Lens Opacities Research Articles

GBF1 deficiency causes cataracts in human and mouse.

Any opacification of the lens can be defined as cataracts, and lens epithelium cells play a crucial role in guaranteeing lens transparency by maintaining its homeostasis. Although several causative genes of congenital cataracts have been reported, the mechanisms underlying lens opacity remain unclear. In this study, a large family with congenital cataracts was collected and genetic analysis revealed a pathological mutation (c.3857C > T, p.T1287I) in the GBF1 gene; all affected individuals in the family carried this heterozygous mutation, while unaffected family members did not. Functional studies in human lens epithelium cell line revealed that this mutation led to a reduction in GBF1 protein levels. Knockdown of endogenous GBF1 activated XBP1s in the unfolded protein response signal pathway, and enhances autophagy in an mTOR-independent manner. Heterozygous Gbf1 knockout mice also displayed typic cataract phenotype. Together, our study identified GBF1 as a novel causative gene for congenital cataracts. Additionally, we found that GBF1 deficiency activates the unfolded protein response and leads to enhanced autophagy, which may contribute to lens opacity.

Intraocular Lens Opacification After Descemet's Membrane Endothelial Keratoplasty-Risk Factors and Outcomes After Intraocular Lens Exchange.

To determine risk factors for intraocular lens opacification (IOLop) after Descemet membrane endothelial keratoplasty (DMEK) and to analyze clinical outcomes after IOL exchange. Cross-Sectional Study: Analysis of all cases of IOL exchange because of post-DMEK IOLop with a minimum of 6-month postoperative follow-up observed in clinic between November 2021 and April 2022. Main outcomes analyzed at the study visit were change in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity after IOL exchange, endothelial cell loss (ECL), and graft survival. An historical cohort of 232 pseudophakic DMEK eyes was retrospectively analyzed to determine risk factors for post-DMEK IOLop. Cross-Sectional Study: Four eyes were observed (median follow-up = 45 (35.5-86.8) months). IOL materials were hydrophilic acrylic IOLs in 2 eyes and hydrophobic-hydrophilic in the other 2. At the study visit, improvement in median best-corrected visual acuity after IOL exchange was statistically significant (0.25 (0.19-0.41) logMAR to 0.00 (0-0.10) logMAR; P = 0.041). ECL ranged between 57.7% and 85.3%, without cases of graft failure. In the historical cohort, 21 eyes (9.05%) had some IOLop. In multivariate logistic regression model (105 eyes where IOL material data was available), IOLs with high water content material (odds ratio = 65.5, P = 0.0005) and rebubbling (odds ratio = 9.51, P = 0.0138) were independent risk factors for post-DMEK IOLop. Post-DMEK IOLop is infrequent, but a non-neglectable proportion of cases may require IOL explantation. IOL exchange is safe and effective in these eyes but may pose a risk for increased ECL. This study confirms that IOL material and number of rebubblings are major risk factors for post-DMEK IOLop.

SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo.

To explore the effect of silent information regulator factor 2-related enzyme 1 (SIRT1) on modulating apoptosis of human lens epithelial cells (HLECs) and alleviating lens opacification of rats through suppressing endoplasmic reticulum (ER) stress. HLECs (SRA01/04) were treated with varying concentrations of tunicamycin (TM) for 24h, and the expression of SIRT1 and C/EBP homologous protein (CHOP) was assessed using real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8 (CCK-8) assay, respectively. In the SRA01/04 cell apoptosis model, which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation, the expression levels of SIRT1, CHOP, glucose regulated protein 78 (GRP78), and activating transcription factor 4 (ATF4) were examined. The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid (4-PBA; an ER stress inhibitor) was investigated. In vivo, age-related cataract (ARC) rat models were induced by sodium selenite injection, and the protective role of SIRT1, activated by SRT1720 intraperitoneal injections, was evaluated through morphology observation, hematoxylin and eosin (H&E) staining, Western blotting, and RT-PCR. SIRT1 expression was downregulated in TM-induced SRA01/04 cells. Besides, in SRA01/04 cells, both cell apoptosis and CHOP expression increased with the rising doses of TM. ER stress was stimulated by TM, as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model. Inhibition of SIRT1 by siRNA knockdown increased ER stress activation, whereas SRT1720 treatment had opposite results. 4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis. In vivo, SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models. SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress. These findings suggest a novel strategy for cataract treatment focused on targeting ER stress, highlighting the therapeutic potential of SIRT1 modulation in ARC development.

