Expression of Concern: Surface modification of intraocular lenses via photodynamic coating for safe and effective PCO prevention.

Expression of Concern for 'Surface modification of intraocular lenses via photodynamic coating for safe and effective PCO prevention' by Junmei Tang et al., J. Mater. Chem. B, 2021, 9, 1546-1556, https://doi.org/10.1039/D0TB02802A.

Correction: Ocular biocompatibility evaluation of POSS nanomaterials for biomedical material applications.

[This corrects the article DOI: 10.1039/C5RA08668J.].

Expression of concern: Synthesis of MA POSS-PMMA as an intraocular lens material with high light transmittance and good cytocompatibility.

Expression of concern for 'Synthesis of MA POSS-PMMA as an intraocular lens material with high light transmittance and good cytocompatibility' by Bailiang Wang et al., RSC Adv., 2014, 4, 52959-52966, https://doi.org/10.1039/C4RA08060B.

Correction: Surface modification of intraocular lenses with hyaluronic acid and lysozyme for the prevention of endophthalmitis and posterior capsule opacification.

[This corrects the article DOI: 10.1039/C4RA13499K.].

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.

Surface modification of intraocular lenses via photodynamic coating for safe and effective PCO prevention.

Posterior capsular opacification (PCO) is an emerging complication in cataract phacoemulsification and intraocular lens (IOL) implantation surgery, mainly stemming from the adhesion, proliferation, and trans-differentiation of the post-surgery residual lens epithelial cells (LECs). Previous investigations have shown that an anti-proliferative drug eluting coating on the IOL surface provides an effective way to inhibit PCO. However, due to the undesirable elution of the anti-proliferative drug, the safety of such modification is one of the important issues to be solved. In this investigation, photodynamic coating was introduced into IOL surface modification. The photosensitizer chlorin e6 grafted α-cyclodextrin (α-CD-Ce6) was synthesized and self-assembled onto the poly(poly(ethylene glycol) methacrylate) (PPEGMA) brush established IOL surface via the supramolecular interaction between α-CD and poly(ethylene glycol) chains. The results of investigation into its optical properties, including transmittance, refractive index, and surface morphology, showed no obvious alterations after photodynamic coating modification on the IOL surface. The in vitro LEC behaviour investigation optimized the photodynamic therapy parameters when light illumination was used for the cell elimination on the photodynamic coating modified IOL. The results have also shown that this functional coating modification effectively eliminates the cells on the surface of the IOL material when treated with light illumination, whereas it keeps excellent cytocompatibility in the absence of light illumination. The investigation of the cell elimination mechanism shows that this kind of functional coating eliminates the adherent cells by ROS induced apoptosis. The in vivo implantation result confirms the excellent PCO inhibition effect, as well as their safety and biocompatibility to the surrounding tissues. As a result, the proposed photodynamic coating provides a safer and effective alternative of IOL modification for preventing PCO.

Drug-Eluting Hydrophilic Coating Modification of Intraocular Lens via Facile Dopamine Self-Polymerization for Posterior Capsular Opacification Prevention.

Posterior capsular opacification (PCO) is the most important complication in cataract phacoemulsification and intraocular lens (IOL) implantation surgery, mainly stemming from the adhesion, proliferation, and transdifferentiation of the postsurgically residual lens epithelial cells (LECs). Previous investigations mainly focused on the hydrophilic surface modification of the IOLs for PCO prevention, such as heparinization. However, the long-term clinical investigations show that there is no significant difference between pristine and heparinized IOLs. In the present study, a synergetic coating with properties of drug-eluting and hydrophilicity was designed and modified onto the IOL surface via facile dopamine self-polymerization. The antiproliferative drug doxorubicin (DOX) was loaded when a polydopamine (PDA) coating was formed on the IOL surface. The hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) could be subsequently grafted onto the drug-loaded PDA coating surface easily. The hydrophilic outer layer could slow down drug-eluting from underneath the drug-incorporated coating. In vitro and in vivo investigations demonstrated that such multifunctionalized coating-modified IOLs could not only thoroughly and effectively prevent PCO development by induced cell apoptosis but also render safety and biocompatibility to the surrounding tissues.

