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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. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo investigate racial and ethnic inequalities in prescription of Netarsudil, one of two anti-glaucoma medications with a novel mechanism to be introduced in the past two decades, among patients with primary open-angle glaucoma.This retrospective cohort matched study, based on electronic health records consisting of 92 million patients in the U.S, utilized Propensity Score Match, Relative Risk, Kaplan–Meier survival, and Chi-Square analysis to identify differences in rates of Netarsudil prescribing between racial and ethnic groups (non-Hispanic White, non-Hispanic Black, non-Hispanic Other Race, and Hispanic).Among the sample of patients that met Primary Open-Angle Glaucoma inclusion criteria (55,942), more White patients were prescribed Netarsudil than Black; (RR:1.24, 95% CI: 1.15-1.34) and Hispanic; (RR:1.63, 95% CI: 1.29-2.07) patients. White patients had higher prescription rates than Black patients in the Midwest (6.5% vs 4.2%; p < 0.0001) and West (11.2% vs 7.1%; p = 0.0002), higher rates than Hispanic patients in the South (4.9% vs. 2.0%; p < 0.0001) and West (11.2% vs. 7.8%; p < 0.008), but lower rates than Black patients in the Northeast (7.2% vs. 13.2%; p < 0.0001).Differences in Netarsudil prescription rates within the United States exist between White and Black patients, and White and Hispanic patients. These differences exist when stratified by regions within the U.S. by varying degrees. Future studies are needed to investigate factors contributing to disparities in accessing new medications and to identify ways to eliminate such barriers to improve equity in care of glaucoma patients, especially among those historically disadvantaged. [ABSTRACT FROM AUTHOR]

Loss and absence of melanocytes due to a number of factors is responsible for vitiligo; known to be the commonest disorder of pigmentation. The aim of the current work was to compare the efficacy and safety of excimer light with topical tacrolimus ointment 0.1% versus excimer light with topical bimatoprost gel 0.01% in treatment of facial vitiligo. The study was carried out on 48 patients presented with facial vitiligo. The patients were divided randomly using sealed envelope method into two groups (24 patients each). Group 1 were treated with excimer light plus topical tacrolimus ointment 0.1% and group 2 treated with excimer light plus topical bimatoprost gel 0.01%. Clinical improvement based on the quartile grading scale at the end of treatment did not show any statistically significant difference between groups. The majority of subjects in both groups experienced good to excellent improvement. Only 20.9% of patients in group 1 and 33.3% of subjects in group 2 achieved less than 50% repigmentation (p = 0.889). Our study demonstrated that 0.01% topical bimatoprost gel in combination with excimer light is considered safe and effective as treatment of nonsegmental facial vitiligo with comparable results to 0.1% tacrolimus. [ABSTRACT FROM AUTHOR]

Introduction: Pharmaceutical residues are widely detected in aquatic environment and can be taken up by nontarget species such as fish. The cytochromes P450 (CYP) represent an important detoxification mechanism in fish, like in humans. In the present study, we assessed the correlation of the substrate selectivities of rainbow trout CYP1A and CYP3A homologues with those of human, through determination of the half-maximal inhibitory concentrations (IC50) of a total sixteen human pharmaceuticals toward CYP1A-like ethoxyresorufin O-deethylase (EROD) and CYP3A-like 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions (RT-S9). Methods: The inhibitory impacts (IC50) of atomoxetine, atorvastatin, azelastine, bimatoprost, clomethiazole, clozapine, desloratadine, disulfiram, esomeprazole, felbinac, flecainide, orphenadrine, prazosin, quetiapine, sulpiride, and zolmitriptan toward the EROD and BFCOD activities in RT-S9 were determined using the IC50 shift assay, capable of identifying time-dependent inhibitors (TDI). Additionally, the nonspecific binding of the test pharmaceuticals to RT-S9 was assessed using equilibrium dialysis. Results: Most test pharmaceuticals were moderate to weak inhibitors of both EROD and BFCOD activity in RT-S9, even if most are noninhibitors of human CYP1A or CYP3A. Only bimatoprost, clomethiazole, felbinac, sulpiride, and zolmitriptan did not inhibit either activity in RT-S9. EROD inhibition was generally stronger than that of BFCOD and some substances (atomoxetine, flecainide, and prazosin) inhibited selectively only EROD activity. The strongest EROD inhibition was detected with azelastine and esomeprazole (unbound IC50 of 3.8 ± 0.5 µM and 3.0 ± 0.8 µM, respectively). None of the test substances were TDIs of BFCOD, but esomeprazole was a TDI of EROD. Apart from clomethiazole and disulfiram, the nonspecific binding of the test pharmaceuticals to the RT-S9 was extensive (unbound fractions <0.5) and correlated well (R2 = 0.7135) with their water-octanol distribution coefficients. Discussion: The results indicate that the P450 interactions in RT-S9 cannot be explicitly predicted based on human data, but the in vitro data reported herein can shed light on the substrate selectivity of rainbow trout CYP1A1 and CYP3A27 in comparison to their human homologues. The IC50 concentrations are however many orders of magnitude higher than average environmental concentrations of pharmaceuticals. The time-dependent EROD inhibition by esomeprazole could warrant further research to evaluate its possible interlinkages with hepatotoxic impacts on fish. [ABSTRACT FROM AUTHOR]

