End-stage AMD device waiting FDA approval

Implantable miniature telescope can return central vision in most, but patient selection remains critical

The implantable miniature telescope is the key part of the CentraSight system for the
treatment of end-stage AMD; other parts include the surgeon and patient selection and
low vision specialists
Source: VisionCare


The telescope after implantation
Source: James Gilman.

In late March of 2009, the Food and Drug Administration (FDA) Ophthalmic Devices Advisory Panel unanimously recommended that the FDA approve the implantable miniature telescope (VisionCare Ophthalmic Technologies, Saratoga, Calif.) for patients with end-stage age-related macular degeneration (AMD). The unanimous recommendation (8-0) included conditions such as post-approval surveillance and labeling suggestions.
“Everyone’s hopeful it will be approved by the end of the first quarter in 2010”,” said Stephen S. Lane, M.D., clinical professor of ophthalmology, University of Minnesota, Minneapolis, and the medical monitor for the FDA clinical trial. He said the FDA and VisionCare are still working out the post-market survey and monitoring details.
The device itself is a visual prosthetic device that “creates” a telephoto lens when placed in the eye, helping to improve visual acuity of patients with bilateral moderate-to-profound visual loss secondary to end-stage AMD, according to the Devices Panel. The device is surgically implanted in the posterior chamber, in place of the eye’s crystalline lens and, like an IOL, is held in position by haptic loops. Magnification is available for 2.2X and 3.0X in two wide-angle models.
“Meticulous surgical technique” and a comprehensive approach to both pre- and post-op patient management are “essential for successful outcomes,” according to Dr. Lane and Baruch D. Kuppermann, M.D., associate professor of ophthalmology, University of California, Irvine. The two co-authors analyzed results of the Phase II/III IMT002 prospective, multicenter study.1
“This device has significant relevance because end-stage AMD is such a devastating disease with overwhelming consequences for the patient. There’s not much currently available that can help make their vision better,” Dr. Lane said.
Although external telescopes have been used in the past, there are not any “significant options for improved distance vision,” Dr. Lane said.
In short, the IMT allows “this desperate group of patients a chance to improve their central vision. In the clinical studies, vision improved by two or more lines in more than 95% of the patients and by 3 lines in over half the patients. When you’re talking about taking patients who are counting fingers to 20/400 or 20/200, that’s a significant improvement in their quality of life.”
The device is not appropriate for all patients with end-stage AMD, however.
“The patients it’s going to help the most are those with certain characteristics: advanced geographic atrophy and truly end-stage disease,” said Jeffrey S. Heier, M.D., vitreoretinal specialist, Boston, and an investigator for the device. “These are patients with wet disease, who are on Lucentis [ranibizumab injection, Genentech, South San Francisco, Calif.] or Avastin [bevacizumab, Genentech] or another anti-VEGF therapy. The most likely success will come for patients who have as relatively stable a disease as possible.”
A key to ensuring device implantation success will be how the patient is screened and “how the images appear at the time of screening. Patients with evolving lesions are not good candidates,” Dr. Heier said. Overall, if there are 1.75 million cases of advanced AMD, “about 400,000 to 500,000 will have geographic atrophy, and some will have disciform scarring as well. It will be difficult to know exactly how many patients may benefit until we start screening them.”

Study results

Results from the Phase II/III study enrolled 218 consecutive subjects at 28 clinical sites (206 underwent the surgical procedure). In order to be included in the study—and its counterpart, IMT-002-LTM, for long-term follow-up—patients had to have clinical retinal findings of geographic atrophy or disciform scar with foveal involvement (determined by fluorescein angiography), evidence of cataract, at least a five-letter improvement on the ETDRS chart with an external telescope, adequate peripheral vision in the eye not scheduled to receive the implant, and had to be willing to participate in post-op visual training/rehabilitation. The long-term study (still underway) is evaluating 129 of the original subjects for an additional 36 months.
The 6-month results found 89% (178 of 201 eyes) had at least a two-line improvement in mean distance or near BCVA. Mean corneal endothelial cell density decreased significantly through 6 months, but then seemed to level off between 6 and 12 months, from a mean baseline of 2,492 cells/mm2 to a mean of 1,870 cells/mm2.
Although the endothelial cell loss “was found to be significant in a number of patients enrolled in the study at the time of surgery, we found it levels off at a 2 to 3% loss per year, which is much more typical of someone who’s had cataract surgery with typical phacoemulsification and IOL implantation,” Dr. Lane said. “I believe the institution of techniques during surgery that we learned with the clinical trial can greatly reduce surgical endothelial cell loss.”
Understanding the patient’s visual limitations and how the device may help improve quality of life is “more than a reasonable tradeoff” for the potential increased endothelial cell loss at the time of surgery, he added.
The key to minimizing dissatisfaction with the device is two-fold: higher baseline levels of endothelial cells and patient motivation.
“Screening will be a major key to the success of this device,” Dr. Heier said. “It’s very clear that’s the case now. People will go through rigorous screening with low vision specialists and need to have realistic expectations for the device.”
Patients who readily adapt to using external telescopes pre-op and who are fully committed to working with low vision specialists before and after surgery will likely be the most successful, he said.

