[Possibilities of physiotherapy in glaucomatous optic neuropathy after glaucoma surgery]. / Vozmozhnosti fizioterapevticheskoi stimulyatsii pri glaukomnoi opticheskoi neiropatii posle antiglaukomnykh operatsii.

The current primary approach to the therapeutic and surgical management of glaucoma is limited to lowering intraocular pressure (IOP). While normalization of IOP stabilizes some functional parameters, there is still potential for further restoration of lost visual function in the post-operative period while maintaining the "therapeutic window". Neuroprotection refers to the modification of retinal ganglion cells and the neuronal microenvironment to promote their survival and function. Numerous studies have identified effective neuroprotective methods for glaucoma; however, their implementation into clinical practice remains a significant challenge. This review presents the most clinically significant treatment strategies, as well as the latest therapeutic advances in physiotherapy.

Effect of brimonidine on vascular density and imagej-derived flow index of optic nerve head and macula in primary open angle glaucoma.

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.

Long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma: a single-surgeon experience.

PURPOSE: To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. METHODS: A 48-month retrospective analysis was performed on n = 133 open angle glaucoma eyes treated with canaloplasty and n = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. RESULTS: Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications (p = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 (p = 0.018 and p = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p = 0.000). CONCLUSION: Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options.

Downregulation of ATP8B2 to Assess Plasmalogen Distribution and Far1 Expression in Primary Trabecular Meshwork Cells.

The trabecular meshwork (TM) from primary open-angle glaucoma (POAG) cases has been found to contain decreased levels of intracellular plasmalogens. Plasmalogens are a subset of lipids involved in diverse cellular processes such as intracellular signaling, membrane asymmetry, and protein regulation. Proper plasmalogen biosynthesis is regulated by rate-limiting enzyme fatty acyl-CoA reductase (Far1). ATPase phospholipid transporting 8B2 (ATP8B2) is a type IV P-type ATPase responsible for the asymmetric distribution of plasmalogens between the intracellular and extracellular leaflets of the plasma membranes. Here we describe the methodology for extraction and culturing of TM cells from corneal tissue and subsequent downregulation of ATP8B2 using siRNA transfection. Further quantification and downstream effects of ATP8B2 gene knockdown will be analyzed utilizing immunoblotting techniques.

OCT angiographic evaluation of changes in macula and optic nerve head vessel density after a water drinking test in glaucomatous and healthy eyes.

PURPOSE: To evaluate the effects of a water drinking test (WDT) on the intraocular pressure (IOP) and vascular density of the optic nerve head and macula in healthy individuals and those with primary open glaucoma using optical coherence tomography angiography. METHODS: In this prospective comparative study, 30 healthy patients and 44 POAG subjects were divided into two groups. The study's outcome measures were the IOP and vessel density of the optic nerve and macular area. After ingesting 1000 ml of water in 5 min, the effect of the WDT on the IOP and the vascular density of the macular area and optic nerve head were measured at baseline and then 20, 40, and 60 min later at intervals of 20 min. RESULTS: The initial IOP in the healthy and glaucomatous eye groups was comparable (15.94 ± 2.6 and 16.87 ± 4.21 mmHg, respectively, P = 0.506). The IOP of both groups peaked at 40' measurements. POAG eyes had significantly higher IOP elevation (4.34 ± 0.30 vs. 2.24 ± 0.30 mmHg, P < 0.001). The glaucomatous eyes had lower radial peripapillary capillary (RPC) and whole macular superficial capillary plexus (SCP) densities at baseline (48.55 ± 5.99 vs. 51.33 ± 3.75) and (48.92 ± 3.41 vs. 45.29 ± 5.29), respectively (P < 0.001). After the WDT, the change in vessel density between groups in the RPC, whole superficial, and deep capillary plexuses was insignificant (SCP and DCP of 0.66 and 0.70, respectively, P = 0.16). CONCLUSION: The WDT caused a significant IOP jump in both glaucomatous and healthy eyes, but generally, the alterations in the glaucomatous eyes were more pronounced. The changes in vascular density in the macula and optic nerve head were similar between the groups.

Causal relationship between central corneal thickness and open-angle glaucoma: Evidence from Mendelian randomization.

Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

Factors associated with non-return after loss to follow up from glaucoma care: An IRIS® Registry (Intelligent Research in Sight) retrospective analysis.

