SYNTHETIC HYDROPHYLIC POLYMERS FOR EYE SURGERY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-22 from National Eye Institute, IRG: VISA
Abstract: The purpose of this research is to develop synthetic polymers and therapeutic devices for preventing and treating eye problems. The three principal objectives are 1. Fluid-lenses with perfluorocarbons -- Studies will be done to develop an improved method for the protection and oxygenation of the cornea in severe dry-eye patients by means of a plastic scleral lens that will maintain a depot of an oxygen-rich fluid between the lens and the cornea. This fluid-lens could also be very useful for the prevention of neuroparalytic keratitis and for the refractive correction of difficult keratoconus cases. Another aim is to develop a fluid-lens for the protection and preservation of the cornea surface from anoxic and mechanical trauma during intravitreous and other posterior pole surgery. To achieve these objectives, we will strive to find a suitable liquid perfluorocarbon or silicone derivative, or emulsion, that dissolves large amounts of oxygen. Such a liquid could be used with fluid-type scleral lenses to maintain a healthy cornea during daily wear or during intraocular surgery. This project involves the interaction of chemistry with ocular toxicology and physiology. 2. Vitreous implant -- Work will continue toward the goal of developing a permanent vitreous implant for the treatment of difficult cases of retinal detachment and other vitreoretinal diseases. These implants consist of very slightly crosslinked aqueous jellies, which are very soft and so elastic that they can be injected into the eye without fragmentation. This research involves a collaboration of polymer chemistry with ophthalmology. 3. Tear evaporimeter -- Development will continue on a new method for diagnosis of dry eye. Using goggles provided with a humidity and temperature sensor, we will investigate the evaporation of water from the surface of the eye under physiological conditions. This device will also be useful for the study of the evaporation of water in contact lens wearers and its relationship to the tight-lens syndrome and to contact lens coating. This investigation applies standard physical concepts to tear physiology. For summary of response to previous summary statement, see page 22.
Keywords: BIOMATERIALS, MOLECULAR CONDENSATIONS, POLYMERS (GENERAL), SURGERY, SURGICAL MATERIALS AND EQUIPMENT, VISUAL SCIENCES A STUDY SECTION, eye surgery, EYE DISORDERS, LACRIMAL, EYE DISORDERS, OPTICAL AIDS, EYE DISORDERS, OPTICAL AIDS, CONTACT LENSES, EYE DISORDERS, RETINA DISORDERS, RETINA DETACHMENT, EYE SURGERY, VITRECTOMY, EYE, CORNEA, EYE, SCLERA, EYE, VITREOUS BODY, INJURIES, WOUND HEALING, PHYSICAL PROPERTIES, COLLOIDS, GELS, PLASTICS, ACRYLIC POLYMERS, PLASTICS, SILICONE RUBBER, TISSUE COMPATIBILITY-TRANSPLANT, IMPLANT, dosage forms, eye prosthesis, HUMAN, CLINICAL, MAMMALS, LAGOMORPHS, MAMMALS, PRIMATES, MONKEYS AND APES, NEW WORLD MONKEYS
Project start date: 1978-01-01
Project end date: 1988-06-30
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SYNTHETIC POLYMERS IN OPHTHALMOLOGY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-32 from National Eye Institute, IRG: VISC
Abstract: This project has two main objectives. The first is to develop vitreous implants and antiproliferative drug-delivery systems to treat complicated retinal detachments and proliferative vitreoretinopathy (PVR). Many patients who are blind from PVR are treated with silicone oil as a long-lasting vitreous implant, but this procedure often results in complications such as cataract, corneal decompensation, oil emulsification, and glaucoma. Intravitreous injections of air, inert gases, saline, and hyaluronan, combined with scleral buckling, give good results with some