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STAR Protocols Dec 2022Laser-induced hypertension in nonhuman primates is used to mimic human glaucoma, the leading cause of irreversible blindness. In this protocol, we detail steps for...
Laser-induced hypertension in nonhuman primates is used to mimic human glaucoma, the leading cause of irreversible blindness. In this protocol, we detail steps for laser-induced ocular hypertension in nonhuman primates by laser photocoagulation of the trabecular meshwork and subsequent intracameral injection. We further describe recording and evaluation of intraocular pressure changes and peripapillary retinal nerve fiber layer thickness. This protocol can assist researchers improve the success rate and repeatability of the procedure and reduce the number of nonhuman primates needed. For complete details on the use and execution of this protocol, please refer to Sun et al. (2022).
Topics: Animals; Humans; Glaucoma; Ocular Hypertension; Intraocular Pressure; Lasers; Primates
PubMed: 36340883
DOI: 10.1016/j.xpro.2022.101801 -
Retina (Philadelphia, Pa.) Jul 2021To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the... (Observational Study)
Observational Study
PURPOSE
To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation.
METHODS
Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure.
RESULTS
Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3-62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P = 0.248).
CONCLUSION
This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Dexamethasone; Drug Implants; Female; Follow-Up Studies; France; Glucocorticoids; Humans; Incidence; Intraocular Pressure; Intravitreal Injections; Macular Edema; Male; Middle Aged; Ocular Hypertension; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Young Adult
PubMed: 33315814
DOI: 10.1097/IAE.0000000000003080 -
Indian Journal of Ophthalmology Jun 2023Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG)...
PURPOSE
Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway.
METHODS
An open-label, real-world, multicentric, observation-based 3-month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first-line therapy. Diurnal IOP measurements, best-corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day-1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months).
RESULTS
Four hundred and sixty-nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once-daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring.
CONCLUSION
We found that netarsudil 0.02% w/v solution monotherapy when used as the first-line treatment in primary open-angle glaucoma and ocular hypertension was both safe and effective.
Topics: Humans; Glaucoma, Open-Angle; Ophthalmic Solutions; Ocular Hypertension; Glaucoma; Intraocular Pressure; Drug-Related Side Effects and Adverse Reactions; Antihypertensive Agents; Treatment Outcome
PubMed: 37322670
DOI: 10.4103/IJO.IJO_25_23 -
International Ophthalmology Jul 2022Steroid-induced ocular hypertension (SIOH) and cataract can result in visual loss. This study evaluated the timetable of SIOH and steroid-induced posterior subcapsular...
PURPOSE
Steroid-induced ocular hypertension (SIOH) and cataract can result in visual loss. This study evaluated the timetable of SIOH and steroid-induced posterior subcapsular cataract (SI-PSC) occurrences in children with systemic autoimmune diseases (SAD) undergoing long-term systemic corticosteroid treatment.
METHODS
Thirty-seven children with SAD treated with long-term oral corticosteroids were enrolled in this study. Intraocular pressure (IOP), SI-PSC occurrences, visual field and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were recorded every 3 months for at least 6 months.
RESULTS
Of the 37 children, with average age 11.0 ± 2.9 years, 22 patients (59.5%) had SIOH, 2 progressed as glaucoma at the 18-month and 3-year follow-up, respectively, and 12 (32.4%) patients had SI-PSC. Among patients with SIOH, 45.5% (10/22) of them had SI-PSC occurrence, and among patients with normal IOP, 13.3% (2/15) of them had SI-PSC. Seventeen patients participated in a longitudinal study with a follow-up period of at least 18 months. The incidence of SIOH started at 1 month 52.9% (9/17) and gradually increased to 70.6% (12/17) at 6 months, then decreased to 35.3% (6/17). SI-PSC onset started at 6 months (17.6%, 3/17), and its occurrence increased to 35.3% (6/17) at 12 months and reached to 41.2% (7/17) at 18 months. The pRNFL was thicker in the children with SIOH than the healthy controls (p = 0.01).
CONCLUSION
SIOH and SI-PSC are common coexistent complications in children with long-term corticosteroids treatment, and the occurrence time is during the first month and 6 months, respectively. Patients with SIOH have a higher probability of cataract.
