New surgical treatment options challenge current standard of care for glaucoma

Nonpenetrating surgical options could alter the glaucoma treatment paradigm, making the current gold standard of filtering surgery one of several possibilities for treating the disease.

The current treatment protocol is shifting toward a more tailored approach based on each patient’s needs, according to Douglas J. Rhee, MD.

Dr. Rhee, an OSN Glaucoma Board Member, said that in the near future, a new paradigm could replace the current “linear protocol.”

“I think, long term, that there will be no more gold standard, meaning, one surgery for all patients,” he said. “In other words, at this point, it doesn’t really appear to me that there’s any one procedure that is perfect. Trabeculectomy, for the longest time, was as perfect as we had. Even though it wasn’t perfect, it was as good as we could get. I think all the surgical procedures and devices have some merit … but they each have their niche.”

Current role of trabeculectomy

Trabeculectomy is still the standard in glaucoma surgery. The procedure has improved greatly since its introduction 2 decades ago, enhancing physicians’ perioperative and intraoperative strategies, Thomas W. Samuelson, MD, OSN Glaucoma Section Editor, said.

The severity of a patient’s glaucoma can direct the decision to use trabeculectomy or a less invasive procedure, according to OSN Glaucoma Section Editor Thomas W. Samuelson, MD. Image: Fleming S

Its problems lie in its postoperative complications profile, in that a serious adverse event can occur years after the surgery has been performed, he said.

“Trabeculectomy, as we perform it now, is a vastly better operation than it was 20 years ago. It’s still not good enough to use as an early intervention strategy,” Dr. Samuelson said.

Despite its complications profile, filtration surgery has one of the best rates of significant IOP reduction among surgical glaucoma treatments. Landmark studies, including the Collaborative Initial Glaucoma Treatment Study and the Advanced Glaucoma Intervention Study, have shown its excellent pressure-lowering effects.

In addition, certain glaucoma subsets, such as angle-closure glaucoma and secondary glaucoma, are most effectively treated with filtration surgery. For some patients who have uncontrolled IOP or who cannot tolerate medication, trabeculectomy is an effective treatment as well.

While many physicians advocate the use of alternative surgical options, including tubes and other devices and procedures, they also say that filtration surgery remains an important, albeit imperfect, treatment option.

“In terms of the primary glaucomas, I think that the nonpenetrating surgeries should replace trabeculectomy as a gold standard. But you have to qualify it: Trabeculectomy fits a role in certain types of disease,” Richard A. Lewis, MD, an OSN Glaucoma Board Member, said.

However, the rate at which trabeculectomy is performed has been declining in recent years. Alan L. Robin, MD, an OSN Glaucoma Board Member, conducted a study 2 years ago that found that use of trabeculectomy decreased by more than 50% as a first-time procedure, based on Medicare claims from 1995 to 2004.

“There are other things that make it harder and harder to get to the stage of trabeculectomy compared to years ago,” Dr. Robin said.

One reason for the decline could be the use of prostaglandin analogues and combination medications as first-line treatment for early to moderate glaucoma, he said. Cataract surgery, performed in mild to moderate glaucoma cases to reduce IOP, has also become a means of reducing pressure instead of glaucoma surgery.

Alternative surgical procedures

Another reason for the decline in the popularity of trabeculectomy is its long-reaching complications caused by the procedure’s filtering bleb, Dr. Robin said. Possible complications of trabeculectomy include hypotony, bleb leak, dysesthesia, shallow anterior chamber, endophthalmitis and choroidal detachment.

While the number of trabeculectomy procedures has decreased, the number of tube shunt procedures has increased. The landmark Tube Versus Trabeculectomy (TVT) Study has helped lead the way in showing the advantages of tubes over trabeculectomy for advanced glaucoma cases.

Other surgical alternatives, such as the Trabectome (NeoMedix), canaloplasty (iScience) and the Ex-PRESS miniature glaucoma shunt (Optonol), have been gaining in popularity and use in the U.S. These devices and procedures are becoming viable options in glaucoma care because they lack many of the complications associated with trabeculectomy.