Ocular dominance shift in refractive cataract surgery: prospective, observational study.

To explore the features of the dominant and nondominant eyes in patients with cataracts and predict ocular dominance shift (ODS) based on preoperative indicators. Changsha Aier Eye Hospital, Changsha, Hunan, China. Prospective, observational study. Patients with age-related cataracts who underwent unilateral cataract surgery were enrolled in this study. Before the procedure, uncorrected distance visual acuity (UDVA) was assessed and noncycloplegic subjective refraction evaluations were conducted to determine corrected distance visual acuity. Total astigmatism, corneal astigmatism, and intraocular astigmatism were measured using OPD-Scan III. Cataract type was assessed using slitlamp biomicroscopy based on the Lens Opacities Classification System III. Ocular dominance (OD) was determined under corrected conditions using the hole-in-card test. Follow-up visits occurred at 1 day, 1 week, and 1 month postoperatively. After 1 month, OD was re-evaluated, and participants completed the 9-item Short-Form Cataract Questionnaire. 94 patients (188 eyes) were enrolled in the study. The analysis showed that the ODS rate of unilateral cataract surgery was 40.4%. In addition, age, UDVA of the nondominant eye, posterior subcapsular cataract, and total astigmatism were risk factors for ODS. No difference in vision-related quality of life was detected between patients who had ODS and those who did not. Several preoperative parameters as potential risk factors of ODS after cataract surgery were identified. These findings provide guidance for predicting changes in the dominant eye and may improve the precise selection of intraocular lenses and implementation of monovision strategies.

Analysis of the performance of the CorneAI for iOS in the classification of corneal diseases and cataracts based on journal photographs

CorneAI for iOS is an artificial intelligence (AI) application to classify the condition of the cornea and cataract into nine categories: normal, infectious keratitis, non-infection keratitis, scar, tumor, deposit, acute primary angle closure, lens opacity, and bullous keratopathy. We evaluated its performance to classify multiple conditions of the cornea and cataract of various races in images published in the Cornea journal. The positive predictive value (PPV) of the top classification with the highest predictive score was 0.75, and the PPV for the top three classifications exceeded 0.80. For individual diseases, the highest PPVs were 0.91, 0.73, 0.42, 0.72, 0.77, and 0.55 for infectious keratitis, normal, non-infection keratitis, scar, tumor, and deposit, respectively. CorneAI for iOS achieved an area under the receiver operating characteristic curve of 0.78 (95% confidence interval [CI] 0.5–1.0) for normal, 0.76 (95% CI 0.67–0.85) for infectious keratitis, 0.81 (95% CI 0.64–0.97) for non-infection keratitis, 0.55 (95% CI 0.41–0.69) for scar, 0.62 (95% CI 0.27–0.97) for tumor, and 0.71 (95% CI 0.53–0.89) for deposit. CorneAI performed well in classifying various conditions of the cornea and cataract when used to diagnose journal images, including those with variable imaging conditions, ethnicities, and rare cases.

Role of actin-binding proteins in cataract formation.