Purpose: Investigating long-term trends in glaucoma medication. Methods: All patients diagnosed with glaucoma and prescribed glaucoma eye drops between 2007 and 2020 in Korea's Health Insurance Review and Assessment Service database participated in this study. A weight was assigned to each prescription using the reciprocal of the total number of prescriptions received by the individual in that year. The number of patients who received each type of glaucoma eye drop prescription was calculated by summing the weights for each year. Results: During the study period, prostaglandin analog eye drop monotherapy was the most frequently given type of glaucoma eye drop prescription. Until 2008, the second most frequently given type of glaucoma eye drop prescription was beta blocker eye drop monotherapy; thereafter, it changed to carbonic anhydrase inhibitor/beta blocker fixed-combination eye drop monotherapy. The prescription proportion of single-ingredient glaucoma eye drops decreased (-1.290%/year, P < 0.001), whereas that of fixed-combination glaucoma eye drops increased (1.291%/year, P < 0.001). The number of glaucoma eye drops prescribed per patient remained constant (-0.00030/year, P = 0.167) with an average of 1.302, while the number of active ingredients prescribed per patient increased (0.01737/year, P < 0.001) from 1.659 in 2007 to 1.896 in 2020. Conclusion: Over 14 years, there was no change in the number of glaucoma eye drops prescribed to individual patients in Korea. However, the number of active ingredients prescribed increased owing to the increased prescription of fixed-combination eye drops. The current trends in glaucoma medication are expected to help establish future treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: To determine NCX 470 (0.1%) and Lumigan® (bimatoprost ophthalmic solution, 0.01%—LUM) intraocular pressure (IOP)-lowering activity after single or repeated (5 days) dosing along with changes in aqueous humor (AH) dynamics. Methods: Ocular hypotensive activity of NCX 470 and LUM was compared with vehicle (VEH) in Beagle dogs using TonoVet®. Non-human primates (NHP) and bioengineered three-dimensional (3D) human Trabecular Meshwork/Schlemm's Canal (HTM/HSC™) constructs exposed to transforming growth factor-β2 (TGFβ2) were used to monitor NCX 470 and LUM-induced changes in AH dynamics. Results: NCX 470 (30 μL/eye) showed greater IOP reduction compared with LUM (30 μL/eye) following single AM dosing [maximum change from baseline (CFBmax) = −1.39 ± 0.52, −6.33 ± 0.73, and −3.89 ± 0.66 mmHg (mean ± standard error of the mean) for VEH, NCX 470, and LUM, respectively]. Likewise, repeated 5 days daily dosing of NCX 470 resulted in lower IOP than LUM across the duration of the study (average IOP decrease across tests was −0.45 ± 0.22, −6.06 ± 0.15, and −3.60 ± 0.22 mmHg for VEH, NCX 470, and LUM, respectively). NCX 470 increased outflow facility (Cfl) in vivo in NHP (CflVEH = 0.37 ± 0.09 μL/min/mmHg and CflNCX470 = 0.64 ± 0.17 μL/min/mmHg) as well as in vitro (CHTM/HSC) in HTM/HSC constructs (CHTM/HSC_VEH = 0.47 ± 0.02 μL/min/mm2/mmHg and CHTM/HSC_NCX470 = 0.76 ± 0.03 μL/min/mm2/mmHg). In addition, NCX 470 increased uveoscleral outflow (FuVEH = 0.62 ± 0.26 μL/min and FuNCX470 = 1.53 ± 0.39 μL/min with episcleral venous pressure of 15 mmHg) leaving unaltered aqueous flow (AHFVEH = 2.03 ± 0.22 μL/min and AHFNCX470 = 1.93 ± 0.31 μL/min) in NHP. Conclusions: NCX 470 elicits greater IOP reduction than LUM following single or repeated dosing. Data in NHP and 3D-HTM/HSC constructs suggest that changes in Cfl and Fu account for the robust IOP-lowering effect of NCX 470. [ABSTRACT FROM AUTHOR]