Surface Modification of Intraocular Lens with Hydrophilic Poly(Sulfobetaine Methacrylate) Brush for Posterior Capsular Opacification Prevention.

Purpose: The intraocular lens (IOL) is a common, yet important, implantable device used in treatment of cataract in clinics. However, the unexpected adhesion of postoperative residual lens epithelial cells (LECs) often causes serious complications, such as posterior capsular opacification (PCO), which lead to vision loss again. In this investigation, a poly(sulfobetaine methacrylate) (PSBMA) brush coating was fabricated on an IOL to generate a hydrophilic surface coating on the IOL for enhanced cell adhesion resistance so as to decrease PCO incidence. Methods: The PSBMA brush coating on the IOL surface was fabricated using surface-initiated reversible addition-fragmentation chain transfer polymerization. X-ray photoelectron spectroscopy (XPS) was used to demonstrate the surface coating preparation. The water contact angle (WCA) measurement was used to test surface hydrophilicity. In vitro LEC culture was use to evaluate the cell behavior on the IOL material surfaces, with or without PSBMA coating modification. Finally, animal cataract surgeries were carried out to evaluate in vivo biocompatibilities and anti-PCO effects. Results: The XPS and WCA measurements illustrate successful surface modification and good surface hydrophilicity. The in vitro cell culture results show that the hydrophilic PSBMA polymer brush coating evidently decreases adhesion and proliferation of LECs. Results of the in vivo cataract surgery with intraocular implantation show that PSBMA modification on the IOL surface does not induce side effects in nearby tissues, whereas posterior capsular hyperplasia can be evidently reduced. Conclusion: The PSBMA brush surface-modified IOL has good in vivo biocompatibility and it can effectively reduce the incidence of postoperative PCO.

Dual drug delivery from hydrophobic and hydrophilic intraocular lenses: in-vitro and in-vivo studies.

Posterior capsule opacification (PCO) still remains the most frequent long term complication after cataract surgery, while endophthalmitis is rare but severe and should be prevented at all cost. Intraocular lenses (IOLs) with different designs (eg. edge and body-haptics angle) and materials (acrylic hydrophobic and acrylic hydrophilic surfaces) have been studied to reduce PCO. For the prevention of endophthalmitis, intracameral injection followed or not by topical treatment with antibiotics and anti-inflammatories are usually prescribed. The objective of this work was to investigate the use of IOLs as controlled release platforms of two drugs, the antibiotic moxifloxacin (MXF) and the anti-inflammatory ketorolac (KTL) that could advantageously substitute the usual treatment. Two types of IOLs were chosen, hydrophobic and hydrophilic. Hydrophobic IOLs have shown better results in the prevention of PCO because they adhere better to the posterior capsular bag, while hydrophilic IOLs are advised in the case of patients with uveitis, glaucoma or diabetes. The IOLs were loaded with MXF + KTL and sterilized by high hydrostatic pressure. Both IOLs reduced the tendency for adhesion of LECs. In vivo tests were done to compare the concentration of the drugs in the aqueous humor obtained after eye drops administration and drug-loaded IOLs implantation. The developed IOLs were able to release MXF and KTL at therapeutic levels, in a sustained way, which contrasts with the eye drops prophylaxis. No PCO signs were detected and histological analyses demonstrated biocompatibility of these devices.

Cellular Microenvironment-Sensitive Drug Eluting Coating on Intraocular Lens for Enhanced Posterior Capsular Opacification Prevention and in Vivo Biocompatibility.

