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Journal of Visualized Experiments : JoVE Feb 2022Glaucoma, the second leading cause of blindness worldwide, is a heterogeneous group of ocular disorders characterized by structural damage to the optic nerve and retinal...
Glaucoma, the second leading cause of blindness worldwide, is a heterogeneous group of ocular disorders characterized by structural damage to the optic nerve and retinal ganglion cell (RGC) degeneration, resulting in visual dysfunction by interrupting the transmission of visual information from the eye to the brain. Elevated intraocular pressure is the most important risk factor; thus, several models of ocular hypertension have been developed in rodents by either genetic or experimental approaches to investigate the causes and effects of the disease. Among those, some limitations have been reported such as surgical invasiveness, inadequate functional assessment, requirement of extensive training, and highly variable extension of retinal damage. The present work characterizes a simple, low-cost, and efficient method to induce ocular hypertension in rodents, based on low-temperature, full-circle cauterization of the limbal vascular plexus, a major component of aqueous humor drainage. The new model provides a technically easy, noninvasive, and reproducible subacute ocular hypertension, associated with progressive RGC and optic nerve degeneration, and a unique post-operative clinical recovery rate that allows in vivo functional studies by both electrophysiological and behavioral methods.
Topics: Animals; Cautery; Disease Models, Animal; Glaucoma; Intraocular Pressure; Ocular Hypertension; Rodentia
PubMed: 35253788
DOI: 10.3791/63442 -
Japanese Journal of Ophthalmology Jul 2022To observe the features and changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in highly myopic ocular hypertension (HM-OHT) patients.
PURPOSE
To observe the features and changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in highly myopic ocular hypertension (HM-OHT) patients.
STUDY DESIGN
Prospective observation study.
METHODS
Individuals who met the inclusion criteria were recruited into three groups: the healthy high myopia (HM), non-highly myopic ocular hypertension (OHT) and HM-OHT group. The spherical equivalent refraction, axial length, intraocular pressure, central corneal thickness and pRNFL thickness were collected and compared between groups. The OHT and HM-OHT group were followed up for 12 months. The changes in pRNFL thickness across the follow-up times were analyzed.
RESULTS
The study included 92 subjects. The mean pRNFL thicknesses were 102.5 ± 11.1 μm in the HM (31 people), 101.9 ± 11.7 μm in the OHT (34 people) and 102.2 ± 12.0 μm in the HM-OHT group (27 people). There was no statistical difference in the mean pRNFL thickness among the three groups. The HM-HOT group and HM group had thicker temporal sectoral (p < 0.05) pRNFL thickness and thinner superior sectoral (p = 0.015) pRNFL thickness than the OHT group. During the 12-month follow-up, the mean pRNFL thickness of the HM OHT group decreased, with an annual reduction of -0.93 ± 0.14 μm. There was a significant difference across the three visits (p < 0.05), while there were no significant differences in the OHT group (p = 0.591).
CONCLUSIONS
After ocular magnification correction, the HM-OHT group did not have thinner pRNFL thickness than the other two groups. However, the thickness decreased significantly over time.
Topics: Follow-Up Studies; Glaucoma; Humans; Myopia; Nerve Fibers; Ocular Hypertension; Prospective Studies; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 35438396
DOI: 10.1007/s10384-022-00916-1 -
Ocular Immunology and Inflammation Nov 2021: We aim to look at the complications encountered by a cohort of pediatric uveitis patients from north India.: Retrospectively, complications seen in patients younger...
: We aim to look at the complications encountered by a cohort of pediatric uveitis patients from north India.: Retrospectively, complications seen in patients younger than 16 years diagnosed with uveitis between January 2006 to March 2015 were noted.: Data of 104 children, with a mean follow-up of 3.40 ± 2.34 years was studied. Cataract (n = 42, 24.00%), band-shaped keratopathy (n = 32, 18.29%) and Glaucoma/OHT (n = 11, 6.29%) were most encountered complications at presentation. Glaucoma/OHT (29.71%; n = 52), cataract (18.86%; n = 33) and maculopathy (n=12;6.86%) were the most common complications at follow up. Maculopathy (35%) and Glaucoma/OHT (20%) were the most common causes of visual acuity ≤3/60.: Cataract is the most critical complication in children with uveitis at presentation and raised intraocular pressure occurs at follow-up, perhaps attributed to the treatment. Maculopathy is the most common cause of blindness in these children.
Topics: Adolescent; Cataract; Child; Child, Preschool; Coloring Agents; Corneal Dystrophies, Hereditary; Female; Fluorescein Angiography; Follow-Up Studies; Glaucoma; Glucocorticoids; Humans; Immunosuppressive Agents; India; Indocyanine Green; Infant; Intraocular Pressure; Male; Microscopy, Acoustic; Ocular Hypertension; Retrospective Studies; Uveitis; Visual Acuity; Visual Field Tests
PubMed: 32649841
DOI: 10.1080/09273948.2020.1762897 -
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 -
[Zhonghua Yan Ke Za Zhi] Chinese... Feb 2015Although the pathogenesis of glaucoma is complicated and multifactorial, elevated intraocular pressure (IOP) remains the most important known risk factor. The higher the... (Review)
Review
Although the pathogenesis of glaucoma is complicated and multifactorial, elevated intraocular pressure (IOP) remains the most important known risk factor. The higher the IOP and the larger the IOP fluctuation, the more damage to the optic nerve. IOP fluctuation can be affected by many factors, such as emotion, exercise and circadian rhythm, etc. Recently, the effects of postural change on IOP fluctuation are receiving more and more attention. This article reviews the effects of different body positions on IOP fluctuation, the effects of surgery, medications and aging on posture-induced IOP fluctuation and the effects of postural change on IOP fluctuation of certain special groups. The possible mechanisms of posture-induced IOP fluctuation are also discussed in this article.
