Risk Of Glaucoma Research Articles

TIMELY REFRACTIVE LANCESECTOMY SHOULD BE CONSIDERED AS A PROPHYLACTIC TREATMENT FOR OPENCLOSURE GLAUCOMA IN PATIENTS WITH MULTIPLE CYSTS OF THE IRIDOCILIARY PROCESSES

This article presents a clinical case of bilateral ophthalmic hypertensin a patient at the presbyopic age with cysts of iridocyliary processes. A bilateral lentectomy was carried out with the implant of multifocal IOLs for refractive purposes. To evaluate the сlinico-functional performance of the treatment, an ultrasound biopsy of the anterior segment of the eye was performed and a hydrodynamic assessment was carried out before and after the operation. The remote results of the treatment allow to conclude that timely extraction of native lens can significantly reduce the risk of open-closure glaucoma in patients with cysts of iridocyliary processes.

Research progress on the pathogenesis of PM2.5 in ophthalmic diseases

PM2.5 is a fine particulate matter with an aerodynamic equivalent diameter of less than or equal to 2.5 μm, and it is the primary pollutant that causes haze. In recent years, numerous research results have shown that PM2.5 is associated with various ophthalmic diseases and its pathogenic mechanism is complex. It can disrupt the homeostasis of the tear film and the function of the meibomian glands, leading to dry eye; increase the risk of allergic and other types of conjunctivitis; may cause blepharitis; affect the homeostasis of the corneal epithelium and promote the development of keratopathy; the correlation with cataract is controversial; it is related to the risk of glaucoma; it is associated with age-related macular degeneration; it may also indirectly promote diabetic retinopathy. Prevention and control measures include controlling the level of PM2.5, strengthening publicity and screening, reducing going out and wearing goggles, etc. PM2.5 is closely related to ophthalmic diseases, but its specific pathogenic mechanism still requires more research to explore.

The impact of different forms of exercise on intraocular pressure, blood flow, and the risk for primary open angle glaucoma.

Primary open angle glaucoma (POAG) is a chronic disease characterized by progressive optic nerve damage and irreversible loss of vision, often diagnosed at late stages. Elevated intraocular pressure (IOP) is the major risk factor for its onset and progression while older age, myopia, genetic factors, blood pressure (BP), and reduced ocular blood flow (OBF) have also been linked to the disease. Different forms of exercise are known to have significant, but variable, effects on IOP, BP, ocular perfusion pressure (OPP), OBF and oxygen metabolism, and ultimately the risk for development and progression of POAG. While population-based studies lack agreement regarding the relationship between exercise and POAG status, data suggests that resistance training causes a short-term increase in IOP, BP, and OPP. Conversely, aerobic exercise has been shown to cause a short-term decrease in IOP and increase in BP and OPP. Research also suggests that following an exercise program over an extended period may lead to a long-term decrease in IOP, however its cessation results in a prompt return to baseline levels. Data suggests normal vascular autoregulation ensures minimal change in OBF following extended exercise unless OPP rises ∼70% above baseline. Although exercise may alter IOP, BP, and OBF, both acutely and chronically, it is currently uncertain if physical activity significantly alters risk for the onset and progression of POAG.

The Development and Validation of a Glaucoma Health Score for Glaucoma Screening Based on Clinical Parameters and Optical Coherence Tomography Metrics

Background/Objectives: This study aims to develop and validate a Glaucoma Health Score (GHS) that incorporates multiple individual glaucoma risk factors to enhance glaucoma detection in screening environments. Methods: The GHS was developed using a retrospective dataset from two clinical sites, including both eyes of glaucoma patients and controls. The model incorporated age, central corneal thickness, intraocular pressure, pattern standard deviation from a visual field threshold 24-2 test, and two parameters from an optical coherence tomography (OCT) test: the average circumpapillary retinal nerve fiber layer thickness and the minimum thickness of the six sectors of the macular ganglion cell plus the inner plexiform layer. The GHS was then validated in two independent datasets: one from primary care sites using Maestro OCT data (test dataset 1) and another from an academic center using DRI OCT Triton (test dataset 2). Results: Both eyes of 51 glaucoma patients and 67 controls were included in the development dataset. Setting the GHS cutoff at 75 points out of 100, test dataset 1, which comprised 41 subjects with glaucoma and 41 healthy controls, achieved an area under the receiver operating characteristic curve (AUROC) of 0.98, with a sensitivity of 71% and specificity of 98%; test dataset 2, which included 53 patients with glaucoma and 53 healthy controls, resulted in an AUROC of 0.95, with a sensitivity of 75% and specificity of 96%. A decision curve analysis across all datasets demonstrated a higher net benefit for the GHS model compared to individual OCT parameters. Conclusions: The GHS offers a feasible, standardized approach for early detection of glaucoma, providing strong specificity and acceptable sensitivity, with clear decision-making benefits in screening settings.