Posterior capsular opacification (PCO) is a common complication after cataract surgery, which often leads to a progressive decline in the patient's vision. It has been established that PCO is related to the adhesion and proliferation of the residual lens epithelial cells (LECs) on the implanted intraocular lens (IOL) after surgery, which blocks visual pathways again. It has been reported that matrix metalloproteinases (MMPs) are greatly up-regulated in the LEC proliferation process. In the present study, an antiproliferative drug, functionalized poly(ethylene glycol) methacrylate (PEGMA), was synthesized using a MMP-2 sensitive peptide as a linkage. This PEGMA derivative polymerizable molecule was then immobilized onto the IOL surface via surface initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization, which resulted in hydrophilic and MMP-2 sensitive drug eluting coatings on the IOL. The in vitro results show that LEC proliferation is inhibited in the presence of enzyme. The in vivo animal experiments with such surface modified IOLs not only indicate significant PCO prevention but also show excellent intraocular biocompatibility with adjacent tissues. All these results suggest that this hydrophilic and MMP-2 sensitive drug eluting surface coating would be a promising way to prevent PCO.

Anti-Adhesive And Antiproliferative Synergistic Surface Modification Of Intraocular Lens For Reduced Posterior Capsular Opacification.

BACKGROUND: Posterior capsular opacification (PCO) is the main complication after intraocular lens (IOL) implantation in cataract surgery, which is the result of lens epithelial cell (LEC) adhesion, proliferation and migration on the IOL and at the lens capsule interface. Hydrophilic surface modification, such as surface heparinization, decreases the cell adhesion, which has been commercialized and used clinically. However, clinical long-term observation results show no significant difference between the pristine and heparinized IOLs. METHODS: To prevent PCO over the long time span, we modified the IOLs with an antiproliferative drug-loaded hydrophilic coating. The antiproliferative drug doxorubicin (DOX)-incorporated chitosan (CHI) nanoparticle was fabricated by sodium tripolyphosphate (TPP) gelation. Such antiproliferative drug-loaded CHI-TPP-DOX nanoparticles (CTDNP) were used as one of the building blocks to prepare polyelectrolyte multilayer with heparin (HEP) via layer-by-layer assembly, obtaining (HEP/CTDNP)n multilayers. The assembly process was characterized by quartz crystal microbalance with dissipation (QCM-D). The drug release behavior of the coating was investigated by ultra-HPLC (UPLC). In vitro cell experiments were carried out to monitor the effects of multifunctional coatings on cellular adhesion, proliferation and migration. And the intraocular implantation was performed on rabbits to evaluate the in vivo PCO inhibitory effect of such surface-functionalized IOLs. RESULTS: The positively charged CTDNP was successfully prepared by ionic gelation. The QCM-D results indicate the successful preparation of the (HEP/CTDNP)n multilayer film. Drug release profiles showed that surface-multifunctionalized IOL had drug-sustained release properties. In vitro cell culture results showed significant inhibition of adhesion, proliferation and migration of LECs after surface modification. The in vivo results showed that the IOLs with multifunctionalized surface can effectively reduce the posterior hyperplasia and Soemmering's ring (SR) formation. CONCLUSION: These findings suggested that such multifunctionalized drug-eluting IOLs can effectively reduce the posterior hyperplasia and SR formation when intraocular implantation has a major impact on reducing PCO incidence. Thus they have a great potential in improving patient vision recovery and maintenance.

Bottom-up fabrication of zwitterionic polymer brushes on intraocular lens for improved biocompatibility.

Intraocular lens (IOL) is an efficient implantable device commonly used for treating cataracts. However, bioadhesion of bacteria or residual lens epithelial cells on the IOL surface after surgery causes postoperative complications, such as endophthalmitis or posterior capsular opacification, and leads to loss of sight again. In the present study, zwitterionic polymer brushes were fabricated on the IOL surface via bottom-up grafting procedure. The attenuated total reflection-Fourier transform infrared and contact angle measurements indicated successful surface modification, as well as excellent hydrophilicity. The coating of hydrophilic zwitterionic polymer effectively decreased the bioadhesion of lens epithelial cells or bacteria. In vivo intraocular implantation results showed good in vivo biocompatibility of zwitterionic IOL and its effectiveness against postoperative complications.

