Treatment Of Glaucoma Research Articles

Cystoid macular edema occurring after intracameral bimatoprost implantation.

This case report aims to report the development of cystoid macular edema (CME) unilaterally following the administration of bimatoprost implant (Durysta) injections in both eyes for the treatment of primary open-angle glaucoma (POAG). An 84-year-old female patient, previously diagnosed with POAG, underwent bimatoprost implant (Durysta) injections in both eyes, spaced one month apart. Subsequently, the patient experienced a gradual decline in visual acuity in her left eye attributed to the development of CME. The condition resolved following a treatment regimen involving topical dexamethasone and nepafenac. The use of bimatoprost implant may lead to the occurrence of CME. Ophthalmologists must vigilantly monitor patients post-implantation, especially if they exhibit visual symptoms or have risk factors for a CME.

Changes in corneal biomechanics in patients with glaucoma: a systematic review and meta-analysis.

Corneal biomechanics has been implicated in a variety of ocular diseases. The purpose of this study was to evaluate the relationship between the glaucoma and corneal biomechanical properties, and exploring the value of corneal biomechanics in the diagnosis and follow-up of glaucoma diseases. We searched studies in PubMed, EMBASE, Web of Science and clinicaltrials.gov., as of October 8, 2022. Only English studies were included, without publication time limit. We also searched the reference lists of published reviews. This meta-analysis was conducted with random-effects models, we used mean difference(MD) to evaluate the outcome, and the heterogeneity was assessed with the I2 statistic. Subgroup analyses were performed under the appearance of high heterogeneity. We used 11 items to describe the characteristics of included studies, publication bias was performed through the Egger's test. The quality assessment were evaluated by Newcastle-Ottawa Scale(NOS) items. A total of 27 eligible studies were identified for data synthesis and assessment. The result of meta-analysis showed that in the comparison of included indicators, the corneal biomechanics values of glaucoma patients were statistically lower than those of normal subjects in a similar age range. The covered indicators included central corneal thickness(CCT) (MD = -8.34, 95% CI: [-11.74, -4.94]; P < 0.001), corneal hysteresis(CH)(MD = -1.54, 95% CI: [-1.88, -1.20]; P < 0.001), corneal resistance factor(CRF)( MD = -0.82, 95% CI: [-1.21, -0.44]; P < 0.001), and intraocular pressure(IOP)( corneal-compensated intraocular pressure (IOPcc): MD = 2.45, 95% CI: [1.51, 3.38]; P < 0.001); Goldmann-correlated intraocular pressure (IOPg): MD = 1.30, 95% CI: [0.41, 2.20]; P = 0.004), they all showed statistical difference. While the value of axial length(AL) did not show statistically different(MD = 0.13, 95% CI: [-0.24, 0.50]; P = 0.48). Corneal biomechanics are associated with glaucoma. The findings can be useful for the design of glaucoma screening, treatment and prognosis.

Predictors and long-term patterns of medication adherence to glaucoma treatment in Denmark—an observational registry study of 30 100 Danish patients with glaucoma

BackgroundSelf-treatment with glaucoma medication (eye drops) has been associated with adherence challenges. Poor adherence results in worse outcomes in terms of visual field loss.ObjectiveTo investigate patterns in medication adherence among...

Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents.

The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2%w/v) and the osmoprotectants betaine (0.40%w/v) and leucine (0.90%w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34nm) and a zeta potential of -13.96 ± 0.78mV. LAT-HA-LIP was isotonic (284.00 ± 1.41mOsmL-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70mNm-1) and viscosity (2.69 ± 0.15mPas-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.

Comparison of GATT versus micropulse transscleral diode laser cyclophotocoagulation combined with GATT in patients with advanced glaucoma.

