Glaucoma Therapy Research Articles

Acute glaucoma attack in a patient recovered from coronavirus infection (case report)

The prevalence of ophthalmic manifestations in COVID-19 ranges from 2 to 32%. The most common ophthalmic disease associated with COVID-19 is viral conjunctivitis, but there are also reports of cases with episcleritis, uveitis, occlusions of the central retinal artery and vein, retinopathy, glaucoma, dry eye syndrome, as well as rare neuroophthalmological manifestations such as diplopia, ophthalmoplegia and nystagmus. This study reports a case of bilateral acute angle-closure glaucoma attack in a patient recovered from severe COVID-19 pneumonia.PURPOSE. To determine the causes of bilateral acute angle-closure glaucoma attack associated with COVID-19 pneumonia, and to evaluate the effectiveness of laser iridotomy and transciliary drainage of the posterior chamber of the eye.METHODS. Bilateral acute angle closure glaucoma attack was observed in a female patient recovered from COVID-19 pneumonia. Low hypermetropia and co-existing cataract were diagnosed in both eyes. In order to normalize the IOP and restore visual acuity, laser iridotomy was performed in both eyes, followed by surgical treatment of glaucoma with transciliary drainage of the posterior chamber in both eyes. After that the patient underwent phacoemulsification with implantation of intraocular lenses (IOL) in both eyes.RESULTS. Laser iridotomy and transciliary drainage of the posterior chamber was performed in both eyes. The target IOP without topical therapy and stabilization of glaucoma were achieved in both eyes. The second step was phacoemulsification with implantation of IOL, which significantly improved visual acuity of both eyes.CONCLUSION. COVID-19 can lead to vision loss and disability, therefore IOP should be monitored in patients that remain in prone position for ventilation for extended periods of time and receive systemic steroid medications. This is especially relevant for patients with a predisposition to glaucoma or with diagnosed glaucoma.

Continuous Optimisation of Experimental Models - an Example from Glaucoma Research

There is a great demand for suitable models to test novel surgical and therapeutic approaches in glaucoma therapy. To address this need and to provide further alternatives to in vivo animal models, we aimed at modifying an established in vitro porcine eye perfusion model. Two weaknesses of the previously established porcine anterior segment model include media leakage during perfusion and setup disintegration due to mechanical instability. To overcome these, we slightly modified the previously used custom-made perfusion dishes and incorporated new components into the model setup. To prevent fluid leakage, we secured the anterior segments more firmly to the perfusion trays using a compression ring, steel screws, and nuts. Customised mounts were used to stabilise the perfusion dish and pressure transducer as a single unit. The mounts were made of polylactide (PLA) and printed using a 3D printer. The use of steel screws and nuts allowed tighter clamping of the anterior segments and prevented medium leakage. Our PLA custom mounts stabilised the entire assembly and facilitated handling during experiments and improved comparability between tested eyes. They also prevented accidental detachment of the pressure transducers, which resulted in more stable pressure curves. Our PLA mounts tolerated incubation temperatures of up to 37 °C and disinfection with enzymatic detergents and 70% ethanol without showing signs of deformation or degradation after four months of regular usage. Modifications introduced to an established in vitro perfusion model improved its efficacy and reproducibility. Our adjusted model is an example of how many models can be optimised through critical analysis, thereby saving resources and providing reliable results in the long run.

Current trends in targeting the oxidative stress in glaucoma (Review).

Glaucoma is a progressive optic neuropathy characterised by retinal ganglion cell degeneration and visual field loss. Glaucoma is considered to be the leading cause of blindness in the industrialised countries. Oxidative damage is an important pathogenic factor in glaucoma, which triggers trabecular meshwork (TM) degeneration, which then leads to intraocular hypertension. Neurodegenerative insults during glaucomatous neurodegeneration initiate an immune response to restore tissue homeostasis. However, the oxidative stress (OS) that develops during the pathogenic processes of glaucoma, along with the agerelated OS, plays a critical role in shifting the physiological equilibrium. In the TM from glaucoma donors, proinflammatory markers were found, which were induced by the activation of a stress response. Chronic changes in the composition of antioxidants found in aqueous humour may induce alterations in TM as well as in the optic nerve head cells. Highlighting the pathogenic role of reactive oxygen species (ROS) in glaucoma has implications in preventing this disease. Various clinical trials are available to test the efficacy of antioxidant drugs in glaucoma management. In this review, we discuss the OS as a therapeutic target, suggesting that the modulation of a pro-oxidant/antioxidant status might be a relevant target for glaucoma prevention and therapy.