retinal detachments. However, these fluids last too short a time to be effective when a retinal tamponade is needed. Specifically, a new silicone-fluorosilicone (SiFO) copolymer oil denser than water will be investigated for use intraoperatively and as a temporary tamponade in retinal detachment surgery. SiFO is advantageous over silicone oil (SiO) in that SiFO is denser and, therefore, can be used to fix detached retinas posteriorly and inferiorly by displacing vitreous and subretinal fluid; SiFO has less of a tendency to emulsify intraocularly than fluorosilicone oil (FSiO). The relative low viscosity of SiFO (200 vs 5000 centistokes for the commonly used SiO and FSiO required to prevent intraocular emulsification) facilitates injection and post-surgical removal of SiFO from the eye. The advantage of using SiFO instead of the perfluorocarbon liquids (currently under investigation as intraoperative tools in retinal detachment surgery) is that SiFO can be retained as an intraocular tamponade for the time needed for a chorioretinal adhesion to form. In retinal detachments complicated by PVR, SiFO-soluble retinoids will be investigated as antiproliferative agents. The release retinoids from injectable microspheres of biodegradable polymers also will be investigated for use in PVR cases not treated with an intravitreous oil. The second objective is to investigate the prevention of contact lens (CL)-induced bacterial keratitis, the worst complication of CL wear. The incidence of infection is the highest with extended-wear hydrogel CLs. Because many people use this modality of visual correction despite the inherent dangers, it is desirable to eliminate or at least reduce the incidence of this devastating complication. Bacterial attachment is the initial step in the pathogenesis of bacterial keratitis. We discovered that certain inert water-soluble polymers of the poloxamer family [alpha-hydro-omega-hydroxypoly(oxyethylene)- poly(oxypropylene)-poly(oxyethylene) block copolymers] significantly decrease gram-negative bacterial adherence to lenses. The poloxamers will be investigated in an animal model of CL overwear to prevent bacterial keratitis.
Keywords: biomaterial compatibility, biomaterial development /preparation, biomaterial evaluation, contact lens, copolymer I, disease /disorder prevention /control, drug design /synthesis /production, eye surgery, keratitis, silicon compound, biotransformation, drug metabolism, fluorocarbon polymer, oxirane, proliferative vitreoretinopathy, retina detachment, surgery material /equipment, toxicant interaction, toxicology, vitreous body, Pseudomonas aeruginosa, laboratory rabbit
Project start date: 1978-01-01
Project end date: 1999-04-30
5R01EY000327-32 (1997): $407915
5R01EY000327-30 (1995): $362621
5R01EY000327-29 (1994): $348260
SYNTHETIC HYDROPHILIC POLYMERS FOR EYE SURGERY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-11 from National Eye Institute, IRG: VIS
Abstract: This project deals with the investigation of synthetic hydrogel and other polymers in relation to their use as therapeutic and cosmetic contact lenses, and as extraocular and intraocular implants in animals will be studied as models for possible use in retinal detachment and vitreous surgery. The sustained release of chemotherapeutic agents from episcleral and intrascleral implants for possible use in the treatment of ocular melanomas and retinoblastoma will be evaluated in vitro, and in animal models. BIBLIOGRAPHIC REFERENCES Huamonte, F., Refojo, M.F., and Banuelos, A. Expandable silicone implants for scleral buckling. III. Experiments in vivo. Arch. Ophthal. 93354-356, 1975. Huamonte, F., Refojo, M.F., and Banuelos, A. Expandable silicone implants for scleral buckling. IV. Experiments with an explant for macular breaks. Arch. Ophthal. 93429-431, 1975.
