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Background: Endothelin is a potent vasoconstrictor and contributes to the regulation of vascular perfusion. Aberrant endothelin-1 (ET-1) levels in aqueous humor have been reported across a variety of vascular diseases of the eye, including glaucoma. These findings suggest that dysregulation of ET-1 production may contribute to glaucoma pathophysiology. In this study, aqueous humor from patients undergoing ocular surgery was assayed for ET-1 abundance and related to the presence of glaucoma. Patients: Open angle glaucoma patients (n=62 total) from the ophthalmology clinics of the University of Iowa Hospitals and Clinics were enrolled in this study and organized into three distinct cohorts based on their diagnostic criteria, including those with primary open angle glaucoma (POAG, n=25 patients), normal tension glaucoma (NTG, n=17 patients), exfoliation glaucoma (XFG, n=8 patients), and normal controls (n=12 patients). Methods: Aqueous humor was collected intraoperatively from patients undergoing surgeries for glaucoma (including minimally invasive glaucoma surgeries, trabeculectomy, or glaucoma drainage device implantation) for samples in the glaucoma cohorts and cataract extraction for those in the control cohort. Aqueous humor was assayed by ELISA to measure and compare ET-1 abundance between the glaucoma cohorts and control cohort. ET-1 levels were also analyzed with linear regression to control for the covariates of age and sex. Results: ET-1 was significantly elevated in the aqueous humor of patients in the POAG (mean ± SD: 7.8 ± 5.1 pg/mL; p = 0.002) and NTG cohorts (6.1 ± 3.0 pg/mL; p = 0.030) compared to the control (4.0 ± 1.9 pg/mL). No significant difference in aqueous ET-1 was detected in the XFG cohort (6.2 ± 4.5 pg/mL; p = 0.230) compared to the control. Significantly higher ET-1 levels were detected in a merged grouping of all glaucoma cohorts (POAG, NTG, XFG) relative to controls (p = 0.021). Analysis of covariance indicated neither age nor sex was associated with ET-1 level (p = 0.60 and p = 0.27), respectively. Controlling for age and sex had minimal influence on the comparison of ET-1 levels in the POAG versus control cohort (p = 0.018) and nominal influence on the comparisons between the NTG (p = 0.089) or XFG cohort (p = 0.15) relative to the control. Conclusions: Elevated ET-1 in aqueous humor was associated with POAG and NTG compared to controls amongst cohorts of patients at the University of Iowa. These data suggest that dysregulation of vascular perfusion may have a role in the pathophysiology of POAG. The analyses of NTG and XFG samples were limited by the relatively small sample sizes. [ABSTRACT FROM AUTHOR]

Abstract Background Endothelin is a potent vasoconstrictor and contributes to the regulation of vascular perfusion. Aberrant endothelin-1 (ET-1) levels in aqueous humor have been reported across a variety of vascular diseases of the eye, including glaucoma. These findings suggest that dysregulation of ET-1 production may contribute to glaucoma pathophysiology. In this study, aqueous humor from patients undergoing ocular surgery was assayed for ET-1 abundance and related to the presence of glaucoma. Patients Open angle glaucoma patients (n=62 total) from the ophthalmology clinics of the University of Iowa Hospitals and Clinics were enrolled in this study and organized into three distinct cohorts based on their diagnostic criteria, including those with primary open angle glaucoma (POAG, n=25 patients), normal tension glaucoma (NTG, n=17 patients), exfoliation glaucoma (XFG, n=8 patients), and normal controls (n=12 patients). Methods Aqueous humor was collected intraoperatively from patients undergoing surgeries for glaucoma (including minimally invasive glaucoma surgeries, trabeculectomy, or glaucoma drainage device implantation) for samples in the glaucoma cohorts and cataract extraction for those in the control cohort. Aqueous humor was assayed by ELISA to measure and compare ET-1 abundance between the glaucoma cohorts and control cohort. ET-1 levels were also analyzed with linear regression to control for the covariates of age and sex. Results ET-1 was significantly elevated in the aqueous humor of patients in the POAG (mean ± SD: 7.8 ± 5.1 pg/mL; p = 0.002) and NTG cohorts (6.1 ± 3.0 pg/mL; p = 0.030) compared to the control (4.0 ± 1.9 pg/mL). No significant difference in aqueous ET-1 was detected in the XFG cohort (6.2 ± 4.5 pg/mL; p = 0.230) compared to the control. Significantly higher ET-1 levels were detected in a merged grouping of all glaucoma cohorts (POAG, NTG, XFG) relative to controls (p = 0.021). Analysis of covariance indicated neither age nor sex was associated with ET-1 level (p = 0.60 and p = 0.27), respectively. Controlling for age and sex had minimal influence on the comparison of ET-1 levels in the POAG versus control cohort (p = 0.018) and nominal influence on the comparisons between the NTG (p = 0.089) or XFG cohort (p = 0.15) relative to the control. Conclusions Elevated ET-1 in aqueous humor was associated with POAG and NTG compared to controls amongst cohorts of patients at the University of Iowa. These data suggest that dysregulation of vascular perfusion may have a role in the pathophysiology of POAG. The analyses of NTG and XFG samples were limited by the relatively small sample sizes.

Objectives: This study aimed to evaluate the postoperative outcomes of the PreserFlo MicroShunt in Asian patients with exfoliation glaucoma. Methods: We used the Kaplan–Meier method to analyze 29 eyes of 29 patients with exfoliation glaucoma (mean age: 80.7 ± 8.3 years; 16 males; 24 eyes with intraocular lens implants; preoperative intraocular pressure [IOP]: 32.5 ± 9.3 mmHg; preoperative antiglaucoma medications: 3.4 ± 1.0; Asian ethnicity: 100%) who underwent PreserFlo MicroShunt surgery alone at Saneikai Tsukazaki Hospital from November 2022 to November 2023. The criteria for survival were a reduction in IOP of ≥20%, no additional glaucoma surgery, and IOP of 5–21 mmHg (condition 1), 5–18 mmHg (condition 2), and 5–15 mmHg (condition 3). Needling and glaucoma eye drops were considered qualified successes. Results: The mean follow-up period was 27.9 weeks, with a reoperation rate of 31% (9 cases). The complete and qualified success survival rates at 24 weeks were 56%, 52%, and 49%, and 67%, 59%, and 53% for conditions 1–3, respectively. The complete and qualified success survival rates at 48 weeks were 47%, 43%, and 45%, and 52%, 46%, and 48% for conditions 1–3, respectively. Conclusions: The postoperative outcomes of the PreserFlo MicroShunt in Asian patients with exfoliation glaucoma demonstrated an approximate 50% success rate at both 24 and 48 weeks, with a reoperation rate of approximately 30%. Caution is warranted when performing PreserFlo MicroShunt in patients with exfoliation glaucoma. [ABSTRACT FROM AUTHOR]

Background and Objectives: To evaluate the surgical outcomes of intraocular lens (IOL) refixation with vitrectomy in patients with elevated intraocular pressure (IOP) due to IOL subluxation. Materials and Methods: Patients with elevated IOP due to IOL subluxation who had undergone IOL refixation with vitrectomy between 1 June 2013 and 31 December 2023 were retrospectively evaluated. The primary outcome measure was surgical success or failure. Surgical success was defined as a reduction of ≥20% in the preoperative IOP or IOP ≤ 21 mmHg (criterion A), IOP ≤ 18 mmHg (criterion B), or IOP ≤ 15 mmHg (criterion C). Reoperation, loss of light perception, and hypotony were considered as surgical failure. The IOP, number of glaucoma medications used, postoperative complications, and visual acuity were evaluated as the secondary outcomes. The surgical outcomes were compared between the glaucoma and ocular hypertension (OH) groups. Results: At 12 months postoperatively, the probability of success was 72.5%, 54.1%, and 28.4% using criterion A, B, and C, respectively, and the mean IOP and mean number of glaucoma medications used had decreased significantly (p < 0.01 and p = 0.03, respectively). Furthermore, the cumulative success rate was significantly higher in the OH group than in the glaucoma (100% vs. 47.4%; p < 0.01) when using criterion A. Additional glaucoma surgery was required only in the glaucoma group. Conclusions: IOL refixation surgery significantly decreases the IOP and number of glaucoma medications required in patients with elevated IOP due to IOL subluxation. Thus, IOL refixation surgery alone without glaucoma surgery might be effective as the primary procedure in such patients. [ABSTRACT FROM AUTHOR]

Exfoliation syndrome and exfoliation glaucoma comprise a unique age-related ocular aggregopathy characterized by the accumulation of protein complex aggregates in different ocular structures. Recent literature and studies have expanded our knowledge of the clinical characteristic features, phenotypical variations, and molecular pathophysiology associated with disease onset or development of glaucoma. Despite years of studies on the various epidemiological, clinical, and molecular facets of the disease, the exact mechanism of disease onset, formation of aggregates, and the events that trigger the development of glaucoma marking irreversibility in the disease remains elusive. This review elaborates on the existing and new insights that we have gained over the years and highlights gaps in the knowledge about the disease that need future exploration.