Bimatoprost is a prostaglandin analog used in cosmetic products designed to stimulate hair growth, including eyebrows. However, limited study-based evidence confirming its efficacy, safety, and patient satisfaction is available. The aim of this study was to investigate whether, and to what extent, bimatoprost affects the density and length of eyebrow hair in young women in comparison to sweet almond oil. The study group included 27 healthy women who used bimatoprost cosmetic preparation once daily for 5 weeks and then crossed over to use sweet almond oil once daily for 5 weeks. Bimatoprost preparation, in comparison to sweet almond oil, improved eyebrow density (70% vs. 30%; p = 0.003) and eyebrow hair elongation (59% vs. 26%; p = 0.014), but not eyebrow hair hydration (59% vs. 89%; p = 0.001) and hair darkness (22% vs. 11%; p = 0.278). The comfort of use was comparable for both preparations (63% vs. 67%; p = 0.996), but treatment satisfaction was significantly higher with bimatoprost (66% vs. 22%; p < 0.001). All reported adverse events were minor, transient, and resolved spontaneously. We conclude that the bimatoprost preparation was significantly more effective than sweet almond oil in improving the density and length of eyebrow hair, with a similar level of safety. Therefore, bimatoprost can be considered an ingredient in cosmetics designed to enhance eyebrow growth; however, further larger studies with extended follow-ups are needed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the time course of biodegradation of an intracameral, biodegradable, sustained-release bimatoprost implant that lowers intraocular pressure without the need for daily eye drops. Methods: In 2 identically designed, randomized, phase 3 clinical trials, adults with open-angle glaucoma or ocular hypertension and open iridocorneal angles inferiorly in the study eye were administered 10- or 15-μg bimatoprost implant (day 1 and weeks 16 and 32) or twice-daily topical timolol 0.5%. Implants were assessed on gonioscopy throughout the studies. Investigators reported whether implants were visible, estimated the size of visible implants relative to their initial size at implantation, and reported the implant location. Data for 10-μg implant placed on day 1 were pooled from both studies for analysis. Results: A total of 372 patients received the 10-μg bimatoprost implant. The degree of implant biodegradation at each follow-up time point was variable among patients. The implant frequently swelled during the initial phase of biodegradation from 6 to 28 weeks. Accelerated biodegradation occurred between 31 and 52 weeks, resulting in 82% of implants absent or ≤25% of initial size by 52 weeks. By month 20, 95% of implants had biodegraded to absent or ≤25% of initial size. The implant was predominantly located inferiorly in the iridocorneal angle. Conclusions: Bimatoprost implant biodegradation in phase 3 studies showed some degree of variability among patients. Clinically significant implant biodegradation was observed in the majority of patients by 12 months. Clinical studies are in progress to further understand implant biodegradation and the ideal timing for implant re-administration. ClinicalTrials.gov NCT02247804; ClinicalTrials.gov NCT02250651.

Objectives The main objective of our study was to assess the adherence of Jordanian patients to their glaucoma treatment after a brief educational session. Methods The current study was a randomized controlled interventional study. One hundred and ninety open-angle glaucoma patients were divided into control and intervention groups. After baseline assessment, patients in the intervention group received an educational session about glaucoma, while patients in the control group only received the usual care. Adherence to medication, eye drop administration technique, and knowledge about glaucoma were assessed at baseline and at follow-up. Key findings The mean MGL adherence scale score baseline value was 0.67 and significantly improved to 0.4 at the follow-up (P -value =.039) for patients in the intervention group. Multivariate regression showed that having less than three kids and experiencing glaucoma medication side effects were negatively correlated with adherence to glaucoma eye drops. The mean Eye Drops Administration scale score for patients in the intervention group improved significantly from 6.25 at baseline to 7.7 at the follow-up (P -value <.001). The mean knowledge scale score for the intervention group patients at baseline was 8.8, which significantly increased to 10 at the follow-up (P -value <.001). The knowledge score was found to be significantly higher for younger patients, those who have higher education levels and health care-related education, patients who rely on the ophthalmologist for glaucoma, and patients with a longer duration glaucoma. Conclusions A short educational session improves patients' adherence, knowledge, and eye drop administration technique in the intervention group significantly. Patients in Jordan have a relatively high adherence to glaucoma medications. Educational sessions should be provided to glaucoma patients to help the patients in managing their condition. [ABSTRACT FROM AUTHOR]