ScAAV2-Mediated Expression of Thioredoxin 2 and C3 Transferase Prevents Retinal Ganglion Cell Death and Lowers Intraocular Pressure in a Mouse Model of Glaucoma.

Elevated intraocular pressure (IOP) in glaucoma causes retinal ganglion cell (RGC) loss and damage to the optic nerve. Although IOP is controlled pharmacologically, no treatment is available to restore retinal and optic nerve function. In this paper, we aimed to develop a novel gene therapy for glaucoma using an AAV2-based thioredoxin 2 (Trx2)-exoenzyme C3 transferase (C3) fusion protein expression vector (scAAV2-Trx2-C3). We evaluated the therapeutic effects of this vector in vitro and in vivo using dexamethasone (DEX)-induced glaucoma models. We found that scAAV2-Trx2-C3-treated HeLa cells had significantly reduced GTP-bound active RhoA and increased phosphor-cofilin Ser3 protein expression levels. scAAV2-Trx2-C3 was also shown to inhibit oxidative stress, fibronectin expression, and alpha-SMA expression in DEX-treated HeLa cells. NeuN immunostaining and TUNEL assay in mouse retinal tissues was performed to evaluate its neuroprotective effect upon RGCs, whereas changes in mouse IOP were monitored via rebound tonometer. The present study showed that scAAV2-Trx2-C3 can protect RGCs from degeneration and reduce IOP in a DEX-induced mouse model of glaucoma, while immunohistochemistry revealed that the expression of fibronectin and alpha-SMA was decreased after the transduction of scAAV2-Trx2-C3 in murine eye tissues. Our results suggest that AAV2-Trx2-C3 modulates the outflow resistance of the trabecular meshwork, protects retinal and other ocular tissues from oxidative damage, and may lead to the development of a gene therapeutic for glaucoma.

Rho-Kinase Inhibitors as Emerging Targets for Glaucoma Therapy.

Glaucoma, the leading cause of irreversible blindness worldwide, is a chronic and progressive optic neuropathy characterized by damage to the optic and retinal nerve fiber layers, which can lead to permanent loss of peripheral or central vision. Reduction of intraocular pressure (IOP) is the only known modifiable risk factor for preventing and treating glaucoma. Rho kinase (ROCK) inhibitors are a new class of glaucoma drugs with a novel mechanism of action and good safety profile. They exert neuroprotective effects, act on the trabecular tissue, increase the outflow of aqueous humor, and reduce intraocular pressure. However, they also cause local adverse reactions, including common conjunctival congestion and subconjunctival bleeding; however, most are self-limiting and temporary. Netarsudil (0.02%), a ROCK inhibitor, relaxes the trabecular meshwork, increases the outflow of aqueous humor, reduces scleral venous pressure, anddirectly decreases IOP. Conjunctival congestion can be reduced if netarsudil is administered at night. The combination of these medications is always more effective than the single drug. Ripasudil (0.4%), another ROCK inhibitor, also lowers IOP; however, conjunctival hyperemia is the most common adverse drug reaction. The purpose of this review is to summarize the effects and adverse reactions of ROCK inhibitors in the experimental trial stage and in clinical treatment in recent years, providing suggestions for future clinical drug use, and research and development to reduce the side effects of these drugs, maximize the potential for reducing IOP, and improve the therapeutic effect.

Takotsubo Cardiomyopathy following Eye Surgery under Local Anesthesia - A Case Report

Introduction: Takotsubo syndrome is extremely rare and usually seen in postmenopausal women. It manifests as acute coronary syndromes (ACS), but coronaries are usually normal and the majority recover completely without residual myocardial damage. Methods: We are reporting one such case, which followed laser therapy for glaucoma under local anesthesia. She fulfilled all the revised Mayo Clinic criteria for diagnosis. Her preoperative cardiac evaluation and computerized tomography coronary angiograms were normal. Results: This report highlights the need for a wide index of suspicion in those presenting as ACS. Surgical procedures however minor they are, even under local anesthesia should not be considered no-risk ones. Conclusion: Takotsubo cardiomyopathy is reversible acute cardiomyopathy that can occur even after minor eye surgery under local anesthesia. Patients may need coronary angiogram and serial echocardiogram at follow-up. It can be prevented by avoiding trigger factors, addressing preexisting neuropsychiatric ailments, and institution of prophylactic beta-blocker therapy.

Glaucoma and Dry Eye Disease: Opportunity to Assess and Treat.

