC) loss and progressive axonal degeneration in Cre-induced Tg.CreMYOCY437H mice. Notably, impaired anterograde axonal transport was observed at the optic nerve head before RGC degeneration, independent of age, indicating that impaired axonal transport contributes to RGC degeneration in Tg.CreMYOCY437H mice. In contrast, axonal transport remained intact in ocular hypertensive mice injected with microbeads, despite significant RGC loss. Our findings indicate that Cre-inducible Tg.CreMYOCY437H mice replicate all glaucoma phenotypes, providing an ideal model for studying early events of TM dysfunction and neuronal loss in POAG.