Thresholds for Glaucoma Surgery

Expert advice on making the right choice.

BY DIANE DONOFRIO ANGELUCCI, CONTRIBUTING EDITOR

The classic step-wise approach to glaucoma management, which served clinicians and patients well for decades, has lately fallen on hard times. What once was a linear process — medical therapy of increasing complexity, followed by laser trabeculoplasty and lastly filtering surgery for end-stage cases — for many patients now resembles a level playing field, one in which pragmatic concerns may trump time-honored tenets of care. “As you evaluate the patient, you have to figure out: is this person going to care for himself or herself?” asks George Spaeth, MD, of Philadelphia's Wills Eye Institute. “If patients are not, there's no sense in wasting their time and their health by asking them to do something they can't do,” he says. “In those patients, you may want to start with surgery” as your initial treatment.

For patients, this is generally a good thing, as more doors are open to them than ever before. Selective laser trabeculoplasty (SLT) is increasingly considered earlier in the disease process to spare patients years or even decades of medical therapy. Meanwhile, for advanced disease, tube shunts have gained favor as an alternative to filtering blebs.

Just what are the appropriate thresholds for choosing one modality over another? A range of individual patient factors — including the type of glaucoma, disease stage, patient compliance, access to care, age, life expectancy, and socioeconomic status — should guide decisions on when and how to begin treatment.

In this article, glaucoma experts share their experiences in mapping out personalized treatment strategies for patients.

First-Line Therapy

A long view is essential in choosing whether to treat a patient. “What is going to happen if this person is not treated?” Dr. Spaeth asks at the outset. If foregoing treatment would subject the patient to visual disability that impacts quality of life, treatment is warranted. “Then, the next question is whether treatment will be of any benefit.”

Dr. Spaeth begins the decision process by identifying the disease stage and rate of change, then plotting these factors plus the patient's life expectancy on a graph to determine how aggressively the patient should be treated. He also weighs the aforementioned socioeconomic status, access to care, associated medical problems and other factors.

Medical therapy is still the preferred first-line therapy 95% of the time, says Theodore Krupin, MD, professor of ophthalmology at Northwestern University. If two medications do not lower pressure sufficiently, he talks with the patient about whether to add a third medication or use SLT. Dr. Krupin prefers SLT over argon laser trabeculoplasty (ALT). “I think SLT produces less inflammation than ALT, while the outcomes are very similar,” he says. If SLT is not successful, he does not repeat it.

If patients do not comply with medication regimens, Dr. Krupin advances more quickly to laser trabeculoplasty (LTP) or possibly even incisional surgery. “In my mind, poor compliance is the same as a medication not working,” Dr. Krupin says.

Kuldev Singh, MD, MPH, professor of ophthalmology and director of glaucoma service at Stanford University, generally begins with medication and uses LTP as an adjunct in a manner similar to Dr. Krupin. In patients with severe disease or a high risk of functional vision loss, he states that he may skip the laser step and go right to surgery after medications, particularly in cases where he hopes to achieve very low pressures.

Dr. Singh generally reserves LTP as initial therapy only for patients who can't afford or tolerate medications. “Generally I rarely perform LTP on younger patients, with the exception being those with pigmentary glaucoma,” he says. “More commonly, I perform SLT on elderly patients, particularly those with mild to moderate disease and risk of vision loss, after medications have been tried or, in some cases, as primary therapy for primary open-angle glaucoma or exfoliative glaucoma.” In patients at low to moderate risk of functional vision loss from disease, Dr. Singh will commonly repeat SLT if necessary, particularly if the patient had a good response with the first treatment.

Although he uses SLT, Dr. Singh says evidence indicates that ALT and SLT work about equally well. “I think SLT is technically easier to perform and may be associated with less inflammation, although when performed correctly, I think ALT and SLT are fairly comparable with regard to efficacy and safety. I certainly believe that ALT is still an acceptable option.”