Background: This study aimed to determine the appropriate target intraocular pressure (IOP) for patients newly diagnosed with exfoliation glaucoma. Research design and methods: The study followed a prospective cohort of newly diagnosed exfoliation patients for three years. The target IOP was defined using three methods to measure visual field deterioration, mean deviation (MD), visual field index (VFI), and guided progression analysis (GPA). Results: Over the three years, the mean deviation (MD) values declined by an average of −3.84 (±2.61) dB, while the visual field index (VFI) values dropped by an average of 9.66 (±6.25) %. The untreated IOP at inclusion was 32.52 ± 5.54 mmHg. At the end of the study (due to treatment), it was 17.94 ± 1.82 mmHg, resulting in a reduction of 14.58 mmHg (45% reduction). Based on the MD and VFI methods, the target IOP for the whole cohort was around 14–15 mmHg, while the target IOP based on GPA was around 15 mmHg. For advanced glaucoma cases, the target IOP was around 13 mmHg. Conclusions: The study concludes that the traditional reported IOP reduction of 20% and/or IOP 18–20 mmHg may not be sufficient for patients newly diagnosed with exfoliation glaucoma. Instead, the study recommends a target IOP of 14–15 mmHg for these patients. Clinical Trial Registration: The study was registered in the website with the number NCT06237764. [ABSTRACT FROM AUTHOR]

Exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) represent a complex matrix of ocular age-related neurodegenerative changes. Numerous decades of research on this disease entity have highlighted the unique clinical features of ocular protein-complex aggregates, which lead to tissue dysfunction of the ocular outflow channels, leading to irreversible optic nerve damage and glaucoma. While genetic studies have reported several genes associated with XFS and XFG, numerous studies have shown their association with common systemic diseases such as ischemic heart disease, cerebrovascular accidents, and hypertension. Environmental factors are also reported to play a role in the disease pathogenesis by epigenetic control of gene expression and partly explain the difference in the prevalence rates of the disease process. Despite the identification of possible triggers for the disease onset or for the development of glaucoma, the exact mechanisms or the role of several reported risk factors in disease pathogenesis remain a mystery. This review comprehensively evaluated the several risk factors in XFS and XFG while discussing the interactive interplay between the risk factors that determine the disease onset or phenotype in XFS and XFG. [ABSTRACT FROM AUTHOR]

Exfoliation syndrome and exfoliation glaucoma comprise a unique age‑related ocular aggregopathy characterized by the accumulation of protein complex aggregates in different ocular structures. Recent literature and studies have expanded our knowledge of the clinical characteristic features, phenotypical variations, and molecular pathophysiology associated with disease onset or development of glaucoma. Despite years of studies on the various epidemiological, clinical, and molecular facets of the disease, the exact mechanism of disease onset, formation of aggregates, and the events that trigger the development of glaucoma marking irreversibility in the disease remains elusive. This review elaborates on the existing and new insights that we have gained over the years and highlights gaps in the knowledge about the disease that need future exploration. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine whether including genetics as a risk factor for progression will improve the accuracy of the models used in newly diagnosed exfoliation glaucoma patients. Methods: This was a prospective cohort study. This study included only patients who were newly diagnosed with exfoliation glaucoma and received treatment upon inclusion. Blood samples were taken from all patients at inclusion to test for the single nucleotide polymorphisms (SNPs) LOXL-1 rs2165241 and rs1048661. Results: This study found that the frequency of SNPs, as well as intraocular pressure (IOP), mean deviation (MD), and visual field index (VFI) values at diagnosis, were significant predictors of visual field deterioration (p ≤ 0.001). This study showed that interaction terms, including SNPs, were highly significant (p ≤ 0.001). Furthermore, logistic regression analysis also showed highly significant results for interaction terms when SNPs were included (p ≤ 0.001). Finally, the area under the curve (AUC) analysis showed an increased value of around 10–20% when SNPs were included. Conclusions: Adding genetic factors to the well-known clinical risk factors can increase the accuracy of models for predicting visual field deterioration in exfoliation glaucoma patients. However, further studies are needed to investigate the role of other genes in this process. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the surgical outcomes of intrascleral intraocular lens (IOL) fixation using ab interno trabeculotomy (LOT) in patients with exfoliation glaucoma with lens subluxation. Study design: Retrospective case series. Methods: Twenty eyes of 18 patients with exfoliation glaucoma and lens or IOL subluxations were included. Three success criteria were based on postoperative intraocular pressure (IOP) (A, ≤15 mmHg; B, ≤18 mmHg; C, ≤21 mmHg). The IOP, number of glaucoma medications, and visual acuity were compared before and after surgery. Success probability was analyzed using Kaplan–Meier survival curves. Cox proportional hazards' regression models were used to examine prognostic factors for surgical failure. Results: The mean follow-up period was 23.4 ± 7.8 months. The mean IOP significantly decreased from 23.2 ± 6.8 mmHg preoperatively to 14.0 ± 4.4 mmHg at 1 year postoperative (P<0.001). Postoperative hyphema and vitreous hemorrhage were observed in seven and 15 eyes, respectively, and washout in the anterior chamber or vitreous cavity was performed in four eyes. Postoperative IOP spikes and hypotony were observed in four eyes each. Glaucoma reoperation was performed in two eyes. The success rates at 12 months were 65%, 85%, and 90% using criteria A, B, and C, respectively. The IOP at 1 month after surgery was a significant prognostic factor for surgical failure according to criterion A (hazard ratio: 1.08; P=0.034). Conclusion: Intrascleral IOL fixation combined with microhook LOT is a promising option in cases of exfoliation glaucoma with subluxated lens/IOL; however, the high rate of postoperative hyphema and vitreous hemorrhage should be noted. [ABSTRACT FROM AUTHOR]

Alterations in ocular microvasculature may contribute to pathogenesis of exfoliation glaucoma (XFG) and may improve monitoring this aggressive type of open angle glaucoma. This work aims to compare the macula vessel density and the relationship between macula vessel density and central visual field mean sensitivity between eyes with XFG and eyes with primary open-angle glaucoma (POAG) of different stages. In this cross-sectional observational study, the macula vessel density values were compared among 52 POAG cases (26 early stage, 26 moderate to advanced stage) and 53 XFG cases (27 early stage, 26 moderate to advanced stage). The vessel density values were evaluated with optical coherence tomography angiography. Vasculature–function and structure–function relationships were analysed by comparing macula vessel density, inner macula thickness and visual field mean sensitivity in early and moderate to advanced stages of XFG and POAG eyes separately. The early stage XFG eyes had a significantly lower global macula vessel density compared with early stage POAG eyes (42.81 ± 3.85% and 46.56 ± 3.90%, respectively; p = 0.02). However, the tendency of XFG eyes for a lower vessel density compared with the POAG eyes did not exhibit any significance in moderate to advanced stages of glaucoma (37.39 ± 5.65% and 38.35 ± 4.67%, respectively; p = 0.9). The macula vessel density (%)–visual field mean sensitivity (1/Lambert) correlation was statistically significant in early stage XFG eyes (r = 0.464 p = 0.01), while no such correlation was notable for the early stage POAG eyes (r = –0.029 p = 0.89). The macula vessel density appears to be more severely affected in early stage XFG than POAG of similar severity, suggesting a relatively greater value of vascular insufficiency in XFG. The significant vasculature-function association in early stage XFG, which was absent in early stage POAG, may infer the importance of macula vessel density in monitoring functional loss in early stages of XFG. [ABSTRACT FROM AUTHOR]

Background and Objectives: To evaluate the surgical outcomes of intraocular lens (IOL) refixation with vitrectomy in patients with elevated intraocular pressure (IOP) due to IOL subluxation. Materials and Methods: Patients with elevated IOP due to IOL subluxation who had undergone IOL refixation with vitrectomy between 1 June 2013 and 31 December 2023 were retrospectively evaluated. The primary outcome measure was surgical success or failure. Surgical success was defined as a reduction of ≥20% in the preoperative IOP or IOP ≤ 21 mmHg (criterion A), IOP ≤ 18 mmHg (criterion B), or IOP ≤ 15 mmHg (criterion C). Reoperation, loss of light perception, and hypotony were considered as surgical failure. The IOP, number of glaucoma medications used, postoperative complications, and visual acuity were evaluated as the secondary outcomes. The surgical outcomes were compared between the glaucoma and ocular hypertension (OH) groups. Results: At 12 months postoperatively, the probability of success was 72.5%, 54.1%, and 28.4% using criterion A, B, and C, respectively, and the mean IOP and mean number of glaucoma medications used had decreased significantly (p < 0.01 and p = 0.03, respectively). Furthermore, the cumulative success rate was significantly higher in the OH group than in the glaucoma (100% vs. 47.4%; p < 0.01) when using criterion A. Additional glaucoma surgery was required only in the glaucoma group. Conclusions: IOL refixation surgery significantly decreases the IOP and number of glaucoma medications required in patients with elevated IOP due to IOL subluxation. Thus, IOL refixation surgery alone without glaucoma surgery might be effective as the primary procedure in such patients.

