IMT trials show significant visual acuity and quality- of-life gains for AMD patients.
ROCHELLE NATALONI, CONTRIBUTING EDITOR
Response to VisionCare Ophthalmic Technologies, Inc.'s (Saratoga, Calif.) Implantable Miniature Telescope (IMT) for end stage age-related macular degeneration (AMD) has been almost universally positive from the outset, and now that phase 2/3 trials are complete, investigators in the multicenter study say that visual acuity (VA) gains have far exceeded their expectations.
The investigational implantable telescope, developed by Isaac Lipshitz, MD, is designed to be a permanent solution for moderate-to-profound vision loss due to advanced, end-stage forms of AMD that have no current surgical or medical treatment options. The telescopic implant is 4-mm long and contains 2 wide-angle glass microlenses. Smaller than a pea and equivalent in thickness to about a dozen IOLs, the vision prosthetic is implanted in 1 eye in an outpatient surgical procedure. The device renders enlarged central vision images over a wide area of the retina to improve central vision in the implanted eye, while the non-operated eye provides peripheral vision for mobility and orientation.
The IMT clinical trial enrolled 200-plus subjects at 28 sites across the country. The Food and Drug Administration (FDA) has assigned VisionCare's premarket approval application (PMA) expedited review status, and speculation suggests that approval will be granted by 2007.
VisionCare Ophthalmic Technologies, Inc.'s Implantable Miniature Telescope (IMT).
BENEFITS OF THE IMT
Unlike external telescopes that can be attached to spectacles for magnification, the IMT, in conjunction with the cornea, acts as a telephoto system to enlarge images 2.2 or 3 times, depending on which of 2 IMT models are used. The implanted device affords obvious aesthetic advantages that are lacking in the external telescope. More importantly, the field of view is improved with the IMT because it contains wide-angle microptics and is closer to the macula, which minimizes the vertex distance.
Significant refinements have been incorporated into the current IMT model since its earlier incarnation in the phase 1 clinical trials. "During phase 1, the device had only a 12Þ-field and the current device affords a wider angle enabling 20Þ to 24Þ of field," says Paul Sternberg, MD, George W. Hale Professor and Chair, Department of Ophthalmology & Visual Sciences at Vanderbilt University. "So from a visual field point of view, the scotoma that was impairing the patient's vision is minimized by the IMT's provision of a larger viewable area."
A MULTIDISCIPLINARY TEAM APPROACH
Interestingly, while the IMT serves a retina patient population, it is implanted by anterior segment surgeons as part of a multi-disciplinary team approach that comprises a retinologist, an anterior segment surgeon, and a low-vision or vision-rehabilitation specialist. According to Chet Kumar, director of business and market development for VisionCare Ophthalmic Technologies, Inc., the retina specialist can be viewed as the 'quarterback' in the multidisciplinary medical model that the IMT requires.
"The patient is a retinal patient affected by bilateral end-stage AMD, but the device needs to be implanted by an anterior segment surgeon in the front of the eye for it to render the proper retinal image," Kumar explains.
"The device is a completely rigid, enclosed glass micro-optic telescope that sits in the capsular bag. It is implanted in the lens capsule just like a standard monofocal IOL," says Mark Packer, MD, a clinical trial investigator and an anterior segment surgeon in Eugene, Ore. "This placement allows the lens capsule to fibrose down around the prosthetic, which prevents it from moving," he explains.
Dr. Packer suggests that the multidisciplinary approach necessary for IMT patient management will require a new paradigm in terms of how patients are managed. "This is going to require cooperation between retina practices and anterior segment practices in a completely new way," he says.
Part of the unknown, at this stage, is how the surgery will be reimbursed. "Generally the consensus among the clinical trial investigators was that implanting the IMT is about 3 times more difficult than performing a standard cataract surgery. A new CPT code is being petitioned because this is not standard cataract surgery in any way," Dr. Packer adds.
WORKING WITH A VISION-REHABILITATION SPECIALIST
The mechanics of the device and skillful implantation are only partially responsible for the vision gains provided by the IMT. The remainder of the outcome is dependent on the patient working with a vision-rehabilitation specialist to learn how to use the device most effectively.
"There was a good deal of emphasis in this clinical trial on postoperative training with low-vision experts," says Dr. Packer. "That's a critical piece of the puzzle. Optimal outcomes really take a team approach that starts with the retinal surgeon identifying appropriate candidates, and then progresses to a skilled cataract surgeon and ultimately ends with the low-vision expert or occupational therapist who can teach the patient how to make the most out of this device."
CLINICAL TRIAL OUTCOMES
The 2-year FDA study of the IMT has culminated in better-than-expected outcomes in terms of VA gains of 3 lines or more in a statistically significant number of subjects, as well as in quality-of-life improvements. The mean age of subjects in the prospective, open-label study was 75, and 53% of participants were male. Preoperative mean VA was 20/316, with a range of 20/80 to 20/800. Subjects could have no active CNV within the preceding 6 months and no previous intraocular or corneal surgery. Of the 217 subjects included in the trial, 206 had successful implantations. Eighty-nine percent of patients gained 2 or more lines of distance or near vision; and 87% improved by 3 or more lines.
