Impact of anterior capsule polishing on capsule opacification and capsule bend after age-related cataract surgery.

PURPOSE: To investigate the effect of anterior capsule polishing on postoperative capsule opacification and capsular bend in patients with age-related cataract displaying normal axial length. SETTING: Eye Hospital of Wenzhou Medical University at Hangzhou. DESIGN: Prospective self-controlled trial. METHODS: Patients with age-related cataracts aged 56 to 84 years displaying normal axial length were enrolled. Before surgery, a coin-toss method was used to randomly select 1 eye for intraoperative 360 degrees anterior capsule polishing (polishing group); the contralateral eye received no treatment (control group). Capsular bend index (CBI), anterior capsule opacification (ACO), posterior capsule opacification (PCO), and anterior capsule opening area (ACOA) were recorded at 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively using swept-source optical coherence tomography and slitlamp examination. RESULTS: 21 patients (42 eyes) were enrolled. Within-group comparisons showed that both groups had significant differences in CBI between 1 week and 1 month postoperatively, and between 6 months and 12 months postoperatively ( P < .05). Between-group comparisons revealed a significant difference in CBI at 1 week postoperatively ( P < .05); at 12 months postoperatively, there was a significant difference in ACOA ( P < .05). There were no significant between-group differences regarding ACO or PCO at any timepoint ( P > .05). CONCLUSIONS: For patients with age-related cataracts and normal axial length, 360 degrees anterior capsule polishing can delay early capsular bag deformation without increasing the risks of ACO and PCO. This approach can also limit contraction of the anterior capsule opening.

Polydopamine based photothermal/photodynamic synchronous coating modified intraocular lens for efficient and safer posterior capsule opacification prevention.

Posterior capsule opacification (PCO), as one of the most common late complications after intraocular lens (IOL) implantation in cataract surgery, seriously affects patients' postoperative vision and surgical satisfaction, and can only be treated by laser incision of the posterior capsule. Although drug eluting coating modification have been proved to inhibit PCO effectively, the complicated coating methods and the potential toxicity of the antiproliferative drugs hinders its actual application. In this study, an indocyanine green (ICG) loaded polydopamine (PDA) coating modified IOL (IP-IOL) was designed to prevented PCO. In vitro and in vivo studies have shown that IP-IOL can effectively eliminate lens epithelial cells and significantly reduce the degree of PCO. At the same time, it still has good imaging quality and optical properties. Furthermore, both the near-infrared irradiation and ICG loaded PDA coating modified IOLs have proved to possess high biological safety to eyes. Thus, with easy preparation and safer near-infrared irradiated photothermal/photodynamic synchronous properties, such ICG loaded PDA coating provides an effective yet easier and safer PCO prevention after IOL implantation.

Self-assembled coating with a metal-polyphenolic network for intraocular lens modification to prevent posterior capsule opacification.

Posterior capsule opacification (PCO) is a main complication after cataract surgery and intraocular lens (IOLs) implantation and is attributed to residual lens epithelial cells (LECs) migrating to the IOL surface and posterior capsules. IOL surface modification has been a newly-developing research filed in recent years; however, the applicability and economical acquisition of modified materials remain unsolved. In this study, we first applied a metal-polyphenolic network coating with a self-assembly technique on the IOL surface by using tannic acid (TA) combined with AlCl3, which are easily acquire and applying on the IOL surface to solve the IOL transmittance affair. Using wound healing and Transwell assay to verify AZD0364 inhibits cell migration (P< 0.05), the lipopolysaccharide-induced macrophage inflammation model to verify pterostilbene (PTE) inhibits the inflammatory reaction (P< 0.01). By optimizes its self-assembly coating parameters and calculating its drug release kinetics, we successfully loaded these two drugs on the coating, named TA (AZD0364/PTE) IOL. Its surface morphology characteristics were analyzed by scanning electron microscope, x-ray photoelectron spectrometer and water contact angle. The optical performance was carefully investigated by optical instruments and equipment (n= 3). Thein vitroresults showed that TA (AZD0364/PTE) IOL can significantly inhibit cell adhesion and acute inflammation (n= 3,P< 0.0001). Importantly, afterin vivoimplantation for 28 d with eight rabbits PCO models in two groups, the TA (AZD0364/PTE) IOL group maintained clear refracting media and decreased the inflammatory reaction compared with the original IOL group (P< 0.05). This study provides a new applicable and economical strategy for preventing PCO and offers a reference for the next generation of IOLs that benefit cataract patients.