Actin has been implicated in lens opacification; however, the specific actin-related pathways involved in cataracts remain unelucidated. In this study, actin-related proteome changes and signaling pathways involved in the development of cataracts were evaluated. The anterior capsule and phacoemulsification (phaco) cassette contents were collected during cataract surgery from 11 patients with diabetic cataract (DC), 12 patients with age-related cataract (ARC), and seven patients with post-vitrectomy cataract (PVC). Untargeted, global identification and quantification of proteins was performed through liquid chromatography-mass spectrometry with the data-independent acquisition (DIA). In phaco cassette samples, proteins with significantly lower expression in ARC than in DC and PVC were involved in various pathways, including actin binding, actin cytoskeleton reorganization, actin filament capping, cortical actin cytoskeleton organization, and small GTPase-mediated signal transduction pathways. In anterior capsules, proteins with significantly lower expression in ARC than in DC and PVC were involved in actin binding and actin cytoskeleton reorganization pathways. Actin cytoskeleton and actin-binding proteins are involved in lens fiber elongation and differentiation. Rho GTPases contribute to actin cytoskeletal reorganization, and their inactivation is linked to abnormal lens fiber migration. These findings link actin binding to lens fiber integrity, lens opacification, and cataracts.

GDF-15 Attenuates the Epithelium-Mesenchymal Transition and Alleviates TGFβ2-Induced Lens Opacity.

We sought to evaluate the efficacy of growth differentiation factor (GDF)-15 treatment for suppressing epithelial-mesenchymal transition (EMT) and alleviating transforming growth factor β2 (TGFβ2)-induced lens opacity. To test whether GDF-15 is a molecule that prevents EMT, we pretreated the culture with GDF-15 in neural progenitor cells, retinal pigment epithelial cells, and lens epithelial cells and then treated with factors that promote EMT, GDF-11, and TGFβ2, respectively. To further investigate the efficacy of GDF-15 on alleviating lens opacity, we used mouse lens explant culture to mimic secondary cataracts. We pretreated the lens culture with GDF-15 and then added TGFβ2 to develop lens opacity (n = 3 for each group). Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure EMT protein and gene expression, respectively. In cell culture, GDF-15 pretreatment significantly attenuated EMT marker expression in cultured cells induced by treatment with GDF-11 or TGFβ2. In the lens explant culture, GDF-15 pretreatment also reduced mouse lens opacity induced by exposure to TGFβ2. Our results indicate that GDF-15 could alleviate TGFβ2-induced EMT and is a potential therapeutic agent to slow or prevent posterior capsular opacification (PCO) progression after cataract surgery. Cataracts are the leading cause of blindness worldwide, with the only current treatment involving surgical removal of the lens and replacement with an artificial lens. However, PCO, also known as secondary cataract, is a common complication after cataract surgery. The development of an adjuvant that slows the progression of PCO will be beneficial to the field of anterior complications.

Research progress on the correlation between cataract occurrence and nutrition.

Cataract is a common eye disease characterized by lens opacity, leading to blurred vision and progressive blindness of the eye. Factors affecting the development of cataracts include nutrition, oxidative stress, micronutrients and inflammatory factors, and also include genetics, toxicity, infrared exposure, hyperuricemia, and mechanical injuries. Among the nutritional factors, a balanced diet, vegetarian diet, dairy products and vegetables are protective against cataracts; high-sodium diet, high intake of carbohydrates and polyunsaturated fatty acids may increase the risk of cataracts; and increased intake of proteins, especially animal proteins, may prevent nuclear cataracts. Intake of antioxidants such as β-carotene, lutein, or zeaxanthin is associated with a reduced risk of cataracts. Minerals such as zinc, selenium, calcium and sodium have also been associated with cataract development. Oxidative stress plays an important role in the development of cataracts and is associated with several antioxidative enzymes and biomarkers such as glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Insulin resistance is also an essential risk factor for cataracts, especially in diabetic patients. In conclusion, understanding these influencing factors helps us to better prevent cataracts. And in this article, we will focus on the important factor of diet and nutrition for a detailed discussion.