Background: Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular hypertension. Its ability to reduce intraocular pressure has established it as a first-line treatment option, improving management and preventing vision loss. In dermatology, bimatoprost has shown promising results in the promotion of hair growth, particularly in the treatment of alopecia and hypotrichosis. Its mechanism of action, stimulating the hair cycle and prolonging the growth phase, has led to the development of bimatoprost-containing solutions for enhancing eyelash growth. Aim: The aim of our review is to provide a brief description, overview, and studies in the current literature regarding the versatile clinical use of bimatoprost in recent years. This can help clinicians determine the most suitable individualized therapy to meet the needs of each patient. Methods: Our methods involve a comprehensive review of the latest advancements reported in the literature in bimatoprost formulations, which range from traditional eye drops to sustained-release implants. These innovations offer extended drug delivery, enhance patient compliance, and minimize side effects. Results: The vast literature published on PubMed has confirmed the clinical usefulness of bimatoprost in lowering intraocular pressure and in managing patients with glaucoma. Numerous studies have shown promising results in dermatology and esthetics in promoting hair growth, particularly in treating alopecia and hypotrichosis. Its mechanism of action involves stimulating the hair cycle and prolonging the growth phase, leading to the development of solutions that enhance eyelash growth. The global use of bimatoprost has expanded significantly, with applications growing beyond its initial indications. Ongoing research is exploring its potential in glaucoma surgery, neuroprotection, and cosmetic procedures. Conclusions: Bimatoprost has shown immense potential for addressing a wide range of therapeutic needs through various formulations and advancements. Promising future perspectives include the exploration of novel delivery systems such as contact lenses and microneedles to further enhance drug efficacy and patient comfort. Ongoing research and future perspectives continue to shape its role in medicine, promising further advancements and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To characterize clinical outcomes following a single administration of bimatoprost SR in eyes with glaucoma in a real-world setting implanted at the slit-lamp. Setting: Tertiary care Glaucoma practice, Glaucoma Associates of Texas, Dallas, Texas. Design: Retrospective interventional case series. Methods: Data were analyzed from consecutive patients receiving a single bimatoprost SR implant from the time of its approval to the time of data collection. All eyes were implanted at the slit-lamp. Eyes with less than 1 month of follow-up were excluded. The primary outcome was median time to next intraocular pressure (IOP)-lowering intervention. Mean IOP and medication use, and changes from baseline, were also assessed through 12 months of follow-up. Results: Overall 129 eyes of 81 patients were analyzed. Following bimatoprost SR administration (replacing a topical prostaglandin analogue [PGA] in most eyes), the median survival time without any further IOP-lowering interventions was between 6– 9 months. Mean IOP remained unchanged from baseline at month 1 (consistent with switch from topical to intracameral PGA therapy) and began to rise at month 3. At month 12, 40.5% of eyes (52 eyes) remained intervention-free, mean medication reduction was 0.5 medications per eye, and 27.8% of eyes (36 eyes) were medication-free. Adverse events were uncommon and most were transient and resolved with or without intervention. Conclusion: This real-world analysis of bimatoprost SR use for glaucoma therapy complements Phase 3 study findings and demonstrates that the implant can safely provide medication reduction through 6 months in most eyes and through 12 months in almost 40% of eyes. [ABSTRACT FROM AUTHOR]

Background: Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. Aim: In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. Methods: This is a prospective intra‐patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. Results: SALT score was reduced significantly during treatment sessions and after a 3‐month follow‐up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow‐up period, respectively (p = 0.000). A general linear model of two‐way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). Conclusion: Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata. [ABSTRACT FROM AUTHOR]