Dry eye disease (DED) has been found to occur at a higher prevalence in individuals with glaucoma than in individuals without glaucoma. The relationship between glaucoma and DED may be, in part, a result of glaucoma therapy. Greater number of antiglaucoma medications used and greater number of antiglaucoma eyedrops instilled per day have been associated with ocular surface disease in patients with glaucoma. Use of antiglaucoma medication has also been associated with higher levels of ocular surface inflammatory markers and ocular surface alterations. There is evidence to suggest that antiglaucoma medications with preservatives and, to some extent, antiglaucoma medication formulations without preservatives may contribute to ocular surface signs and symptoms. Trabeculectomy for glaucoma has also been associated with ocular surface signs related to DED; however, there may be benefits of trabeculectomy and other procedures for glaucoma due to reduced use of antiglaucoma medications. Patients with glaucoma with ocular surface disease have been found to have greater ocular surface symptoms, poorer vision-related quality of life, and poorer antiglaucoma medication adherence compared with patients with glaucoma without ocular surface disease. Because of the potential negative impact of DED on patients with glaucoma, patients with glaucoma may benefit from evaluation for DED. Management of DED in patients with glaucoma may include modifications to antiglaucoma medications and use of treatments for DED.

Advancement in Understanding Glaucoma: A Comprehensive Review.

Glaucoma, a silent thief of sight, remains a significant cause of irreversible blindness due to a substantial number of undiagnosed and untreated cases. To combat this insidious disease effectively, a multifaceted approach is imperative. Early detection is paramount in the battle against glaucoma. Patient history, including family history, plays a pivotal role in identifying those at risk. A comprehensive understanding of a patient's genetic predisposition can significantly enhance the accuracy of diagnosis and detection of suspicious cases. Treatment options include prescription eye drops, oral medicines, laser treatment, surgery, or a combination of approaches. Trabeculectomy involves the surgical creation of an aqueous humor drainage channel, while laser trabeculoplasty enhances aqueous outflow by modifying the trabecular meshwork. However, these procedures pose certain risks and complications. Exploration of alternative treatments with lower risks is underway. These innovative approaches hold promise in reducing the burdens associated with conventional treatments such as trabeculectomy. However, the effectiveness of these alternatives in the long term remains a subject of ongoing research. Neuroprotective drugs have also been in development to halt the progression of glaucoma. However, their success remains uncertain due to challenges, such as a lack of understanding of the underlying mechanisms, scarcity of suitable drugs, and regulatory hurdles in gaining approval. In essence, the overarching goal of glaucoma therapy is to reduce intraocular pressure through various means - medications, laser procedures, or innovative methods. The aim is to slow down the disease's progression, thereby preserving vision and improving the patient's quality of life. In conclusion, addressing the challenge of glaucoma requires a comprehensive approach encompassing early detection, innovative treatments, and ongoing research into potential cures. Only through concerted efforts can we hope to reduce the impact of this sight-stealing disease on individuals and society as a whole.

Factors Affecting Glaucoma Medication Adherence and Interventions to Improve Adherence: A Narrative Review.

Glaucoma is a leading cause of vision loss. First line therapy for primary open angle glaucoma (POAG) are topical ocular hypotensive drops. Patient adherence with topical therapy for glaucoma is a significant challenge with a reported adherence of 60%. The purpose of this review is to discuss factors associated with glaucoma adherence (including demographic factors, cost, patient education, health beliefs, treatment burden and regimen, and physical limitations) and to explore potential interventions to improve medication adherence. Articles included in this review were found by searching PubMed and Google Scholar using the key words "Glaucoma Treatment Adherence" and "Glaucoma Treatment Compliance." Data from this review demonstrates that higher medication cost, lower patient education/literacy levels, and being of African and Hispanic descent are associated with lower medication adherence rates. The data is inconclusive on whether medication regimen complexity lowers patient medication adherence rates. Interventions that have successfully improved medication adherence rates for minority patients have focused on building trust and addressing fears and false beliefs. For cost, explicit physician communication to patients regarding medication cost is important and can help the physician determine any patient concerns about cost. Outside the USA, adherence has been improved through adherence-contingent rebate systems and government subsidies. Most interventions that aim to increase adherence target patient education and literacy with the following interventions demonstrating efficacy: written instructions targeting glaucoma-specific health literacy, literacy level appropriate glaucoma education videos, and interactive and personalized educational programs. More clinic infrastructure and programs that utilize patient reminder tools and patient educators could help physicians and patients in support of these personalized action plans.