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

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

Mild Photothermal Therapy Prevents Posterior Capsule Opacification through Cytoskeletal Remodeling.

Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.

NIR-triggered thermosensitive polymer brush coating modified intraocular lens for smart prevention of posterior capsular opacification.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.

Inhibition of anterior capsule opacification and contraction by the elevated anterior rim of the intraocular lens optic.

PURPOSE: To verify the anterior capsule opacification (ACO) and contraction (ACC) of the ZCB00V intraocular lens (IOL), made of the same material as the AR40e with a high ACC rate. STUDY DESIGN: Retrospective cohort study. METHODS: We evaluated 35 patients at 1 week, 1, 3 and 6 months post phacoemulsification with either a ZCB00V (n = 35) or FY-60AD (n = 34) IOL implantation. The ACC rate was calculated using retroillumination images of the anterior segment, and the ACO was measured using anterior segment photographs and image analysis software. The contact grade between the IOL and anterior capsule was estimated from the Pentacam® images. RESULTS: The postoperative ACC rates (mean ± standard deviation) at 3 months were 1.03%±2.54% for the ZCB00V and, and 7.12%±9.47% for the FY-60AD. The ZCB00V-implanted eyes showed a significantly lower postoperative ACC at 1 week, 3 months, and 6 months (P < 0.01). On the other hand, the FY-60AD-implanted eyes had more pronounced ACO, and a significantly larger area of opacification (62.24%±21.32% vs. 16.90%±8.34%; P = 0.0005). Pentacam® analysis revealed a space between the anterior capsule and IOL surface in the ZCB00V-implanted eyes, whereas the anterior capsule firmly adhered to the IOL surface in the FY-60AD-implanted eyes. CONCLUSION: The ACC and ACO were significantly lower in eyes with ZCB00V IOLs compared to those with the FY-60AD. The anterior segment image analysis revealed that the elevated anterior rim of the ZCB00V IOL prevented adhesion between the anterior capsule and IOL optic surface, suggesting an open capsule effect.

Rotating the Intraocular Lens to Prevent Posterior Capsular Opacification in Cataract Surgeries.

Posterior capsule opacification (PCO) is a common postoperative complication of extracapsular cataract surgery, which is caused by the proliferation and migration of lens epithelial cells and can affect long-term visual outcomes significantly. The most effective treatment for PCO is neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy; however, this treatment is associated with posterior segment complication and can break the stability of capsular bag, affecting the position and function of trifocal or toric intraocular lenses (IOLs). Advances in surgical procedures, IOL design, and pharmacy have reduced the rate of PCO in recent years, concentrating on the inhibition of proliferative lens epithelial cells (LECs). This protocol aimed to clear LECs more thoroughly during phacoemulsification and IOL implantation. The first several steps, including clear corneal incision, continuous circular capsulorhexis, hydrodissection, hydrodelineation, and phacoemulsification, were completed as conventional procedures. After placing the IOL into the capsular bag, rotation of the IOL by at least 360° was performed using an irrigation/aspiration tip or a hook, with slight stress on the posterior capsule. Some residuals occurred in the originally transparent capsular bag after rotation of the IOLs. Then, these materials and the viscoelastic were cleared completely using an irrigation/aspiration system. A clear posterior capsule was observed after the surgery in patients undergoing this method. This method of rotating IOLs is a simple, effective, and safe way to prevent PCO by clearing residual LECs and can be carried out without extra tools or skills.

Plasmin-Induced Lens Epithelial Cells Detachment for the Reduction of Posterior Capsular Opacification.

Purpose: We sought to evaluate the efficacy and safety of plasmin injection in the capsular bag during the cataract operation for the prevention of posterior capsule opacification. Methods: Thirty-seven anterior capsular flaps taken from phacoemulsification surgery were immersed in either 1 µg/mL plasmin (plasmin group, n = 27) or phosphate-buffered saline (control group, n = 10) for 2 minutes and photographed after fixation and nuclear staining to compare the numbers of residual lens epithelial cells. In the animal experiments, the plasmin solution was injected into the capsular bag and remained for 5 minutes during hydrodissection or after lens extraction. The degree of posterior capsular opacity of the rabbits at 2 months were photographed by slit lamp biomicroscopy. In HLE-B3 cell culture, the cell detachment rate, proliferation, and apoptosis after the plasmin digestion were analyzed. Results: The residual lens epithelial cell numbers on the capsule after plasmin treatment were 168 ± 190.7/mm2 in the 1 µg/mL plasmin group, which was significantly lower than that of the control (1012 ± 798.8/mm2; P < 0.0001). In a rabbit model, the treatment of plasmin resulted in a significantly clearer posterior capsule compared with that of the control group at 2 months postoperatively. Conclusions: This study suggested that plasmin injection can induce effective lens epithelial cell detachment, which could be a promising adjunctive treatment to further improve the success rate in posterior capsule opacification prevention. Translational Relevance: Plasmin injection for lens epithelial cell detachment could significantly decrease the number of residual lens epithelial cells. This approach could be a promising treatment incorporating the current treatment approach to further improve the success rate in posterior capsule opacification prevention.

