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Experimental Eye Research Apr 2023Prostaglandin (PG) receptors represent important druggable targets due to the many diverse actions of PGs in the body. From an ocular perspective, the discovery,... (Review)
Review
Prostaglandin (PG) receptors represent important druggable targets due to the many diverse actions of PGs in the body. From an ocular perspective, the discovery, development, and health agency approvals of prostaglandin F (FP) receptor agonists (FPAs) have revolutionized the medical treatment of ocular hypertension (OHT) and glaucoma. FPAs, such as latanoprost, travoprost, bimatoprost, and tafluprost, powerfully lower and control intraocular pressure (IOP), and became first-line therapeutics to treat this leading cause of blindness in the late 1990s to early 2000s. More recently, a latanoprost-nitric oxide (NO) donor conjugate, latanoprostene bunod, and a novel FP/EP3 receptor dual agonist, sepetaprost (ONO-9054 or DE-126), have also demonstrated robust IOP-reducing activity. Moreover, a selective non-PG prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI), was discovered, characterized, and has been approved in the United States, Japan and several other Asian countries for treating OHT/glaucoma. FPAs primarily enhance uveoscleral (UVSC) outflow of aqueous humor (AQH) to reduce IOP, but cause darkening of the iris and periorbital skin, uneven thickening and elongation of eyelashes, and deepening of the upper eyelid sulcus during chronic treatment. In contrast, OMDI lowers and controls IOP by activation of both the UVSC and trabecular meshwork outflow pathways, and it has a lower propensity to induce the aforementioned FPA-induced ocular side effects. Another means to address OHT is to physically promote the drainage of the AQH from the anterior chamber of the eye of patients with OHT/glaucoma. This has successfully been achieved by the recent approval and introduction of miniature devices into the anterior chamber by minimally invasive glaucoma surgeries. This review covers the three major aspects mentioned above to highlight the etiology of OHT/glaucoma, and the pharmacotherapeutics and devices that can be used to combat this blinding ocular disease.
Topics: Humans; Latanoprost; Aqueous Humor; Glaucoma; Ocular Hypertension; Intraocular Pressure; Antihypertensive Agents
PubMed: 36803996
DOI: 10.1016/j.exer.2023.109415 -
Journal of Ocular Pharmacology and... Apr 2015Despite the availability of modern surgical procedures, new drug delivery techniques, health authority-approved single topical ocular drugs, and combination products... (Review)
Review
Despite the availability of modern surgical procedures, new drug delivery techniques, health authority-approved single topical ocular drugs, and combination products thereof, there continues to be an unmet medical need for novel treatment modalities for preserving vision. This is especially true for the treatment of glaucoma and the high risk factor often associated with this ocular disease, elevated intraocular pressure (IOP). Undesirable local or systemic side effects, frequency of dosing, lack of sustained IOP lowering, and lack of prevention of diurnal IOP spikes are among the greatest challenges. The very recent discovery, characterization, and publication of 2 novel IOP-lowering agents that pertain to the renin-angiotensin and kallikrein-kinin axes potentially offer novel means to treat and control ocular hypertension (OHT). Here, some contextual introductory information is provided first, followed by more detailed discussion of the properties and actions of diminazene aceturate (DIZE; a novel angiotensin-converting enzyme-2 activator) and FR-190997 (a nonpeptide bradykinin receptor-2 agonist) in relation to their anti-OHT activities in rodent and cynomolgus monkey eyes, respectively. It is anticipated that these compounds will pave the way for future discovery, development, and marketing of novel drugs to treat glaucoma and thus help save sight for millions of people afflicted with this slow progressive optic neuropathy.
Topics: Angiotensins; Animals; Antihypertensive Agents; Bradykinin; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Renin-Angiotensin System
PubMed: 25599263
DOI: 10.1089/jop.2014.0114 -
Journal of Neuro-ophthalmology : the... Dec 2022The identification of glaucomatous optic neuropathy in the setting of optic disc drusen (ODD) is a challenge, and the decision of whether to offer treatment in the form... (Review)
Review
BACKGROUND
The identification of glaucomatous optic neuropathy in the setting of optic disc drusen (ODD) is a challenge, and the decision of whether to offer treatment in the form of intraocular pressure (IOP) reduction is controversial. Here, we present a series of patients with coexisting ocular hypertension and ODD to evaluate clinical features, treatment options, and progression of optic neuropathy. In addition, a review of the literature on ODD with elevated IOP is provided.
