Evaluation of Dose-Response Relationship in Novel Extended Release of Targeted Nucleic Acid Nanocarriers to Treat Secondary Cataracts.

Purpose: The present study aimed to determine the dose-response relationship between targeted nanocarriers released from a novel, sustained release formulation and their ability to specifically deplete cells responsible for the development of posterior capsular opacification (PCO) in month-long, dynamic cell cultures. Methods: Injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) triblock copolymer hydrogels were loaded with either a low or a high dose of doxorubicin-loaded antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: A lower dose of nanocarriers in hydrogel depleted BAI1+ cells at a slower rate than the higher dose, whereas both reached over 90% BAI1+ cellular nonviability at 28 days. Both treatment groups also significantly lowered the relative abundance of BAI1+ cells in the population compared with the control group. Conclusions: Controlled release of a lower dose of nanocarriers can still achieve therapeutically relevant effects in the prevention of PCO, while avoiding potential secondary effects associated with the administration of a higher dose.

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca2+-dependent AMPK/mTOR pathway.

AIM: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. METHODS: LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. RESULTS: The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. CONCLUSION: A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Transcriptome exploration of ferroptosis-related genes in TGFß- induced lens epithelial to mesenchymal transition during posterior capsular opacification development.

BACKGROUND: Posterior capsular opacification (PCO) is the main reason affecting the long-term postoperative result of cataract patient, and it is well accepted that fibrotic PCO is driven by transforming growth factor beta (TGFß) signaling. Ferroptosis, closely related to various ocular diseases, but has not been explored in PCO. METHODS: RNA sequencing (RNA-seq) was performed on both TGF-ß2 treated and untreated primary lens epithelial cells (pLECs). Differentially expressed genes (DEGs) associated with ferroptosis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate their biological function. Additionally, protein-to-protein interactions among selected ferroptosis-related genes by PPI network and the top 10 genes with the highest score (MCC algorithm) were selected as the hub genes. The top 20 genes with significant fold change values were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our analysis revealed 1253 DEGs between TGF-ß2 treated and untreated pLECs, uncovering 38 ferroptosis-related genes between two groups. Among these 38 ferroptosis-related genes,the most prominent GO enrichment analysis process involved in the response to oxidative stress (BPs), apical part of cell (CCs),antioxidant activity (MFs). KEGG were mainly concentrated in fluid shear stress and atherosclerosis, IL-17 and TNF signaling pathways, and validation of top 20 genes with significant fold change value were consistent with RNA-seq. CONCLUSIONS: Our RNA-Seq data identified 38 ferroptosis-related genes in TGF-ß2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-ß2 stimulation.

Photo-controllable drug releasing bulk polyacrylic intraocular lens material for safer posterior capsular opacification prevention.

Posterior capsular opacification (PCO) is the most common complication that occurs after intraocular lens (IOL) implantation in cataract therapy. In recent years, IOLs have been developed as drug delivery platforms, but concerns over the safety of uncontrolled proliferative drug release have arisen. Therefore, a controlled drug release strategy is needed for safer PCO prevention. In this study, a new monomer contained coumarin group was introduced in material preparation, and poly(ethylene glycol phenyl ether methacrylate-co-2-(2-ethoxyethoxy) ethyl acrylate-co-7-(2-methacryloyloxyethoxy)-4-methylcoumarin) (PEEC) acrylic IOL materials were synthesized. The antiproliferative drug 5-fluorouracil (5-FU) could be chemically grafted to the PEEC IOL materials easily via a light induced [2 + 2] cycloaddition reaction with the coumarin group, getting drug-loaded IOL (PEEC@5-FU IOL). The PEEC@5-FU IOL exhibited excellent optical and mechanical properties and biocompatibility. More importantly, the loaded 5-FU could be easily controlled from release by light irradiation via photo-dissociation of the cyclobutane ring that was obtained by the [2 + 2] cycloaddition reaction of 5-FU and coumarin. The in vitro and in vivo experiments demonstrated that such photo-controllable drug release IOL could effectively prevent PCO after implantation in a safe way.

Improvements to a GLCM-based machine-learning approach for quantifying posterior capsule opacification.

