OBJECTIVE: 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).
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.

BACKGROUND: The use of the PreserFlo microshunt is gaining popularity owing to its ease of implantation and reduced need for postoperative intervention compared to conventional trabeculectomy.
METHODS: However, microshunt exposure remains a severe complication of PreserFlo surgery, particularly in patients with a thin Tenon capsule and conjunctiva. However, the actual thickness and intensity of the Tenon capsule or conjunctiva can be confirmed only during surgery.
METHODS: Exfoliation glaucoma with previous several glaucoma surgeries with thinner Tenon capsule or conjunctiva.
METHODS: We performed PreserFlo implantation with a surgical technique to recover a thin Tenon capsule and conjunctiva by creating a half-thickness rectangular scleral flap under the shunt and covering it over the microshunt until the distal part, similar to the bridge.
RESULTS: The patient had better intraocular pressure control with positive cosmetic appearance using this technique.
CONCLUSIONS: This technique will be beneficial for both preventing exposure and holding down the top, in addition to improving cosmetic appearance.

BACKGROUND: The purpose of this study was to investigate the visual and refractive outcomes in patients with pseudoexfoliation (PXF) undergoing routine cataract surgery and to compare the accuracy of intraocular lens (IOL) power calculation formulae.
METHODS: Retrospective case-series study from Shamir medical center, a public hospital, Israel. Medical records of patients who underwent routine cataract surgery between January 2019 and August 2021 were investigated. Postoperative visual acuity and manifest refraction were examined. The error in predicted refraction and IOL power calculation accuracy within a range of ± 0.50 to ± 1.00 diopters were compared between different IOL calculating formulae.
RESULTS: 151 eyes of 151 patients ages 73.9 ± 7.1 years were included in this study- 58 eyes in the PXF group and 93 eyes in the control group. The mean absolute error (MAE) for the BUII formula was 0.63D ± 0.87 for the PXF group and 0.36D ± 0.48 for the control group (p < 0.05). The MAE for the Hill-RBF 3.0 formula was 0.61D ± 0.84 for the PXF group and 0.42D ± 0.55 for the control group (p = 0.05). There were significant differences in MAE and MedAE between PXF group and control group measures (p < 0.05). In the PXF group there were no significant differences between the different formulae.
CONCLUSIONS: There were significant differences in accuracy of IOL power calculations in all formulae between PXF group and control group measures. PXF patients show hyperopic shift from predicted refraction. Barret universal II formula had the highest proportion of eyes with absolute error in prediction below or equal to 0.50 D in both PXF and control groups.

OBJECTIVE: To characterize glaucoma progression in early-stage patients with retinal nerve fiber layer (RNFL) using the change analysis software (CAS), which was utilized to track RNFL thinning.
METHODS: We retrospectively analyzed 92 eyes of 92 patients with early-stage glaucoma. Patients were divided into two subgroups based on their diagnosis of pseudoexfoliation glaucoma (PEG) and primary open-angle glaucoma (POAG). A complete ophthalmologic examination was performed on all patients. Additionally, automated perimetry was conducted on each patient. Furthermore, Fourier-domain optical coherence tomography (OCT) was employed to measure RNFL and central corneal thickness. Using the OCT device\'s CAS, we computed the annual rate of total and glaucomatous RNFL thinning for each patient.
RESULTS: A total of 44 PEG and 48 POAG patients were included in the study. The right eye measurements of these patients were analyzed and compared. The two groups were not significantly different in age, gender, and the number of visits per year (p > 0.05, for each). However, the difference between the mean RNFL thickness at baseline (91.39 ± 10.71 and 96.9 ± 8.6 µm) and at the last visit (85.2 ± 15.76 µm and 91.56 ± 9.58 µm) was statistically significant between the two groups (p = 0.043, p = 0.039, respectively). Additionally, the difference in annual RNFL thinning rates (1.43 ± 0.81 µm and 1.07 ± 0.32 µm) between the two groups was statistically significant (p = 0.009).
CONCLUSIONS: The annual rate of glaucomatous RNFL loss in early-stage PEG patients (1.23 µm) was higher than in POAG patients (0.87 µm). However, despite these loss rates, scotoma was not detected in the visual field tests of these patients. Therefore, using CAS in the follow-up of early-stage glaucoma patients is a useful alternative for monitoring glaucomatous progression. Furthermore, this method can be utilized in future research for the diagnosis and follow-up of glaucoma in special populations (e.g., those with pathological myopia or high hyperopia) that are not included in normative databases.

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.