Higher risk and earlier onset glaucoma in Cushing's syndrome.

Glaucoma incidence in patients with endogenous Cushing's syndrome (CS) has never been established. We aim to assess the risk for glaucoma among CS patients compared to controls and determine the age of disease onset. A nationwide retrospective matched-cohort study of patients with endogenous CS diagnosed between 2000 and 2023. Patients with CS were matched in a 1:5 ratio, with a control group individually matched for age, sex, socioeconomic status and body mass index. Main outcomes were the incidence of glaucoma and disease onset. A total of 609 patients [396 women (65%); mean age 48.1 ± 17 years] were included in the CS group and 3018 controls. Follow-up duration was 14.6 years (IQR 9.8-20.2) for the study group. The aetiology of hypercortisolism was divided into pituitary (259, 42.6%), adrenal (206, 33.8%) and unconfirmed aetiology (144, 23.6%) patients. At baseline, 44 (7.2%) CS patients had a diagnosis of glaucoma, compared with 151 (5%) controls. The overall risk for glaucoma was 74% higher in patients with CS compared with matched controls (hazard ratio = 1.74, p = 0.002). Patients with CS who developed glaucoma were younger (mean age of 62 ± 14.7 years) than controls (mean ± SD age, 62 ± 14.7 years), (p = 0.02). The overall risk for glaucoma in CS was high for both patients in remission and patients with persistent hypercortisolism (p = 0.048). Patients with active hypercortisolism experienced an earlier glaucoma onset (82.1 ± 88.0 months). Endogenous CS is associated with increased risk for glaucoma regardless of remission status and develops at a younger age compared with the general population.

Associations of human blood metabolome with optic neurodegenerative diseases: a bi-directionally systematic mendelian randomization study

BackgroundMetabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited.MethodsTwo-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies.ResultsAll the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases.ConclusionsBy integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.

Sodium-glucose cotransporter 2 inhibitors and glaucoma in patients with type 2 diabetes

Purpose: Pleiotropic cardiovascular benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been demonstrated in patients with type 2 diabetes mellitus due to vascular remodeling effects. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study is to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes. DesignTarget trial emulation using a population-based, propensity score-matched clinical cohort approach. MethodsSetting: Population-based, propensity score-matched clinical cohort study. Study Population: Adults with type 2 diabetes in the United States who newly initiated treatment with SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP4i), or glucagon-like peptide-1 receptor agonists (GLP1RA) between 2013 and 2023. After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Participants were matched based on age at index, race and sex, comorbidities, and concomitant use of medications. ExposureTreatment with SGLT2i for type 2 diabetes. Main Outcome Measure(s)Incidence of new-onset glaucoma and its subtypes after initiation of SGLT2i, DPP4i, or GLP1RA. Subgroup analyses were performed to demonstrate the effect of individual SGLT2i on incident glaucoma. ResultsPatients on SGLT2i compared to those on DPP4 had a lower risk of glaucoma (HR: 0.815, 95% confidence interval [CI]: 0.794, 0.837), including open-angle glaucoma (HR: 0.755, 95%CI: 0.729, 0.781) and primary angle-closure glaucoma (HR: 0.592, 95%CI: 0.540, 0.650). Among all SGLT2i, ertugliflozin (HR: 0.668, 95%CI: 0.512, 0.871) was associated with the lowest risk of glaucoma, followed by empagliflozin (HR: 0.727, 95%CI: 0.696, 0.759), then dapagliflozin (HR: 0.814, 95%CI: 0.774, 0.855). The protective effect of SGLT2i on glaucoma was validated when compared with GLP1RA (HR: 0.932, 95%CI: 0.906, 0.959). Conclusions: Patients on SGLT2i, especially ertugliflozin and empagliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i, an association that was less robust but significant in a sensitivity analysis using GLP1RA as the active comparator. SGLT2i had a protective effect for both open-angle glaucoma and angle-closure glaucoma.