Topics: Circadian Rhythm; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Optic Nerve; Posture; Risk Factors
PubMed: 25908006
DOI: No ID Found -
Scientific Reports Jul 2018We explored the involvement of FP receptor and endogenous prostaglandins (PGs) in transient ocular hypertension (OH) induced by PGE2 or PGF2α in mouse eyes. PGE2 and...
We explored the involvement of FP receptor and endogenous prostaglandins (PGs) in transient ocular hypertension (OH) induced by PGE2 or PGF2α in mouse eyes. PGE2 and PGF2α were topically applied to induce transient OH in Wild-type (WT) and FP-, EP1-, EP2-, and EP3-deficient (knockout [KO]) mice. To suppress endogenous PG production, the non-steroidal anti-inflammatory drug nepafenac was applied topically before treatment. PGE2 and PGF2α induced significant OH in the WT, FPKO, and EP1-3KO mice compared to the control 30 min after instillation, and the increase in IOP at 30 or 60 min after instillation in FPKO mice was significantly higher than that in the WT mice. The effects of PGF2α on the increase in IOP were significantly weaker than those of PGE2, especially in EP1KO and EP3KO mice. Transient OH induced by PGE2 and PGF2α was significantly attenuated by nepafenac treatment in FPKO mice. Transient OH was induced by PGE2 and PGF2α in WT, FPKO, and EP1-3KO mice, which was enhanced in FPKO mice. This OH was significantly diminished by nepafenac treatment in FPKO mice, suggesting that FP receptor may have an important naïve physiological role in the eye, and could regulate IOP elevation during PG-associated ocular inflammation.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Inflammation; Intraocular Pressure; Male; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Ocular Hypertension; Prostaglandins; Receptors, Prostaglandin; Time Factors
PubMed: 30038227
DOI: 10.1038/s41598-018-29273-1 -
International Journal of Molecular... Dec 2022Previously, we developed a simple procedure of intracameral injection of silicone oil (SO) into mouse eyes and established the mouse SOHU (SO-induced ocular hypertension...
Previously, we developed a simple procedure of intracameral injection of silicone oil (SO) into mouse eyes and established the mouse SOHU (SO-induced ocular hypertension under-detected) glaucoma model with reversible intraocular pressure (IOP) elevation and significant glaucomatous neurodegeneration. Because the anatomy of the non-human primate (NHP) visual system closely resembles that of humans, it is the most likely to predict human responses to diseases and therapies. Here we tried to replicate the mouse SOHU glaucoma model in rhesus macaque monkeys. All six animals that we tested showed significant retinal ganglion cell (RGC) death, optic nerve (ON) degeneration, and visual functional deficits at both 3 and 6 months. In contrast to the mouse SOHU model, however, IOP changed dynamically in these animals, probably due to individual differences in ciliary body tolerance capability. Further optimization of this model is needed to achieve consistent IOP elevation without permanent damage of the ciliary body. The current form of the NHP SOHU model recapitulates the severe degeneration of acute human glaucoma, and is therefore suitable for assessing experimental therapies for neuroprotection and regeneration, and therefore for translating relevant findings into novel and effective treatments for patients with glaucoma and other neurodegenerations.
Topics: Humans; Mice; Animals; Macaca mulatta; Silicone Oils; Glaucoma; Ocular Hypertension; Intraocular Pressure; Disease Models, Animal
PubMed: 36555536
DOI: 10.3390/ijms232415896 -
Harefuah Mar 2023Netarsudil ophthalmic solution 0.02% is a new treatment for open-angle glaucoma and ocular hypertension, which was approved for treatment in the United States and in the... (Review)
Review
Netarsudil ophthalmic solution 0.02% is a new treatment for open-angle glaucoma and ocular hypertension, which was approved for treatment in the United States and in the European Commission. The drug is a rho- kinase inhibitor (ROCK) that lowers intraocular pressure by enhancing the outflow at the trabecular meshwork and decreasing both aqueous humor production and episcleral venous pressure. This literature review aims to present this new treatment, characterize its specific mechanism of action, and discuss its effect and adverse events profile. The efficacy and safety of the drug were studied in the ROCKET and MERCURY clinical trials, in which Netarsudil was compared to other common drugs, including Timolol (Beta-blocker), Latanoprost (Prostaglandin analog), and a combination drop containing Netarsudil and Latanoprost. These trials showed a reduction of 16%-21% in the intraocular pressure (IOP) when using Netarsudil. Moreover, it was found that when using a combination of Netarsudil and Latanoprost, 64.5% of these patients achieved ≥30% reduction in mean diurnal IOP versus 28.8% of patients treated only with Netarsudil and 37.2% of patients treated only with Latanoprost (P<0.0001). The most common adverse event reported was conjunctival hyperemia, which was more frequent in patients using Netarsudil. However, this did not significantly affect the drug tolerance.