BACKGROUND: Posterior capsular opacification (PCO) is a common complication following cataract surgery that leads to visual disturbances and decreased quality of vision. The aim of our study was to employ a machine-learning methodology to characterize and validate enhancements applied to the grey-level co-occurrence matrix (GLCM) while assessing its validity in comparison to clinical evaluations for evaluating PCO. METHODS: One hundred patients diagnosed with age-related cataracts who were scheduled for phacoemulsification surgery were included in the study. Following mydriasis, anterior segment photographs were captured using a high-resolution photographic system. The GLCM was utilized as the feature extractor, and a supported vector machine as the regressor. Three variations, namely, GLCM, GLCM+C (+axial information), and GLCM+V (+regional voting), were analyzed. The reference value for regression was determined by averaging clinical scores obtained through subjective analysis. The relationships between the predicted PCO outcome scores and the ground truth were assessed using Pearson correlation analysis and a Bland-Altman plot, while agreement between them was assessed through the Bland-Altman plot. RESULTS: Relative to the ground truth, the GLCM, GLCM+C, and GLCM+V methods exhibited correlation coefficients of 0.706, 0.768, and 0.829, respectively. The relationship between the PCO score predicted by the GLCM+V method and the ground truth was statistically significant (p < 0.001). Furthermore, the GLCM+V method demonstrated competitive performance comparable to that of two experienced clinicians (r = 0.825, 0.843) and superior to that of two junior clinicians (r = 0.786, 0.756). Notably, a high level of agreement was observed between predictions and the ground truth, without significant evidence of proportional bias (p > 0.05). CONCLUSIONS: Overall, our findings suggest that a machine-learning approach incorporating the GLCM, specifically the GLCM+V method, holds promise as an objective and reliable tool for assessing PCO progression. Further studies in larger patient cohorts are warranted to validate these findings and explore their potential clinical applications.

Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish.

Cataract is the leading cause of blindness worldwide. It can be treated by surgery, whereby the damaged crystalline lens is replaced by a synthetic lens. Although cataract surgery is highly effective, a relatively common complication named posterior capsular opacification (PCO) leads to secondary loss of vision. PCO is caused by abnormal proliferation and migration of residual lens epithelial cells (LECs) that were not removed during the surgery, which results in interruption to the passage of light. Despite technical improvements to the surgery, this complication has not been eradicated. Efforts are being made to identify drugs that can be applied post-surgery, to inhibit PCO development. Towards the goal of identifying such drugs, we used zebrafish embryos homozygous for a mutation in plod3 that develop a lens phenotype with characteristics of PCO. Using both biased and unbiased approaches, we identified small molecules that can block the lens phenotype of the mutants. Our findings confirm the relevance of zebrafish plod3 mutants' lens phenotype as a model for lens epithelium-derived cataract and add to our understanding of the molecular mechanisms that contribute to the development of this pathology. This understanding should help in the development of strategies for PCO prevention.

Analysis of the capsular bend in posterior capsular opacification using anterior segment optical coherence tomography.

PURPOSE: To investigate the link between the capsular bend and the morphological types and characteristics of posterior capsular opacification (PCO) using anterior segment optical coherence tomography. METHODS: Thirty eyes with PCO were examined, and three types of PCO were identified: pearl, fibrosis, and mixed. We assessed anterior capsular overlap, intraocular lens-capsule adhesion, and capsular bending. In addition to measuring the intraocular lens-posterior capsule distance and capsule bending angle (CBA), the PCO parameters (area, density, and score at 6-, 5-, and 3-mm intraocular lens optic regions) were recorded. The associations between capsular bend and PCO type and characteristics were investigated. A control group of 12 eyes without PCO was used to compare the study variables. RESULTS: With p values greater than 0.001, there was a statistically significant difference in the mean PCO area and score at the 6-, 5-, and 3-mm optic zones in different PCO types, with the pearl type having the highest value, followed by the mixed type, and finally the fibrosis type. The PCO group had a significantly higher mean CBA than the control group (P = 0.001). CBA was positively related to intraocular lens-posterior capsule distance, PCO area, and PCO score at the 6-, 5-, and 3-mm zones (P = 0.001). The receiver operating characteristic curve's cut-off point for CBA was 96.85° when comparing PCO cases to controls. Partial overlap and incomplete adhesion were statistically more common in the PCO eyes than in the control (P = 0.001, 0.003, respectively). CONCLUSION: PCO types and CBA have a strong relationship with PCO score and intraocular lens-posterior capsule space. In PCO's eyes, CBA has a cut-off value of 96.85°.