Macular perfusion, thickness, and sensitivity in phacovitrectomy versus lens-sparing vitrectomy in rhegmatogenous retinal detachment

Purpose The aim of this study was to compare phacovitrectomy (phacoPPV) to lens-sparing pars plana vitrectomy (PPV) with respect to macular perfusion, thickness, and sensitivity in phakic patients with rhegmatogenous retinal detachment. Patients and methods This is a prospective, comparative, nonrandomized, interventional study that included 31 phakic eyes with primary rhegmatogenous retinal detachment. The patients were divided into two groups according to the preoperative lens status: group A who had significant cataract and group B who did not have significant cataract. Group A included 17 eyes for which phacoPPV was performed, while group B included 14 eyes for which lens-sparing PPV was performed. All patients were preoperatively evaluated clinically and with A-scan ultrasonography and were followed up for 4 months after surgery. Optical coherence tomography angiography (OCTA) and microperimetry were done at 2 and 4 months, postoperatively. Results The OCTA showed that the lens-sparing PPV was associated with significantly larger foveal avascular zone area (0.4±0.2 mm2) compared to the phacoPPV (0.2±0.1 mm2) at 2 months (P=0.048), as well as at 4 months (0.4±0.1 mm2vs. 0.2±0.1 mm2, respectively, P=0.044). However, the foveal avascular zone perimeter showed no statistically significant differences between the two groups at 2 and 4 months postoperatively. At 2 months, the deep vascular plexus (DVP) parafoveal vessel density was statistically significantly higher in the phacoPPV group (47.9±4.7%) compared to the PPV group (36.4±11.9%) (P=0.048), while at 4 months it was the DVP foveal vessel density that showed a significantly higher mean in the phacoPPV group (35.4±11.9%) compared to the PPV group (20.3±16.1%) (P=0.036). No other statistically significant intergroup differences were found with respect to other parameters for macular perfusion, and other DVP parameters. Similarly, the macular sensitivity, as well as the ganglion cell complex, and the central subfield thicknesses were comparable between the two groups. The visual outcome was also comparable at 2 and 4 months between the two groups. Conclusion PhacoPPV and lens-sparing vitrectomy were comparable with respect to OCTA, microperimetry, and visual acuity. The limited differences are too preliminary and the decision to do phacoPPV rather than lens-sparing PPV needs to be based on other determinants like the presence of preoperative lens opacity.

Ocular characteristics and outcomes of phacoemulsification in patients with cataract after renal transplantation.

To explore ocular characteristics of patients with cataracts after renal transplantation and analyze the results of phacoemulsification combined with intraocular lens (IOL) implantation. Patients with cataracts after renal transplantation and control patients who underwent phacoemulsification combined with IOL implantation were enrolled. All patients underwent phacoemulsification combined with IOL implantation. Visual acuity, intraocular pressure, type of lens opacity, corneal endothelial cell density, and ocular biological parameters were evaluated before surgery. Visual prognosis, dry eye, and postoperative complications were monitored for 6months after phacoemulsification. We analyzed 25 eyes of 16 patients after renal transplantation and 30 eyes of 21 control patients. The most common type of cataract of renal transplantation group was posterior subcapsular, while the most common type of cataract of control group was cortical. Significant differences in corneal astigmatism, white-to-white ratio, and keratometry values were observed between the groups. The postoperative visual acuity of both groups significantly improved following surgery. Postoperative complications, such as the degree of anterior and posterior capsule opacification and the incidence of a requirement of neodymium-doped yttrium aluminum garnet laser capsulotomy, were significantly lower in the renal transplantation group. Moreover, secondary glaucoma occurred in two eyes in the renal transplantation group. This study showed that cataracts after renal transplantation were mostly posterior subcapsular. Postoperative visual acuity recovered well in most patients, with reduced incidence of postoperative complications. This study suggested that phacoemulsification combined with IOL implantation was safe and effective, providing a reference for multi-focal IOL implantation in kidney transplant recipients.

A Case of Unexplained Opacity of an Intraocular Lens

The patient is an elderly female, 81 years old. On September 24, 2022, he was admitted to the hospital for "blurred vision in his right eye, photophobia and tears for more than 1 year". The patient complained that he had undergone phacoemulsification resection intraocular lens implantation of cataract in the right eye in a hospital in Liling City in 2020 due to blurred vision in both eyes for more than 3 years , and the blurred vision was reduced after surgery. Now due to the blurred vision of the right eye, which is progressively worsening and the vision is decreasing, he came to our hospital for treatment.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract.