"I think it's amazing that you can take a patient with a big macular scar and very poor vision and bring them up so significantly. I had a patient who was 20/400 and ended up being 20/80, which is within the realm of decent functional vision. The idea that that was possible was very surprising to me," says Dr. Packer.
The study protocol allowed for 17% or less endothelial cell loss following implantation at 1 year. The final assessment indicated that there was actually a 25% cell loss. "Most of this cell loss occurred during the surgeons' learning curves. There was a higher rate of cell loss between the preop exam and 3-month follow-up than for the remainder of the follow-up period. The average cell count dropped from 2500 down to about 2000 from the preoperative visit to the three-month visit. After that it typically stabilized at about 1900 for the remainder of the follow-up period," explains Dr. Packer. "The initial cell loss is clearly due to surgical technique. I think there's very little chance that the cell loss is due to the presence of the device in the eye. I'm confident that it's due to implantation technique."
Similarly, Stephen Lane, MD, of the department of ophthalmology at the University of Minnesota, also a clinical investigator and medical monitor for the IMT clinical trials, recently reported that endothelial cell density from baseline to 6 and 12 months after [IMT] implantation was reduced due to trauma from the surgical procedure, but was compatible with a healthy cornea. His report in Current Opinions in Ophthalmology concluded that meticulous surgical technique and a comprehensive, multispecialty approach to preoperative and postoperative patient management are essential for successful outcomes.
NOT AN EASY PROCEDURE
Dr. Packer pointed out that the surgical procedure is not an easy one given that the device requires an incision ranging in size from 10 mm to 12 mm, and that the 'plastic haptic,' or 'carrier device,' as the haptics are referred to, has to be placed in the capsular bag. "It's not immediately obvious how to do that," he pointed out, so it took some refinement before surgeons were up to speed.
"Postoperative corneal edema on day 1 was one of the correlations used in the clinical study. If the subject had no corneal edema, or only 1+, the mean loss of endothelial cells was about 13%, but if there was 2+ or greater corneal edema on day 1, then the loss was about 35%," says Dr. Packer. "This is a very significant difference in terms of how well the cornea looked on the first day after surgery with respect to how the endothelium looked long term. Clearly the learning curve is an issue," he says. But, he adds, the clinically meaningful VA and quality-of-life gains outweigh the risks in this older AMD population.
CHOOSING THE RIGHT PATIENT
The learning curve is an issue for recipients, as well. "We require that patients have a trial period with an external telescope and a low-vision expert to see how easily they can learn how to use to device to its full potential. They also have to be able to make a commitment to working with the low vision expert afterwards," says Dr. Sternberg. "Success absolutely requires some rehabilitation and training."
Evaluation of the outcomes of the National Eye Institute's Visual
Function Questionnaire (NEI-VFQ), which was used to gauge postoperative changes
quality of life, suggests that the commitment and rehabilitation are well worth the effort in the vast majority of patients. According to Henry Hudson, MD, principal investigator, Retina Centers, P.C. Tucson, AZ, all of the relevant subcategories showed a clinically significant amount of improvement. Quality-of-life benefits were associated with improvement of vision in the IMT eye, while significant improvement was not associated with change in vision in the fellow eye.
Dr. Hudson and colleagues are currently gathering additional data in an extension study of an additional 50 patients. "We are using a patient assessment survey and an external telescopic simulator to try to define the ideal IMT patient in an effort to narrow the eventual IMT recipients to only those who will really try to optimize it," he says. "This study includes more intensive pre and postoperative evaluation so that we can weed out people who aren't willing to do the hard work."
During phase 1 of the IMT clinical trials, Dr. Hudson says, the aim was simply to implant the devices. The phase 2/3 trials saw investigators asking more questions, such as which eye was preferred for distance vision, in an attempt to improve outcomes. "This is a major procedure, and explanting one of these devices is difficult, so we'd like to get only the best candidates," he said.
Patient expectations play a crucial role. "Some patients' expectations are not met by the optical capability of the device; others are moderately psycho-socially impaired, which precludes them from being good candidates. Some have a decline in their health, or lose their transportation or have some lifestyle change that prevents them from returning for all of the follow-up rehabilitation sessions. There are many more factors than just the stage of the patient's disease that come into play, and now we are trying to identify them ahead of time," says Dr. Hudson.
There are approximately 500 000 to 800 000 people who have end-stage AMD, according to Dr. Hudson, and his clinical experience suggests that 75% of them already have had cataract surgery, which makes the IMT-eligible patient population approximately 120 000.
Despite current advances in the treatment of macular degeneration, Dr. Sternberg points out, there continues to be large numbers of patients who have significant vision loss from macular degeneration in both eyes whether it be from the wet or dry form of AMD.
"The IMT has the potential to be very beneficial to these patients," he says, adding that case selection is going to be critical. "It's way too soon to say who the ideal candidate is. However, we are learning more and more about how to identify the proper patients to make sure that those who receive it are most likely to be able to use it and benefit from it."