-
Biology Direct Oct 2023The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56... (Meta-Analysis)
Meta-Analysis Review
The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.
Topics: Humans; Glaucoma, Open-Angle; Antihypertensive Agents; Genome-Wide Association Study; Timolol; Genotype
PubMed: 37833756
DOI: 10.1186/s13062-023-00423-4 -
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 -
Indian Journal of Ophthalmology Nov 2023Pediatric ocular examinations are often a challenge in the outpatient setting due to limited cooperation of the child. Hence an evaluation under anesthesia (EUA) or...
Pediatric ocular examinations are often a challenge in the outpatient setting due to limited cooperation of the child. Hence an evaluation under anesthesia (EUA) or sedation is important for a holistic ophthalmic examination. It can be combined with short procedures, such as suture removal and corneal scrappings, both for diagnosis and for the management of several ophthalmic disorders. It can also be performed before planning a surgical intervention to record the baseline characters and formulate or refine a surgical plan. Every EUA must be used as a chance to perform a complete ophthalmic examination rather than perform a single task such as recording the intraocular pressure. This article aims to provide a protocol that can be followed for a complete EUA.
Topics: Child; Humans; Glaucoma; Intraocular Pressure; Tonometry, Ocular; Physical Examination; Anesthesia
PubMed: 37870002
DOI: 10.4103/IJO.IJO_3259_22 -
Ophthalmology Sep 2023To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. (Meta-Analysis)
Meta-Analysis
PURPOSE
To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population.
DESIGN
Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium.
PARTICIPANTS
The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants.
METHODS
We examined associations of 4 categories of systemic medications-antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only.
MAIN OUTCOME MEASURES
Glaucoma prevalence and IOP.
RESULTS
In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic β-blockers (β coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP.
CONCLUSIONS
We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Intraocular Pressure; Antihypertensive Agents; Glaucoma; Adrenergic beta-Antagonists; Calcium Channel Blockers; Diuretics; Hypoglycemic Agents; Lipids
PubMed: 37150298
DOI: 10.1016/j.ophtha.2023.05.001 -
International Journal of Molecular... May 2024The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along... (Review)
Review
The ocular glymphatic system subserves the bidirectional polarized fluid transport in the optic nerve, whereby cerebrospinal fluid from the brain is directed along periarterial spaces towards the eye, and fluid from the retina is directed along perivenous spaces following upon its axonal transport across the glial lamina. Fluid homeostasis and waste removal are vital for retinal function, making the ocular glymphatic fluid pathway a potential route for targeted manipulation to combat blinding ocular diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Several lines of work investigating the bidirectional ocular glymphatic transport with varying methodologies have developed diverging mechanistic models, which has created some confusion about how ocular glymphatic transport should be defined. In this review, we provide a comprehensive summary of the current understanding of the ocular glymphatic system, aiming to address misconceptions and foster a cohesive understanding of the topic.
Topics: Humans; Glymphatic System; Animals; Optic Nerve; Retina; Eye; Glaucoma
PubMed: 38891923
DOI: 10.3390/ijms25115734 -
Biomedicine & Pharmacotherapy =... Sep 2023Reactive oxygen species (ROS) overproduction plays an essential role in the etiology of ischemic/hypoxic retinopathy caused by acute glaucoma. NADPH oxidase (NOX) 4 was...
Inhibition of NOX4 with GLX351322 alleviates acute ocular hypertension-induced retinal inflammation and injury by suppressing ROS mediated redox-sensitive factors activation.
Reactive oxygen species (ROS) overproduction plays an essential role in the etiology of ischemic/hypoxic retinopathy caused by acute glaucoma. NADPH oxidase (NOX) 4 was discovered as one of the main sources of ROS in glaucoma. However, the role and potential mechanisms of NOX4 in acute glaucoma have not been fully elucidated. Therefore, the current study aims to investigate the NOX4 inhibitor GLX351322 that targets NOX4 inhibition in acute ocular hypertension (AOH)-induced retinal ischemia/hypoxia injury in mice. Herein, NOX4 was highly expressed in AOH retinas, particularly the retinal ganglion cell layer (GCL). Importantly, the NOX4 inhibitor GLX351322 reduced ROS overproduction, inhibited inflammatory factor release, suppressed glial cell activation and hyperplasia, inhibited leukocyte infiltration, reduced retinal cell senescence and apoptosis in damaged areas, reduced retinal degeneration and improved retinal function. This neuroprotective effect is at least partially associated with mediated redox-sensitive factor (HIF-1α, NF-κB, and MAPKs) pathways by NOX4-derived ROS overproduction. These results suggest that inhibition of NOX4 with GLX351322 attenuated AOH-induced retinal inflammation, cellular senescence, and apoptosis by inhibiting the activation of the redox-sensitive factor pathway mediated by ROS overproduction, thereby protecting retinal structure and function. Targeted inhibition of NOX4 is expected to be a new idea in the treatment of acute glaucoma.