To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Enhancing Cataract Detection through Hybrid CNN Approach and Image Quadration: A Solution for Precise Diagnosis and Improved Patient Care

Cataracts, characterized by lens opacity, pose a significant global health concern, leading to blurred vision and potential blindness. Timely detection is crucial, particularly in regions with a shortage of ophthalmologists, where manual diagnosis is time-consuming. While deep learning and convolutional neural networks (CNNs) offer promising solutions, existing models often struggle with diverse datasets. This study introduces a hybrid CNN approach, training on both full retinal fundus images and quadrated parts (i.e., the fundus images divided into four segments). Majority voting is utilized to enhance accuracy, resulting in a superior performance of 97.12%, representing a 1.44% improvement. The hybrid model facilitates early cataract detection, aiding in preventing vision impairment. Integrated into applications, it supports ophthalmologists by providing rapid, cost-efficient predictions. Beyond cataract detection, this research addresses broader computer vision challenges, contributing to various applications. In conclusion, our proposed approach, combining CNNs and image quadration enhances cataract detection’s accuracy, robustness, and generalization. This innovation holds promise for improving patient care and aiding ophthalmologists in precise cataract diagnosis.

Retinal image quality assessment in diabetic-retinopathy screening: Real world evidence from a lower-middle income country

Objectives: Sight loss due to diabetic retinopathy (DR) is preventable by early detection and treatment. Digital retinal imaging is the most widely practiced method of screening of DR. Poor quality of images is a major hinder to implement systematic DR screening using digital retinal imaging in low- and middle-income countries with a high prevalence of lens opacities. We aimed to identify the proportion of ungradable images using hand-held retinal imaging and predictors of image gradability in a DR screening feasibility study conducted in Sri Lanka. Material and Methods: The present study is a retrospective data analysis of a validation study conducted to assess the diagnostic test accuracy of a held-held digital retinal imaging model integrated into a tertiary level medical clinic. Two selected physician graders underwent formal training to assess retinal image quality using a “four-quadrant method of assessing gradability.” The procedure was a subjective image quality assessment performed by the physician graders manually, that is, images with more than 50% of the field with poor clarity and not suitable for retinopathy grading were classified as ungradable. Two-field (Field-1: macula centered, Field-2: disc centered) non-mydriatic and mydriatic retinal images were captured (Type of camera: Zeiss-Visuscout 100®, Germany) in a consecutive sample of people with diabetes attended for routine medical care and assessed for quality and graded by two independent physician graders on-site. The reference test was a mydriatic biomicroscopic examination conducted at a separate eye clinic by an experienced specialist retinologist. Mixed model regression analysis was conducted to assess the predictors of gradability. Results: A total of 700 individuals (5508 gradability data points) were included in the study. The proportion of ungradable images in non-mydriatic imaging was 30% for Grader 1 and 24% for Grader 2 and went down to 7% and 5%, respectively, for Grader 1 and 2 after dilating the pupils using mydriatic agents. Non-mydriatic images had almost 20 times higher odds (odds ratio [OR] 19.7, 95% confidence interval [CI] 15.1–25.8) of being rated as ungradable compared to mydriatic images. With the increase of each year in age, the odds of having ungradable digital retinal images in a patient increased by 7% (OR 1.07, 95% CI 1.05–1.09). For visual acuity increase in each level of the Log-MAR scale, the odds of having ungradable images increased by 40% (OR 1.40, 95% CI 1.30–1.51). In lens opacity, 54% higher odds of ungradability were observed when present nuclear opalescence (OR 1.54, 95% CI 1.39–1.70) and posterior subcapsular opacity (OR 1.54, 95% CI 1.24–1.92). Conclusion: Non-mydriatic methods may not be suitable as a primary DR screening strategy in countries with a high prevalence of cataracts. Increasing age, poor visual acuity, and the presence of lens opacity are factors that would affect image quality. The capacity to deliver services for managing cataracts may be an important determinant in achieving effective coverage of digital surveillance of DR in low- and middle-income countries.

