Posterior capsular opacification (PCO) causes the vision that has been restored after cataract surgery to become blurred again. YAG laser treatment for PCO not only incurs additional costs but also poses risks of complications, including glaucoma and retinal disorders. Effective prevention and management of PCO remain an area requiring active research. Photodynamic therapy (PDT) utilizes a photosensitizer (PS) to transform oxygen into reactive oxygen species (ROS) under specific wavelengths of light, thereby inducing apoptosis. Given its minimal invasiveness and high specificity, PDT has been extensively applied in the treatment of conditions characterized by abnormal cell proliferation, such as tumors. Considering the pathogenesis of PCO, PDT has demonstrated promising clinical application potential in ophthalmic disease treatment. This review examines the impact of photodynamic therapy on the biological behavior of lens epithelial cells (LECs) and its efficacy in treating PCO. It also discusses the advantages and disadvantages of different photosensitizers and their clinical application potential.

The human eye, with its remarkable resolution of up to 576 million pixels, grants us the ability to perceive the world with astonishing accuracy. Despite this, over 2 billion people globally suffer from visual impairments or blindness, primarily because of the limitations of current ophthalmic treatment technologies. This underscores an urgent need for more advanced therapeutic approaches to effectively halt or even reverse the progression of eye diseases. The rapid advancement of nanotechnology offers promising pathways for the development of novel ophthalmic therapies. Notably, photothermal nanomaterials, particularly well-suited for the transparent tissues of the eye, have emerged as a potential game changer. These materials enable precise and controllable photothermal therapy by effectively manipulating the distribution of the thermal field. Moreover, they extend beyond the conventional boundaries of thermal therapy, achieving unparalleled therapeutic effects through their diverse composite structures and demonstrating enormous potential in promoting retinal drug delivery and photoacoustic imaging. This paper provides a comprehensive summary of the structure-activity relationship between the photothermal properties of these nanomaterials and their innovative therapeutic mechanisms. We review the latest research on photothermal nanomaterial-based treatments for various eye diseases. Additionally, we discuss the current challenges and future perspectives in this field, with a focus on enhancing global visual health.

Intraocular lenses (IOLs) play a pivotal role in restoring vision following cataract surgery. The evolution of polymeric biomaterials has been central to addressing challenges such as biocompatibility, optical clarity, mechanical stability, and resistance to opacification. This review explores essential requirements for IOL biomaterials, emphasizing their ability to mitigate complications like posterior capsule opacification (PCO) and dysphotopsias while maintaining long-term durability and visual quality. Traditional polymeric materials, including polymethyl methacrylate (PMMA), silicone, and acrylic polymers, are critically analyzed alongside cutting-edge innovations such as hydrogels, shape memory polymers, and light-adjustable lenses (LALs). Advances in polymer engineering have enabled these materials to achieve enhanced flexibility, transparency, and biocompatibility, driving their adoption in modern IOL design. Functionalization strategies, including surface modifications and drug-eluting designs, highlight advancements in preventing inflammation, infection, and other complications. The incorporation of UV-blocking and blue-light-filtering agents is also examined for their potential in reducing retinal damage. Furthermore, emerging technologies like nanotechnology and smart polymer-based biomaterials offer promising avenues for personalized, biocompatible IOLs with enhanced performance. Clinical outcomes, including visual acuity, contrast sensitivity, and patient satisfaction, are evaluated to provide an understanding of the current advancements and limitations in IOL development. We also discuss the current challenges and future directions, underscoring the need for cost-effective, innovative polymer-based solutions to optimize surgical outcomes and improve patients' quality of life.

Posterior capsular opacification (PCO) is a common complication following cataract surgery, which can lead to a significant vision loss. This study introduces a facile method for developing a metformin-derived hydrogel (HCM6) stabilized by dynamic covalent bonds among natural polymers. This hydrogel demonstrates antifibrotic properties, on-demand drug release, pH responsiveness, injectability, and self-healing capabilities. Our in vitro experiments confirmed that the HCM6 hydrogel exhibits excellent biocompatibility, inhibiting lens epithelial cell migration, and transforming growth factor-2β (TGFβ2)-induced α-smooth muscle actin (α-SMA) expression in lens epithelial cells. In vivo studies conducted in a rat extracapsular lens extraction (ECLE) model revealed that HCM6 significantly suppressed PCO after 21 days of implantation with no observed pathological effects on surrounding tissues or the optic nerve. According to our experimental results, the inhibitory mechanism of PCO may be attributed to metformin's suppressive effect on lens cell migration, epithelial-mesenchymal transition (EMT), and lens fiber formation. In summary, the long-acting, controllable, and on-demand release characteristics of the HCM6 hydrogel not only provide an effective strategy for preventing PCO but also offer new avenues for treating undesirable proliferative conditions in ophthalmology and beyond.

Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery. However, the current intraocular lens (IOL) implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications. Herein, a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable, in situ curable, and adjustable IOL (FHTAB IOL). The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA, combined with BP NS, TA, and Ag NPs. FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation. The designed injectable FHTAB IOL possesses high transparency and transmittance, with a refractive index similar to the natural lens and adjustable properties. It was stabilized as a refractive medium without any leakage in the eye. In addition, the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo. This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.

