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Purpose: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population., Design: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium., Participants: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants., Methods: We examined associations of 4 categories of systemic medications-antihypertensive medications (β-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only., Main Outcome Measures: Glaucoma prevalence and IOP., Results: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic β-blockers was associated with a lower IOP (β coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic β-blockers (β coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic β-blockers (β coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (β coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP., Conclusions: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic β-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Prcis: In the Thessaloniki Eye Study (TES) incidence phase population, frequent dietary salt intake was potentially associated with increased risk of open angle glaucoma in antihypertensive users., Purpose: The aim was to examine the association between dietary salt intake and glaucoma by antihypertensive use in the TES population., Materials and Methods: The study population included TES incidence phase participants. Dietary salt intake frequency was assessed by self-report. Outcomes included prevalence of any open angle glaucoma (OAG), primary open angle glaucoma (POAG), and pseudoexfoliation (PEX). Covariates included demographics, cardiovascular disease, migraines, diabetes, steroid use, smoking, history of cataract surgery, central corneal thickness, intraocular pressure, blood pressure, and antihypertensive use. Logistic regression was used to examine associations between frequency of salt intake and glaucoma, controlling for covariates and stratified by antihypertensive use., Results: The study included 1076 participants 80.5±4.4 years old, of whom 518 were female. There were 89/1076 (8.3%) participants with any OAG, 46/789 (5.8%) with POAG, and 287/1030 (27.9%) with PEX. In participants with antihypertensive use, frequent versus never salt intake was associated with increased risk of any OAG [adjusted odds ratio (aOR)=2.65, 95% confidence interval (CI)=1.12, 6.28; n=784] and POAG (aOR=3.59, 95% CI=1.16, 11.11; n=578) overall, and additionally in participants with diastolic blood pressure <90 mm Hg (aOR=2.42, 95% CI=1.00, 5.84; n=735) for OAG. There were no statistically significant adjusted associations between salt intake and PEX, or in participants without antihypertensive use., Conclusions: In TES participants assessed for OAG in the prevalence and incidence phases, frequent salt intake may be associated with increased OAG in those who take antihypertensive medication. Further investigation is needed of salt intake and glaucoma in hypertensive individuals., Competing Interests: Disclosure: F.T.: Pfizer (financial support); Novartis (financial support, consultant); Bayer (financial support); Alcon (financial support); Thea (financial support); Omikron (financial support, consultant), Rheon (financial support), Bausch & Lomb (financial support). P.F.: Thea (honoraria). A.H.: Received remuneration from AdOM, Qlaris, Luseed, and Cipla for serving as a consultant, and he serves on the board of AdOM, Qlaris, and Phileas Pharma. A.H. holds an ownership interest in AdOM, Luseed, Oxymap, Qlaris, Phileas Pharma, and QuLent. All relationships listed above are pursuant to Icahn School of Medicine’s policy on outside activities. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The present study evaluates the differences in the prevalence of the signs and symptoms of ocular surface disease (OSD) in patients with PEX glaucoma (PEXG), compared to other glaucoma types (non-PEXG)., Methods: Patients with non-PEXG and PEXG were prospectively examined for the presence and severity of OSD signs and questioned for symptoms using the OSDI (ocular surface disease index) questionnaire., Results: 116 patients were prospectively enrolled (58 non-PEXG and 58 PEXG). PEXG subjects who were older, had lower central corneal thickness (CCT) values, at a more advanced glaucoma stage and required more IOP lowering drops. OSD signs were prevalent in both groups: conjunctival hyperemia (74.5% non-PEXG vs. 94.8% PEXG), eyelid redness (70.7% vs. 96.6%), conjunctival (74.1% vs. 93.1%) and corneal fluorescein staining (81% vs. 93.1%) and abnormal TFBUT (82.8% vs. 87.9%). When adjusted for potential confounders, (older age, thinner CCT, more advanced glaucoma in PEXG) eyelid redness remained the only parameter significantly associated with PEXG, being 11 times more likely to occur in this group ( p = 0.037)., Conclusion: Subjects with PEXG presented a higher frequency of signs of OSD compared to other glaucoma types. When accounting for confounding factors, the only difference between the groups was the significantly higher presence (11 times more likely) of eyelid redness in PEXG, suggesting, in addition to glaucoma treatment, the impact of PEX on ocular surface integrity.

