-
ACS Nano Nov 2023Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and...
Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and the unwanted overproduction of peroxynitrite. Herein, a denitrifying hollow mesoporous organosilica nanoparticle (HMMN) with framework cohybridization is first constructed to encapsulate -nitroso--acetyl-d,l-penicillamine (SNAP) to produce SNAP@HMMN with dual capacities of selective peroxynitrite removal and controllable NO release. Featuring a large corneal permeability, the well-designed SNAP@HMMN can achieve trans-corneal delivery to reach the target trabecular meshwork (TM)/Schlemm's canal (SC) site. Upon light irradiation, the intraocular pressure (IOP) is appropriately lowered in an adjustable and long-lasting manner while the outflow tissues are protected from nitrative damage, which is expected to realize precision on-demand glaucoma therapy with little biosafety concern, promising significant clinical translational potential.
Topics: Humans; Nitric Oxide; Peroxynitrous Acid; Nanomedicine; Glaucoma; Intraocular Pressure
PubMed: 37906948
DOI: 10.1021/acsnano.3c02685 -
Expert Opinion on Therapeutic Targets 2023Elevated intraocular pressure (IOP) is a well-recognized risk factor for development of primary open angle glaucoma (POAG), a leading cause of irreversible blindness.... (Review)
Review
INTRODUCTION
Elevated intraocular pressure (IOP) is a well-recognized risk factor for development of primary open angle glaucoma (POAG), a leading cause of irreversible blindness. Ocular hypertension is associated with excessive extracellular matrix (ECM) deposition in trabecular meshwork (TM) resulting in increased aqueous outflow resistance and elevated IOP. Hence, therapeutic options targeting ECM remodeling in TM to lower IOP in glaucomatous eyes are of considerable importance.
AREAS COVERED
This paper discusses the complex process of ECM regulation in TM and explores promising therapeutic targets. The role of Transforming Growth Factor-β as a central player in ECM deposition in TM is discussed. We elaborate the key regulatory processes involved in its activation, release, signaling, and cross talk with other signaling pathways including Rho GTPase, Wnt, integrin, cytokines, and renin-angiotensin-aldosterone. Further, we summarize the therapeutic agents that have been explored to target ECM dysregulation in TM.
EXPERT OPINION
Targeting molecular pathways to reduce ECM deposition and/or enhance its degradation are of considerable significance for IOP lowering. Challenges lie in pinpointing specific targets and designing drug delivery systems to precisely interact with pathologically active/inactive signaling. Recent advances in monoclonal antibodies, fusion molecules, and vectored nanotechnology offer potential solutions.
Topics: Humans; Glaucoma, Open-Angle; Intraocular Pressure; Glaucoma; Trabecular Meshwork; Extracellular Matrix; Aqueous Humor
PubMed: 38069479
DOI: 10.1080/14728222.2023.2293748 -
Journal Francais D'ophtalmologie Oct 2023These guidelines are a consensus of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in a third of the cases after...
These guidelines are a consensus of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in a third of the cases after corticosteroid implant intravitreal injections. They update the first guidelines published in 2017. Two implants are marketed in France: the dexamethasone implant (DEXi) and the fluocinolone acetonide implant (FAci). It is essential to assess the pressure status before injecting a patient with a corticosteroid implant. A molecule-specific monitoring of the intraocular pressure is needed throughout the follow-up and at the time of reinjections. Real-life studies have allowed optimizing the management algorithm by significantly increasing the safety of these implants. Corticosteroid testing with DEXi should be performed before switching to FAci to optimize pressure tolerance of FAci. Beyond topical hypotensive treatments, selective laser trabeculoplasty may be considered in the therapeutic arsenal for the management of steroid-induced OHT and subsequent injections.
Topics: Humans; Dexamethasone; Ophthalmology; Ocular Hypertension; Glaucoma; Glucocorticoids; Intraocular Pressure; Adrenal Cortex Hormones; Intravitreal Injections; Steroids; Retina; Drug Implants
PubMed: 37302867
DOI: 10.1016/j.jfo.2023.05.001 -
BMC Ophthalmology Sep 2023This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma. (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis summarize the evidence for the association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.
METHODS
Eligible studies reporting an association between H. pylori infection and Glaucoma were identified through an extensive search of the Excerpta Medica (EMBASE), Web of Science, Scopus, and PubMed databases and an assessment of the reference list of the top articles until October 2022. Analysis was performed with random effects model using Stata 16.
