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MIGS implants make headway with support of larger companies
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Based on safety and efficacy evidence gathered from studies over a fairly long period of time, microstents promise to become a well-established option in glaucoma management.
Three devices have been acquired by large eye care companies: the Xen gel stent (AqueSys) by Allergan, the CyPass micro-stent (Transcend Medical) by Alcon and the InnFocus microshunt (InnFocus) by Santen.
According to Tarek Shaarawy, MD, MSc, “The marketing machines of these companies will push these technologies from a niche into the mainstream. Their role is going to increase, and in a few years there will be a flourishing in the use of these devices, not only by the glaucoma surgeon but much more importantly by the phaco surgeon.”
Drainage implants have a long history in glaucoma surgery. What is new in the latest generation is the “minimally invasive” approach that, through a process of trial and error and after several failed attempts, has achieved encouraging results with a few devices. The common goal is to lower IOP, enhancing aqueous outflow through the subconjunctival space (Xen and InnFocus), the trabecular meshwork and Schlemm’s canal (Glaukos iStent and Ivantis Hydrus) or the suprachoroidal space (CyPass). Most of these procedures are performed ab interno.
Image: Shaarawy T
Patient selection, realistic expectations are key
Choosing which device to use should depend first on eye anatomy and target pressure, Herbert Reitsamer, MD, PhD, said.
“It depends on whether you have sufficient conjunctival tissue available, on whether the angle is open and wide enough. There can be plenty of different obstacles in the way of choosing a particular stent. Target pressure is also important, which depends on a variety of factors, not just on glaucoma stage. For instance, a young patient with early glaucoma may require a lower target pressure than an older patient with advanced glaucoma,” he said.
However, there is a limit to the potency of minimally invasive glaucoma surgery (MIGS) implants. Reitsamer was involved in most of the European MIGS trials, and currently Xen is, in his opinion, the one that can achieve the lowest IOP levels.
“However, if you need IOP in the low teens, like 10 mm Hg to 12 mm Hg, there is no MIGS implant so far that can give you that pressure without drops in addition. If you have patients who do not tolerate drops, and they are more and more, no MIGS procedures can give you this very low pressure. This is one of the major shortcomings. You gain surgical safety, but if you don’t reach the necessary target pressure, the goal of therapy is missed,” he said.
Shaarawy said that virgin eyes and combination with cataract surgery are additional factors that lead to best results. All things considered, patient selection and realistic expectations are key.
“If you select your patients well, these devices lead to good results. We may have to lower our expectations, so that neither us nor our patients get disappointed, but within their limits they are good and safe procedures, and I am sure the future will bring even better results and a longer list of indications,” he said.
Shaarawy has taken part in the Xen, InnFocus and CyPass studies, and he has used all MIGS implants frequently.
“There is one of them that I prefer, but since my preference is based on ease of use, comfort level and the results I have seen rather than objective evidence, I don’t think this qualifies as important information to share with my colleagues,” he said.
Whether eye stents will be the way to make surgery become first-line treatment, it is too early to tell.
“I still think we should start with medications. In a few selected cases we may start with SLT instead, but we don’t have enough experience and knowledge to start a patient on surgery immediately,” Shaarawy said.
Making surgery accessible to a large number of patients
Microstents will play an important role in the management of glaucoma, according to Magda Rau, MD. They will offer an alternative to multiple medications for people with ocular surface disorders, a minimally invasive alternative rather than classic glaucoma surgery.
“It’s going to be a breakthrough that makes surgery accessible to a large number of patients,” she said. “Small companies have done a tremendous job developing and investigating eye stents, and now big companies like Alcon will be able to push this technology into the market. Insurance companies in all countries will recognize that it is worthwhile to pay for MIGS implants because they are relatively low cost and can save sight for a lot of people.”
Rau prefers blebless procedures, mainly the CyPass.