Purpose: To study and compare the efficacy and safety profile of Rho-kinase inhibitor (netarsudil 0.02%) and prostaglandin analog (bimatoprost 0.01%) both as monotherapy and in combination. Design: Prospective, randomized, monocentric, open-label clinical trial. Methods: Patients ≥20 years of age with primary open-angle glaucoma or ocular hypertension (IOP >21 mmHg) were recruited and randomized to receive either netarsudil 0.02%, netarsudil 0.02% + bimatoprost 0.01%, or bimatoprost 0.01% once daily for a period of 12 weeks. IOP and side effects were documented at 4, 8, and 12 weeks. Results: The mean treated IOP ranged 17.51–18.57 mmHg for netarsudil, 15.80–16.46 mmHg for bimatoprost, and 14.00–14.87 mmHg for the combination therapy group. The mean IOP reduction from baseline at 4, 8, and 12 weeks was found to be statistically significant (P < 0.001) in all three groups. The safety profile of netarsudil/bimatoprost combination was consistent with each constituent individually. The only frequently observed ocular adverse event was conjunctival hyperemia, which was seen mostly in netarsudil and netarsudil + bimatoprost groups (P < 0.001). Conclusion: The IOP-lowering effect of netarsudil 0.02% once daily is non-inferior to bimatoprost 0.01% in patients with POAG and ocular hypertension with acceptable ocular safety, and the combination therapy achieved a higher IOP-lowering effect. This group of medications can be a useful adjunct in patients on maximal therapy.

Purpose: To assess the effectiveness and safety of bimatoprost sustained release (SR) glaucoma implant as a treatment for open-angle glaucoma and ocular hypertension in a real-world private practice setting with a significant American Indian population. Methods: This retrospective study included 156 eyes from adult patients who received a single injection of bimatoprost implant between June 2020 and May 2022 at the Oklahoma Eye Surgeons. Patients were stratified by baseline intraocular pressure (IOP) (≥ 21 mmHg versus IOP< 21 mmHg). The co-primary endpoints were changes in the mean IOP and the number of topical IOP-lowering medications from baseline to Month 6. Results: At 6 months, eyes with baseline IOP≥ 21 mmHg had a significantly lower mean IOP (19.85± 8.01 versus 26.25± 4.84 mmHg; p< 0.0001) and the mean number of IOP-lowering medications (1.04± 1.44 versus 1.38± 1.50; p=0.048) compared with baseline. One year after implantation, 73.58% of eyes had a ≥ 20% reduction in IOP, 41.51% were medication-free and 30.19% were receiving at least one fewer medication. Among eyes with baseline IOP< 21 mmHg, there was a significant reduction in the mean number of IOP-lowering medicines by Month 6 (0.61± 1.03 versus 1.93± 1.21 at baseline; p< 0.0001), with no change in IOP. At 12 months, 24.27% of eyes had a ≥ 20% decrease in IOP, 43.69% of eyes did not require any medications and 63.11% had at least one fewer medication compared with baseline. An analysis using Welch's two-sample t–test showed no significant differences in the outcomes between the overall population and the American Indian population (number of eyes, 23). Conclusion: Bimatoprost SR glaucoma implant lowered IOP in eyes with high, uncontrolled baseline IOP, while it reduced the number of medications in eyes with a controlled baseline IOP. No clinically meaningful and statistically significant differences in the efficacy of bimatoprost were observed in patients of American Indian descent. [ABSTRACT FROM AUTHOR]

Purpose: To study and compare the efficacy and safety profile of Rho-kinase inhibitor (netarsudil 0.02%) and prostaglandin analog (bimatoprost 0.01%) both as monotherapy and in combination. Design: Prospective, randomized, monocentric, open-label clinical trial. Methods: Patients ≥20 years of age with primary open-angle glaucoma or ocular hypertension (IOP >21 mmHg) were recruited and randomized to receive either netarsudil 0.02%, netarsudil 0.02% + bimatoprost 0.01%, or bimatoprost 0.01% once daily for a period of 12 weeks. IOP and side effects were documented at 4, 8, and 12 weeks. Results: The mean treated IOP ranged 17.51–18.57 mmHg for netarsudil, 15.80–16.46 mmHg for bimatoprost, and 14.00–14.87 mmHg for the combination therapy group. The mean IOP reduction from baseline at 4, 8, and 12 weeks was found to be statistically significant (P < 0.001) in all three groups. The safety profile of netarsudil/bimatoprost combination was consistent with each constituent individually. The only frequently observed ocular adverse event was conjunctival hyperemia, which was seen mostly in netarsudil and netarsudil + bimatoprost groups (P < 0.001). Conclusion: The IOP-lowering effect of netarsudil 0.02% once daily is non-inferior to bimatoprost 0.01% in patients with POAG and ocular hypertension with acceptable ocular safety, and the combination therapy achieved a higher IOP-lowering effect. This group of medications can be a useful adjunct in patients on maximal therapy. [ABSTRACT FROM AUTHOR]