To compare the efficacy of gonioscopy-assisted transluminal trabeculotomy (GATT) versus micropulse transscleral diode laser cyclophotocoagulation(MP-TDLC) combined with GATT in the treatment of advanced glaucoma. This retrospective comparative study study included 82 patients (82 eyes) with a diagnosis of advanced glaucoma: 36 patients underwent GATT, and 46 underwent GATT + MP-TDLC. Intraocular pressure (IOP) changes in patients who underwent GATT and GATT MP-TDLC were analyzed retrospectively at regular intervals during the 6-month follow-up period. For the 82 patients included in this study, the mean ± SD IOPs before the procedures were 27.2 ± 8.5 mmHg in the GATT group and 26.6 ± 6.9 mmHg in the GATT + MP-TDLC group (p = 0.866), and the numbers of glaucoma medications used were 3.41 ± 0.5 in the GATT group and 3.36 ± 0.4 in the GATT + MP-TDLC group (p = 0.605). The mean IOP after GATT was 13.6 ± 3.9 mmHg at day 1, 13.9 ± 3.7 mmHg at week 1, 14.6 ± 4.0 mmHg at month 1, 15.3 ± 4.3 mmHg at month 3, and 14.7 ± 3.3 mmHg at month 6. In the GATT + MP-TDLC group, the postoperative day 1, week 1, month 1, month 3, and month 6 IOP values were 12.4 ± 2.5, 11.8 ± 1.8, 12.1 ± 2.0, 11.8 ± 1.09, and 11.8 ± 1.5 mmHg, respectively. GATT was found to be effective in the treatment of patients with advanced glaucoma, and results closer to the targeted low teens IOP values were obtained with GATT + MP-TDLC.

Solanum nigrum Toxicity and Its Neuroprotective Effect Against Retinal Ganglion Cell Death Through Modulation of Extracellular Matrix in a Glaucoma Rat Model.

Purpose: Glaucoma is a complex degenerative optic neuropathy characterized by loss of retinal ganglion cells (RGCs) leading to irreversible vision loss and blindness. Solanum nigrum has been used for decades in traditional medicine system. However, no extensive studies were reported on its antiglaucoma properties. Therefore, this study was designed to investigate the neuroprotective effects of S. nigrum extract on RGC against glaucoma rat model. Methods: High performance liquid chromatography and liquid chromatography tandem mass spectrometry was used to analyze the phytochemical profile of aqueous extract of S. nigrum (AESN). In vitro, {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide} (MTT) and H2DCFDA assays were used to determine cell viability and reactive oxygen species (ROS) production in Statens Seruminstitut Rabbit Cornea cells. In vivo, AESN was orally administered to carbomer-induced rats for 4 weeks. Intraocular pressure, antioxidant levels, and electrolytes were determined. Histopathological and immunohistochemical analysis was carried out to evaluate the neurodegeneration of RGC. Results: MTT assay showed AESN exhibited greater cell viability and minimal ROS production at 10 μg/mL. Slit lamp and funduscopy confirmed glaucomatous changes in carbomer-induced rats. Administration of AESN showed minimal peripheral corneal vascularization and restored histopathological alterations such as minimal loss of corneal epithelium and moderate narrowing of the iridocorneal angle. Immunohistochemistry analysis showed increased expression of positive BRN3A cells and decreased matrix metalloproteinase (MMP)-9 activation in retina and cornea, whereas western blot analysis revealed downregulation of extracellular matrix proteins (COL-1 and MMP-9) in AESN-treated rats compared with the diseased group rats. Conclusions: AESN protects RGC loss through remodeling of MMPs and, therefore, can be used for the development of novel neurotherapeutics for the treatment of glaucoma.

Additional Guidance on the Use of the PRESERFLO™ MicroShunt in the Treatment of Glaucoma: Insights from a Second Delphi Consensus Panel.