Cascade reaction triggering and photothermal AuNPs@MIL MOFs doped intraocular lens for enhanced posterior capsular opacification prevention.

Posterior capsular opacification (PCO) is the most common complication after cataract surgery. Present strategies can't meet the clinical needs of long-term prevention. This research reports a novel intraocular lens (IOL) bulk material with high biocompatibility and synergistic therapy. Gold nanoparticles (AuNPs) doped MIL-101-NH2 metal-organic frameworks (MOFs) (AuNPs@MIL) was firstly fabricated via in situ reductions. Then the functionalized MOFs were uniformly mixed with glycidyl methacrylate (GMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA) to form the nanoparticle doped polymer (AuNPs@MIL-PGE), and which was used to fabricate IOL bulk materials. The materials' optical and mechanical properties with different mass contents of nanoparticles are investigated. Such bulk functionalized IOL material could efficiently remove residual human lens epithelial cells (HLECs) in the capsular bag in the short term, and can prevent PCO on demand in the long run by near-infrared illumination (NIR) action. In vivo and in vitro experiments demonstrate the biosafety of the material. The AuNPs@MIL-PGE exhibits excellent photothermal effects, which could inhibit cell proliferation under NIR and doesn't cause pathological effects on the surrounding tissues. Such functionalized IOL can not only avoid the side effects of the antiproliferative drugs but also realize the enhanced PCO prevention in clinical practice.

Inhibition of Posterior Capsule Opacification by Adenovirus-Mediated Delivery of Short Hairpin RNAs Targeting TERT in a Rabbit Model.

PURPOSE: Posterior capsule opacification (PCO) is the most common postoperative complication after cataract surgery and cannot yet be eliminated. Here, we investigated the inhibitory effects of telomerase reverse transcriptase (TERT) gene silencing on PCO in a rabbit model. METHODS: After rabbit lens epithelial cells (LECs) were treated with adenovirus containing short hairpin RNAs (shRNA) targeting TERT (shTERT group), adenovirus containing scramble nonsense control shRNA (shNC group) or PBS (control group), quantitative real-time polymerase chain reaction and Western blotting were used to measure the expression levels of TERT, and a scratch assay was performed to assess the LEC migration. New Zealand white rabbits underwent sham cataract surgery followed by an injection of adenovirus carrying shTERT into their capsule bag. The intraocular pressure and anterior segment inflammation were evaluated on certain days, and EMT markers (α-SMA and E-cadherin) were evaluated by Western blotting and immunofluorescence. The telomerase activity of the capsule bag was detected by ELISA. At 28 d postoperatively, hematoxylin and eosin staining of the cornea and iris and electron microscopy of the posterior capsule were performed. RESULTS: Application of shTERT to LECs downregulated the expression levels of TERT mRNA and protein. The scratch assay results showed a decrease in the migration of LECs in the shTERT group. In vivo, shTERT decreased PCO formation after cataract surgery in rabbits and downregulated the expression of EMT markers, as determined by Western blotting and immunofluorescence. In addition, telomerase activity was suppressed in the capsule bag. Despite slight inflammation in the iris, histologic results revealed no toxic effects in the cornea and iris. CONCLUSION: TERT silencing effectively reduces the migration and proliferation of LECs and the formation of PCO. Our findings suggest that TERT silencing may be a potential preventive strategy for PCO.

Celastrol-based nanomedicine hydrogels eliminate posterior capsule opacification.

