Impact of Social Vulnerability Index on the Development of Severe Visual Impairment or Blindness From Glaucoma.

PURPOSE: To evaluate whether geocoded social risk factor data predict the development of severe visual impairment or blindness due to glaucoma during follow-up using a large electronic health record (EHR) database. DESIGN: Cohort study. METHODS: Patients diagnosed with open-angle glaucoma (OAG) at a tertiary care institution. All eyes had glaucomatous visual field defects at baseline. Sociodemographic and ocular data were extracted from the EHR, including age, gender, self-reported race and ethnicity, insurance status, OAG type, prior glaucoma laser or surgery, baseline disease severity using Hodapp-Anderson-Parrish criteria, mean intraocular pressure (IOP) during follow-up, and central corneal thickness. Social vulnerability index (SVIndex) data at the census tract level were obtained using geocoded patient residences. Mixed-effects Cox proportional hazard models were completed to assess for the development of severe visual impairment or blindness during follow-up, defined as BCVA ≤ 20/200 at least at the last two clinic visits or standard automated perimetry (SAP) mean deviation (MD) ≤ -22dB confirmed on two tests. RESULTS: A total of 4,046 eyes from 2,826 patients met inclusion criteria and were followed for an average of 4.3 ± 2.2 years. Severe visual impairment or blindness developed in 79 eyes (2.0%) from 76 patients (2.7%) after an average of 3.4 ± 1.8 years, leading to an incidence rate of severe visual impairment or blindness of 0.5% per year. Older age (adjusted hazards ratio [HR] 1.36 per decade, P = .007), residence in areas with higher SVIndex (HR 1.56 per 25% increase, P < .001), higher IOP during follow-up (HR 3.01 per 5 mmHg increase, P < .001), and moderate or severe glaucoma at baseline (HR 7.31 and 26.87, P < .001) were risk factors for developing severe visual impairment or blindness. Concordance index of the model was 0.88. Socioeconomic, minority status/language, and housing type/transportation SVIndex themes were key contributors to developing severe visual impairment or blindness. CONCLUSIONS: Risk factors for developing glaucoma-related severe visual impairment or blindness included older age, elevated IOP during follow-up, moderate or severe disease at baseline, and residence in areas associated with greater social vulnerability. In addition to ocular risk factors, geocoded EHR data regarding social risk factors could help identify patients at high risk of developing glaucoma-related visual impairment.

The risk of open angle glaucoma in young adults with allergic diseases: a Nationwide cohort study.

This study investigated the potential associations between allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) and the development of primary open-angle glaucoma. We utilized authorized data from the Korean National Health Information Database (KNHID), which provides comprehensive medical claims data and information from the National Health Screening Program. We compared the baseline characteristics of subjects with and without allergic diseases and calculated the incidence and risk of glaucoma development. Cox proportional hazard regression analysis was used to determine the risk of glaucoma development in subjects with allergic diseases. A total of 171,129 subjects aged 20-39 with or without allergic diseases who underwent a general health examination between 2009 and 2015 were included. Subjects with allergic diseases exhibited a higher incidence of glaucoma compared to the control group. The hazard ratio (HR) of glaucoma onset was 1.49 and 1.39 in subjects with at least one allergic disease before and after adjusting for potential confounding factors, respectively. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development (aHR 1.73) after adjusting for confounders. Allergic rhinitis showed an increased risk for incident glaucoma after adjustment (aHR 1.38). Asthma showed the lowest but still increased risk for glaucoma (aHR 1.22). The associations were consistent in all subgroup analyses stratified by sex, smoking, drinking, exercise, diabetes, hypertension, dyslipidemia, or history of steroid. In conclusion, allergic diseases are associated with increased risk of glaucoma development. Among allergic diseases, atopic dermatitis showed the highest risk for glaucoma development followed by allergic rhinitis and asthma.

Epidemiology and Treatment of Patients With Primary Open Angle Glaucoma in Germany: A Health Claims Data Analysis.

