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News in Review
A Look at Today's Ideas and Trends
Two New Ideas for Presbyopic Eyes
The hallway chatter at the spring ASCRS meeting in San Francisco included talk of two high-tech ideas that someday might be to IOLs what LASIK has become to spectacles.
One idea for restoring youthful accommodating power to the aging, presbyopic eye involves a polymer gel that mimics the mechanical properties of the natural crystalline lens. The other involves a procedure that allows the eye to regenerate.
Both approaches have been demonstrated in animal models; either one of them has the potential to solve a problem with the current generation of accommodating IOLs, which is that they often lose zooming capacity due to capsular fibrosis.
Gel that mimics natural lens. “What we have is proof of principle,” said Thom Terwee, engineer and manager of biophysics for AMO Groningen BV (the Dutch branch of Advanced Medical Optics). That proof is a gel with a refractive index of approximately 1.43, and the elasticity of a young crystalline lens, developed in Groningen by a team of polymer chemists and biophysical scientists.
First, the Dutch team had to determine the modulus, or “squishiness,” of the natural lens, which they did by measuring cadaver eyes. “When we found this figure, we could match it with polymer science,” Mr. Terwee explained.
The result was a highly viscous silicone prepolymer consisting of two substances that, when mixed together and injected with a standard needle, turn into a gel inside the capsular bag. Entry is through a 1-millimeter capsulorhexis, an optimal size for plugging the tear. Mr. Terwee credited the surgical skill of ophthalmologist Steven Koopmans, MD, University of Groningen, as one of the main reasons the procedure worked.
And it did work—for up to nine months in adolescent rhesus monkeys. Accommodative amplitude in the refilled lenses started at 6.5 D.
But by nine months it decreased to 2.5 D. The problem: postimplant rapid proliferation of lens epithelial cells (LECs) that triggered lens sclerosis.
Now back at the drawing board, Mr. Terwee’s team is investigating the use of anti-inflammatory eye drops to prevent such a strong LEC response in the capsular bag.
Regenerating the eye. A similar problem has plagued the lens regeneration work of Arlene E. Gwon, MD, medical research investigator for AMO in California. The same cells that cause posterior capsular opacification after IOL implants are the type she harnessed to regenerate the crystalline lens in animal models.
In a review of regeneration research dating back to 1825,1 Dr. Gwon explained that lens regeneration follows a course similar to embryological development: The LECs first cover the anterior and posterior capsule, then progressively add cell layers that eventually orient themselves to form a normal-appearing crystalline lens. A variety of known growth factors may play a part in this process, including fibroblast growth factor and insulinlike growth factor.
Reporting at ASCRS on her research, which began in the early 1980s, Dr. Gwon outlined how she had succeeded in regenerating a new lens that fills the capsular bag as early as two months following endocapsular lens extraction.
The procedure entails cutting a 2-mm capsulorhexis, then patching the tear with a collagen shield. Provided the anterior and posterior capsules don’t stick together, the normal stages of embryonic growth may begin within two weeks, and the new lens may fill the capsular bag, forming a normal, spherically shaped new lens, in as little as two months. However, some kind of cellular disturbance causes a star-shaped opacity to appear in the lens nucleus.
To prevent this aberrant growth, Dr. Gwon inserted a biodegradable scaffold onto which the cells could cling. But the small amount of Restylane, a biodegradable hyaluronic acid approved for cosmetic purposes, was not resorbed in the capsular bag as intended. Instead, the lens grew around it, resulting in a second complication: central opacity.
Though full regeneration of a crystalline lens has not yet been demonstrated, Dr. Gwon believes that the human lens epithelium is capable of proliferation and differentiation. She said redirecting lens cells to grow in a normal manner “is a real possibility.”
The first analysis of the results from the Tube Versus Trabeculectomy (TVT) glaucoma study showed some clear differences in the incidence of complications and in the procedures’ ability to control IOP, study leaders reported at this year’s American Glaucoma Society meeting.