Purpose: Exfoliation glaucoma is a common and aggressive type of glaucoma with high prevalence in Scandinavia. The aim of this study was to elucidate whether the allele frequencies of two single nucleotide polymorphisms (SNPs) located in LOXL1 were associated with the progression of exfoliation glaucoma in Swedish patients. Methods: In this non‐randomised cohort study, we enrolled patients with exfoliation glaucoma, and they performed at least five reliable visual field tests. Blood samples were collected, and genotyping was performed using competitive allele‐specific PCR genotyping. Glaucoma progression was evaluated using the guided glaucoma progression analysis (GPA), mean deviation (MD) difference and rate of progression (ROP). In addition, associations between allele frequencies and glaucoma progression were tested using logistic regression for GPA and linear regression for MD and ROP. Results: We enrolled a total of 130 patients in the study. The general genetic model showed statistical significance for LOXL1_rs2165241 (p = 8 × 10−7, Fisher's exact test) and LOXL1_rs1048661 (p = 2 × 10−6, Fisher's exact test). Regression analyses using an additive genetic model showed significant values for LOXL1_rs2165241SNP in relation to GPA, MD and ROP as outcomes (p = 1.8 × 10−4, 4 × 10−2, 6 × 10−4) and for LOXL1_rs1048661 SNP in relation to GPA, MD and ROP (p = 7 × 10−5, 8 × 10−3, 2 × 10−4). Conclusions: This was the first study to show an association of the SNPs LOXL1_rs2165241 and LOXL1_rs1048661 with the progression of exfoliation glaucoma. Further large‐scale studies are required to verify these findings. [ABSTRACT FROM AUTHOR]

Several studies have suggested a possible relationship between exfoliation syndrome (XFS) and abdominal aortic aneurysm (AAA). A systematic literature review was undertaken to investigate this potential association. The systematic literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines. Clear definitions of XFS and AAA were used to identify eligible studies via an unrestricted search of the PubMed interface from 1979 to October 31st, 2021. After review, 876 citations were gathered and evaluated for inclusion, from which 22 articles were included. Of these 22, 16 were excluded because they did not assess the relationship between AAA and XFS or provide primary data. Ultimately, six studies were included in this literature review. Half of the studies explored AAA prevalence in a population with or without XFS, and the other half explored the opposite. Three studies supported XFS as a risk factor for the development of AAA, and the other three found this relationship to be inconclusive. This systematic review revealed inconsistent results regarding an association between AAA and XFS. A large database study including XFS and AAA patients would be useful in further determining if an association does in fact exist. [ABSTRACT FROM AUTHOR]

Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous system. Defects in Hcy metabolism have been associated with many neurodegenerative diseases including glaucoma, i.e., the leading cause of blindness. However, the pathophysiology of elevated Hcy and its eligibility as a risk factor for glaucoma remain unclear. We aimed to provide a comprehensive review of the relationship between elevated Hcy levels and glaucoma. Through a systemic search of the PubMed and Google Scholar databases, we found that elevated Hcy might play an important role in the pathogenesis of glaucoma. Further research will be necessary to help clarify the specific contribution of elevated Hcy in the pathogenesis of glaucoma. A discovery and conceptual understanding of Hcy-associated glaucoma could be the keys to providing better therapeutic treatment, if not prophylactic treatment, for this disease. [ABSTRACT FROM AUTHOR]

Purpose: A pilot study of electronic medical records (EMR) in Utah was undertaken to investigate exfoliation syndrome and exfoliation glaucoma (XFS/XFG) in abdominal aortic aneurysm (AAA) patients. In a subsequent retrospective cohort study of Utah XFS/XFG patients and population controls, the risk of AAA was examined. Methods: EMR of a statewide healthcare population were obtained from the Utah Population Database (UPDB) which links decades of medical records with Utah demographic and vital records data. In a pilot study, 7167 patients ages ≥40 years identified with AAA diagnosed from 1996 to 2015, based on International Classification of Diseases (ICD) version 9/10 codes, were included. A univariable hazards model was used to determine the risk of XFS/XFG in AAA patients. An XFS/XFG outcome based on ICD 9/10 codes in AAA patients and in 5:1 sex‐ and age‐matched non‐AAA controls was determined. A retrospective cohort of 3412 XFS/XFG patients ages ≥50 years diagnosed from 1996 to 2020 and 10 227 3:1 sex‐ and age‐matched controls who underwent ≥1 dilated eye examination(s) were recently identified and updated diagnoses of AAA were obtained. Multivariable logistic regression was used to estimate AAA risk in XFS/XFG patients compared with controls. In a subset of XFS/XFG patients, chart reviews were conducted to confirm clinically diagnosed AAA. Results: In the AAA pilot, 20 patients (0.3%) and 118 controls (0.3%) developed XFS/XFG, respectively. We observed no increased risk of XFS/XFG in AAA patients compared with non‐AAA‐matched controls (HR = 0.99, 95% CI 0.6–1.6). Among XFS/XFG study patients and controls, 122 patients (3.6%) and 376 controls (3.7%) had an AAA diagnosis. We likewise observed no increased risk of AAA in XFS/XFG patients (OR = 0.97, 95% CI 0.8–1.2). In 14 XFS/XFG patients with an ICD 9/10 diagnosis of AAA who underwent chart review, a clinical diagnosis of AAA was confirmed in 9 patients (64.3%). Conclusion: Our findings do not support an association between AAA and XFS/XFG. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the macular spectral domain optical coherence tomography (SD-OCT) measurements of the segmented inner retinal layers in patients with exfoliation syndrome (XFS), exfoliation glaucoma (XFG). Methods: This prospective cross-sectional study included 28 eyes with XFS, 47 eyes with XFG, and 29 healthy controls. Thickness of the inner retinal layers, including retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) was obtained from the horizontal SD-OCT scans. Functional correlation of structural parameters was analyzed using the mean sensitivity (MS) values on 10–2 visual fields. Results: The RNFL, GCL, and IPL were thinnest in eyes with XFG. Among these retinal layers, IPL was significantly thinner in eyes with XFS than healthy controls (p = 0.02) and the IPL thickness was significantly correlated with the corresponding MS scores on 10–2 visual fields (r = 0.492, p = 0.02) in eyes with XFS. Neither GCL nor RNFL thickness values demonstrated significant correlations with functional parameters in eyes with XFS (r = 0.377, p = 0.08; r = 0.212, p = 0.34). In eyes with XFG, the IPL thickness correlated with the visual field MS scores (r = 0.572, p = 0.0007), similar to the correlation of GCL (r = 0.585, p = 0.0005) thickness with visual field scores. Conclusions: Segmented analysis of the macular IPL thickness presented a significant correlation with the 10–2 visual field scores not only in eyes with XFG but also in eyes with XFS. With respect to early dendritic/synaptic alterations in animal models, larger and longitudinal studies are encouraged to determine the predictive value of the IPL thickness for conversion of XFS to XFG. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine whether including genetics as a risk factor for progression will improve the accuracy of the models used in newly diagnosed exfoliation glaucoma patients. Methods: This was a prospective cohort study. This study included only patients who were newly diagnosed with exfoliation glaucoma and received treatment upon inclusion. Blood samples were taken from all patients at inclusion to test for the single nucleotide polymorphisms (SNPs) LOXL-1 rs2165241 and rs1048661. Results: This study found that the frequency of SNPs, as well as intraocular pressure (IOP), mean deviation (MD), and visual field index (VFI) values at diagnosis, were significant predictors of visual field deterioration (p ≤ 0.001). This study showed that interaction terms, including SNPs, were highly significant (p ≤ 0.001). Furthermore, logistic regression analysis also showed highly significant results for interaction terms when SNPs were included (p ≤ 0.001). Finally, the area under the curve (AUC) analysis showed an increased value of around 10–20% when SNPs were included. Conclusions: Adding genetic factors to the well-known clinical risk factors can increase the accuracy of models for predicting visual field deterioration in exfoliation glaucoma patients. However, further studies are needed to investigate the role of other genes in this process.