PRCIS: Based on a large administrative database of German claims data, our study provides current estimates of the prevalence and incidence of primary open angle glaucoma (POAG) in Germany and describes selected outcomes for prevalent patients with POAG. PURPOSE: To estimate the prevalence and incidence of POAG in Germany, to describe the patient population in terms of comorbidity burden, routine care, and overall healthcare resource utilization (HCRU) and associated costs, and to describe treatment patterns over time in patients undergoing relevant laser procedures. MATERIALS AND METHODS: Based on anonymized German claims data, we carried out a retrospective, noninterventional study covering calendar years 2016-2021. RESULTS: For the adult German population (≥18 y), we estimated a POAG 1-year prevalence of 1.70% and a 1-year incidence of 0.17% in 2018; both increased with age, peaking in 80- to 89-year-olds. Prevalence and incidence were lower in 2020 (1.65% and 0.16%, respectively), the first year of the SARS-CoV-2 pandemic. Most patients solely received topical treatment. Most surgically treated patients underwent laser trabeculoplasty, followed by laser iridotomy, trabeculectomy, and filtration operations with implant. In patients undergoing laser trabeculoplasty, the treatment regimen was nearly unchanged in the second year after, compared with 2 years before the procedure. Multimorbidity was commonly observed; 75.5% of patients had arterial hypertension and 50.0% had disorders of lipoprotein metabolism and other lipidemias, compared with 60.1% and 39.2%, respectively, in an age- and sex-matched control sample. CONCLUSIONS: Our study provides insights into epidemiology and routine care of POAG in Germany and HCRU in prevalent patients. There was little change in treatment regimens in patients who underwent laser trabeculoplasty, 2 years after the procedure. Most patients were multimorbid highlighting the need for comprehensive care.

Assessment of Causality Between Diet-Derived Antioxidants and Primary Open-Angle Glaucoma: A Mendelian Randomization Study.

Purpose: This study aimed to investigate the genetic causal relationships among diet-derived circulating antioxidants, primary open-angle glaucoma (POAG), and glaucoma-related traits using two-sample Mendelian randomization (MR). Methods: Genetic variants associated with diet-derived circulating antioxidants (retinol, ascorbate, ß-carotene, lycopene, α-tocopherol, and γ-tocopherol) were assessed as absolute and metabolic instrumental variables. POAG and glaucoma-related traits data were derived from a large, recently published genome-wide association study database; these traits included intraocular pressure (IOP), macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and vertical cup-to-disc ratio (vCDR). MR analyses were performed per outcome for each exposure. Results: We found no causal association between six diet-derived antioxidants and POAG using the International Glaucoma Genetics Consortium data. For absolute antioxidants, the odds ratios (ORs) ranged from 1.011 (95% confidence interval [CI], 0.854-1.199; P = 0.895) per natural log-transformed ß-carotene to 1.052 (95% CI, 0.911-1.215; P = 0.490) for 1 µmol/L of ascorbate. For antioxidant metabolites, the OR ranged from 0.998 (95% CI, 0.801-1.244; P = 0.989) for ascorbate to 1.210 (95% CI, 0.870-1.682; P = 0.257) for γ-tocopherol, using log-transformed levels. A similar result was obtained with the FinnGen Biobank. Furthermore, our results showed no significant genetic association between six diet-derived antioxidants and glaucoma-related traits. Conclusions: Our study did not support a causal association among six diet-derived circulating antioxidants, POAG, and glaucoma-related traits. This suggests that the intake of antioxidants may not have a preventive effect on POAG and offers no protection to retinal nerve cells. Translational Relevance: This study provides valid evidence regarding the use of diet-derived antioxidants for glaucoma patients.

Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis.

Trends in Childhood Glaucoma Prevalence and Incidence in South Korea, 2002-2019: A Nationwide Population-Based Study.