The PRESERFLO™ MicroShunt (PMS) has been proven to significantly lower intraocular pressure (IOP) in patients with glaucoma and has been available for use since 2019. With increasing published evidence and growing experience of glaucoma surgeons, the aim of this modified Delphi panel was to build on the findings of a previous Delphi panel conducted in 2021 and provide further guidance on the role of the PMS to treat patients with glaucoma in Europe. Thirteen European glaucoma surgeons experienced in the PMS procedure participated in a 3-round modified Delphi panel. A targeted literature review and expert steering committee guided Round 1 questionnaire development. Consensus was pre-defined at a threshold of ≥ 70% of panellists selecting 'strongly agree'/'agree' or 'strongly disagree'/'disagree' for 6-point Likert scale questions or ≥ 70% selecting the same option for multiple or single-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions. In total, 28% (n = 9/32), 52% (n = 16/31) and 91% (n = 10/11) of statements reached consensus in Rounds 1, 2 and 3, respectively. There was agreement that the PMS may be used in patients with pigmentary, post-trauma or post-vitrectomy glaucoma and for patients with uveitic glaucoma without active inflammation. The PMS may be more suitable for patients with contact lenses than other subconjunctival filtering surgeries, without eliminating bleb-associated risks. Consensus was reached that combining PMS implantation and phacoemulsification may be as safe as standalone PMS surgery, but further efficacy data are required. Following a late rise in IOP ≥ 4months post-surgery, topical aqueous suppressant drops or bleb revision may be suitable management options. This Delphi panel builds on the considerations explored in the 2021 Delphi panel and provides further detailed guidance for glaucoma surgeons on the use of the PMS, reflecting the availability of novel evidence and surgical experience. Videos are available for this article.

The PRAMOS Study: PRostaglandin Analogues Monotherapy-Awareness Survey on Ocular Surface Involvement.

Even though the local tolerance of prostaglandin (PG) analogues has improved drastically since the introduction of preservative-free (PF) eye drops, prescription patterns still vary widely among practitioners and between countries and could have an impact on the ocular surface of treated patients and, in consequence, their adherence. The aim of this study is to explore the prescribing patterns of PG analogues monotherapy in France and to evaluate their impact on ocular surface status. This was a national multicenter cross-sectional observational study that was conducted by 18 glaucoma experts in France. Patients over 18years of age and receiving monotherapy with topical PG analogues for the treatment of ocular hypertension and/or glaucoma, with no history of prior glaucoma surgery, were consecutively selected from the glaucoma outpatient clinics of participating physicians and underwent an ocular surface examination. A total of 344 eyes of 344 patients were enrolled between November 2022 and November 2023. Prescribed PG monotherapy was PF in 271 (78.7%) patients. Clinical history and ocular surface evaluation indicated that 79.4% of the study population (n = 273) presented with at least one symptom or clinical sign of dry eye and that three patients out of four had an unstable tear film. Subgroup analysis comparing preserved and PF PG analogues showed a higher prevalence of conjunctival hyperemia and corneal staining in the preserved group. Multivariate analysis identified conjunctival hyperemia as consistently associated with preservative use (odds ratio = 7.654; p = 0.003 for moderate conjunctival hyperemia). This study highlights the growing trend toward PF PG analogue prescriptions by specialists in France. However, ocular surface issues remain prevalent, impacting patient adherence and treatment efficacy. Comprehensive ocular surface examinations are crucial in glaucoma management to enhance long-term tolerance, compliance, and overall treatment success.

Novel Biomaterials in Glaucoma Treatment

Glaucoma is a significant cause of blindness worldwide, and its treatment remains challenging. The disease progressively leads to damage to the optic disc and thus loss of visual acuity and visual field. High intraocular pressure (IOP) is a common risk factor. There are three major methods to treat this disease: topical, laser, and surgical. None of these are completely satisfactory; therefore, alternatives using new biomaterials are being sought. Since biomaterial engineering has experienced significant growth in recent decades, its products are gradually being introduced to various branches of medicine, with the exception of ophthalmology. Biomaterials, such as glaucoma drainage implants, have been successfully used to treat glaucoma. There is significant ongoing research on biomaterials as drug delivery systems that could overcome the disadvantages of topical glaucoma treatment, such as poor intraocular penetration or frequent drug administration. This article summarizes the use of novel biomaterials for glaucoma treatment presented in the literature. The literature search was based on articles published in English on PubMed.gov, Cochranelibrary.com, and Scopus.com between 2018 and 2023 using the following term “biomaterials in glaucoma.” A total of 103 published articles, including twenty-two reviews, were included. Fifty-nine articles were excluded on the basis of their titles and abstracts.