Intraoperative management of axial posterior capsular opacities during cataract surgery in six dogs.

Background: Posterior capsular opacification (PCO) is a cause of decreased vision after canine cataract surgery. PCO can appear in the months following surgery but can also be present at the time of surgery. Aims: To describe the intraoperative management of marked axial PCO during canine cataract surgery through a retrospective case series study of six cases. Methods: Six dogs (six eyes) with cataracts were included in this study. A complete ophthalmologic examination including electroretinography and ocular ultrasound was performed. After conventional phacoemulsification, a marked PCO obstructing the visual axis was found in five cases, previously diagnosed by ultrasound in the sixth. An axial posterior capsulorhexis (APC) was performed in all cases, before or after implantation of the intraocular lens (IOL). For the four cases implanted before APC, the posterior capsule (PC) was visualized either by positioning the IOL laterally in the bag with viscoelastic or through the optic of the implant. After perforation of the PC with a 30-Gauge needle, APC was initiated with Vannas curved scissors, then finalized with Utrata forceps to obtain a circular axial opening (3 mm diameter). In each case, a moderate anterior vitrectomy was performed through the APC (under the IOL when initially placed), then the IOL centered and the viscoelastic was removed. Results: Six dogs (Beagle, German Shepherd, Cavalier King Carles, French pointing dog, American bully, Beagle Harrier) aged 11 to 94 months (mean 51.8) were included. The mean follow-up period was 15.5 months (range 10-22). Visual function with capsular axial transparency and well-centered IOL, without complications during the follow-up period, was preserved for each eye. Conclusion: APC combined with moderate anterior vitrectomy appears to be effective in the treatment of marked axial PCO obstructing the visual axis during canine cataract surgery.

Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract.

BACKGROUND: Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein. METHODS: C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-ß2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit. RESULTS: ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased. Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-ß2 treatment. These effects were reversed by ARG1 knockdown. The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes. Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-ß2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression. Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients. CONCLUSIONS: ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients.

Fibrotic cataracts can be classified as anterior subcapsular cataract or posterior capsular opacification depending on where fibrosis occurs. The mechanism of fibrotic cataracts is not fully understood. Fibrotic opacities induced by trauma, inflammation, or radiation can accumulate underneath the anterior lens capsule, causing anterior subcapsular cataract. Posterior capsular opacification is one of the most common complications of phacoemulsification with intraocular lens implantation, with a high incidence in young patients. We show for the first time that ARG1 can regulate EMT in fibrotic cataracts. TGF-ß2 is the main cause of fibrosis in LECs. The expression of ARG1 and fibronectin in LECs increased after TGF-ß2 treatment or mouse lens capsular injury. We investigated the specific molecular mechanisms by which ARG1 regulates EMT in fibrotic cataracts. The mRNA expression of enzymes of the arginase-related pathway was decreased due to knockdown of ARG1 expression in HLECs. These effects were reversed by ARG1 overexpression. Additionally, knockdown of ARG1 decreased collagen 1A1, fibronectin, and vimentin expression; superoxide levels; and cell migration and increased NO levels. These effects were reversed by ARG1 overexpression. Pharmacological blockade of the ARG1 pathway with CB-1158 reduced the proliferation of LECs and decreased fibronectin, α-SMA, collagen 1A1, and vimentin expression in mouse lenses. We believe that ARG1 promotes the production of collagen 1A1 by directly activating the arginase pathway and leads to lens fibrosis by reducing NO production and increasing superoxide levels, providing a new mechanism for the prevention and treatment of fibrotic cataracts. Video Abstract.

