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Methods in Molecular Biology (Clifton,... 2023Glaucoma is a neurodegenerative disease that leads to the loss of retinal ganglion cells (RGC) and thus to blindness. There are numerous experimental models used for the...
Glaucoma is a neurodegenerative disease that leads to the loss of retinal ganglion cells (RGC) and thus to blindness. There are numerous experimental models used for the study of this pathology. Among the different models, episcleral vein photocoagulation is one of the most widely used. In this model there is a transient increase in intraocular pressure that returns to normal values about 7 days after induction of ocular hypertension (OHT). In addition, typical glaucoma changes, such as loss of RGC, thinning of the optic nerve fiber layer, and glial activation, occur in this model. All these changes have been described in detail over time after OHT induction. In this chapter, we describe the detailed method of OHT induction in Swiss albino mice by diode laser photocoagulation of limbal and episcleral veins.
Topics: Mice; Animals; Neurodegenerative Diseases; Ocular Hypertension; Glaucoma; Retinal Ganglion Cells; Intraocular Pressure; Lasers; Disease Models, Animal
PubMed: 37558959
DOI: 10.1007/978-1-0716-3409-7_6 -
Molecular Aspects of Medicine Dec 2023More than 76 million people worldwide are afflicted with the neurodegenerative eye diseases described and grouped together as glaucoma. A common feature amongst the many... (Review)
Review
More than 76 million people worldwide are afflicted with the neurodegenerative eye diseases described and grouped together as glaucoma. A common feature amongst the many forms of glaucoma is chronically elevated intraocular pressure (IOP) within the anterior chamber of the eye that physically damages the retina, optic nerve and parts of the brain connected with visual perception. The mediators of the contusing raised IOP responsible for such damage and loss of vision include locally released inflammatory agents, tissue remodeling enzymes and infiltrating immune cells which damage the retinal ganglion cell (RGC) axons and eventually kill a significant number of the RGCs. Additional culprits include genetic defects of the patient that involve aberrations in receptors, enzymes and/or endogenous ligands and possible over- or under-production of the latter. Other genetic abnormalities may include issues with signal transduction machinery within key cells of critical tissues in the front (e.g. trabecular meshwork [TM] and Schlemm's canal [SC]) and back of the eye (e.g. retinal ganglion cells and their axons). Genome-wide associated studies (GWAS) coupled with next generation sequencing have provided powerful linkage of certain gene defects and polymorphic variants to the onset and progression of diseases of the tissues involved in fluid dynamics in the TM and SC, and many retinal elements (lamina cribosa, optic nerve head) at the back of the eye which cause ocular hypertension (OHT) and glaucomatous optic neuropathy (GON), respectively. Despite the availability of some drugs, fluid drainage microshunts and full surgical techniques to lower and control intraocular pressure, the major modifiable biomarker of open-angle and other forms of glaucoma, their side-effect profiles, less than optimum effectiveness and short duration of action present opportunities to clinically manage the glaucomas with next generation of treatments with high therapeutic indices, including gene therapies. Thus, identification, characterization and deployment of genetic data coupled with traditional drug discovery and novel gene replacement, gene editing and genetic engineering technologies may provide some solutions to the aforementioned problems. These aspects will be discussed in this article.
Topics: Animals; Humans; Disease Models, Animal; Glaucoma; Ocular Hypertension; Intraocular Pressure; Retina
PubMed: 37976898
DOI: 10.1016/j.mam.2023.101218 -
Developments in Ophthalmology 1999
Review
Topics: Antihypertensive Agents; Cryotherapy; Filtering Surgery; Glaucoma; Glucocorticoids; Humans; Incidence; Intraocular Pressure; Ocular Hypertension; Scleritis; Uveitis
PubMed: 10627919
DOI: 10.1159/000060737 -
Current Opinion in Ophthalmology Mar 2007To discuss current knowledge of global risk assessment in ocular hypertension. (Review)
Review
PURPOSE OF REVIEW
To discuss current knowledge of global risk assessment in ocular hypertension.
