Development Of Posterior Capsule Opacification Research Articles

MT6 Global Systematic Review on the Incidence of Nd:Yag Laser Capsulotomy Post-Cataract Surgery in Eyes Implanted with the Clareon Intraocular Lens (IOL) Implanted Eyes

The improvements in surgical technique has made cataract surgery an increasingly safe procedure, posterior capsule opacification (PCO), however, remains the most common complication post-cataract surgery. PCO development has been associated with IOL design, IOL biomaterial, and other factors. Nd:YAG laser capsulotomy is used to treat clinically significant PCO.

Vascular endothelial cell-derived exosomal miR-1246 facilitates posterior capsule opacification development by targeting GSK-3β in diabetes mellitus

Posterior capsule opacification (PCO) is a serious complication after cataract surgery. Diabetes could increase the occurrence of PCO, but the mechanism is still unclear. The purpose of this study is to investigate the role of small extracellular vesicles (sEVs) derived from diabetic aqueous humor in PCO process. Intraoperatively-derived aqueous humor sEVs from patients with diabetic related cataract (DRC) promoted the epithelial-mesenchymal transition (EMT) and metastasis of human lens epithelial cells (LECs). Via mouse PCO surgical model and DiI labeled fluorescence detection of sEVs, the sEVs derived from vascular endothelium were discovered directly contacting with LECs. Furthermore, we demonstrated that high-glucose-cultured human umbilical vein endothelial cells (HUVEC) -derived sEVs facilitated EMT process of HLE-B3 using co-culture model in vitro. miRNA-seq data and GEO datasets analysis revealed that miR-1246 was essential in EMT process with diabetes. The miR-1246 was highly expressed in diabetic aqueous humor sEVs and high-glucose-treated vascular-endothelial-cell-derived sEVs. Moreover, miR-1246 promoted the metastasis and EMT process of HLE-B3 cells by directly targeting GSK-3β. Inhibiting miR-1246 could negatively regulated EMT. This finding might serve as a potential therapy for diabetic PCO.

Posterior capsule opacification following implantation of hydrophilic compared to hydrophobic intraocular lenses

Purpose The aim of this study was to compare the onset of posterior capsule opacification (PCO) in patients who underwent hydrophilic intraocular lens (IOLs) implantation compared with hydrophobic IOL implantation. Patients and methods This is a retrospective, comparative, observational study that was conducted on patients who sought medical advice at the Ophthalmology Outpatient Clinic of the Ophthalmology Department, Ain Shams University, Cairo, Egypt, and underwent uneventful phacoemulsification cataract surgery and hydrophilic or hydrophobic acrylic nonheparinized IOL implantation. The electronic medical records were searched for surgeries performed by equal-caliber experienced surgeons. All enrolled cases underwent ‘in-the-bag’ implantation of a square-edged IOL after continuous curvilinear capsulorhexis with cortical cleanup. The evaluated data included age, sex, medical history, date of phacoemulsification cataract surgery, type of implanted IOL, and the duration till Nd : YAG capsulotomy was needed. The patients were divided into two groups: group 1 (29 eyes of 29 patients), which underwent hydrophilic acrylic IOL implantation, and group 2 (27 eyes of 27 patients), which underwent hydrophobic acrylic IOL implantation. Results There was no statistically significant difference between the hydrophilic and hydrophobic IOLs regarding the time of onset of postoperative PCO development [median=1.92 years, interquartile range=1.17–2.75 in group 1 and 1.34 years (0.5–2.41) in group 2, P=0.192). In addition, there was no statistically significant relation between the onset of PCO and the general medical condition of the enrolled patients, including diabetes mellitus, hypertension, hepatitis C virus, renal disease, systemic lupus erythematosus, hypocalcemia, and patients on chemotherapy (P>0.05). Conclusion There was no statistically significant difference in the onset of PCO development with different IOL materials. Moreover, the patients’ general medical condition did not show a significant association with PCO incidence.