Posterior capsular opacification and Nd:YAG capsulotomy rates in patients implanted with square-edged and non-square-edged intraocular lenses in manual small-incision cataract surgery: A randomized controlled study.

Purpose: To study posterior capsular opacification (PCO) and neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomy rates in patients implanted with square-edged and non-square-edged intraocular lenses (IOLs) in manual small-incision cataract surgery (MSICS). Setting: Tertiary eye care center. Design: Prospective, comparative, and randomized controlled study. Methods: This study included patients with senile cataracts scheduled for MSICS and IOL implantation. One eye of each patient was randomized to the implantation of square-edged (S group) or non-square-edged IOL (NSQ group). An independent observer analyzed PCO at 6, 12, 18, and 24 months under slit-lamp illumination. Results: A total of 104 eyes were included in this study. The mean age of the participants in the two groups was 63.2 (±8.2) years, and there were 65 (62.5%) men and 39 women (37.5%). The mean best-corrected visual acuity (BCVA) values at 6, 12, and 18 months were 0.157 (±0.10), 0.11 (±0.12), and 0.12 (±0.11), respectively, in the S group and 0.17 (±0.10), 0.17 (±0.12), and 0.20 (±0.17), respectively, in the NSQ group. At 12 (P = 0.03) and 18 months (P = 0.01) follow-up, the BCVA of the S group was significantly better than that of the NSQ group. Four eyes in the NSQ group and one eye in the S group required Nd:YAG. Conclusion: Evaluation of PCO and Nd:YAG capsulotomy rates showed that the 360° square of the posterior IOL edge plays a role in the prevention of PCO. Owing to the low cost of the material and the easy availability of IOLs manufactured from it, square-edged IOL has a definite role in the prevention of PCO in MSICS.

Bilateral limbal stem cell deficiency with xeroderma pigmentosum in a young Asian child.

Key Clinical Message: Xeroderma pigmentosum is an autosomal recessive disorder with various ocular manifestations of which bilateral limbal stem cell deficiency is a rare manifestation. Timely diagnosis and meticulous management are vital in these cases to prevent irreversible ocular sequelae. Abstract: Bilateral limbal stem cell deficiency (LSCD) can be a rare manifestation in patients afflicted with xeroderma pigmentosum (XP). The authors report a rare case of a 12-year-old boy who presented with redness and defective vision and was diagnosed with bilateral LSCD and hyperpigmented lesion over the face and trunk suggestive of XP.

The effect of Nd:YAG Laser applied in the posterior capsule opacification on retinal and choroidal structures.

PURPOSE: To assess the effect of neodymium:yttrium-aluminum-garnet (Nd-YAG) laser procedure on the choroid and retina in patients who developed posterior capsular opacification (PCO) after cataract surgery. METHODS: In this study, 32 eyes of 30 patients who underwent Nd:YAG laser treatment for PCO were evaluated. Visual acuity (VA), intraocular pressure (IOP), central macular thickness (CMT) with optical coherence tomography device (OCT), ganglion cell layer (GCL), inner plexiform layer (IPL), retinal nerve fiber layer (RNFL) and subfoveal choroidal thickness (SCT) were measured. Choroidal vascular index (CVI) was calculated from HD line images obtained by spectral domain OCT with the software Image J. RESULTS: The mean age of the patients participating in the study was 60.1 ± 8.9 years. There was no significant difference in IOP, CMT, RNFL, GCL, IPL and SCT values ​​in all comparisons before and after laser (p>0.05 for all values). While Nd:YAG laser pretreatment CVI was 63.2 ± 3.2%, it was 66.8 ± 2.9% at 1 week and 67.1 ± 2.6% at 1 month after laser treatment. A significant difference was detected in the comparison of pre-laser CVI and post-laser 1 week and 1 month CVI (p<0.05 for all values). DISCUSSION: CVI was found to be significantly higher in the post-laser period in patients who underwent Nd:YAG laser. As far as the author knows, this study is the first research in the literature to evaluate this relationship. CVI can be used to evaluate choroidal vascular changes after Nd:YAG laser.

Long-Term Outcomes of Posterior Capsular Opacification in Highly Myopic Eyes and Its Influencing Factors.

