Cataractous Lenses Research Articles

Dehydroalanine and dehydrobutyrine in aging and cataractous lenses reveal site-specific consequences of spontaneous protein degradation.

Protein post-translational modifications (PTMs) have been associated with aging and age-related diseases. PTMs are particularly impactful in long-lived proteins, such as those found in the ocular lens, because they accumulate with age. Two PTMs that lead to protein-protein crosslinks in aged and cataractous lenses are dehydroalanine (DHA) and dehydrobutyrine (DHB); formed from cysteine/serine and threonine residues, respectively. The purpose of this study was to quantitate DHA and DHB in human lens proteins as a function of age and cataract status. Human lenses of various ages were divided into five donor groups: transparent lenses (18-22-year-old, 48-64-year-old, and 70-93-year-old) and cataractous human lenses of two age groups (48-64-year-old lenses, and 70-93-year-old lenses) and were subjected to proteomic analysis. Relative DHA and DHB peptide levels were quantified and compared to their non-modified peptide counterparts. For most lens proteins containing DHA or DHB, higher amounts of DHA- and DHB-modified peptides were detected in aged and cataractous lenses. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in age-related nuclear cataract (ARNC), (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. There was no indication that DHA or DHB levels were dependent on lens region. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins. DHA and DHB formation may induce structural effects that make proteins less soluble in water that leads to age-related protein insolubility and possibly aggregation and light scattering.

Outcomes of vitreoretinal surgery in eyes with retinitis pigmentosa without retinal detachment.

Outcomes of retinal detachment (RD) have been discussed in detail in many reports of patients with retinitis pigmentosa (RP). This study tries to understand the outcomes of vitreoretinal (VR) surgery for indications other than RD in the eyes with RP. This is a retrospective study that includes clinical data from January 2013 to December 2021. Patients with RP who were treated with a VR surgical intervention were included in the study. The primary outcome of the study was to assess the changes in best-corrected visual acuity. Forty-four eyes of 40 patients with RP were included in the study. Nearly half of the eyes (43%, 19/44) presented from 1month to 1year after the onset of diminished vision, with or without floaters. The mean ± standard deviation (SD) best-corrected visual acuity (BCVA) at presentation was 1.30 ± 0.79 logMAR (20/400 ± 20/125). The major surgical indications were vitreous opacities (43.2%, 19/44) and subluxated/dislocated cataractous lenses (25%, 11/44). The median follow-up duration was 8months (interquartile range (IQR): 1.5-27). Approximately 77% (34/44) of the eyes had improvement in vision. The mean postoperative BCVA at the last follow-up was 0.95 ± 0.73 logMAR (p-value: 0.03). Most eyes with RP recovered well after VR surgical interventions, with short-term improvements in visual acuity. It may be crucial to address the vitreous opacities and membranes as they hinder the residual central island of vision in RP. However, appropriate counselling is required regarding the progressive nature of retinal neuronal degeneration.

Development of a Web-Based Algorithm for Understanding the Intraocular Lens-Based Surgery in Stable and Progressing Keratoconus for Non-Specialist Ophthalmologists

Purpose To propose an algorithm to facilitate lens-based surgery in keratoconus. Methods A literature review was performed to prepare a software algorithm based on cone location, stability, best spectacle-corrected distance visual acuity (BSCVA) level and whether there is a clear or cataractous lens. The software usability was assessed through a 10-question questionnaire and two hypothetical keratoconus case histories (moderately simple and moderately complex) given to 15 trainees. The usability questionnaires were graded on a Likert scale (1 = strongly disagree to 5 = strongly agree) and two case histories (1 = very difficult to 7 = very easy). Results The algorithm can be found at https://www.sussexeyelaserclinic.co.uk/keratoconus/. Thirteen trainees completed the questionnaire. 91.9% would frequently use it; for 100%, it was easy to use independently without technical support; for 63.7%, it was strongly integrated; for 100%, it was consistent; 100% thought that most people would learn to use it quickly, 91.9% found the system not cumbersome to use, felt very confident to use it and need not learn a lot to use it. The first case was found easy by 63.7% and the second by 45%. Conclusion We present an algorithm as a guide for lens-based surgery in stable and progressing keratoconus, which is classified based on cone location. This algorithm will help trainee and “non-specialist” ophthalmic surgeons understand the pre-operative planning for the surgery and referral to the “specialist” corneal surgeon, considering factors such as progression, BSCVA, keratometry, topography and apex location of the cone in keratoconus patients.