To investigate biomarkers of intra-ocular pressure (IOP) decrease after cataract surgery with trabecular washout in pseudo-exfoliative (PEX) glaucoma. A single-center observational prospective study in PEX glaucoma patients undergoing cataract surgery with trabecular washout (Goniowash) was performed from 2018 to 2021. Age, gender, visual acuity, IOP, endothelial cell count, central corneal thickness, medications, were collected over 16-month follow-up. Multivariable binomial regression models were implemented. 54 eyes (35 subjects) were included. Mean preoperative IOP (IOPBL) was 15.9 ± 3.5 mmHg. Postoperative IOP reduction was significant at 1-month and throughout follow-up (p < 0.01, respectively). IOPBL was a predictive biomarker inversely correlated to IOP decrease throughout follow-up (p < 0.001). At 1 and 12 months of follow-up, IOP decrease concerned 31 (57.4%) and 34 (63.0%) eyes with an average IOP decrease of 17.5% (from 17.6 ± 3.1 to 14.3 ± 2.2 mmHg) and 23.0% (from 17.7 ± 2.8 to 13.5 ± 2.6 mmHg), respectively. Performance (AUC) of IOPBL was 0.85 and 0.94 (p < 0.0001, respectively), with IOPBL threshold ≥ 15 mmHg for 82.1% and 96.8% sensitivity, 84.2% and 75.0% specificity, 1.84 and 3.91 IOP decrease odds-ratio, respectively. All PEX glaucoma patients with IOPBL greater than or equal to the average general population IOP were likely to achieve a significant sustainable postoperative IOP decrease.

OBJECTIVE: Exfoliation syndrome (XFS) is a systemic disease of elastin-rich tissues involving a deposition of fibrillar exfoliative material (XFM) in the anterior chamber of the eye, which can promote glaucoma. The purpose of this study was to create mice with CRISPR/Cas9-induced variations in candidate genes identified from human genome-wide association studies (GWAS) and screen them for indices of XFS.
METHODS: Variants predicted to be deleterious were sought in the Agpat1, Cacna1a, Loxl1, Pomp, Rbms3, Sema6a, and Tlcd5 genes of C57BL/6J mice using CRISPR/Cas9-based gene editing. Strains were phenotyped by slit-lamp, SD-OCT imaging, and fundus exams at 1-5 mos of age. Smaller cohorts of 12-mos-old mice were also studied.
RESULTS: Deleterious variants were identified in six targets; Pomp was recalcitrant to targeting. Multiple alleles of some targets were isolated, yielding 12 strains. Across all genotypes and ages, 277 mice were assessed by 902 slit-lamp exams, 928 SD-OCT exams, and 358 fundus exams. Homozygosity for Agpat1 or Cacna1a mutations led to early lethality; homozygosity for Loxl1 mutations led to pelvic organ prolapse, preventing aging. Loxl1 homozygotes exhibited a conjunctival phenotype of potential relevance to XFS. Multiple other genotype-specific phenotypes were variously identified. XFM was not observed in any mice.
CONCLUSIONS: This study did not detect XFM in any of the strains. This may have been due to species-specific differences, background dependence, or insufficient aging. Alternatively, it is possible that the current candidates, selected based on proximity to GWAS signals, are not effectors acting via monogenic loss-of-function mechanisms.

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.

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- β signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.

OBJECTIVE: To investigate the extracellular matrix and cellular components in lens capsules extracted from patients with dead bag syndrome (DBS) through immunohistochemistry.
METHODS: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan, and Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah.
METHODS: Immunohistochemical experimental study.
METHODS: 9 capsular bag specimens from DBS cases, as well as 2 control specimens from late-postoperative in-the-bag intraocular lens dislocation cases related to previous vitrectomy, pseudoexfoliation, and blunt trauma were included. They were processed for histopathology; unstained sections were obtained from each one and analyzed by immunohistochemistry targeting collagen type IV, laminin, vimentin, collagen type I, and fibronectin.
RESULTS: Immunohistochemistry in DBS showed lens capsule stained for basement membrane components. The outer part of the anterior capsule that was split from the inner part was more markedly stained for type IV collagen as compared with the posterior part. Faint staining for fibrous posterior capsular opacification (PCO) components, for example, collagen type I and fibronectin, was detected in limited areas, but the major portion of the capsule was free from these components. Small spotty vimentin-positive materials, suggesting the presence of cell debris, were also detected in limited samples.
CONCLUSIONS: Small amounts of fibrotic PCO components were detected in capsules extracted from patients with DBS, but their major parts were free from PCO components. Current findings suggest small amounts of lens epithelial cells were present after surgery and secreted fibrous components before undergoing cell death process.