PURPOSE: Loss to follow-up (LTFU) in primary open-angle glaucoma (POAG) can lead to undertreatment, disease progression, and irreversible vision loss. Patients who become LTFU either eventually re-establish glaucoma care after a lapse or never return to the clinic. The purpose of this study is to examine a large population of POAG patients who became LTFU to determine the proportion that return to care and to identify demographic and clinical factors associated with non-return after LTFU. DESIGN: Retrospective longitudinal cohort study PARTICIPANTS: Patients with a diagnosis of POAG with a clinical encounter in 2014 in the IRIS® Registry (Intelligent Research in Sight) METHODS: We examined follow-up patterns for 553,663 patients with POAG who had an encounter in the IRIS Registry in 2014 by following their documented clinic visits through 2019. LTFU was defined as exceeding one calendar year without an encounter. Within the LTFU group, patients were classified as returning after a lapse in care (return after LTFU) or not (non-return after LTFU). MAIN OUTCOME MEASURES: Proportion of patients with non-return after LTFU and baseline demographic and clinical characteristics associated with non-return among LTFU POAG patients. RESULTS: Among 553,663 POAG patients, 277,019 (50%) had at least one episode of LTFU over the 6-year study period. Within the LTFU group, 33% (92,471) returned to care and 67% (184,548) did not return to care. Compared to those who returned to care, LTFU patients with non-return were more likely to be older (age >80 years; RR=1.48; 95% CI: 1.47-1.50), to have unknown/missing insurance (RR=1.31; 95% CI: 1.30-1.33), and to have severe-stage POAG (RR=1.13; 95% CI: 1.11-1.15). Greater POAG severity and visual impairment were associated with non-return with a dose-dependent relationship in the adjusted model that accounted for demographic characteristics. Among those with return after LTFU, almost all returned within 2 years of last appointment (82,201; 89%) rather than 2 or more years later. CONCLUSION: Half of POAG patients in the IRIS Registry had at least one period of LTFU, and two-thirds of LTFU POAG patients did not return to care. More effort is warranted to re-engage the vulnerable POAG patients who become LTFU.

Comparison of corneal endothelial cell density reduction between primary open-angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery.

PURPOSE: We compared corneal endothelial cell (CED) loss after Ex-Press (EXP) surgery between patients with primary open-angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX). PATIENTS AND METHODS: This was a single-facility retrospective study. We included glaucoma patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after (at 12, 24, and 36 months) EXP surgery by noncontact specular microscopy and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test. RESULTS: We included 119 eyes that underwent EXP surgery, including 60 POAG eyes and 59 PEX eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm2 after 3 years. At the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower, at 85.0 ± 19.5%, in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy. CONCLUSIONS: EXP surgery decreased the corneal endothelial cell populations in PEX patients faster than POAG patients.

The anterior scleral thickness in primary open-angle glaucoma with high myopia.

Purpose: This study aimed to investigate and compare the anterior scleral thickness (AST) among high myopia (HM), primary open-angle glaucoma (POAG), and POAG with HM (HMPOAG) groups. Methods: Thirty-two HM eyes, 30 POAG eyes, and 31 HMPOAG eyes were included. The Schlemm's canal (SC) area, trabecular meshwork (TM) thickness, scleral spur (SS) length, and AST were measured using swept-source optical coherence tomography. AST was measured at 0 mm (AST0), 1 mm (AST1), 2 mm (AST2), and 3 mm (AST3) from SS. Results: The HMPOAG group had significantly thinner AST, SS length, and TM thickness than the HM and POAG groups (all p < 0.05). In addition, the SC area of the HMPOAG group was also significantly smaller than that of the HM group (p < 0.001). Conclusion: The HMPOAG group had the thinnest AST, shortest SS, thinnest TM, and smallest SC. The thinnest AST might contribute to the shortest SS, and further to the thinnest TM and smallest SC in the HMPOAG group. AST might be a novel clinical indicator in the prediction and evaluation of POAG.

Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

PURPOSE: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). METHODS: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. MAIN OUTCOME MEASURE: Proportion of patients with POAG after stratification according to the GRS. RESULTS: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10-4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10-6). CONCLUSIONS: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The diagnostic ability of peripapillary vessel density in primary open-angle glaucoma suspects.

OBJECTIVE: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. METHODS: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. RESULTS: The global (P<0.001), nasal (P=0.003), and inferior (P=0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r=0.492, P=0.023) and rim area (r=0.483, P=0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r=0.648, P=0.001), the nasal RNFL thickness (r=0.441, P=0.045), the rim area (r=0.439, P=0.046) and the GCC thickness (r=0.472, P=0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36%, specificity 72.73%, cutoff value 45%), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. CONCLUSION: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

Association of Open-Angle Glaucoma with Dementia in California Medicare Beneficiaries.