Learning curves

Surgical implantation of the device is very different “from anything we’ve done recently as cataract surgeons in that the device is very large,” Dr. Lane said (the device measures 4.4 mm in height and 3.6 mm in diameter contained within a 6 mm plate, with a 13 mm overall length). Even though the device has haptics, “it really does not follow the standard characteristics of an IOL; it’s a low-vision device that’s being placed in the eye through a large incision.”
He said most cataract surgeons might believe the implantation technique is taking a step backward, as they’ve been used to smaller incisions during the recent past with the advances that have been made in small incision phacoemulsification and foldable IOLs.
“This is really not a lens implant,” he cautioned. “There’s a different mechanism for placing it.” Additionally, the device is larger and heavier than might be expected (about 115 mg free-standing) and its haptics are “less flexible than found on one-piece PMMA IOLs.”2 The implant will require additional surgical time, as well as a retrobulbar block and sutures.2
Techniques learned from the study investigators led to a recommendation of 10 to 11 mm incision sizes as most effective, Dr. Lane said.
“We’re really not trying to minimize the wound size,” he said. “The device can be implanted through a smaller incision, but you run the risk of higher endothelial cell loss.”
In his hands, he prefers to use “copious” amounts of ophthalmic viscoelastic devices “on the lens implant and to maintain the chamber, and to perform as atraumatic insertion of the device as possible.”
He recommends using a cohesive OVD to open the capsular bag and maintain the space, and a dispersive OVD over the device itself.

Patient commitment

The implant is part of a comprehensive rehabilitation process that involves the ophthalmologist, low-vision specialist, and patient.
“One of the things we’ve emphasized is that our best success with these patients has come when there’s an experienced corneal/cataract surgeon, retina specialist, and low vision experts involved,” Dr. Lane said. “The team approach has yielded the best results.”
Follow-up surgical care is “less important than follow-up with a low vision expert,” Dr. Lane said. “They teach patients how to use their new vision. These are people who have gotten used to minimal or no central vision. The implant produces a larger image over the damaged macula, so the non-IMT eye sees peripherally and the IMT eye is used to see centrally.”
Dr. Heier agreed that the “happiest and most successful patients in the study were those who worked with the low vision specialists to ensure they got both the initial and long-term benefits of the device.” He said the patient commitment to follow-up is critical—especially in the first year after device implantation.
“Our role as ophthalmologists becomes more typical after implantation—much like post-cataract follow-up to ensure there were no surgical complications. The majority of it, though, is between the patient and the low-vision experts,” Dr. Heier said.

References:
1. Lane SS and Kuppermann BD. The Implantable Miniature Telescope for macular degeneration. Curr Opin Ophthalmol. 2006;17:94-98.
2. Colby KA, Chang DF, Stulting RD, Lane SS. Surgical placement of an optical prosthetic device for end-stage macular degeneration: The implantable miniature telescope. Arch Ophthalmol. 2007;125(8):1118-1121.

Editors’ note: Dr. Lane is the medical monitor for the IMT and a consultant for VisionCare (Saratoga, Calif.). Dr. Heier is the retina medical monitor for the IMT, an investigator for the device, and a consultant for VisionCare.

Contact information

Heier: 617-314-2694, jsheier@eyeboston.com
Lane: 651-275-3000, sslane@associatedeyecare.com