Hydrophilic modification of intraocular lens via surface initiated reversible addition-fragmentation chain transfer polymerization for reduced posterior capsular opacification.

Phacoemulsification followed with intraocular lens (IOL) implantation is the most effective clinical surgeries in treating cataracts. However, posterior capsular opacification (PCO), a common complication of this surgery, may cause vision decrease after surgery. PCO is mainly caused by the adhesion, proliferation and trans-differentiation of the residual lens epithelial cells (LEC) after surgery. Surface modification of IOL to reduce the LEC adhesion is of great importance in PCO prevention. Herein, surface initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization was utilized to modify the IOL materials for generating a comb-like polyethylene glycol (PEG) brush coating on the surface. The ATR-FTIR, XPS, and contact angle characterizations indicate the successful immobilization of the RAFT agent, as well as the subsequent SI-RAFT polymerization of PEG macromonomer. More interestingly, the PEG brush coating shows excellent hydrophilicity on the surface. The in vitro LEC culture and bacteria adhesion results show that the hydrophilic modification can effectively reduce the bio-adhesion. The in vivo implantation results show that the PEG brush modified IOL presents good biocompatibility, and significantly decreases the posterior capsular hyperplasia. These results demonstrate that the surface modification of IOL with excellent hydrophilic brush via SI-RAFT may provide a good alternative for IOL anti-PCO modification.

Surface PEGylation of intraocular lens for PCO prevention: An in vivo evaluation.

Posterior capsular opacification (PCO) is a common complication in cataract surgery. The development of PCO is attributed to the combination of adhesion, migration, proliferation, and transdifferentiation of the residual lens epithelial cells (LEC) onto the interface of intraocular lens (IOL) material and lens posterior, in which the initial adhesion is the beginning step and plays important roles. In the present study, hydrophilic polyethylene glycol (PEG) was immobilized onto IOL surface via plasma-aided chemical grafting procedure. The attenuated total reflection - Fourier transform infrared (ATR-FTIR) and contact angle (CA) - measurements indicate the successful surface PEGylation, as well as the excellent hydrophilicity of the surfaces. Compared with pristine IOL, the PEGylation does not influent its optical property, whereas the initial adhesion of LEC is greatly inhibited. In vivo ocular implantation results show that the PEGylated IOL presents good in vivo biocompatibility, and can effectively prevent the PCO development.

Hydrated polysaccharide multilayer as an intraocular lens surface coating for biocompatibility improvements.

Posterior capsule opacification (PCO) is a significant complication of intraocular lens (IOL) implantation in cataract surgery, in which the adhesion and proliferation of lens epithelial cells (LECs) on the IOL surface play important roles. In the present study, a highly swollen hyaluronic acid (HA)/chitosan (CHI) polyelectrolyte multilayer was fabricated on the IOL surface via the layer by layer technique. Quartz crystal microbalance with dissipation (QCM-D) results not only show the successful construction of the multilayer, but also indicate its hydrogel-like swollen property. The water content of the (HA/CHI)5 multilayer is around 400%, as obtained by thermogravimetry (TG) analysis. Compared with a pristine IOL, the polysaccharide multilayer modification does not influence its optical property, whereas the adhesion and proliferation of LECs are greatly inhibited. In vivo ocular implantation results show that such a polysaccharide multilayer modification presents good in vivo biocompatibility, and has positive effects on reducing PCO development.

Hydrophobic modification of polymethyl methacrylate as intraocular lenses material to improve the cytocompatibility.