INTRODUCTION: The purpose of this study was to evaluate the long-term outcomes of posterior capsular opacification (PCO) in highly myopic eyes and its influencing factors. METHODS: Patients undergoing phacoemulsification with intraocular lens implantation and followed up for 1-5 years were included in this prospective cohort study. The severity of PCO was evaluated using EPCO2000 software system, with the area of central 3.0 mm (PCO-3 mm) and within the capsulorhexis (PCO-C) both being analyzed. Percentage of eyes after Nd:YAG capsulotomy, as well as clinically significant PCO (defined as eyes with visual-impairing PCO or after capsulotomy), were also included as outcome variables. RESULTS: A total of 673 highly myopic eyes [axial length (AL) ≥ 26 mm] and 224 control eyes (AL < 26 mm) were analyzed. The mean follow-up time was 34.0 ± 9.0 months. PCO was more severe in highly myopic eyes compared with controls with regard to higher EPCO scores (P < 0.001 for both PCO-3 mm and PCO-C), higher capsulotomy rate (P = 0.001), higher clinically significant PCO rate (P < 0.001) and shorter PCO-free survival time (P < 0.001). Extreme myopia (AL ≥ 28 mm) would further aggravate PCO in terms of higher EPCO scores (PCO-3 mm: P = 0.017; PCO-C: P = 0.013) and higher clinically significant PCO rate (P = 0.024) compared with other myopic eyes. In highly myopic eyes, AL [odds ratio (OR) 1.124, P = 0.004] and follow-up duration (OR 1.082, P < 0.001) were independent risk factors for clinically significant PCO after cataract surgery. CONCLUSION: Highly myopic eyes had more severe PCO in the long term. Longer AL and follow-up duration were associated with higher risk of PCO. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT03062085).

The complication rate following Neodymium-doped Yttrium Aluminum Garnet laser posterior capsulotomy for posterior capsular opacification in patients with and without comorbidities.

Purpose: To study the complication rate following Nd: YAG posterior capsulotomy posterior capsular opacification (PCO) in patients with and without comorbid conditions. Methods: This was a prospective, interventional, comparative, and observational study. A total of 80 eyes, consisting of 40 eyes without ocular comorbidities (group A) and 40 eyes with ocular comorbidities (group B) that were being treated with Nd: YAG capsulotomy for PCO, were included. Visual outcome and complications of Nd: YAG capsulotomy were studied. Results: The mean age of group A patients was 61.65 ± 8.85 years and that of group B patients was 63 ± 10.46 years. Of the total, 38 (47.5%) were men and 42 (52.5%) were women. In group B, the ocular comorbidities were moderate nonproliferative diabetic retinopathy (NPDR) (n = 14 eyes; 14/40 = 35%), subluxated intraocular lens (IOL; <2 clock hours of subluxation; n = 6), age-related macular degeneration (ARMD; n = 6), post-uveitic eyes (having old signs of uveitis, no episode of uveitis since the last 1 year; n = 5), and operated cases of traumatic cataract (n = 4). The mean energy required in groups A and B was 46.95 ± 25.92 and 42.62 ± 21.85 mJ, respectively (P = 0.422). The average energy requirement in Grade 2, Grade 3, and Grade 4 PCO was 22.30, 41.62, and 79.52 mJ, respectively. An increase in intraocular pressure (IOP) of >5 mmHg from pre-YAG levels was observed in one patient in each group on day 1 postprocedure, for which medical treatment was given to both patients for 7 days. One patient in each group had IOL pitting. No patient had any other complications attributable to ND:YAG capsulotomy. Conclusion: Nd:YAG laser posterior capsulotomy is a safe procedure for PCO in patients with comorbidities. Visual outcomes were excellent after Nd:YAG posterior capsulotomy. Although a transient increase in IOP was noted, the response to treatment was good and a long-term increase in IOP was not observed.

HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2.