Keywords: MOLECULAR CONDENSATIONS, POLYMERS (GENERAL), SURGICAL ADHESIVES, VISUAL SCIENCES STUDY SECTION, eye surgery, ANTIBIOTICS, BIOMATERIALS, EYE DISORDERS, OPTICAL AIDS, EYE DISORDERS, OPTICAL AIDS, CONTACT LENSES, EYE DISORDERS, RETINA AND CHOROID DISORDERS, RETINA DETACHMENT, EYE SURGERY, VITRECTOMY, EYE, SCLERA, INJURIES, WOUND HEALING, NEOPLASMS OF SENSE ORGANS, EYE NEOPLASMS, NEOPLASMS OF SENSE ORGANS, EYE NEOPLASMS, RETINOBLASTOMA, NEOPLASTIC THERAPY, ANTINEOPLASTIC AGENTS, PHYSICAL PROPERTIES, COLLOIDS, GELS, PIGMENT CELL NEOPLASMS, MELANOMA, STEROIDS, TISSUE COMPATIBILITY-TRANSPLANT, IMPLANT, eye prosthesis, silicon, MAMMALS, ARTIODACTYLA, CATTLE*, MAMMALS, LAGOMORPHS*
Project start date: 1973-01-01
Project end date: 1977-12-31
SYNTHETIC HYDROPHYLIC POLYMERS FOR EYE SURGERY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-21 from National Eye Institute, IRG: VISA
Abstract: The purpose of this research is to develop synthetic polymers and therapeutic devices for preventing and treating eye problems. The three principal objectives are 1. Fluid-lenses with perfluorocarbons -- Studies will be done to develop an improved method for the protection and oxygenation of the cornea in severe dry-eye patients by means of a plastic scleral lens that will maintain a depot of an oxygen-rich fluid between the lens and the cornea. This fluid-lens could also be very useful for the prevention of neuroparalytic keratitis and for the refractive correction of difficult keratoconus cases. Another aim is to develop a fluid-lens for the protection and preservation of the cornea surface from anoxic and mechanical trauma during intravitreous and other posterior pole surgery. To achieve these objectives, we will strive to find a suitable liquid perfluorocarbon or silicone derivative, or emulsion, that dissolves large amounts of oxygen. Such a liquid could be used with fluid-type scleral lenses to maintain a healthy cornea during daily wear or during intraocular surgery. This project involves the interaction of chemistry with ocular toxicology and physiology. 2. Vitreous implant -- Work will continue toward the goal of developing a permanent vitreous implant for the treatment of difficult cases of retinal detachment and other vitreoretinal diseases. These implants consist of very slightly crosslinked aqueous jellies, which are very soft and so elastic that they can be injected into the eye without fragmentation. This research involves a collaboration of polymer chemistry with ophthalmology. 3. Tear evaporimeter -- Development will continue on a new method for diagnosis of dry eye. Using goggles provided with a humidity and temperature sensor, we will investigate the evaporation of water from the surface of the eye under physiological conditions. This device will also be useful for the study of the evaporation of water in contact lens wearers and its relationship to the tight-lens syndrome and to contact lens coating. This investigation applies standard physical concepts to tear physiology. For summary of response to previous summary statement, see page 22.