Aim: To formulate an injectable thermosensitive micelle-hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-ß1. Celastrol prevents epithelial-mesenchymal transition in lens epithelial cells induced by TGF-ß1 through the TGF-ß1/Smad2/3/TEAD1 signaling pathway. In vivo efficiency evaluations showed that CMG demonstrated an excellent inhibitory effect on PCO in rabbits and had no obvious tissue toxicity. Conclusion: Injectable CMG may represent a promising ophthalmic platform for preventing PCO. This versatile injectable micelle-hydrogel hybrid represents a clinically relevant platform to achieve localized therapy and controlled release of drugs in other disease therapies.

Nanoporous Gold Ring-Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the leading complication after cataract surgery, and is mainly induced by the proliferation and migration of residual lens epithelial cells (LECs). Although numerous attempts have been made to reduce the incidence of PCO, this complication remains a critical challenge in postoperative visual recovery. This study aims to report a functionalized intraocular lens (R-IOL) with a region-confined photothermal effect for the active prevention of PCO after implantation. The outer rim of R-IOL (non-optical area) is decorated with a nanoporous gold (NPG) ring, which can effectively eliminate the LECs around R-IOL, ultimately inhibiting the migration of LECs from the periphery to the visual axis center in the initial stage, and preventing the subsequent PCO. Furthermore, the mechanism of LECs elimination can be attributed to apoptosis induced by mild photothermal therapy. After in vivo implantation for 30 days, PCO is rarely observed in the R-IOL group, whereas the considerably higher incidence of PCO (75%) is found in the pristine IOL (P-IOL) group. The region-confined photothermal effect based on NPG not only provides an active strategy to effectively prevent PCO, but also introduces new opportunities for the treatment of undesirable hyperplasia.

Role of fibronectin and IOL surface modification in IOL: Lens capsule interactions.

Posterior Capsule Opacification (PCO) is one of the most common complications of cataract surgery. While studies have shown that IOL material properties and fibronectin adsorption may affect IOL-induced PCO in the clinical setting, the mechanism governing such interactions is not totally understood. Since strong adhesion forces between IOLs and posterior capsules (PCs) have been shown to impede cell infiltration and thus reduce PCO formation, this study was designed to assess whether fibronectin adsorption and IOL material properties would impact the IOL:PC adhesion force and cell infiltration using a PCO predictive in vitro model and a macromolecular dye imaging model, respectively. Our results showed that fibronectin adsorption significantly increased the adhesion forces and reduced simulated cell infiltration between acrylic foldable IOLs and the PC at physiological temperature in comparison to fibronectin-free controls. This fibronectin-mediated strong IOL: PC bond may be contributing to low PCO rates in the clinic for acrylic foldable IOLs. In addition, acrylic foldable IOLs coated with Di(ethylene glycol) (Diglyme), a hydrophilic coating known to reduce protein adsorption, was tested for its ability to alter adhesion force and cell infiltration. We observed that IOLs coated with Diglyme coating greatly reduced surface hydrophobicity and fibronectin adsorption of acrylic foldable IOLs. Furthermore, Diglyme coated IOLs showed significantly reduced adhesion force and increased simulated cell infiltration at the IOL:PC interface. The overall results support the hypothesis that IOL surface properties and their ability to adsorb fibronectin may have great impact on the IOL:PC adhesion force. A tight binding between IOLs and PC may contribute to the reduction of cell infiltration and thus the PCO incidence rate in the clinic.

Posterior capsular vacuuming to avoid PCO formation.

AIM: To retrospectively evaluate the effectiveness of the capsular vacuuming technique in reducing posterior capsule opacification (PCO). METHODS: Group 1 of the study consisted of 2752 eyes of 2752 patients with a cataract who had undergone phacoemulsification and IOL implantation surgery with anterior, equatorial, and posterior capsular polishing between January 2010 and December 2014. Group 2 consisted of 2761 eyes of 2761 patients with a cataract who had undergone phacoemulsification and IOL implantation surgery with anterior, equatorial, and posterior capsular polishing as well as posterior capsular vacuuming between January 2010 and December 2014. RESULTS: The mean patient age was 63.45 ± 12.23 years (range, 43-89) in Group 1 and 64.02 ± 13.36 years (range, 40-91) in Group 2. The two groups did not significantly differ with respect to age, sex, preoperative and postoperative uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) measurements (p > 0.05). At the 5-year follow-up, 253 eyes (9.19%) in Group 1 developed PCO requiring Nd:YAG laser capsulotomy, whereas 24 eyes (0.86%) in Group 2 developed PCO requiring Nd:YAG laser capsulotomy (p < 0.001). During capsular vacuuming, posterior capsule rupture was observed in the shape of a hole in only 2 eyes in Group 2. But the IOLs were implanted in the capsular bag in all eyes in both groups. CONCLUSION: PCO is the most common complication of cataract surgery; therefore, surgical technique is important in preventing PCO formation. We recommend posterior capsular vacuuming together with anterior, equatorial, and posterior capsular polishing, as this method significantly reduced the PCO rate.