To explore the application and potential ferroptosis mechanisms of sonodynamic therapy (SDT) using titanium dioxide nanoparticles (TiO2-NPs) as sonosensitizers for the prevention of posterior capsule opacification (PCO).

We fabricated TiO2-NP-coated intraocular lenses (TiO2-IOLs) using the spin-coating method, followed by ultrasound activation of the photosensitizer TiO2. In vitro experiments were performed with human lens epithelial cells (HLECs) to explore the appropriate concentration of TiO2 and ultrasonic parameters. Investigations included reactive oxygen species (ROS) generation, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) western blot analysis, lipid peroxidation assays, and transcriptomics analysis. Finally, TiO2-IOLs were implanted in rabbit eyes to explore the in vivo performance of SDT.

Through both in vitro and in vivo experiments, the study determined that the ultrasound parameters of 5-minute duration, 1-MHz frequency, 50% duty cycle, and 1.2-W/cm2 intensity were reliable and valid for killing HLECs without damaging other ocular structures. In vitro experiments demonstrated that SDT generated excess ROS, which disrupted the mitochondrial membrane potential and significantly reduced the GSH content. Additionally, the downregulation of GPX4, accumulation of lipid peroxides, and alteration of mitochondrial morphology were observed, suggesting that ferroptosis may be the underlying mechanism. The RNA-sequencing analysis results also showed an increase in the expression of multiple pro-ferroptosis genes and the ferroptosis marker gene PTGS2. Animal experiments preliminarily demonstrated the safety and effectiveness of SDT in treating PCO in vivo.

TiO2-IOLs combined with SDT effectively prevented PCO by generating ROS and intracellular ferroptosis.

This review article provides a comprehensive overview of the advancements in using nanosuspensions for controlled drug delivery in ophthalmology. It highlights the significance of ophthalmic drug delivery due to the prevalence of eye diseases and delves into various aspects of this field. The article explores molecular mechanisms, drugs used, and physiological factors affecting drug absorption. It also addresses challenges in treating both anterior and posterior eye segments and investigates the role of mucus in obstructing micro- and nanosuspensions. Nanosuspensions are presented as a promising approach to enhance drug solubility and absorption, covering formulation, stability, properties, and functionalization. The review discusses the pros and cons of using nanosuspensions for ocular drug delivery and covers their structure, preparation, characterization, and applications. Several graphical representations illustrate their role in treating various eye conditions. Specific drug categories like anti-inflammatory drugs, antihistamines, glucocorticoids, and more are discussed in detail, with relevant studies. The article also addresses current challenges and future directions, emphasizing the need for improved nanosuspension stability and exploring potential technologies. Nanosuspensions have shown substantial potential in advancing ophthalmic drug delivery by enhancing solubility and absorption. This article is a valuable resource for researchers, clinicians, and pharmaceutical professionals in this field, offering insights into recent developments, challenges, and future prospects in nanosuspension use for ocular drug delivery.

Glistenings often occur after implanting the intraocular lens (IOL) due to the formation of numerous microvacuoles (MVs) and may lead to deterioration of vision quality. Previous studies showed the formation of MVs was associated with the hydrophobicity of IOL materials. Yet, the mechanism remains an open question due to the complexity of IOL polymer networks. In this study, two commercialized IOLs with similar hydrophobicity are found distinct in the formation of MVs. The 3D growth kinetics of MVs during cooling processes are captured for the first time by digital holographic microscopy (DHM) and the components of MVs are measured by DHM and Raman spectroscopy. The results reveal that the growth of MVs stems from the microphase separation of water and surrounding IOL polymers. A polymer swelling model is thus proposed to describe the microphase separation process which is found dependent on the elasticity of IOL polymer networks. The total volume of MVs is determined by the IOL hydrophobicity, while the elastic force of IOL polymer networks determines the number density and size of MVs. This study demonstrates an approach for characterizing the phase separation of crosslinked polymeric materials in biosystems and sheds lights on the refinement of IOL materials. STATEMENT OF SIGNIFICANCE: Glistenings due to the formation of numerous microvacuoles (MVs) in intraocular lens (IOL) can occur after IOL implantation, which may induce poor quality of vision. However, the underlying mechanism of MVs formation is still an open question. This study establishes an in-situ 3D imaging platform to monitor growth kinetics of the MVs in IOLs, which allows to uncover the mechanism of glistenings formation resulting from the microphase separation. The findings imply the material hydrophobicity influences the total volume of MVs, while the local elasticity of IOL polymer networks determines the number density and the size of MVs. This study offers a new approach for characterizing phase separation in crosslinking biosystems and sheds lights on the refinement of IOL materials.

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

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.

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.

