The challenges involved in developing an implantable optical device to give sight back to sufferers of end-stage age-related macular degeneration (AMD) are nothing short of immense. Not only must developers understand the disease and create a device that will bring maximum benefit to the patient, there are biocompatibility and sterility issues to address - plus of course the key issue of how to implant the device into the eye itself.
But following a clinical trial involving more than 200 patients at 28 leading ophthalmology clinics across the US and now with the all important FDA approval under its belt, VisionCare Ophthalmic Technologies, a privately held specialty medical device company based in California, is finally in a position to offer end-stage AMD patients its implantable telescope technology.
“Our device is the first of its kind. It is the first FDA-approved implantable medical device demonstrated to improve visual acuity and quality of life in individuals with end-stage AMD,” says Chet Kumar, VisionCare’s VP of business and market development. “There is truly an un-met need for these patients as no drugs or surgical procedures are available to reverse the effects of macular degeneration.”
The optics involved
A close-up of a patient's eye, six weeks after the telescope was implanted. Credit: James Gilman/CRA
VisionCare’s implantable telescope projects an image that would normally be destined for the damaged macula onto healthy retinal cells instead. However, as cells in this peripheral retinal location generate images at a lower resolution, it is essential to magnify the image.
“Unfortunately, if you take any image and magnify it, the field of view decreases,” commented Aharoni. “When we magnify the image on to the retina, instead of having the naturally wide field of view of a normal eye, people have a limited and smaller field of view. A normal eye has a detection field of view of anywhere between 90 to 130 degrees, not necessarily all at high resolution. Our two telescope platforms are wide-angle, offering a magnification of 2.2x and 3x with a relatively large field of view of 24 degrees and 20 degrees, respectively.”
To enable patients to compensate for the peripheral retina being used for central vision, VisionCare only implants its telescope technology into one eye. The implanted eye restores the patient’s central vision, while the untreated eye retains peripheral vision for mobility and orientation. Although this sounds disconcerting, patients are reported to adapt within a few weeks.
The telescope is implanted in an outpatient procedure and involves removing the eye’s natural lens. “The patient’s natural lens focuses images onto the macula, but in end-stage AMD, the macula is no longer functioning and providing central vision,” explained Kumar. “The telescope implant is surgically placed in the capsular bag after the lens has been removed. We essentially use the space where that natural lens was to secure the telescope implant.”
Measuring just 3.6 mm in diameter, the implantable telescope is essentially a telephoto device that, in combination with the cornea, creates a telescopic effect that magnifies objects in view. The device is composed of a sealed glass capsule which contains all of the bi-convex and bi-concave convergent and divergent micro-lenses confined within air pockets to create a magnified image on the retina.
Measuring just 3.6 mm in diameter, the telescopic device is implanted into only one of the patient's eyes - enabling the untreated eye to carry on providing peripheral vision to aid mobility and orientation. Credit: VisionCare.
VisionCare has now completed two clinical trials. An initial trial ran from 2000 to 2002, while the pivotal clinical trial started in 2003 and led to the recent FDA approval. This trial involved many high profile and leading ophthalmology institutions, including the Johns Hopkins University, the Massachusetts Eye and Ear Infirmary and the Wills Eye Institute in Philadelphia.
“The pivotal trial showed that we can improve visual acuity on the eye chart; improve a patient’s quality of life because of the vision we can give back, and finally that the telescope can be implanted safely,” commented Kumar. “We have long-term data with patients five years down the line post-surgery. That’s why the FDA ophthalmic devices advisory panel unanimously recommended our technology for approval.”
Ophthalmologists involved in the study also sing the praises of the implantable telescope technology. “Despite the past decade of advancements in macular degeneration therapies, retina specialists still did not have a treatment for the many wet- and dry-AMD patients who progressed to end-stage disease,” said Julia Haller, Ophthalmologist-in-Chief of the Wills Eye Institute. “Starting today, we can provide these patients with new hope.”
Just like a normal telescope, the implanted device magnifies the image in front of the eye. But instead of being focused onto the macula, that image is projected onto the healthy part of the patient's retina, which has not been affected by AMD and is normally used for peripheral vision. Credit: VisionCare.
“This is truly a breakthrough technology for AMD patients as their treatment options have been limited until now,” added Kathryn Colby, an ophthalmic surgeon at the Massachusetts Eye and Ear Infirmary. “The clinical results from the pivotal FDA trial have proved that we can place this tiny telescope prosthesis inside the eye to help patients see better and, for some, even to levels at which they can recognize people and facial expressions that they could not before.”