Topics: Animals; Mice; Glaucoma; Inflammation; NADPH Oxidase 4; NADPH Oxidases; Ocular Hypertension; Oxidation-Reduction; Reactive Oxygen Species; Retinal Diseases; Piperazines; Thiophenes
PubMed: 37399715
DOI: 10.1016/j.biopha.2023.115052 -
Romanian Journal of Ophthalmology 2024Several ocular adverse effects have been attributed to Topiramate, a sulfonamide derivative. It can cause problems in the eye such as choroidal effusion syndrome, acute...
UNLABELLED
Several ocular adverse effects have been attributed to Topiramate, a sulfonamide derivative. It can cause problems in the eye such as choroidal effusion syndrome, acute angle closure glaucoma, myopic shift, visual field defects, and Myokymia. If not identified early, it can be vision-threatening. It is commonly used for migraine prophylaxis, partial onset, and generalized tonic-clonic seizures. It has also been prescribed for bipolar disorder and alcoholism. The risk of adverse reactions with this drug is 3%. The prognosis is favorable if it is discontinued early and prompt therapy is initiated.
OBJECTIVE
This article reported a case series of topiramate-induced ocular complications.
MATERIALS AND METHODS
The patients presented with high intraocular pressure and blurred vision following a topiramate prescription for headache.
CONCLUSION
Timely recognition and intervention can prevent potential visual loss in such cases.
Topics: Humans; Topiramate; Glaucoma, Angle-Closure; Myopia
PubMed: 38617722
DOI: 10.22336/rjo.2024.14 -
Molecular Aspects of Medicine Dec 2023Glaucoma is the leading cause of irreversible blindness worldwide. Currently the only effective treatment for glaucoma is to reduce the intraocular pressure, which can... (Review)
Review
Glaucoma is the leading cause of irreversible blindness worldwide. Currently the only effective treatment for glaucoma is to reduce the intraocular pressure, which can halt the progression of the disease. Highlighting the importance of identifying individuals at risk of developing glaucoma and those with early-stage glaucoma will help patients receive treatment before sight loss. However, some cases of glaucoma do not have raised intraocular pressure. In fact, glaucoma is caused by a variety of different mechanisms and has a wide range of different subtypes. Understanding other risk factors, the underlying mechanisms, and the pathology of glaucoma might lead to novel treatments and treatment of underlying diseases. In this review we present the latest research into glaucoma including the genetics and molecular basis of the disease.
Topics: Humans; Glaucoma; Intraocular Pressure
PubMed: 37856931
DOI: 10.1016/j.mam.2023.101220 -
Progress in Retinal and Eye Research May 2024Glaucoma is the leading cause of irreversible blindness globally. The disease causes vision loss due to neurodegeneration of the retinal ganglion cell (RGC) projection... (Review)
Review
Glaucoma is the leading cause of irreversible blindness globally. The disease causes vision loss due to neurodegeneration of the retinal ganglion cell (RGC) projection to the brain through the optic nerve. Glaucoma is associated with sensitivity to intraocular pressure (IOP). Thus, mainstay treatments seek to manage IOP, though many patients continue to lose vision. To address neurodegeneration directly, numerous preclinical studies seek to develop protective or reparative therapies that act independently of IOP. These include growth factors, compounds targeting metabolism, anti-inflammatory and antioxidant agents, and neuromodulators. Despite success in experimental models, many of these approaches fail to translate into clinical benefits. Several factors contribute to this challenge. Firstly, the anatomic structure of the optic nerve head differs between rodents, nonhuman primates, and humans. Additionally, animal models do not replicate the complex glaucoma pathophysiology in humans. Therefore, to enhance the success of translating these findings, we propose two approaches. First, thorough evaluation of experimental targets in multiple animal models, including nonhuman primates, should precede clinical trials. Second, we advocate for combination therapy, which involves using multiple agents simultaneously, especially in the early and potentially reversible stages of the disease. These strategies aim to increase the chances of successful neuroprotective treatment for glaucoma.
Topics: Glaucoma; Humans; Animals; Intraocular Pressure; Retinal Ganglion Cells; Disease Models, Animal; Neuroprotective Agents; Neurodegenerative Diseases
PubMed: 38527623
DOI: 10.1016/j.preteyeres.2024.101261 -
Cells Aug 2023Advances in RNA-sequencing technologies have led to the identification of molecular biomarkers for several diseases, including neurodegenerative diseases, such as... (Review)
Review
Advances in RNA-sequencing technologies have led to the identification of molecular biomarkers for several diseases, including neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's diseases and Amyotrophic Lateral Sclerosis. Despite the nature of glaucoma as a neurodegenerative disorder with several similarities with the other above-mentioned diseases, transcriptional data about this disease are still scarce. microRNAs are small molecules (~17-25 nucleotides) that have been found to be specifically expressed in the CNS as major components of the system regulating the development signatures of neurodegenerative diseases and the homeostasis of the brain. In this review, we sought to identify similarities between the functional mechanisms and the activated pathways of the most common neurodegenerative diseases, as well as to discuss how those mechanisms are regulated by miRNAs, using RNA-Seq as an approach to compare them. We also discuss therapeutically suitable applications for these disease hallmarks in clinical future studies.
Topics: Humans; Neurodegenerative Diseases; RNA-Seq; Homeostasis; Glaucoma; MicroRNAs
PubMed: 37681887
DOI: 10.3390/cells12172155