Novel postzygotic RASA1 mutation in a patient with Parkes Weber syndrome: A case report and literature review.

Not only germline but also postzygotic mutations in the RASA1 or EPHB4 genes can lead to capillary malformation-arteriovenous malformation (CM-AVM) syndrome. As it is not always possible to clinically distinguish between constitutional variants and postzygotic mosaicism, a sufficiently high sequencing depth must be used in genetic diagnostics to detect both. Capillary malformation-arteriovenous malformation (CM-AVM) syndrome, with or without Parkes Weber syndrome, is a rare autosomal dominant disease caused by pathogenic RASA1 or EPHB4 variants. Up to 80% of CM-AVM cases have an affected parent. Gene panel sequencing was performed for a 4-year-old girl with multiple CMs, two capillary stains on the left leg, and associated overgrowth of the second toe. We also reviewed published cases with mosaic RASA1 and EPHB4 mutations. A mosaic RASA1 loss-of-function mutation was detected with a variant allele frequency (VAF) of 20% in the blood and oral epithelial cells of the index patient. The literature review illustrates that the severity of the clinical phenotype does not correlate with the VAF. We also identified a germline nonsense variant in the patient's TEK gene. However, inactivating TEK variants do not cause a vascular phenotype but can confer an increased risk for primary congenital glaucoma with variable expressivity. The case presented here illustrates that the choice of the sequencing depth of a diagnostic next-generation sequencing test for CM-AVM patients should always take mosaicism into account and that a good knowledge of the sequenced genes and associated disease mechanisms is necessary for adequate genetic counseling.

Amlodipine increases risk of primary open-angle glaucoma

BackgroundThe use of calcium channel blockers is associated with primary open-angle glaucoma (POAG) in a statistically meaningful but minor way. In general, those who had received calcium channel blocker medication were at a 23% increased risk of developing glaucoma in comparison to those who had never taken the antihypertensive drugs. We wished to confirm this association and examine POAG genes that might be involved, since the genetics has not yet been analyzed.MethodsWe used MedWatch and UK Biobank data to evaluate the effects of amlodipine on POAG and intraocular pressure (IOP). We analyzed three POAG-associated single-nucleotide polymorphisms: rs9913911, an intron variant in growth arrest-specific 7 (GAS7), one of the genes that influences IOP; rs944801, an intron variant within CDKN2B-AS1, and rs2093210, an intron variant within SIX6, known to be associated with vertical cup-disc ratio, an important optic nerve head parameter that is often used to define or diagnose glaucoma.ResultsAmlodipine use in MedWatch doubled the prevalence of POAG, from 0.0805 to 0.177%, a small but significant increase. Multivariate analysis by logistic regression of UK Biobank data revealed that POAG risk was significantly increased with age, male sex, major alleles of rs9913911 (GAS7) and rs944801 (CDKN2B-AS1), and minor allele of rs2093210 (SIX6). Amlodipine increased POAG risk by 16.1% (P = 0.032). Amlodipine has not been associated with increased IOP. We confirmed this lack of association and in addition found that GAS7, associated with IOP, was not associated with POAG risk and amlodipine. But CDKN2B-AS1 and SIX6, POAG genes not associated with IOP, were associated with POAG and amlodipine.ConclusionsAmlodipine, a frequently prescribed drug and first line treatment for hypertension, has a potentially hazardous relationship with POAG. Knowledge of this link can guide the prescribing of alternate drugs for hypertensive individuals who have glaucoma or are at risk for it. Diuretics and β-blockers are not associated with POAG or increased IOP and could be substituted for amlodipine in hypertensive patients at risk POAG.Trial registrationNone.Graphical

Validating and updating the OHTS-EGPS model predicting 5-year glaucoma risk among ocular hypertension patients using electronic records