Evaluation of Nd:YAG laser capsulotomy results in patients who underwent cataract extraction and intraocular lens implantation with the endocapsular phacoemulsification method

Background/Aim: Posterior capsular opacification (PCO) is a common complication that develops after cataract surgery, and it can be treated neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy. In this study, we aimed to investigate the effects of different intraocular lenses (IOLs) on the development of posterior capsule opacification (PCO), to determine the time between surgery and Nd:YAG laser capsulotomy, and to evaluate the efficacy, effectiveness, and complications of capsulotomy in patients who underwent cataract surgery with the phacoemulsification method and subsequently developed PCO. Methods: The cohort study included one eye of each of 153 cases (63 males, 90 females) who underwent cataract surgery with the phacoemulsification method in our clinic from August 1, 2006, through August 1, 2008, and subsequently developed PCO. According to the type of IOL implanted, the cases were divided into three groups: polymethylmethacrylate IOL (Group 1), hydrophilic acrylic IOL (Group 2), and hydrophobic acrylic IOL (Group 3). The control examinations of the patients who underwent Nd:YAG laser capsulotomy were undertaken before capsulotomy and at the first week, first month, and third month after capsulotomy. Results: Visual acuity improvement was detected in 96.7% of the 153 cases. It was determined that 9.1% of the cases had an intraocular pressure (IOP) increase of more than 5 mmHg at the third hour after capsulotomy and approached baseline values at the end of 1 week. The mean total energy used in all the cases was 37.20 (14.70) mjl. The mean total energy used in 14 patients with an IOP elevation of above 5 mmHg was 71.07 (10.59) mjl. Nd:YAG laser capsulotomy was performed at an average of 6.29 (4.91) months in Group 1, 7.81 (4.35) months in Group 2, and 17.7 (12.35) months in Group 3. After capsulotomy, clinically significant cystoid macular edema was observed in 1.9% of the cases, IOL damage in 3.9%, and vitreous hemorrhage in 0.6%. Conclusion: In this study, the incidence of PCO development was found to be lower in the patients who underwent hydrophobic acrylic IOL implantation; therefore, this type of lens should be preferred for implantation. Although Nd:YAG laser capsulotomy is an outpatient treatment method that can be applied quickly and can increase visual acuity, it can also lead to complications. To eliminate most of these complications, it would be beneficial to minimize the energy used during the laser procedure.

Role of Decorin in the Lens and Ocular Diseases

Decorin is an archetypal member of the small leucine-rich proteoglycan gene family and is involved in various biological functions and many signaling networks, interacting with extra-cellular matrix (ECM) components, growth factors, and receptor tyrosine kinases. Decorin also modulates the growth factors, cell proliferation, migration, and angiogenesis. It has been reported to be involved in many ischemic and fibrotic eye diseases, such as congenital stromal dystrophy of the cornea, anterior subcapsular fibrosis of the lens, proliferative vitreoretinopathy, et al. Furthermore, recent evidence supports its role in secondary posterior capsule opacification (PCO) after cataract surgery. The expression of decorin mRNA in lens epithelial cells in vitro was found to decrease upon transforming growth factor (TGF)-β-2 addition and increase upon fibroblast growth factor (FGF)-2 addition. Wound healing of the injured lens in mice transgenic for lens-specific human decorin was promoted by inhibiting myofibroblastic changes. Decorin may be associated with epithelial-mesenchymal transition and PCO development in the lens. Gene therapy and decorin administration have the potential to serve as excellent therapeutic approaches for modifying impaired wound healing, PCO, and other eye diseases related to fibrosis and angiogenesis. In this review, we present findings regarding the roles of decorin in the lens and ocular diseases.

Nd:YAG Laser Capsulotomy Rates in the Netherlands; Practice Variation and Association with Physician Practice Styles.

