IMT trials show significant visual acuity and quality- of-life gains for AMD patients.
NATALONI, CONTRIBUTING EDITOR
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
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
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
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
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."
Retinal Physician, Issue: July 2006