Technological Advances in a Therapy of Primary Open-Angle Glaucoma: Insights into Current Nanotechnologies.

Glaucoma is a leading cause of irreversible blindness and is characterized by increased intraocular pressure (IOP) and progressive optic nerve damage. The current therapeutic approaches for glaucoma management, such as eye drops and oral medications, face challenges including poor bioavailability, low patient compliance, and limited efficacy. In recent years, nanotechnology has emerged as a promising approach to overcome these limitations and revolutionize glaucoma treatment. In this narrative review, we present an overview of the novel nanotechnologies employed in the treatment of primary open-angle glaucoma. Various nanosystems, including liposomes, niosomes, nanoparticles, and other nanostructured carriers, have been developed to enhance the delivery and bioavailability of antiglaucoma drugs. They offer advantages such as a high drug loading capacity, sustained release, improved corneal permeability, and targeted drug delivery to the ocular tissues. The application of nanotechnologies in glaucoma treatment represents a transformative approach that addresses the limitations of conventional therapies. However, further research is needed to optimize the formulations, evaluate long-term safety, and implement these nanotechnologies into clinical practice. With continued advancements in nanotechnology, the future holds great potential for improving the management and outcomes of glaucoma, ultimately preserving vision and improving the lives of millions affected by this debilitating disease.

Pirfenidone release from ophthalmic implants – perspectives for a drug-eluting microstent for glaucoma therapy

Abstract Elevated intraocular pressure is the main risk factor for glaucoma and its adjustment to physiological levels can prevent progression of the disease. If conventional drop-based glaucoma therapy fails, surgical interventions such as trabeculectomy or the application of implants, which drain aqueous humour from the eye and thus reduce intraocular pressure, are used as final therapeutic procedures. These interventions are becoming increasingly minimally invasive and the drainage implants are getting steadily smaller, which is why these interventions are now called microinvasive glaucoma surgery (MIGS). Both, surgery and drainage implant-based glaucoma therapy are limited by wound healing processes and fibrosis that occlude the newly created drainage pathways for the aqueous humour. To suppress unwanted postoperative fibrosis coupled with an increased extracellular matrix production, cytostatics like mitomycin c or 5- fluorouracil are currently used, which are associated with side effects. Therefore, more specific antifibrotic agents are key for a durable functionality of the interventions in glaucoma therapy. In this study a specific active substance (pirfenidone, PFD) was added in a polymer matrix for controlled release. Previous studies have shown that the release of pirfenidone from a thermoplastic silicone polycarbonate elastomer, which could be used as a material for a glaucoma drainage implant, has been relatively fast. To decelerate the release the influence of the alternate polymers Poly-L-Lactide (PLLA) and Poly-D,LLactide (PDLLA) as alternative drug carriers was investigated. Furthermore, a reduction of the pirfenidone content was used to delay the release.

Research trends of worldwide ophthalmologic randomized controlled trials in the 21st century: A bibliometric study

BackgroundRandomized controlled trials (RCTs) are often considered the gold standard and the cornerstone for clinical practice. However, bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet. This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century. MethodsGlobal ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection. The number of publications, country/region, institution, author, journal, and research hotspots of RCTs were analyzed using HistCite, VOSviewer, CiteSpace, and Excel software. Results2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs, with the United States leading in the number of volumes and research field, and the Moorfields Eye Hospital contributing to the most publications. Ophthalmology received the greatest number of publications and co-citations. Jeffrey S. Heier owned the most publications and Jost B. Jonas owned the most co-citations. The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts, and anti-vascular endothelial growth factor (VEGF) therapy (ranibizumab), topical ocular hypotensive medication, laser trabeculoplasty. Anti-VEGF therapy for age-related macular degeneration (AMD), DME (diabetic macular edema), and DED, the use of new diagnostic tools, and myopia were the hottest research highlights. Anti-VEGF therapy, prompt laser, triamcinolone, and verteporfin photodynamic therapy for AMD, DME, and CNV (choroidal neovascularization), DED, myopia, and open-angle glaucoma were the research hotspots with the longest duration. The future research hotspots might be DED and the prevention and control of myopia. ConclusionsOverall, the number of global ophthalmologic RCTs in the 21st century was keeping growing, there was an imbalance between the regions and institutions, and more efforts are required to raise the quantity, quality, and global impact of high-quality clinical evidence in developing countries/regions.

Connective tissue growth factor: Role in trabecular meshwork remodeling and intraocular pressure lowering.