ObjectiveTo validate and update the OHTS-EGPS model predicting risk of conversion from OHT to glaucoma using electronic medical records (EMR). DesignEvaluation and update of a risk prediction algorithm using EMRs and linked visual field (VF) tests. ParticipantsNewly diagnosed OHT patients attending hospital glaucoma services in England. Inclusion criteria: IOP 22-32 mmHg (either eye); normal baseline VF test, defined as Glaucoma Hemifield Test (GHT) ‘within normal range’ in a reliable VF test; at least two VF tests in total; no significant ocular co-morbidities. MethodsRisk factors: age, ethnicity, sex, IOP, vertical cup-to-disc ratio, central corneal thickness, VF pattern standard deviation, family history of glaucoma, systemic hypertension, diabetes mellitus, glaucoma treatment. Glaucoma conversion was defined as two consecutive and reliable VF tests with GHT ‘outside normal limits’ and/or need for glaucoma surgery. For validation, the OHTS-EGPS model was applied to predict a patient’s risk of developing glaucoma in 5 years. In the updating stage, the OHTS-model was re-fitted by re-estimating the baseline hazard and regression coefficients. The updated model was cross-validated and several variants were explored. Main Outcome MeasuresMeasures of discriminative ability (c-index) and calibration (calibration slope) were calculated and pooled across hospitals using random effects meta-analysis. ResultsFrom a total of 138,461 patients from ten hospital glaucoma services in England 9030 patients with OHT fitted the inclusion criteria. A total of 1530 (16.9%) patients converted to glaucoma during this follow-up period. The OHTS-EGPS model provided a pooled c-index of 0.61 (95% confidence interval: 0.60, 0.63), ranging from 0.55 to 0.67 between hospitals. The pooled calibration slope was 0.45 (0.38, 0.51), ranging from 0.25 to 0.64 among hospitals. The overall re-fitted model performed better than the OHTS-EGPS model, with a pooled c-index of 0.67 (0.65, 0.69), ranging from 0.65 to 0.75 between hospitals. ConclusionsWe performed an external validation of the OHTS-EGPS model in a large English population. Re-fitting the model achieved modest improvements in performance. Given the poor performance of the OHTS-EGPS model in our population, one should use caution in its application to populations that differ from those in the OHTS and EGPS.

Nocturnal Artificial Light Exposure in Expectant Mothers and Risk of Congenital Glaucoma

Abstract Background While the impact of light pollution on human health is gaining recognition, its role in transmitting the effects of maternal exposure to the fetus remains unclear. This study is to investigate the association between exposure to artificial light at night (ALAN) during pregnancy and risk of congenital glaucoma. Methods All birth cohorts spanning from 2008 to 2011 in urban areas of South Korea, comprising over 90% of the total population, were identified in the Korean National Health Insurance database. Average levels of ALAN at the residential addresses of mothers during pregnancy were estimated using time-varying satellite data for a composite view of persistent night-time illumination at ∼1 km2 scale.The odd ratios (ORs) and 95% confidence intervals (CIs) of the association between residential ALAN and risk of congenital glaucoma - was computed using logistic regression. These calculations were adjusted for socio-demographic factors and area-level risk factors (night-time traffic noise and particulate matter with an aerodynamic diameter ≤ 10 μm). Results A total of 745,458 mother-father-child trios (mean [SD] age of the mothers, 32.4 [3.8] years; 387,275 [52.0%] boy) were included in the study. In fully adjusted models, an IQR (21.8 nW/cm2/sr) increase in ALAN level was associated with an OR of 1.12 (95% CI: 1.05, 1.19) for incident congenital glaucoma. The exposure-response curve demonstrated an upward slope with a threshold at approximately 62 nW/cm2/sr. Conclusions In this nationwide population-based case-control study, higher levels of residential ALAN during pregnancy were associated with increased risk of congenital glaucoma. Future studies with more detailed information on exposure, individual adaptive behaviors and potential mediators are warranted. Key messages • This study indicates an association between elevated levels of ALAN exposure in pregnant women and a heightened risk of congenital glaucoma in their offspring. • These results are consistent with a growing body of evidence underscoring the detrimental effects of ALAN on health, reinforcing its potential role as a risk factor for congenital glaucoma.

The Association between Intermittent Fasting and Glaucoma.