METHODS
Six patients with ODD and a history of ocular hypertension are presented. Components of the examination and imaging modalities used to establish the diagnosis of ODD were recorded and a description of ocular hypertension history, glaucoma testing, and the potential treatment of IOP were also provided.
RESULTS
In this series, 4 of 6 patients with concurrent ocular hypertension and ODD showed progression of optic neuropathy as assessed by visual field or retinal nerve fiber layer thickness. Of the 2 patients who did not show evidence of progression, 1 was treated with IOP-lowering medications and 1 was observed off treatment. Of the 4 patients who showed evidence of progression, all 4 were initially treated with IOP-lowering medications and 2 ultimately went on to have trabeculectomy surgery. In the patients with progressive optic neuropathy, lowering the IOP seemed to halt the progression suggesting there was a pressure-sensitive component.
CONCLUSIONS
Distinguishing changes to the optic nerve, particularly the structural changes at the lamina cribrosa of true glaucomatous optic neuropathy in the setting of ODD, is a challenge. Careful consideration of risk factors including age, presenting features, progression indicators, and management goals is to be accounted for in the decision to offer treatment. We see the presence ODD in the patients with ocular hypertension as an additional risk for progressive changes to the nerve fiber layer and visual field that needs to be considered when determining whether to initiate therapy. Our data suggest that treatment of IOP in the patients with ocular hypertension with ODD and evidence of progression reduces the risk of further progression. Further work is needed to determine whether progression of optic neuropathy in the setting of coexisting ODD and ocular hypertension is related mechanistically to predominantly an ODD-type process, a glaucomatous process, or a combination thereof.
Topics: Humans; Optic Disk Drusen; Intraocular Pressure; Ocular Hypertension; Glaucoma; Optic Nerve Diseases
PubMed: 35916300
DOI: 10.1097/WNO.0000000000001647 -
Asia-Pacific Journal of Ophthalmology... 2016Primary angle-closure glaucoma (PACG) is a progressive optic nerve degeneration and is defined as a glaucomatous optic neuropathy with associated characteristic... (Review)
Review
Primary angle-closure glaucoma (PACG) is a progressive optic nerve degeneration and is defined as a glaucomatous optic neuropathy with associated characteristic enlargement of optic disc cupping and visual field loss that is secondary to ocular hypertension caused by closure of the drainage angle. Angle closure is caused by appositional approximation or adhesion between the iris and the trabecular meshwork. The main treatment strategy for PACG lies in the reduction of intraocular pressure, reopening of the closed angle, and possible prevention of further angle closure. There is no universally agreed best surgical treatment for PACG. Trabeculectomy, goniosynechialysis (GSL), glaucoma implant, and cyclodestructive procedures are effective surgical options. Each of them plays an important role in the management of PACG with its own pros and cons. Accumulating evidence is available to show the effectiveness of visually significant and visually nonsignificant cataract extraction in the treatment of PACG. Trabeculectomy and GSL are often combined with cataract extraction, which may offer additional pressure control benefits to patients with PACG. This review article will discuss laser peripheral iridotomy, argon laser peripheral iridoplasty, and surgeries such as GSL, phacoemulsification, and phaco plus glaucoma surgeries that lower intraocular pressure and also alter the anterior segment and/or drainage angle anatomy. Currently, glaucoma implants and cyclodestruction are mainly reserved for PACG patients who have failed previous filtering operations. Their role as initial surgical treatment for PACG will not be discussed.