Additional surgical options, including the Gold Micro-Shunt (Solx) and iStent (Glaukos), are not approved by the U.S. Food and Drugs Administration but have been studied and used elsewhere in the world.

Many of the new nonpenetrating procedures enhance the natural outflow system and improve function of the trabecular meshwork, a “completely different strategy,” from the one used in the filtering process in penetrating surgery, Dr. Samuelson said.

Each surgical device and procedure offers different results to different glaucoma patients. For instance, patients with severe disease might require a new drainage system through trabeculectomy or tube shunt surgery, while those with milder disease could be “candidates for less invasive techniques that enhance physiological outflow,” he said.

“Some glaucoma patient types might be more amenable to an approach that enhances outflow facility. … But other patients may require a complete bypass, and of those, the Tube Versus Trabeculectomy Study will help us determine whether that bypass should be trabeculectomy or perhaps an aqueous drainage device. Then you have a few other procedures, like endoscopic cyclophotocoagulation, that may have a role for select patient types as well,” Dr. Samuelson said.

A patient’s stage of glaucoma and individual needs are important components in choosing the most effective surgical treatment.

“Severity of glaucoma may influence the choice of operation, but you also have to consider other factors, like whether the person has had prior ocular surgery and the degree of conjunctiva scarring. Certainly if there is significant scarring of the conjunctiva, trabeculectomy has little chance of working, especially for the long term,” Steven J. Gedde, MD, an OSN Glaucoma Board Member, said.

Treating mild glaucoma

Several devices and procedures are effective as surgical treatment options in less advanced glaucoma cases. One of those options, the Trabectome, lowers pressure by creating a direct communication between the anterior chamber and collecting channels. It accomplishes communication via thermal plasma that removes the trabecular meshwork, Dr. Rhee said.

Douglas J. Rhee

By removing the trabecular meshwork, the “anatomic side of resistance,” he said, is bypassed. The device accesses a distal portion of the eye’s natural drainage system.

“Of the published literature thus far, I think the Trabectome has a very good safety profile. Nothing is risk-free. Is it possible to get serious complications from a Trabectome? Of course it is, like it is for any procedure, including laser or medication. Any intervention can lead to a serious adverse event,” Dr. Rhee said.

He said the device can also be indicated for patients with moderate to advanced glaucoma who are controlled on medications but need cataract surgery. The device can help reduce the risk of pressure spikes in those cases.

The device has limited use in some cases that require significant pressure reduction, Dr. Rhee said. In his own experience using the Trabectome, he has found that it does not often go below a certain pressure reduction threshold.

“It’s very rare that you get a patient with a pressure less than 14 mm Hg,” he said. “Not that it doesn’t happen – it does. But you cannot reliably have it do that. So if you have a patient who needs a very low pressure, this is not an ideal situation.”

Canaloplasty is another effective procedure for patients with mild to moderate glaucoma. The procedure works with use of the iTrack microcatheter, which is inserted through Schlemm’s canal, dilating the canal and placing it on a “stretch,” according to Dr. Lewis, who has studied the procedure. A Descemet’s window permits “fluid to percolate out, not just through the meshwork, but through Descemet’s window, into the scleral lake,” he said.

Dr. Lewis said the procedure enhances outflow facility without creating a bleb.

“What makes it different from trabeculectomy is that in a trabeculectomy, you’re creating an artificial fistula and an artificial bleb of the conjunctiva. You’re depending on the conjunctiva for function through this hole, which creates both short- and long-term complications because the conjunctiva was probably not intended to be a filtering system,” he said. “The canaloplasty is more physiologic. It depends on the conventional outflow system. It doesn’t create an artificial one. There’s no bleb, and there’s no dependence on the conjunctiva.”

Richard A. Lewis

Two-year results of a study that Dr. Lewis and colleagues performed examining canaloplasty show that pressure remained between 14 mm Hg and 16 mm Hg after the procedure, with cataract surgery playing a role in lower IOP. The study showed that the canal system was not scarred.

The procedure also demonstrated good long-term safety results.

