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Ophthalmology Nov 2018In an elegant example of bench-to-bedside research, a hypothesis that cells in the outflow pathway actively regulate conventional outflow resistance was proposed in the... (Review)
Review
In an elegant example of bench-to-bedside research, a hypothesis that cells in the outflow pathway actively regulate conventional outflow resistance was proposed in the 1990s and systematically pursued, exposing novel cellular and molecular mechanisms of intraocular pressure (IOP) regulation. The critical discovery that pharmacologic manipulation of the cytoskeleton of outflow pathway cells decreased outflow resistance placed a spotlight on the Rho kinase pathway that was known to regulate the cytoskeleton. Ultimately, a search for Rho kinase inhibitors led to the discovery of several molecules of therapeutic interest, leaving us today with 2 new ocular hypotensive agents approved for clinical use: ripasudil in Japan and netarsudil in the United States. These represent members of the first new class of clinically useful ocular hypotensive agents since the US Food and Drug Administration approval of latanoprost in 1996. The development of Rho kinase inhibitors as a class of medications to lower IOP in patients with glaucoma and ocular hypertension represents a triumph in translational research. Rho kinase inhibitors are effective alone or when combined with other known ocular hypotensive medications. They also offer the possibility of neuroprotective activity, a favorable impact on ocular blood flow, and even an antifibrotic effect that may prove useful in conventional glaucoma surgery. Local adverse effects, however, including conjunctival hyperemia, subconjunctival hemorrhages, and cornea verticillata, are common. Development of Rho kinase inhibitors targeted to the cells of the outflow pathway and the retina may allow these agents to have even greater clinical impact. The objectives of this review are to describe the basic science underlying the development of Rho kinase inhibitors as a therapy to lower IOP and to summarize the results of the clinical studies reported to date. The neuroprotective and vasoactive properties of Rho kinase inhibitors, as well as the antifibrotic properties, of these agents are reviewed in the context of their possible role in the medical and surgical treatment of glaucoma.
Topics: Antihypertensive Agents; Aqueous Humor; Benzoates; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Isoquinolines; Ocular Hypertension; Sulfonamides; Translational Research, Biomedical; beta-Alanine; rho-Associated Kinases
PubMed: 30007591
DOI: 10.1016/j.ophtha.2018.04.040 -
Cells Oct 2023The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRβ), has been implicated in the development of primary open-angle glaucoma... (Review)
Review
The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRβ), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e., GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have a lower expression of GRβ, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. An increased expression of GRβ can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. The endogenous expression of GRβ in the TM may relate to differences in the development of GC-OHT in the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease-modifying therapies to better treat these two sight threatening forms of glaucoma. The purpose of this timely review is to highlight the pathological and clinical features of GC-OHT and GIG, mechanisms responsible for GC responsiveness, potential therapeutic options, as well as to compare the similar features of GIG with POAG.
Topics: Humans; Mice; Animals; Glucocorticoids; Receptors, Glucocorticoid; Glaucoma, Open-Angle; Hydrocortisone; Glaucoma; Ocular Hypertension; Iatrogenic Disease
PubMed: 37887296
DOI: 10.3390/cells12202452 -
European Journal of Ophthalmology Mar 2019To assess tolerability and efficacy following a switch from benzalkonium chloride-latanoprost to preservative-free latanoprost in patients with glaucoma or ocular... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE:
To assess tolerability and efficacy following a switch from benzalkonium chloride-latanoprost to preservative-free latanoprost in patients with glaucoma or ocular hypertension.
METHODS:
A total of 140 patients with glaucoma or ocular hypertension controlled with benzalkonium chloride-latanoprost for at least 3 months were switched to treatment with preservative-free latanoprost. Assessments were made on days 15, 45, and 90 (D15, D45, and D90) and included best-corrected visual acuity, intraocular pressure, slit lamp examination, fluorescein staining, tear film break-up time, patient symptom evaluation, and subjective estimation of tolerability.