To determine the practice variation in rate of Nd:YAG laser capsulotomy within one year after cataract surgery and to identify possible associations with physician practice styles. All hospitals and private clinics in The Netherlands. Retrospective observational study. In the national medical claims database, we identified all laser capsulotomies performed in the Netherlands within a year after cataract surgery in the years 2016 and 2017. Centres with the lowest and highest percentages of Nd:YAG laser capsulotomies were interviewed on their physician practice styles related to the development of posterior capsule opacification. The incidence of Nd:YAG laser capsulotomy varied between 1.2% and 26.0% in 2016 (median 5.0%) and between 0.9% and 22.7% in 2017 (median 5.0%). The rate of capsulotomy was highly consistent over time for each centre (Pearson correlation coefficient, 0.89, P < 0.001). In general, ophthalmology centres with a high rate of Nd:YAG laser capsulotomy more often did not (routinely) polish the posterior lens capsule, performed cortex removal with coaxial irrigation/aspiration (instead of bimanual), and more often used hydrophilic IOLs (compared to only using hydrophobic IOLs). We found a significant practice variation in performing Nd:YAG laser capsulotomy within one year after cataract surgery in the Netherlands. Routinely polishing the posterior capsule, using bimanual I/A, and the use of hydrophobic IOLs are associated with a lower incidence in Nd:YAG laser capsulotomy. Incorporating these practice styles may lower the practice variation and thus prevent added medical burden for the patient and decrease costs.

Surface modification of commercial intraocular lens by zwitterionic and antibiotic-loaded coating for preventing postoperative endophthalmitis

After cataract surgery, to prevent possible postoperative endophthalmitis (POE) caused by attached pathogenic bacteria onto the surface of implanted intraocular lens (IOL), various antibiotic-loaded IOLs have been proposed and widely studied to inhibit bacterial infection. However, most of these developed antibiotic-loaded IOLs still suffer from shortcomings such as insufficient drug loading, short release time, poor biocompatibility, and risk of secondary infection. Herein, we propose a zwitterionic and high-drug loading coating for surface modification of commercial hydrophobic IOL with both antifouling and antibacterial properties to effectively prevent POE. In this strategy, zwitterionic poly(carboxylbetaine-co-dopamine methacrylamide) copolymers (pCBDA) and dopamine (DA) were first robustly co-deposited onto IOL surface via facile mussel-inspired chemistry, resulting in a hydrophilic coating (defined as PCB) without sacrificing the high light transmittance of the native IOL. Subsequently, amikacin (AMK), an amine-rich antibiotic was reversibly conjugated onto the coating through the acid-sensitive Schiff base bonds formed by the reaction between amino and catechol groups, with high-drug payload over ∼35.5 μg per IOL and 30 days of sustained drug release under weak acid environment. Benefiting from the antifouling property of zwitterionic pCBDA copolymers, the intraocularly implanted PCB/AMK-coated IOL could effectively resist the adhesion and proliferation of residual LECs to inhibit the development of posterior capsule opacification (PCO) without affecting the normal ocular tissues, demonstrating excellent in vivo biocompatibility. Moreover, the synergy of zwitterionic pCBDA and conjugated AMK with acidic-dependent release behavior endowed this PCB/AMK-coated IOL strong antibacterial activity against both in vitro biofilm formation and in vivo postoperative Staphylococcus aureus infection, suggesting its promising application in preventing POE.

Positive resolution of the wound-healing response in lens epithelial cells by Ti3C2T x MXene coatings for use in accommodative intraocular lens devices

Cataract surgery removes the diseased lens of the eye replacing it with an intraocular lens, restoring visual acuity. However, accommodation, the lens’ ability to provide dynamic change in focus, is lost. A number of accommodative intraocular lens (AIOL) designs have been considered although none have provided a truly effective clinical AIOL. Two-dimensional titanium carbide (Ti3C2T x ) MXene has been used as a transparent conductive electrode within an AIOL feasibility study. Nevertheless, the potential for Ti3C2T x to repress excessive inflammation and promote wound healing following cataract surgery has not been considered. Cataract surgery can trigger chronic inflammation and epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LECs), producing a fibrotic mass across the posterior capsule known as posterior capsule opacification (PCO). With a large surface area and capacity for surface functionalisation, MXene has properties enabling a dual purpose AIOL design with an additional therapeutic role in the repression of pathways leading to PCO development. In this study, Ti3C2T x MXene was investigated to determine its impact on pathways leading to chronic inflammation and EMT using an in vitro LECs model. Ti3C2T x MXene was synthesised and characterised using UV-vis spectroscopy, dynamic light scattering and scanning electron microscopy. Changes in markers linked to inflammation and EMT in Ti3C2T x -treated LECs were measured using enzyme linked immunosorbent assays, quantitative polymerase chain reaction, scratch assay, RNA sequencing for whole-cell gene expression profiling and lipidomics analysis. Ti3C2T x significantly reduced the expression of pro-inflammatory cytokines by interleukin 1 beta primed LECs and did not advocate EMT, promoting a positive resolution of the wound healing response. This study supports the role of Ti3C2T x within an AIOL design with the potential to repress key developmental pathways leading to PCO.

