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Survey of Ophthalmology 2023Glaucoma is a chronic, progressive disease leading to irreversible blindness if left untreated; however, since reducing intraocular pressure has proven to be successful... (Review)
Review
Glaucoma is a chronic, progressive disease leading to irreversible blindness if left untreated; however, since reducing intraocular pressure has proven to be successful in slowing disease progression, little is known about the natural history of untreated glaucoma. This knowledge can be valuable in guiding management decisions in the era of personalized medicine. A systematic search was performed in Medline (PubMed), Embase, and Web of Science in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRIMSA) guidelines. The rate of structural and/or functional progression and conversion to glaucoma or to a more advanced stage of glaucoma are discussed for ocular hypertension and different types of open-angle glaucoma. Forty-three studies were included. Different rates of progression were found both among and within the different diagnostic groups that belong to the open-angle glaucoma spectrum. The highest rate was found in pseudoexfoliation glaucoma, followed by high tension glaucoma, normal tension glaucoma, and ocular hypertension, in decreasing order. The lowest rate was observed in glaucoma suspects. The known rates of progression provide valuable prognostic information for ophthalmologists and patients. Nonetheless, due to high variability among patients, individual progression cannot be accurately predicted and repeated follow-up examinations are required to estimate individual progression.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma; Ocular Hypertension; Intraocular Pressure; Eye
PubMed: 36563707
DOI: 10.1016/j.survophthal.2022.12.001 -
The Cochrane Database of Systematic... Aug 2022Open-angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the... (Review)
Review
BACKGROUND
Open-angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the treatment sequence.
OBJECTIVES
To assess the effects of laser trabeculoplasty for treating OAG and ocular hypertension (OHT) when compared to medication, glaucoma surgery or no intervention. We also wished to compare the effectiveness of different laser trabeculoplasty technologies for treating OAG and OHT.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; LILACS, ClinicalTrials.gov and the WHO ICTRP. The date of the search was 28 October 2021. We also contacted researchers in the field.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing laser trabeculoplasty with no intervention, with medical treatment, or with surgery in people with OAG or OHT. We also included trials comparing different types of laser trabeculoplasty technologies.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane. Two authors screened search results and extracted data independently. We considered the following outcomes at 24 months: failure to control intraocular pressure (IOP), failure to stabilise visual field progression, failure to stabilise optic neuropathy progression, adverse effects, quality of life, and costs. We graded the 'certainty' of the evidence using GRADE.
MAIN RESULTS
We included 40 studies (5613 eyes of 4028 people) in this review. The majority of the studies were conducted in Europe and in the USA. Most of the studies were at risk of performance and/or detection bias as they were unmasked. None of the studies were judged as having low risk of bias for all domains. We did not identify any studies of laser trabeculoplasty alone versus no intervention. Laser trabeculoplasty versus medication Fourteen studies compared laser trabeculoplasty with medication in either people with primary OAG (7 studies) or primary or secondary OAG (7 studies); five of the 14 studies also included participants with OHT. Six studies used argon laser trabeculoplasty and eight studies used selective laser trabeculoplasty. There was considerable clinical and methodological diversity in these studies leading to statistical heterogeneity in results for the primary outcome "failure to control IOP" at 24 months. Risk ratios (RRs) ranged from 0.43 in favour of laser trabeculoplasty to 1.87 in favour of medication (5 studies, I = 89%). Studies of argon laser compared with medication were more likely to show a beneficial effect compared with studies of selective laser (test for interaction P = 0.0001) but the argon laser studies were older and the medication comparator group in those studies may have been less effective. We considered this to be low-certainty evidence because the trials were at risk of bias (they were not