Dr. Spaeth, however, tends to use ALT or SLT before medical therapy in patients with primary open-angle glaucoma, pigmentary glaucoma or glaucoma associated with pseudoexfoliation syndrome who are older than 40 or preferably older than 50. “I think the LTP is a wonderful treatment for those patients as the initial therapy,” he says. “Now if that therapy doesn't work, and it may not, then you go on to some sort of medical treatment.” He begins with IOP-lowering drops if patients prefer not to have LTP.

“If I haven't achieved my target intraocular pressure with reasonably tolerated medical therapy that the patient can comply with and I'm within 4 to 6 mm Hg of my target, I will do LTP,” says Donald Budenz, MD, MPH, professor of ophthalmology, epidemiology and public health at the University of Miami. “If I'm so far out of where I need to be, knowing that LTP might lower pressure at most 4 to 6 mm Hg, I'll skip that step and go straight to incisional surgery.” If LT P is not successful, he is not likely to repeat it. “If somebody's already had LTP, redoing it doesn't have a huge benefit.” In fact, he says, the literature suggests that repeating ALT can actually cause the pressure to become uncontrolled.

Advancing to Incisional Surgery

In weighing whether to perform incisional surgery, Dr. Spaeth follows the same process he does for other treatments: considering the patient's stage of disease, rate of change and life expectancy.

Dr. Budenz takes into account patient compliance with medications, severity of disease and life expectancy when contemplating surgery. “I don't mind exposing patients to medications and laser, which are generally safe,” he says, but if the IOP remains above the target despite those interventions, he's more apt to monitor for signs of progression before moving to incisional surgery. “My basic guiding principle when I do introduce surgery is to ask if the patient will go blind eventually in their lifetime if I do not do glaucoma surgery.”

For angle-closure glaucoma, uveitic glaucoma and traumatic glaucoma, Dr. Budenz skips LTP. “But in other types of glaucoma,” such as POAG, pigmentary, normotensive, or pseudoexfoliative, “one can do the laser step and, if it doesn't work, always go to surgery.” He generally doesn't start with surgery except in primary congenital glaucoma.

If medications and SLT have not lowered IOP sufficiently, Dr. Krupin moves forward with incisional surgery, but he rarely chooses surgery as a first option. “The threshold is very much dependent upon how much damage there is,” he says. “The more damage, the more aggressive you'll be.” However, Dr. Krupin downplays the value of life expectancy in making decisions. “I don't know how to judge life expectancy,” he says, pointing out that his oldest trabeculectomy patient was 95 years old at the time of surgery, and is currently 102.

“Severity of disease and risk of blindness are important in determining whether or not I recommend SLT or skip the laser step and go to surgery,” Dr. Singh says. He usually reserves incisional surgery for patients in whom medications and LTP have failed but will skip the laser step if it is highly unlikely that laser will lower IOP to a level that is necessary to significantly slow disease progression in those with severe disease. “I tend not to perform incisional glaucoma surgery for patients at low risk of lifetime functional glaucomatous vision loss even if IOP has not been lowered to a desired level that could be attained with surgery.”

As with all medical decisions, he says, glaucoma management should be based upon the expected risk versus benefit of the various options. “If the expected risk of a treatment outweighs benefit based upon a variety of patient factors, including disease severity, prior rates of progression, approximate expected lifespan and others, surgery should not be performed, regardless of any predetermined target IOP.” Proceeding with surgery to achieve a predetermined target may be suboptimal in such circumstances.

Weighing Surgical Options

With advances in aqueous shunt designs and research suggesting improved success rates compared with trabeculectomy,¹ shunts are increasingly used in patients with vision-threatening glaucoma. From 1995 to 2004, the number of trabeculectomies performed in Medicare beneficiaries decreased by 53% in eyes without previous surgery, whereas the number of aqueous shunting procedures increased by 184%.² The coming decade will no doubt witness a flourishing of additional options. Alcon's recent purchase of Optonol, maker of the Ex-Press mini shunt, signals that category's potential for further development.