“I don’t have experience with the Xen because I don’t like the idea of using mitomycin, which is expensive and has side effects, nor the idea of having a bleb. I use the iStent in some cases, but in patients with a sufficiently wide angle, Shaffer 3 or 4, my best choice is the CyPass,” she said.
The CyPass creates permanent drainage toward the suprachoroidal space. Suprachoroidal outflow may account for about half of the aqueous humor drainage. There are fenestrations all along the tube, which enhance the outflow, and the lumen is 0.3 mm. The operation is ab interno through a 1.8-mm temporal incision. The stent is placed between the sclera and choroid in the supraciliary suprachoroidal space, adapting to the curvature of the globe.
Rau has taken part in European studies of the CyPass, including the pilot studies and the post-market CyCLE study. Following the results of the COMPASS study, the CyPass was approved by the FDA in the U.S.
“All studies confirmed that the CyPass is effective in reducing IOP and that the effects are maintained even after 4 years. In my group of patients, IOP was reduced to less than 21 mm Hg in 100% of cases and to less than 15 mm Hg in 60% of cases. Approximately 20% of patients are off medications or have significantly reduced medications,” she said.
However, Rau noted that glaucoma is by nature a progressive disease.
“Sometimes progression cannot be stopped and we have to add more medications. In some cases we have to perform trabeculectomy, but this is possible because CyPass spares the conjunctiva,” she said.
Bypassing medication compliance issues
In the future, for the mild stages of glaucoma, stent surgery may become first-line treatment before starting medications, according to Lilit Voskanyan, MD, PhD.
“Eye stents work well, and the only complication is that they may not work. Both patients and doctors have a tough time with compliance to medications, and IOP fluctuation is also a problem. Stents are better for stability of IOP. Even with pressure in the high teens, the optic nerve is not affected because IOP is stable,” she said.
Voskanyan has participated in studies with the iStent and has implanted hundreds of patients; many of them, 40% to 50% of those with mild to moderate glaucoma, are stable and still off medications after 5 years.
Three generations of the iStent have been produced over the years. The first generation, iStent, is an L-shaped titanium tube that connects the anterior chamber with Schlemm’s canal and allows aqueous outflow to bypass the trabecular meshwork. The second, iStent inject, is cone-shaped and smaller, and the third, iStent Supra, uses the suprachoroidal drainage pathway.
“I use them all and very much like the possibility of combining them to enhance efficacy. All of them are good individually for mild to moderate glaucoma, while for advanced glaucoma, I like to combine [the first and third generations] to have the advantage of two drainage pathways,” Voskanyan said.
Combination with cataract surgery also enhances results.
“I have patients with both eyes implanted and only one combined with cataract surgery. This second eye does a lot better and is off medications while the first one is not,” she said.
Armenia has a high prevalence of glaucoma and a high number of people for whom medications are too expensive. Stent surgery is affordable and bypasses the problems of cost-related poor compliance.
“We have done a lot with the iStent. In the beginning we had a high percentage of non-responders because we were treating patients with advanced glaucoma. But now, with clearer indications and accurate patient selection, failure rate is down to 10% in my patients,” she said.
Voskanyan wishes to be able to understand before surgery who are the best responders.
“Sometimes you have two patients with identical angle conditions and everything else just fine, and when they go through surgery, one does well and the other does not respond,” she said.
A less invasive alternative to trabeculectomy
According to Ike K. Ahmed, MD, FRCS, MIGS procedures that aim at the internal outflow pathways, such as iStent, CyPass and Hydrus, have good synergy with cataract surgery but are not always potent enough to be used in most cases as a standalone procedure.
“They are applicable to the group of patients who are more in the mild to moderate phases with the purpose of reducing medications rather than dropping IOP,” he said.
For those patients who require a very low target IOP, stents that drain in the subconjunctival space and create a bleb, such as Xen and InnFocus, are his preferred approach because they have the highest chance to get people off medications and reach low pressure targets, “which is the ultimate combination we look for in most glaucoma patients.”