Patients with primary open-angle glaucoma, pigmentary glaucoma, pseudoexfoliation and congenital glaucoma have benefited from the procedure, Dr. Lewis said.

Canaloplasty has a learning curve and can be challenging to master, he said, so iScience provides training courses to assist physicians in obtaining the necessary skills.

A device that creates a bleb, the Ex-PRESS miniature glaucoma shunt, is another surgical treatment option for mild to moderate glaucoma. The Ex-PRESS has a wider range of indications than classic filtration surgery and can be offered as an option in the earlier stages of the disease, if not as a first-line treatment.

The device lowers IOP by diverting the aqueous humor from the anterior chamber to the subscleral and subconjunctival spaces to form a filtration bleb. Its predetermined restricted lumen (50 µm or 200 µm) makes the aqueous flow in a more controlled, predictable and standardized way, with a lower rate of complications.

A study by Netland and colleagues found that 3-year results of 231 eyes treated with Ex-PRESS implantation alone and 114 eyes treated with Ex-PRESS implant combined with phacoemulsification both had surgical success at about 95%.

To date, more than 35,000 Ex-PRESS shunts have been implanted worldwide, with good results and a low rate of complications.

“Surgery is also different and can be defined as minimally penetrating because no tissue excision or removal is required,” Elie Dahan, MD, senior glaucoma consultant at Ein Tal Eye Center in Tel Aviv, Israel, said. “The advantage over classic nonpenetrating surgical procedures, however, is the shorter learning curve. It can be implanted by both a glaucoma specialist and a general ophthalmologist.”

Treating moderate glaucoma

For moderate glaucoma cases that require more pressure-lowering results than milder cases, an additional surgical option is also available, but not in the United States. The iStent trabecular micro-bypass implant, in U.S. trials for FDA approval, offers potential benefits similar to those of viscocanalostomy. It lowers IOP without the formation of a filtering bleb and, therefore, without affecting the conjunctiva. It is delivered ab interno through a clear corneal incision, advanced through the trabecular meshwork and implanted through a pre-loaded applicator into Schlemm’s canal.

“Since 50% to 90% of resistance to aqueous outflow is in the trabecular meshwork, it makes sense to have a bypass device that creates a pathway for the aqueous to drain directly from the anterior chamber to the Schlemm’s canal,” Ike K. Ahmed, MD, FRCSC, an OSN Glaucoma Board Member, said.

Ike K. Ahmed

The first studies were conducted in Europe and looked at the results of one stent implantation in combination with cataract surgery. A 22% mean IOP reduction was obtained, and the mean number of medications dropped from 1.7 to 0.5 per eye.

Dr. Ahmed and colleagues found that better results can be obtained with more than one stent because multiple bypasses further reduce outflow resistance.

“In a consecutive series of 25 patients with [primary open-angle glaucoma] or [pseudoexfoliation glaucoma], we evaluated the results of the implantation of two or three eye stents in combination with cataract surgery. The follow-up ranged from 6 months to 1 year,” he said.

Mean IOP decreased from 20.5 mm Hg preoperatively to 14.2 mm Hg with two stents and to 12.7 mm Hg with three stents. Three stents also appear to be more effective in reducing medication use, which dropped from three to 1.5 with two stents and to zero with three stents. Results remain stable beyond the 1-year endpoint of the study.

The biggest advantage compared with trabeculectomy is the near absence of any serious sight-threatening complications, with results that are reasonable in terms of efficacy, Dr. Ahmed said.

“We are trying to overcome the biggest drawback of non-traditional surgery, which is the limitation in IOP-lowering capability. This study shows that we may be able to obtain results beyond our own expectations with trabecular bypass surgery,” he said. “In addition, we are able to titrate the number of stents required for a given patient, from one to three or, theoretically, even more, depending on the target pressure and disease severity.”

Treating advanced glaucoma

For those glaucoma patients who require more advanced and immediate pressure-lowering effects, there are innovations on the horizon, including a technology that U.S. physicians could gain access to soon, the Gold Micro-Shunt. The laser used in the procedure is available in the U.S., but the shunt itself is not yet approved by the FDA. It has been used and studied extensively in Europe.

