Although selective laser trabeculoplasty (SLT) is a recognized method for the treatment of glaucoma, the exact changes in the target tissue and mechanism for its intraocular pressure lowing effect are still unclear. The purpose of this review is to summarize the potential mechanisms of SLT on trabecular meshwork both in vivo and in vitro, so as to reveal the potential mechanism of SLT. SLT may induce immune or inflammatory response in trabecular meshwork (TM) induced by possible oxidative damage etc, and remodel extracellular matrix. It may also induce monocytes to aggregate in TM tissue, increase Schlemm\'s canal (SC) cell conductivity, disintegrate cell junction and promote permeability through autocrine and paracrine forms. This provides a theoretical basis for SLT treatment in glaucoma.

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.

BACKGROUND: The iStent (Glaukos Corporation; Laguna Hills, CA, USA) is one of the minimally invasive glaucoma devices. It can be inserted at the time of phacoemulsification or as a stand-alone procedure to lower the intraocular pressure (IOP).
OBJECTIVE: Our aim was to conduct a systematic review and meta-analysis comparing the effect of iStent insertion at the time of phacoemulsification with phacoemulsification alone in patients with ocular hypertension or open-angle glaucoma.
METHODS: We searched EMBASE, MEDLINE (OVID and PubMed), CINAHL, and Cochrane Library for articles published between 2008 and June 2022 (PRISMA 2020 for the checklist). Studies comparing the IOP-lowering effect of iStent with phacoemulsification versus phacoemulsification alone were included. The endpoints were IOP reduction (IOPR) and the mean reduction in the number of glaucoma drops. A quality-effects model was used to compare both surgical groups.
RESULTS: Ten studies were included, reporting on 1,453 eyes. Eight hundred fifty three eyes had the combined iStent and phacoemulsification, and 600 eyes underwent phacoemulsification alone. IOPR was higher in the combined surgery at of 4.7 ± 2 mm Hg compared to 2.8 ± 1.9 mm Hg in phacoemulsification alone. A greater decrease in postoperative eye drops was noted in the combined group having a decrease of 1.2 ± 0.3 eye drops versus of 0.6 ± 0.6 drops in isolated phacoemulsification. The quality effect model showed an IOPR weighted mean difference (WMD) of 1.22 mm Hg (confidence interval [CI]: [-0.43, 2.87]; Q = 315.64; p < 0.01; I2 = 97%) and decreased eye drops WMD 0.42 drops (CI: [0.22, 0.62]; Q = 42.6; p < 0.01; I2 = 84%) between both surgical groups. Subgroup analysis shows that the new generation iStent may be more effective in reducing IOP.
CONCLUSIONS: iStent has a synergetic effect with phacoemulsification. The reduction of IOP and glaucoma eye drops was higher when iStent is combined with phacoemulsification compared with isolated phacoemulsification.

Presently, there is no efficacious treatment for glaucomatous optic neuropathy; the current treatment is focused on lowering intraocular pressure (IOP). Studies have demonstrated the safety and efficacy of selective laser trabeculoplasty (SLT) in reducing the IOP in eyes with open-angle (OAG) glaucoma or ocular hypertension (OH). Moreover, the European Glaucoma Society has instated SLT as the first-line or adjunctive treatment in OAG or OH, reiterating its clinical significance. In this review, we outline the old and the new roles of SLT, with an emphasis on clinical practice, and look further into its renewed appeal and future developments.

A literature review of selective laser trabeculoplasty (SLT) energy dose-response found no definitive relationship between intraocular pressure (IOP) reduction with respect to total or pulse energy, race, pigmentation, or application pattern.
SLT is a safe and effective treatment for lowering IOP. Although evidence is mounting for the advantage of its use as a first-line treatment for IOP reduction, the SLT procedures in use vary widely. The purpose of this literature review was to investigate whether there were any relationships between SLT energy and efficacy for lowering IOP in the published literature.
A literature review was undertaken that included studies in which energy levels required for successful SLT treatment were investigated: in general, with respect to angle pigmentation, race or ethnicity, and treatment arc extent.
There was no indication that higher (or lower) energy used in the treatment leads to greater (or less) IOP reduction. Similar results were obtained regarding the level of trabecular meshwork pigmentation. Race was not found to be associated with altered dose response in SLT. There were indications that treating the full 360 degrees, as opposed to smaller arcs, could be beneficial for more IOP reduction. IOP reduction from SLT was found to be similar to that provided by topical medications.
The optimal energy level of SLT needed for IOP reduction has not yet been definitively established, with all reported pulse energies resulting in similar IOP reduction. Furthermore, similar lack of conclusive findings exists regarding optimal SLT energy dosage for use in different races and degrees of trabecular meshwork pigmentation. This parameter and each of the abovementioned factors requires further research.