To examine the association between intermittent fasting ("breakfast skipping") and glaucoma in the National Health and Nutrition Examination Survey (NHANES). Retrospective, cross-sectional study of adult participants of the 2005-2008 NHANES aged 40 years and older. Intermittent fasting was defined as skipping breakfast on both days of the NHANES dietary interview. Glaucoma was defined by 1) self-reported glaucoma diagnosis, 2) cup-to-disc (CDR) ≥0.6 in at least one eye, and 3) Possible, probable or definite glaucoma based on clinical judgment of retinal imaging of individuals with CDR ≥0.6 in at least one eye. Covariates included age, sex, race/ethnicity, body mass index, blood pressure, and waist circumference. Chi-Square and Fisher Exact Test were used for categorical variables and t-test for continuous variables. All data were weighted based on the NHANES multistage sampling design. The population included 7,081 individuals ≥40 years old, of whom 946 (13.4%) reported skipping breakfast on both interview days; 482 (6.8%) individuals self-reported glaucoma diagnosis, 549 (7.8%) individuals had glaucoma based on CDR ≥0.6 and 343 (6.0%) individuals had glaucoma based on clinical judgment. Diagnosis of glaucoma by all definitions was associated with older age and Black or Latinx/Hispanic ethnicity (P=0.004) but was not associated with intermittent fasting status (P=0.151). In the 2005-2008 NHANES population, intermittent fasting, defined as breakfast skipping, was not associated with decreased risk of glaucoma diagnosis overall. Further studies are needed to examine the potential effects of intermittent fasting on glaucoma risk.

Drug-associated glaucoma: A real-world study based on the Food and Drug Administration adverse event reporting system database.

This study aims to assess the risk of drug-associated glaucoma and track its epidemiological characteristics using real-world data. Adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2023 were analysed. Disproportionality analysis and the Bayesian Confidence Propagation Neural Network algorithm were used. The study classified drugs associated with glaucoma, assessed risk levels, and compared drug-induced times across different categories. Eight hundred and five drugs were linked to glaucoma in the FAERS database. Disproportionality analysis identified 46 drugs with significant risk, mainly adrenergic medications (clobetasol propionate, fluocinolone acetonide), antihypertensives (hydrochlorothiazide), insulin (insulin human), anticholinergics (umeclidinium, darifenacin), VEGF inhibitors (brolucizumab, faricimab), and psychotropics (topiramate, ziprasidone). The top three high-risk drugs were clobetasol propionate, umeclidinium, and fluocinolone acetonide. The shortest drug-induced times were observed with indacaterol, salmeterol, and umeclidinium. Anticholinergic medications had the shortest drug-induced time among all categories. Females (62.5%) and the elderly (average age 63.5 ± 16.8 years) were predominantly affected. Reports of drug-associated glaucoma increased over the years. Preventing drug-associated glaucoma is more effective than treatment. Identifying the risk and drug-induced times of systemic and ophthalmic drugs can reduce occurrence risk. Clinical practitioners should be vigilant and inform patients of these risks.

Lifestyle modifications and environmental risk factors for glaucoma

Purpose of review To summarize recent evidence about the association between different lifestyle modifications and environmental risk factors and glaucoma. Recent findings Incorporating moderate exercise into the routine of glaucoma patients may help slow the progression of the condition. However, caution should be taken when using swim goggles, and it may be advisable to avoid certain yoga positions and heavy weight-lifting exercises, as they have been linked to intraocular pressure (IOP) spikes and potential risks for glaucoma patients. Various relaxation techniques may lower IOP. The evidence remains inconclusive about the association between vitamins intake and glaucoma. Dietary nitric oxide has been associated with a lower risk of glaucoma. Higher smoking intensity has been linked to faster visual field decline and retinal nerve fiber layer thinning. Additionally, there is currently insufficient evidence to support the use of marijuana in managing glaucoma, with side effects outweighing the proposed benefits. A significant association has been found between air pollutants and ganglion cell layer thinning, as well as a greater burden of glaucoma. Summary Lifestyle and environmental factors are increasingly recognized as significant contributors to glaucoma development and progression. These modifications should be integrated into a comprehensive treatment approach alongside medications or surgical interventions.

Controlled Elevation of Intraocular Pressure (CEI) Glaucoma Model in Rats.