Dr. Singh generally uses trabeculectomy more often than tube shunts as initial surgery for patients with primary open-angle glaucoma. “Usually I reserve tubes for patients with failed trabeculectomy but do use them in place of trabeculectomy in subgroups of patients, including some with inflammatory neovascular and infantile glaucoma,” he says.

Dr. Budenz also tends to prefer trabeculectomy. “As an initial surgery, I generally do trabeculectomy, unless it's a complicated glaucoma like uveitic glaucoma, neovascular glaucoma, iridocorneal ICE syndrome— all those secondary glaucomas,” he says. But for “garden variety” angle-closure glaucoma or a secondary open-angle glaucoma, such as pigmentary or Pseudoexfoliation glaucoma, he opts for trabeculectomy first. “If it doesn't work, I can always move to a tube as a second operation,” he says.

“I've been using aqueous drainage devices for a long time, and I have a lot of respect for them, and my surgical procedure of choice is to do a trabeculectomy,” Dr. Krupin says. He opts for tube shunts primarily if a patient has excessive limbal scarring, peripheral anterior synechiae or a poor prognosis with trabeculectomy. “But in my mind I have to have some reason to go to a tube, and if I have a case that has not had prior surgery and everything looks OK, I think I get good results with the trabeculectomy.”

He appreciates the flexibility in treating complications after trabeculectomy. “With trabeculectomy, if I'm having trouble with it, there are things I can do,” Dr. Krupin says. “I can do needling at the slit lamp and have a reasonable success to improve the bleb. You can't do that with a tube.”

“Even in patients who have so-called risk factors for trabeculectomy failure — young patients, for instance, or those who have ocular inflammation — I still prefer to do a trabeculectomy because in my hands I tend to get better results with a trabeculectomy than with other procedures,” Dr. Spaeth says. “However, the procedure is highly labor intensive, at the time of surgery and postoperatively.” Placing releasable sutures, in a manner that will assure the best chance of a well-formed anterior chamber and will allow gradual downward titration of pressure postoperatively, is time consuming, he says.

“I was not a fan of mitomycin C the way it used to be used. However, I now use mitomycin, 0.4 mg/ml, in association with almost every trabeculectomy, but it is used in a manner that is ‘the opposite’ of the way it used to be employed,” Dr. Spaeth continues. “Specifically, cottonoids are soaked in mitomycin, and then one cottonoid is placed about 12 mm posterior to the limbus along the medial side of the superior rectus muscle so that the cottonoid disappears, leaving only its blue tail visible; then I place another a similar distance from the limbus alongside the lateral side of the superior rectus, then along the superior margin of the medial rectus and another along the superior margin of the lateral rectus. After 30 seconds to three minutes, the blue tails of the cottonoids are used to pull the sponges out from where they were. No mitomycin is placed over the area where the scleral flap is to be developed.”

Because of the risk of double vision with tube shunts, Dr. Spaeth prefers to not use them in patients with good sight in both eyes. He also does not use them in patients with very thin scleras. However, he considers patients good candidates for drainage device surgery if they have had previous trabeculectomies that were properly done but failed and patients in whom the conjunctiva is very badly damaged. He does not use antifibrotics during tube shunt procedures.

In considering the options, the decision also depends on the surgeon's success rates with various procedures, Dr. Krupin says. “A lot of people are not being trained to do trabeculectomies. They are more comfortable performing a surgical procedure they learned during their training.”

Antifibrotic Use

Another area where opinions and approaches may vary based on surgical preference and patient factors is the role of antifibrotic agents.

Dr. Budenz, for one, always uses an antifibrotic for trabeculectomies. “If someone is at low risk for failure, typically elderly Caucasians, I will use intraoperative and selective postoperative 5-fluorouracil (5-FU) injections to avoid the long-term complications of mitomycin, such as bleb leaks and infection. But if someone is at high risk for failure — African Americans and young people — I will generally use mitomycin because I do think that the success rates are better,” he says.