Aniridia with secondary glaucoma and cataractous subluxated lens with ptosis with unilateral epicapsular star

Aniridia with secondary glaucoma and cataractous subluxated lens with ptosis with unilateral epicapsular star

Varied ocular manifestations of Marfan’s syndrome in a family

Marfan’s syndrome may present with varied ocular manifestations, major being ectopia lentis. The purpose of this presentation is to present the case of four members of a family presenting with Marfan’s syndrome showing myriad of ocular manifestations. The father, 45 year old male presented with bilateral ectopia lentis (inferiorly subluxated lenses) with raised IOP (33mmHg) in both the eyes. His eldest daughter, 18 year old, also shared similar findings. His second daughter (14 year old) had inferiorly subluxated lens in one eye and anteriorly dislocated lens with corneal opacity in other. Third daughter (13 year old) had intercalary and equatorial staphyloma with anteriorly dislocated cataractous lens with flat AC and raised IOP in right eye and inferiorly subluxated lens in left eye. There was history of death of a male child in the family due to some systemic disease at the age of eight. Systemic examination of the patients revealed no neurological deficits. Cardiovascular system examination was unremarkable. Hands and fingers were long and slender with hyperflexible joints. The ophthalmological management of Marfan’s patients is challenging and periodic follow up is needed. Surgical procedure may be required. Each case needs to be evaluated individually to analyse the risks and benefits of the procedures.

Upregulation of EphA2 is associated with apoptosis in response to H2O2 and UV radiation-induced cataracts

In this article, we examine the role of erythropoietin-producing hepatocellular receptor A2 (EphA2) in the apoptosis of lens epithelial cells (LECs) in H2O2 and UV radiation-induced cataracts. We treated SRA01/04 cells with H2O2 or ultraviolet (UV) radiation to create a cataract cell model. We constructed a cataract lens model by exposing mice to UV radiation. We used CCK8 assays, Annexin V-FITC analysis, and immunohistochemical staining to explore proliferation and apoptosis of the cataract model. Thereafter, we used quantitative real-time PCR (qPCR) analysis, Western blot assays, and immunofluorescence to determine gene and protein expression levels. We also employed Crispr/Cas9 gene editing to create an EphA2 knockout in SRA01/04 cells. Results: H2O2 or UV radiation induced SRA01/04 cells showed EphA2 gene upregulation. CCK8 and apoptosis assays showed that EphA2 over-expression (OE) reduced epithelial cell apoptosis, but knockout of EphA2 induced it in response to H2O2 and UV radiation, respectively. Mutation of the EphA2 protein kinase domain (c.2003G > A, p. G668D) had a limited effect on cell apoptosis. In vivo, the EphA2 protein level increased in the lenses of UV-treated mice. Our results showed that EphA2 was upregulated in SRA01/04 cells in response to H2O2 and UV radiation. Mutation of the EphA2 protein kinase domain (c.2003G > A, p. G668D) had a limited effect on H2O2 and UV radiation-induced cell apoptosis. We confirmed this change with an experiment on UV-treated mice. The present study established a novel association between EphA2 and LEC apoptosis.

Unbalanced redox status network as an early pathological event in congenital cataracts

The lens proteome undergoes dramatic composition changes during development and maturation. A defective developmental process leads to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early-onset forms of lens opacity, with the remainder being of unknown etiology. To gain a better understanding of cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W-Ub) that recapitulates most of the early pathological changes seen in human congenital cataracts. We performed mass spectrometry-based tandem-mass-tag quantitative proteomics in E15, P1, and P30 control or K6W-Ub lenses. Our analysis identified targets that are required for early normal differentiation steps and altered in cataractous lenses, particularly metabolic pathways involving glutathione and amino acids. Computational molecular phenotyping revealed that glutathione and taurine were spatially altered in the K6W-Ub cataractous lens. High-performance liquid chromatography revealed that both taurine and the ratio of reduced glutathione to oxidized glutathione, two indicators of redox status, were differentially compromised in lens biology. In sum, our research documents that dynamic proteome changes in a mouse model of congenital cataracts impact redox biology in lens. Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age-related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.