Experimental elevation of intraocular pressure (IOP), a major glaucoma risk factor, has been a mainstay of research into mechanisms of glaucomatous optic nerve damage for decades. Methods that produce sustained IOP elevation can mimic the chronic nature of glaucoma and produce optic nerve damage. However, the pressure course for individual animals can be variable, unpredictably high at times, and difficult to monitor with current tonometry methods. All of this can complicate correlations of pressure history with axonal injury. An alternative is to control the extent and duration of IOP elevation over a period of several hour-long enough to produce axonal injury and gene expression changes within the optic nerve head that may indicate cellular mechanisms of glaucomatous optic nerve damage. The prolonged general anesthesia that this requires does have the potential to reduce systemic blood pressure, which may contribute to axonal injury in the face of elevated IOP. This chapter will describe our Controlled Elevation of IOP (CEI) model in laboratory rats. We will include methods for applying this to several animals at a time, as well as how to maintain blood pressure, oxygenation, and body temperature to ensure that the resulting injury and tissue events reflect the effects of elevated IOP on optic nerve tissues and not simply reduced ocular perfusion and ischemia.

Association Between Glaucoma and Brain Structural Connectivity Based on Diffusion Tensor Tractography: A Bidirectional Mendelian Randomization Study.

Glaucoma is a neurodegenerative ocular disease that is accompanied by cerebral damage extending beyond the visual system. Recent studies based on diffusion tensor tractography have suggested an association between glaucoma and brain structural connectivity but have not clarified causality. To explore the causal associations between glaucoma and brain structural connectivity, a bidirectional Mendelian randomization (MR) study was conducted involving glaucoma and 206 diffusion tensor tractography traits. Highly associated genetic variations were applied as instrumental variables and statistical data were sourced from the database of FinnGen and UK Biobank. The inverse-variance weighted method was applied to assess causal relationships. Additional sensitivity analyses were also performed. Glaucoma was potentially causally associated with alterations in three brain structural connectivities (from the SN to the thalamus, from the DAN to the putamen, and within the LN network) in the forward MR analysis, whereas the inverse MR results identified thirteen brain structural connectivity traits with a potential causal relationship to the risk of glaucoma. Both forward and reverse MR analyses satisfied the sensitivity test with no significant horizontal pleiotropy or heterogeneity. This study offered suggestive evidence for the potential causality between the risk of glaucoma and brain structural connectivity. Our findings also provided novel insights into the neurodegenerative mechanism of glaucoma.

Association of Ambient Air Pollution Exposure With Incident Glaucoma: 12-Year Evidence From the UK Biobank Cohort.

Glaucoma is the leading cause of irreversible blindness worldwide. Despite growing concerns about air quality and its impact on ocular health, there remains a knowledge gap regarding the long-term association between air pollution and glaucoma risk. This study investigates the relationship between exposure to ambient air pollution and incidence of glaucoma. In this prospective study, we used land use regression models to estimate levels of various air pollutants, including fine particulate matter (PM2.5), PM2.5 absorbance, PM2.5-10, PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). Incidents of glaucoma were ascertained through routinely collected hospital admission records. Multivariate Cox proportional hazards models were used to examine the associations between air pollution exposure and glaucoma incidence, adjusting for potential confounding sociodemographic, physical, and lifestyle factors. Data from 481,113 participants were included. Over a median follow-up of 12.8 years, 9224 incident cases of glaucoma were identified. In the maximally adjusted model, per interquartile range increase in PM2.5 was associated with a 3% greater risk of developing glaucoma (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.048). Participants in the highest quartile had a 10% increased risk of developing glaucoma compared to those in the lowest quartile (HR = 1.10, 95% CI = 1.03 to 1.17, P = 0.005). Higher levels of exposure to ambient air pollutants, particularly PM2.5, are associated with an increased risk of developing glaucoma. These results highlight the potential public health impact of ambient air pollution on glaucoma risk and underscore the urgent need for further research into targeted environmental interventions in this domain.