Two-dimensional ultrathin Ti3C2 MXene nanosheets coated intraocular lens for synergistic photothermal and NIR-controllable rapamycin releasing therapy against posterior capsule opacification.

Posterior capsule opacification (PCO) is one of the most frequent late-onset complications after cataract surgery. Several kinds of drug-eluting intraocular lenses (IOL) were designed for sustainable drug release to suppress ocular inflammation, the proliferation of lens epithelial cells (LECs) and the development of PCO after cataract surgery. Despite previous advances in this field, the drug-loaded IOLs were limited in ocular toxicity, insufficient drug-loading capacity, and short release time. To prevent PCO and to address these drawbacks, a novel drug-loaded IOL (Rapa@Ti3C2-IOL), prepared from two-dimensional ultrathin Ti3C2 MXene nanosheets and rapamycin (Rapa), was fabricated with a two-step spin coating method in this study. Rapa@Ti3C2 was prepared via electrostatic self-assembly of Ti3C2 and Rapa, with a loading capacity of Rapa at 92%. Ti3C2 was used as a drug delivery reservoir of Rapa. Rapa@Ti3C2-IOL was designed to have the synergistic photothermal and near infrared (NIR)-controllable drug release property. As a result, Rapa@Ti3C2-IOL exhibited the advantages of simple preparation, high light transmittance, excellent photothermal conversion capacity, and NIR-controllable drug release behavior. The Rapa@Ti3C2 coating effectively eliminated the LECs around Rapa@Ti3C2-IOL under a mild 808-nm NIR laser irradiation (1.0 W/cm−2). Moreover, NIR-controllable Rapa release inhibited the migration of LECs and suppressed the inflammatory response after photothermal therapy in vitro. Then, Rapa@Ti3C2-IOL was implanted into chinchilla rabbit eyes, and the effectiveness and biocompatibility to prevent PCO were evaluated for 4 weeks. The Rapa@Ti3C2-IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and no obvious pathological damage was observed in surrounding healthy tissues. In summary, the present study offers a promising strategy for preventing PCO via ultrathin Ti3C2 MXene nanosheet-based IOLs with synergistic photothermal and NIR-controllable Rapa release properties.

The Royal College of Ophthalmologists' National Ophthalmology Database study of cataract surgery: Report 9, Risk factors for posterior capsule opacification.

Posterior Capsule Opacification (PCO) is the most common long-term post-operative adverse occurrence after cataract surgery often requiring treatment with YAG laser posterior capsulotomy. This study aimed to identify potential risk factors, known at the time of cataract surgery, that influence the development of PCO. A retrospective study of publicly funded cataract surgery from The Royal College of Ophthalmologists' National Ophthalmology Database. Eligible for analysis were 500,872 cataract operations performed in 41 participating centres. The 500,872 operations were performed on 243,167 (48.5%) left eyes and 257,705 (51.5%) right eyes from 373,579 patients by 2196 surgeons. Post-cataract PCO was recorded for 61,778 (12.3%) eyes and the six month, one, three, five and nine year observed rates of PCO were 2.3%, 4.4%, 19.7%, 34.0% and 46.9% respectively. Different PCO profiles were observed between IOL materials and the identified risk factors that increased the risk of developing PCO included hydrophilic IOL material, axial length >26 mm, the presence of high myopia and implantation of lower IOL powers and previous vitrectomy surgery, along with younger age and female gender. Many factors influence the development of PCO relating to the patient, the eye, the lens and the surgery. Some factors are modifiable such as IOL material, therefore the opportunity exists to attempt to reduce PCO rates, benefitting patients and the UK NHS.

TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development

Background: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, in which increased levels of transforming growth factor-beta 2 (TGF-β2) accelerate PCO formation; however, the pathological mechanisms are not fully understood. This study aims to explore the regulation mechanism of TGF-β2 in PCO formation via its autophagic functions. Methods: The autophagic effect of TGF-β2 was detected by transmission electron microscopy (TEM), Western blotting, and immunofluorescence analysis. The association between autophagy and the epithelial–mesenchymal transition (EMT) was evaluated by qPCR and Western blotting. The transcriptome analysis was used to uncover the molecular mechanism of TGF-β2-induced PCO formation. Results: TGF-β2 specifically promotes autophagy flux in human lens epithelial cells. The activation of autophagy by rapamycin can promote EMT marker synthesis and improve cell migration. However, the inhibition of autophagy by 3-MA attenuates EMT. To uncover the molecular mechanisms, we performed RNA sequencing and found that TGF-β2 elevated tumor protein p53-inducible nuclear protein2 (TP53INP2) expression, which was accompanied by a nuclear-to-cytoplasm translocation. Moreover, the knockdown of TP53INP2 blocked the TGF-β2-induced autophagy and EMT processes, revealing that TP53INP2 plays an important role in TGF-β2-induced autophagy during EMT. Conclusions: Taken together, the results of this study suggested that TP53INP2 was a novel regulator of PCO development by TGF-β2, and notably, TP53INP2, may be a potential target for the pharmacological treatment of PCO.

Interfering Hsa_circRNA_0060640 Suppresses TGF-β2-Induced Proliferation, Motility and EMT in Human Lens Epithelium Cells by Targeting miR-214-3p and Collagen Type I alpha2 Chain

BackgroundCircular RNA (circRNA) is a novel star factor in the research of ocular diseases including cataract and the most common postoperative complication posterior capsule opacification (PCO). Hsa_circRNA_0060640 (circ_0060640) is an age-related cataract-related circRNA. However, its role in cataractogenesis is unrevealed yet.MethodsPCO in vitro model was established in human lens epithelium cells (hLECs) induced by transforming growth factor-beta2 (TGF-β2). RNA and protein expressions were respectively detected by quantitative PCR and western blotting. Direct interaction between two RNAs was predicted by Starbase tool and confirmed by dual-luciferase reporter assay. MTS and EdU assays measured cell proliferation; Transwell, starch wound and western blotting assays evaluated cell motility and epithelial-mesenchymal transition (EMT).ResultsCirc_0060640 expression is higher in anterior lens capsule tissues from human cataractous eyes and TGF-β2-stimulated hLECs cells line SRA01/04. RNA interference of circ_0060640 could prevent SRA01/04 cells from TGF-β2-induced cell proliferation, migration and invasion, accompanied with decreased N-cadherin and α-smooth muscle actin and increased E-cadherin. Mechanistically, circ_0060640 directly controls microRNA (miR)-214-3p expression and then regulates gene expression of collagen type I alpha2 chain (COL1A2). Notably, COL1A2 inhibition is underlying the protective role of circ_0060640 silencing and miR-214-3p ectopic expression in TGF-β2-stimulated SRA01/04 cells.ConclusionCirc_0060640 is a novel cataract-related gene and its silencing could block TGF-β2-evoked hLECs proliferation, motility and EMT in vitro via targeting miR-214-3p-COL1A2 axis. Therefore, targeting circ_0060640 via RNA interference might be a treatment strategy for PCO development.

Sustained Release of Antibody-Conjugated DNA Nanocarriers from a Novel Injectable Hydrogel for Targeted Cell Depletion to Treat Cataract Posterior Capsule Opacification.