masked) and there was unexplained heterogeneity. There was evidence from two studies (624 eyes) that argon laser treatment was associated with less failure to stabilise visual field progression compared with medication (7% versus 11%, RR 0.70, 95% CI 0.42 to 1.16) at 24 months and one further large recent study of selective laser also reported a reduced risk of failure at 48 months (17% versus 26%) RR 0.65, 95% CI 0.52 to 0.81, 1178 eyes). We judged this outcome as moderate-certainty evidence, downgrading for risk of bias. There was only very low-certainty evidence on optic neuropathy progression. Adverse effects were more commonly seen in the laser trabeculoplasty group including peripheral anterior synechiae (PAS) associated with argon laser (32% versus 26%, RR 11.74, 95% CI 5.94 to 23.22; 624 eyes; 2 RCTs; low-certainty evidence); 5% of participants treated with laser in three studies of selective laser group had early IOP spikes (moderate-certainty evidence). One UK-based study provided moderate-certainty evidence that laser trabeculoplasty was more cost-effective. Laser trabeculoplasty versus trabeculectomy Three studies compared laser trabeculoplasty with trabeculectomy. All three studies enrolled participants with OAG (primary or secondary) and used argon laser. People receiving laser trabeculoplasty may have a higher risk of uncontrolled IOP at 24 months compared with people receiving trabeculectomy (16% versus 8%, RR 2.12, 95% CI 1.44 to 3.11; 901 eyes; 2 RCTs). We judged this to be low-certainty evidence because of risk of bias (trials were not masked) and there was inconsistency between the two trials (I = 68%). There was limited evidence on visual field progression suggesting a higher risk of failure with laser trabeculoplasty. There was no information on optic neuropathy progression, quality of life or costs. PAS formation and IOP spikes were not reported but in one study trabeculectomy was associated with an increased risk of cataract (RR 1.78, 95% CI 1.46 to 2.16) (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Laser trabeculoplasty may work better than topical medication in slowing down the progression of open-angle glaucoma (rate of visual field loss) and may be similar to modern eye drops in controlling eye pressure at a lower cost. It is not associated with serious unwanted effects, particularly for the newer types of trabeculoplasty, such as selective laser trabeculoplasty.
Topics: Argon; Glaucoma; Glaucoma, Open-Angle; Humans; Ocular Hypertension; Optic Nerve Diseases; Trabeculectomy
PubMed: 35943114
DOI: 10.1002/14651858.CD003919.pub3 -
Cell Death & Disease Aug 2023Glaucoma is a group of diseases that leads to chronic degeneration of retinal ganglion cell (RGC) axons and progressive loss of RGCs, resulting in vision loss. While...
Glaucoma is a group of diseases that leads to chronic degeneration of retinal ganglion cell (RGC) axons and progressive loss of RGCs, resulting in vision loss. While aging and elevated intraocular pressure (IOP) have been identified as the main contributing factors to glaucoma, the molecular mechanisms and signaling pathways triggering RGC death and axonal degeneration are not fully understood. Previous studies in our laboratory found that overactivation of autophagy in DBA/2J::GFP-LC3 mice led to RGC death and optic nerve degeneration with glaucomatous IOP elevation. We found similar findings in aging GFP-LC3 mice subjected to chronic IOP elevation. Here, we further investigated the impact of autophagy deficiency on autophagy-deficient DBA/2J-Atg4b and DBA/2J-Atg4b mice, generated in our laboratory via CRISPR/Cas9 technology; as well as in Atg4b mice subjected to the experimental TGFβ2 chronic ocular hypertensive model. Our data shows that, in contrast to DBA/2J and DBA/2J-Atg4b littermates, DBA/2J-Atg4b mice do not develop glaucomatous IOP elevation. Atg4b deficiency also protected against glaucomatous IOP elevation in the experimental TGFβ2 chronic ocular hypertensive model. Atg4 deletion did not compromise RGC or optic nerve survival in Atg4b mice. Moreover, our results indicate a protective role of autophagy deficiency against RGC death and ON atrophy in the hypertensive DBA/2J-Atg4b mice. Together, our data suggests a pathogenic role of autophagy activation in ocular hypertension and glaucoma.
Topics: Animals; Mice; Mice, Inbred DBA; Glaucoma; Ocular Hypertension; Autophagy; Disease Models, Animal; Retinal Ganglion Cells
PubMed: 37620383
DOI: 10.1038/s41419-023-06086-3 -
Journal of AAPOS : the Official... Oct 2022To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of...
PURPOSE
To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of glaucoma.