Connective tissue growth factor (CTGF) is a distinct signaling molecule modulating many physiological and pathophysiological processes. This protein is upregulated in numerous fibrotic diseases that involve extracellular matrix (ECM) remodeling. It mediates the downstream effects of transforming growth factor beta (TGF-β) and is regulated via TGF-β SMAD-dependent and SMAD-independent signaling routes. Targeting CTGF instead of its upstream regulator TGF-β avoids the consequences of interfering with the pleotropic effects of TGF-β. Both CTGF and its upstream mediator, TGF-β, have been linked with the pathophysiology of glaucomatous optic neuropathy due to their involvement in the regulation of ECM homeostasis. The excessive expression of these growth factors is associated with glaucoma pathogenesis via elevation of the intraocular pressure (IOP), the most important risk factor for glaucoma. The raised in the IOP is due to dysregulation of ECM turnover resulting in excessive ECM deposition at the site of aqueous humor outflow. It is therefore believed that CTGF could be a potential therapeutic target in glaucoma therapy. This review highlights the CTGF biology and structure, its regulation and signaling, its association with the pathophysiology of glaucoma, and its potential role as a therapeutic target in glaucoma management.

Cell-Based Therapies for Glaucoma.

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways. However, proper integration within the retina and projection to the brain by the newly regenerated neuronal cells remain major hurdles. Meanwhile, a range of methods for in vitro differentiation have been developed to derive retinal cells from a variety of cell sources, including embryonic and induced pluripotent stem cells. More recently, there has been growing interest in the implantation of glial cells as well as cell-derived products, including neurotrophins, microRNA, and extracellular vesicles, to provide functional support to vulnerable structures such as RGC axons and the ONH. These approaches offer the advantage of not relying upon the replacement of degenerated cells and potentially targeting earlier stages of disease pathogenesis. In order to translate these techniques into clinical practice, appropriate cell sourcing, robust differentiation protocols, and accurate implantation methods are crucial to the success of cell-based therapy in glaucoma. Translational Relevance: Cell-based therapies for glaucoma currently under active development include the induction of endogenous regeneration, implantation of exogenously derived retinal cells, and utilization of cell-derived products to provide functional support.

Stable Gastric Pentadecapeptide BPC 157-Possible Novel Therapy of Glaucoma and Other Ocular Conditions.

Recently, stable gastric pentadecapeptide BPC 157 therapy by activation of collateral pathways counteracted various occlusion/occlusion-like syndromes, vascular, and multiorgan failure, and blood pressure disturbances in rats with permanent major vessel occlusion and similar procedures disabling endothelium function. Thereby, we revealed BPC 157 cytoprotective therapy with strong vascular rescuing capabilities in glaucoma therapy. With these capabilities, BPC 157 therapy can recover glaucomatous rats, normalize intraocular pressure, maintain retinal integrity, recover pupil function, recover retinal ischemia, and corneal injuries (i.e., maintained transparency after complete corneal abrasion, corneal ulceration, and counteracted dry eye after lacrimal gland removal or corneal insensitivity). The most important point is that in glaucomatous rats (three of four episcleral veins cauterized) with high intraocular pressure, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, nor- mal retinal and choroidal blood vessel presentation, and normal optic nerve presentation. The one episcleral vein rapidly upgraded to accomplish all functions in glaucomatous rats may correspond with occlusion/occlusion-like syndromes of the activated rescuing collateral pathway (azygos vein direct blood flow delivery). Normalized intraocular pressure in glaucomatous rats corresponded to the counteracted intra-cranial (superior sagittal sinus), portal, and caval hypertension, and aortal hypotension in occlusion/occlusion-like syndromes, were all attenuated/eliminated by BPC 157 therapy. Furthermore, given in other eye disturbances (i.e., retinal ischemia), BPC 157 instantly breaks a noxious chain of events, both at an early stage and an already advanced stage. Thus, we further advocate BPC 157 as a therapeutic agent in ocular disease.

Impact of Latanoprost Antiglaucoma Eyedrops and Their Excipients on Toxicity and Healing Characteristics in the Ex Vivo Eye Irritation Test System.