PURPOSE: Posterior capsular opacification is the most common complication after cataract surgery. Abnormal proliferation, migration, epithelial-mesenchymal transition, and extracellular matrix synthesis of residual lens epithelial cells are considered to be the main pathogenic mechanisms. Hepatocyte nuclear factor 4α has been reported to regulate epithelial-mesenchymal transition in different tumors. Our objective was to investigate the role and mechanism of hepatocyte nuclear factor 4α in posterior capsular opacification. METHODS: Hepatocyte nuclear factor 4α expression was tested in posterior capsular opacification rat lens capsules and cell models. Hepatocyte nuclear factor 4α was knocked down using small hairpin RNA. Cell viability was measured by Cell Counting Kit-8 assay. Cell migration ability was evaluated by wound healing and Transwell assays. Epithelial-mesenchymal transition markers were detected by Western blotting. Transcriptome sequencing was used to screen for downstream effectors of hepatocyte nuclear factor 4α. Chromatin immunoprecipitation and a dual luciferase reporter assay were used to determine the binding of hepatocyte nuclear factor 4α to the MMP2 promoter region. RESULTS: Hepatocyte nuclear factor 4α was downregulated in posterior capsular opacification tissue and cell models. In vitro studies showed that hepatocyte nuclear factor 4α deletion facilitated cell proliferation, migration, and epithelial-mesenchymal transition protein marker expression in lens epithelial cells. Hepatocyte nuclear factor 4α knockdown promoted epithelial-mesenchymal transition and migration of lens epithelial cells via MMP2. Mechanistically, hepatocyte nuclear factor 4α decreased MMP2 expression by binding to the MMP2 promoter region. Hepatocyte nuclear factor 4α deletion also promoted epithelial-mesenchymal transition in rat lens capsules. CONCLUSIONS: We demonstrated that hepatocyte nuclear factor 4α inhibited epithelial-mesenchymal transition of lens epithelial cells by directly binding to the MMP2 promoter region and inhibiting the expression of MMP2, thus leading to retardation of posterior capsular opacification formation and development, suggesting that hepatocyte nuclear factor 4α is a potential therapeutic target for posterior capsular opacification.

Glutaredoxin 1 protects lens epithelial cells from epithelial-mesenchymal transition by preventing casein kinase 1α S-glutathionylation during posterior capsular opacification.

Oxidative stress drives protein S-glutathionylation, which regulates the structure and function of target proteins and is implicated in the pathogenesis of many diseases. Glutaredoxin 1 (Grx1), a cytoplasmic deglutathionylating enzyme, maintains a reducing environment within the cell under various conditions by reversing S-glutathionylation. Grx1 performs a wide range of antioxidant activities in the lens and prevents protein-thiol mixed disulfide accumulation, reducing protein-protein aggregation, insolubilization, and apoptosis of lens epithelial cells. Oxidative stress is related to epithelial-mesenchymal transition (EMT) during posterior capsular opacification (PCO). However, whether Grx1-regulated protein S-glutathionylation plays an essential role in PCO remains unclear. In this study, we revealed that Grx1 expression was decreased in mice following cataract surgery. Furthermore, the absence of Grx1 elevated oxidative stress and protein S-glutathionylation and aggravated EMT in both in vitro and in vivo models. Concurrently, these results could be reversed by Grx1 overexpression. Notably, liquid chromatography-tandem mass spectrometry results showed that casein kinase 1α (CK1α) was susceptible to S-glutathionylation under oxidative stress, and CK1α S-glutathionylation (CK1α-SSG) was mediated at Cys249. The absence of Grx1 upregulated CK1α-SSG, subsequently decreasing the CK1α-induced phosphorylation of ß-catenin at Ser45. The consequential downregulation of degradative ß-catenin and upregulation of its nuclear translocation activated the Wnt/ß-catenin signaling pathway and aggravated EMT. In conclusion, the downregulated expression of Grx1 in mice following cataract surgery aggravated EMT by upregulating the extent of CK1α-SSG. To the best of our knowledge, our study is the first to report how S-glutathionylation regulates CK1α activity under oxidative stress.

Analysis of influencing factors associated with the time between cataract surgery and Nd:YAG laser posterior capsulotomy.