Plant-based diets and the risk of age-related cataract: a case-control study

PurposeCataract, or lens opacification, is a major public health burden accounting for more than half of all blindness worldwide. Plant-based dietary indices provide a unique approach to investigating a modifiable risk for age-related cataracts (ARC). The purpose of this study was to investigate the association between plant-based diet indices and risk of ARC.Design/methodology/approachThis case-control study was conducted on 97 patients with newly diagnosed ARC and 198 healthy people (as a control group) in Iran. Convenience sampling and a food frequency questionnaire were used. Three plant-based dietary indices were used based on the health promoting qualities of food items, the overall plant-based diet index (PDI), healthful plant-based diet index (H-PDI) and unhealthful plant-based diet index (U-PDI) which comprised refined carbohydrates and highly processed foods. The plant-based dietary indices were used to investigate relationships with risk of ARC.FindingsAfter adjusting for potential covariates, no significant association between a higher adherence to O-PDI and risk of ARC. As well, a higher adherence to H-PDI was inversely associated with the risk of ARC (OR = 0.35,95%CI:0.16–0.78). In contrast, there was a significant positive association between a higher adherence to U-PDI and the risk of ARC (OR = 3.67,95%CI:1.66 – 8.15).Originality/valueThe findings of this study have underscored the potential impact of the quality of plant-based food selections on the likelihood of developing ARC. Therefore, adopting a plant-based diet that is rich in nutrient-dense plant-based foods while being low in unhealthy options may have the potential to reduce the risk of ARC.

Spatial-temporal comparison of Eph/Ephrin gene expression in ocular lenses from aging and knockout mice.

Cataracts, defined as any opacity in the transparent ocular lens, remain the leading cause of blindness and visual impairment in the world; however, the etiology of this pathology is not fully understood. Studies in mice and humans have found that the EphA2 receptor and the ephrin-A5 ligand play important roles in maintaining lens homeostasis and transparency. However, due to the diversity of the family of Eph receptors and ephrin ligands and their promiscuous binding, identifying functional interacting partners remains a challenge. Previously, 12 of the 14 Ephs and 8 of 8 ephrins in mice were characterized to be expressed in the mouse lens. To further narrow down possible genes of interest in life-long lens homeostasis, we collected and separated the lens epithelium from the fiber cell mass and isolated RNA from each compartment in samples from young adult and middle-aged mice that were either wild-type, EphA2-/- (knockout), or ephrin-A5 -/- . Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was implemented to compare transcript levels of 33 Eph and ephrin gene variants in each tissue compartment. Our results show that, of the Eph and ephrin variants screened, 5 of 33 showed age-related changes, and 2 of 33 showed genotype-related changes in lens epithelium. In the isolated fibers, more dynamic gene expression changes were observed, in which 12 of 33 variants showed age-related changes, and 6 of 33 showed genotype-related changes. These data allow for a more informed decision in determining mechanistic leads in Eph-ephrin-mediated signaling in the lens.

Feasibility of shear wave elastography for evaluating lens stiffness in patients with age-related cataracts: A quantitative analysis

BackgroundShear wave elastography (SWE) is a novel imaging technique that provides quantitative assessments of tissue stiffness. This non-invasive method offers real-time, quantitative measurements and has been widely applied to various tissues, providing valuable diagnostic insights. PurposeThis study aimed to investigate the feasibility of using SWE to evaluate the stiffness of the lens in patients with age-related cataracts. Materials and methodsA comparative analysis involving 92 patients diagnosed with age-related cataracts and 39 healthy controls was conducted. Lens stiffness was quantified using SWE measurements. The lens nucleus of all participants was graded based on the Lens Opacities Classification System II (LOCS II). Correlations between the stiffness of the lens and age were also analyzed. ResultsThe study indicates that both the stiffness of the lens and the lens nucleus were significantly higher in patients with age-related cataracts compared to healthy controls (P < 0.001). In patients with age-related cataracts, although lens nucleus stiffness variations across different grades of cataract severity were not statistically significant, all grades displayed increased stiffness relative to healthy controls. Additionally, a significant positive correlation between lens stiffness and age was observed in all participants (P < 0.001). ConclusionSWE appears to be a promising imaging technique for quantitatively assessing the mechanical characteristics of the lens in patients with age-related cataracts.