Corneal epithelial toxicity and delayed healing process have already been attributed to preservatives or some excipients. We study the effects of galenic components in antiglaucoma drugs such as benzalkonium chloride (BAC) or surfactants like macrogolglycerol hydroxystearate 40 (MGHS40) on corneal toxicity in an exvivo system mimicking chronic use. Latanoprost-containing eyedrops are available with and without preservatives on the market. Unpreserved, they are available in different formulations with various excipients like MGHS at different concentrations (0%, 2.5%, and 5%). We studied these in the exvivo bioreactor (EVEIT) on initially injured rabbit corneas. The drugs were applied six times daily for observation periods of 3 or 5days. BAC, 5% MGHS40 solution, and 0.18% hyaluronic acid served as controls. Macroscopic photographic, biochemical methods and corneal integrity quantification were used for evaluation. Toxicity was assessed by measuring wound healing and corneal fluorescein sodium permeability and was confirmed by histology studies. The BAC-preserved formulation resulted in high corneal toxicity, which was expected. Interestingly, the preservative-free (PF) formulation containing 5% MGHS40, carbomer, macrogol4000, and sorbitol showed the highest corneal toxicity, followed by the control formulation with equal MGHS40 concentration, which presented significantly less damage. No toxicity was shown by eyedrops containing 2.5% MGHS40 or salts only. Our study demonstrates a significant corneal toxicity of certain formulations of PF antiglaucoma ophthalmic drugs containing 5% MGHS40 with other excipients compared to other formulations with lower MGHS40 concentrations (2.5% or 0%), or even compared to the solution containing 5% MGHS alone. This suggests a concentration-dependent toxicity of MGHS40, especially in interaction with other excipients, which may increase its epithelial toxicity, and that has to be considered in clinical glaucoma therapy. Further single-component formulation trials are needed to support this interpretation.

Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy.

Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.

Glaucoma Treatment Patterns in Sub-Saharan Africa.

Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma. Laser therapy was underutilized where they were available. Physicians were more likely to recommend surgery in severe glaucoma, laser therapy in mild glaucoma, while recommendation of medical therapy did not depend on glaucoma severity. To characterize treatment patterns for newly diagnosed glaucoma in sub-Saharan Africa (SSA). This was a multicenter cross-sectional study of adults newly diagnosed with glaucoma at 27 eye care centers in 10 African countries. In addition to demographic and clinical data, physician treatment recommendations (medication, laser, surgery, or no treatment) were recorded. Statistical analyses were performed using STATA version 14.0. Data from 1201 patients were analyzed. Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma (69.4%), with laser (13.2%), surgery (14.9%), and no treatment (2.5%) recommended to the remaining patients. All sites had medical therapy available and most (25/27, 92.6%) could provide surgical treatment; only 16/27 (59.3%) sites offered laser, and at these sites, 30.8% of eyes were recommended to undergo primary laser procedures. As glaucoma severity increased, the laser was recommended less, surgery more, and medications unchanged. Patient acceptance of medical therapy was 99.1%, laser 88.3%, and surgery 69.3%. Medical therapy for first-line glaucoma management is preferred by most physicians in SSA (69%). Laser therapy may be underutilized at centers where it is available. These findings underscore the need for comparative studies of glaucoma treatments in SSA to inform the development of evidence-based treatment guidelines and of programs to reduce glaucoma blindness in SSA. Strategic approaches to glaucoma therapy in SSA must address the question of whether medical therapy is the most optimal first-line approach in this setting.

Exploring Penetration Ability of Carbonic Anhydrase Inhibitor-Loaded Ultradeformable Bilosome for Effective Ocular Application.

Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6h and trans-corneal permeability of 8.78 ± 0.14cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy.

Exosome-based crosstalk in glaucoma pathogenesis: a focus on oxidative stress and neuroinflammation.

Exosomes are membrane-bound tiny particles that are released by all live cells that contain multiple signal molecules and extensively participate in numerous normal physical activities and pathologies. In glaucoma, the crucial role of exosome-based crosstalk has been primarily revealed in animal models and ex vivo cell studies in the recent decade. In the aqueous drainage system, exosomes derived from non-pigment ciliary epithelium act in an endocrine manner and specifically regulate the function of the trabecular meshwork to cope with persistent oxidative stress challenges. In the retina, a more complicated regulatory network among microglia, retinal neurons, retinal ganglial cells, retinal pigment epithelium, and other immune effector cells by exosomes are responsible for the elaborate modulation of tissue homeostasis under physical state and the widespread propagation of neuroinflammation and its consequent neurodegeneration in glaucoma pathogenesis. Accumulating evidence indicates that exosome-based crosstalk depends on numerous factors, including the specific cargos they carried (particularly micro RNA), concentration, size, and ionization potentials, which largely remain elusive. In this narrative review, we summarize the latest research focus of exosome-based crosstalk in glaucoma pathogenesis, the current research progress of exosome-based therapy for glaucoma and provide in-depth perspectives on its current research gap.