Nearly half of the 212 patients in TVT developed postoperative complications in the first year after surgery, and most of those came in the trabeculectomy eyes, said coinvestigator Leon W. Herndon, MD, associate professor of ophthalmology at Duke University. Nearly two-thirds of the 96 patients with postop complications were in the trabeculectomy group, he said (P = 0.001). But not all complications are equal (see chart).
The nonvalved Baerveldt implant used in the study also had a statistically significant edge in showing a lower cumulative probability of failure during the year, reported study cochairman Steven J. Gedde, MD, associate professor of ophthalmology at the University of Miami.
The implant was more likely than trabeculectomy to maintain adequate IOP control without persistent hypotony or requirement for additional surgery, Dr. Gedde said. But the tube group needed twice as many medications to keep their IOP in check.
Intraoperative complications did not differ between the two groups, nor did the incidence of additional operations to manage complications, Dr. Herndon said.
When a third-year medical student’s clinical clerkship note describes a patient’s disease with ophthalmic implications, but the eye examination is ignored completely, then something is very wrong with the way we’re educating future physicians,” said ophthalmology professor Linda S. M. Lippa, MD, director of ophthalmology medical education and member of the Dean’s College of Medical Educators at the University of California-Irvine.
A paper that she and three primary care colleagues published in the January Ophthalmology1 laid out some sorry facts:
“In an increasingly crowded curriculum, medical schools marginalize subspecialty areas,” Dr. Lippa said. “Most schools no longer require an ophthalmology clerkship. Skills are eroding and consult requests forgotten. Unless departments work to reverse this trend, patient medical care will suffer.”
Presentation of her initial data in 2002 to the California Consortium for the Assessment of Clinical Competence was a wake-up call. Consequently, either fundus photos or a simulator exercise have been included in the statewide Clinical Performance Examination since 2003. Her work has sparked interest from the Association of American Medical Colleges’ clinical skill task force, the Association of University Professors of Ophthalmology and the National Board of Medical Examiners.
“Early results from ongoing studies with UC-Irvine’s new and innovative curriculum indicate that students enjoy practicing with CLEO —who doesn’t blink or complain—and their performance subsequently improves in charted exams, on formal simulator testing and observed patient exams,” said Dr. Lippa.
“Now, increasingly, medical schools across the country are adding funduscopic simulator teaching and, more important, objective eye examination skills assessments to their curriculum,” she said.
Charles L. Schepens died March 28 after suffering a stroke a day earlier. He was 94.
Among Dr. Schepens’ many contributions to ophthalmology were development of the binocular indirect ophthalmoscope, and of modern techniques of retinal detachment surgery, especially scleral buckling using silicone materials. He also established the Retina Foundation, Boston, now known as The Schepens Eye Research Institute.
Eight days before his death, Dr. Schepens was made a Knight of the Legion of Honor, France’s highest award, for his service to the French Resistance in World War II and for his advancements in diagnosis and treatment of retinal diseases. In 2003, the Academy presented him with its Laureate Award, recognizing him as “the father of modern retinal surgery” and as one of the first to understand that progress in the clinic is tied to ophthalmic research. The Consul General of France in Boston, Mr. François Gauthier, gave a speech during a ceremony honoring Dr. Charles Schepens with the French Legion of Honor on March 21, 2006.
Dr. Schepens was born in Belgium in 1912. After medical school he studied in 1937 in Utrecht in the Netherlands, with Henricus Weve, MD, a specialist in treatment of retinal detachment. Then he went into service with the Belgian air force, joined the Resistance, and moved to the Basque town of Mendive to work with the French Underground. In 1945, he did his fellowship at Moorfields in London, after which he became a fellow in ophthalmic research at Harvard University. In 1949 he established and became the director of the retina service at the Massachusetts Eye and Ear Infirmary, the first such service of its kind.
The Ophthalmic Heritage & Museum of Vision has an excellent, brief biography about Dr. Schepens, complete with personal photos at: http://www.aaofoundation.org/what/heritage/exhibits/online/Schepens.cfm.
In 2003, Dr. Schepens received the Laureate Award from the American Academy of Ophthalmology, its highest honor. For a link to this recognition, please visit: http://www.aao.org/member/awards/laureate/schepens.cfm.