Purpose: To compare a novel, sustained release formulation and a bolus injection of a targeted nanocarrier for the ability to specifically deplete cells responsible for the development of posterior capsule opacification (PCO) in week-long, dynamic cell cultures. Methods: A novel, injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer hydrogel was engineered for the sustained release of targeted, nucleic acid nanocarriers loaded with cytotoxic doxorubicin (G8:3DNA:Dox). Human rhabdomyosarcoma (RD) cells were used due to their expression of brain-specific angiogenesis inhibitor 1 (BAI1), a specific marker for the myofibroblasts responsible for PCO. Under constant media flow, nanocarriers were injected into cell cultures as either a bolus or within the hydrogel. Cells were fixed and stained every other day for 7 days to compare targeted depletion of BAI1+ cells. Results: The formulation transitions to a gel at physiological temperatures, is optically clear, noncytotoxic, and can release G8:3DNA:Dox nanocarriers for up to 4 weeks. In RD cell cultures, G8:3DNA:Dox nanocarriers specifically eliminated BAI1+ cells. The bolus nanocarrier dose showed significantly reduced cell depletion overtime, while the sustained release of nanocarriers showed increased cell depletion over time. By day 7, <2% of BAI1+ cells were depleted by the bolus injection and 74.2% BAI1+ cells were targeted by the sustained release of nanocarriers. Conclusions: The sustained release of nanocarriers from the hydrogel allows for improved therapeutic delivery in a dynamic system. This method can offer a more effective and efficient method of prophylactically treating PCO after cataract surgery.

Long-term incidence of posterior capsular opacification in patients with non-infectious uveitis

Little is known about the long-term incidence of posterior capsule opacification (PCO) after cataract surgery in patients with uveitis. This retrospective study included 211 eyes of 146 patients with non-infectious uveitis who underwent cataract surgery and implantation of an Acrysof SN60WF (Surface: plasma-treated, Optic and Haptic: hydrophobic acrylic), iSert XY-1 (Surface: UV-ozone-treated, Optic and Haptic: hydrophobic acrylic), or iSert 251/255 (Surface: UV-ozone-treated, Optics: hydrophobic acrylic, Haptic: polymethyl methacrylate). The cumulative incidences of PCO and subsequent yttrium–aluminum-garnet (Nd:YAG) capsulotomy over the 5-year follow-up were analyzed, and patients who were implanted with different intraocular lenses (IOLs) were compared. Mixed-effects Cox proportional hazard models showed that, compared with the Acrysof group, the iSert XY-1 group had higher risks of PCO (adjusted HR, 7.26; 95% CI, 1.82–28.8) and Nd:YAG capsulotomy (adjusted HR, 6.50; 95% CI, 1.55–27.2). Similar results were obtained when the Acrysof group was compared with the iSert 251/255 group for PCO (adjusted HR, 8.22; 95% CI, 2.35–28.7) and Nd:YAG capsulotomy (adjusted HR, 8.26; 1.90–36.0). These data suggest that a plasma-treated surface, hydrophobic acrylic optic and hydrophobic acrylic haptic, of the IOL could enhance biocompatibility even under inflammatory conditions, thus suppressing PCO development.

The Influence of Inflammation in Posterior Capsule Opacification Development

Abstract Cataract represents the reduction of the transparency of the crystalline lens. Cataract surgery is the most commonly performed surgical procedure worldwide. One of the most common postoperative complication of successfully performed cataract surgery is a development of posterior capsule opacification (PCO). In the postoperative period, lens epithelial cells (LECs) undergo proliferation, migration and differentiation, which is clinically manifested by the development of PCO. Inflammation has a central role in these processes. Cytokines, such as transforming growth factor β, fibroblast growth factor, interleukin 1, interleukin 6, matrix metalloproteinases have a huge effect on the activity of LECs. Understanding these processes can find a great usage in clinical practice. By prescribing anti-inflammatory therapy in the early postoperative period, the incidence of PCO can be significantly reduced.

Geometry of Acrylic, Hydrophobic IOLs and Changes in Haptic-Capsular Bag Relationship According to Compression and Different Well Diameters: A Bench Study Using Computed Tomography.

