Traditional surgical therapies for open-angle glaucoma such as trabeculectomy and aqueous shunts attempt to lower IOP by redirecting aqueous outflow to the subconjunctival space. What if surgeons could improve outflow with an ab interno approach that bypasses the trabecular meshwork and reroutes aqueous from the anterior chamber directly into Schlemm's canal without disrupting the scleral surface? Such was the thought process that led Richard A. Hill, MD, to the concept behind the iStent trabecular bypass (Glaukos Corporation, Laguna Hills, CA).
Realizing a Concept
Working with a design team from Glaukos Corporation, Dr. Hill developed a small, L-shaped, micromachined, titanium device that is inserted into the eye through a 1.0- to 1.5-mm clear corneal incision. The inflow portion of the stent (the short side of the “L”) is positioned near the trabecular meshwork, and the outflow portion (the long side of the “L”) is inserted into Schlemm's canal. Physiologic pressure in the anterior chamber drives the aqueous fluid through the stent's 120-µm lumen and into Schlemm's canal. Once it is the canal, the aqueous passes through collector channels and into the episcleral venous system.
Clinical Results
Interim data from a prospective, nonrandomized, historically controlled, open-label, multicenter, multicountry,
24-month clinical study1 showed that the iStent effectively and safely lowered IOP when it was implanted in glaucomatous eyes during cataract surgery. Interim 6-month results from the same study presented during the 16th Annual Meeting of the American Glaucoma Society in San Francisco showed that the mean IOP in 47 patients decreased from 21.5 to 15.8 mm Hg 6 months after they received the iStent. In addition, the number of ocular hypotensive medications used by the patients decreased significantly from 1.5 to 0.5 during the same period.2
Glaukos Corporation is currently enrolling patients in a phase 3, randomized, comparative, controlled, parallel-assignment FDA trial of the iStent. The company is also conducting phase 4 European trials in phakic and pseudophakic eyes to evaluate the device's efficacy and safety.
Although no data are currently available for the FDA study, several investigators involved in the trials shared their experiences with the device with Glaucoma Today.
Figure 1. The iStent is shown next to a penny to demonstrate its small size.
(All artwork courtesy of Glaukos Corporation.)
Notes From the OR
Louis “Skip” Nichamin, MD, is Medical Director of Laurel Eye Clinic in Brookville, Pennsylvania, and is a scientific advisor to Glaukos Corporation. To date, he has implanted several iStent microstents as part of the ongoing FDA clinical trial.
“The average outcome has been promising,” he said in an interview with GToday. “IOPs have dropped uniformly in my implanted patients, and my results so far are very similar to those seen in European trials.”
Dr. Nichamin stated that the iStent has several advantages, many of which can be attributed to the device's ab interno placement compared with more invasive surgical treatments for glaucoma. “Because it does not scar the trabecular meshwork or conjunctiva, treatment with the iStent does not preclude filtering surgery or other trabecular procedures if these become necessary later,” he said. He added that postoperative care with the iStent is easier than after a trabeculectomy, because surgeons do not have to worry about maintaining the bleb or preventing leaks that can cause hypotony.
Figure 2. The iStent facilitates the flow of aqueous from the anterior chamber directly into Schlemm's canal.
L. Jay Katz, MD, is Director of the Glaucoma Service at Wills Eye Hospital and Professor of Ophthalmology at Jefferson Medical College (both in Philadelphia), and he is a member of Glaukos Corporation's scientific advisory board. He noted that any type of ocular surgery has associated risks but that the implantation of an iStent is less likely to cause infections or other serious complications than a trabeculectomy or the placement of a tube shunt.
“Potential complications of the iStent may include chronic inflammation, clogging of the stent's lumen, migration of the stent into other parts of the eye, and poor function if the device is not placed directly into Schlemm's canal,” Dr. Katz told GToday. “Although most of these complications have not occurred, we should be aware that they are possible.”
E. Randy Craven, MD, is a principal with Glaucoma Consultants of Colorado in Littleton, Associate Clinical Professor at the University of Colorado School of Medicine in Denver, and a clinical investigator for Glaukos Corporation. He has seen few complications with the several iStents he has implanted as part of the FDA clinical trial.
“The area around Schlemm's canal is vascular, so it is common to see minor blood reflux when the stent is positioned properly within this structure,” Dr. Craven said in an interview with GToday. “I think it is important that my patients have achieved postoperative IOPs of approximately 14 mm Hg on no medications.”
Figure 3. This slit-lamp photograph shows the iStent inside the eye.
Practical Considerations
Drs. Nichamin and Craven agree that, like most new surgical procedures, implanting the iStent can be challenging at first.
“The learning curve with the iStent's current design and available instrumentation is fairly steep,” commented Dr. Nichamin. “I learned the technique in the wet lab on cadaveric eyes, but, even then, the first two cases I performed were challenging. By the time I performed my fourth case, I was more comfortable with the procedure.”
When asked about specific obstacles to the implantation procedure, he replied, “Subtle changes in the positioning of the patient's head, the microscope, and the gonioprism can make the procedure more challenging, I sometimes have difficulty visualizing the anterior chamber angle through the gonioprism, especially if blood refluxes into the trabecular meshwork. Obstacles like these can make it difficult to see the small structures I am targeting and undermine my confidence that the stent is in the proper anatomic position.”