RECENT FINDINGS
The ophthalmologist treating patients with ocular hypertension is frequently faced with the clinical dilemma of which patients to treat and how vigorous treatment should be. The goal of risk assessment for glaucoma is to identify patients at greatest risk for symptomatic vision loss. Risk factors can be identified by history such as age, race, and family history or can be clinically observed by examination such as elevated intraocular pressure, optic nerve head appearance, central corneal thickness, and visual field abnormalities. Risk assessment is a well accepted tool in other fields of medicine. Parallels can be drawn between the evolution of risk assessment for coronary artery disease and glaucoma. Validated risk calculators for ocular hypertension are currently available mostly derived from the Ocular Hypertension Treatment Study.
SUMMARY
The aim of assessing global risk for conversion from ocular hypertension to glaucoma is to identify patients who are most likely to benefit from early treatment. Calculation of risk should be accompanied by thorough analysis of risks, benefits, and alternatives for the individual patient.
Topics: Age Factors; Disease Progression; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Prevalence; Risk Assessment; Risk Factors; United States
PubMed: 17301610
DOI: 10.1097/ICU.0b013e32808373a2 -
Acta Ophthalmologica May 2018To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension.
METHODS
We searched PubMed, EMBASE and clinicaltrials.gov for studies that fit our inclusion criteria in this network meta-analysis. Randomized controlled trials that report data on efficacy and safety of medications for POAG or ocular hypertension are included. Data on intra-ocular pressure (IOP) lowering effect and incidence of adverse events including hyperaemia and ocular discomfort were extracted and used in mixed-comparison analysis.
RESULTS
This study includes 72 randomized trials. Data were available on 12 medical treatments of POAG or ocular hypertension. Of 66 possible comparisons of outcome efficacy, 15 treatments were compared directly. Compared to prostaglandin analogues (PGA), beta-blockers (BB) showed relatively weaker ability to lower IOP, followed by α2-adrenergic agonists (AA) and carbonic anhydrase inhibitors (CAI). For dual therapy, regimens composed of a combination of PGA with another treatment demonstrated more powerful IOP lowering efficacy, while the combination of two non-PGA drugs had lower efficacy in controlling IOP than PGA alone. There was no statistical significance in combinations that did not include PGA on efficacy of IOP control. In terms of tolerance, PGA alone leads to more severe hyperaemia than any other monotherapy regimen, while BBs have the lowest effect on the incidence of hyperaemia. Most dual therapy regimens containing PGA also lead to serious hyperaemia, with the exception of PGA + AA. Compared to regimens containing PGA, those with BB are less likely to cause hyperaemia.
CONCLUSION
Our network meta-analysis showed that PGAs provide best IOP lowering effect among all the monotherapy regimen. Combination of PGA and other category of drugs leads to better IOP decrease. Combination of BB and another non-PGA drug may have less ocular side-effects than PGA alone.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Network Meta-Analysis; Ocular Hypertension
PubMed: 29144028
DOI: 10.1111/aos.13568 -
American Journal of Ophthalmology Sep 2004To develop a model for estimating the global risk of disease progression in patients with ocular hypertension and to calculate the "number-needed-to-treat" (NNT) to... (Review)
Review
PURPOSE
To develop a model for estimating the global risk of disease progression in patients with ocular hypertension and to calculate the "number-needed-to-treat" (NNT) to prevent progression to blindness as an aid to practitioners in clinical decision making.
DESIGN
Development of a mathematical model for estimating risk of glaucoma progression.
METHODS
Population-based studies of patients with ocular hypertension and glaucoma were reviewed by a panel of glaucoma specialists. Measures of disease progression risks derived from three long-term studies and assumptions based on the available data were used to estimate the risk of progression from ocular hypertension to glaucoma and glaucoma to unilateral blindness for untreated and treated patients over a 15-year period. Using these estimates, the NNT (1/absolute risk reduction on treatment) to prevent unilateral blindness in one patient with ocular hypertension was calculated.
RESULTS
In untreated patients, the estimated risk of progression from ocular hypertension to unilateral blindness was 1.5% to 10.5% and in treated patients, the estimated risk of progression was 0.3% to 2.4% over 15 years. From these estimates, between 12 and 83 patients with ocular hypertension will require treatment to prevent one patient from progressing to unilateral blindness over a 15-year period.
CONCLUSION
Global risk assessment that incorporates all available data plays a vital role in managing patients with ocular hypertension. A more precise understanding of long-term vision loss should be factored into decisions pertaining to the initiation of glaucoma therapy. Undoubtedly, these estimates will evolve and change with the availability of new population-based epidemiologic information and improvements in multivariable model testing.