Glaucoma is one of the leading causes of irreversible blindness in developed countries, and intraocular pressure (IOP) is primary and only treatable risk factor, suggesting that to a significant extent, glaucoma is a disease of IOP disorder and pathological mechanotransduction. IOP-lowering ways are limited to decreaseing aqueous humour (AH) production or increasing the uveoscleral outflow pathway. Still, therapeutic approaches have been lacking to control IOP by enhancing the trabecular meshwork (TM) pathway. Trabecular meshwork cells (TMCs) have endothelial and myofibroblast properties and are responsible for the renewal of the extracellular matrix (ECM). Mechanosensitive cation channels, including Piezo1 and TRPV4, are abundantly expressed in primary TMCs and trigger mechanostress-dependent ECM and cytoskeletal remodelling. However, prolonged mechanical stimulation severely affects cellular biosynthesis through TMC mechanotransduction, including signaling, gene expression, ECM remodelling, and cytoskeletal structural changes, involving outflow facilities and elevating IOP. As for the functional coupling relationship between Piezo1 and TRPV4 channels, inspired by VECs and osteoblasts, we hypothesized that Piezo1 may also act upstream of TRPV4 in glaucomatous TM tissue, mediating the activation of TRPV4 via Ca2+ inflow or Ca2+ binding to phospholipase A2(PLA2), and thus be involved in increasing TM outflow resistance and elevated IOP. Therefore, this review aims to help identify new potential targets for IOP stabilization in ocular hypertension and primary open-angle glaucoma by understanding the mechanical transduction mechanisms associated with the development of glaucoma and may provide ideas into novel treatments for preventing the progression of glaucoma by targeting mechanotransduction. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible blindness, and early detection and treatment are crucial for preventing vision loss. This review aims to provide an overview of current diagnostic and treatment standards, recent medical and technological advances, and current challenges and future outlook for wearable glaucoma diagnostics and therapeutics. Conventional diagnostic techniques, including the rebound tonometer and Goldmann Applanation Tonometer, provide reliable intraocular pressure (IOP) measurement data at single-interval visits. The Sensimed Triggerfish and other emerging contact lenses provide continuous IOP tracking, which can improve diagnostic IOP monitoring for glaucoma. Conventional therapeutic techniques include eye drops and laser therapies, while emerging drug-eluting contact lenses can solve patient noncompliance with eye medications. Theranostic platforms combine diagnostic and therapeutic capabilities into a single device. Advantages of these platforms include real-time monitoring and personalized medication dosing. While there are many challenges to the development of wearable glaucoma diagnostics and therapeutics, wearable technologies hold great potential for enhancing glaucoma management by providing continuous monitoring, improving medication adherence, and reducing the disease burden on patients and healthcare systems. Further research and development of these technologies will be essential to optimizing patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: A sustained-release, biodegradable, intracameral 10-μg bimatoprost implant (Durysta) is approved for single administration per eye to lower intraocular pressure (IOP) in open-angle glaucoma (OAG) and ocular hypertension (OHT). The purpose of this study was to evaluate the IOP-lowering effectiveness and safety of a single implant administration per eye in patients with OAG or OHT in a real-world clinical setting. Methods: This was a retrospective, single-site study involving 105 consecutive adult patients with OAG or OHT treated with the bimatoprost implant in 1 or both eyes in routine clinical practice. Available medical records of the patients for 12 months or longer after the initial implant administration were reviewed, and data including IOP, IOP-lowering medication and procedure use, and safety outcomes were collected and analyzed. The analysis used ranges of follow-up because of the real-world setting. Results: The study included 197 eyes (85.3% diagnosed with OAG, 94.9% pseudophakic, and 83.8% with angle grade 4). IOP reduction was observed through 1 year after the bimatoprost implant administration. Mean IOP was 16.6 mmHg at baseline and 13.3 mmHg at 11– 13 months, with the mean number of topical IOP-lowering medications used reduced from 1.4 at baseline to 0.2 at 11– 13 months. IOP and IOP-lowering medication use were similarly reduced in eyes treated with both selective laser trabeculoplasty (SLT) and bimatoprost implant (including 66 eyes with their last SLT before implant administration and 28 eyes with their last SLT after implant administration). There were no cases of treatment-emergent corneal edema after bimatoprost implant administration, and no eye required implant removal. Conclusion: A single bimatoprost implant administration safely and effectively reduced IOP for up to 1 year and decreased the need for topical IOP-lowering medications in eyes with OAG or OHT with or without previous or subsequent SLT. [ABSTRACT FROM AUTHOR]