The Benefits and Limitations of Conventional Outflow
One of the principal benefits of the iStent procedure is that it utilizes the eye's natural, pressure-dependent, steady-state physiologic outflow system and thus virtually eliminates the potential for hypotony that can occur with external glaucoma drainage devices. Although the same mechanism may be a limitation for patients who need to achieve IOPs in the single digits, current data suggest that most patients can achieve their target IOPs with the iStent.1,2
According to Dr. Katz, the iStent cannot be expected to produce IOPs as low as those achieved by trabeculectomy (< 10 mm Hg), because the episcleral veins exert a steady-state pressure of 9 to 11 mm Hg on the eye's natural physiological outflow system. “Even if the iStent is supplemented with a canaloplasty or another procedure that dilates Schlemm's canal, it will never produce IOPs lower than 10 mm Hg,” he said. “Patients who need low target IOPs will likely need to use topical medications (in combination with the iStent) to achieve them.”
Dr. Nichamin does not see the physiologic limit as a serious problem. “Most patients who will receive the iStent do not need to achieve IOPs of less than 10 mm Hg,” he said. “Right now, this procedure is performed on cataract patients who also have glaucoma and IOPs between 20 and 24 mm Hg. If we can lower their IOP to between 13 and 18 mm Hg and get them off medications, we will have done them a real service.” Patients who need to achieve IOPs of 8 or 9 mm Hg are probably better candidates for conventional filtering surgery with an antimetabolite, he added.
Dr. Craven suggested that even patients in whom the iStent fails to lower IOP could benefit from the procedure indirectly. “Most glaucoma specialists feel that elevated IOP in open-angle glaucoma is caused by a blockage in the trabecular meshwork,” he said. “If the surgeon is certain he placed the iStent correctly and the patient's IOP does not drop, the mechanism of glaucoma probably is not poor trabecular drainage. The patient may need filtration surgery or an external drainage device to achieve lower IOPs.”
Dr. Nichamin supports this idea. He stated that glaucoma patients whose pressures are reasonably well controlled or marginally controlled by medications would probably be better served by the implantation of an iStent before proceeding to more complex surgery.
Treatment Hierarchy
Most of the clinical data for the iStent come from patients who received the device during cataract surgery. Ongoing phase 4 European studies, however, are investigating the iStent's safety and efficacy in phakic eyes as a standalone procedure.
A feasibility study in which six patients received the iStent without concurrent cataract extraction showed a mean reduction in IOP from 20.2 ±6.3 mm Hg preoperatively to between 12 and 13 mm Hg immediately postoperatively. By 12 months postoperatively, the patients' IOPs had stabilized to between 14 and 15 mm Hg, and all of them were using fewer ocular hypotensive medicines.3
“I suspect we will eventually use a trabecular bypass procedure like the iStent as first-line therapy for early glaucoma,” said Dr. Craven. “It is a relatively benign physiologic solution that could be a good first step to lower[ing] IOP in people with very high pressures. The iStent will probably replace laser trabeculoplasty in my treatment algorithm.”
Drs. Katz and Nichamin anticipate acceptance of the iStent as a combined procedure with cataract surgery by surgeons who envision the device as an alternative to trabeculectomy or endoscopic cyclophotocoagulation. “Since the doctor is already in the eye, why not implant the iStent?” asked Dr. Nichamin. “I envision implanting this device as a standalone procedure, perhaps after argon laser trabeculoplasty and before trabeculectomy.”
In some cases, surgeons can use more than one implant to titrate the IOP toward targeted pressures or to achieve maximal IOP lowering, commented Dr. Katz. “In vitro experiments performed by Douglas H. Johnson, MD, at the Mayo Clinic in Rochester, Minnesota, suggest that outflow from Schlemm's canal appears to be circular and segmental,” he said “Theoretically, one could increase the iStent's IOP-lowering potential by inserting multiple devices into different parts of the canal.”4
Conclusion
The iStent appears to be a promising new treatment for lowering IOP in patients with open-angle glaucoma. Interim data from ongoing studies show that the iStent safely lowers IOPs to the midteens and reduces patients' dependence on hypotensive medications. “The iStent is a small, relatively noninvasive device that restores the eye's physiological outflow,” said Dr. Craven. “I think it is a good potential first-line microsurgical treatment option for patients whose pressures are not adequately controlled with currently available IOP-lowering therapy.”
E. Randy Craven, MD, may be reached at (303) 797-1900; ercraven@glaucdocs.com.
L. Jay Katz, MD, may be reached at (215) 928-3197;
ljkwayne@aol.com.
Louis “Skip” Nichamin, MD, may be reached at (814) 849-8344; ldnichamin@aol.com.
1. Feijoo JG, Garcia-Sanchez J. The trabecular microbypass stent (iStent): a safe surgical alternative for primary open-angle glaucoma. Poster presented at: The International Glaucoma Society Meeting; March 28-31, 2007; Athens, Greece.
2. Samuelson TW, Katz LK, Spiegel D. Exploring Schlemm's canal to restore physiologic outflow in glaucoma. Poster presented at: The 16th Annual Meeting of the American Glaucoma Society; March 4, 2006; Charleston, SC.
3. Spiegel D, Wetzel W, Haffner DS, Hill RA. Initial clinical experience with the trabecular micro-bypass stent in patients with glaucoma. Adv Ther. 2007;24:161-170.
4. Bahler CK, Smedley GT, Zhou J, Johnson DH. Trabecular bypass stents decrease intraocular pressure in cultured human anterior segments. Am J Ophthalmol. 2004;138:988-994.