Topics: Adolescent; Autoimmune Diseases; Cataract; Child; Glaucoma; Humans; Intraocular Pressure; Longitudinal Studies; Ocular Hypertension; Steroids
PubMed: 35048245
DOI: 10.1007/s10792-022-02217-5 -
Current Opinion in Pharmacology Feb 2024Recent advancements in prostaglandin analogs (PGAs) have reinforced their role in managing intraocular pressure (IOP). Latanoprost excels in 24-h IOP control, while... (Review)
Review
Recent advancements in prostaglandin analogs (PGAs) have reinforced their role in managing intraocular pressure (IOP). Latanoprost excels in 24-h IOP control, while various PGAs offer similar effectiveness and side effects, generic PGAs perform as well as branded ones, and a notable IOP rise observed upon PGA discontinuation. Formulations with or without preservatives show comparable IOP reduction and adherence, often surpassing benzalkonium chloride (BAK)-preserved options. Emergent PGAs, such as latanoprostene bunod, fixed-dose netarsudil combined with latanoprost, and omidenepag Isopropyl, offer enhanced or non-inferior IOP reduction. The bimatoprost implant introduces a novel administration method with effective IOP reduction. These developments underscore ongoing progress in PGA-focused ophthalmological research. This article offers a comprehensive review of available prostanoid analogs and explores new developments.
Topics: Humans; Latanoprost; Glaucoma, Open-Angle; Antihypertensive Agents; Ophthalmic Solutions; Glaucoma; Ocular Hypertension; Intraocular Pressure; Prostaglandins, Synthetic; Treatment Outcome
PubMed: 38160646
DOI: 10.1016/j.coph.2023.102424 -
Eye (London, England) Jan 2020Despite advances in our knowledge of the aetiology and pathophysiology of glaucoma, the sole proven, effective intervention for treating primary open-angle glaucoma... (Review)
Review
Despite advances in our knowledge of the aetiology and pathophysiology of glaucoma, the sole proven, effective intervention for treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT) remains lowering of intraocular pressure (IOP) to prevent further progression and visual loss. The purpose of this review is to evaluate the treatment choices available to newly diagnosed POAG and OHT patients. We review the existing literature on treatments currently available to newly diagnosed POAG and OHT patients and discuss their role in the treatment paradigm of POAG and OHT. We consider different factors that may be important when offering a choice of treatment to newly diagnosed POAG and OHT patients as well as describing new glaucoma treatments in development and future directions for treatment.
Topics: Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Tonometry, Ocular
PubMed: 31685971
DOI: 10.1038/s41433-019-0633-6 -
Progress in Brain Research 2020To study short and long-term effects of acute ocular hypertension (AOHT) on inner and outer retinal layers, in adult Sprague-Dawley rats AOHT (87mmHg) was induced for...
To study short and long-term effects of acute ocular hypertension (AOHT) on inner and outer retinal layers, in adult Sprague-Dawley rats AOHT (87mmHg) was induced for 90min and the retinas were examined longitudinally in vivo with electroretinogram (ERG) recordings and optical coherent tomography (OCT) from 1 to 90 days (d). Ex vivo, the retinas were analyzed for rod (RBC) and cone (CBC) bipolar cells, with antibodies against protein kinase Cα and recoverin, respectively in cross sections, and for cones, horizontal (HZ) and ganglion (RGC) cells with antibodies against arrestin, calbindin and Brn3a, respectively in wholemounts. The inner retina thinned progressively up to 7d with no further changes, while the external retina had a normal thickness until 30d, with a 20% thinning between 30 and 90d. Functionally, the a-wave showed an initial reduction by 24h and a further reduction from 30 to 90d. All other main ERG waves were significantly reduced by 1d without significant recovery by 90d. Radial sections showed a normal population of RBCs but their terminals were reduced. The CBCs showed a progressive decrease with a loss of 56% by 30d. In wholemount retinas, RGCs diminished to 40% by 3d and to 16% by 30d without further loss. Cones diminished to 58% and 35% by 3 and 7d, respectively and further decreased between 30 and 90d. HZs showed normal values throughout the study. In conclusion, AOHT affects both the inner and outer retina, with a more pronounced degeneration of the cone than the rod pathway.
Topics: Acute Disease; Animals; Disease Models, Animal; Electroretinography; Glaucoma; Ocular Hypertension; Rats; Rats, Sprague-Dawley; Retina; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Retinal Horizontal Cells; Tomography, Optical Coherence
PubMed: 32958209
DOI: 10.1016/bs.pbr.2020.07.003 -
International Journal of Molecular... Jun 2022To explore the role of atorvastatin in regulating intraocular pressure (IOP) in glaucoma , and to investigate its related molecular pathway , an ocular hypertension...