Relationships between Frailty and the Risk of Glaucoma in Middle-aged and Older Adults

PurposeIncreased frailty in older individuals increases health risks, but its relationship with glaucoma, the leading cause of irreversible blindness in middle-aged and older adults, is unclear. We investigated the association between frailty and glaucoma in a large-scale representative sample and explored possible causal relationships. DesignCombined cross-sectional and Mendelian randomization (MR) study. ParticipantsIn the cross-sectional analysis, we included 5744 participants of the US National Health and Nutrition Examination Surveys 2005–2008 aged ≥40. For the MR analysis, frailty genome-wide association study (GWAS) data were sourced from a UK Biobank and TwinGen meta-analysis, and GWAS data on glaucoma subtypes were derived from FinnGen. MethodsAccording to the 49-item frailty index, we classified participants into nonfrail (≤0.10), prefrail (0.10−0.21), and frail (>0.21) groups. Using survey-weighted logistic regression models adjusted for multiple covariates, we explored the association between frailty and glaucoma. We further assessed causation using MR. Main Outcome MeasuresThe associations between different levels of frailty (nonfrail, prefrail, and frail) and glaucoma, as well as causal relationships between genetically predicted frailty and various subtypes of glaucoma (primary open-angle glaucoma, primary angle-closure glaucoma, normotensive glaucoma, exfoliation glaucoma, and suspected glaucoma). ResultsAfter adjusting for covariates, higher frailty levels were significantly associated with glaucoma in frail individuals (odds ratio [OR]=1.83, 95% confidence interval [CI]=1.05–3.19, P=0.036) but not prefrail (OR=1.90, 95% CI=0.99–3.64, P=0.052). The association was significantly stronger among male participants (P interaction=0.042). The variation in the association between frailty and glaucoma did not reach statistical significance across age groups (P interaction=0.575) or race groups (P interaction=0.092). MR revealed that genetically predicted frailty was linked to greater risks for primary open-angle glaucoma (OR=1.67, 95% CI=1.24–2.25, P=0.001), primary angle-closure glaucoma (OR=2.78, 95% CI=1.48–5.20, P=0.001), exfoliation glaucoma (OR=1.70, 95% CI=1.18–2.43, P=0.004), and suspected glaucoma (OR=1.74, 95% CI=1.30–2.34, P<0.001), but not for normotensive glaucoma (OR=1.01, 95% CI=0.61–1.68, P=0.956). ConclusionsOur study revealed an association between frailty and increased glaucoma risk and emphasized the significance of glaucoma screening in frail individuals. Targeted healthcare strategies can help prevent or delay irreversible blindness among middle-aged and older adults.

Serum lipid and lipoprotein profiles and their association with intraocular pressure in primary open-angle glaucoma: an observational cross-sectional study in the Chinese population

BackgroundGlaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP).MethodsThe study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG.ResultsAfter adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 – -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 – -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 – -0.0008) in patients with POAG.ConclusionsSignificantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk.

Exploration of potential drug targets for Glaucoma by plasma proteome screening

BackgroundGlaucoma is the leading cause of irreversible blindness. However, the current available treatment methods are still unsatisfactory. Therefore, the exploration of new drug targets for the treatment of glaucoma is of paramount importance. MethodsWe conducted two-sample Mendelian randomization (MR) using plasma protein quantitative trait loci (pQTL) data from two datasets (n = 734, n = 4907) and their instrumental variables to investigate the causal relationship between plasma proteins and glaucoma. The analysis was validated by replacing the exposure and outcome cohorts. Additionally, we utilized protein-protein interaction networks to assess the associations between these potential drug targets and existing drug targets. ResultsThrough two-sample Mendelian randomization analysis, we identified causal relationships between Glaucoma and the following proteins: AZU1, OBP2B, ENPP5, INPP5B, KREMEN1, LYPLAL1, and PTPRJ. External validation confirmed the protective effect of LYPLAL1 on Glaucoma, while ENPP5, KREMEN1, and PTPRJ increased the risk of Glaucoma. Reverse MR and Steiger filtering did not indicate any reverse causal associations of the aforementioned proteins with Glaucoma. ConclusionOur study demonstrates a causal impact of ENPP5, KREMEN1, PTPRJ, and LYPLAL1 on the risk of Glaucoma. These findings suggest that these four proteins may serve as promising drug targets for Glaucoma treatment. SignificanceCurrently, the pharmacological treatment of glaucoma primarily focuses on lowering intraocular pressure, which has its limitations. Targeted therapy is a personalized treatment approach that aims to inhibit or block the development and progression of diseases such as cancer and inflammation by selectively acting on specific biomolecules or signaling pathways. Our research employs a two-sample Mendelian randomization (MR) method, integrating a large amount of GWAS and pQTL data to perform MR analysis. This has enabled us to explore several plasma proteins as potential drug targets for glaucoma, providing direction and a research foundation for future investigations into glaucoma drug targets.