“Pressure lowering is quite similar to trabeculectomy but is obtained in a more controlled, efficient, less invasive manner. Easier postoperative management and, ultimately, safer blebs make it attractive,” Ahmed said.
The Xen is made of a soft collagen-derived gelatin material. It is implanted ab interno and creates a diffuse outflow of aqueous from the anterior chamber into the subconjunctival space. The InnFocus is a micro-tube made of SIBS, a soft biomaterial used for many years in coronary stents. It also drains subconjunctivally and requires ab externo implantation through a small conjunctival opening.
“Right now we don’t have head-to-head comparative data. Certainly there is more surgical dissection required with the InnFocus and the InnFocus may get pressure lower by a couple of points, but the Xen is a very efficient procedure. It is ab interno and requires no conjunctival dissection. In patients who are more likely to scar down, with a higher risk of bleb fibrosis, who need the lowest possible target IOP, the InnFocus might be the preference, while in patients who are not expected to scar down or heal very fast and don’t need pressure as low as with trabeculectomy, I might prefer the Xen, but it is hard to say that right now because we don’t have enough data or experience to compare the two devices,” Ahmed said.
His success rate with both devices, on their own or combined with cataract surgery, is high, he said.
“They make it realistic to think that we may replace trabeculectomy, and I already find myself using them even more than trabeculectomy because of the enhanced safety and control of the procedure,” he said. – by Michela Cimberle
- References:
- Ahmed II, et al. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2014.07.004.
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- Lenzhofer M, et al. Fourth year long-term follow-up results after minimally invasive transscleral Xen glaucoma gel stent ab interno implantation in a prospective multicenter trial. Free paper presented at: Congress of the European Society of Cataract and Refractive Surgeons; Sept. 10-14, 2016; Copenhagen, Denmark.
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- For more information:
- Ike K. Ahmed, MD, FRCS, an OSN U.S. Edition Glaucoma Board Member, is director of the Glaucoma and Advanced Anterior Surgical fellowship at the University of Toronto. He can be reached at Credit Valley EyeCare, 3200 Erin Mills Parkway, Unit 1, Mississauga, Ontario L5L 1W8, Canada; email: ike.ahmed@utoronto.ca.
- Magda Rau, MD, OSN Europe Edition Associate Editor, is medical director of Augenklinik Cham, Germany. She can be reached at Augenklinik Cham, Cham, Bavaria, Germany, 93413; email: info@augenklinik-cham.de.
- Herbert Reitsamer, MD, PhD, is senior physician and professor at Parcelsus University of Salzburg, Austria. He can be reached at Salzburger Landeskliniken – Landeskrankenhaus, Müllner Hauptstr. 48, A-5020 Salzburg, Austria; email: ha.reitsamer@gmail.com.
- Tarek Shaarawy, MD, MSc, OSN Europe Edition Board Member, is head of glaucoma at Geneva University Hospital. He can be reached at Hôpitaux universitaires de Genève, 22 rue Alcide Jentzer, 1211 Genève 14, Switzerland; email: tarek.shaarawy@hcuge.ch.
- Lilit Voskanyan, MD, PhD, is head of glaucoma at Malayan Ophthalmologic Center in Yeravan, Armenia. She can be reached at Ophthalmologic Center after S. V. Malayan, Yerevan, Republic of Armenia; email: lilit.voskanyan@yahoo.com.
Disclosures: Ahmed reports he is a consultant to Alcon, Allergan, Glaukos, InnFocus and Ivantis. Rau reports no relevant financial disclosures. Reitsamer reports he is a consultant to Allergan, Abbott Medical Optics, AqueSys, KeloTec, Novartis, Santen, Schwind eye-tech solutions, Transcend and Zeiss. Shaarawy reports no relevant financial disclosures. Voskanyan reports she is a consultant to Glaukos.
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