Objective: To determine if exfoliation syndrome (XFS) is associated with hearing loss (HL) or vestibular dysfunction. Data Sources: PubMed, Scopus, CINAHL, and Cochrane Library through April 1, 2022. Review Methods: Two reviewers independently screened abstracts, selected articles for inclusion, and extracted data. Studies included for qualitative analysis conducted audiometric, tympanometric, or vestibular evaluations on all subjects. Results: Twenty‐one publications (1148 patients with XFS and 1212 controls) were included in the systematic review, and 16 publications (968 patients with XFS and 1147 controls) in the meta‐analysis. Greater severity of HL was seen for patients with XFS compared to controls across all frequencies (odds ratio [OR] 8.8 [7.3–10.2]). Patients with XFS were more likely to have moderate to profound sensorineural HL (OR 1.8 [1.3–2.5]), and less likely to have none to mild HL (OR 0.34 [0.17–0.67]) or no HL (OR 0.37 [0.28–0.50]). Three studies found patients with XFS had lower tympanometric peaks. Two studies found that abnormal vestibular testing results could be more common for patients with XFS. Conclusions: HL is associated with XFS. A sensorineural component to HL is confirmed, and mixed HL is possible. Given the high prevalence and infrequent diagnosis of XFS, the authors hypothesize that the current understandings of presbycusis might be improved by further investigation in XFS. Laryngoscope, 133:1025–1035, 2023 [ABSTRACT FROM AUTHOR]

Abstract Background To examine the risk factors for an early postoperative intraocular pressure (IOP) increase after ab interno trabeculotomy using a Kahook Dual Blade (KDB trabeculotomy). Methods A retrospective study was performed in 76 exfoliation glaucoma (EXG) eyes and 56 primary open angle glaucoma (POAG) eyes that underwent KDB trabeculotomy, with or without cataract surgery at Kumamoto University Hospital. Postoperative high IOP was classified as IOP≥20 mmHg (within three months after surgery, whether persistent or temporary), transient IOP≥20 mmHg (IOP≥20 mmHg after surgery, then dropped below 20 mmHg), and the presence of IOP spikes (≥ 10 mmHg from baseline). Risk factors were examined using logistic regression analysis. Results The preoperative mean IOP (SD) was 24.98 (7.23) mmHg in patients with EXG and 21.28 (6.58) mmHg in patients with POAG. IOP was reduced by 32.1% in patients with EXG and by 17.7% in patients with POAG at 6 months after surgery. Postoperative IOP≥20 mmHg was observed in 56.6% of EXG patients and in 51.8% of POAG patients. IOP spikes occurred in 15.8% of EXG patients and in 14.3% of POAG patients. Logistic regression analysis showed that factors with significant odds ratios (ORs) were age (OR = 0.866, 95% CI = 0.793–0.945), preoperative medication use (OR = 2.02, 95% CI = 1.17–3.49), trabeculotomy in combination with cataract surgery (OR = 0.0674, 95% CI = 0.015–0.303), and IOP at day 1 (OR = 1.41, 95% CI = 1.18–1.68) for postoperative IOP≥20 mmHg, the IOP at day 1 (OR = 1.1, 95% CI = 1.03–1.17) for transient IOP≥20 mmHg, and age (OR = 0.948, 95% CI = 0.901–0.997) and preoperative IOP (OR = 0.83, 95% CI = 0.736–0.936) for IOP spikes. Conclusion Although KDB trabeculotomy is an effective treatment for patients with EXG and POAG, patients who take multiple preoperative medications and have a high IOP on day 1 require careful follow-up to prevent postoperative IOP elevation.

Masaki Tanito,1 Yotaro Matsuoka2 1Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan; 2Division of Ophthalmology, Matsue Red Cross Hospital, Matsue, Shimane, JapanCorrespondence: Masaki Tanito, Department of Ophthalmology, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan, Tel +81-853-20-2284, Fax +81-853-20-2278, Email mtanito@med.shimane-u.ac.jpBackground: We report the real-world distribution of glaucoma types and glaucoma surgeries in each age or sex group in our department.Methods: The department database of Matsue Red Cross Hospital, a tertiary care hospital, for eyes surgically treated to manage glaucoma between April 2014 and March 2018 was searched. Patient age, sex, disease type, and surgical procedure were collected from the database. The age was stratified by ≤ 64 years (young), 65– 74 years (pre-old), 75– 89 years (old), and ≥ 90 years (oldest-old or super-old).Results: In the database, 2036 consecutive surgeries (70.3 ± 14.4 years; 1015 males) were identified. Among all subjects, primary open-angle glaucoma (POAG) (42.7%) was the most frequent identifiable glaucoma type followed by primary angle-closure disease (PACD) (18.8%) and exfoliation glaucoma (17.9%). The glaucoma types differed significantly among the age groups (P < 0.0001); POAG was the most frequent type of glaucoma in young and pre-old groups, while PACD and exfoliation glaucoma were the most frequent glaucoma types in the oldest-old group. Among all subjects, trabeculotomy or other goniotomy/gonio-bypass surgery (41.7%) was the most frequent glaucoma surgery followed by long-tube shunt (22.1%) and trabeculectomy (16.2%). The glaucoma surgeries performed differed significantly among the age groups (P < 0.0001). The frequency of trabeculectomy was the highest in the young group (27.8%), trabeculotomy was the highest in the pre-old (42.6%) and old (46.6%) groups, and long tube shunt (41.3%) and cataract extraction + goniosynechialysis (32.6%) were the highest in the oldest-old group. The glaucoma type (P < 0.0001) and surgeries performed (P < 0.0001) differed significantly between sex groups; the rates of PACD and cataract extraction + goniosynechialysis were remarkably higher in female than male group.Conclusion: The types of glaucoma and required glaucoma surgeries differ among the different age groups and sexes. Primary angle-closure disease and exfoliation glaucoma are the major glaucoma types in the old and oldest-old age groups.Keywords: primary open-angle glaucoma, POAG, primary angle-closure disease, PACD, exfoliation glaucoma, trabeculotomy, trabeculectomy, minimally invasive glaucoma surgery, MIGS, cataract extraction

Purpose: Ipilimumab is an immune checkpoint inhibitor that occasionally causes ophthalmic immune-related adverse events (irAEs) such as dry eye, uveitis, and episcleritis. We report a case of ipilimumab-related uveitis and refractory hypotony with a flat anterior chamber (AC) in a trabeculectomized eye with exfoliation glaucoma. Observation: A 69-year-old man with a history of cataract surgery and trabeculectomy for exfoliation glaucoma in the right eye presented with blurred vision at 2 months after initiation of ipilimumab for metastatic malignant melanoma (day 0). Although no ophthalmic irAEs were observed at the first visit, he developed iritis, vitreous opacity, and choroidal detachment by day 18.As a result of the irAEs, the scheduled course of ipilimumab was canceled and he was instead treated with corticosteroids (eye drops and systemic). The symptoms progressed, and on day 32 visual acuity was light perception, with a flat AC, hypotony maculopathy, and severe choroidal detachment in the right eye. The patient received two AC formations with a viscoelastic substance, but the flat AC and hypotony recurred. Because the effects of the surgeries were temporary, high doses of corticosteroids were administered. AC depth, anterior uveitis, intraocular pressure, and choroidal detachment resolved by day 91. Conclusions: Ophthalmologists and oncologists should be aware of the rare but severe irAEs, and careful follow-up is required for ophthalmic irAEs caused by ipilimumab, especially in cases with a history of glaucoma surgery.

