Injectable IOLs are Possible but not Probable
This article was published in Ocular Surgery News on September 1, 1991.
Irving J. Arons
Ophthalmic Consulting Group
Arthur D. Little
The injectable lens, which has been called the “lens of the future,” remains only a possibility. A factor that could delay or block its introduction to the marketplace is the war underway between industry and government agencies for gaining control of the spiraling health care costs. That war could have a dampening effect on the development of new technologies.
The concept of injecting a soft polymer into an evacuated lens capsule was first conceived by Kessler, MD, in 1964. But it was the work of David Schanzlin, MD, and his co-workers at the Doheny Eye Clinic that futhered the research efforts started by Kessler. Initial work was sponsored by the Beckman Institute and later by Allergan Medical Optics, when Schanzlin, Jim Davenport, Duane Mason, and George Wright formed Innovative Surgical Products.
The early idea was to use phacoemulsification techniques to remove most of the lens nucleus, leaving the lens capsule intact. An enzyme solution would then be injected to remove any remaining lens epithelial cells, and then a polymerizable silicone polymer was to be inserted through a 22-gauge syringe needle. The polymer would gel, sealing off the opening to form a soft lens that would completely fill the lens capsule and hopefully be capable of achieving accommodation using the ciliary muscles attached through the zonules to the capsule.
Elusive Dream
According to our notes from a private meeting attended in 1985 and reports of the program in early 1987, the "dream" was close to fruition. However, several problems were encountered that led to the eventual shutdown of this major research project. It later reverted to a smaller effort within the overall research efforts being carried out at AMO.
Some of the major obstacles yet to be overcome, included requirements of a biomaterial for use as an injectable IOL as listed below.
The material must:
● be optically transparent and of appropriate refractive index, and remain clear throughout its useful life;
● be a liquid or semi-solid and be injectable through a small gauge needle;
● quickly set up or polymerize without leaking from the injection hole, and with minimal shrinkage, heating or gas release;
● completely fill the lens capsule without voids (i.e., a known volume of material has to be delivered/the volume of the filled capsule must be known or calculable);
● be soft/pliable, but firm (similar to the natural lens), biocompatible, adhere to the capsule walls, and contain an appropriate UV inhibitor to protect the back of the eye from incident UV radiation;
● be cytotoxic, or contain cytotoxins to inhibit growth of lens epithelial cells to prevent opacification of the capsule walls.
Research efforts
Low-level research efforts are under way by at least two companies, AMO and Domilens (with research into the use of collagen materials as the injectable polymer at the latter company), and at several eye research institutes: Bascom Palmer and Bethesda Eye Institutes, Doheny Eye Institute at the University of Southern California School of Medicine, and the Center for IOL Research at the University of Utah.
In addition to the work in progress on developing injectable polymers and insertion techniques, work is also under way in the use of inflatable balloons to contain and form the injectable lens. This latter work is being done by Drs. Okihiro Nishi of Osaka, Japan; Irvin Kalb of Westport, Connecticut; and Jim Deacon of the Department of Bioengineering and Ophthalmology at the University of Utah.
At one time, Vision Technologies International claimed to have been undertaking a research effort aimed at developing an injectable IOL, but recent correspondence with that firm has confirmed that its efforts have ceased.
One of the major problems encountered in the various research efforts has been the residual lens epithelial cells causing opacification of the lens capsule. Research under way at Houston Biotechnology, originated at Baylor College of Medicine, is aimed at preventing this occurrence. The firm has developed a monoclonal antibody, now in clinical test, that can be injected into the capsular space at the time of the cataract removal to inhibit or prevent the opacification action by binding to the epithelial cells.
"No incision" laser surgery
One of the major problems encountered with the development of the injectable lens was the need for complete removal of all lens fragments and cellular matter before a liquid lens could be injected. The usual methods employed involved various solutions that could be injected to soften and emulsify the lens protein, including enzymes. However, according to the researchers at Innovative Surgical Products, the pioneers in this technique, these techniques were difficult to perform in the animal models employed.
One of the hopes for the future of injectable lenses is the possibility of using laser energy to emulsify the lens cortex for complete and easy removal. Several research groups have made attempts at combining laser probes with irrigation/aspiration removal equipment. Several years ago, a small start-up firm in Southern Florida, Photon Sources, developed a prototype laser-I/A device, but after its first announcement, was never heard from again.
More recently, two ophthalmologists independently developed laser phaco-type devices. Drs. Patricia Bath, MD, and James Dodick, MD, have both lectured on and demonstrated their respective devices, one a direct laser ablator and the other utilizing a titanium shield at the end of a laser probe to generate shock waves to fracture the lens material. However, the most likely laser devices to accomplish this task are based on newer non-invasive photocoagulation techniques.
Two recent laser development stage companies, Phoenix Laser Systems and Intelligent Surgical Laser, both located in California, have independently developed accurately focused photocoagulation laser systems that can be scanned into and across the lens cortex, causing it to emulsify within the capsule without damaging surrounding capsular tissue. Neither laser system requires the use of probes entering the lens capsule as both rely on the accurate focus of the laser beam from outside the eye to accomplish the emulsification of the lens material.
If early experiments with this technique are successful in animal models (and the first trial results reported by ISL were encouraging), it could possibly lead to the long-awaited method for cleanly breaking up the bulk of the lens material for easy removal by an irrigation/aspiration device. This would be followed by a syringe injection of an enzyme to remove the remaining cortical debris, leaving a clean capsule for injection of a liquid polymer to recreate a potentially viable "soft" lens that might retain accommodation from the intact capsular zonules attached to the ciliary muscles.
Since both the laser work and development of a truly injectable lens material are still several years from reality, we do not anticipate an injectable lens will be ready for use in clinical practice for the forseeable future.