RESULT
Twenty-four studies were included in the systematic review. This study involved 1602 glaucoma patients and 2800 control individuals. The combined RRs of cohort studies and overall combined ORs of case-control studies showed a significant correlation between H. pylori infection and Glaucoma. Subgroup analysis showed that glaucoma patients had a higher risk of having H. pylori infection if they were residents of Europe countries (Cohort: RR: 1.69; 95% CI: 1.3-2.19) and (Case-Control: RR: 3.71; 95% CI: 2.07-6.64), if they had POAG type (Cohort: RR: 1.76; 95% CI: 1.37-2.27) and (Case-Control: RR: 3.71; 95% CI: 2.934.70), if their diagnostic method of HP was histology (Cohort: RR: 1.95; 95% CI: 1.26-3.01) and (Case-Control: RR: 4.06; 95% CI: 2.28-7.22), and if they were over 60 years old (Cohort: RR: 1.63; 95% CI: 1.33-2.00) and (Case-Control: RR: 2.95; 95% CI: 2.27-3.83).
DISCUSSION
The results of this meta-analysis suggest a statistically significant association between Helicobacter pylori infection and Primary Open-Angle Glaucoma.
Topics: Humans; Middle Aged; Helicobacter Infections; Glaucoma, Open-Angle; Helicobacter pylori; Case-Control Studies; Glaucoma
PubMed: 37697285
DOI: 10.1186/s12886-023-03111-z -
Biomedical Physics & Engineering Express Dec 2023A detailed analysis of the corneal retardation timeas a highly related parameter to the intraocular pressure (IOP), and its plausible role as an indicator of ocular...
A detailed analysis of the corneal retardation timeas a highly related parameter to the intraocular pressure (IOP), and its plausible role as an indicator of ocular hypertension disease.A simple theoretical expression foris derived within the corneal viscoelastic model of Kelvin-Voigt with 3 elements. This retardation time can be easily calculated from the well-known signal and pressure amplitudes of non-contact tonometers like the Ocular Response Analyzer (ORA). Then, a population-based study was performed where 100 subjects aged from 18 to 30 were analyzed (within this group, about 10% had an elevated IOP with more than 21 mmHg).A clear relationship between the corneal retardation time and the corneal-compensated intraocular pressure (IOP) was found, underlying the risk for ocular hypertensive (OHT) subjects with lowervalues to develop hypertension illnesses (due to the inability of poorly viscoelastic corneas to absorb IOP fluctuations, resulting in probable optic nerve damage).Our results might provide an useful tool to systematically discern which OHT patients (and even those with normal IOP values) are more likely to suffer glaucoma progression and, consequently, ensure an early diagnosis.
Topics: Humans; Glaucoma; Ocular Hypertension; Intraocular Pressure; Tonometry, Ocular; Cornea
PubMed: 38055990
DOI: 10.1088/2057-1976/ad12fa -
Expert Opinion on Investigational Drugs 2023Glaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line... (Review)
Review
INTRODUCTION
Glaucoma is a leading cause of blindness with intraocular pressure (IOP) as the only known modifiable risk factor. Prostaglandin FP receptor agonists are the first-line medical treatment for glaucoma and ocular hypertension. Despite their efficacy, their IOP lowering effect may be insufficient requiring second agents, and poor patient compliance to medical therapy may preclude their full effect.
AREAS COVERED
This literature review examines the novel FP receptor drugs and drug delivery devices in clinical phase trials for treatment of glaucoma. Three novel drugs targeting FP receptors were identified, including latanoprostene bunod, NCX 470, and sepetaprost. Additionally, sustained drug delivery devices in early clinical phase trials included intracameral implants, punctal plugs, ocular rings, and contact lenses.
EXPERT OPINION
NO hybrid FP receptor agonists and dual FP/EP3 receptor agonists may show promise as novel medical therapies with greater efficacy than approved prostaglandin analogs in clinical use, with a similar safety profile. Alternatively, drug delivery systems may provide a similar IOP lowering effect to existing agonists but overcome issues with patient compliance and convenience. A personalized approach to drug delivery devices may be required to ensure the most appropriate fit for the patient according to the invasiveness and duration of therapy desired.
Topics: Humans; Glaucoma; Ocular Hypertension; Receptors, Prostaglandin; Intraocular Pressure; Prostaglandins, Synthetic; Antihypertensive Agents
PubMed: 37929314
DOI: 10.1080/13543784.2023.2279146 -
International Ophthalmology Clinics Oct 2023
Topics: Humans; Cataract Extraction; Glaucoma; Cataract; Intraocular Pressure
PubMed: 37755448
DOI: 10.1097/IIO.0000000000000481 -
International Ophthalmology Oct 2023To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with... (Observational Study)
Observational Study
PURPOSE
To investigate the ocular surface inflammation in patients with primary open angle glaucoma and ocular hypertension by analyzing tears and to compare findings with healthy controls.
METHODS
Observational case-control study. Tear samples were collected by 5 µl microcapillary tube from 24 patients with glaucoma treated by antiglaucoma drops, 9 non-treated patients with ocular hypertension and 45 healthy controls. Tears were analyzed from right eye by multiplex Bio-Plex system for the presence of 6 cytokines: IL1β, IL10, IL4, IFNγ, MIF and VEGF.