Keywords: BIOMATERIALS, MOLECULAR CONDENSATIONS, POLYMERS (GENERAL), SURGERY, SURGICAL MATERIALS AND EQUIPMENT, VISUAL SCIENCES A STUDY SECTION, eye surgery, EYE DISORDERS, LACRIMAL, EYE DISORDERS, OPTICAL AIDS, EYE DISORDERS, OPTICAL AIDS, CONTACT LENSES, EYE DISORDERS, RETINA DISORDERS, RETINA DETACHMENT, EYE SURGERY, VITRECTOMY, EYE, CORNEA, EYE, SCLERA, EYE, VITREOUS BODY, INJURIES, WOUND HEALING, PHYSICAL PROPERTIES, COLLOIDS, GELS, PLASTICS, ACRYLIC POLYMERS, PLASTICS, SILICONE RUBBER, TISSUE COMPATIBILITY-TRANSPLANT, IMPLANT, dosage forms, eye prosthesis, HUMAN, CLINICAL, MAMMALS, LAGOMORPHS, MAMMALS, PRIMATES, MONKEYS AND APES, NEW WORLD MONKEYS
Project start date: 1978-01-01
Project end date: 1988-04-30
SYNTHETIC HYDROPHILIC POLYMERS FOR EYE SURGERY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-12 from National Eye Institute, IRG: VIS
Abstract: The purpose of this project is to develop synthetic polymers and therapeutic devices to be used in treating eye problems, and to investigate the psychochemical and physiological properties of materials used in opthalmology such as contact lenses, artificial corneas, vitreous substitutes and scleral buckling materials for retinal detachment surgery. The sustained release of chemotherapeutic agents DTIC and BCNU from ocular implants for possible use in the treatment of ocular malignancies will be evaluated in vitro and in animal models. Poly(2-hydroxyethyl acrylate), PHEA, is a soft polymer that absorbs water to form a softer hydrogel. Because this polymer is soft and pliable not only in the hydrated state but also in its dry state, it provides advantages over other scleral buckling materials for retinal detachment surgery particularly for cases of thin sclera, and reoperations. Surgery will be performed in rabbit eyes in order to critically evaluate the tissue tolerance and the possible advantages and disadvantages of PHEA compared to other available scleral implants for retinal surgery. The oxygen permeability of corneal contact lenses is of importance for the physiology of the cornea. A diversity of new contact lenses, both soft and hard, are becoming available. An oxygen permeability apparatus has been developed and will be used to determine the permeability of oxygen dissolved in water through available contact lenses under controlled conditions. BIBLIOGRAPHIC REFERENCES Refojo, M.F. Contact lenses. In Bikales, R.N. (ed.) Supplement to Vol. 1 of the Encyclopedia of Polymer Science and Technology, New York, Wiley-Interscience, 1976, in press. Refojo, M.F. Reversible binding of chlorhexidine gluconate to hydrogel contact lenses. Cont. and Intraocular Lens Med. J. 247-56, 1976.
Keywords: MOLECULAR CONDENSATIONS, POLYMERS (GENERAL), SURGICAL ADHESIVES, VISUAL SCIENCES STUDY SECTION, eye surgery, ANTIBIOTICS, BIOMATERIALS, EYE DISORDERS, OPTICAL AIDS, EYE DISORDERS, OPTICAL AIDS, CONTACT LENSES, EYE DISORDERS, RETINA AND CHOROID DISORDERS, RETINA DETACHMENT, EYE SURGERY, VITRECTOMY, EYE, SCLERA, INJURIES, WOUND HEALING, NEOPLASMS OF SENSE ORGANS, EYE NEOPLASMS, NEOPLASMS OF SENSE ORGANS, EYE NEOPLASMS, RETINOBLASTOMA, NEOPLASTIC THERAPY, ANTINEOPLASTIC AGENTS, PHYSICAL PROPERTIES, COLLOIDS, GELS, STEROIDS, TISSUE COMPATIBILITY-TRANSPLANT, IMPLANT, eye prosthesis, silicon, MAMMALS, LAGOMORPHS*
Project start date: 1973-01-01
Project end date: 1977-12-31
5R01EY000327-27 (1992): $327459
SYNTHETIC POLYMERS IN OPHTHALMOLOGY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-31 from National Eye Institute, IRG: VISC
Project start date: 1978-01-01
Project end date: 1998-04-30
5R01EY000327-31 (1996): $392590
SYNTHETIC HYDROPHILIC POLYMERS FOR EYE SURGERY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute 20 Staniford St Boston, Ma 02114
Grant 5R01EY000327-07 from National Eye Institute, IRG: VIS