PRCIS: This nationwide analysis identified the prevalence and incidence of childhood glaucoma for an 18-year period. The prevalence and incidence of primary congenital glaucoma showed increasing trends. Juvenile open angle glaucoma, meanwhile, showed a decreasing tendency. PURPOSE: We aimed to determine the trends in the prevalence and incidence of childhood glaucoma in the entire population of South Korea. PATIENTS AND METHODS: A nationwide retrospective cohort study was performed with an age-specific and sex-specific population of South Korea. The Korean National Health Insurance Service claims database for 2002 to 2019 was accessed to identify cases of ophthalmologist-confirmed primary childhood glaucoma [ie, primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG)]. Incidence for PCG was estimated for a same-birth-year population, while that for JOAG was estimated using age-specific and sex-specific population figures. To verify the glaucoma cases, we also analyzed the diagnostic codes as well as any information on medication prescriptions and/or ocular-surgery history. RESULTS: During the 18-year observational period, totals of 505 and 7538 patients were diagnosed with PCG and JOAG, respectively. The mean prevalences of PCG and JOAG were 3.96±0.72 and 14.17±5.18, respectively. The prevalence of PCG showed an overall increasing trend during the study period, but the pattern was not significant ( ß =0.049, P =0.143); that of JOAG, meanwhile, showed a significant decreasing tendency ( ß =-0.713, P =0.001). PCG prevalence showed no difference between urban and rural areas, but JOAG showed a higher prevalence in rural areas ( P <0.001). As for mean incidence, the rates for PCG and JOAG were 1.54±0.49 and 5.02±1.95 (per 100,000 person-years), respectively, and were higher in males ( P <0.001 and P =0.013). CONCLUSION: This study identified childhood glaucoma prevalence and incidence in a general population of East Asian ethnicity. This data could help to promote a better understanding of the typical epidemiological features and clinical courses of childhood glaucoma patients.

Incidence of glaucoma filtration surgery from disease onset of open-angle glaucoma.

AIMS: To investigate the rate and risk factors of undergoing glaucoma filtration surgery (GFS) in patients with newly diagnosed open-angle glaucoma (OAG). METHODS: This is a population-based historic cohort study, consisting of 9420 patients older than 45 years diagnosed with OAG during 1997-2010. Follow-up spanned from 1997 to 2017. We obtained data for trabeculectomy (TRE), deep sclerectomy (DS), and glaucoma drainage implant (GDI) surgeries from national administrative healthcare registers by hospital billing data. We plotted the cumulative incidence of GFS and carried out a multivariate Poisson regression analysis adjusted for age, sex, hospital district, systemic comorbidities, and the number of IOP-lowering drugs. We reported incidence rate ratios (IRR) with 95% confidence intervals (CI) for GFS after the onset of OAG. RESULTS: The cumulative incidence of GFS at 5 years from OAG onset was 3.1% and at 10 years 5.4%. Age over 80 years at baseline was associated with lower GFS incidence (IRR 0.51, CI 0.31-0.84). The number of IOP-lowering drugs in the first 2 years of treatment correlated with the risk of GFS increasing from (IRR 3.23, CI 2.32-4.50) for two drugs, (IRR 7.44, CI 5.28-10.47) for three and to (IRR 14.95, CI 10.38-21.52) for four drugs. CONCLUSION: This study characterized the treatment path of OAG from diagnosis to surgical intervention refining the role of GFS among glaucoma therapies.

Inferring glaucoma status from prescriptions, diagnoses, and operations data: A Danish nationwide study.

PURPOSE: To assess a new method for inferring glaucoma status using prescriptions data. METHODS: The study population comprised all individuals living in Denmark in the period 1995 to 2018 and included 6,930,571 individuals. We used information from The National Prescription Registry on claimed prescriptions as the basis for our study (N = 223,592). We inferred glaucoma status using data on claimed prescriptions, in-hospital ICD-10 diagnoses, and in-hospital glaucoma surgeries. We infer glaucoma status in three ways using the prescription pattern: glaucoma inferred by (i) the use of a first claimed prescription, (ii) the use of a second claimed prescription with a gap of at least 90 days, and (iii) the use of a third claimed prescription for glaucoma medication, again with a gap of at least 90 days between prescriptions. Furthermore, we compared the results with alternative indications for glaucoma, namely in-hospital ICD-10-diagnosed glaucoma and in-hospital glaucoma surgery. RESULTS: We first determined that glaucoma status could be inferred from claimed prescription data and found that a single claimed prescription was highly correlated with the more restricted composite measure of glaucoma (R2 = 0.80, p <0.0001), with a kappa coefficient of 80%. Focusing on individuals with a confirmed in-hospital glaucoma diagnosis, we found a high sensitivity of 88% using anti-glaucomatous prescriptions as a surrogate marker for primary open-angle glaucoma (POAG). We then derived several descriptive insights. The prevalence of glaucoma increased during the period from 1996 to 2018, while the incidence was constant. We also found a decreasing trend in the ratio of the number of people diagnosed annually in hospitals to the number of people filling prescriptions. This indicated a relative increase in the number of patients treated or managed in the secondary sector. Finally, using data on diagnoses and claimed prescriptions, we found that the proportion of total noncompliant patients, i.e., patients who do not claim their prescription at any time in the study period (two decades) was at most 11.8%. This share is calculated on the basis of diagnosed patients who did not have surgery. The results was not sensitive to the glaucoma inference rule. CONCLUSION: Anti-glaucomatous medicine prescriptions can be used to infer glaucoma status, with useful implications for epidemiological research. The sensitivity is particularly high for primary open-angle glaucoma (POAG).

Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study.

OBJECTIVES: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma. DESIGN: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). SETTING: Three tertiary glaucoma centres in the USA. PARTICIPANTS: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies. OUTCOME MEASURES: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time. RESULTS: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years). CONCLUSION: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people. TRIAL REGISTRATION NUMBER: NCT00221897 and NCT00221923.

Treatment Outcomes for Juvenile Open Angle Glaucoma in Thailand.

PRCIS: Juvenile open angle glaucoma (JOAG) patients with thick central corneas and negative family history were more likely to undergo surgery, mainly trabeculectomy with half requiring additional surgery within 10 years. PURPOSE: To assess the characteristics and treatment outcomes of patients with JOAG in Thailand. PATIENTS AND METHODS: This retrospective, multicenter study included all patients diagnosed with JOAG over 12 years from 2 tertiary hospitals in Bangkok, Thailand. RESULTS: A total of 200 eyes from 104 patients were included in this study. The mean age of onset was 24.0±10.1 years (range: 5-40 y), with male predominance (60.5%). Over 90% of patients had bilateral JOAG and 25% had a positive family history. Negative family history (adjusted odds ratio=4.59, P =0.02) and thick central corneal thickness were surgical predictors (every 10 µm adjusted odds ratio=1.29, P =0.01). Over 70% of cases needed glaucoma surgery. Trabeculectomy with Mitomycin-C was performed on 131 eyes (65.5%) with a cumulative probability of complete success of 71.0%, 57.8%, 39.2%, and 26.9% and qualified success of 86.3%, 73.6%, 64.8%, and 45.7% at 1, 3, 5, and 10 years, respectively. The mean follow-up after surgery was 94.9 ± 69.8 months (range: 13-153 mo). There were no serious postoperative complications. Myopia and the number of baseline glaucoma medications were significantly associated with surgical failure. CONCLUSIONS: Trabeculectomy with mitomycin C was the most common primary surgery performed in Thai patients with JOAG, and successfully reduced intraocular pressure without significant complications. Patients with thicker corneas were more likely to undergo surgery. By 10 years, half of the patients required additional surgery and risk factors for failure included myopia and the number of medications.

Chronic Open Angle Glaucoma: a Biopsychosocial Approach to Patient Care.

It is estimated that 2.2 billion people are affected by impaired vision resulting from eye conditions. Chronic open angle glaucoma (COAG) is one such condition, which primarily affects older adults, and is linked to other factors such as genetic predisposition, high blood pressure, diabetes and smoking. By 2025, it is projected that 44% of the UK's ageing population will have COAG. Vision loss due to this condition is irreversible. In this article, Penelope Stanford discusses the bioscience of COAG, and provides information on access to care and patient interventions.

Association between statin use and open-angle glaucoma: a nested case-control study using the Japanese claims database.