PURPOSE: To examine the associations between open-angle glaucoma (OAG) subtypes and dementia in 2019 California (CA) Medicare beneficiaries. DESIGN: Retrospective cross-sectional study. METHODS: OAG diagnosis was determined by the International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes in Part B claims, including the following OAG subtypes: primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), pseudoexfoliative glaucoma (PXG), and pigmentary glaucoma (PG). Diagnoses of any dementia, Alzheimer's dementia (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD) were identified by ICD-10 diagnosis codes. Covariates included: demographics, systemic diseases, depression, hearing loss, obesity, smoking and alcohol-related disorders, and long-term aspirin, anticoagulant, and antithrombotic or antiplatelet use. Univariate and multivariable logistic regression models were used to assess the associations between OAG and dementia, adjusting for all covariates. Age-stratified analysis was also performed for beneficiaries aged 65-74 years, 75-84 years, and 85+ years. RESULTS: Among 2,431,150 CA Medicare beneficiaries included in this study, 104,873 (4.3%) had POAG, 9,199 (0.4%) had NTG, 4,045 (0.2%) had PXG and 1,267 (0.05%) had PG. The overall prevalence of any dementia was 3.2% (n=79,009). In adjusted analyses, the odds of any dementia were lower for beneficiaries with all OAG subtypes compared to beneficiaries without glaucoma (odds ratio [OR]=0.74 for POAG, OR=0.74 for PXG, OR=0.60 for NTG, and OR=0.38 for PG; p<0.01). In age-stratified analyses, beneficiaries with PXG had greater odds of VD (OR: 2.84, p=0.006, [aOR]: 2.18, p=0.04) in the youngest age stratum (65-74 years) compared to patients with no glaucoma. The odds for any dementia were lower for beneficiaries with all OAG subtypes compared to beneficiaries without glaucoma in the oldest, but not in the youngest age stratum. CONCLUSIONS: In the 2019 CA Medicare population, PXG is associated with an increased likelihood of VD in beneficiaries 65-74 years old, while other subtypes of POAG are associated with a decreased likelihood of any dementia. These findings may suggest selection bias since older adults who continue to follow up with glaucoma care may be more cognitively intact. Further studies are needed to better understand the complex relationship between glaucoma, dementia, and their subtypes.

Evaluation of the lamina cribrosa after topical latanoprost therapy in primary open-angle glaucoma or ocular hypertension.

PURPOSE: To investigate that the changes of lamina cribrosa (LC) thickness and depth after latanoprost therapy in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. METHODS: In this single-center prospective cross-sectional study, 35 eyes from 35 patients with POAG or OHT (study group) and 26 age- and gender- matched healthy individuals (control group) were included. All participants were examined by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode for LC thickness and depth measurements at the first visit before latanoprost therapy and at visits after 1 (second visit) and 3 (third visit) months of latanoprost therapy. RESULTS: The mean LC thickness in both horizontal and vertical scans of the study group were thinner than the control group (p < 0.001, for both). During latanoprost therapy in the study group, the LC thickness values in horizontal scans significantly differed over the three visits, gradually increased (p < 0.05). There was significantly decrease in LC depth in horizontal scans between the first and third visits, and the second and third visits (p = 0.003 and p = 0.008, respectively). The gradual decrease in LC depth in vertical scans was observed at all visits, but the statistically significant difference was between the first and third visits only (p = 0.048). CONCLUSION: POAG/OHT patients showed more LC thinning compared with healthy individuals. The significant increase in LC thickness and the significant decrease in LC depth were detected after IOP reduction therapy with latanoprost in ocular hypertensive/ glaucomatous eyes.

The TGFß Induced MicroRNAome of the Trabecular Meshwork.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor ß (TGFß) in the anterior segment of the eye. Understanding how TGFß affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-ß1 and -ß2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFß-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Elevated VEGF-A Levels in the Aqueous Humor of Patients With Primary Open Angle Glaucoma.