To assess the association between intakes of total alcohol and individual alcoholic beverages and the incidence of exfoliation glaucoma/glaucoma suspect (XFG/XFGS) status. Prospective cohort study. A total of 195 408 participants in the Nurses' Health Study (1980–2018), the Health Professionals Follow-up Study (1986–2018), and the Nurses' Health Study II (1991–2019) were followed biennially. Eligible participants at each 2-year risk period were ≧ 40 years and free of XFG/XFGS status with available data on diet and ophthalmic examination findings. Cumulatively averaged total (primary exposure) and individual alcoholic beverage (beer, wine, and liquor) intakes from validated dietary information every 2-4 years. Confirmed incident XFG/XFGS status using medical records. We used per-eye Cox proportional hazards models, accounting for intereye correlations, to estimate multivariate-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). During 6 877 823 eye-years of follow-up, 705 eyes with XFG/XFGS status were documented. Greater total alcohol consumption was associated significantly with higher XFG/XFGS status risk: the MVRR for XFG/XFGS status for cumulatively averaged alcohol consumption of ≧15 g/day or more versus nondrinking was 1.55 (95% CI, 1.17–2.07; P = 0.02 for trend). Long- and short-term alcohol intake was associated significantly with XFG/XFGS status risk, with the strongest associations with cumulatively averaged alcohol intake as of 4 years before diagnosis (MVRR ≥ 15 g/day vs. nondrinking, 1.65; 95% CI, 1.25–2.18; P = 0.002 for trend). Compared with nondrinkers, consuming ≧ 3.6 drinks of beer, wine, or liquor per week was associated with the following MVRRs for XFG/XFGS status: 1.26 (95% CI, 0.89–1.77; P = 0.40 for trend), 1.30 (95% CI, 1.00–1.68; P = 0.15 for trend), and 1.46 (95% CI, 1.15–1.85; P = 0.01 for trend), respectively. We did not observe interactions by age, latitude, residential tier, or intakes of folate or vitamin A (P > 0.40 for interaction); however, the association between alcohol and XFG/XFGS status was suggestively stronger for those without a family history of glaucoma (P = 0.10 for interaction). Long-term alcohol consumption was associated with a higher risk of XFG/XFGS status. Our findings provide further clues regarding the XFG/XFGS etiology. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and minimally invasive glaucoma surgery (MIGS), visual and refractive outcomes were compared between eyes implanted with non-toric and toric IOLs during iStent triple procedures. Methods: In this retrospective study, open angle glaucoma eyes with preexisting corneal astigmatism of -1.5 diopter (D) or more and implanted with non-toric (n = 9) or toric (n = 9) IOLs were included. The main outcome measures were the intergroup difference in the uncorrected visual acuity (UCVA) and refractive astigmatism at 3 months postoperatively. Results: Preoperatively, the logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism were equivalent between the groups. Postoperatively, the logMAR UCVA (non-toric, 0.45 ± 0.31; toric, 0.14 ± 0.15; P = 0.021) was significantly better and the refractive astigmatism (non-toric, -2.03 ± 0.63 D; toric, -0.67 ± 0.53 D; P = 0.0014) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (-0.21, P = 0.020) and refractive astigmatism (+ 1.72 D, P = 0.0039). Vector analyses showed the postoperative centroid magnitude and confidence eclipses of refractive astigmatism was less in the toric group (0.47 D at 173°±0.73D) than the non-toric group (1.10 D at 2°±1.91D). Postoperatively, 78% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 11% in the non-toric group. Surgically induced astigmatism (non-toric, 0.18 D at 65°; toric, 0.29 D at 137°) did not differ between groups. Conclusion: Use of toric IOLs is a reasonable option for better visual outcomes when the combined cataract and iStent surgery is performed in glaucomatous eyes with corneal astigmatism. [ABSTRACT FROM AUTHOR]

Lysyl oxidase-like 1 encoded by the LOXL1 gene is a member of the lysyl oxidase family of enzymes that are important in the maintenance of extracellular matrix (ECM)-rich tissue. LOXL1 is important for proper elastic fiber formation and mice lacking LOXL1 (Loxl1−/−) exhibit systemic elastic fiber disorders, such as pelvic organ prolapse, a phenotype associated with exfoliation syndrome (XFS) in humans. Patients with XFS have a significant risk of developing exfoliation glaucoma (XFG), a severe form of glaucoma, which is a neurodegenerative condition leading to irreversible blindness if not detected and treated in a timely fashion. Although Loxl1−/− mice have been used extensively to investigate mechanisms of pelvic organ prolapse, studies of eyes in those mice are limited and some showed inconsistent ocular phenotypes. In this study we demonstrate that Loxl1−/− mice have significant anterior segment biometric abnormalities which recapitulate some human XFS features. We then focused on the peripapillary sclera (PPS), a critical structure for maintaining optic nerve health. We discovered quantitative and qualitive changes in ultrastructure of PPS, such as reduced elastic fibers, enlarged collagen fibrils, and transformed collagen lamella organization detected by transmission electron microscopy (TEM). Importantly, these changes corelate with altered tissue biomechanics detected by Atomic Force Microscopy (AFM) of PPS in mice. Together, our results support a crucial role for LOXL1 in ocular tissue structure and biomechanics, and Loxl1−/− mice could be a valuable resource for understanding the role of scleral tissue biomechanics in ocular disease.

Background: To examine the risk factors for an early postoperative intraocular pressure (IOP) increase after ab interno trabeculotomy using a Kahook Dual Blade (KDB trabeculotomy).Methods: A retrospective study was performed in 76 exfoliation glaucoma (EXG) eyes and 56 primary open angle glaucoma (POAG) eyes that underwent KDB trabeculotomy, with or without cataract surgery at Kumamoto University Hospital. Postoperative high IOP was classified as IOP≥20 mmHg (within three months after surgery, whether persistent or temporary), transient IOP≥20 mmHg (IOP≥20 mmHg after surgery, then dropped below 20 mmHg), and the presence of IOP spikes (≥ 10 mmHg from baseline). Risk factors were examined using logistic regression analysis.Results: The preoperative mean IOP (SD) was 24.98 (7.23) mmHg in patients with EXG and 21.28 (6.58) mmHg in patients with POAG. IOP was reduced by 32.1% in patients with EXG and by 17.7% in patients with POAG at 6 months after surgery. Postoperative IOP≥20 mmHg was observed in 56.6% of EXG patients and in 51.8% of POAG patients. IOP spikes occurred in 15.8% of EXG patients and in 14.3% of POAG patients. Logistic regression analysis showed that factors with significant odds ratios (ORs) were age (OR = 0.866, 95% CI = 0.793-0.945), preoperative medication use (OR = 2.02, 95% CI = 1.17-3.49), trabeculotomy in combination with cataract surgery (OR = 0.0674, 95% CI = 0.015-0.303), and IOP at day 1 (OR = 1.41, 95% CI = 1.18-1.68) for postoperative IOP≥20 mmHg, the IOP at day 1 (OR = 1.1, 95% CI = 1.03-1.17) for transient IOP≥20 mmHg, and age (OR = 0.948, 95% CI = 0.901-0.997) and preoperative IOP (OR = 0.83, 95% CI = 0.736-0.936) for IOP spikes.Conclusion: Although KDB trabeculotomy is an effective treatment for patients with EXG and POAG, patients who take multiple preoperative medications and have a high IOP on day 1 require careful follow-up to prevent postoperative IOP elevation. [ABSTRACT FROM AUTHOR]

Carotenoids have antioxidant properties, and the accumulation of advanced glycation end products (AGEs) is associated with reactive oxygen species production; they have attracted attention as factors predictive of the onset and progression in glaucoma. Fingertip measurement is applicable for carotenoids and AGEs due to its noninvasiveness and simplicity. The study included 663 eyes of 663 Japanese subjects (357 males, 306 females). The mean age was 69.9 years with a standard deviation of 11.0. The study population comprised participants with primary open-angle glaucoma (PG) (n = 358), exfoliation glaucoma (EG) (n = 168), and controls (n = 137). Multivariate models suggested that lower skin carotenoid (SC) levels were associated with male gender (standard β = −0.14), AGE scores (−0.24), and a history of intraocular surgery (−0.22). Higher SC levels were associated with higher vegetable intake scores (0.21 for score 3) and diabetes (0.10). However, no association was seen between SCs and glaucoma type. AGEs levels were negatively associated with carotenoid scores (−0.25), PG (−0.15), and smoking habits (−0.26) and positively correlated with EG (0.14). SCs and AGEs were negatively correlated in the single regression analysis (r = −0.20, p < 0.0001). In conclusion, higher levels of AGEs may be candidates for systemic biomarkers of glaucoma associated with the exfoliation syndrome. SC levels can reflect self-reported daily vegetable intake. [ABSTRACT FROM AUTHOR]

Tolga Kocatürk,1 Maja Zivkovic,2 Volkan Dayanır3 1Department of Ophthalmology, Aydın Adnan Menderes University, Aydın, Turkey; 2Department of Ophthalmology, Medical Faculty, University of Nis, Nis, Serbia; 3Department of Ophthalmology, Batıgöz Hospital, Izmir, TurkeyCorrespondence: Tolga KocatürkAydın Adnan Menderes Universitesi, Tip FakultesiHastanesi, Goz Hast, AD, Aydin, 09100, TurkeyTel +90 533 344 4111Fax +90 256 214 6495Email tolgakocaturk@gmail.comPurpose: To compare the vascular measurements obtained from fovea including foveal avascular zone (FAZ) with optical coherence tomography angiography (OCTA) between patients with exfoliation glaucoma (XFG) and healthy controls.Methods: This cross-sectional comparative study included 54 XFG patients and 94 healthy subjects. All subjects were given a complete ophthalmological examination including visual field testing, retinal nerve fiber layer and macular ganglion cell complex analysis. OCTA was performed to evaluate the vascular features of fovea including FAZ. The measurements of vessel density (VD), perfusion density (PD) and FAZ values were segmented and calculated using the inbuilt software on OCTA. Receiver operating characteristic (ROC) analyses were performed to determine the best cut-off values to detect the disease.Results: In the XFG group, decreased VD, PD and FAZ values were observed. ROC analysis showed an obvious separation, differentiating the patients with XFG from the healthy controls at cut-off value of 19.55 with a sensitivity (sen) of 92.3% and a specificity (spe) of 81.9%) for VD total and 21.20 (sen:100 and spe:78.7) for VD parafoveal; 0.36 (sen:98.1and spe:76.6) for PDtotal and 0.378 (sen:96.2and spe:84) for PDparafoveal; 0.635 (sen: 79.3 and spe:72) for FAZ circulatory index.Conclusion: The results support the findings of decreased microvascular density on foveal region in XFG. The cut off values of the changes in the foveal parameters in patients with exfoliation may be useful in evaluation of future glaucoma management to show how far a particular exfoliative eye is positioned from an healthy eye and how close to XFG.Keywords: exfoliation glaucoma, optical coherence tomography angiography, foveal avascular zone

Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. Retrospective case study. A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7–20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4–11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes of flanged intraocular lens fixation combined with microhook trabeculotomy. Patients and methods: This study was a retrospective case series and included nine eyes of nine exfoliation glaucoma patients with subluxated lens or intraocular lens who underwent flanged intraocular lens fixation combined with microhook trabeculotomy between May 2019 and February 2020 at the Kochi University Hospital. The mean best-corrected visual acuity, intraocular pressure, and number of antiglaucoma medications were compared before and after surgery. Results: The mean follow-up period was 5.67 ± 2.50 months. The mean best-corrected visual acuity improved significantly from 0.83 ± 0.72 preoperatively to 0.22 ± 0.34 at the last visit (p = 0.015). The mean intraocular pressure had significantly reduced from 27.1 ± 8.12 mmHg preoperatively to 13.2 ± 3.73 at the last visit (p = 0.008). The mean number of antiglaucoma medications decreased significantly from 4.56 ± 1.88 to 2.0 ± 1.0 at the last visit (p = 0.008). Postoperative intraocular pressure control to 21 mmHg or lower was achieved or maintained in all patients. Postoperative vitreous hemorrhage was observed in six eyes (66.7%), two of which needed reoperation. Conclusions: This study showed that flanged intraocular lens fixation combined with microhook trabeculotomy might be effective for exfoliation glaucoma with subluxated lens or intraocular lens. [ABSTRACT FROM AUTHOR]

Abstract Background The present study aimed to compare visual field progression in new-diagnosed exfoliation versus open-angle glaucoma patients. Methods Retrospective study. The study included patients with new-diagnosed primary open-angle and exfoliation glaucoma. All patients were followed for 3 years with reliable visual fields. At least five reliable fields were needed for inclusion. Exfoliation and open-angle glaucoma were defined based on the European Glaucoma Society guidelines. Visual field evaluation was performed using the software threshold 24–2 of the Humphrey Field Analysis. Outcomes: Visual field progression. For visual field progression, three different strategies were used: mean deviation (MD), visual field index (VFI), and the guided progression analysis (GPA). Results The study included 128 subjects, of the 54 in the open-angle and 74 in the exfoliation glaucoma group. The MD difference values were higher in the exfoliation (− 3.17 dB) than in the primary open-angle (− 1.25 dB) glaucoma group in the three-year follow-up period. The difference between groups was significant (t-test, p =

Objective: To identify clinical factors associated with conversion to exfoliation glaucoma (XFG) in exfoliation syndrome (XFS) patients who are most at risk of progression to XFG within 3 years for increased surveillance and early preventive interventions., Design: A retrospective patient cohort study design was employed., Subjects: A source population of XFS patients ≥ 50 years was identified from electronic medical records in the Utah Population Database. From this, 487 study patients with one or more dilated eye examinations before chart-confirmed XFS onset in 2011 or later and ≥ 3 years of subsequent eye examinations were selected for study., Methods: We implemented binomial linear mixed models with L1-penalized estimation to select variables associated with conversion. Models included a random intercept to account for within-patient correlation for eye-level data. Candidate demographic, lifestyle, systemic, and ocular comorbidities data were obtained, and diagnoses were categorized as binary (history or no history). These potential factors between conversion and nonconversion patients were used in model selection of variables jointly predictive of conversion. Odds ratios and confidence intervals were calculated using the link logit., Main Outcome Measures: To determine the main outcome of conversion to XFG following an index diagnosis of XFS compared with nonconversion within 3 years, clinical records of each subject's left and right eyes were assessed to confirm XFS and date of onset and date of XFG onset, if conversion occurred. Clinical measurements (e.g., intraocular pressure [IOP], cup-to-disc ratio, provider notes, and IOP-lowering procedures and medications) were used to corroborate conversion status., Results: Eighteen variables jointly predicted XFG conversion within 3 years correctly in 71% of patient eyes. The odds of conversion were the highest for exudative age-related macular degeneration (AMD), 2.3-fold (P = 0.004). Other predictive variables included nonexudative AMD (P = 0.05), primary open angle glaucoma (P < 0.001), obstructive sleep apnea (P = 0.03), and ocular hypertension (P = 0.003) diagnosed before XFS onset., Conclusions: We determined a set of clinically relevant factors that predicted which newly diagnosed XFS patients progressed to XFG within 3 years. A planned validation will independently confirm if these prognostic indicators hold promise in other settings., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The present study aimed to identify whether former smoking was a risk factor for visual field progression in exfoliation glaucoma patients., Methods: Prospective nonrandomised cohort study. The study included patients diagnosed with exfoliation glaucoma. All included patients were followed for three years (± three months) with reliable visual fields. At least five reliable visual fields needed to be included in the study. Exfoliation glaucoma was defined using the European Glaucoma Society Guidelines. The visual fields were tested using the 24-2 test strategy of the Humphrey Field Analyzer. Smoking was assessed through questionnaires. Outcomes: Visual field progression. Three different approaches were used: difference in mean deviation (MD), rate of progression (ROP), and guided progression analysis (GPA)., Results: In total, n  = 113 patients were included; among them, n  = 57 were smokers. Smoking was a significant predictor for visual field progression in the three models (MD/ROP/GPA) studied ( p  = 0.01/ p  = 0.001/p ≤ 0.001), even adjusting for intraocular pressure (IOP). Other predictors were included in the MD model: IOP at diagnosis ( p  = 0.04) and selective laser trabeculoplasty (SLT) treatment ( p  = 0.01). Other predictors were in the ROP model: Visual field index ( p  = 0.005), number of medications ( p  = 0.001) and SLT treatment ( p  = 0.001). The number of medications was another predictor in the GPA model ( p  = 0.002)., Conclusions: Former smoking induced visual field deterioration in all models studied. Smoking status should be considered when establishing the glaucoma diagnosis. Increased glaucoma care should be provided to former smokers to slow the progression of the disease., Competing Interests: Declaration of conflicting interestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To investigate the relationship between exfoliation syndrome (XFS) and systemic diseases. Methods: A population-based, retrospective study with control group was conducted using the electronic medical database of Maccabi Health Services, the second largest Health Maintenance Organization (HMO) in Israel. Study population included Maccabi members from January 2003 to April 2016. Cases consisted of patients diagnosed with XFS regardless of glaucoma. The control group included Maccabi members without XFS, matched on age, sex, and ancestry, that were examined by an ophthalmologist within the last year. Main outcome measures: Associations between XFS and systemic diseases. Results: We identified 16,388 patients with XFS, in whom 40.3% (n = 6613) had glaucoma. The control group included 14,015 patients. Mean age was 78.3 ± 8.9 years and 76.2 ± 8.5 years for the XFS and control group, respectively. In unconditional logistic regression analyses, after adjusting for age, sex, and ancestry, XFS was significantly associated with risk of cardiovascular diseases including hypertension (OR 1.07, 95% CI 1.01–1.13, p = 0.02), myocardial infarction (OR 1.21, 95% CI 1.17–1.31, p < 0.0001), and congestive heart failure (OR 1.70, 95% CI 1.55–1.88, p < 0.0001) as well as higher risk for high creatinine (OR 1.28, 95% CI 1.2–1.37, p < 0.0001). Diabetes mellitus and body mass index were inversely associated with XFS (OR 0.70, 95% CI 0.67–0.73, p < 0.0001 and OR 0.88, 95% CI 0.84–0.93, p < 0.0001, respectively). Overall cancer diagnoses were more common in the XFS group (OR 1.05, 95% CI 1.0–1.1, p = 0.05). XFS was associated with more hospitalizations (mean 5 ± 5.3 hospitalizations in the XFS group and 3.3 ± 4.0 in the controls, p < 0.0001). Conclusion: XFS is significantly associated with cardiovascular systemic diseases (in a population living in Israel and predominantly born in Russia). [ABSTRACT FROM AUTHOR]

Pseudoexfoliation glaucoma (XFG) is an aggressive form of secondary open angle glaucoma, characterised by the production of exfoliation material and is estimated to affect 30 million people worldwide. Activation of the TGF-β pathway by TGF-β1 has been implicated in the pathogenesis of pseudoexfoliation glaucoma. To further investigate the role of TGF-β1 in glaucomatous changes in the trabecular meshwork (TM), we used RNA-Seq to determine TGF-β1 induced changes in the transcriptome of normal human trabecular meshwork (HTM) cells. The main purpose of this study was to perform a hypothesis-independent RNA sequencing analysis to investigate genome-wide alterations in the transcriptome of normal HTMs stimulated with TGF-β1 and investigate possible pathophysiological mechanisms driving XFG. Our results identified multiple differentially expressed genes including several genes known to be present in exfoliation material. Significantly altered pathways, biological processes and molecular functions included extracellular matrix remodelling, Hippo and Wnt pathways, the unfolded protein response, oxidative stress, and the antioxidant system. This cellular model of pseudoexfoliation glaucoma can provide insight into disease pathogenesis and support the development of novel therapeutic interventions.