Topics: Blindness; Decision Making; Disease Progression; Glaucoma; Humans; Models, Biological; Models, Theoretical; Ocular Hypertension; Risk Assessment; Risk Factors
PubMed: 15364230
DOI: 10.1016/j.ajo.2004.04.054 -
Expert Opinion on Investigational Drugs Oct 2016Intraocular pressure (IOP) is the most significant modifiable risk factor to prevent onset or progression of glaucoma. Glaucoma prevalence continues to increase,... (Review)
Review
INTRODUCTION
Intraocular pressure (IOP) is the most significant modifiable risk factor to prevent onset or progression of glaucoma. Glaucoma prevalence continues to increase, emphasizing the need for improved ocular hypotensive treatment options. To try to improve on both tolerance and IOP control of currently available therapies, different receptors or mechanisms are being explored to reduce IOP more effectively and to improve tolerance.
AREAS COVERED
We review synthetic topical and oral drugs in early development for the management of ocular hypertension and glaucoma.
EXPERT OPINION
New therapeutic agents for IOP control have been discovered; some appear to be reasonably tolerated. IOP reduction may be limited with some agents, but other benefits although unproven may compensate for this, such as less ocular surface disease, enhanced neuro-protection or increased ocular blood flow. Further product development promises improved treatment options for ocular hypertensives and glaucoma sufferers.
Topics: Animals; Antihypertensive Agents; Disease Progression; Drug Design; Drugs, Investigational; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension
PubMed: 27548834
DOI: 10.1080/13543784.2016.1223042 -
International Ophthalmology Clinics Apr 2024
Topics: Humans; Glaucoma; Ocular Hypertension; Intraocular Pressure
PubMed: 38525982
DOI: 10.1097/IIO.0000000000000493 -
Oftalmologia (Bucharest, Romania : 1990) 2009Steroid induced ocular hypertension and glaucoma represent iatrogenic changes of pharmacogenic nature. They are mainly due to exogenous steroids following ocular... (Review)
Review
Steroid induced ocular hypertension and glaucoma represent iatrogenic changes of pharmacogenic nature. They are mainly due to exogenous steroids following ocular periocular, intravitreal and systemic administration. Elevated ocular pressure is brought about by structural trabecular changes as well as obstruction of the outflow ways of the aqueous humor localized within the trabecular juxtacanalicular area. Although mostly raised ocular pressure spontaneously descends to basal values after ceasing the steroid therapy, progressive optic nerve damages and glaucomatous visual field defects may occur. Therapy of steroid induced ocular hypertension and glaucoma is similar to that of ocular hypertension and primary open-angle glaucoma.
Topics: Algorithms; Antihypertensive Agents; Glaucoma, Open-Angle; Glucocorticoids; Humans; Intraocular Pressure; Ocular Hypertension; Risk Factors; Trabeculectomy; Treatment Outcome
PubMed: 19899544
DOI: No ID Found -
Drugs 2006When to treat the patient who presents with ocular hypertension has been a question that has 'stumped' the ophthalmic community for decades. Population-based studies and... (Review)
Review
When to treat the patient who presents with ocular hypertension has been a question that has 'stumped' the ophthalmic community for decades. Population-based studies and intervention trials have provided the basis for understanding why we consider treating such patients. Although the EGPS (European Glaucoma Prevention Study) did not demonstrate that reducing intraocular pressure (IOP) with dorzolamide prevented the onset of glaucoma compared with individuals receiving a placebo, the investigators of the OHTS (Ocular Hypertension Treatment Study) found that the treatment of ocular hypertension can be delayed with topical medication when treated patients were compared with an observation group. There are differences in inclusion criteria, study design and retention rates between the EGPS and the OHTS, which may have led to the discrepancies in outcomes between these two studies. These differences provide a basis for understanding the relevance of the findings of both trials to clinical practice. The clinician should consider key risk factors such as age, thin corneal thickness measurements, large cup-to-disc ratio and mean IOP when determining who should be treated. However, the ultimate decision of when to treat will be determined by other issues such as life expectancy, the general health of the patient and the number of risk factors. Clearly, the treatment of only high-risk patients with ocular hypertension should be considered.
Topics: Aged; Aging; Cornea; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Risk
PubMed: 16789790
DOI: 10.2165/00003495-200666080-00001