Comparison of INTREPID® balanced and hybrid tips on anterior capsule rupture in ex vivo porcine eyes.

Phacoemulsification has emerged as the global standard for cataract surgery, and various novel methods, tools, and agents have promoted surgical efficiency and reduced complications. Conventionally, the phaco tip, which cleaves and aspirates the cataractous lens, has been mainly constructed of metal. In this study, the risk of anterior capsule rupture was evaluated under conditions of different power modes, longitudinal (Mode-L), torsional (Mode-T), or both (Mode-LT), and different aspiration powers (0 or 200 mmHg), using a traditional metal phaco tip (Group-M) or a new phaco tip with a high-strength polymer overmold on the needle edge (Group-P), which was developed to reduce the risk of capsule rupture. One hundred twenty porcine eyes were used for experiments within a setting of typical human physiological intraocular pressure. We found that Group-M showed capsule rupture with a smaller ultrasound power than did Group-P, regardless of power mode or aspiration power. In Group-M, there was no significant difference in risk of capsule rupture among power modes, however in Group-P, capsule rupture was least likely to occur with Mode-T. These results provide useful information for inexperienced ophthalmologists to improve surgical safety.

Cataract surgery following penetrating keratoplasty in children.

Following penetrating keratoplasty, cataract surgery warrants certain modifications to ensure maximum survival of the graft. To emphasize the intraoperative challenges and surgical manipulations to be followed. The surgeon makes a superior sclerocorneal tunnel avoiding the graft host junction. Dispersive viscoelastic is used. Continuous curvilinear capsulorhexis is done. Cataractous lens aspirated with a low flow rate. The intraocular lens is placed in the bag. Superior peripheral iridectomy and primary posterior capsulorhexis are done. The wound closed with two interrupted 10-0 nylon sutures. Graft host junction integrity is maintained. Ensure 1. Good intraoperative corneal visibility, 2. Avoid graft host junction for main port incision 3. Generous dispersive viscoelastic use/soft shell technique to protect the corneal endothelium, 4. Avoid phaco energy in case of soft cataracts/low phaco energy and flow rates, 5. Phaco probe to be meticulously oriented away from corneal endothelium, 6. Primary posterior capsulorhexis to be done as in any pediatric cataract surgery, 7. Make sure of the graft host junction integrity at the end of the surgery, 8. Restrict to a single port whenever possible. https://youtu.be/tu4R5JangYs.

Lens Thickness in Atopic Cataract: A Case-Control Study.

To examine whether atopic cataracts are associated with thinner lenses. Department of Ophthalmology, Jikei University Hospital, Tokyo, Japan. Retrospective matched case-control study. A total of 31 eyes with atopic cataracts, 62 with non-atopic cataracts, and 31 without cataracts were analyzed. Each group was matched for age (± 4 years) and sex. The mean lens thickness (LT) was 3.76 ± 0.40, 3.94 ± 0.49, and 4.11 ± 0.40 mm in eyes with atopic cataracts, non-atopic cataracts, and normal lenses, respectively. Repeated-measures analysis of variance showed that the LT in the atopic cataract group was significantly thinner than that in the non-atopic cataract (P = 0.036) and normal lens (P < 0.001) groups. In multivariate logistic regression analysis, a thinner LT was negatively correlated with age (OR 0.91, 95% CI 0.86-0.96) and positively correlated with anterior subcapsular cataract (ASC) (OR 5.61, 95% CI 1.97-15.99). Atopy was not a significant factor. Twenty-four of the 62 eyes (38.7%) with non-atopic cataracts and 24 of the 31 eyes (77.4%) with atopic cataracts had ASC. The lenses of eyes with atopic cataracts were thinner than those of controls. Atopic cataracts frequently present with anterior subcapsular opacity, which is associated with lens thinning.