BACKGROUND/AIM: The purpose of the current study was to compare the vascular endothelial growth factor-A (VEGF-A) levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically significant correlations. PATIENTS AND METHODS: This was an observational cross-sectional study. Aqueous humor samples (50-100 µl) were collected under aseptic conditions, from the anterior chamber at the start of glaucoma or cataract surgery. The levels of VEGF-A were measured using a multiplex bead-based immunoassay. RESULTS: Aqueous humor samples were obtained from 76 participants: 39 with POAG and 36 with age-related cataracts as controls. VEGF-A levels were significantly elevated in the POAG group (166.37±110.04 pg/ml, p=0.011) compared to the control group (119.02±49.09 pg/ml). The receiver operating characteristic (ROC) analysis showed that VEGF-A had significant prognostic ability for POAG (AUC=0.67; p=0.006). An optimal cut-off for VEGF-A was found to be 148.5 pg/ml with a sensitivity of 54%, specificity of 81.1%, positive prognostic value (PPV) of 75% and negative prognostic value (NPV) of 62.5%. Logistic regression analysis showed that after adjusting for sex and age, patients with VEGF-A higher than 148.5 pg/ml had almost 10 times greater likelihood for POAG. CONCLUSION: VEGF-A is elevated in patients with POAG and can potentially have a prognostic ability for these patients.

XEN45 Implant in Medically Controlled vs. Uncontrolled Eyes-Differential IOP Changes in Real-Life Conditions.

Background: To assess intraocular pressure (IOP) changes and complications after XEN45 implants in medically controlled eyes (MCE) vs. medically uncontrolled eyes (MUE). Methods: A retrospective study, in a tertiary referral hospital, on mild-to-moderate primary open-angle glaucoma (POAG) cases under topical medication, including 32 eyes with IOP < 21 mmHg (MCE group) and 30 eyes with IOP ≥ 21 mmHg (MUE group). The success criteria using Kaplan-Meier analysis was IOP < 21 mmHg without medications (complete success) or fewer drugs than preoperatively (qualified success) at the last visit, without new surgery or unresolved hypotony. Results: No significant preoperative differences were found between the groups. The mean IOP was 15.6 ± 3.8 mmHg in MCE and 15.1 ± 4.1 mmHg in the MUE group (p > 0.05; Mann-Whitney test) at the end of the follow-up (mean of 26.1 ± 15.6 months and 28.3 ± 15.3 months, respectively) (p = 0.414, Mann-Whitney Test). The device caused a significant IOP reduction at 24 h in both groups. Thereafter, the MCE group significantly tended to increase IOP, recovering baseline values at 1 month and maintaining them until the end of the follow-up. In contrast, in the MUE group, the IOP values tended to be similar after the first reduction. No relevant complications and no significant differences between the groups in the survival analysis were found. Conclusions: XEN45 provided stable IOP control in both the MCE and MUE group without important complications in the medium term. The IOP increasing in the MCE group, after a prior decrease, led to restored baseline values 1 month after surgery. The homeostatic mechanism that causes the rise in the IOP to baseline values and its relationship with failure cases remains to be clarified.

The accuracy of self-reported family history in glaucoma in Brazil.

PURPOSE: To evaluate the accuracy of a positive self-reported glaucoma family history. MATERIAL AND METHODS: Cross-sectional study. Each subject was asked if they had a first-degree relative diagnosed with glaucoma. If their answer was affirmative, the relative was invited to attend on ophthalmic evaluation and underwent complementary exams to confirm or exclude the glaucoma diagnosis. Only one relative was included per subject. RESULTS: We included 204 subjects in the study (102 subjects and their respective relatives). The accuracy of family history of glaucoma was 76.96% of the cases. In the univariable analysis, subjects with college degree had 2.34 [(P = 0.010; 95% confidence interval (CI) 1.18-4.63)], with higher family income 3.72 (P = 0.003; 95% CI 1.57-8.85) and those with health insurance 3.42 (P = 0.001; 95% CI 1.67-6.98) more chances to have a true positive family history for glaucoma. In the multivariable logistic regression analysis, none of the variables presented significant association. CONCLUSION: Around 24% of patients may not provide reliable information about family history for glaucoma. When asking about a glaucoma family history, clinicians should consider the real accuracy of this self-reported data.

Joint effects of air pollution and genetic susceptibility on incident primary open-angle glaucoma.