For primary cases, Dr. Budenz uses 50 mg/ml 5-FU for five minutes intraoperatively on three to four Weck-Cel sponges and rinses copiously with Tissue-sol or BSS. Then he uses up to five injections of 5 mg 5-FU in 0.5 ml solution subconjunctivally 180 degrees from the bleb during the first two weeks after surgery, depending on bleb vascularity. He uses 0.4 mg/ml mitomycin C for two to five minutes on three to four Weck-Cel sponges intraoperatively. The sponges are applied to the sclera with the conjunctiva draped over the top.

However, Dr. Budenz doesn't use antifibrotics with tubes. “People have tried it with tubes, and although a few of our glaucoma colleagues are using it, the literature doesn't support its benefit, so I haven't been using it,” he says.

Dr. Krupin uses antifibrotics in all trabeculectomy cases, preferring 5-FU. He cuts 1.5 mm to 2 mm pieces from a 7 x 4 mm Weck-Cel sponge, which are soaked with 50 mg/ml 5-FU or 0.4 mg/ml mitomycin C. He applies four or five pieces to a wide surface area for three minutes under Tenon's on the sclera before creating the scleral flap. He irrigates with BSS after removing the sponges. Dr. Krupin does not use antifibrotics with tube shunts.

“In the hands of experienced surgeons, I think 5-FU and mitomycin C are probably equally effective and safe adjuncts to primary trabeculectomy for lower risk for failure patients, including those with primary open-angle glaucoma, but for higher risk for failure eyes, like second trabeculectomies or eyes with inflammatory, neovascular or congenital glaucoma, I think mitomycin C is probably more effective,” says Dr. Singh, who tends to use mitomycin C in most patients undergoing trabeculectomy but acknowledges that 5-FU use may be equally appropriate in many.

“One should also keep in mind that how these agents are used, as well as how the trabeculectomy technique is modified based upon such use, will also significantly impact outcomes,” Dr. Singh says. (For more information on intraoperative mitomycin C vs. 5-FU in trabeculectomy, see reference 3.) He uses 0.4 mg/ml mitomycin C for one to three minutes, depending on the risk factors for scarring, using four small Weck-Cel sponges, applied over a broad surface area, over 4 clock hours, from the limbus to about 10 mm posterior to the limbus, and tends to tie his trabeculectomy flap sutures on the tight side, hoping to avoid single-digit IOPs in the early postoperative period. He does not use antifibrotics with tube shunts.

Individualized Treatment

Regardless of preferences, it's important to keep in mind that there is no procedure of choice or medication of choice in treating patients with glaucoma, Dr. Spaeth says. “There is a procedure of choice for a particular individual and there is a medication of choice for a particular individual.” Beyond that, the doors are wide open.

“You have to be somewhat flexible, and there is not one sequence that is good for every patient,” Dr. Krupin says. “And there are some types of glaucoma that don't have as good a response to LTP, so you have to approach each patient as to what their problems are and what their level of disease is and put everything together for that patient.” OM

Editor's Note: Drs. Spaeth, Krupin and Budenz do not have a financial interest related to this article. Dr. Singh is a consultant for Alcon, Allergan and Santen.

References

1. Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL. Three-year follow-up of the Tube Versus Trabeculectomy Study. Am J Ophthalmol. 2009: 148:670-684.
2. Ramulu PY, Corcoran KJ, Corcoran SL, Robin AL. Utilization of various glaucoma surgeries and procedures in Medicare beneficiaries from 1995 to 2004. Ophthalmology. 2007;114:2265-2270.
3. Singh K, Mehta K, Shaikh N, et al. Trabeculectomy with Intraoperative mitomycin C versus 5-fluorouracil: Prospective randomized clinical trial. Ophthalmology. 2000: 107:2305-2309.