Manufacturing and characterisation of 3D-printed sustained-release Timolol implants for glaucoma treatment.

Timolol maleate (TML) is a beta-blocker drug that is commonly used to lower the intraocular pressure in glaucoma. This study focused on using a 3D printing (3DP) method for the manufacturing of an ocular, implantable, sustained-release drug delivery system (DDS). Polycaprolactone (PCL), and PCL with 5 or 10% TML implants were manufactured using a one-step 3DP process. Their physicochemical characteristics were analysed using light microscopy, scanning electronic microscopy (SEM), differential scanning calorimetry (DSC) / thermal gravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). The in vitro drug release was evaluated by UV-spectrophotometry. Finally, the effect of the implants on cell viability in human trabecular meshwork cells was assessed. All the implants showed a smooth surface. Thermal analysis demonstrated that the implants remained thermally stable at the temperatures used for the printing, and FTIR studies showed that there were no significant interactions between PCL and TML. Both concentrations (5 & 10%) of TML achieved sustained release from the implants over the 8-week study period. All implants were non-cytotoxic to human trabecular cells. This study shows proof of concept that 3DP can be used to print biocompatible and personalised ocular implantable sustained-release DDSs for the treatment of glaucoma.

Non-invasive FBG-based contact lens for continuous intraocular pressure monitoring

The intraocular pressure (IOP), or pressure inside the eye, is one of the key indicator for glaucoma diagnosis and treatment. The present work shows the design and fabrication of a non-invasive Fiber Bragg Grating (FBG) based contact lens for continuous IOP monitoring. By employing wet etching to reduce the FBG diameter, FBG based contact lens sensitivity and mechanical flexibility are enhanced. The contact lens is made of an optical fiber with a small core diameter that has an inscribed FBG of length 3 mm and is etched for a length of 40 mm to facilitate coiling the eFBG during fabrication. The soft contact lens was fabricated using flexible thin film technology with a transparent and flexible etched Fiber Bragg Grating (eFBG) integrated within flexible polydimethylsiloxane (PDMS) for sensing corneal deformations brought about by IOP variations. Experimental studies on the bionic eyeball model show that the Bragg wavelength shift is highly linear (r2 = 0.9694), with a very good sensitivity of 49.243 pm/mmHg in the IOP pressure range of 0 to 50 mmHg. Due to its ease of fabricating, simplicity of design, and ability to continuously measure pressure with good repeatability and stability, the proposed sensor thus offers a potential solution for IOP monitoring.

A new mouse-fixation device for IOP measurement in awake mice

Glaucoma is an irreversible blinding eye disease. The mechanisms underlying glaucoma are complex. Up to now, no successful remedy has been found to completely cure the condition. High intraocular pressure (IOP) is an established risk factor for glaucoma and the only known modifiable factor for glaucoma treatment. Mice have been widely used to study glaucoma pathogenesis. IOP measurement is an important tool for monitoring the potential development of glaucomatous phenotypes in glaucoma mouse models. Currently, there are two methods of IOP measurement in mice: invasive and non-invasive. As the invasive method can cause corneal damage and inflammation, and most of the noninvasive method involves the use of anesthetics. In the course of our research, we designed a mouse fixation device to facilitate non-invasive measurements of mouse IOPs. Using this device, mouse IOPs can be accurately measured in awake mice. This device will help researchers to accurately assess mouse IOP without the use of anesthetics.

Evaluating the effect of pulse energy on femtosecond laser trabeculotomy (FLT) outflow channels for glaucoma treatment in human cadaver eyes.

