Surface Modification And The Biocompatibility Research Of Silicone Intraocular Lens

With the development of phacoemulsification and foldable intraocular lens(IOL) insertion,the material and design of the IOL have been in a continuous evolution.One of the most important parameters in successful IOL application is the biocompatibility of the materials.The most biocompatible material should prevent or minimize the host-cell response and lens epithelial cell(LEC)proliferation.Among various IOLs,silicone intraocular lenses are one of the most frequently used soft IOLs.Recent survey of ASCRS reports that silicone IOLs are second in popularity to hydrophobic acrylic IOLs.Silicone IOLs have excellent properties,such as relatively inert,flexibility,chemical stability, autoclavability,and suitable refractive index.However,it has been found that the silicone IOLs surfaces are easy to adhere bacteria,cells,and silicone oil,which can cause the high incidence of endophthalmitis,inflammation,IOL decentration, posterior synechia,and limit the use in diabetes and retina disease eyes.These disadvantages of silicone IOL surface limit its wide application.Therefore,the surface modification of silicone IOLs may be a promising approach to improve their biocompatibility and reduce implantation complication without a change in bulky properties. In the first part,we chose a phospholipid-containing monomer(2-methacryloyloxyethyl phosphoryl-choline,MPC),which be regarded as a biomimetic component of cell membrane,to modify the surface of silicone IOL using the plasma technique.The excellent biocompatibility of MPC containing polymers has been confirmed by various phenomena such as being quite inert in biological systems, reducing protein absorption,inhibiting bacterial adhesion,and suppressing cell attachment.Biomaterials modified with phospholipid analogues have great potential for a wide range of medical applications including soft contact lens,membranes for artificial kidney,vascular prosthesis,and urological devices with low biofouling,etc.As a biomaterial,the IOL implants are primarily in the immediate vicinity of uveal tissue as well as in direct contact with lens capsular bag tissue,which causes a specific pathophysiological reaction of inflammatory cell and LECs.The reactive pattern of both tissues is generally considered as the indicators of IOL's biocompatibility.Amon has proposed dividing the biocompatibility of IOLs into uveal and capsular biocompatibility.In fact,a particular IOL may have excellent uveal biocompatibility,characterized by minimal foreign-body giant cells on the surface of the lens and low postoperative aqueous flare measurements,yet have poor capsular biocompatibility,characterized by lens epithelial overgrowth or capsule contraction.Therefore,it behooves us to find an ideal IOL that provides maximum uveal and capsular biocompatibility.The IOL surface character,especially the hydrophilic or hydrophobic of IOLs surface influence the uveal and capsular biocompatibility in different way.The uveal tissues reaction such as macrophage and foreign-body giant cells adhesion,aqueous flare,synechia of the iris,etc.were seen more often on hydrophobic IOLs than hydrophilic IOLs.However,the LECs proliferation and migration were seen extensively in hydrophilic lenses,resulting in the higher incidence of posterior capsular opacification(PCO)in hydrophilic IOL groups than hydrophobic.Therefore,the second part of this study was to design and prepare a newly anterior surface modified silicone IOL,which has a hydrophilic anterior surface,while still keeping its original hydrophobic posterior surface,so as to reduce postoperative complications.PartⅠ:The manufacture and character detection of silicone intraocular lens surface modified by phospholipid moietiesObjectiveTethering the hydrophilic moieties on silicone IOL surface to improve the surface hydrophilicity,suppress the cell,bacteria and silicone oil attachment,enhance the surface biocompatibility,reduce the complication,and widen the application.Methods2-methacryloyloxyethyl phosphorylcholine(MPC)was tethered onto the silicone IOL surface through air plasma treatment.Chemical changes on the IOL surface were characterized by X-ray photoelectron spectroscopy(XPS)to confirm the covalent binding of MPC.The hydrophilicity of the control and modified IOLs was compared by the measurements of water contact angle.Morphologies of the IOL surfaces were observed by scanning electron microscopy(SEM)to optimize the plasma treatment process.The biocompatibility of the IOLs was evaluated by platelet adhesion,macrophage cell culture,and LEC attachment.Two different techniques,direct counting of viable adherent bacteria released by sonication,and SEM were used to observe and compare the adherence of S.epidermidis to the IOLs after 1- and 18-h incubation.The silicone oil adhesion was analyzed by in vitro test and Image analysis was performed to evaluate the percentage of silicone oil coverage of the anterior and posterior surfaces of IOL optic.Results:XPS analysis confirmed that the test IOLs were surface-modified with MPC.It was