According to Kumar, many ophthalmic institutes are now interested in becoming treatment centers. Here, the patient would undergo a strict screening process to ensure that they would benefit from the devices before having surgery. Centers would also provide post-operative care and training on how to adapt to the new levels of vision. “We initially plan to launch across the US, and then expand to Europe and beyond,” commented Kumar.
from University of Arkansas - Little Rock, September 29, 2010
In 1931, the Lion’s Club International began a national program promoting the use of white canes to help the blind “see.” Now, scientists at University of Arkansas-Little Rock are turning to the organization to test a next generation “smart” cane – one that provide details and dimension to enable the sightless to navigate in an a physical environment.
Once the device is built, Ye will partner with rehabilitation specialists at Lions World Services for the Blind — whose headquarters is next door to the UALR campus — and students at the Arkansas School for the Blind in Little Rock to help test the smart canes.
“There are no devices available that assist blind travelers in the way that Dr. Ye hopes the Smart cane will,” said Dr. Larry Dickerson, chief executive officer and president of Lions World Services for the Blind. “We are eager for him to develop a working prototype. We will evaluate its effectiveness and perhaps suggest refinements with the help of our clients who come from all over the United States and our experienced staff.”
Ye and his team of researchers will use Flash LADAR (laser detection and ranging) (LADAR) 3-dimensional imaging sensor to provide the blind user a more detailed “picture” of a physical environment.
Electronic white canes used by the blind and visually impaired people have been around for several years. But Ye’s research hopes to create computer software that can detail where a staircase or a doorway is located in a room; where a drop off in the floor exists; or where an overhead bulkhead can be found. The core technology is 3D data segmentation. Once the program is created, it can be installed in a portable “cane” and provide information orally to a visually impaired person, who then can know the lay of the land.
“This is crucial navigational information that is difficult to obtain by using a conventional white cane,” Ye said. “The data segmentation method can also provide obstacle information such as an overhang obstacle or drop-off. The project’s hypothesis is that a single Flash LADAR sensor can solve blind navigation problems — avoiding obstacles and way-finding. Thus it is possible to build portable navigational device.”
The term “way-finding” refers to how blind people move toward a destination. Finding waypoints, such as stairways, hallways, and the awareness of his or her position contribute to the goal to move from one point to another.
Throughout history, blind and visually impaired peoplehave used canes, staffs — even sighted people used sticks as traveling aids. From the biblical era shepherd’s staffs to the dapper walking sticks of the 19th century, canes have been used as tools for traveling.
A Brief History of the White Cane:
In the early 1920s, a British photographer, blinded following an accident and uncomfortable with traffic around his home, painted his walking stick white to help the sighted take notice of him.
In 1931, the Lions Club International began a national program promoting the use of white canes for persons who are blind.
When the blind veterans of World War II returned to America, the form and the use of the white cane was further altered when Dr. Richard Hoover developed the ”long cane” or “Hoover” method of cane travel.
These white canes, designed to be used as mobility devices, returned the cane to its original role as a tool for mobility, but maintained the symbolic role as an identifier of blind independence.
One Shot of Gene Therapy and Children with Congenital Blindness Can Now See
from University of Pennsylvania School of Medicine , Oct 24, 2009
Born with a retinal disease that made him legally blind, and would eventually leave him totally sightless, the nine-year-old boy used to sit in the back of the classroom, relying on the large print on an electronic screen and assisted by teacher aides. Now, after a single injection of genes that produce light-sensitive pigments in the back of his eye, he sits in front with classmates and participates in class without extra help. In the playground, he joins his classmates in playing his first game of softball.
His treatment represents the next step toward medical science's goal of using gene therapy to cure disease. Extending a preliminary study published last year on three young adults, the full study reports successful, sustained results that showed notable improvement in children with congenital blindness.
Researchers from the University of Pennsylvania School of Medicine and the Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia have used gene therapy to safely improve eyesight
The study, conducted by researchers from the University of Pennsylvania School of Medicine and the Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia, used gene therapy to safely improve vision in five children and seven adults with Leber's congenital amaurosis (LCA). The greatest improvements occurred in the children, all of whom are now able to navigate a low-light obstacle course—one result that the researchers call "spectacular." Although the patients did not attain normal eyesight, half of them (six of 12) improved enough that they may no longer be classified as legally blind. "The clinical benefits have persisted for nearly two years since the first subjects were treated with injections of therapeutic genes into their retinas," said senior author Jean Bennett, M.D., Ph.D., F.M. Kirby professor of Ophthalmology at the University of Pennsylvania School of Medicine. For Bennett, the results build on nearly 20 years of gene studies on hereditary blindness, starting with pioneering work in mice and dogs. "These remarkable results," she added, "have laid a foundation for applying gene therapy not only to other forms of childhood-onset retinal disease, but also to more common retinal degenerations."
"Children who were treated with gene therapy are now able to walk and play just like any normally sighted child," said co-first author Albert M. Maguire, M.D., an associate professor of Ophthalmology at Penn and a physician at Children's Hospital. "They can also carry out classroom activities without visual aids."