PURPOSE: To retrospectively analyze the clinical data of large samples of YAG laser posterior capsulotomy, and to explore the influencing factors of time from cataract surgery to YAG laser capsulotomy (TFCSTLC), so as to provide reference for the occurrence and treatment of real-world posterior capsular opacification (PCO). METHODS: 1093 patients (1093 eyes) with PCO who underwent YAG laser posterior capsulotomy from 2014 to 2019 in the largest eye center of northwest China were analyzed retrospectively. The gender, age, systemic complications, material, and design of intraocular lens (IOL) and TFCSTLC were recorded. The test and Wilcoxon rank sum test were applied to analyze and compare the average TFCSTLC values under different factors, and the relationship between each factor and TFCSTLC was analyzed by multiple linear regression. RESULTS: The average TFCSTLC was 19.2 (range, 7.9 ∼ 31.2) months. There were significant statistical differences in TFCSTLC among the implanted single focus versus multifocal IOLs (P < 0.001), diabetic versus non-diabetic patients (P < 0.001), high myopia versus non-high myopia patients (P = 0.003). Multiple linear regression analysis demonstrated that TFCSTLC was negatively correlated in patients with diabetes mellitus versus with no history of diabetes mellitus (coefficient, -5.36; 95% confidence interval [CI], -8.30 to -2.41; P < 0 .001), and multifocal IOL versus a single focus IOL implanted (coefficient, -5.56 ; 95% CI, -9.01 to -2.11; P = 0.002). CONCLUSIONS: TFCSTLC may be affected by many factors in the real world. The YAG laser posterior capsulotomy time was sooner in patients with a history of diabetes mellitus and multifocal IOL implanted.

Refractive Changes After Nd:YAG Capsulotomy in Pseudophakic Eyes.

Purpose: To analyze refractive changes after neodymium: yttrium-aluminum-garnet (Nd:YAG) posterior capsulotomy in pseudophakic eyes. Patients and Methods: Patients who underwent Nd:YAG capsulotomy after cataract surgery from January 2013 to April 2022 were included in this retrospective study. Sphere, cylinder, spherical equivalent (SE), axis, and corrected distance visual acuity (CDVA) were compared pre- and postoperatively in 683 eyes of 548 patients at one month (n = 605 eyes) and one year (n = 211 eyes). Patients with both one-month and one-year follow-ups (n = 133) were also compared. Eyes were stratified into single-piece (n = 330), three-piece (n = 30), and light adjustable lenses (LALs) (n = 16). Pre- and postoperative measurements were analyzed within each group. Results: Cylinder was significantly decreased at one-month (difference: 0.042±0.448 D, p = 0.006) and one-year (difference: 0.101±0.455 D, p = 0.003) compared to preoperative measurements. No significant change in sphere or axis was observed at follow-up visits (p > 0.05). CDVA significantly improved at both time points (p < 0.05). No significant change in any parameters between the one-month and one-year groups was observed (p > 0.05). There was significant improvement in CDVA in the single and three-piece lens groups (p < 0.0001 and p = 0.026, respectively), with no change in the LAL group (p > 0.05). Conclusion: There were no changes in sphere, axis, or spherical equivalent after Nd:YAG capsulotomy. However, cylindrical error and CDVA were significantly better after the procedure. Lens type did not impact refractive parameters postoperatively.

Complications of pupil expansion devices: a large real-world study.