Posterior capsule opacification (PCO) remains the most common cause of vision loss post cataract surgery. The clinical management of PCO formation is limited to either physical impedance of residual lens epithelial cells (LECs) by implantation of specially designed intraocular lenses (IOL) or laser ablation of the opaque posterior capsular tissues; however, these strategies cannot fully eradicate PCO and are associated with other ocular complications. In this review, we critically appraise recent advances in conventional and nanotechnology-based drug delivery approaches to PCO prophylaxis. We focus on long-acting dosage forms, including drug-eluting IOL, injectable hydrogels, nanoparticles and implants, highlighting analysis of their controlled drug-release properties (e.g., release duration, maximum drug release, drug-release half-life). The rational design of drug delivery systems by considering the intraocular environment, issues of initial burst release, drug loading content, delivery of drug combination and long-term ocular safety holds promise for the development of safe and effective pharmacological applications in anti-PCO therapies.

The deployment of structures that enable localized release of bioactive molecules can result in more efficacious treatment of disease and better integration of implantable bionic devices. The strategic design of a biopolymeric coating can be used to engineer the optimal release profile depending on the task at hand. As illustrative examples, here advances in delivery of drugs from bone, brain, ocular, and cardiovascular implants are reviewed. These areas are focused to highlight that both hard and soft tissue implants can benefit from controlled localized delivery. The composition of biopolymers used to achieve appropriate delivery to the selected tissue types, and their corresponding outcomes are brought to the fore. To conclude, key factors in designing drug-loaded biopolymeric coatings for biomedical implants are highlighted.

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.

Posterior capsular opacification (PCO) is the most common complication after cataract surgery, which is primarily caused by the proliferation of the residual lens epithelial cells (LECs) in the lens capsule. Previous studies have demonstrated that a drug-eluting intraocular lens (IOL), aimed to in situ eliminate LECs, are an effective and promising way to prevent PCO. However, because of the potential toxicities of the antiproliferative drugs to the adjacent tissues, the safety of such drug-eluting IOLs is still a highly important issue to be solved. In this investigation, a facile photodynamic coating-modified IOL was developed for effective and safer PCO prevention. An annular poly(lactide-co-glycolic acid) (PLGA) coating loaded with photosensitizer chlorin e6 (Ce6) was prepared by a spin-coating technique. The optical property investigations showed that the Ce6@PLGA coating was particularly suitable for the IOL surface modification. The in vitro cell culture investigation showed that Ce6@PLGA coating-modified IOLs effectively eliminated LECs when treated with light illumination, whereas it appeared to have good cytocompatibility without irradiation. The investigation of the cell elimination mechanism showed that the apoptosis of HLECs may be associated with the cytomembrane disruption induced by ROS, which is generated by the photodynamic coating during light illumination. The in vivo implantation experiments confirmed the desired PCO prevention effect, as well as the safety to and biocompatibility with the surrounding tissues. Thus, the facile Ce6@PLGA coating will provide an effective yet safe alternative of IOL surface modification for PCO prevention.

Posterior capsular opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and differentiation of residual lens epithelial cells (LECs) on the surface of the intraocular lens (IOL). Although drug-loaded IOLs have been successfully developed, the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability. In this investigation, an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome. The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin (Dox) through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction. In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome, compared with free Dox, thus resulting in superior anti-proliferation effect. In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility. We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.

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.

Posterior capsular opacification (PCO) is the most common complication resulting from cataract surgery and limits the long-term postoperative visual outcome. Using Nd:YAG laser-assisted posterior capsulotomy for the clinical treatment of symptomatic PCO increases the risks of complications, such as glaucoma, retinal diseases, uveitis, and intraocular lens (IOL) pitting. Therefore, finding how to prevent PCO development is the subject of active investigations. As a replacement organ, the IOL is implanted into the lens capsule after cataract surgery, but it is also associated with the occurrence of PCO. Using IOL as a medium for PCO prophylaxis is a more facile and efficient method that has demonstrated various clinical application prospects. Thus, scientists have conducted a lot of research on new intraocular lens fabrication methods, such as optimizing IOL materials and design, and IOL surface modification (including plasma/ultraviolet/ozone treatment, chemical grafting, drug loading, coating modification, and layer-by-layer self-assembly methods). This paper summarizes the research progress for different types of intraocular lenses prepared by different surface modifications, including anti-biofouling IOLs, enhanced-adhesion IOLs, micro-patterned IOLs, photothermal IOLs, photodynamic IOLs, and drug-loading IOLs. These modified intraocular lenses inhibit PCO development by reducing the residual intraoperative lens epithelial cells or by regulating the cellular behavior of lens epithelial cells. In the future, more works are needed to improve the biosecurity and therapeutic efficacy of these modified IOLs.

Advances in cataract surgery have increased the demand for intraocular lens (IOL) materials. At present, the progress of IOL materials mainly contains further improving biocompatibility, providing better visual quality and adjustable ability, reducing surgical incision, as well as dealing with complications such as posterior capsular opacification (PCO) and ophthalmitis. The purpose of this review is to describe the research progress of relevant IOL materials classified according to different clinical purposes. The innovation of IOL materials is often based on the common IOL materials on the market, such as silicon and acrylate. Special properties and functions are obtained by adding extra polymers or surface modification. Most of these studies have not yet been commercialized, which requires a large number of clinical trials. But they provide valuable thoughts for the optimization of the IOL function.