Topics: Antihypertensive Agents; Combined Modality Therapy; Disease Management; Glaucoma Drainage Implants; Glaucoma, Angle-Closure; Humans; Iridectomy; Laser Therapy; Ocular Hypertension; Optic Nerve Diseases; Phacoemulsification; Trabeculectomy
PubMed: 26886121
DOI: 10.1097/APO.0000000000000180 -
Eye (London, England) May 2018Over the past two decades, selective laser trabeculoplasty (SLT) has increasingly become an established laser treatment used to lower intraocular pressure in open-angle... (Review)
Review
Over the past two decades, selective laser trabeculoplasty (SLT) has increasingly become an established laser treatment used to lower intraocular pressure in open-angle glaucoma and ocular hypertensive patients. In this review we trace the origins of SLT from previous argon laser trabeculoplasty and review the current role it has in clinical practice. We outline future directions of SLT research and introduce emerging technologies that are further developing this intervention in the treatment paradigm of glaucoma.
Topics: Glaucoma; Humans; Laser Therapy; Ocular Hypertension; Trabeculectomy
PubMed: 29303146
DOI: 10.1038/eye.2017.273 -
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 -
Journal of Glaucoma Dec 2022An increased risk of ocular hypertension was seen in Cushing's disease.
PRCIS
An increased risk of ocular hypertension was seen in Cushing's disease.
INTRODUCTION
Systemic steroid use is a significant risk factor for increased intraocular pressure (IOP). The incidence of ocular hypertension may rise to 30%-40% of the general population due to topical or systemic glucocorticoid usage. However, the incidence of ocular hypertension in endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to surgical resection, remain unknown.
MATERIALS AND METHODS
The IOP, visual field, and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing's disease (CD) admitted to a tertiary pituitary center for surgery from January to July 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period served as controls. We calculated the odds ratio (OR), identified the risk factors of developing ocular hypertension, and presented postoperative trends of the IOP.
RESULTS
A total of 52 patients (38.4±12.4 y old) with CD were included. The IOP was higher in patients with CD (left 19.4±5.4 mm Hg and right 20.0±7.1 mm Hg) than in patients with acromegaly (left 17.5±2.3 mm Hg and right 18.6±7.0 mm Hg, P =0.033) and patients with NFPA (left 17.8±2.6 mm Hg and right 17.4±2.4 mm Hg, P =0.005). A total of 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension compared with 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The OR of developing ocular hypertension in patients with CD was 5.1 [95% confidence interval (CI), 1.3-25.1, P =0.029] and 6.6 (95% CI, 1.8-30.3, P =0.007) when compared with the 2 control groups. Among patients with CD, those with a higher urine-free cortisol were more likely to develop ocular hypertension (OR=19.4, 95% CI, 1.7-72.6). The IOP decreased at 1 month after surgery in patients with CD, and the change was sustained for 3 months after surgery.
CONCLUSIONS
An increased risk of ocular hypertension was seen in CD and suggests that endogenous hypercortisolemia should be considered as part of the glaucoma assessment. This result warrants the discretion of both ophthalmologists and neuroendocrinologists.
Topics: Humans; Intraocular Pressure; Pituitary ACTH Hypersecretion; Acromegaly; Ocular Hypertension; Glaucoma; Tonometry, Ocular
PubMed: 35980841
DOI: 10.1097/IJG.0000000000002113 -
Eye (London, England) May 2018Central corneal thickness (CCT) is an important parameter in the assessment of any potential glaucoma patient. While it affects prognosis in ocular hypertension, its... (Review)
Review
Central corneal thickness (CCT) is an important parameter in the assessment of any potential glaucoma patient. While it affects prognosis in ocular hypertension, its value in patients diagnosed with glaucoma is less certain. There are several biological factors and genetic components that may influence glaucoma progression, which have been associated with thinner CCT. The CCT itself can be affected by several factors including ethnicity, age, sex, glaucoma medications, genetics, and the subtype of glaucoma. Besides, there is variability in the measurement of CCT between difference types of devices. These factors need to be considered in the evaluation of glaucoma patients' CCT and its effect on interpretation of intraocular pressure levels and risk stratification.
Topics: Age Factors; Cornea; Genetic Predisposition to Disease; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Risk Factors; Sex Factors
PubMed: 29445115
DOI: 10.1038/s41433-018-0033-3 -
Journal of Glaucoma Jun 2022For patients with glaucoma, metabolic syndrome was associated with higher intraocular pressure and greater central corneal thickness. Patients with metabolic syndrome...