Modelling of an ultrasound-based system for cataract detection and classification

Cataract is a cloudiness in the lens of the eye affecting its transparency. Surgical cataract removal is the only therapeutic approach. Phacoemulsification is the most common surgical procedure, in which ultrasound energy is used to emulsify the cataractous lens. The hardness of the cataract determines the optimal energy for the phacoemulsification procedure. The objective of this work is to model an ultrasoundbased system for cataract detection and classification. It was developed a computational tool for simulating the propagation of A-scan ultrasound in the eye, using the k-Wave MATLAB toolbox. Considering the computational resources available and the dimensions of cataractous microstructures, it was determined a suitable resolution that enables the simulation of ultrasound propagation through the cataractous eye in 2D and 3D. Being so, a pixel size of 8 µm was stablished. A matrix representing the eye structures was constructed in MATLAB. Since on simulations it was considered a focalized probe only the central part of the eye matrix was used. It was observed that 2D and 3D simulated signals present some differences, mainly in the amplitudes of the echoes corresponding to the interfaces of the eye. The chosen resolution was suitable for the purpose of this work. The simulation tool shows good versatility for evaluating diverse aspects of A-scan biometry.

Ultrasound Diagnosed Traumatic Bilateral Cataractous Ectopia Lentis: A Case Report and Review

Introduction: Ectopia lentis is defined simply as lens displacement which may either be partial or complete. It most commonly results from orbital trauma in over fifty percent (50%) of cases, and majority are unilateral. However, traumatic bilateral ectopia lentis is rare. Hereditary connective tissue diseases may also cause ectopia lentis (usually bilateral). The role of imaging is very crucial in early identification of ocular pathologies following trauma. Ocular sonography, being the cheaper, safer and very readily available modality in most low and middle income countries, becomes handy in the initial imaging work-up of patients with ocular trauma. Objectives: To report a rare case of traumatic bilateral cataractous ectopia lentis in an elderly female patient. To review pertinent literature about this condition. To justify the role of various imaging modalities, and particularly highlight the usefulness of ultrasound for evaluating cases of ocular trauma especially in emergency situations. Case Report: The case of a 75-year old female who had blunt trauma to her eyes, and never sought immediate specialized medical care, but instead chose to patronise a traditional healing home. Her visual impairment gradually deteriorated, necessitating a late presentation for imaging at our private radiodiagnostic facility in Agbor, Nigeria. Imaging using ocular sonography, revealed bilateral displaced cataractous lenses with associated vitreous haemorrhage, necessitating an immediate, but a late referral for specialized care. Conclusion: Emergency ocular sonogram is of utmost importance in cases of acute ocular trauma, as it can help identify ocular pathologies promptly.

Absorbed cataractous lens and management – A case series

Absorption of a natural crystalline lens is very rare. It can be spontaneous or secondary due to ocular trauma or associated with multiple ocular and systemic conditions. In common perception, absorbed cataracts are considered difficult to manage surgically and are associated with poor surgical outcomes. Further, such cataract is rarely encountered in day-to-day clinical practice. Here, we report a case series of absorbed cataracts due to different etiologies managed surgically based on a thorough preoperative evaluation that led to good visual outcomes.

The great escape: Partially prolapsed cataractous lens stuck in a perforated corneal wound

The great escape: Partially prolapsed cataractous lens stuck in a perforated corneal wound

Vacuum-assisted levitation of posteriorly dislocated cataract lens

Abstract We describe a technique that uses 23 G pars plana vitrectomy without using fragmatome or perfluorocarbon liquid to manage a posteriorly dislocated cataract lens. The vacuum of the vitrector is used to levitate the lens up to the iris plane and then it is delivered using a wire-Vectis through a sclerocorneal tunnel. Subsequently, scleral fixation of an intraocular lens is performed.

ATCUN-like Copper Site in βB2-Crystallin Plays a Protective Role in Cataract-Associated Aggregation.

