In late August, Alcon surprised the ophthalmic world by withdrawing the CyPASS Micro-stent from the market due to issues with significant endothelial cell loss in a post-ap­proval study called COMPASS-XT. Surgeons have been left wondering about the data that went into the decision, the mechanism behind the cell loss and how to handle existing glaucoma patients who already have the CyPASS in their eyes.

In the COMPASS-XT study, which was a three-year extension of the original two-year COMPASS study that was used to secure approval of the device, researchers studied the safety and efficacy in patients who underwent cataract surgery plus CyPASS implantation, compared to cataract surgery alone. The exact rates of cell loss still have not been shared by Alcon. “What we do know from the COMPASS study is that ECL was similar between the phaco-CyPASS arm and the phaco-only control arm,” says Malik Kahook, MD, professor of ophthalmology and the Slater Family Endowed Chair in Ophthalmology at the University of Colorado School of Medicine. “We don’t have access to the data beyond the two-year COMPASS trial data. Alcon recently reported that the ECL difference between control and study arms increased after the two-year time point. We don’t know what the exact numbers are for either arm of the study at this time, though Alcon did share that the number of patients with severe ECL (>30-percent loss from baseline) was more than two times higher in the CyPASS arm. It will be of interest to all practitioners to get the specific numbers so we can better understand the issue at hand.”

At this point, the mechanism by which the CyPASS induces the cell loss hasn’t been explicitly defined either. Atlanta glaucoma specialist Reay Brown, who participated in the COMPASS study and presented the pivotal results at the annual meetings of the American Academy of Ophthalmology and the American Society of Cataract and Refractive Surgery, was completely surprised by the withdrawal. “It was a total surprise to me that this happened,” he says. “I thought the cornea wouldn’t have any problems at all. It’s mystifying that you can put in an anterior-chamber IOL that’s much bigger and seems to be more of a potential problem, and have those patients do very well, while this tiny device that seems very stable can cause the kind of endothelial cell loss that Alcon has seen in its five-year data.” 

Surgeons speculate that the problems may have something to do with devices that protrude too far outside the tissue in which they’re implanted, which is just below the trabecular meshwork. “At this time, we have very little specific information from Alcon on the mechanism of ECL, and it is not clear if they have a firm understanding of the mechanism either,” says Dr. Kahook. “What has been made public is that there is an association between devices that are positioned too far into the anterior chamber and the observed ECL over time. It is not clear if devices moved postoperatively, other than anecdotal reports by physicians on discussion boards. Anything beyond this would be pure speculation.”

Sacramento glaucoma specialist, Richard Lewis, who consults for Alcon, says the revelations about endothelial cell loss need to be put into context. “The surgeons in the original COMPASS trial were good surgeons who were given a new device and instructed on approximately where to put it, but there wasn’t really good guidance in terms of how far to put it into the eye,” he says. “Some surgeons I’ve spoken to like to see the tip of the tube [poking out of the tissue] while others like to put it farther in. Fast forward to today; if we were to do the study now, we’d put the device flush with the tissue—there’d be no extension. But we didn’t know that then. So, the data is a little bit misleading, because it was a brand-new device with a learning curve. Someone had to put the first set of devices in, and just as with iStent and Hydrus, all of us learned along the way as we did it.

“Also, no other device has been requested to perform a five-year follow-up of endothelial cells,” Dr. Lewis continues. “You could argue that it’s good that they did so, but perhaps if Alcon had known it was going to be followed for five years, greater precautions would have been taken, and better training administered, before they enrolled these patients. Perhaps they could have gotten better surgical outcomes if they had these surgeons do five or 10 patients before they entered the study, so they could develop a better surgical skill set.”

Surgeons are now left to manage current CyPASS patients, and are adopting their own systems for dealing with them until more official recommendations are released. “I put some CyPASS devices in the week before it was withdrawn,” says Dr. Brown. “That led to a weird conversation a week later: ‘Mrs. Jones, you’re doing well with your CyPASS that I put in last week, and oh, by the way, it’s been recalled.’ But that’s what you have to do. I then explain as much as I know to them. I’m monitoring them with endothelial cell counts. On a conference call shortly after the withdrawal was announced, Alcon’s Steve Lane, MD, shared the impression that the more the CyPASS was exposed into the AC, the greater the endothelial cell loss. This leads to the question: Should we push the existing ones farther in? A few people on the call had experience doing that, and said it was difficult to push in farther, so they didn’t advise it.”

Though there haven’t been any official recommendations, some surgeons are going back to the OR and trimming CyPASS stents that appear to be protruding too far, with some specifically saying you don’t want more than one of the retention rings at the top of the device showing. “Right now, the guidelines of what should be trimmed are being worked out,” Dr. Lewis says. He adds that the trimming procedure doesn’t appear very involved. “I haven’t done it yet, but I have one coming up in a few weeks,” he says. “I told the patient it should just take a few minutes. The surgeon visualizes it, cuts it and is done.” 

Dr. Brown says he’s hesitant to trim a device, though. “My own approach to something like this is, first, do no harm,” he says. “I have patients who are now seven years out post-implantation who have no problems, and it makes it hard for me to do something that carries with it its own endothelial cell trauma. If you’re going to trim the end of a tube, you’re going to have some endothelial cell loss from that, as well. It’s hard to know what to do at this point.”

While surgeons await the ASCRS recommendations on the CyPASS situation, many of them say they’re in mourning over a device that had a lot of potential. “I really hope it comes back,” says Dr. Brown. “I think it filled a niche that was really important. It had enough efficacy to help patients who had real glaucoma damage, and you could use it at any point in the glaucoma cycle. I put it in several patients who had previously undergone tube shunts, trabeculectomy, angle surgery—basically every operation we have for glaucoma—and they did really well with the CyPASS. It had been the answer to a prayer.”  REVIEW