found that,after the tethering of MPC,the hydrophilicity of the IOL can be improved significantly and permanently.The platelet adhesion and activation was suppressed after surface modification.Macrophage and LEC attachment on the IOL surface were obviously reduced(P＜0.05),no obvious cell shape change and fibrous metaplasia was observed.The MPC modified IOLs exhibited significantly reduced adhesion of S.epidermidis(P＜0.05)and also suppressed the accumulation of bacteria and biofilm production after incubation.The mean silicone oil coverage of the hydrophilic MPC modified IOLs was sharply reduced compared to the about 100% silicone oil coverage on the silicone optic IOLs(P＜0.05).ConclusionThe results implied that the MPC-modified silicone IOLs possess better biocompatibility,which will reduce the implantation complication,such as inflammation,endophthalmitis,capsule contraction and silicone oil adhesion.PartⅡ:The production and application in rabbits of a new intraocular lens with MPC-modified hydrophilic anterior surface while keeping the silicone hydrophobic posterior surfaceObjectiveThe purpose of this study was to design and prepare a newly anterior surface modified silicone IOL,which has a hydrophilic anterior surface to reduce postoperative inflammation reaction,while still keeping its original hydrophobic posterior surface to inhibit PCO development.MethodsThis was achieved by grafting the MPC on the silicone IOL anterior surface using plasma-induced in site polymerization.The hydrophilicity of IOL surface was characterized by contact angle test.The physic and optic properties were determined by national standards.Thirty-six rabbit eyes were randomly operated on with phacoemulsification and implantation of 3 foldable lenses:a new anterior surfaced hydrophilic modified silicone IOL(n=12),a control silicone IOL(n=12)and a hydrogel IOL(n=12).Postoperative follow-up was 1,3,7,30,60,and 90 days after surgery.At each visit,all rabbits were observed by slitlamp examination approximately to evaluate anterior chamber inflammation,posterior synechia and IOL dislocation.Postoperative inflammation was assessed by measuring aqueous flare with a laser flare-cell meter at the same time point.Standardized digital slitlamp images of posterior capsule opacification(PCO)were taken and PCO was evaluated using EPCO 2000 Software.The rabbits were killed three months after operation,the PCO formation was evaluated using the Miyake-Apple posterior photographic technique.The IOLs were extracted from rabbits eyes and cells attached on its surface were observed by light microscopy with Giemsa stained and were also observed by SEM.Histological sections of globe were prepared and stained with hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and Masson's trichrome to document proliferation of LECs and extracellular matrix in capsular bag.Immunohistochemistry for collagenⅠ,collagenⅢ,fibronection andα-SMA was also done to evaluate mesenchymal transition in LECs.The anterior capsular and posterior capsular were processed for transmission electron microscopy.ResultsThe contact angle data of MPC modified IOL showed a significant increase of hydrophilicity of anterior surface,compared to untreated controls,while still keeping the hydrophobic of posterior surface.The physic and optic properties of modified silicone IOLs meet the national standards.The slitlamp examination showed that two eyes with silicone IOLs presented posterior synechia and IOL dislocation,one eyes with hydrogel IOLs was found IOL dislocation,no obvious inflammation was found in eyes with anterior MPC-modified IOLs.Aqueous flare results showed that there was no statistically difference among the three groups in the measured time point. The EPCO analysis and Miyake-Apple evaluation revealed that the hydrogel IOLs had higher incidence of PCO compared to anterior MPC-modified IOLs and silicone IOLs(P＜0.05),but there were no statistically significant difference between MPC-modified IOLs and silicone IOLs groups(P＞0.05).The light microscopy observation showed that there were more cell attachment on silicone IOLs than anterior MPC-modified IOLs and hydrogel IOLs(P＜0.05).Histopathological, Immunohistochemistry and transmission electron microscopy analysis demonstrate the LECs/cortex remnants had some growth started from the haptics toward the visual axis while stopped at the optic periphery of the silicone IOL and MPC modified IOL keeping silicone posterior surface.The central posterior capsule is clear in both cases.In contrast,in hydrogel IOLs,the LECs and extracellular matrix could apparently continue growing toward the center of the optic,thus leading to the opacification of central posterior capsule.ConclusionThe new designed IOLs had hydrophilic anterior surface and hydrophobic posterior surface by grafting MPC on the anterior surface of silicone IOLs.The new designed IOLs have excellent uveal biocompatibility,characterized by minimal foreign-body giant cells on the surface of the IOLs and low postoperative aqueous flare measurements,and have good capsular biocompatibility,characterized by low incidence of PCO.