The trabecular meshwork regulates aqueous humour outflow from the anterior chamber of the eye. It does this by establishing a tunable outflow resistance, defined by the interplay between cells and their extracellular matrix (ECM) milieu, and the molecular interactions between ECM proteins. During normal tissue homeostasis, the ECM is remodelled and trabecular cell behaviour is modified, permitting increased aqueous fluid outflow to maintain intraocular pressure (IOP) within a relatively narrow physiological pressure. Dysfunction in the normal homeostatic process leads to increased outflow resistance and elevated IOP, which is a primary risk factor for glaucoma. This review delineates some of the changes in the ECM that lead to gross as well as some more subtle changes in the structure and function of the ECM, and their impact on trabecular cell behaviour. These changes are discussed in the context of outflow resistance and glaucoma.

The human eye has a unique immune architecture and behavior. While the conjunctiva is known to have a well-defined lymphatic drainage system, the cornea, sclera, and uveal tissues were historically considered \"alymphatic\" and thought to be immune privileged. The very fact that the aqueous outflow channels carry a clear fluid (aqueous humor) along the outflow pathway makes it hard to ignore its lymphatic-like characteristics. The development of novel lymphatic lineage markers and expression of these markers in aqueous outflow channels and improved imaging capabilities has sparked a renewed interest in the study of ocular lymphatics. Ophthalmic lymphatic research has had a directional shift over the last decade, offering an exciting new physiological platform that needs further in-depth understanding. The evidence of a presence of distinct lymphatic channels in the human ciliary body is gaining significant traction. The uveolymphatic pathway is an alternative new route for aqueous outflow and adds a new dimension to pathophysiology and management of glaucoma. Developing novel animal models, markers, and non-invasive imaging tools to delineate the core anatomical structure and physiological functions may help pave some crucial pathways to understand disease pathophysiology and help develop novel targeted therapeutic approaches for glaucoma.

Microinvasive glaucoma surgery has gained popularity over the past decade. It can be performed using three different mechanisms. In the present review, we focused on Schlemm\'s canal (SC)-based surgery, which increases aqueous humor (AH) outflow into the aqueous veins by either removal of the trabecular meshwork (TM) or an increase in the tension in the TM. In primary open-angle glaucoma (POAG), the TM is the most likely region for increased AH outflow resistance. Theoretically, removal of the TM can improve the AH outflow; hence, glaucoma specialists focus on microsurgical dissection of the TM. In this review, we analyzed the available literature to examine SC-related microsurgical modalities based on the histopathological proofs of the localization of resistance of the AH outflow. First, we considered the role, anatomy, and physiology of the TM and SC. We referred to studies that describe the mechanisms and potential pathways, related to increased intraocular pressure in the POAG, that are targeted using the SC-related microsurgical interventions. Next, we took a closer look at the gonioscopic tools necessary for an ab-interno approach and explored incision canal surgery: ab-interno trabeculectomy using different instrumentation (Trabectome®, Kahook Dual Blade) and variations of the technique. Thereafter, we discussed ab-interno canaloplasty, explaining the technique and reviewing its effectiveness. Finally, we presented the scope for future research in the field. Although the iStent also targets SC by bypassing it, this device has been reviewed extensively elsewhere.

UNASSIGNED: Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH).
UNASSIGNED: This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care.
UNASSIGNED: Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.

Assessment of the anterior chamber angle (ACA) is an essential part of the ophthalmological examination. It is intrinsically related to the diagnosis and treatment of glaucoma and has a role in its prevention. Although slit-lamp gonioscopy is considered the gold-standard technique for ACA evaluation, its poor reproducibility and the long learning curve are well-known shortcomings. Several new imaging techniques for angle evaluation have been developed in the recent years. However, whether these instruments may replace or not gonioscopy in everyday clinical practice remains unclear. This review summarizes the last findings in ACA evaluation, focusing on new instruments and their application to the clinical practice. Special attention will be given to the comparison between these new techniques and traditional slit-lamp gonioscopy. Whereas ultrasound biomicroscopy and anterior segment optical coherence tomography provide quantitative measurements of the anterior segment\'s structures, new gonio-photographic systems allow for a qualitative assessment of angle findings, similarly to gonioscopy. Recently developed deep learning algorithms provide an automated classification of angle images, aiding physicians in taking faster and more efficient decisions. Despite new imaging techniques made analysis of the ACA more objective and practical, the ideal method for ACA evaluation has still to be determined.