Purpose: To assess the risk for uveitis, pseudophakic cystoid macular edema (PCME), and posterior capsular opacification (PCO) associated with the use of pupil expansion devices in cataract surgery. Design: A retrospective comparative cohort study. Participants: Patients who underwent routine cataract surgery with and without pupil expansion devices at the Department of Ophthalmology, Bristol Eye Hospital, UK, between January 2008 and December 2017. Methods: This study included 39,460 eyes operated without a pupil expansion device and 699 eyes operated with the device. Odds ratios for uveitis and PCME when using a pupil expansion device were calculated using univariate and multivariate regression analysis, having age, gender, diabetes, pseudoexfoliation, and pupil expansion device as independent variables. Multivariate Cox regression controlling for age and gender was used to estimate hazard ratios (HR) for Nd : YAG laser capsulotomies. Results: Postoperative uveitis and PCME were reported in 3.9% and 2.7% of the eyes operated with a pupil expansion device compared to 2.3% and 1.3% operated without the device (p=0.005 and p=0.002, respectively). In univariate regression analysis, eyes with pupil expansion devices showed a higher risk of postoperative uveitis or PMCE after cataract surgery (OR 1.88, 95%CI 1.39-2.55, p<0.001). In multivariate regression analysis, the risk for PMCE was greater among diabetic patients and in eyes with a pupil expansion device than in those without (OR 1.50, 95%CI 1.24-1.83, P<0.001; OR 1.90, 95%CI 1.16-3.11, P=0.01). In Cox regression analysis adjusted for the patient's age and gender, the use of a pupil expansion device was associated with higher Nd : YAG laser capsulotomy rates (HR 1.316, 95%CI 1.011-1.714, P=0.041). Conclusion: In our large cohort study, the use of pupil expansion devices in cataract surgery was associated with an increased risk of major postoperative complications. Effective anti-inflammatory treatment and follow-up are warranted in eyes operated with a pupil expansion device.

Capsulotomía Nd-Yag Láser en Pseudofáquicos con OCP

Una de las causas de la disminución de la visión es la catarata. El tratamiento es la extracción del cristalino opaco con reemplazo por un lente intraocular (LIO). La opacidad de cápsula posterior (OCP) es una complicación frecuente a largo plazo. Las modificaciones en el diseño del LIO tanto del material y la forma tienen mayor importancia para prevenir la OCP. Como tratamiento está la capsulotomía neodimio YAG láser. Objetivo: identificar la OCP relacionado con el tipo de LIO implantado en pacientes pseudofáquicos en la FBO, entre el periodo de marzo del 2019 hasta febrero del 2022. Métodos: estudio observacional, tipo analítico, subtipo cohorte histórica, retro- prospectiva y longitudinal, con enfoque de análisis estadístico de tipo cuantitativo. Resultados: predominó el género femenino con un 60 % y un 40 % representaba al masculino; un 60,3 % del total tenían entre 65 a 80 años. La OCP en los 3 tipos de lentes intraoculares (acrílico y PMMA) ocasionó una disminución en la agudeza visual: el 37 %, predominó, por el LIO hidrofóbico, 36 % por el LIO PMMA y destacamos que el 27 % fue por el LIO hidrofílico. La incidencia de OCP a 5 años fue del 32 %. No se registró ningún efecto adverso en nuestro estudio. Conclusiones: la OCP provoca una baja de agudeza visual leve a moderada en los 3 tipos de LIOs; con un mínimo predominio de BAV leve para el tipo de LIO hidrofóbico comparado con el hidrofílico. Además después de la capsulotomía un gran porcentaje tiene entre 20/20 a 20/25 de AV mejor corregida.

One of the causes of decreased vision is cataract. Treatment is removal of the cloudy lens with replacement by an intraocular lens (IOL). Posterior capsule opacity (PCO) is a common long-term complication. Modifications in the design of the IOL both in terms of material and shape are of greater importance in preventing PCO. Treatment is neodymium YAG laser capsulotomy. Objective: to identify the PCO related to the type of IOL implanted in pseudophakic patients in the FBO, from March 2019 to February 2022. Methods: observational study, analytical type, historical cohort subtype, retro-prospective and longitudinal, with a quantitative statistical analysis approach. Results: the female gender predominated with 60% and 41% represented the male; 60.3% of the total was between 65 and 80 years old. PCO in the 3 types of intraocular lenses (acrylic and PMMA) caused a decrease in visual acuity: 37%, predominated, due to the hydrophobic IOL, 36% due to the PMMA IOL and we highlight that 27% was due to the hydrophilic IOL. The incidence of PCO at 5 years was 32%. No adverse effect was recorded in our study. Conclusion: PCO causes mild to moderate visual acuity loss in all 3 types of IOLs; with a minimal predominance of mild AVB for the hydrophobic IOL type compared to the hydrophilic one. In addition, after capsulotomy, a large percentage has between 20/20 and 20/25 better corrected visual acuity.