Femtosecond laser trabeculotomy (FLT) creates aqueous humor outflow channels through the trabecular meshwork (TM) and is an emerging noninvasive treatment for open-angle glaucoma. The purpose of this study is to investigate the effect of pulse energy on outflow channel creation during FLT. An FLT laser (ViaLase Inc.) was used to create outflow channels through the TM (500 μm wide by 200 μm high) in human cadaver eyes using pulse energies of 10, 15, and 20 μJ. Following treatment, tissues were fixed in 4% paraformaldehyde. The channels were imaged using optical coherence tomography (OCT) and assessed as full thickness, partial thickness, or not observable. Pulse energies of 15 and 20 μJ had a 100% success rate in creating full-thickness FLT channels as imaged by OCT. A pulse energy of 10 μJ resulted in no channels (n = 6), a partial-thickness channel (n = 2), and a full-thickness FLT channel (n = 2). There was a statistically significant difference in cutting widths between the 10 and 15 μJ groups (p < 0.0001), as well as between the 10 and 20 μJ groups (p < 0.0001). However, there was no statistically significant difference between the 15 and 20 μJ groups (p = 0.416). Fifteen microjoules is an adequate pulse energy to reliably create aqueous humor outflow channels during FLT in human cadaver eyes. OCT is a valuable tool when evaluating FLT.

Identification, crystallization, and first X-ray structure analyses of phenyl boronic acid-based inhibitors of human carbonic anhydrase-II

Human carbonic anhydrases (hCAs) play a central role in various physiological processes in the human body. HCAs catalyze the reversible hydration of CO2 into HCO3−, and hence maintains the fluid and pH balance. Overexpression of CA II is associated with diseases, such as glaucoma, and epilepsy. Therefore, CAs are important clinical targets and inhibition of different isoforms, especially hCA II is used in treatment of glaucoma, altitude sickness, and epilepsy. Therapeutically used CA inhibitors (CAI) are sulfonamide-based, such as acetazolamide, dichlorphenamide, methazolamide, ethoxzolamide, etc. However, they exhibit several undesirable effects such as numbness, tingling of extremities, malaise, metallic taste, fatigue, renal calculi, and metabolic acidosis. Therefore, there is an urgent need to identify safe and effective inhibitors of the hCAs. In this study, different phenyl boronic acids 1–5 were evaluated against bovine (bCA II) and hCA II. Among all, compound 1 (4-acetylphenyl boronic acid) was found to be active against bCAII and hCA II with IC50 values of 246 ± 0.48 and 281.40 ± 2.8 μM, respectively, while the remaining compounds were found in-active. Compound 1 was identified as competitive inhibitor of hCA II enzyme (Ki = 283.7 ± 0.002 μM). Additionally, compound 1 was found to be non-toxic against BJ Human fibroblast cell line. The X-ray crystal structure for hCA II in-complex with compound 1 was evaluated to a resolution of 2.6 Å. In fact, this the first structural analysis of a phenyl boron-based inhibitor bound to hCA II, allowing an additional structure-activity analysis of the compounds. Compound 1 was found to be directly bound in the active site of hCA II by interacting with His94, His119, and Thr199 residues. In addition, a bond of 3.11 Å between the zinc ion and coordinated boron atom of the boronic acid moiety of compound 1 was also observed, contributing to binding affinity of compound 1 for hCA II. PDB ID8IGF.

Triazolopyrimidine derivatives: An updated review on recent advances in synthesis, biological activities and drug delivery aspects.

Molecules containing triazolopyrimidine core showed diverse biological activities, including anti-Alzheimer, antidiabetes, anticancer, antimicrobial, antituberculosis, antiviral, antimalarial, anti-inflammatory, anti-parkinsonism activities, and treatment of glaucoma. Triazolopyrimidines have around 8 isomeric structures including the most stable 1,2,4-triazolo[1,5-a] pyrimidine ones. Triazolopyrimidines were obtained by using various chemical reactions, among them a) 1,2,4-triazole nucleus annulation to pyrimidine, b) pyrimidines annulation to 1,2,4-triazole structure, c) 1,2,4-triazolo[l,5-a] pyrimidines rearrangement, and d) pyrimido-tetrazine rearrangement. This review discusses synthetic methods, recent pharmacological actions and drug delivery perspectives of triazolopyrimidines.

Drug-Induced Liver Injury During a Glaucoma Neuroprotection Clinical Trial.