The association between statins and open-angle glaucoma (OAG) remains controversial. This study investigated the relationship between statins and OAG in Japanese patients with dyslipidemia using the Japanese administrative claims database. A nested case-control study using two models was conducted using the JMDC claims database (01/2005-01/2020). The onset of OAG: index date was defined as the diagnosis of glaucoma, prescription of anti-glaucoma drugs, or surgery of glaucoma. For each case, a maximum of 10 age-, sex-, and calendar year/month-matched controls were randomly selected by risk-set sampling with replacement. The number of statin prescriptions during the exposure assessment period, which was identified as the 12-month (model 1) or 24-month (model 2) periods prior to the index date, was used as an indicator for statin exposure. Adjusted odds ratios (aORs) and 95% confidence interval (CI) were estimated using conditional logistic regression analyses. We identified 375,373 patients with newly diagnosed dyslipidemia. Of these, 6180 cases and 61,792 controls (model 1) and 4153 cases and 41,522 controls (model 2) were selected. Statin use was not identified as a significant risk factor for OAG (model 1: aOR 0.98, 95% CI 0.93-1.03, model 2: aOR 0.97, 95% CI 0.91-1.04). Compared with nonexposure, short-term exposure (< 2 years) to statins was not related to an increased risk of OAG in the Japanese working-age population with dyslipidemia.

Association of the nasopharyngeal carcinoma and the subsequent open glaucoma development: a nationwide cohort study.

This study aimed to investigate the possible association between nasopharyngeal carcinoma (NPC) and following open angle glaucoma (OAG). A retrospective research applying the National Health Insurance Research Database (NHIRD) of Taiwan was conducted with a follow up period from January 1, 2000 to December 31, 2016. There were 4184 and 16736 participants that selected and categorized into the NPC and non-NPC groups after exclusion. The major outcome of our study was the development of OAG according to diagnostic codes, exam and managements. The Cox proportional hazard regression was employed to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the two groups. In this study, a numbers of 151 and 513 OAG episodes occurred in the NPC and non-NPC groups and the NPC population showed a significantly higher incidence of OAG compared to the non-NPC population in multivariable analysis (aHR: 1.293, 95% CI: 1.077-1.551, p = 0.0057). Besides, the cumulative probability of OAG was significantly higher in the NPC group than that in the non-NPC population (p = 0.0041). About other risk factor for OAG, age older than 40 years old, diabetes mellitus and persistent steroid usage were related to OAG occurrence (all p < 0.05). In conclusion, the NPC may be an independent risk factor of following OAG development.

Presence and severity of migraine is associated with development of primary open angle glaucoma: A population-based longitudinal cohort study.

PURPOSE: To examine the association between the presence and severity of migraine and development of primary open-angle glaucoma (POAG) using a nationwide population-based longitudinal cohort data. METHODS: Data were retrieved from the Korean National Health Insurance Service for 2,716,562 individuals aged ≥ 40 years and assessed for the development of POAG from 2009 through 2018. Subjects were classified into the following 3 groups: healthy control subjects, subjects with mild migraine, and those with severe migraine. Hazard ratios (HR) of glaucoma development were calculated for each group. Subgroup analyses of subjects stratified by age, sex, lifestyle factors (smoking, drinking, and body mass index (BMI)), and comorbidities (diabetes, hypertension, and dyslipidemia). RESULTS: During the 9-year follow-up period, the incidence rate of POAG per 1000 person-years was 2.41 and 3.25 in subjects without and with migraine, respectively. Among the migraine group, the incidence rate was 3.14 and 3.89 in mild and severe subgroups, respectively. The HR was 1.355 (95% CI, 1.300-1.412) and 1.188 (95% CI, 1.140-1.239) before and after adjusting for potential confounding factors in the migraine group per se. Regarding the severity of migraine, the adjusted HRs were 1.169 (95% CI, 1.117-1.224) in the mild migraine group, and 1.285 (95% CI, 1.166-1.415) in the severe migraine group compared to the control group. The results were consistent in subgroup analyses after stratifying by age, sex, lifestyle factors, and comorbidities. CONCLUSIONS: Migraine is associated with increased risk of POAG development. Furthermore, chronic and severe migraine is associated with greater risk of POAG development.

Glaucoma: Diagnosis and Management.