Keywords: MOLECULAR CONDENSATIONS, POLYMERS (GENERAL), SURGICAL ADHESIVES, eye surgery, BIOMEDICAL ENGINEERING, BIOMATERIALS, CYCLIC AMINO ACIDS, PROLINE, EYE DISORDERS, OPTICAL AIDS, EYE SURGERY, KERATOPLASTY, EYE, SCLERA, EYE, VITREOUS BODY, INJURIES, WOUND HEALING, NEUROPHYSIOLOGY (GENERAL), PHYSICAL PROPERTIES, COLLOIDS, GELS, TISSUE COMPATIBILITY-TRANSPLANT, IMPLANT, VISUAL SCIENCES STUDY SECTION, eye prosthesis, MAMMALS, LAGOMORPHS*, MAMMALS, UNGULATES, CATTLE*, OPTICS, MICROSCOPY, ELECTRON*, RADIOAUTOGRAPHY*
Project start date: 1969-01-01
Project end date: 1972-12-31
Grants awarded to Miguel F Refojo
SYNTHETIC POLYMERS IN OPHTHALMOLOGY
Miguel F Refojo, Senior Scientist Emeritus
Schepens Eye Research Institute
20 Staniford St
boston, Ma 02114
Grant 2R01EY000327-28 from National Eye Institute, IRG: VISC
Abstract: This project has two main objectives. The first is to develop vitreous implants and antiproliferative drug-delivery systems to treat complicated retinal detachments and proliferative vitreoretinopathy (PVR). Many patients who are blind from PVR are treated with silicone oil as a long-lasting vitreous implant, but this procedure often results in complications such as cataract, corneal decompensation, oil emulsification, and glaucoma. Intravitreous injections of air, inert gases, saline, and hyaluronan, combined with scleral buckling, give good results with some retinal detachments. However, these fluids last too short a time to be effective when a retinal tamponade is needed. Specifically, a new silicone-fluorosilicone (SiFO) copolymer oil denser than water will be investigated for use intraoperatively and as a temporary tamponade in retinal detachment surgery. SiFO is advantageous over silicone oil (SiO) in that SiFO is denser and, therefore, can be used to fix detached retinas posteriorly and inferiorly by displacing vitreous and subretinal fluid; SiFO has less of a tendency to emulsify intraocularly than fluorosilicone oil (FSiO). The relative low viscosity of SiFO (200 vs 5000 centistokes for the commonly used SiO and FSiO required to prevent intraocular emulsification) facilitates injection and post-surgical removal of SiFO from the eye. The advantage of using SiFO instead of the perfluorocarbon liquids (currently under investigation as intraoperative tools in retinal detachment surgery) is that SiFO can be retained as an intraocular tamponade for the time needed for a chorioretinal adhesion to form. In retinal detachments complicated by PVR, SiFO-soluble retinoids will be investigated as antiproliferative agents. The release retinoids from injectable microspheres of biodegradable polymers also will be investigated for use in PVR cases not treated with an intravitreous oil. The second objective is to investigate the prevention of contact lens (CL)-induced bacterial keratitis, the worst complication of CL wear. The incidence of infection is the highest with extended-wear hydrogel CLs. Because many people use this modality of visual correction despite the inherent dangers, it is desirable to eliminate or at least reduce the incidence of this devastating complication. Bacterial attachment is the initial step in the pathogenesis of bacterial keratitis. We discovered that certain inert water-soluble polymers of the poloxamer family [alpha-hydro-omega-hydroxypoly(oxyethylene)- poly(oxypropylene)-poly(oxyethylene) block copolymers] significantly decrease gram-negative bacterial adherence to lenses. The poloxamers will be investigated in an animal model of CL overwear to prevent bacterial keratitis
Keywords: biomaterial development /preparation, biomaterial evaluation, contact lens, disease prevention /control, drug design /synthesis /production, eye surgery, implant compatibility, keratitis, polymer, silicon compound biotransformation, drug metabolism, fluorocarbon polymer, poloxalene, proliferative vitreoretinopathy, retina detachment, surgery material /equipment, toxicant interaction, toxicology, vitreous body Pseudomonas aeruginosa, laboratory rabbit
Project start date: 1978-01-01
Project end date: 1998-04-30
2R01EY000327-28 (1993): $344909