If I were a glaucoma patient, perhaps more than any other attribute, I would want my surgeon to respect surgical risk and reward. For example, if I had mild or moderate disease with low risk for functional impairment, I would rather have a safer procedure that doesn’t risk central acuity, even if that meant I would still require one or two medications. This would be especially true if the initial procedure didn’t limit my chance for surgical success with a more aggressive procedure should it become necessary.

Recent advances in glaucoma surgery and pharmacology have bolstered this safety-first strategy for mild to moderate disease. The winning formula of “MIGS and meds” is worth a try for most glaucoma patients, except perhaps those at highest risk for functional impairment.

Canal-based surgery adds this much-needed safety attribute to our glaucoma surgical offerings. For decades, procedures such as trabeculectomy and aqueous drainage devices, or “tube shunts,” have been the most efficacious IOP-lowering procedures. These procedures, when indicated, are effective for most patients. That said, if the surgeon isn’t prudent, glaucoma surgery may worsen the overall well-being of a small but significant percentage of patients. For example, a patient with mild or moderate visual field (VF) loss who sustains a suprachoroidal hemorrhage or bleb-related endophthalmitis is worse off as a direct result of the surgery, not the disease. This scenario has played out in my career, and every case has always lingered in my psyche. It is one thing when progression of the actual disease worsens a patient’s quality of life — it is another when it is iatrogenic in nature. Fortunately, we now can select our surgical procedure to better match the disease risk for individual patients.

Surgical decision-making has never been easy; now it is more complex, as technology has expanded the options to manage glaucoma.

For example:

• Which procedure do you choose for the patient whose mild disease has progressed despite medical and/or laser therapy? Does the choice change for moderate or severe disease?
• How about the patient undergoing coincident cataract surgery?
  • Or the monocular patient?
  • On anticoagulants?
  • With rapid progression?
  • With severe but stable disease and controlled IOP?
  • The patient with mild disease, but very high IOP?

In the past, surgeons would likely have performed trabeculectomy for most of these scenarios. Today, with experience, contemporary glaucoma surgeons are gaining insight into the myriad surgical options, their attributes and shortcomings, and hence the proper selection for individualized scenarios.

This discussion is limited to canal-based procedures utilizing an indwelling permanent device, such as iStent (Glaukos) or Hydrus (Ivantis), which I choose for patients undergoing combined cataract and glaucoma surgery when the glaucoma is mild to moderate and the IOP is not extremely high. I also employ canal-based combined surgery for patients with advanced glaucoma when the VF is stable or very slowly progressive and IOP is reasonably well controlled.

In the latter instance, I tell patients to expect to continue one or two medications postoperatively. I have found most patients want a safer surgical option, even if they still need some medications afterward. In my experience, once patients know their options, only a small percentage accepts significant surgical risk for the chance to be medication-free postoperatively.

Trabecular microbypass devices (TMBDs)

Canal-based glaucoma surgery is founded on the principle that the inner wall of Schlemm’s canal is the primary site of outflow resistance for aqueous humor. While most believe this to be true, undoubtedly some patients have additional sites of resistance distal to the trabecular meshwork, such as within the canal itself, or in downstream collector channels or aqueous veins. TMBDs provide a direct conduit permitting flow from the anterior chamber into the canal but have no known effect on the distal system. Hydrus differs from iStent somewhat in that it provides a direct inlet and scaffolding or tensioning of the inner wall, putting it on stretch for an 8-mm section of the canal. In vitro perfusion studies have shown that this tensioning improves outflow.

iStent

iStent is a snorkel-shaped, 1.0 mm x 0.3 mm heparin-coated, titanium device and currently the only FDA-approved TMBD. I was an investigator in the US PMA trial comparing iStent combined with cataract surgery (its approved indication) to cataract surgery alone.

The trial showed modest efficacy but impeccable safety. Patients receiving cataract surgery combined with iStent had statistically lower IOP and were on statistically less medication than patients receiving cataract surgery alone. A greater proportion of iStent patients than controls achieved IOP of 21 mm Hg or less without medications at one year (72% vs. 50%, P < 0.001).¹ This difference persisted at two years (61% vs. 50%, P = 0.036) according to a second study, though this study was not powered for two-year results.² Per protocol, medications were added postoperatively to maintain an IOP of less than 21 mm Hg. iStent patients required fewer medications than controls at one year (0.2 +/- 0.6 medications vs. 0.4 +/- 0.7 medications, P = 0.016), but the difference was no longer statistically significant at two years — again, the study was not adequately powered for two-year endpoints. This was due to the dropout of some subjects, as well as the expected decay of IOP improvement over time. A larger population would be needed to demonstrate that a small difference is statistically significant.

Before their trial experience, participating U.S. surgeons were naïve to iStent surgery. Postapproval studies suggest that results could improve with “intelligent placement” experience and a better understanding of intraoperative clues of outflow anatomy.^3,4 Berdahl et al recently published successful results with iStent in an off-label use involving pseudophakic eyes.⁵

The second-generation iStent (iStent inject) is in FDA trials. This device has the advantage of more straightforward implantation as two devices are implanted from a single preloaded injector in an attempt to gain access to more collector channels.

I will address some common questions that arise when implanting the iStent in conjunction with cataract surgery.

Combined surgery indications

I perform combined cataract and glaucoma surgery on most patients who need treatment of their IOP. TMBD placement is by far the most common glaucoma procedure that I employ coincident with cataract surgery.