Glaucoma is a group of eye disorders characterized by progressive deterioration of the optic nerve that can lead to vision loss. Primary open-angle glaucoma (POAG) is the most common form in the United States. The risk of POAG increases with age, family history of glaucoma, type 2 diabetes mellitus, hypotension, hypothyroidism, obstructive sleep apnea, cardiovascular disease, and myopia. Up to one-half of patients are undiagnosed because a diagnosis often requires monitoring over years to document changes suggesting POAG. These include a cup-to-disc ratio of 0.3 or greater, intraocular pressure greater than 21 mm Hg on tonometry, nerve fiber layer defects identified on optical coherence tomography, and reproducible visual field defects. Topical intraocular pressure-lowering medications and selective laser trabeculoplasty are first-line treatments for POAG. Although POAG screening in the general adult population is not recommended, primary care physicians can help decrease POAG-related vision loss by identifying patients with risk factors and referring them for evaluation by an eye specialist. Medicare covers evaluations in patients at high risk. Primary care physicians should encourage medication adherence and identify barriers to treatment. The other type of glaucoma is angle-closure glaucoma, in which the flow of aqueous humor is obstructed. Angle-closure glaucoma can occur acutely with pupillary dilation and is an ophthalmologic emergency. The goal of treatment for acute angle-closure glaucoma is to reduce intraocular pressure quickly with medications or surgery, then prevent the recurrence of the obstruction to aqueous flow by a definitive ophthalmologic procedure.

Genetic Associations Between Smoking- and Glaucoma-Related Traits.

Purpose: The purpose of this study was to describe the genetic relationship between smoking and glaucoma. Methods: We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants. Results: We identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (-0.18 mm Hg per SD, 95% confidence interval [CI] = -0.30 to -0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (-0.09 mm Hg per SD, 95% CI = -0.17 to -0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13). Conclusions: MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma. Translational Relevance: Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.

Estimating the Length of the Preclinical Detectable Phase for Open-Angle Glaucoma.

Importance: A 50% reduction of glaucoma-related blindness has previously been demonstrated in a population that was screened for open-angle glaucoma. Ongoing screening trials of high-risk populations and forthcoming low-cost screening methods suggest that such screening may become more common in the future. One would then need to estimate a key component of the natural history of chronic disease, the mean preclinical detectable phase (PCDP). Knowledge of the PCDP is essential for the planning and early evaluation of screening programs and has been estimated for several types of cancer that are screened for. Objective: To estimate the mean PCDP for open-angle glaucoma. Design, Setting, and Participants: A large population-based screening for open-angle glaucoma was conducted from October 1992 to January 1997 in Malmö, Sweden, including 32 918 participants aged 57 to 77 years. A retrospective medical record review was conducted to assess the prevalence of newly detected cases at the screening, incidence of new cases after the screening, and the expected clinical incidence, ie, the number of new glaucoma cases expected to be detected without a screening. The latter was derived from incident cases in the screened age cohorts before the screening started and from older cohorts not invited to the screening. A total of 2029 patients were included in the current study. Data were analyzed from March 2020 to October 2021. Main Outcomes and Measures: The length of the mean PCDP was calculated by 2 different methods: first, by dividing the prevalence of screen-detected glaucoma with the clinical incidence, assuming that the screening sensitivity was 100% and second, by using a Markov chain Monte Carlo (MCMC) model simulation that simultaneously derived both the length of the mean PCDP and the sensitivity of the screening. Results: Of 2029 included patients, 1352 (66.6%) were female. Of 1420 screened patients, the mean age at screening was 67.4 years (95% CI, 67.2-67.7). The mean length of the PCDP of the whole study population was 10.7 years (95% CI, 8.7-13.0) by the prevalence/incidence method and 10.1 years (95% credible interval, 8.9-11.2) by the MCMC method. Conclusions and Relevance: The mean PCDP was similar for both methods of analysis, approximately 10 years. A mean PCDP of 10 years found in the current study allows for screening with reasonably long intervals, eg, 5 years.

Long-term effects of obstructive sleep apnea and its treatment on open-angle glaucoma: a big-data cohort study.