Today's Glaucoma Drainage Shunts: Each Has Unique Advantages

By Andrew Rabinowitz, MD

With the release of recent data from the Tube vs. Trabeculectomy (TVT) study, glaucoma shunts are no longer playing second fiddle to trabeculectomy as a preferred surgical option. In coming years, it is anticipated that glaucoma specialists will increase their use of shunts, either as an alternative to trabeculectomy or at an earlier stage in the management of individual cases.

Today, the most widely used glaucoma shunts are the Ahmed (New World Medical), the Baerveldt (AMO), the Molteno3 (IOP) and the Ex-Press Mini-Shunt (recently acquired by Alcon). There is general agreement that there is no single “best” glaucoma shunt, with the choice of shunt determined by surgeon preference and the patient's individual needs.

Each of the popular shunts has its own advantages. Surgeons hail the Ahmed's ease of implantation in a one-stage procedure and many like the valve feature that is designed to lower IOP quickly and reduce the potential of hypotony. The non-valved Baerveldt and Molteno shunts are both larger, capable of draining away more fluid and have solid reputations for long-lasting effectiveness.

Insights Into Shunt Use

The greatest challenge with implantation of aqueous shunts is limiting the early postoperative complications. The most common and potentially catastrophic of these is hypotony. Excessive hypotony can be devastating to the success of the surgery and to the health of the eye.

Today's commercially available shunts can be separated into two categories: valved and non-valved devices. Non-valved shunts consist of a plate connected to a silicone tube with an unobstructed lumen. The tube reaches from the base of the plate to its endpoint, which can be placed in the anterior or posterior chamber. Non-valved devices have straw-like lumens with no flow-restricting capabilities. With these devices, aqueous leaves the intraocular environment and is then expressed onto the anterior surface of the plate, which is sutured to the sclera.

Valved shunts have flow-restriction leaflets similar to cardiac valves. These valves are designed to shut when the IOP falls to a specific level. Closure of the valves prevents aqueous from leaving the eye when the IOP falls to a level beyond which the eye could become hypotonous. The theoretical advantage of the valved system is that there is a lower likelihood of the IOP dropping too low at any point postoperatively.

Probably the most commonly implanted shunt today is the Ahmed. This valved device allows for implantation without the need to ligate the tube. The non-valved shunts require some type of flow restriction or obstruction at the time of surgery so as to prevent excessive early hypotony.

With the non-valved shunts, surgeons attempt to limit postop hypotony by using some method of tube obstruction. This tube obstruction generally lasts four to six weeks. During this time, a fibrovascular cocoon forms around the plate of the device. This cocoon serves as an extrascleral reservoir to collect aqueous humor. From this cocoon, the aqueous then is absorbed into the venous system and is removed from the extraocular environment.

If the tube is not ligated or obstructed in some fashion, the early aqueous egress tends to be excessive and prevents the eye from re-establishing a normotensive state.

Proper Shunt Implantation

The majority of shunts are placed on the superior scleral hemifields, which provide a more predictable and safer area for implantation. Specifically, the supero-temporal quadrant provides the best balance between safety and efficacy. The superonasal quadrant is the second choice for implantation but can lead to a greater likelihood of strabismus. I believe that the inferior hemifields should be avoided due to an unacceptably high complication rate, including but not limited to excessive hypotony and globe-threatening endophthalmitis.

Implantation of an aqueous shunt involves suturing the plate of the device onto the sclera. Prior to this step, the device is usually “primed” or tested to ensure proper function. Once the plate is properly affixed to the sclera, the tube is then assessed for length and trimmed with a bevel that is oriented anteriorly for anterior chamber placement or posteriorly for posterior chamber placement.