IntroductionCharacteristics of the haptics and optic–haptic junction (OHJ) of an intraocular lens (IOL) affect IOL position in the capsular bag, positional stability, and the development of posterior capsule opacification. Therefore, the haptics and OHJ have a role in determining initial and long-term visual outcomes after cataract surgery. Understanding differences in the haptics and OHJ of available IOLs and in the relationships between the haptics of each IOL and the capsular bag across a range of capsular bag sizes might inform selection of an IOL model for individuals.PurposeTo evaluate the geometry of five currently marketed, commonly used one-piece hydrophobic acrylic monofocal IOLs and changes in haptic–capsular bag relationships according to capsular bag size using a range of compression well diameters.MethodsAcrySof SN60WF, CT LUCIA 621PY, enVista MX60, TECNIS ZCB00, and Vivinex XY1 IOLs were scanned with computed tomography (CT) in a dry, uncompressed state for quantitative analyses of haptic and OHJ dimensions and qualitative assessment of geometry. CT scanning was done after IOL placement into a series of compression wells (11.5, 11.0, 10.0, and 9.0 mm) for analyses of haptic angle of contact (AoC) and capsular bag contact (CBC). IOL axial alignment and haptic–capsular bag relationships were assessed on side-view and 3-dimensional top-view images, respectively.ResultsThe qualitative and quantitative evaluations highlighted differences in haptic and OHJ geometry and dimensions across the five IOLs. All haptic dimensions (length, thickness, surface area, volume) and all OHJ dimensions (surface area and volume) were greatest for the CT LUCIA 621PY IOL. Compared to the IOL that had the smallest measurement for each parameter, the value for the CT LUCIA 621PY IOL was 31–91% larger. The lens with the largest OHJ surface area and volume showed values that were 500% and 240% greater than the corresponding values for the lens with the smallest OHJ surface area and OHJ volume. The AoC and CBC values decreased with increasing well size for all IOLs. The CT LUCIA 621PY had the greatest AoC and CBC values for all well sizes and the smallest percentage change in AoC and CBC comparing the values from the 9.0 mm and 11.5 mm wells.ConclusionThe in vitro evaluations in this study highlight differences in the haptic and OHJ geometric characteristics of the five IOLs studied. The collected evidence refutes opinions that all hydrophobic acrylic one-piece IOLs are the same and supports the idea that individual IOLs can have relative advantages and disadvantages that depend on the individual case. We believe the knowledge of geometry is necessary for the surgeon to have the opportunity to select the best “customized” option in the individual case as a result of anatomical conditions and secondary diagnoses. Our bench study shows how big the differences are in currently available monofocal hydrophobic acrylic lenses.

Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues

Recent reports have challenged the notion that the lens is immune-privileged. However, these studies have not fully identified the molecular mechanism(s) that promote immune surveillance of the lens. Using a mouse model of targeted glutathione (GSH) deficiency in ocular surface tissues, we have investigated the role of oxidative stress in upregulating cytokine expression and promoting immune surveillance of the eye. RNA-sequencing of lenses from postnatal day (P) 1-aged Gclcf/f;Le-CreTg/- (KO) and Gclcf/f;Le-Cre−/− control (CON) mice revealed upregulation of many cytokines (e.g., CCL4, GDF15, CSF1) and immune response genes in the lenses of KO mice. The eyes of KO mice had a greater number of cells in the aqueous and vitreous humors at P1, P20 and P50 than age-matched CON and Gclcw/w;Le-CreTg/- (CRE) mice. Histological analyses revealed the presence of innate immune cells (i.e., macrophages, leukocytes) in ocular structures of the KO mice. At P20, the expression of cytokines and ROS content was higher in the lenses of KO mice than in those from age-matched CRE and CON mice, suggesting that oxidative stress may induce cytokine expression. In vitro administration of the oxidant, hydrogen peroxide, and the depletion of GSH (using buthionine sulfoximine (BSO)) in 21EM15 lens epithelial cells induced cytokine expression, an effect that was prevented by co-treatment of the cells with N-acetyl-l-cysteine (NAC), a antioxidant. The in vivo and ex vivo induction of cytokine expression by oxidative stress was associated with the expression of markers of epithelial-to-mesenchymal transition (EMT), α-SMA, in lens cells. Given that EMT of lens epithelial cells causes posterior capsule opacification (PCO), we propose that oxidative stress induces cytokine expression, EMT and the development of PCO in a positive feedback loop. Collectively these data indicate that oxidative stress induces inflammation of lens cells which promotes immune surveillance of ocular structures.