STUDY OBJECTIVES: The relationship between open-angle glaucoma (OAG) and obstructive sleep apnea (OSA) is unclear. The long-term risk for OAG after OSA diagnosis has not been investigated. Therefore, we assessed the risk for OAG among patients with OSA over a 12-year follow-up period using nationwide, population-based data. METHODS: The OSA group was randomly selected from among 3.5 million individuals registered with the National Health Insurance Service. The non-OSA group was obtained through propensity score matching considering several variables. The primary endpoint was glaucoma diagnosis. RESULTS: The OSA and non-OSA groups both included 6,369 individuals. The overall hazard ratio for OAG in the OSA group was 1.42 (95% confidence interval [CI]: 1.19-1.69). In subgroup analysis, the hazard ratio for OAG was 1.94 (95% CI: 1.57-2.41) for those aged > 60 years, 1.50 (95% CI: 1.20-1.89) for those with diabetes mellitus, 1.53 (95% CI: 1.26-1.86) for those with hypertension, and 0.71 (95% CI: 0.52-0.96) for those with a history of OSA surgery. CONCLUSIONS: Over the 12-year follow-up, the risk for OAG increased after OSA diagnosis. Further research will be necessary to determine if treating OSA can mitigate this association. CITATION: Lee T-E, Kim JS, Yeom SW, Lee MG, Lee JH, Lee H-J. Long-term effects of obstructive sleep apnea and its treatment on open-angle glaucoma: a big-data cohort study. J Clin Sleep Med. 2023;19(2):339-346.

Background polygenic risk modulates the association between glaucoma and cardiopulmonary diseases and measures: an analysis from the UK Biobank.

AIMS: To assess whether associations of cardiopulmonary conditions and markers with glaucoma differ by background genetic risk for primary open angle glaucoma (POAG). METHODS: We constructed a POAG polygenic risk score (PRS) using genome-wide association study summary statistics from a large cross-ancestry meta-analysis. History of glaucoma (including self-report and codes for POAG, 'other glaucoma' or unspecified glaucoma), history of common cardiopulmonary conditions and cardiopulmonary measures were assessed in the UK Biobank. Stratifying by PRS decile 1 (lowest risk) versus decile 10 (highest risk), separate multivariable models were estimated to assess the associations of cardiopulmonary diseases or factors with glaucoma, adjusting for age, sex, smoking and medication use. A Bonferroni correction was used to adjust p values for multiple comparisons. RESULTS: Individuals in POAG PRS decile 1 (417 cases, 44 458 controls; mean age 56.8 years) and decile 10 (2135 cases, 42 413 controls; mean age 56.7 years) were included. Within decile 1, glaucoma cases had significantly higher glycated haemoglobin (38.5 vs 35.9 mmol/mol) and higher prevalence of diabetes (17.5% vs 6.5%), dyslipidaemia (31.2% vs 18.3%) and chronic kidney disease (CKD) (6.7% vs 2.0%) than controls (adjusted p<0.0013 for each). Within decile 10, glaucoma was associated with higher prevalence of dyslipidaemia (27.7% vs 17.3%, p=6.9E-05). The magnitude of association between glaucoma and diabetes, CKD and glycated haemoglobin differed between deciles 1 and 10 (contrast test p value for difference <0.05). CONCLUSION: The relations between systemic conditions and glaucoma vary by underlying genetic predisposition to POAG, with larger associations among those who developed glaucoma despite low genetic risk.

Increased risk of open-angle glaucoma in non-smoking women with obstructive pattern of spirometric tests.

To investigate differences in the prevalence of open-angle glaucoma (OAG) between different pulmonary function types. A population-based, cross-sectional analysis was conducted using Korean National Health and Nutrition Examination Surveys from 2008 to 2011. A total of 8941 subjects ≥ 40 years of age were analyzed. Chronic obstructive pulmonary disease (COPD) was defined as the ratio between first second of forced expiration (FEV1) and forced vital capacity (FVC) below 70%. The prevalence of glaucoma, as defined by the International Society of Geographical and Epidemiological Ophthalmology, was the main outcome. OAG was more prevalent in women with COPD (8.0% vs. 4.8% normal, P = 0.001) compared to women with normal pulmonary function. Intraocular pressure (IOP) of women with COPD were 13.3 (0.2) mmHg (13.9 (0.1) mmHg for normal function, P = 0.182). Never-smokers were more prevalent in women with COPD and glaucoma (92.9% vs. 52.4% normal function; P < 0.001). COPD was found to increase the risk of glaucoma in women (OR 2.077, P = 0.017) and even further in non-smoking women (OR 2.711, P = 0.003). Women with COPD showed a higher glaucoma prevalence despite similar IOP in comparison to women with normal pulmonary function. Non-smoking COPD is significantly associated with open-angle glaucoma in women.