BACKGROUND: Air pollutants are important exogenous stimulants to eye diseases, but knowledge of associations between long-term exposure to air pollutants and the risk of primary open-angle glaucoma (POAG) is limited. This study aimed to determine whether long-term exposure to air pollutants, genetic susceptibility, and their joint effects lead to an elevated risk of incident POAG. METHODS: This is a population-based prospective cohort study from UK Biobank participants with complete measures of air pollution exposure and polygenetic risk scores. Cox proportional hazard models were fitted to assess the individual and joint effects of long-term exposure to air pollutants and genetics on the risk of POAG. In addition, the effect modification of genetic susceptibility was examined on an additive or multiplicative scale. RESULTS: Among 434,290 participants with a mean (SD) age of 56.5 (8.1) years, 6651 (1.53 %) were diagnosed with POAG during a median follow-up of 13.7 years. Long-term exposure to air pollutants was associated with an increased risk of POAG. The hazard ratios associated with per interquartile range increase in PM2.5, PM2.5 absorbance, PM10, NO2, and NOX individually ranged from 1.027 (95 % CI: 1.001-1.054) to 1.067 (95 % CI: 1.035-1.099). Compared with individuals residing in low-pollution areas and having low polygenic risk scores, the risk of incident POAG increased by 105.5 % (95 % CI: 78.3 %-136.9 %), 79.7 % (95 % CI: 56.5 %-106.5 %), 103.2 % (95 % CI: 76.9 %-133.4 %), 89.4 % (95 % CI: 63.9 %-118.9 %), and 90.2 % (95 % CI: 64.8 %-119.5 %) among those simultaneously exposed to high air pollutants levels and high genetic risk, respectively. Genetic susceptibility interacted with PM2.5 absorbance and NO2 in an additive manner, while no evidence of multiplicative interaction was found in this study. Stratification analyses revealed stronger effects in Black people and the elderly. CONCLUSION: Long-term air pollutant exposure was associated with an increased risk of POAG incidence, particularly in the population with high genetic predisposition.

Long-Term Systemic Use of Calcium Channel Blockers and Incidence of Primary Open-Angle Glaucoma.

PURPOSE: To evaluate the association between the systemic use of calcium channel blockers (CCBs) and primary open-angle glaucoma (POAG) using a diverse nationwide dataset. DESIGN: Retrospective cohort study. SUBJECTS: 213 424 individuals aged 40 years and older in the National Institutes of Health All of Us dataset, notable for its demographic, geographic, and medical diversity and inclusion of historically underrepresented populations. Patients with a diagnosis of POAG prior to use of any kind of antihypertensive medication were excluded. METHODS: Bivariate and multivariable regression analyses were performed to evaluate associations between CCB use and POAG. Calcium channel blocker use was further divided into exposure to dihydropyridine CCBs and nondihydropyridine CCBs, and subgroup analyses were performed using chi-square and Fisher tests. MAIN OUTCOME MEASURES: Diagnosis of POAG. RESULTS: Within our cohort, 2772 participants (1.3%) acquired a diagnosis of POAG, while 210 652 (98.7%) did not. Among patients who developed POAG, the mean age was 73.3 years, 52.5% were female, and 48.2% identified as White. Among patients with POAG, 32.6% used 1 or more CCB, 28.2% used a dihydropyridine CCB, and 2.2% used a nondihydropyridine CCB. In bivariate analysis, use of any CCBs was associated with an increased risk of POAG (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.27-1.31, P < 0.001). In multivariable analysis adjusting for age, gender, race, ethnicity, and comorbidities such as diabetes, hyperlipidemia, and hypertension, use of any CCBs remained associated with an increased risk of developing POAG (OR: 1.52, 95% CI: 1.33-1.74, P < 0.001). When stratified by type of CCB, the use of dihydropyridine CCBs (OR: 1.31, 95% CI: 1.14-1.50, P < 0.001) was associated with increased POAG risk. CONCLUSIONS: Use of dihydropyridine CCBs was associated with a significantly higher risk of developing POAG, both before and while adjusting for demographic factors and comorbid medical conditions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

An eternal hunt for glaucoma.

In the first issue of Graefe's Archive from 1854, Albrecht von Graefe wrote about glaucoma. Glaucoma comes from the Greek word "glaukos," gleaming, which was first used by Homer around 800 BCE. Since then, glaukos and glaucoma have taken on many different meanings. The terms blindness, cataract and glaucoma were used interchangeably and twisted together in incomprehensible contexts. Over 2500 years of glaucoma theories were upset by the discovery of the ophthalmoscope in 1851. The first reports of increased intraocular pressure appeared in the mid-seventeenth century, but it took over 200 years for this elevated pressure to be accepted by the ophthalmological community. The discovery of glaucoma simplex in 1861 was an important step forward. What did doctors know about glaucoma before 1850 and why did it take so long to classify glaucoma in its various categories? And why is it that we still do not know what the cause is for primary open angle glaucoma? I will try to answer some of these questions after a historical overview.