The shunt works to utilize drainage devices through the suprachoroidal space, “a very natural pathway of aqueous filtration, exploited by the Gold Micro-Shunt,” according to Gabriel Simón, MD, PhD, inventor of the device and director of the Gabriel Simón Institute in Spain.

Inserted through a 2.8-mm incision at the limbus, the shunt creates a bridge between the anterior chamber and the supraciliary space. The difference in pressure gradient between these two areas draws the aqueous from the anterior chamber through the microtubules of the implant, lowering IOP without creating a bleb.

From the clinical point of view, results are “astonishing,” according to Dr. Simón.

“I’m not saying that we have achieved the perfect product, but I think we are heading to perfection. Although there are some cases in which the shunt doesn’t work as well as we would like, we have some idea of why this happens,” he said. “On the other hand, we have a big number of cases, more than 70%, in which we achieve the pressure we want, and we are talking about very aggressive glaucoma, where all other ways of lowering pressure have been tried and failed.”

TVT Study

The main surgical alternative traditionally used in treating advanced glaucoma cases has been aqueous drainage tubes. Like trabeculectomy, the Ahmed glaucoma valve (New World Medical), the Baerveldt glaucoma shunt (Abbott Medical Optics) and Molteno tube shunt (Molteno Ophthalmic) also bypass the natural outflow system. The devices have shown significant reductions in pressure in refractory glaucoma cases that are at high risk of failure with standard filtration surgery.

Dr. Gedde and colleagues are conducting the TVT Study. The multicenter, randomized clinical trial is looking at the safety and efficacy of a 350-mm² Baerveldt glaucoma implant compared with trabeculectomy with mitomycin C. The 212 patients in the study have undergone previous cataract surgery and/or failed filtering surgery. Patients were randomized to receive either a tube shunt or trabeculectomy.

The study’s 3-year results show that tube shunt surgery had higher surgical success than trabeculectomy based on prospectively defined success and failure criteria. Both surgeries had similar reductions in mean IOP and number of glaucoma medications at 3 years postop.

Patients who received trabeculectomy had a higher rate of complications after surgery than patients who had tube shunt implantation, the study found. Rates of serious complications were the same between filtration and tube shunt surgery.

Dr. Gedde said tube shunts are typically used to treat refractory glaucoma cases at high risk for surgical failure. The TVT Study demonstrated that the devices could be beneficial to more patient populations than previously thought.

“The TVT Study enrolled patients at lower risk for surgical failure than have traditionally had tube shunt surgery,” he said. “For example, some of the patients in the TVT Study had only a clear corneal phacoemulsification cataract extraction as their qualifying prior surgery. The TVT Study shows that tube shunts are a very appropriate surgical option in eyes with previous cataract and/or glaucoma surgery, and the use of these devices should be expanded beyond just refractory glaucomas.”

Research, including from Dr. Robin and colleagues’ review of Medicare records and 1996 and 2007 surveys by the American Glaucoma Society, has charted the increased use of tube shunt surgery. Physicians are gaining additional information about these devices from studies such as the TVT Study, Dr. Gedde said.

Steven J. Gedde

“One commonly held opinion among glaucoma surgeons is that low levels of IOP cannot be achieved with tube shunts, and the pressures typically settle in the high teens postoperatively,” he said. “However, the TVT Study results do not support this perception. The average pressures at 3 years was 13 mm Hg with tube shunts, and the proportion of patients that had pressures of 14 mm Hg or less was over 60%.”

He said tube shunts are “one of the leading candidates” among alternatives to trabeculectomy, but other options need to be explored using a prospective multicenter approach. He encouraged researchers to conduct randomized clinical trials comparing other surgical options to trabeculectomy.

“Randomized clinical trials like the TVT Study offer the highest level of evidence-based information for comparing different surgical procedures,” Dr. Gedde said. “It is my hope that these other promising new procedures will also be compared with the gold-standard trabeculectomy in randomized prospective studies in the future.” – by Erin L. Boyle and Michela Cimberle

Is surgery ever indicated as a primary glaucoma treatment option, and if so, in what cases would it be indicated?