Topics: Humans; United States; Glaucoma, Open-Angle; Latanoprost; rho-Associated Kinases; Ophthalmic Solutions; Antihypertensive Agents; Ocular Hypertension; Glaucoma; Intraocular Pressure; Timolol; Treatment Outcome
PubMed: 36966373
DOI: No ID Found -
Expert Opinion on Drug Safety Oct 2022Elevated intraocular pressure (IOP) is the most important modifiable risk factor for irreversible sight loss in open-angle glaucoma (OAG). The topical fixed-dose...
Reviewing the evidence surrounding preservative-free tafluprost/timolol fixed-dose combination therapy in open-angle glaucoma and ocular hypertension management: a focus on efficacy, safety, and tolerability.
INTRODUCTION
Elevated intraocular pressure (IOP) is the most important modifiable risk factor for irreversible sight loss in open-angle glaucoma (OAG). The topical fixed-dose combination (FC) of preservative-free (PF) tafluprost (0.0015%) and timolol (0.5%) (tafluprost/timolol) is among the second-line IOP-lowering options for OAG and ocular hypertension (OHT).
AREAS COVERED
PubMed searches identified publications reporting key evidence from randomized controlled trials (RCTs) and real-world studies examining the safety, tolerability, and IOP-lowering efficacy of PF tafluprost/timolol FC therapy in OAG/OHT management.
EXPERT OPINION
Glaucoma patients are more likely to have ocular surface disease, and treatment should be individualized so that target response may be achieved while considering tolerability and quality of life, according to European Glaucoma Society guidelines. PF FC therapies, such as PF tafluprost/timolol FC, avoid ocular surface exposure to toxic preservative agents and reduce the required number of treatment administrations. These properties may enhance treatment tolerability and adherence, resulting in improved IOP-lowering efficacy and disease control. Treatment outcomes from RCTs and real-world studies examining PF tafluprost/timolol FC therapy support this hypothesis, with significant IOP reductions and/or improvements in tolerability parameters demonstrated, regardless of the prior topical therapy used and even when switched directly to PF tafluprost/timolol FC treatment (without washout).
Topics: Humans; Timolol; Intraocular Pressure; Antihypertensive Agents; Drug Combinations; Ocular Hypertension; Glaucoma, Open-Angle; Glaucoma; Preservatives, Pharmaceutical
PubMed: 36250245
DOI: 10.1080/14740338.2022.2135701 -
International Journal of Molecular... Jan 2023Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal...
Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta-blockers (BB) and prostaglandin analogues (PGA). Prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single-nucleotide polymorphisms were genotyped by real-time PCR assays: prostaglandin-F2α receptor (rs3766355, rs3753380); cytochrome-P450 2D6 (rs16947, rs769258); and beta-2-adrenergic receptor (rs1042714). Other studied variables were mean deviation (MD) of visual field, previous ocular interventions, medical treatment, baseline (bIOP), and treated intraocular pressure (tIOP). From a total of 139 eyes, 71 (51.1%) were left eyes. The main diagnosis was primary open angle glaucoma (66.2%). A total of 57 (41%) eyes were under three or more medications (PGA + BB + other) and, additionally, 57 eyes (41%) had had some kind of glaucoma surgery. The mean bIOP and tIOP were 26.55 ± 8.19 and 21.01 ± 5.54 mmHg, respectively. Significant differences in tIOP were found between heterozygous (HT) (21.07 ± 0.607 mmHg) and homozygous (HM) (20.98 ± 0.639 mmHg) rs3766355 with respect to wildtype individuals (16 ± 1.08 mmHg) ( = 0.031). The MD values presented significant differences between wildtype rs3766355 (-2 ± 2.2 dB), HT (-3.87 ± 4 dB), and HM carriers (-9.37 ± 9.51 dB) ( = 0.009). Significant differences were also observed between the MD in wildtype rs3753380 (-6.1 ± 8.67 dB), HT (-9.02 ± 8.63 dB), and HM carriers (-9.51 ± 7.44 dB) ( = 0.017). Patients carrying the variant rs3766355 in HM or HT presented clinically-significantly higher tIOP than wildtype patients. Additionally, some differences in MD were found in rs3766355 and rs3753380 carriers, and the more alleles that were affected, the worse the MD value, meaning greater severity of the glaucoma. Poor response to treatment and more visual field damage may be associated with being a carrier of these mutated alleles.
Topics: Humans; Glaucoma, Open-Angle; Prospective Studies; Antihypertensive Agents; Glaucoma; Ocular Hypertension; Intraocular Pressure; Adrenergic beta-Antagonists; Genotype; Phenotype; Prostaglandins, Synthetic
PubMed: 36768422
DOI: 10.3390/ijms24032093