METHODS
This was a retrospective sequential cohort study of children <18 years diagnosed as GS between 2013 and 2019, based on clinical (C-GS) and CGRN (CGRN-GS) criteria. Children with penetrating ocular trauma, steroid-response, treated ocular hypertension, and glaucoma at presentation were excluded. Outcomes included glaucoma, treated ocular hypertension, nonglaucomatous cupping (pseudoglaucomatous or physiologic), or persistent GS. Secondary outcomes were characteristics of children who progressed to glaucoma.
RESULTS
A total of 887 children (mean age, 9.3 ± 4.7 years) were diagnosed as C-GS, because of optic nerve appearance (83%), family history (25%), ocular hypertension (15%), periocular lesion (4% [eg, Sturge-Weber]), blunt-trauma history (3%), ocular anomaly (2%), and systemic/genetic syndrome (1.5%). Outcomes among 487 children with one or more follow-up visits (mean, 1.7 ± 1.6 years) included 14 (3%) with glaucoma, 98 (20%) with physiologic cupping, 50 (10%) with prematurity-associated cupping, and 1 (0.2%) with treated ocular hypertension; 324 (67%) remained GS. Of children lost to follow-up, 116 (29%) were suspected physiologic or pseudoglaucomatous. Glaucoma diagnosis occurred at a mean age of 8.4 ± 5.5 years, based on elevated intraocular pressure (IOP; 79%), optical coherence tomography changes (43%), disk changes (21%), or field defects (14%). Risk factors for glaucoma were baseline IOP of ≥24 (P = 0.01) and periocular lesion (P = 0.008). Results from 773 children who met CGRN-GS criteria were similar.
CONCLUSIONS
Risk of conversion to glaucoma diagnosis among children with glaucoma suspect status appears low. Baseline cup:disk ratio and family history of glaucoma were not predictive of glaucoma diagnosis. Baseline IOP >24 and presence of a periocular lesion carry higher risk.
Topics: Child; Humans; Child, Preschool; Adolescent; Intraocular Pressure; Retrospective Studies; Cohort Studies; Ocular Hypertension; Glaucoma
PubMed: 36113699
DOI: 10.1016/j.jaapos.2022.05.010 -
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 -
Investigative Ophthalmology & Visual... Feb 2022Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating... (Review)
Review
Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.
Topics: Animals; Aqueous Humor; Consensus; Disease Models, Animal; Glaucoma; Intraocular Pressure; Mice; Ocular Hypertension; Tonometry, Ocular; Trabecular Meshwork
PubMed: 35129590
DOI: 10.1167/iovs.63.2.12 -
Graefe's Archive For Clinical and... Jan 2024PURPOSE : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda) with... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
PURPOSE : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT).
METHODS
MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3.
RESULTS
Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%).
CONCLUSIONS
Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.
Topics: Humans; Glaucoma, Open-Angle; Timolol; Bimatoprost; Latanoprost; Prospective Studies; Intraocular Pressure; Antihypertensive Agents; Tonometry, Ocular; Ocular Hypertension; Ophthalmic Solutions; Treatment Outcome; Double-Blind Method; Benzoates; beta-Alanine
PubMed: 37615697
DOI: 10.1007/s00417-023-06192-0 -
BMJ Open Ophthalmology Dec 2023This study aims to determine the incidence and risk of open-angle glaucoma or ocular hypertension (OHT) following ocular steroid injections using healthcare claims data.
BACKGROUND/AIMS
This study aims to determine the incidence and risk of open-angle glaucoma or ocular hypertension (OHT) following ocular steroid injections using healthcare claims data.
METHODS
We retrospectively reviewed deidentified insurance claims data from the IBM MarketScan Database to identify 19 156 adult patients with no prior history of glaucoma who received ocular steroid injections between 2011 and 2020. Patient demographics and steroid treatment characteristics were collected. Postinjection glaucoma/OHT development was defined as a new diagnosis of glaucoma/OHT, initiation of glaucoma drops, and/or surgical or laser glaucoma treatment. Cox proportional hazards models were used to determine the risk of glaucoma/OHT development within 5 years after first steroid injection.