Cataract is the leading cause of blindness worldwide, and it is caused by crystallin damage and aggregation. Senile cataractous lenses have relatively high levels of metals, while some metal ions can directly induce the aggregation of human γ-crystallins. Here, we evaluated the impact of divalent metal ions in the aggregation of human βB2-crystallin, one of the most abundant crystallins in the lens. Turbidity assays showed that Pb2+, Hg2+, Cu2+, and Zn2+ ions induce the aggregation of βB2-crystallin. Metal-induced aggregation is partially reverted by a chelating agent, indicating the formation of metal-bridged species. Our study focused on the mechanism of copper-induced aggregation of βB2-crystallin, finding that it involves metal-bridging, disulfide-bridging, and loss of protein stability. Circular dichroism and electron paramagnetic resonance (EPR) revealed the presence of at least three Cu2+ binding sites in βB2-crystallin, one of them with spectroscopic features typical for Cu2+ bound to an amino-terminal copper and nickel (ATCUN) binding motif, which is found in Cu transport proteins. The ATCUN-like Cu binding site is located at the unstructured N-terminus of βB2-crystallin, and it could be modeled by a peptide with the first six residues in the protein sequence (NH2-ASDHQF-). Isothermal titration calorimetry indicates a nanomolar Cu2+ binding affinity for the ATCUN-like site. An N-truncated form of βB2-crystallin is more susceptible to Cu-induced aggregation and is less thermally stable, indicating a protective role for the ATCUN-like site. EPR and X-ray absorption spectroscopy studies reveal the presence of a copper redox active site in βB2-crystallin that is associated with metal-induced aggregation and formation of disulfide-bridged oligomers. Our study demonstrates metal-induced aggregation of βB2-crystallin and the presence of putative copper binding sites in the protein. Whether the copper-transport ATCUN-like site in βB2-crystallin plays a functional/protective role or constitutes a vestige from its evolution as a lens structural protein remains to be elucidated.

Characterization of a Novel Gja8 (Cx50) Mutation in a New Cataract Rat Model.

To describe a novel spontaneous cataract inbred strain isolated from large-scale breeding SD rats, identify the responsible gene mutation, and understand how this mutation affects lens function. Exome sequencing of 12 cataract-associated genes was performed in the affected and healthy relatives. Sequences of rat wild-type or mutant gap junction protein alpha 8 gene (Gja8) were transfected into cells. The expression level of protein was assayed by Western blot analysis. Subcellular localization of connexin 50 (Cx50) was analyzed in confocal fluorescent images. Wound-healing, 5-ethynyl-2'-deoxyuridine incorporation, and attachment assay were performed to characterize the cell migration, proliferation and adhesion. The abnormality was found to be inheritable in an autosomal semi-dominant pattern through different mating patterns. We found a G to T transversion at codon 655 in Gja8, leading to a substitution of valine by phenylalanine (p.V219F). Gja8V219F/+ heterozygotes expressed nuclear cataract while Gja8V219F/V219F homozygotes manifested microphthalmia in addition to cataract. Histology revealed fiber disorders and loss of organelle-free zone in the mutant lens. Cx50V219F altered its location in HeLa cells and inhibited the proliferation, migration and adhesion abilities of HLEB3 cells. The mutation also reduced the expression of focal adhesion kinase and its phosphorylation. The c.655G>T mutation (p.V219F) is a novel mutation in Gja8, inducing semi-dominant nuclear cataracts in a new spontaneous cataract rat model. The p.V219F mutation altered Cx50 distribution, inhibited lens epithelial cell proliferation, migration, and adhesion, and disrupted fiber cell differentiation. As a consequence, the nuclear cataract and small lens formed.

Enzymatic and biochemical properties of lens in age-related cataract versus diabetic cataract: A narrative review.

Cataract is the leading cause of blindness worldwide. There is an increased incidence of cataract formation in the diabetic population due to several factors. Diabetes mellitus accelerates the development of cataract. Oxidative stress results in most of the diabetic complications including diabetic cataract. Oxidative stress leading to the expression of various enzymes has also been proven as crucial for cataractous changes in the lens in old age. A narrative review was undertaken to investigate the expression of different biochemical parameters as well as enzymes in diabetic and senile cataracts. Identification of these parameters is crucial for the prevention and treatment of blindness. Combinations of MeSH terms and key words were used to do literature search in PubMed. The search resulted 35 articles and among them, 13 were relevant to the topic and were included in synthesis of results. Seventeen different types of enzymes were identified in the senile and diabetic cataracts. Seven biochemical parameters were also identified. Alteration in biochemical parameters and expression of enzymes were comparable. Majority of the parameters were raised or altered in diabetic cataract compared to senile cataract.