Irving J. Arons
Ophthalmic Consulting Group
Arthur D. Little
The injectable lens, which has been called the “lens of the future,” remains only a possibility. A factor that could delay or block its introduction to the marketplace is the war underway between industry and government agencies for gaining control of the spiraling health care costs. That war could have a dampening effect on the development of new technologies.
The concept of injecting a soft polymer into an evacuated lens capsule was first conceived by Kessler, MD, in 1964. But it was the work of David Schanzlin, MD, and his co-workers at the Doheny Eye Clinic that futhered the research efforts started by Kessler. Initial work was sponsored by the Beckman Institute and later by Allergan Medical Optics, when Schanzlin, Jim Davenport, Duane Mason, and George Wright formed Innovative Surgical Products.
The early idea was to use phacoemulsification techniques to remove most of the lens nucleus, leaving the lens capsule intact. An enzyme solution would then be injected to remove any remaining lens epithelial cells, and then a polymerizable silicone polymer was to be inserted through a 22-gauge syringe needle. The polymer would gel, sealing off the opening to form a soft lens that would completely fill the lens capsule and hopefully be capable of achieving accommodation using the ciliary muscles attached through the zonules to the capsule.
Elusive Dream
According to our notes from a private meeting attended in 1985 and reports of the program in early 1987, the "dream" was close to fruition. However, several problems were encountered that led to the eventual shutdown of this major research project. It later reverted to a smaller effort within the overall research efforts being carried out at AMO.
Some of the major obstacles yet to be overcome, included requirements of a biomaterial for use as an injectable IOL as listed below.
The material must:
● be optically transparent and of appropriate refractive index, and remain clear throughout its useful life;
● be a liquid or semi-solid and be injectable through a small gauge needle;
● quickly set up or polymerize without leaking from the injection hole, and with minimal shrinkage, heating or gas release;
● completely fill the lens capsule without voids (i.e., a known volume of material has to be delivered/the volume of the filled capsule must be known or calculable);
● be soft/pliable, but firm (similar to the natural lens), biocompatible, adhere to the capsule walls, and contain an appropriate UV inhibitor to protect the back of the eye from incident UV radiation;
● be cytotoxic, or contain cytotoxins to inhibit growth of lens epithelial cells to prevent opacification of the capsule walls.
Research efforts
Low-level research efforts are under way by at least two companies, AMO and Domilens (with research into the use of collagen materials as the injectable polymer at the latter company), and at several eye research institutes: Bascom Palmer and Bethesda Eye Institutes, Doheny Eye Institute at the University of Southern California School of Medicine, and the Center for IOL Research at the University of Utah.
In addition to the work in progress on developing injectable polymers and insertion techniques, work is also under way in the use of inflatable balloons to contain and form the injectable lens. This latter work is being done by Drs. Okihiro Nishi of Osaka, Japan; Irvin Kalb of Westport, Connecticut; and Jim Deacon of the Department of Bioengineering and Ophthalmology at the University of Utah.
At one time, Vision Technologies International claimed to have been undertaking a research effort aimed at developing an injectable IOL, but recent correspondence with that firm has confirmed that its efforts have ceased.
One of the major problems encountered in the various research efforts has been the residual lens epithelial cells causing opacification of the lens capsule. Research under way at Houston Biotechnology, originated at Baylor College of Medicine, is aimed at preventing this occurrence. The firm has developed a monoclonal antibody, now in clinical test, that can be injected into the capsular space at the time of the cataract removal to inhibit or prevent the opacification action by binding to the epithelial cells.
"No incision" laser surgery
One of the major problems encountered with the development of the injectable lens was the need for complete removal of all lens fragments and cellular matter before a liquid lens could be injected. The usual methods employed involved various solutions that could be injected to soften and emulsify the lens protein, including enzymes. However, according to the researchers at Innovative Surgical Products, the pioneers in this technique, these techniques were difficult to perform in the animal models employed.
One of the hopes for the future of injectable lenses is the possibility of using laser energy to emulsify the lens cortex for complete and easy removal. Several research groups have made attempts at combining laser probes with irrigation/aspiration removal equipment. Several years ago, a small start-up firm in Southern Florida, Photon Sources, developed a prototype laser-I/A device, but after its first announcement, was never heard from again.
More recently, two ophthalmologists independently developed laser phaco-type devices. Drs. Patricia Bath, MD, and James Dodick, MD, have both lectured on and demonstrated their respective devices, one a direct laser ablator and the other utilizing a titanium shield at the end of a laser probe to generate shock waves to fracture the lens material. However, the most likely laser devices to accomplish this task are based on newer non-invasive photocoagulation techniques.
Two recent laser development stage companies, Phoenix Laser Systems and Intelligent Surgical Laser, both located in California, have independently developed accurately focused photocoagulation laser systems that can be scanned into and across the lens cortex, causing it to emulsify within the capsule without damaging surrounding capsular tissue. Neither laser system requires the use of probes entering the lens capsule as both rely on the accurate focus of the laser beam from outside the eye to accomplish the emulsification of the lens material.
If early experiments with this technique are successful in animal models (and the first trial results reported by ISL were encouraging), it could possibly lead to the long-awaited method for cleanly breaking up the bulk of the lens material for easy removal by an irrigation/aspiration device. This would be followed by a syringe injection of an enzyme to remove the remaining cortical debris, leaving a clean capsule for injection of a liquid polymer to recreate a potentially viable "soft" lens that might retain accommodation from the intact capsular zonules attached to the ciliary muscles.
Since both the laser work and development of a truly injectable lens material are still several years from reality, we do not anticipate an injectable lens will be ready for use in clinical practice for the forseeable future.
posted by Irv Arons @ 9:22 PM
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