RESULTS
Overall, 3932 (20.5%) patients were diagnosed with new glaucoma/OHT, 3345 (17.5%) started glaucoma drops and 435 (2.27%) required a laser or surgical glaucoma procedure within 5 years of first steroid injection. Triamcinolone subconjunctival injections were associated with a lower risk of glaucoma/OHT development than retrobulbar or intravitreal steroid injections (p<0.001, HR 0.68, 95% CI 0.59 to 0.79), whereas the 0.59 mg fluocinolone acetonide intravitreal implant had the highest risk of glaucoma/OHT development (p=0.001, HR 2.01, 95% CI 1.34 to 3.02). The risk of glaucoma/OHT development was also higher for patients receiving multiple steroid injections (p<0.001), with the largest increase in risk occurring after three total steroid injections.
CONCLUSION
Patients receiving ocular steroid injections are at risk of developing glaucoma/OHT, even with no prior glaucoma/OHT diagnosis or treatment. Patients should be closely monitored for the development of glaucoma following ocular steroid injections, particularly in the setting of intravitreal and/or repeated steroid administration.
Topics: Adult; Humans; Intraocular Pressure; Glaucoma, Open-Angle; Retrospective Studies; Intravitreal Injections; Ocular Hypertension; Glaucoma; Vitreous Body; Steroids
PubMed: 38135349
DOI: 10.1136/bmjophth-2023-001508 -
Archivos de La Sociedad Espanola de... Aug 2021To determine the prevalence and factors associated with the development of ocular hypertension and glaucoma, in patients undergoing penetrating keratoplasty, in the Eye...
OBJECTIVE
To determine the prevalence and factors associated with the development of ocular hypertension and glaucoma, in patients undergoing penetrating keratoplasty, in the Eye Clinic of the city of Bogotá.
METHOD
A retrospective cross-sectional study was conducted, and 130 eyes of patients undergoing penetrating keratoplasty were analyzed at the Eye Clinic in Bogotá, between January 2015 and August 2018. Demographic and clinical data were obtained, and it was determined by bivariate analysis, the association factors and the prevalence of the pathology under study.
RESULTS
Prevalence of ocular hypertension was 27.69% and glaucoma 10%. Average age 48.93 ± 18.63 years; higher frequency of presentation in men (61.5%). Statistically significant association factors were male sex (PR 2.59), presence of peripheral anterior synechiae (PR 1.83), history of trauma (PR 2.16), prior PK (PR 2.10) and graft failure (PR 2.04). Post-KP glaucoma only had statistically significant association with bullous keratopathy (PR 2.76).
CONCLUSIONS
Ocular hypertension and glaucoma had a high prevalence after penetrating keratoplasty, and the association factors were similar to those reported in other international studies. Knowing these factors, allows focusing surveillance and treatment in these patients to avoid blindness due to damage of the optic nerve or corneal graft.
Topics: Cross-Sectional Studies; Glaucoma; Humans; Keratoplasty, Penetrating; Male; Middle Aged; Ocular Hypertension; Prevalence; Retrospective Studies; Risk Factors
PubMed: 34340779
DOI: 10.1016/j.oftale.2020.09.019 -
Journal of Glaucoma Sep 2020Glaucoma remains the world's leading cause of irreversible blindness and though intraocular pressure (IOP) is the most prevalent risk factor and only reliable... (Review)
Review
Glaucoma remains the world's leading cause of irreversible blindness and though intraocular pressure (IOP) is the most prevalent risk factor and only reliable therapeutic target, a number of systemic disease associations have been reported. Metabolic syndrome (MetS) is a constellation of findings that includes systemic hypertension, abdominal obesity, glucose intolerance, and dyslipidemia. MetS is becoming increasingly common worldwide, with prevalence up to 40% in some countries. Not only is MetS a significant cause of morbidity, but it is also associated with an increase in all-cause mortality. Reports have been conflicting regarding the association of individual components of MetS, including systemic hypertension and diabetes, with elevated IOP or glaucoma. However, though limitations in the existing literature are present, current evidence suggests that MetS is associated with IOP as well as glaucoma. Additional studies are needed to clarify this association by incorporating additional metrics including assessment of central corneal thickness as well as optic nerve structure and function. Future studies are also needed to determine whether lifestyle modification or systemic treatment of MetS could reduce the incidence or progression of glaucoma.
Topics: Glaucoma; Humans; Intraocular Pressure; Metabolic Syndrome; Ocular Hypertension; Risk Factors; Tonometry, Ocular
PubMed: 32618805
DOI: 10.1097/IJG.0000000000001593