RESULTS:
Mean best-corrected visual acuity remained unchanged during the study. Mean intraocular pressure compared with baseline (D0) remained stable throughout the study (D0, 15.9 mmHg (standard deviation = 2.6); D90, 15.3 mmHg (standard deviation = 2.4); p < 0.006). Tear film break-up time improved or remained unchanged relative to baseline in 92% of patients at D45 and in 93% at D90. Moderate-to-severe conjunctival hyperemia was seen in 56.8% of patients at D0, but this figure decreased to 13.7%, 2.2%, and 1.6% at D15, D45, and D90, respectively. Subjective assessment of tolerability (0-10 scale) indicated improvement with change of therapy (mean score: 5.3 (standard deviation = 2.2) at D0 versus 1.9 (standard deviation = 1.7) at D90; p < 0.0001).
CONCLUSION:
Preservative-free latanoprost has at least the same intraocular pressure-lowering efficacy as benzalkonium chloride-latanoprost, with a better tolerability profile. This may translate into greater control of treatment and improved quality of life.
Topics: Antihypertensive Agents; Drug Tolerance; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Preservatives, Pharmaceutical; Treatment Outcome
PubMed: 29998767
DOI: 10.1177/1120672118785280 -
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... 2016Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle... (Review)
Review
Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. The mechanism by which SLT lowers IOP is not completely understood and is likely multifactorial. Published studies indicate that SLT is at least as effective as argon laser trabeculoplasty or medications at lowering IOP in many forms of glaucoma. In addition to IOP reduction, SLT may decrease IOP fluctuation and can be successfully used as primary or adjunctive therapy for the management of both early and advanced glaucoma. However, SLT may not be effective in certain forms of glaucoma, and the IOP-lowering effect seems to wane with time. High pretreatment IOP is the strongest predictor of treatment success, even in patients with normal-tension glaucoma. Repeatability of SLT has been controversial, but recent evidence suggests that it can be successfully repeated to achieve additional or recurrent IOP reduction, even in eyes that only had a modest response to initial treatment. Adverse events are uncommon after SLT, and the most common complications such as discomfort and inflammation are typically mild and transient. Further investigation is required to determine the optimal treatment parameters for SLT treatment. Limited evidence suggests that SLT is cost-effective as primary therapy for patients with glaucoma.
Topics: Glaucoma, Open-Angle; Humans; Intraocular Pressure; Laser Therapy; Ocular Hypertension; Trabeculectomy
PubMed: 26886122
DOI: 10.1097/APO.0000000000000175 -
Health Technology Assessment... Jun 2012To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of... (Review)
Review
OBJECTIVES
To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways.
DESIGN
A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model.
SETTING
Primary and secondary care.
PARTICIPANTS
Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences).
INTERVENTIONS
We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community.
MAIN OUTCOME MEASURES
Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs).
RESULTS
The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence.
LIMITATIONS
Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates.
CONCLUSIONS
For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment.
FUNDING
The National Institute for Health Research Health Technology Assessment Programme.
Topics: Administration, Ophthalmic; Age Factors; Antihypertensive Agents; Cohort Studies; Cost-Benefit Analysis; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Mass Screening; Models, Theoretical; Ocular Hypertension; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 22687263
DOI: 10.3310/hta16290 -
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 -
BMC Endocrine Disorders Sep 2022Ocular hypertension (OHT) is an important clinical feature of thyroid-associated orbitopathy (TAO).While the prevalence and outcome of OHT in TAO remains unclear. This...
PURPOSE
Ocular hypertension (OHT) is an important clinical feature of thyroid-associated orbitopathy (TAO).While the prevalence and outcome of OHT in TAO remains unclear. This study investigates this in moderate-severe active TAO.
METHODS
Sixty-eight patients with active moderate-severe TAO were recruited, 49 of whom were treated with 12-week GC therapy.The clinical and biochemical parameters were collected.Treatment outcomes were evaluated after GC therapy.
