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Background: Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance., Methods: A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed., Results: The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro . Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion., Conclusions: The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.

Glaucoma is the leading cause of irreversible vision loss worldwide, and reduction of intraocular pressure (IOP) is the only factor that can be interfered to delay disease progression. As the first line and preferred method to treat glaucoma, eye drops have many shortcomings, such as low bioavailability, poor patient compliance, and unsustainable therapeutic effect. In this study, a highly efficient brimonidine (BRI) silicone rubber implant (BRI@SR@TPU implant) has been designed, prepared, characterized, and administrated for sustained relief of IOP to treat glaucoma. The in vitro BRI release from BRI@SR@TPU implants shows a sustainable release profile for up to 35 d, with decreased burst release and increased immediate drug concentration. The carrier materials are not cytotoxic to human corneal epithelial cells and conjunctival epithelial cells, and show good biocompatibility, which can be safely administrated into rabbit's conjunctival sac. The BRI@SR@TPU implant sustainably released BRI and effectively reduced IOP for 18 d (72 times) compared to the commercial BRI eye drops (6 h). The BRI@SR@TPU implant is thus a promising noninvasive platform product for long-term IOP-reducing in patients with glaucoma and ocular hypertension.

Glaucoma is the global leading cause of irreversible blindness. It is a chronic progressive disorder and, therefore, often requires long-term management with drugs on patients' discretion. However, there is a shortage of antiglaucoma drugs in the current market due to their low bioavailability. This is because there are multiple biological barriers of the human eyes, thereby leading to increased demands for frequent dosage regimen per day of these drugs, which could result in concomitant side effects and eventually reduced patient compliance. Recently, nanomedicines have become optimized alternatives to conventional ophthalmic formulations due to advantages of improved barrier permeability, sustained drug release, tissue targeting, and lowered systemic absorption of instilled medications. These merits provide the active ingredients in these nanomedicines an effective manner to reach the ideal concentrations at sites of damaged nerves, offering a promising platform for neuroprotective treatment of these conditions. In this study, nanomedicines and nanomedicine-based novel strategies for pharmacotherapy of glaucoma were reviewed, including liposomes, niosomes, nanoparticles, and dendrimers. This article intends to offer a comprehensive review of frontier progresses as well as hotspots and issues that appeared in the field of nanomedicines, which may enable a practical flourish in the future. STATEMENT OF SIGNIFICANCE: Recent novel pharmaceutical strategies toward glaucoma, a chronic blinding ocular disease that currently requires frequent daily dosage regimen, based on nanomedicines and nanomaterials have been comprehensively reviewed in this manuscript. The collection of field hotspots and issues in the late years should offer a quick grasp of the general concept and up-to-date threads upon the refinement of existing treatment patterns for glaucoma. Meanwhile, the Conclusion and Future Perspective section given at the end of the text brings out the possible shortages and opinions in terms of ideal research direction, which hopefully could facilitate a future practical flourish in the area., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To compare intraocular pressure (IOP) measurements obtained using the Topocon noncontact tonometer (NCT), the Goldmann applanation tonometer (GAT), and the Corvis ST (CST), a newly developed tonometer with features of visualization and measurement of the corneal deformation response to an air impulse. A secondary objective was to assess the agreement among the devices., Methods: Fifty-nine participants, including glaucoma patients (36 cases) and control volunteers (23 cases), were enrolled. One eye was selected randomly for further study. IOP measurements were obtained with the CST, NCT, and GAT by two experienced clinicians. IOP values were compared. Intraobserver variability and interobserver variability were assessed by the coefficient of variation and intraclass correlation coefficient. Device agreement was calculated by Bland-Altman analysis., Results: Mean IOP for all examined eyes was 18.9 ± 5.8 mm Hg for CST, 21.3 ± 6.8 mm Hg for NCT, and 20.3 ± 5.7 mm Hg for GAT. There was no statistically significant difference in IOP measurements among the tonometers except between the CST and NCT. Correlation analysis showed a high correlation between each pair of devices (all P < 0.001). The CST displayed the best intraobserver variability and interobserver variability. Bland-Altman analysis revealed a bias between CST and GAT, CST and NCT, and GAT and NCT of -1.3, -2.4, and -1.1 mm Hg, with 95% limits of agreement of -6.2 to 3.5 mm Hg, -10.1 to 5.2 mm Hg, and -8.3 to 6.2 mm Hg, respectively., Conclusions: The CST offers an alternative method for measuring IOP. IOP measurements taken with these devices may not be interchangeable.

PurposeTo evaluate the in vivo changes in the Schlemm's canal (SC) in patients with primary angle-closure glaucoma (PACG) after trabeculectomy using spectral-domain optical coherence tomography (SD-OCT).MethodsForty eyes of 40 patients with PACG who underwent trabeculectomy were included. All participants underwent SD-OCT. The diameter and area of SC were examined and measured before and within 1 month after trabeculectomy. All SD-OCT images were processed using adaptive compensation algorithm to improve contrast and image quality. Multivariate linear regression analysis was performed for predictors of percentage change in the mean SC diameter and area.ResultsThe mean age of participants was 60.5 ± 14.6 years. Adaptive compensation significantly increased the percentage of sections in which SC was observable in the subjects studied from 52.5% (21/40) to 75.0% (30/40), which has acceptable intraobserver and interobserver repeatability. There was a significant increase in the SC diameter and area at the follow-up examination compared with the baseline value (SC diameter: 34.2 ± 6.2 μm vs. 28.4 ± 6.1 μm; SC area: 8117 ± 1942 μm(2) vs. 5200 ± 996 μm(2); all P < 0.001). After multivariate analysis, the only variable related to changes in SC was percentage change in IOP (SC diameter, P = 0.002; SC area, P < 0.001). In addition, the magnitude of the change in the SC area also correlated with angle opening distance at 750 μm from the scleral spur at baseline.ConclusionsExpansion of SC was observed after trabeculectomy in PACG patients. The degree of SC expansion was related to the extent of the IOP decrease.

Purpose: To investigate whether asiatic acid (AA) can improve the quantity and function of retinal ganglion cells (RGCs), as well as how AA regulates synaptic pathways in rat models with chronic glaucoma. Methods: In our study, a rat model of chronic glaucoma was prepared via the electrocoagulation of the episcleral veins. The numbers of surviving RGCs were counted via retrograde Fluorogold labeling, and a whole-cell patch clamp was used to clamp RGCs in normal retinal sections and in retinal sections 4 weeks after glaucoma induction. Results: Retrograde-Fluorogold-labeled RGC loss caused by persistent glaucoma was decreased by AA. Additionally, AA reduced the postsynaptic current produced by N-methyl-D-aspartate (NMDA) and diminished miniature glutamatergic excitatory neurotransmission to RGCs. On the other hand, AA increased miniature gamma-aminobutyric acid (GABA)-ergic inhibitory neurotransmission to RGCs and enhanced the GABA-induced postsynaptic current. The excitability of the RGC itself was also decreased by AA. RGCs in glaucomatous slices were less excitable because AA decreased their spontaneous action potential frequency and membrane potential, which led to a hyperpolarized condition. Conclusions: AA directly protected RGCs in a chronic glaucoma rat model by lowering their hyperexcitability. To enhance RGCs' survival and function in glaucoma, AA may be a viable therapeutic drug. [ABSTRACT FROM AUTHOR]

Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit's conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma. [ABSTRACT FROM AUTHOR]