The development of posterior capsule opacification (PCO) after intraocular lenses (IOL) implantation for dealing with cataract is mainly due to the severe loss of the human lens epithelial cells (HLECs) during surgery contact. A novel poly (hedral oligomeric silsesquioxane-co-methyl methacrylate) copolymer (allyl POSS-PMMA) was synthesized by free radical polymerization method to promote the adhesion of HLECs. FT-IR and (1)H NMR measurements indicated the existence of POSS cage in the product, which demonstrated the successful synthesis of allyl POSS-PMMA copolymer. Effect of allyl POSS in the hybrids on crystal structure, surface wettability and morphology, optical transmission, thermodynamic properties and cytocompatibility was investigated in detail. X-ray diffraction peaks at 2θ∼11° and 12° indicated that POSS molecules had aggregated and crystallized. Thermogravimetric analysis-differential scanning calorimeter and optical transmission measurements confirmed that the allyl POSS-PMMA copolymer had high glass transition temperatures (more than 100°C) and good transparency. The hydrophilicity and morphology of PMMA and copolymers surfaces were characterized by static water contact angle and atomic force microscopy. The results revealed that the surface of the allyl POSS-PMMA copolymer displayed higher hydrophobicity and higher roughness than that of pure PMMA. The surface biocompatibility was evaluated by morphology and activity measurement with HLECs in vitro. The results verified that the surface of allyl POSS-PMMA copolymer films had more HLECs adhesion and better spreading morphology than that of PMMA film.

Bis(3,5-dimeth-oxy-phen-yl)phosphinic acid.

In the crystal structure of the title compound, C(16)H(19)O(6)P, inter-molecular O-H⋯O inter-actions link the mol-ecules into chains parallel to the b axis. These chains are linked by C-H⋯π and π-π inter-actions [centroid-centroid distance = 3.7307 (29) Å] into a three-dimensional network. The dihedral angle between the benzene rings is 73.5 (1)°. The C and O atoms of all four methoxy groups lie very close to the mean planes of their attached rings; the C atoms are 0.055 (2)-0.1038 (1) Šout of the mean plane of the attached rings.

Bis(4-amino-2-chloro-phen-yl) disulfide.

The title compound, C(12)H(10)Cl(2)N(2)S(2), features an S-S bond [2.0671 (16) Å] that bridges two 4-amino-2-chloro-phenyl rings with a C-S-S-C torsion angle of -84.2 (2)°. The two benzene rings are twisted with respect to each other at a dihedral angle of 39.9 (2)°. Inter-molecular N-H⋯S hydrogen bonding is present in the crystal structure.

Detection of arbitrarily-shaped clusters using a neighbor-expanding approach: a case study on murine typhus in south Texas.

BACKGROUND: Kulldorff's spatial scan statistic has been one of the most widely used statistical methods for automatic detection of clusters in spatial data. One limitation of this method lies in the fact that it has to rely on scan windows with predefined shapes in the search process, and therefore it cannot detect cluster with arbitrary shapes. We employ a new neighbor-expanding approach and introduce two new algorithms to detect cluster with arbitrary shapes in spatial data. These two algorithms are called the maximum-likelihood-first (MLF) algorithm and non-greedy growth (NGG) algorithm. We then compare the performance of these two new algorithms with the spatial scan statistic (SaTScan), Tango's flexibly shaped spatial scan statistic (FlexScan), and Duczmal's simulated annealing (SA) method using two datasets. Furthermore, we utilize the methods to examine clusters of murine typhus cases in South Texas from 1996 to 2006. RESULT: When compared with the SaTScan and FlexScan method, the two new algorithms were more flexible and sensitive in detecting the clusters with arbitrary shapes in the test datasets. Clusters detected by the MLF algorithm are statistically more significant than those detected by the NGG algorithm. However, the NGG algorithm appears to be more stable when there are no extreme cluster patterns in the data. For the murine typhus data in South Texas, a large portion of the detected clusters were located in coastal counties where environmental conditions and socioeconomic status of some population groups were at a disadvantage when compared with those in other counties with no clusters of murine typhus cases. CONCLUSION: The two new algorithms are effective in detecting the location and boundary of spatial clusters with arbitrary shapes. Additional research is needed to better understand the etiology of the concentration of murine typhus cases in some counties in south Texas.