RESULTS
The prevalence of OHT was 44.85% in moderate-severe active TAO patients,including 81.97% of mild hypertension, 13.11% of moderate hypertension and 4.92% of severe hypertension. Clinical and biochemical parameters had no significant difference between OHT patients and non-OHT patients,such as age, sex distributions, smoking status, the kind and the duration of thyroid disease,the duration of eye symptoms and the level of FT3,FT4,TSH, TR-Ab, and Tpo-Ab, Tg-Ab(all P > 0.05). After GC therapy,the intraocular pressure(IOP) in OHT eyes decreased significantly (P < 0.05), while IOP in non-OHT eyes remained unchanged (P > 0.05).There was no significant difference in CAS and the effective rate of GC therapy between OHT eyes and non-OHT eyes (P > 0.05).
CONCLUSION
In moderate-severe active TAO, the prevalence of OHT was 44.85%, most of which were mild hypertension.OHT was relieved by GC therapy,which had no effect on the efficacy of GC therapy.Our results will enhance physicians' confidence in GC therapy.
Topics: Glucocorticoids; Graves Ophthalmopathy; Humans; Hypertension; Ocular Hypertension; Thyrotropin
PubMed: 36151558
DOI: 10.1186/s12902-022-01153-w -
Clinical & Experimental Optometry May 2022Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure,...
Systemic hypertension or hypertension is a very common chronic age-related disease worldwide. It is typically characterised by a sustained elevation of blood pressure, particularly when the systolic blood pressure and/or diastolic blood pressure are of more than 140 mmHg and 90 mmHg, respectively. If hypertension is not well controlled, it may lead to an increased risk of stroke and heart attack. It has been shown that hypertension is linked to various ocular diseases, including cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma is the most common form of the disease and is usually characterised by an increase in intraocular pressure. This condition, together with normal tension glaucoma, constitutes open angle glaucoma. Systemic hypertension has been identified as a risk factor for open angle glaucoma. It is speculated that blood pressure is involved in the pathogenesis of open angle glaucoma by altering intraocular pressure or ocular blood flow, or both. Recent evidence has shown that both extremely high and low blood pressure are associated with increased risk of open angle glaucoma. Additional pathogenic mechanisms, including increased inflammation likely to be involved in the development and progression of these two diseases, are discussed.
Topics: Blood Pressure; Glaucoma, Open-Angle; Humans; Hypertension; Intraocular Pressure; Ocular Hypertension; Tonometry, Ocular
PubMed: 34402761
DOI: 10.1080/08164622.2021.1964332 -
Scientific Reports Jun 2020Low ocular perfusion pressure (OPP) has been proposed as an important risk factor for glaucoma development and progression, but controversy still exists between studies.... (Meta-Analysis)
Meta-Analysis
Low ocular perfusion pressure (OPP) has been proposed as an important risk factor for glaucoma development and progression, but controversy still exists between studies. Therefore, we conducted a systematic review and meta-analysis to analyze the association between OPP and open-angle glaucoma (OAG). Studies were identified by searching PubMed and EMBASE databases. The pooled absolute and standardised mean difference in OPP between OAG patients and controls were evaluated using the random-effects model. Meta-regression analysis was conducted to investigate the factors associated with OPP difference between OAG patients and controls. A total of 43 studies were identified including 3,009 OAG patients, 369 patients with ocular hypertension, and 29,502 controls. The pooled absolute mean difference in OPP between OAG patients and controls was -2.52 mmHg (95% CI -4.06 to -0.98), meaning significantly lower OPP in OAG patients (P = 0.001). Subgroup analyses showed that OAG patients with baseline IOP > 21 mmHg (P = 0.019) and ocular hypertension patients also had significantly lower OPP than controls (P < 0.001), but such difference in OPP was not significant between OAG patients with baseline IOP of ≤21 mmHg and controls (P = 0.996). In conclusion, although no causal relationship was proven in the present study, our findings suggest that in patients with high baseline IOP, who already have a higher risk of glaucoma, low OPP might be another risk factor.
Topics: Glaucoma, Open-Angle; Humans; Ocular Hypertension; Ocular Hypotension; Risk Factors
PubMed: 32572072
DOI: 10.1038/s41598-020-66914-w