Objective: The objective of this study was to determine the 12-year incidence of open-angle glaucoma (OAG), with further classification into primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG), in an elderly White population., Design: A longitudinal, population-based study in urban Northern Greece., Participant: Surviving cohort of the 2554 Thessaloniki Eye Study subjects 60 years and above who had the baseline examination., Methods: The surviving cohort was re-examined 12 years after baseline, using the same methodology and the same standard operating procedures as in the baseline examination. The definitions of glaucoma and pseudoexfoliation were consistent throughout the study. The 12-year incidences of OAG, POAG, and PEXG with corresponding 95% confidence intervals (CIs) were calculated for the whole study population, consisting of clinic-visit and home-visit participants. The population at risk was defined as those who did not meet the study criteria for the diagnosis of glaucoma in either eye at baseline., Main Outcome Measures: Twelve-year incidence of OAG, with further classification into POAG and PEXG., Results: Of 1468 eligible subjects in the surviving cohort, 1092 were examined (participation rate 74%). Mean age at baseline was 68.9±4.6 years. Mean follow-up time was 11.6±1.6 years. The 12-year incidence of OAG was 4.4% (95% CI: 3.3-5.8); 0.37% per year. In the overall population the incidence of POAG and PEXG was 2.1% (95% CI: 1.3-3.2) and 2.3% (95% CI: 1.5-3.4), respectively. The corresponding incidence proportions were 2.9 (95% CI: 1.8-4.3) in those without PEX and 8.9 (95% CI: 5.8-12.9) in those with PEX at baseline and/or incidence. The latter was strongly associated with higher odds for incident glaucoma (odds ratio=3.34, 95% CI: 1.83-6.08, P<0.001). Of all incident OAG cases, 11.1% (95% CI: 4.4-24) had baseline intraocular pressure >21 mm Hg., Conclusions: The incidence of OAG was similar or higher compared with other White populations. The incidence of glaucoma in those with PEX was higher compared with the incidence of glaucoma in those without PEX., Competing Interests: Disclosure: P.F.: lecturing honorarium from Thea. A.H.: has received remuneration from Adom, Qlaris, and Luseed for serving as a consultant, and he serves on the board of Adom and Phileas Pharma. He also holds an ownership interest in AdOM, Luseed, Oxymap, Phileas Pharma, and QuLent. All relationships listed above are pursuant to Icahn School of Medicine’s policy on outside activities. F.T.: grants/research support from Pfizer, Novartis, Alcon, Thea, Bayer and Omikron; honoraria or consultation fees from Alcon, Novartis, Thea, Bayer, and Omikron. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness., Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function., Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome., Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function., Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses., Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome., Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.

Purpose: To assess the association of potential risk factors with early and late age-related macular degeneration (AMD) in the Thessaloniki Eye Study (TES) population Design: Population-based, cross-sectional study of subjects over age of 60 living in Thessaloniki, Greece Methods: Subjects without any AMD features and subjects with early and late AMD (neovascular AMD or geographic atrophy) were identified in the TES cohort using standardized procedures and masked grading of stereo color fundus photos. Demographic, lifestyle, systemic and other ophthalmic covariates were also collected during a detailed examination process. Their association with AMD was investigated using univariate and multivariate adjusted logistic regression models., Results: Among the 2108 participants with gradable photos, the grading process identified 1204 subjects with no AMD, 848 subjects with early AMD, and 56 subjects with late AMD (24 with geographic atrophy and 32 with neovascular AMD). In multivariate analysis, compared to no AMD, late AMD was positively associated with older age (OR:1.16; 95%CI:1.10-1.22 per year of age), current smoking (smoking vs. never smoking, OR:2.34; 95%CI:1.12-4.90), prior cataract surgery (cataract surgery vs. no cataract surgery OR:2.06; 95%CI:0.96-4.40), marital status (divorced/separated vs. married, OR:3.10; 95%CI:1.08-8.93) and with 60% lower odds when sleeping in the afternoon (yes vs. no, OR:0.40; 95%CI:0.22-0.72). Early AMD was positively associated with older age (OR: 1.03; 95%CI:1.01-1.05 per year of age) and negatively with higher pulse pressure (OR:0.99; 95%CI:0.98-0.99 per mmHg)., Conclusions: In TES, apart for well-known risk factors for AMD like age, smoking, and cataract surgery, two novel behavioral risk factors for prevalent late AMD were suggested. Sleeping in the afternoon was associated with 60% decreased odds for late AMD and 67% decreased odds for neovascular AMD. Being divorced/separated compared to married was associated with 3-fold higher odds for late AMD. Large longitudinal population-based studies will be necessary to further establish the potential late AMD risk effects of these two novel factors, to demonstrate potential implications of underlying pathogenetic mechanisms, and to explore preventive measures and therapeutic targets.

Prescribing medical therapy for the treatment of glaucoma can be a complex process since many parameters should be taken into consideration regarding its achievements and limits. Today, a variety of options, including multiple drug classes and multiple agents within classes, are available to the clinician, but caution should be given to their side effects and contraindications. Glaucoma patients with preexisting ocular surface disease should be treated with caution, and preferably with preservative-free formulations, as there is an increased risk for symptom deterioration. The development and use of fixed-combination therapies has reduced the preservative-related side effects that threaten patient adherence and has minimized the washout effect of multiple instillations. Adherence to medical treatment is not only crucial to its efficacy but also to its cost-effectiveness. Further factors to consider are that there are patients who are nonresponders to treatment, and also that the target intraocular pressure (IOP) cannot be reached in all patients, regardless of the response to treatment. The progression of damage can occur even under maximum medical treatment or maximally tolerated medical treatment, and regardless of whether low IOP levels are reached. Furthermore, there is some conflict between medical treatment and quality of life due to long-term everyday use and to side effects of treatment. New molecules and new delivery systems are being investigated to open new horizons in glaucoma management. Although the general rule is to initiate glaucoma management with medical treatment, the limits of medical therapy should be considered to identify those patients in need of surgical management., (© 2017 S. Karger AG, Basel.)