To explore the role of atorvastatin in regulating intraocular pressure (IOP) in glaucoma , and to investigate its related molecular pathway , an ocular hypertension model was generated by intravitreal injection of an adenoviral vector encoding transforming growth factor (TGF)‑β2 in the right eye of BALB/cJ mice, while the left was treated with an empty control adenovirus. To determine its anti‑intraocular hypertension role, these induced hyper‑IOP mice were gavaged with atorvastatin (20 mg/kg/day). Furthermore, extracellular matrix (ECM) factors were examined in the primary human trabecular meshwork (HTM) cells followed atorvastatin (0~200 µM) treatment . Whole genome microarray was employed to identify potential therapeutic target molecules associated with ECM regulation. Unilateral murine ocular hypertension was induced, via intravitreal injection of the adenoviral vector carrying the human TGF‑β2 gene (Ad.hTGF‑β2), raising IOP from 12±1.6 to 32.3±0.7 mmHg (n=6, P<0.05) at day 15, which plateaued from day 15 to 30. Atorvastatin administration from day 15 to 30 decreased IOP from 32.3±0.7 to 15.4±1.1 mmHg (n=6, P<0.05) at day 30. Additionally, atorvastatin administration changed the morphology of cultured HTM cells from an elongated and adherent morphology into rounded, less elongated and less adherent cells, accompanied with suppressed expression of ECM. Gene Ontology and Genome analysis revealed that FGD4 (FYVE, RhoGEF and PH domain containing 4) might be a key factor contributing to these changes. Our data demonstrated that atorvastatin reduced TGF‑β2‑induced ocular hypertension , perhaps via modifying cellular structure and decreasing ECM, using the FGD4 signaling pathway, as demonstrated in HTM cells. Our findings provide some useful information for the management of glaucoma, with statin therapy revealing a potential novel therapeutic pathway for glaucoma treatment.
Topics: Animals; Atorvastatin; Cells, Cultured; Extracellular Matrix; Glaucoma; Intraocular Pressure; Mice; Microfilament Proteins; Ocular Hypertension; Trabecular Meshwork; Transforming Growth Factor beta2
PubMed: 35417030
DOI: 10.3892/ijmm.2022.5132 -
Survey of Ophthalmology 2020The aqueous humor (AH) outflow pathways definition is still matter of intense debate. To date, the differentiation between conventional (trabecular meshwork) and... (Review)
Review
The aqueous humor (AH) outflow pathways definition is still matter of intense debate. To date, the differentiation between conventional (trabecular meshwork) and unconventional (uveoscleral) pathways is widely accepted, distinguishing the different impact of the intraocular pressure on the AH outflow rate. Although the conventional route is recognized to host the main sites for intraocular pressure regulation, the unconventional pathway, with its great potential for AH resorption, seems to act as a sort of relief valve, especially when the trabecular resistance rises. Recent evidence demonstrates the presence of lymphatic channels in the eye and proposes that they may participate in the overall AH drainage and intraocular pressure regulation, in a presumably adaptive fashion. For this reason, the uveolymphatic route is increasingly thought to play an important role in the ocular hydrodynamic system physiology. As a result of the unconventional pathway characteristics, hydrodynamic disorders do not develop until the adaptive routes cannot successfully counterbalance the increased AH outflow resistance. When their adaptive mechanisms fail, glaucoma occurs. Our review deals with the standard and newly discovered AH outflow routes, with particular attention to the importance they may have in opening new therapeutic strategies in the treatment of ocular hypertension and glaucoma.
Topics: Animals; Aqueous Humor; Glaucoma; Humans; Intraocular Pressure; Lymphatic Vessels; Ocular Hypertension; Trabecular Meshwork
PubMed: 31622628
DOI: 10.1016/j.survophthal.2019.10.002 -
Clinical & Experimental Optometry Nov 2019Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP)... (Review)
Review
Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. The IOP-lowering actions of LBN are mediated by dual mechanisms of the molecule for increasing aqueous humour outflow. The prostaglandin analogue moiety (latanoprost acid) increases uveoscleral outflow, whereas nitric oxide, released by the nitric oxide-donating moiety (butanediol mononitrate), increases outflow through the trabecular meshwork and the Schlemm's canal. The clinical efficacy and safety of LBN 0.024% in patients with open-angle glaucoma or ocular hypertension were established in two similarly designed, double-masked, pivotal phase 3 studies, APOLLO and LUNAR, the pooled three-month efficacy phase of which demonstrated significantly greater IOP-lowering of once-daily LBN 0.024% over twice-daily timolol 0.5% at all time points. Additional support for the IOP-lowering effects of LBN 0.024% was provided by two phase 2 studies in patients with open-angle glaucoma or ocular hypertension (a dose ranging study versus latanoprost and a 24-hour IOP crossover study versus timolol) and a phase 1 study of healthy volunteers with IOP in the normal range. In addition, long-term efficacy and safety were demonstrated in the open-label safety-extension phases of the phase 3 pivotal studies and a phase 3 52-week open-label study of patients with open-angle glaucoma (including normal-tension glaucoma) or ocular hypertension. In conclusion, LBN 0.024% has demonstrated both short-term and long-term IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension, including in healthy volunteers and patients with IOP in the normal range, without apparent clinically-limiting safety or tolerability concerns.
Topics: Animals; Clinical Trials as Topic; Glaucoma, Open-Angle; Humans; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic
PubMed: 30614563
DOI: 10.1111/cxo.12853