References:

• The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes within race. Seven-year results. Ophthalmology. 1998;105(7):1146-1164.
• Ahmed KI. Multiple iStent Schlemm’s canal implants with phaco. Paper presented at: Annual Meeting of the American Glaucoma Society; March 5-8, 2009; San Diego, Calif.
• Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126(4):498-505.
• Francis BA, See RF, Rao NA, Minckler DS, Baerveldt G. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma. 2006;15(1):68-73.
• Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL; Tube Versus Trabeculectomy Study Group. Three-year follow-up of the Tube Versus Trabeculectomy Study [published online ahead of print Aug. 11, 2009]. Am J Ophthalmol. doi:10.1016/j.ajo.2009.06.018.
• Kanner EM, Netland PA, Sarkisian SR Jr, Du H. Ex-PRESS miniature glaucoma device implanted under a scleral flap alone or combined with phacoemulsification cataract surgery. J Glaucoma. 2009;18(6):488-491.
• Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: circumferential viscodilation and tensioning of Schlemm’s canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults: interim clinical study analysis. J Cataract Refract Surg. 2007;33(7):1217-1226.
• Ramulu PY, Corcoran KJ, Corcoran SL, Robin AL. Utilization of various glaucoma surgeries and procedures in Medicare beneficiaries from 1995 to 2004. Ophthalmology. 2007;114(12):2265-2270.
• Simón G. Two-year results of a gold micro-shunt implant for reduction of IOP. Paper presented at: XXIV Congress of the European Society of Cataract and Refractive Surgeons; September 11, 2006; London, England.

• Ike K. Ahmed, MD, FRCSC, can be reached at Credit Valley EyeCare, 3200 Erin Mills Parkway, Unit 1, Mississauga, Ontario L5L 1W8, Canada; 905-820-6789; fax: 905-820-0111; e-mail: ike.ahmed@utoronto.ca. Dr. Ahmed is a consultant for Glaukos, iScience and Solx, and has received speaking honorarium from Optonol.
• Elie Dahan, MD, can be reached at Ein Tal Eye Center, 17 Brandeis St., Tel Aviv, 62001 Israel; e-mail: elie.dahan@gmail.com. Dr. Dahan is a consultant for Optonol.
• Steven J. Gedde, MD, can be reached at Bascom Palmer Eye Institute, 900 NW 17th St., Miami, FL 33136; 305-326-6435; fax: 305-326-6474; e-mail: sgedde@med.miami.edu. Dr. Gedde has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
• Richard A. Lewis, MD, can be reached at Grutzmacher & Lewis Surgical Eye Specialists, 1515 River Park Drive, Sacramento, CA 95815; 916-649-1515; fax: 916-649-1516; e-mail: rlewiseyemd@yahoo.com. Dr. Lewis is a consultant to iScience Interventional.
• Douglas J. Rhee, MD, can be reached at Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02144; 617-573-3670; fax: 617-573-3707; e-mail: dougrhee@aol.com. Dr. Rhee has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.
• Alan L. Robin, MD, can be reached at Mid-Atlantic Glaucoma Experts, 6115 Falls Road, Suite 333, Baltimore, MD 21209; 410-377-2422; 410-377-7960; e-mail: arobin@glaucomaexpert.com. Dr. Robin is a consultant to Alcon, Glaukos and Cascade.
• Thomas W. Samuelson, MD, can be reached at Minnesota Eye Consultants, 701 E. 24th St., Suite 100, Minneapolis, MN 55404; 612-813-3628; fax: 612-813-3656; e-mail: twsamuelson@mneye.com. Dr. Samuelson is a consultant for iScience, AMO, Alcon Surgical and Glaukos.
• Gabriel Simón, MD, PhD, can be reached at Instituto Gabriel Simón, Minerva 7, 08006 Barcelona, Spain; 34-932387122; fax: 34-932387123; e-mail: gabrielsimon@dr-simon.net. Dr. Simón has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.