Maguire and Bennett have been researching inherited retinal degenerations for nearly 20 years. Leber's congenital amaurosis, the target of this current study, is a group of inherited blinding diseases that damages light receptors in the retina. It usually begins stealing sight in early childhood and causes total blindness during a patient's twenties or thirties. Currently, there is no treatment for LCA.
Walking along a dimly lit, simulated street route, the children were able to negotiate barriers they bumped into before the surgery. Another child, who since birth, could only see light and shadows, stared into his father's face and said he could see the color of his eyes. Later they played soccer together.
For children and adults in the study, functional improvements in vision followed single injections of genes that produced proteins to make light receptors work in their retinas.
The 12 subjects ranged in age from 8 to 44 years old at the time of treatment. Four of the children, aged 8 to 11, are the world's youngest individuals to receive gene therapy for a non-lethal disease (A fifth subject was 17 years old). On the other end of the age scale, the 35-year-old man and 44-year-old woman are the oldest patients to ever receive gene therapy for retinal degeneration.
from Advanced Cell Technology, Inc and Technology Review , June 17, 2009
An experimental therapy using human embryonic stem cells to treat degenerative eye diseases has proved safe and effective in animal studies, and may begin early human trials in the next few months if it receives approval from the Food and Drug Administration. If granted approval, the therapy will be the second embryonic-stem-cell-based treatment to progress to human trials, and it will provide a test case for further applications of stem cells.
While scientists have made huge advances using stem cells to treat diseases in animal models, testing these experimental therapies in humans poses some unique challenges. One is proving that the cells are safe: embryonic stem cells, which can develop into any tissue type in the body, carry the risk of forming tumors. Another challenge is the threat of immune rejection of the transplanted cells; in most cases, introducing foreign cells would require a patient to take powerful drugs for life to suppress the immune system, as is the case with organ transplants. For that reason, the first stem-cell therapies have focused on the eye and nervous system, so-called immune-privileged sites that do not experience this response to foreign cells.
Geron, a biotech company based in Menlo Park, CA, received FDA approval in January for a trial to treat patients with acute spinal-cord injuries with cells derived from embryonic stem cells.
This latest treatment for eye disease, developed byAdvanced Cell Technology (ACT), based in Worcester, MA, uses human embryonic stem cells to re-create a type of cell in the retina that supports the photoreceptors needed for vision. These cells, called retinal pigment epithelium (RPE), are often the first to die off in age-related macular degeneration and other eye diseases, which in turn leads to loss of vision. Several years ago, scientists found that human embryonic stem cells could be a source of RPE cells, and subsequent studies found that these cells could restore vision in mouse models of macular degeneration.
This microscopic image shows a cross section of the retina of a rat with a degenerative eye disease that received a transplant of retinal cells derived from human embryonic stem cells. The middle layer of speckled green represents several layers of photoreceptors, which developed in response to the transplant. Untreated animals lost all but a single layer.
Credit: Advanced Cell Technology
In a recent study published online in the journal Stem Cells, researchers from ACT and Oregon Health Sciences University show that their stem-cell therapy provides a long-term benefit in animal models of vision loss. A second experiment tested the long-term safety of the cells in mice--an important requirement for moving into human testing--and found no evidence that the cells cause tumors.
To test the efficacy of the cell transplants, the researchers injected RPE cells derived from embryonic-stem-cell lines into the eyes of rats with a genetic defect in their RPE that causes their vision to gradually deteriorate. After three months, the retinas of treated rats had many more photoreceptors than those of untreated diseased rats, and the treated animals performed better in vision tests; however, their performance in the tests diminished with time. The transplants were also able to improve vision in a mouse model of Stargardt's disease, a rare but untreatable illness that causes blindness early in life.
Stem Cell Contact Lenses Can Cure Blindness in Less Than a Month
from the Australian, May 28, 2009
Three Australians have had their sight restored thanks to their own stem cells and ordinary contact lenses
Individuals with low or no vision will be excited about a new research effort in Australia that restored sight to 3 blind individuals in less than a month by contact lenses cultured in stem cells.
To obtain the stem cells the Researchers took less than a millimeter on the side of each patients cornea. They then cultured stem cells from the tissue in extended wear contact lenses.
The surface of the patients' corneas was cleaned and and the lenses inserted. Within 10 to 14 days the stem cells began to attach to the cornea, replenishing damaged cells. Satisfied that the stem cells were doing their job, the researcher removed the lenses and the patients have been seeing with new eyes for the last 18 months.
Although the innovative technique was used to reverse blinding corneal disease, it promises to be a quick, painless and cheap treatment for other visual disorders. To read more about it, click here.