(1) Background: Exfoliation syndrome (XFS) is a common cause of secondary open angle glaucoma. In 1971, Faulkner et al. estimated the prevalence of XFS among 50 Navajo Nation residents as 38%. Given that XFS can cause irreversible blindness secondary to glaucoma (XFG), this study aims to identify the current prevalence of XFS among Navajo Nation residents within the Four Corners region of the U.S. (2) Methods: A retrospective chart review was conducted from 2016 to 2021 for patients aged 18 and older. All patients with XFS or XFG diagnosed by slit lamp exam were identified through chart review. (3) Results: Of the 1152 patient charts available for review, eight patients (11 eyes) were diagnosed with XFS with three patients (4 eyes) demonstrating concomitant XFG. Within this XFS population, 50% of the patients identified as male, with a mean age of 73 years. The overall prevalence of XFS was 0.7% and the overall prevalence of XFG was found to be 0.26%. The rate of XFG among patients with XFS was 37.5%. (4) Conclusion: Compared to Faulkner’s study of Navajo Nation residents in 1971, our findings show a considerably lower prevalence of XFS at 0.7%. We present the largest study to date of XFS among this population.

Aim: This study aimed to investigate the role of functionally significant polymorphisms of the MMP1, MMP3, and MMP9 genes in the development of exfoliation glaucoma (XFG) in the Caucasian population of Central Russia. Methods: The study sample consisted of 724 participants, including 328 patients with XFG and 396 individuals in the control group. The participants were of Russian ethnicity (self-reported) born in Central Russia. The participants were genotyped at 8 functionally significant polymorphisms of the MMP genes (rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 MMP9, rs679620 MMP3, and rs1799750 MMP1). The association analysis was performed using logistic regression. Two polymorphisms, which were associated with XFG, and 12 polymorphisms linked to them (r2 ≥ 0.8) were analyzed for their functional significance in silico. Results: Allele C of rs3918249 MMP9 was associated with XFG according to the additive model (OR = 0.75, 95% CI: 0.56–0.93, pperm = 0.015), and allele G of the rs2250889 MMP9 locus was associated with XFG according to the additive (OR = 1.59, 95% CI: 1.10–2.29, pperm = 0.013) and dominant (OR = 1.68, 95% CI: 1.11–2.56, pperm = 0.016) models. Two XFG-associated loci of the MMP9 gene and 12 SNPs linked to them had a significant regulatory potential (they are located in the evolutionarily conserved regions, promoter and enhancer histone marks, the DNAase-hypersensitivity regions, a region binding to regulatory protein, and a region of regulatory motifs) and may influence the expression of 13 genes and alternative splicing of 4 genes in various tissues and organs related to the pathogenesis of XFG. Conclusion: Allele C rs3918249 MMP9 decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 MMP9 locus increased risk for XFG (OR = 1.59–1.68) in the Caucasian population of Central Russia. [ABSTRACT FROM AUTHOR]

Background: Pseudoexfoliation syndrome (PES) is an age-related systemic condition that predominantly affects ocular structures and is characterized by the deposition of material on the lens, ciliary body, zonules, corneal endothelium, iris, and pupillary margin. We compared the corneal endothelial morphology, anterior segment parameters, corneal densitometry, and corneal topographic characteristics between the clinically affected and apparently normal fellow eyes of patients with clinically unilateral PES., Methods: This was a comparative, cross-sectional study of 34 patients with clinically unilateral PES. The anterior segment was examined using a Scheimpflug imaging system, and the corneal endothelium was assessed using a noncontact specular microscope. Corneal endothelial cell density, polymegathism, and pleomorphism were assessed using the specular microscope. Furthermore, the Scheimpflug camera was used to measure the corneal power of the flat and steep axis, mean corneal power, maximum keratometry, anterior chamber angle, anterior chamber depth, anterior chamber volume, corneal volume, and the corneal thickness at the apex point, center of the pupil, and the thinnest point. Corneal densitometry was evaluated at two concentric zones (0-2 mm and 0-12 mm)., Results: In total, 68 eyes from 34 patients were ultimately included in the study. The mean (standard deviation) age of the patients was 73.38 (8.75) years (range: 50-87 years). Among the included patients, 17 (50%) were male and 17 (50%) were female. The anterior segment parameters did not significantly differ between eyes with PES and their clinically unaffected fellow eyes (all P > 0.05). Similarly, no statistically significant difference was observed in corneal endothelial morphology (all P > 0.05)., Conclusions: Our measured parameters do not differ between the clinically affected eye and the clinically unaffected fellow eye. This supports the theory that PES is a bilateral disorder. Considering the variety of complications associated with PES, bilateral involvement should be assumed in the clinical and surgical management of patients with clinically unilateral PES. In the future, new research could increase our understanding of this syndrome., Competing Interests: None., (© Author(s).)

Background: The effects of trabeculectomy on anterior segment parameters have been widely investigated. However, the stabilization time for various glaucoma types after trabeculectomy remains debatable. We investigated the effect of mitomycin C-augmented trabeculectomy on ocular anterior segment parameters in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) during short-term follow-up using the Pentacam HR., Methods: In this retrospective observational study, consecutive patients diagnosed with medically uncontrolled POAG or PXG who underwent MMC-augmented trabeculectomy were recruited. All individuals underwent detailed ocular examinations. All trabeculectomies were performed by a single surgeon using the same technique. Anterior segment parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV), anterior chamber angle (ACA), and central corneal thickness (CCT) were measured using the Pentacam HR, along with intraocular pressure (IOP) using a Goldmann applanation tonometer, pre-operatively and at 1-week, 1-month, and 3-month post-operative visits., Results: We included 80 patients with a median (range) age of 58.0 (41.0-86.0) years having a nearly similar sex ratio. The study groups were matched according to sex and age (both P > 0.05). The group-by-time interaction was significant for CCT and ACV (both P < 0.05) but not for IOP, ACD, and ACA (all P > 0.05). The mean (standard deviation [SD]) IOP, ACD, and ACA were comparable between groups (all P > 0.05) during the 3-month period; however, they changed significantly over time in both groups (all P < 0.001). The mean CCT and ACV were comparable between groups at each time point (all P > 0.05), except at the 1-month post-operative visit, at which the mean (SD) ACV was significantly lower in the PXG group ( P < 0.05). We found a comparable mean (SD) CCT between paired visits in each group (all P > 0.05), except for the mean (SD) CCT at 3 months, which was significantly lower than that at the 1-month post-operative visit in the PXG group ( P < 0.05). We found a comparable mean (SD) ACV between paired visits in each group (all P > 0.05); however, it was significantly lower at the 1-month post-operative versus the baseline visit in both groups and resumed a significantly higher value at the 1-month versus the 1-week visit and at the 3-month versus the 1-month visit in the PXG group (all P < 0.05)., Conclusions: We observed significant changes in IOP, ACD, and ACA over 3 months after post-augmented trabeculectomy in eyes with POAG and PXG; however, the majority of anterior segment parameters were comparable between the two groups. Further large-scale studies with longer follow-up periods should be conducted to verify the post-operative fluctuations in these parameters in POAG and PXG., Competing Interests: None., (© Author(s).)