A 22-gauge needle is then used to enter the eye to create an entrance tract for the tube. The tube is then placed through this tract and anchored to the sclera with 9-0 nylon sutures. The tube is then fenestrated anterior to the tie-off. A piece of sclera or pericardium is then sutured over the tube from the limbus to the base of the plate. A patch graft is laid over the tube to prevent erosion of this tubing through the sclera. Once the patch is properly placed, Tenon's layer and the conjunctiva are then closed in a watertight fashion. When the wounds are closed, IOP can be adjusted by creating a temporal paracentesis and either adding or removing balanced saline or viscoelastic materials.

Shunt Selection

In cases that require immediate IOP control, the Ahmed device offers an opportunity to place the shunt without the use of an obturator or ligature. The flow-restrictor valve system prevents IOP from dropping too low too early. The surface area of the single-plate Ahmed is roughly 180 mm. The device can be easily placed in any single quadrant. If the patient is deemed to need greater IOP control than that achieved with a single-plate Ahmed, the surgeon can opt to install a double-plate Ahmed shunt. The double-plate device involves operating in two quadrants. This requires more extensive surgery but in general does not increase surgical risks.

If a surgeon wishes to achieve lower long-term IOP without having to perform two-quadrant surgery, the Baerveldt 350 mm non-valved device is an excellent choice. Because the device is placed under two muscles, the larger plate size can be deployed without having to violate two quadrants. Most surgeons ligate the tube with a 6-0 or 7-0 Vicryl suture. The ligation suture will dissolve in about four to six weeks, allowing full flow to the plate at that time.

The Molteno3 functions similarly to the Baerveldt device.

The Ex-Press is a relative hybrid of an aqueous shunt and a trabeculectomy. It is a metallic stent inserted into the anterior chamber under a standard scleral flap, which can be identical to the flap created for trabeculectomy.

Unlike a trabeculectomy, which involves the removal of a block of trabecular tissue followed by an iridectomy, the Ex-Press is placed into the eye once the flap has been fashioned. The Ex-Press does not require removing any trabecular or scleral tissue. Additionally, it does not require, in most instances, the creation of a surgical iridectomy. This simplifies the surgery by removing these two steps. Following insertion, the scleral flap is closed with either absorbable or permanent suture. The conjunctiva and Tenon's are then closed above the flap.

This procedure may provide an excellent platform for less-experienced surgeons to transition from trabeculectomy to the addition of aqueous shunts to their surgical arsenal.

The options will expand further as newer miniature shunts reach the market. The iStent from Glaukos (Laguna Hills, Calif) is implanted ab-interno in Schlemm's canal in combination with cataract surgery, allowing aqueous humor to flow directly into Schlemm's canal toward the episcleral drainage system while bypassing the trabecular meshwork. The blebless procedure can be performed under topical anesthesia and spares conjunctival tissue, thereby preserving future treatment options. Multiple iStents can be used concurrently for greater IOP lowering effect, an approach now being studied. Reported complications have been minimal, with no instances of hypotony, post-surgical flat chambers or choroidal effusion observed.

The Solx Gold (Solx, Boston) and the Aquashunt from Opko Health are other blebless shunts. Solx Gold is a 3 mm x 6 mm plate containing numerous microtubular channels that bridge the anterior chamber and the suprachoroidal space, promoting uveoscleral outflow. The Aquashunt is inserted through a full-thickness scleral incision to the level of the suprachoroidal space, then sutured in place. The company suggests that its relatively simple implantation procedure will make it appealing to general ophthalmologists who do not normally perform a large number of glaucoma surgeries.

But that remains to be proven, and glaucoma shunts still primarily remain in the hands of experienced glaucoma specialists.

Andrew Rabinowitz, MD, is the glaucoma specialist at Barnet, Dulaney Perkins Eye Center, Phoenix, Ariz. His surgical techniques have been used in educational films demonstrating the appropriate usage of glaucoma shunts. He has no financial interest in any of the products mentioned in this article. Dr. Rabinowitz can be reached via e-mail at andrewrabinowitz@aol.com.