Thin film nanoarchitectonics of layer-by-layer assembly with reduced graphene oxide on intraocular lens for photothermal therapy of posterior capsular opacification.

Due to development of surgical techniques and intraocular lens (IOL) implants, vision can often be restored in cataracts patients. However, posterior capsular opacification (PCO) has become the most common and challenging complication in cataracts surgery. While various approaches such as surface modification and drug prophylaxis have been investigated to prevent PCO development, there is no standard treatment that is sufficiently safe and effective to meet clinical demands. Near-infrared (NIR) light-triggered photothermal therapy is an attractive noninvasive treatment for PCO prophylaxis. We fabricated a new type of IOL with excellent biocompatibility, stability, and photothermal conversion property. Polyethyleneimine (PEI) and graphene oxide (GO) were layer-by-layer assembled on model polymethylmethacrylate and IOL substrates, and the thickness, surface roughness, and wettability of the substrates with different numbers of bilayers were evaluated. After the reduction of GO to reduced GO (rGO), a rGO/PEI multilayer thin film with good stability and photothermal conversion capability was obtained. The rGO/PEI multilayer coating was able to induce apoptosis in lens epithelium cells under 808-nm NIR laser irradiation in vitro. Finally, rGO@IOL was implanted into rabbit eyes, and the biocompatibility and ability to prevent PCO were evaluated for 5 weeks. The rGO@IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and did not induce obvious pathological effects in surrounding healthy tissues. The rGO@IOL implant with good biocompatibility, good physicochemical stability, and excellent photothermal conversion property shows promise for clinical application in PCO prophylaxis.

A polydopamine-based photodynamic coating on the intraocular lens surface for safer posterior capsule opacification conquering.

Intraocular lens (IOL) is the indispensable implant for cataract surgery. However, posterior capsular opacification (PCO) happens in high incidence after IOL implantation. PCO is caused by adhesion, proliferation, and trans-differentiation of the residual human lens epithelial cells (HLECs). Despite the great achievements in surface coating and antiproliferative drug loading on the intraocular lens (IOL) for effective PCO prevention, the complex fabrication process and potential toxicity of the drugs still limit their clinical applications and commercial mass production. In this investigation, a convenient and efficient photodynamic therapy (PDT) coating fabricated by facile yet economical and practical dopamine self-polymerization was applied to IOL surface modification for PCO prevention. The optical properties of IOL, such as light transmittance, imaging quality and refractive index, remain unchanged after modification. Using an in vitro cell assay, the parameters of PDT were optimized. The PDT coating shows excellent biocompatibility in darkness and eliminates LECs significantly under irradiation. The research on the cell elimination mechanism showed that reactive oxygen species (ROS) mainly induced cell apoptosis. In vivo experiments demonstrated that the implantation of modified IOLs can prevent PCO effectively. As a result, this work provides a safe, simple and effective PDT coating for the IOL surface to reduce the incidence of PCO.

Foldable Bulk Anti-adhesive Polyacrylic Intraocular Lens Material Design and Fabrication for Posterior Capsule Opacification Prevention.

Posterior capsular opacification (PCO) is a primary complication after phacoemulsification combined with intraocular lens (IOL) implantation, which is attributed to adhesion, proliferation, and migration of residual lens epithelial cells on IOL. Although surface hydrophilic coating is considered to be a powerful way to inhibit PCO incidence after surgery, it requires complex post-production processes, thus limiting their applicability. In comparison, bulk modification is a stable, effective, and facile IOL synthesis method for PCO prevention. Herein, a new anti-adhesive IOL material was designed and successfully synthesized by radical copolymerization of ethylene glycol phenyl ether methacrylate (EGPEMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA). The physicochemical properties of P(EGPEMA-co-EA) copolymer materials, including chemical structure, mechanical, thermal, surface, and optical properties, were analyzed by using 1H NMR spectroscopy, FT-IR spectroscopy, tensile test, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), water contact angle measurement, and UV-vis spectroscopy. The elongation at break and the modulus of elasticity of the copolymer were tunable through the change of the composition of monomers. Compared to other components, the tensile results showed that P(EGPEMA-co-EA) materials (70% EGPEMA in mass ratio, F7) are suitable for the preparation of foldable intraocular lens with lower elastic modulus and higher elongation at break. TGA and DSC showed that the material has high thermal stability, and the glass transition temperature of F7 material is 16.1 °C. The water contact angle measurement results showed that the introduction of EA improved the hydrophilicity of the material. The percentage of transmittance of all copolymers at 400-800 nm is above 85%. Then, the biocompatibility of the materials was evaluated by in vitro assay and subcutaneous implantation. Both in vitro results and subcutaneous implantation experiments showed that the designed IOL materials exhibited a good anti-adhesion effect and no cytotoxicity. Finally, phacoemulsification and IOL intraocular implantation were performed, and the in vivo results confirmed the good PCO prevention ability as well as the biocompatibility of the new IOL materials.