Background Pseudoexfoliation syndrome (PEX) is characterized by a dandruff-like substance in the anterior chamber, composed of various glycoproteins that have an unclear origin. Its deposition is observed on the pupillary margin, lens zonules, and trabecular meshwork. Proteomic studies have identified numerous proteins in the affected individuals, suggesting associations with systemic conditions like heart disease, stroke, and Alzheimer's disease. However, the systemic associations of PEX remain inconclusive, particularly in regions like southern India. Materials and methods A cross-sectional study was conducted on 114 participants. Pseudoexfoliation was graded as mild, moderate, and severe as per standard photographic grading. Systemic examinations included blood pressure measurements, electrocardiography (ECG), and blood investigations for serum lipid profile, fasting and postprandial blood sugar levels, and serum C-reactive protein levels. Small incision cataract surgery was performed for all the patients. Intraoperative complications and postoperative status were recorded. Results Thirty-eight patients (33.3%) had mild PEX, 44 (38.6%) had moderate PEX, and 32 (28.1%) had severe PEX. Hypertension was present in 54 participants (47.4%), diabetes in 21 (18.4%), coronary artery disease in nine (7.9%), and cerebrovascular accidents in three (2.6%). The mean systolic blood pressure was 140.39 mmHg and the mean diastolic blood pressure was 90.37 mmHg. Systolic blood pressure exceeded 140 mmHg in 29 participants (90.6%) with severe PEX, while diastolic blood pressure surpassed 90 mmHg in 26 participants with severe PEX, both with a p-value of 0.001. Mean fasting and postprandial blood sugar levels were 103.80 ± 31.81 mg/dl and 131.72 ± 48.24 mg/dl, respectively. Serum lipid profiles showed mean low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), cholesterol, and triglyceride levels of 103.00 ± 34.49 mg/dl, 29.04 ± 15.51 mg/dl, 172.73 ± 43.34 mg/dl, and 129.33 ± 64.65 mg/dl respectively. Electrocardiographic results indicated that 54 participants (47.37%) had abnormal ECG including rate abnormality in 13.2%, conduction defects in 12.3%, ischemic changes in 10.5%, and structural defects in 11.4%. Eighty-seven percent of patients had non-dilating pupils and iris atrophy, 13.2% had zonular dialysis and intraoperatively, 78% had capsulorhexis extension, 49.12% had difficult nucleus prolapse, and 28.95% had posterior capsular rent. Conclusion This study highlights the significantly elevated parameters of systemic vascular diseases in PEX patients, like elevated blood pressure and more frequent cardiac anomalies, emphasizing the need for comprehensive systemic evaluation and careful preoperative assessment for ocular comorbidities., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. BLDE (Deemed to be University) Institutional Ethical Committee issued approval BLDE (DU)/IEC/687/2022-23. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patil et al.)

Purpose: To evaluate the macular choroidal thickness (CT) and central macular thickness (CMT) in exfoliation syndrome (XFS), exfoliation glaucoma (XFG) and age-matched healthy subjects using spectral-domain optical coherence tomography (SD-OCT) and to investigate the correlations of CT and CMT with ganglion cell complex (GCC). Materials and Methods: This study included patients diagnosed with XFS, XFG, and healthy volunteers. CMT was analyzed with standard OCT protocol while CT was analyzed with enhanced depth imaging (EDI) modality in all subjects. Results: The study included; 41 eyes with XFS, 62 eyes with XFG and 30 eyes of healthy subjects. The mean CMT were; 253.3 ± 35.8 µm, 258.5 ± 43.4 µm and 255.1 ± 29.9 µm in the XFS, XFG and control group respectively (p=0.52). The mean CT in XFS group was significantly thinner than XFG and control (p<0.001). In XFS group, we detected weak positive correlations of average ganglion cell layer+inner plexiform layer (GCL+IPL) thickness and minimum GCL+IPL thickness with CT (R= +0.23, R=+0.21 respectively, p=0.15, p=0.19). In XFG patients, average GCL+IPL thickness and minimum GCL+ IPL thickness showed weak negative correlations with CMT (R= -0.22, R= -0.18 respectively, p=0.008, p=0.15), but there was no correlation between GCC parameters and CT measurements (R= -0.12, R= -0.09 respectively, p=0.32, p=0.52). Conclusions: In XFS group, choroidal changes may be an early indicator for transformation of XFS to XFG. Relatively thicker choroid in XFG group may be related to the reversibility of this situation with treatment. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to compare the effects of exfoliation (XF) on surgically induced astigmatism (SIA) in patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG) after trabeculectomy. Materials and Methods: Twenty-one eyes with POAG and 22 eyes with XFG were included in this prospective clinical study. The eyes had uncomplicated initial trabeculectomy with 5-fluorouracil (5-FU). All cases underwent a complete ocular examination including corneal topography at baseline and at postoperative first, third, and sixth months. SIA was calculated by the vector analysis method using the Holladay-Cravy-Koch formula. Results: The mean SIA values were 0.92±0.35 diopter (D), 0.96±0.34 D, and 0.82±0.34 at the first, third, and sixth months, respectively, in the POAG group and 1.17±0.43 D, 1.25±0.44 D, and 1.05±0.42 D at the first, third, and sixth months, respectively, in the XFG group. Significant differences existed between the groups at postoperative first and third months, but no significant difference was observed at the sixth month (p=.040, p=.027, p=.061, respectively). At the sixth month, with the rule (WTR) astigmatism rates were 76% in the POAG group and 45% in the XFG group (p=.039). Significant correlations were found between the SIA values, and intraocular pressure changes were observed at the first and sixth months (r=-0.502, p=.017; r=-0.520 p=.013) in the XFG group. Conclusion: SIA values in XFG patients after trabeculectomy were higher in the early period compared to POAG patients. This may be due to local inflammation caused by XF and its effect on corneal biomechanics. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to compare visual field progression in new-diagnosed exfoliation versus open-angle glaucoma patients.Methods: Retrospective study. The study included patients with new-diagnosed primary open-angle and exfoliation glaucoma. All patients were followed for 3 years with reliable visual fields. At least five reliable fields were needed for inclusion. Exfoliation and open-angle glaucoma were defined based on the European Glaucoma Society guidelines. Visual field evaluation was performed using the software threshold 24-2 of the Humphrey Field Analysis.Outcomes: Visual field progression. For visual field progression, three different strategies were used: mean deviation (MD), visual field index (VFI), and the guided progression analysis (GPA).Results: The study included 128 subjects, of the 54 in the open-angle and 74 in the exfoliation glaucoma group. The MD difference values were higher in the exfoliation (- 3.17 dB) than in the primary open-angle (- 1.25 dB) glaucoma group in the three-year follow-up period. The difference between groups was significant (t-test, p = < 0.001). The difference in VFI was calculated for the 3 years follow-up period. The difference was higher in the exfoliation (- 7.65%) than in the primary open (- 1.90%) glaucoma group (t-test, p = < 0.001). The GPA showed progression in 58% of cases in exfoliation, and 13% in primary open glaucoma group (Chi-square, p = < 0.001).Conclusion: The present study found a more frequent and faster visual field progression in exfoliation than in primary open-angle glaucoma patients. New-diagnosed exfoliation glaucoma patients must be controlled and treated more strictly than primary open-angle glaucoma patients to avoid visual field deterioration. [ABSTRACT FROM AUTHOR]

Exfoliation syndrome is generally considered a progressive age‐related systemic disorder of the extracellular matrix, which is clinically characterized through the observation of flaky white aggregates on ocular tissues. Exfoliation syndrome is directly linked to exfoliative glaucoma in elderly patients, where it is known as the most common identifiable cause of open‐angle glaucoma. Despite the identification of various risk factors associated with exfoliation syndrome, the exact pathogenesis of this syndrome has not been fully elucidated. There is a growing number of genome‐wide association studies in different populations around the world to identify genetic factors underlying exfoliation syndrome. Besides variants in LOXL1 and CACNA1A genes, new loci have been recently identified which are believed to be associated with exfoliation syndrome. Among different genetic factors, functional variants might help to better understand mechanisms underlying this systemic disorder. Besides genetic factors, epigenetic regulation of different gene expression patterns has been thought to play a role in its pathogenesis. Other factors have been also considered to be involved in the development of exfoliation syndrome at cellular organelles level where mitochondrial impairment and autophagy dysfunction have been suggested in relation to exfoliation syndrome. This review addresses the most recent findings on genetic factors as well as cellular and molecular mechanisms involved in both the development and progression of exfoliation syndrome. [ABSTRACT FROM AUTHOR]

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH.

Advanced glycation end products (AGEs), which are the products of a non-enzymatic reaction between reducing sugars and other macromolecules, are critical in aging, as well as metabolic and degenerative diseases. To assess the involvement of AGEs in glaucoma, skin autofluorescence (sAF) level, which is a measurement of AGEs’ accumulation, was compared among Japanese patients with glaucoma (316 with primary open-angle glaucoma (PG) and 127 exfoliation syndrome and glaucoma (EG)) and controls (133 nonglaucomatous controls) (mean age 71.6 ± 12.8 years, 254 men and 322 women). The sAF values were estimated from the middle fingertip using a 365 nm light-emitting diode for excitation and detection at 440 nm emission light. The estimated AGE values (arbitrary unit) were 0.56 ± 0.15, 0.56 ± 0.11, and 0.61 ± 0.11 in the control, PG, and EG groups, respectively (p < 0.0001, analysis of variance); and were significantly higher in the EG group than the control (p = 0.0007) and PG (p < 0.0001) groups. After adjustment for various demographic parameters by multivariate analyses, male sex (standard β = 0.23), EG (0.19), and diabetes (0.09) were associated with higher AGE levels; PG (−0.18) and smoking (−0.19) were associated with lower AGE levels. Age, visual acuity, intraocular pressure, glaucoma medications, lens status, and systemic hypertension were not associated with AGEs. The high AGE level in EG suggested that specific oxidation and glycation mechanisms underlie the glaucoma pathogenesis associated with pseudoexfoliation syndrome.