PRCIS
For patients with glaucoma, metabolic syndrome was associated with higher intraocular pressure and greater central corneal thickness. Patients with metabolic syndrome were more likely to have ocular hypertension.
PURPOSE
The purpose of this study was to determine whether glaucomatous optic neuropathy, also known as glaucoma, and ocular hypertension are more likely to occur in patients with metabolic syndrome.
PATIENTS AND METHODS
Patients in Olmsted County, MN, were identified as having metabolic syndrome based on diagnosis codes, laboratory values, and/or medication use to meet 3 or more of the 5 standard criteria for diagnosing metabolic syndrome: systemic hypertension, hyperglycemia, hypertriglyceridemia, reduced high-density lipoprotein cholesterol, and central adiposity defined by increased body mass index. Patients with glaucoma, including primary open angle, low tension, pigment dispersion, and pseudoexfoliation, were identified using diagnostic codes. The charts of patients with glaucoma were individually reviewed to collect visual acuity, intraocular pressure, cup to disc ratio, central corneal thickness, visual field mean deviation, retinal nerve fiber layer thickness, and treatment of intraocular pressure. Patients with ocular hypertension were separately identified and similarly evaluated.
RESULTS
For patients with glaucoma, those with metabolic syndrome had higher intraocular pressure and greater central corneal thickness compared with those without metabolic syndrome. After adjustment for central corneal thickness, there was no longer a significant difference in intraocular pressure between groups. Metabolic syndrome was also associated with the diagnosis of ocular hypertension, and although central corneal thickness trended higher in patients with metabolic syndrome, it did not attain statistical significance.
CONCLUSION
In Olmsted County, though metabolic syndrome was associated with ocular hypertension and higher intraocular pressure in patients with glaucoma, the results were likely related to a thicker central corneal in this patient population.
Topics: Cornea; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Metabolic Syndrome; Ocular Hypertension; United States
PubMed: 34860182
DOI: 10.1097/IJG.0000000000001968 -
Ophthalmologica. Journal International... 2022To compare the incidence, risk factors, treatment, and outcomes associated with intravitreal triamcinolone-acetonide (TA) and dexamethasone-implant (Dex)-induced ocular...
PURPOSE
To compare the incidence, risk factors, treatment, and outcomes associated with intravitreal triamcinolone-acetonide (TA) and dexamethasone-implant (Dex)-induced ocular hypertension (OHT).
METHODS
This retrospective study reviewed 1,549 TA and Dex administrations in 1,075 eyes of 897 patients. Intraocular pressure (IOP) values were monitored for a period of 6 months following intravitreal injection(s) and patients were categorized as steroid-responders (SR): IOP≥21 mm Hg, and steroid non-responders (NR): IOP≤20 mm Hg. Glaucoma patients, glaucoma suspects, uveitis, trauma, and less than 1 month of IOP follow-up cases were excluded from the study. The incidence of IOP rise, time and magnitude of IOP rise, and its management procedures were studied. Ocular and systemic associations with OHT incidence were investigated. Statistical analysis was performed using SPSS.23 and p < 0.05 was considered significant.
RESULT
Twenty-eight percent of TA and 17% of Dex administered eyes developed OHT. Male subjects and elderly people (greater than 40 years of age) are at higher risk for OHT following steroid treatment. A high percentage of IOP rise was observed on day 1 (41%) for TA-SR, and after 1 month (50%) for Dex-SR. IOP rise was found to be more severe (>30 mm Hg) for TA-SR compared to Dex-SR (p = 0.006). 6% TA-SR required trabeculectomy with medically uncontrollable IOP. Myopia is a risk factor for secondary OHT, whereas diabetes mellitus and hypercholesterolemia are protective of it.
CONCLUSION
Twenty-eight percent of TA and 17% of Dex administrations developed OHT. Early and severe IOP rises were more common in TA than among Dex administrations. Myopia is a risk for Dex-OHT.
Topics: Humans; Male; Aged; Retrospective Studies; Incidence; Dexamethasone; Glucocorticoids; Drug Implants; Ocular Hypertension; Intraocular Pressure; Triamcinolone Acetonide; Glaucoma; Intravitreal Injections; Risk Factors; Myopia
PubMed: 35468616
DOI: 10.1159/000522504