There are several ongoing, worldwide clinical trials with a cumulative target enrollment of over 1300 participants on the role of nicotinamide (a specific form of vitamin B3) as a therapeutic neuroprotective treatment for glaucoma. We describe a serious adverse event of drug-induced liver injury (DILI) likely related to the use of 3 grams/day nicotinamide in a glaucoma clinical trial (clinicaltrials.gov identifier: NCT05695027) based in the United States. This report is important to share with the medical community, as other participants in glaucoma nicotinamide trials globally may have similar adverse events and many patients are using nicotinamide as a health supplement without medical supervision. We recommend that investigators, physicians, and patients remain vigilant about DILI as they seek novel vision-preserving neuroprotective therapies.

Metformin in Glaucoma Treatment.

The objective of this study was to evaluate the potential beneficial impact of metformin on glaucoma risk factors and explore the underlying mechanisms. The goal is to contribute to the development of novel treatment strategies for glaucoma. We searched for studies that assessed the effects of metformin on glaucoma risk factors and the associated underlying mechanisms. Our search included electronic databases such as PUBMED, EMBASE, and clinicaltrials.gov. Unfortunately, we did not find any clinical trials that specifically investigated the impact of metformin on glaucoma. However, data from experimental studies demonstrated the capability of metformin to modulate various pathways that could contribute to neuroprotection in glaucoma. In order to develop comprehensive treatment strategies that fully utilize the therapeutic potential of metformin in glaucoma management, rigorous clinical studies are imperative. These studies are necessary to establish both the safety and efficacy of metformin in the context of glaucoma treatment.

Modern trends in the treatment of glaucoma

In nearly all Russian regions, glaucoma ranks first among the causes of disability due to ophthalmic pathology, which is in line with global trends of glaucoma incidence growth and its leading position among the causes of irreversible blindness. Treatment of glaucoma is aimed at lowering intraocular pressure (IOP). This review presents the main current trends in the treatment of glaucoma: drug therapy, laser surgery, fistulizing, drainage and non-penetrating surgery, as well as the latest micro-invasive glaucoma surgery (MIGS).Currently, the pharmaceutical market offers many antihypertensive drops. Fixed-dose combinations of drugs have been proposed to increase treatment adherence, and effective drug delivery methods are being developed, which lower IOP with minimal side effects. Further development of laser surgery makes it both a method of choice for the initial treatment (selective laser trabeculoplasty) and expands its capabilities for various stages of glaucoma (micropulse cyclophotocoagulation). All this significantly reduces the frequency of classical macroinvasive antiglaucoma operations. The previously existing gap between conservative medical therapy and antiglaucoma surgery is filled by the newest MIHG procedures. In recent years, at all stages of primary open-angle glaucoma therapy, the emergence of new pharmaceuticals, methods and implants has been noted. These constitute the purpose of this publication.

Virtual and experimental screening of new melatonin bioisosteres for the treatment of glaucoma

Background. Melatonin is an endogenous regulator of intraocular pressure (IOP), but its effectiveness as a drug for glaucoma treatment is limited.The  aim of  the  study. To develop and  to  validate a  virtual screening method to identify bioisosteric analogs of melatonin that are promising for study as agents that reduce intraocular pressure.Results. A database containing structural and experimental affinity information for 48 individual reference compounds was created. Risk assessments for mutagenic, carcinogenic, irritant and reproductive toxicity were performed in DataWarrior based on substructural analysis and identification of fragments that are markers of relevant toxicity. A virtual screening of 2457 structures was carried out and 25 compounds from the selected ones were experimentally studied for their effect on intraocular pressure (IOP) in intact rats. 10 of the 25 prioritized compounds were found to significantly reduce IOP; compound RU-398 reduced IOP by 40 %, K-165 – by 40.9 %, and RU-615 reduced glaucoma by 33.3 %.Conclusion. The  effectiveness of  virtual screening after experimental validation was 40 %. The identified active compounds are promising for further study and development as the agents for the treatment of glaucoma.

Spanlastic-laden nanogel as a plausible platform for dermal delivery of bimatoprost with superior cutaneous deposition and hair regrowth efficiency in androgenic alopecia

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.