An Evaluation of the Inhibition Effects of Cell Migration of Aspirin Soaking 360°Square-Edge Intraocular Lens in an in Vitro Lens Capsule Model.

PURPOSE: This study performs to evaluate the Hydrophobic and Hydrosmart 360°square-edge intraocular lens drug delivery of Aspirin using an in vitro lens capsular model. METHODS: Cell counting kit-8 assay was used to calculate 50% inhibiting concentration values in both SRA01/04 and HLE-B3 cells. Hoechst staining and transwell assay were used to detect cell proliferation and cell migration. The in vitro lens capsule model was established mainly with a special transwell-col and cell climbing sheet, in which an intraocular lens and the TGF-ß2 were added. The ultraviolet spectrophotometer was used to measure the drug concentrations released in vitro. Cell-exclusion zone assay was used to detect the cell migration in the in vitro capsular model. RESULTS: It shows that cell morphology and distribution of SRA01/04 in the in vitro lens capsular model were closer to those in vivo. The results revealed that there could be significant inhibiting effects on cell migration of the hydrosmart intraocular lens with a sustained drug release in vitro in 7 days, while the hydrophobic intraocular lens drug delivery of Aspirin was mainly performed only from day 1 to day 3. CONCLUSIONS: Results showed the developed hydrosmart intraocular lens could release Aspirin continuously in vitro to inhibit the cell migration of lens epithelial cells.

Centrifugally concentric ring-patterned drug-loaded polymeric coating as an intraocular lens surface modification for efficient prevention of posterior capsular opacification.

Posterior capsular opacification (PCO) is the main postoperative complication after intraocular lens (IOL) implantation in cataract surgery, because of the proliferation of the residual lens epithelial cells (LECs) in the lens capsule. Drug-eluting IOLs, aimed to develop an in situ drug delivery device, are the promising concept in recent years. As IOLs are optical devices other than implants, the feasibility and applicability remain a challenge for drug-eluting coatings. In this investigation, a centrifugally concentric ring-patterned drug-loaded poly(lactide-co-glycolic acid) (PLGA) coating was designed and fabricated by the spin coating technique. The concentric ring-patterned morphologies and the drug loading and release properties were carefully investigated, and the spin coating parameters were optimized. A concentric annular coating with a thin center and thick periphery was obtained, which was particularly suitable for the surface modification of IOLs, as the visual pathway of the intraocular light transmission greatly requires good light transmittance of the IOLs. IOLs with the immunosuppressant cyclosporin A (CsA)-loaded coating (CsA @ PLGA) modification were then fabricated for PCO prevention. The in vitro LECs culture results showed that the CsA @ PLGA coating-modified IOLs significantly inhibited cell proliferation and induced cell death. Western blot analysis showed that the efficient cell inhibition behavior of CsA was due to the autophagy-mediated cell death pathway. The in vivo intraocular implantation results confirmed the desired PCO inhibition effect. Thus, the centrifugally concentric ring-patterned drug-loaded PLGA coating obtained by the spin coating technique provides a simple yet effective alternative of IOL modification for PCO prevention. STATEMENT OF SIGNIFICANCE: • Concentric ring-patterned polymer coating, specifically for drug-eluting IOL fabrication, was developed by the spin coating technique. • The immunosuppressant CsA inhibited LEC proliferation through the autophagy-mediated cell death pathway. • Concentric ring-patterned CsA-eluting IOLs exhibited reliable in vivo PCO prevention. • The drug-eluting IOLs fabricated by the simple and economical spin coating technique have a great potential in clinical translation.