While I often perform trabeculectomy or tube shunt surgery with severe disease or extremely high IOP, and gonioscopic-assisted transluminal trabeculotomy when performing “stand-alone” canal surgery, I find iStent lends itself nicely to combined surgery with phacoemulsification for several reasons. For example, once surgeons are facile at the procedure, it is extremely safe and involves minimal tissue manipulation. The US PMA trial on iStent showed no measurable difference in adverse events or visual acuity outcomes between those receiving phacoemulsification plus iStent vs. phaco alone.¹ In addition, the trabecular outflow pathway is familiar and physiological — the mechanism of action is synergistic with cataract surgery’s favorable effect on IOP. That cataract surgery itself lowers IOP is the foundation for MIGS surgery, especially for canal-based procedures involving TMBD.

While open to debate, it seems logical that procedures that divert aqueous to noncanal pathways (the subconjunctival or supraciliary space) are less complementary to phacoemulsification. One might reason that such procedures compete with cataract surgery’s effect on outflow. If cataract surgery benefits canal-based outflow, diverting aqueous to the subconjunctival or the supraciliary space might negate some of this effect.

With comparative data and time, we will better understand which strategy is most helpful for individual patients. For now, I prefer canal-based outflow as my safest, most physiological and least intrusive surgical option.

Even so, with the FDA’s recent approval of CyPass (Alcon) for use with coincident cataract surgery, I have started using the supraciliary approach in select patients who might otherwise have received trabeculectomy. I find CyPass implantation more straightforward than canal-based surgery, but I also find a greater potential for tissue disruption. Moreover, without the episcleral venous backstop inherent to canal surgery, the supraciliary approach increases the chance for transient hyphema and hypotony. While my CyPass experience is still relatively new, supraciliary surgery has a definite role among my preferred surgical offerings. I am still determining which patients will most benefit from it.

Hydrus

The Hydrus is an 8-mm canal scaffolding device comprised of nitinol, a nickel and titanium alloy. Like iStent, the Hydrus is implanted at the time of cataract surgery utilizing the same incision as the cataract procedure. The potential advantages of Hydrus: it provides a direct conduit for aqueous to enter the canal, and the device dilates and puts tension on the canal for 8 mm, roughly 3 to 4 clock hours (compared to iStent, which is only 1 mm in length).

One might suspect that Hydrus is more difficult to place due to its length, but in most published studies surgeons quickly learn implantation. Moreover, the device’s 8-mm length leaves no doubt about its anatomic location within the canal, while the 1-mm iStent can be more difficult to verify. However, iStent’s size makes it possible to implant in noncanal locations, such as ciliary body or superficially within the canal’s inner wall.

Numerous studies published on Hydrus include the Hydrus II trial⁶ performed in Europe, which mirrors the prospective and the randomized protocol currently underway in the US, the PMA Hydrus III trial. Hydrus II and Hydrus III each include medication washout schedules preoperatively and at one and two years postoperatively. The Hydrus II trial results showed that cataract surgery combined with Hydrus implantation provided superior IOP and medication reductions at one and two years compared to cataract surgery alone. Adverse events were uncommon and the only device-related complication were localized peripheral anterior synechiae, which to date have not been clinically significant.

Summary

The MIGS family of surgical glaucoma procedures provides the unprecedented opportunity to individualize care for our patients. Surgeons’ many options for patients now include enhanced outflow into the canal, the supraciliary space and subconjunctival space. Canal-based surgery offers a very safe and controlled option for those at low risk of functional impairment. As surgeons gain experience with implantation technique and location, results will likely improve. OM

REFERENCES

1. Samuelson TW, Katz LJ, Wells JM, et al. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthalmology. 2011; 118:459 – 467.
2. Craven ER, Katz LJ, Wells JM, Giamporcaro JE. Cataract surgery with trabecular micro-bypass stent implantation in patients with mild-to-moderate open-angle glaucoma and cataract: two-year follow-up. J Cataract Refract Surg. 2012; 38:1339 – 1345.
3. Trabecular micro-bypass stent implantation during small-incision cataract surgery for open-angle glaucoma or ocular hypertension: Long-term results. Neuhann TH. J Cataract Refract Surg. 2015;41:2664-2671.
4. Fellman RL, Feuer WJ, Grover DS. Episcleral venous fluid wave correlates with Trabectome outcomes: intraoperative evaluation of the trabecular outflow pathway. Ophthalmology. 2015; 122:2385–2391.
5. Evaluation of a Trabecular Micro-Bypass Stent in Pseudophakic Patients With Open-Angle Glaucoma. Ferguson TJ, Berdahl JP, Schweitzer JA, Sudhagoni R. J Glaucoma. 2016;25:896-900.
6. Pfeiffer N, Garcia-Feijoo J, Martinez-de-la-Casa JM, et al. A Randomized Trial of a Schlemm’s Canal Microstent with Phacoemulsification for Reducing Intraocular Pressure in Open-Angle Glaucoma. Ophthalmology. 2015; 122:1283–1293.

About the Author

Thomas W. Samuelson, MD, specializes in glaucoma and anterior segment surgery. He is a founding partner of Minnesota Eye Consultants, as well as adjunct associate professor at the University of Minnesota and co-director of the glaucoma service at Hennepin County Medical Center in Minneapolis. Dr. Samuelson is past president of the International Society of Spaeth Fellows — Wills Eye Hospital’s Glaucoma Fellows Society and served on the executive boards of the American Glaucoma Society and ASCRS.

Financial disclosures: Dr. Samuelson has been a consultant for Alcon, AcuMems, Aerie Pharmaceuticals, Allergan, Abbott Medical Optics, AqueSys, Endo Optiks, Equinox, Glaukos, Inotek, Ivantis, Merck, Ocular Surgery News, Ono Pharma USA, QlT, Santen, SLACK, Inc. and Transcend Medical.