The local wound environment is a key determinant of the outcome of TGFβ signaling on the fibrotic response of CD44+ leader cells in an ex vivo post-cataract-surgery model

The cytokine transforming growth factor beta (TGFβ) has a role in regulating the normal and pathological response to wound healing, yet how it shifts from a pro-repair to a pro-fibrotic function within the wound environment is still unclear. Using a clinically relevant ex vivo post-cataract surgery model that mimics the lens fibrotic disease posterior capsule opacification (PCO), we investigated the influence of two distinct wound environments on shaping the TGFβ-mediated injury response of CD44+ vimentin-rich leader cells. The substantial fibrotic response of this cell population occurred within a rigid wound environment under the control of endogenous TGFβ. However, TGFβ was dispensable for the role of leader cells in wound healing on the endogenous basement membrane wound environment, where repair occurs in the absence of a major fibrotic outcome. A difference between leader cell function in these distinct environments was their cell surface expression of the latent TGFβ activator, αvβ3 integrin. This receptor is exclusively found on this CD44+ cell population when they localize to the leading edge of the rigid wound environment. Providing exogenous TGFβ to bypass any differences in the ability of the leader cells to sustain activation of TGFβ in different environments revealed their inherent ability to induce pro-fibrotic reactions on the basement membrane wound environment. Furthermore, exposure of the leader cells in the rigid wound environment to TGFβ led to an accelerated fibrotic response including the earlier appearance of pro-collagen + cells, alpha smooth muscle actin (αSMA)+ myofibroblasts, and increased fibrotic matrix production. Collectively, these findings show the influence of the local wound environment on the extent and severity of TGFβ-induced fibrotic responses. These findings have important implications for understanding the development of the lens fibrotic disease PCO in response to cataract surgery wounding.

Metformin attenuates the epithelial-mesenchymal transition of lens epithelial cells through the AMPK/TGF-β/Smad2/3 signalling pathway

Posterior capsule opacification (PCO) is a common ocular fibrosis disease related to the epithelial-mesenchymal transition (EMT) of human lens epithelial cells (HLECs). However, safe and effective drugs that prevent or treat PCO are lacking. Metformin (Mtf) has been used to treat fibrosis-related diseases affecting many organs and tissues, but its effect on ocular fibrosis-related diseases is unclear. We investigated whether Mtf can inhibit EMT and fibrosis in HLECs to prevent and treat PCO and elucidated the potential molecular mechanism. Here, we established an HLEC model of TGF-β-induced EMT and found that 400 μM Mtf inhibited vertical and lateral migration and EMT-related gene and protein expression in HLECs. Smad2/3 are downstream molecules of TGF-β that enter the nucleus to regulate EMT-related gene expression during the occurrence and development of PCO. We revealed that Mtf suppressed TGF-β-induced Smad2/3 phosphorylation and nuclear translocation. Mtf induces AMP-activated protein kinase (AMPK) phosphorylation. In this study, we found that Mtf induced the activation of AMPK phosphorylation in HLECs. To further explore the mechanism of Mtf, we pretreated HLECs with Compound C (an AMPK inhibitor) to repeat the above experiments and found that Compound C abolished the inhibitory effect of Mtf on HLEC EMT and the TGF-β/Smad2/3 signalling pathway. Thus, Mtf targets AMPK phosphorylation to inhibit the TGF-β/Smad2/3 signalling pathway and prevent HLEC EMT. Notably, we first illustrated the AMPK/TGF-β/Smad2/3 signalling pathway in HLECs, which may provide a new therapeutic strategy for PCO.

Factors Affecting Posterior Capsule Opacification in the Development of Intraocular Lens Materials.

Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule over the visual axis of the newly implanted intraocular lens (IOL). The developmental pathways underlying PCO are yet to be fully understood and the current literature is contradictory regarding the impact of the recognised risk factors of PCO. The aim of this review is firstly to collate the known biochemical pathways that lead to PCO development, providing an up-to-date chronological overview from surgery to established PCO formation. Secondly, the risk factors of PCO are evaluated, focussing on the impact of IOLs’ properties. Finally, the latest experimental model designs used in PCO research are discussed to demonstrate the ongoing development of clinical PCO models, the efficacy of newly developed IOL technology, and potential therapeutic interventions. This review will contribute to current PCO literature by presenting an updated overview of the known developmental pathways of PCO, an evaluation of the impact of the risk factors underlying its development, and the latest experimental models used to investigate PCO. Furthermore, the review should provide developmental routes for research into the investigation of potential therapeutic interventions and improvements in IOL design in the aid of preventing PCO for new and existing patients.