Glaucoma is the world's leading cause of permanent blindness, influenced by numerous variables, including socio-demographic factors. This review considered existing management practices and innovative methods of drug delivery, as well as how they relate to patient adherence and therapy costs. Literatures were compiled using search engines including ScienceDirect, PubMed, Google Scholar and WHO database. The eye is a complex organ with various anatomical barriers presenting significant challenges in treating glaucoma due to poor patient compliance with topical ocular medications. Advanced drug delivery systems like implants, nano or microparticles, punctal plugs, contact lenses, topical ring-type systems, gels, and other depot systems such as intracameral, supraciliary, and intravitreal applied in the extraocular, periocular, or intraocular sites, significantly enhance medication absorption, reduce adverse effects, and improve patient compliance. Poor treatment adherence, stemming from various reasons, lead to inadequate glaucoma management, increasing direct (34 to 45 %) and indirect costs (55 to 66 %) of therapy. As a result, a variety of treatments including enhanced drug delivery systems have been tested to address these concerns, and some modern pharmaceuticals and drug delivery technologies are being developed. [ABSTRACT FROM AUTHOR]

Ripasudil, a rho-associated protein kinase inhibitor ophthalmic solution, shows a protective effect in preventing excessive scarring in vitro. This study aims to evaluate the safety and efficacy of ripasudil for glaucoma patients submitted to the needling procedure. In this prospective, multicenter, single-arm study, we included 20 eyes of 20 patients with glaucoma who underwent the needling procedure without antimetabolites. All patients administered ripasudil after needling for three months. The primary endpoint of this study was the safety of ripasudil in patients, and the secondary endpoint was the change in IOP at 12 weeks after the needling procedure. No serious complications were found in the patients. One eye experienced pruritus and conjunctival follicle, while another eye had conjunctival follicle. These complications were transient and resolved quickly after discontinuation of ripasudil. The mean preoperative IOP was 14.6 ± 4.6 mmHg, which decreased to 11.0 ± 4.7 mmHg (p = 0.0062) at 1 week postoperatively. The IOP reduction effect continued to 12 weeks (11.8 ± 3.1 mmHg; p = 0.0448). The administration of the ROCK inhibitor, ripasudil, after the needling procedure is safe and effective in maintaining IOP for 12 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Heat shock protein (Hsp) 90 is one of the most abundant proteins in unstressed cells and regulates stability and functional maintenance of client proteins. In ocular tissue, Hsp90 is widely expressed in the cornea and retina and has multiple roles in these tissues. The expression of HSPs was induced in the retinas of glaucomatous patients and laser-induced glaucoma in monkey while their mechanisms remain to be elucidated. For this reason, we tried to elucidate the role of Hsp90 in intraocular pressure (IOP) regulation in rabbits. Methods: IOP was measured by a pneumatonometer before and after intracameral injection of Hsp90 inhibitors. The aqueous flow rate was measured by fluorophotometry. Trans-epithelial electrical resistance was measured in primary human trabecular meshwork cells. Results: 17-AAG, a specific Hsp90 inhibitor, significantly lowered IOP at concentrations of more than 30 μm in normotensive rabbits. Other Hsp90 inhibitors also significantly lowered IOP in normotensive rabbits at a dose of 100 μm. No reduction of aqueous humor production was observed by injection of 17-AAG in rabbits. Topical administration of pilocarpine tended to attenuate the IOP-lowering effects induced by the Hsp90 inhibitor. No reduction of trans-epithelial electrical resistance was observed by inhibition of Hsp90 in culture cells. Conclusions: These results indicated that intraocular Hsp90 regulates IOP, and the inhibition of Hsp90 by Hsp90 inhibitor decreases IOP without affecting aqueous humor production in rabbits. Further research in elucidating the mechanism of Hsp90 inhibitors will result in a better understanding of the role of Hsp90 in the regulation of IOP. [ABSTRACT FROM AUTHOR]

Purpose : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). Methods: MERCURY-3 was a 6-month prospective, double–masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. Results: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). Conclusions: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT. [ABSTRACT FROM AUTHOR]