Transient anterior subcapsular vacuolar lens opacities after Tanito microhook trabeculotomy: report of six cases

ObjectiveTo present six cases exhibiting transient anterior subcapsular vacuolar lens opacities following early postoperative Tanito microhook trabeculotomy (TMH) performed by the same surgeon.MethodsSix patients who underwent lens-sparing TMH at Meizankai Shimizu Eye Clinic from November 2021 to May 2023, and developed anterior subcapsular vacuolar lens opacities postoperatively were reviewed. Detailed records of surgeries, follow-up findings were collected and reported.ResultsIn all six cases, anterior vacuolar subcapsular lens opacities were observed on the day after surgery, gradually decreasing without affecting visual acuity or contrast sensitivity. In all cases, without any specific interventions, the opacities disappeared by 21 months postoperatively.ConclusionAnterior subcapsular cataracts, characterized by a vacuolar appearance and transient existence, should be recognized as an early complication of ab interno glaucoma surgery, possibly linked to use of distributed ophthalmic viscosurgical devices and excessive anterior chamber irrigation leading to traumatic cataracts on the lens surface.

Intraoperative quantitative crystalline lens nuclear opacities analysis based on crystalline lenSx platform

PurposeThe main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract.MethodsThis study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract.ResultsThe pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P < 0.001, 95%CI 0.620–0.919), which had a good degree of differentiation (Fig. 2a). The calibration curve showed good agreement between predicted and actual probability.ConclusionThe nuclear density measurement on SD-OCT images can serve as an objective and reliable indicator for quantifying nuclear density.

Loss of αBa-crystallin, but not αA-crystallin, increases age-related cataract in the zebrafish lens

The vertebrate eye lens is an unusual organ in that most of its cells lack nuclei and the ability to replace aging protein. The small heat shock protein α-crystallins evolved to become key components of this lens, possibly because of their ability to prevent aggregation of aging protein that would otherwise lead to lens opacity. Most vertebrates express two α-crystallins, αA- and αB-crystallin, and mutations in each are linked to human cataract. In a mouse knockout model only the loss of αA-crystallin led to early-stage lens cataract. We have used the zebrafish as a model system to investigate the role of α-crystallins during lens development. Interestingly, while zebrafish express one lens-specific αA-crystallin gene (cryaa), they express two αB-crystallin genes, with one evolving lens specificity (cryaba) and the other retaining the broad expression of its mammalian ortholog (cryabb). In this study we used individual mutant zebrafish lines for all three α-crystallin genes to determine the impact of their loss on age-related cataract. Surprisingly, unlike mouse knockout models, we found that the loss of the αBa-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age. Loss of αA-crystallin did not increase the prevalence of cataract. We also used single cell RNA-Seq and RT-qPCR data to show a shift in the lens expression of zebrafish α-crystallins between 5 and 10 days post fertilization (dpf), with 5 and 6 dpf lenses expressing cryaa almost exclusively, and expression of cryaba and cryabb becoming more prominent after 10 dpf. These data show that cryaa is the primary α-crystallin during early lens development, while the protective role for cryaba becomes more important during lens aging. This study is the first to quantify cataract prevalence in wild-type aging zebrafish, showing that lens opacities develop in approximately 25% of fish by 18 months of age. None of the three α-crystallin mutants showed a compensatory increase in the expression of the remaining two crystallins, or in the abundant βB1-crystallin. Overall, these findings indicate an ontogenetic shift in the functional importance of individual α-crystallins during zebrafish lens development. Our finding that the lens-specific zebrafish αBa-crystallin plays the leading role in preventing age-related cataract adds a new twist to our understanding of vertebrate lens evolution.