RESULTS
Significantly higher concentrations of IL1β and IL10 (glaucoma or ocular hypertension vs. healthy controls, p < 0.0001), VEGF (glaucoma vs. ocular hypertension, p < 0.05; ocular hypertension vs. healthy controls, p < 0.02) and MIF (glaucoma vs. healthy controls, p < 0.03) were detected in patients' tears. Both patient groups have activated to a significantly lower extent the Th1 pathway represented by IFNγ than Th2 pathway represented by IL10 (p < 0.001) and, at the same time, the IFNγ/IL4 ratio was significantly increased in healthy controls (p < 0.001) and patients with ocular hypertension (p < 0.02) compared to glaucoma individuals.
CONCLUSION
This study shows that secretion of inflammation-related cytokines by conjunctival cells is increased in both, glaucoma and ocular hypertension patients and can be detected in their tears. Nevertheless, data indicates stronger ocular surface inflammation in non-treated follow-up patients diagnosed with ocular hypertension than in glaucoma subjects treated by antiglaucoma drops.
Topics: Humans; Cytokines; Glaucoma, Open-Angle; Case-Control Studies; Interleukin-10; Interleukin-4; Vascular Endothelial Growth Factor A; Intraocular Pressure; Glaucoma; Ocular Hypertension; Tears; Inflammation; Antihypertensive Agents; Ophthalmic Solutions
PubMed: 37318666
DOI: 10.1007/s10792-023-02763-6 -
Scientific Reports Jul 2023This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical... (Randomized Controlled Trial)
Randomized Controlled Trial
This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps < 0.05). Compared with the SLT group, the latanoprost group had a significant and stable decrease in IOP after treatment. The latanoprost group had a more pronounced reduction in IOP at weeks 4 and 12 (P < 0.05) but had no difference at week 1 (P = 0.097). As a first-line treatment, both SLT and latanoprost eye drops are effective in newly diagnosed POAG and OHT patients. However, the latanoprost eye drops may be better in decreasing mean and peak 24-h IOP and thus controlling 24-h IOP fluctuation compared to SLT.
Topics: Humans; Latanoprost; Glaucoma, Open-Angle; Trabeculectomy; Ophthalmic Solutions; Prospective Studies; Antihypertensive Agents; Ocular Hypertension; Glaucoma; Intraocular Pressure; Laser Therapy; Lasers; Treatment Outcome
PubMed: 37500642
DOI: 10.1038/s41598-023-38550-7 -
WIREs Mechanisms of Disease 2024Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying... (Review)
Review
Glaucoma is a heterogeneous group of progressive diseases that leads to irreversible blindness. Secondary glaucoma refers to glaucoma caused by a known underlying condition. Pseudoexfoliation and pigment dispersion syndromes are common causes of secondary glaucoma. Their respective deposits may obstruct the trabecular meshwork, leading to aqueous humor outflow resistance, ocular hypertension, and optic neuropathy. There are no disease-specific interventions available for either. Pseudoexfoliation syndrome is characterized by fibrillar deposits (pseudoexfoliative material) on anterior segment structures. Over a decade of multiomics analyses taken together with the current knowledge on pseudoexfoliative glaucoma warrant a re-think of mechanistic possibilities. We propose that the presence of nucleation centers (e.g., vitamin D binding protein), crosslinking enzymes (e.g., transglutaminase 2), aberrant extracellular matrix, flawed endocytosis, and abnormal aqueous-blood barrier contribute to the formation of proteolytically resistant pseudoexfoliative material. Pigment dispersion syndrome is characterized by abnormal iridolenticular contact that disrupts iris pigment epithelium and liberates melanin granules. Iris melanogenesis is aberrant in this condition. Cytotoxic melanogenesis intermediates leak out of melanosomes and cause iris melanocyte and pigment epithelium cell death. Targeting melanogenesis can likely decrease the risk of pigmentary glaucoma. Skin and melanoma research provides insights into potential therapeutics. We propose that specific prostanoid agonists and fenofibrates may reduce melanogenesis by inhibiting cholesterol internalization and de novo synthesis. Additionally, melatonin is a potent melanogenesis suppressor, antioxidant, and hypotensive agent, rendering it a valuable agent for pigmentary glaucoma. In pseudoexfoliative glaucoma, where environmental insults drive pseudoexfoliative material formation, melatonin's antioxidant and hypotensive properties may offer adjunct therapeutic benefits. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.
Topics: Humans; Antioxidants; Melatonin; Intraocular Pressure; Glaucoma; Glaucoma, Open-Angle
PubMed: 37669762
DOI: 10.1002/wsbm.1628