Исследование предоперационной симметрии дистанции «экватор хрусталика – цилиарные отростки» у пациентов с сочетанием возрастной катаракты с клиническими проявлениями инволюционной соединительнотканной дисплазии

Purpose. Study of state of the Zonule of Zinn in patients with combination senile cataract with systemic involutional connective tissue dysplasia. Material and methods. 97 patients (97 eyes) – combination senile cataract with involutional pathology in connective tissue (the main group). 1st subgroup: 31 patients with kyphoscoliotic deformity of the 3d and 4th degree (classification by V.D. Chaklin (1973)); 2nd subgroup – 66 patients with chronic venous insufficiency 2nd and 3d degree (the CEAP classification) against the background of varicose veins of the lower extremity. Patients of both subgroups were comparable in terms of cataract stages and nuclear cataract lens density in Buratto classification. The control group – 55 patients (55 eyes) similar sex and age with senile cataracts without involutional connective tissue pathology. We estimated the symmetry of distance «lens equator – ciliary processes» in 2 meridians: at 6 and 12 hours. The presence of asymmetry of 0.3 mm or more was sign of weak zonular support (according to ultrasonic biomicroscopy). Results. In the control group, the distance was 0.3 mm in 3 eyes (5%), with intraoperative formation of folds in the anterior capsule. In 10 eyes of the 1st subgroup of the main group (32%), the presence of distance asymmetry was revealed: intraoperative, signs of subluxation of the lens of the 1st degree were detected in 7 eyes. In the 2nd subgroup of the main group, distance asymmetry was detected in 24 eyes (37%). Folded anterior lens capsule was determined intraoperative in 14 eyes (21%) during anterior capsulorhexis and lens mobility during nucleus emulsification. Conclusion. A statistically significant difference in frequency of asymmetries of distances «lens equator – ciliary processes» in 2 opposite meridians was revealed between groups of patients with senile cataract against the background of systemic somatic involutional pathology of connective tissue and without it (35% vs. 5%; p &lt; 0.01). Keywords: senile cataract, Zonule of Zinn, involutional changes in connective tissue, ultrasound biomicroscopy

Severe anterior persistent fetal vasculature: the role of anterior retinal elongation on prognosis.

This study aims to investigate surgical outcomes of eyes with severe anterior persistent fetal vasculature (PFV) and the role of associated anatomical anomalies on prognosis. This is a retrospective, comparative case series of 32 eyes of 31 patients who underwent vitreoretinal surgery for severe anterior PFV, defined as fibrovascular tissue totally covering the back of cataractous lens. Based on the degree of anterior retinal elongations, cases were classified as follows: group 1, eyes with well-developed pars plana and minor/no abnormalities (n = 11, 34%); group 2, eyes with partially developed pars plana and broad-based elongations (n = 9, 28%); and group 3, eyes with no visible pars plana and fibrovascular membrane having 360° continuity with peripheral retina (n = 12, 38%). Complications and functional and anatomical outcomes were investigated. The median surgical age was 2 (1-12) months. The median follow-up was 26 (6-120) months. Seventy-three percent in group 1 achieved finger counting or better vision with a single surgery and without any pupillary/retinal complication. Groups 2 and 3 required 2.1 ± 0.9 and 2.6 ± 1.2 surgeries on average. Pupillary obliteration and RD occurred in 33% and 22% in group 2 and 58% and 67% in group 3. Retina remained attached after silicone oil removal in 89% of group 2 and 25% of group 3. Phthisis developed in 50% in group 3. Peripheral retinal anomalies are common in severe anterior PFV and have a major impact on prognosis. Prognosis is favorable in cases with mild-to-moderate anomalies with appropriate management of possible retinal tears. In eyes with 360° retinal elongations, severe fibrous proliferation and eventual eye loss are common.