Introduction: Sustained-release intraocular implants provide a therapeutic option for open-angle glaucoma (OAG) and ocular hypertension (OHT) patients who are non-compliant with eyedrops. Currently, there are no published patient-reported outcome (PRO) measures that assess treatment satisfaction with intraocular implants. To address this gap, a new PRO instrument, the Allergan Satisfaction with Treatment Experience Questionnaire (ASTEQ), has been developed in accordance with Food and Drug Administration guidance. Methods: Qualitative research interviews were conducted among patients with OAG/OHT who had received three intraocular injections of a sustained-release bimatoprost (10 or 15 µg) implant within the clinical trial setting. A preliminary conceptual framework capturing treatment satisfaction concepts in glaucoma, as identified from the literature, was used to develop a semi-structured interview guide. A concept elicitation (CE) interview to identify aspects of the glaucoma treatment experience pertinent to intraocular implants provided content for a draft instrument. A cognitive debriefing (CD) interview to test the instrument's interpretability, relevance, and validity informed its subsequent refinement. Interview analysis followed a grounded theory approach to identify data patterns and relationships. Results: CE interviews (n = 19) indicated that participants' main considerations in rating satisfaction with implant treatment were physical comfort during preparation for the implant and implant administration, anxiety about the procedure, frequency of implant administration, possible side effects, convenience and accessibility of the implant, relationship with the clinician, and lifestyle fit. Draft ASTEQ revision based on CD interviews (n = 20) and readability tests yielded a nine-item ASTEQ instrument comprising satisfaction with overall implant experience and frequency of administration, occurrence/bother of immediate and long-term side effects, worry about implant administration and possible risks/side effects, and physical discomfort during preparation for the implant and implant administration. Conclusion: The ASTEQ instrument has demonstrated content validity in patients with OAG/OHT treated with a sustained-release bimatoprost implant. Further research is necessary to evaluate its psychometric properties. [ABSTRACT FROM AUTHOR]

Bimatoprost (BIM) is a prostaglandin F2α analogs originally approved for the treatment of glaucoma and ocular hypertension. Recent studies have highlighted its potential to boost hair growth. The objective of this investigation is to challenge the potential of spanlastics (SLs) as a surfactant-based vesicular system for promoting the cutaneous delivery of BIM for the management of alopecia. BIM-loaded spanlastics (BIM-SLs), composed of Span as the main vesicle component and Tween as the edge activator, were fabricated by ethanol injection method. The formulated BIM-SLs were optimized by 23 full factorial design. The optimized formula (F1) was characterized for entrapment efficiency, surface charge, vesicle size, and drug release after 12 h (Q12h). The optimized formula (F1) exhibited high drug entrapment efficiency (83.1 ± 2.1%), appropriate zeta potential (−19.9 ± 2.1 mV), Q12h of 71.3 ± 5.3%, and a vesicle size of 364.2 ± 15.8 nm, which favored their cutaneous accumulation. In addition, ex-vivo skin deposition studies revealed that entrapping BIM within spanlastic-based nanogel (BIM-SLG) augmented the dermal deposition of BIM, compared to naïve BIM gel. Furthermore, in vivo studies verified the efficacy of spanlastic vesicles to boost the cutaneous accumulation of BIM compared to naive BIM gel; the AUC0-12h of BIM-SLG was 888.05 ± 72.31 μg/mL.h, which was twice as high as that of naïve BIM gel (AUC0-12h 382.86 ± 41.12 μg/mL.h). Intriguingly, BIM-SLG outperforms both naïve BIM gel and commercial minoxidil formulations in stimulating hair regrowth in an androgenetic alopecia mouse model. Collectively, spanlastic vesicles might be a potential platform for promoting the dermal delivery of BIM in managing alopecia.

This document discusses the use of a device that provides precise cooling of the skin during medical procedures. The device uses infrared sensors and CO2 cryogen to cool the skin to a specific temperature and duration. A study showed that using the device during injections for acne reduced pain and had no adverse effects. The device was also found to be effective for providing anesthesia during platelet-rich plasma (PRP) treatment for hair loss. The authors suggest that further research is needed to confirm the device's efficacy and explore other potential applications. Another section of the document discusses the use of hyaluronic acid injections for aesthetic sequelae after cleft lip surgery. The study evaluated the psychological impact, safety, and feasibility of the treatment, as well as ultrasound changes in the tissues. Seven patients were included in the study, and the results showed improvement in quality of life and scar appearance. [Extracted from the article]