Patient Management
UPDATE: Nonpenetrating Filtering Surgery for Glaucoma
There's renewed interest in this approach, but when should you use it instead of trabeculectomy?
By Stephen Bylsma, M.D., Santa Maria, Calif.

The recent FDA approval of the collagen AquaFlow "wick" drainage device, which is used concurrently with nonpenetrating deep sclerectomy (NPDS), has sparked renewed interest in the nonpenetrating approach to incisional glaucoma surgery.

NPDS was first described decades ago by Thomas Zimmerman, M.D., but early procedures produced fibrosis at the incision site. Russian surgeons achieved longer-term success in the 1990s by adding a collagen implant under the superficial flap. (That implant was brought to the United States as the AquaFlow.) During the same decade, Robert Stegman, M.D., popularized viscocanalostomy, another variant of NPDS in which viscoelastic is used to dilate Schlemm's canal.

However, despite improvements in tools, techniques and outcomes, NPDS continues to be controversial. I believe this reflects our poor understanding of the mechanisms of action involved in NPDS, and the paucity of long-term data.

What isn't controversial is that the nonpenetrating procedures are safer than standard trabeculectomy, with or without antimetabolites. The incidence of prolonged hypotony, choroidal detachment or effusion, shallow anterior chamber, and reduction of initial visual acuity is lower with nonpenetrating procedures than with trabeculectomy. This is a direct result of the retention of a more physiologically-normal resistance to outflow of aqueous humor in the case of NPDS.

Let's look at how this happens surgically.

Comparing NPDS and trabeculectomy

Whether you treat a patient with NPDS or trabeculectomy, some aspects of care will be more difficult than others. When performing NPDS, finding Schlemm's canal and removing the inner wall complex can be challenging. However, once the procedure is completed, the rest of the case should go smoothly. In comparison, trabeculectomy is quite straightforward in the OR; the hard part is the post-op management and care.

Nonpenetrating deep sclerectomy derives its name from the excision of a deep scleral block of tissue overlying Schlemm's canal, including the outer wall of the canal. The deep sclerectomy "unroofs" Schlemm's canal, exposing the inner wall of the canal and the underlying trabecular meshwork. (The inner wall of Schlemm's canal is intimately connected with the juxtacanalicular meshwork, believed to be the site of highest resistance to outflow of aqueous humor.)

Although removal of the outer wall of Schlemm's canal causes some egress of aqueous humor, the physical removal of the inner wall-juxtacanalicular complex as a separate step (using forceps) produces a more dramatic outflow. Aqueous is now able to transit the more porous corneoscleral and uveal portions of the trabecular meshwork that remain. The site remains nonpenetrating, however, because some trabecular meshwork is still present. This allows a relatively normal physiological resistance to outflow, preventing hypotony.

Compare that to what happens during trabeculectomy. Any penetration into the anterior chamber in excess of 50 microns will allow the resistance to outflow to drop to zero, and the typical sclerostomy is more than 1 square mm. Unless viscoelastic was placed prior to the sclerostomy, aqueous rushes out and the iris prolapses into the ostomy.

Following the peripheral iridectomy, repositioning and suturing the superficial flap into place creates a new, surgically-titrated resistance to outflow. Thus, the "art of trabeculectomy," to a large degree, is the knowledge of just how to use the superficial flap to manufacture enough resistance to outflow to prevent hypotony, yet still permit the appropriate amount of outflow to lower IOP and discourage fibrosis.

These two techniques create very different safety issues:

• After trabeculectomy, the resistance to outflow created by the superficial flap varies, leading to the need for suture lysis, needling of the bleb, and other post-op modulations.
• NPDS is forgiving in its ability to regulate outflow because the presence of the normal, albeit thinned, trabecular meshwork regulates outflow within a normal physiological range. Eyes undergoing successful NPDS have a much more uniform outflow and appearance without post-op intervention.

Most glaucoma specialists (who generally have few complications after trabeculectomy) agree that NPDS is associated with quicker recovery and fewer postoperative interventions.

The question of long-term control

On the other hand, there is some debate about the efficacy of the NPDS procedures. After all, the point of filtering surgery is to achieve IOP control over many years or decades. The uncertainty about NPDS is largely due to the lack of long-term data for the newer versions of the procedure.

To date, the most significant long-term, peer-reviewed data comes from studies up to 5 years in duration using the Aqua-Flow collagen "wick" implant conducted by Dr. Andre Mermoud. (See the Journal of Cataract and Refractive Surgery, 2001; 27[11]:1770-8). Data presented to the FDA for approval of the AquaFlow mirrors the results obtained by Dr. Mermoud.

In contrast to NPDS, an abundance of data confirms the efficacy of penetrating surgery. In fact, trabeculectomy with antimetabolites remains the gold standard to which all other procedures are compared for efficacy.

Antimetabolites: the pros and cons

Antimetabolites are critical to the long-term efficacy of trabeculectomy. In particular, two anticancer medications, Mitomycin-C (MMC) and 5-Fluorourocil (5FU), prevent postoperative fibrosis of the superficial scleral flap and episclera. They're critical to maintaining the patency of the site and controlling IOP over the long term, and many surgeons use them for this purpose. (This use will probably remain off-label. The companies manufacturing these medications aren't motivated to go through an arduous FDA approval when their products are currently in frequent use without FDA approval.)

Unfortunately, it's becoming apparent that late complications do occur following the use of antimetabolites. Late leaking filtering blebs are becoming more common, especially after higher-dose MMC, because the conjunctiva isn't able to maintain and repair itself in the presence of an ischemic bleb. These leaking blebs create a high risk of infection and require intervention. Lower doses of antimetabolites are less likely to cause these late leaks, but lower doses have been associated with more fibrosis and less long-term efficacy.

Antimetabolite use with the NPDS procedures is less common. While the IOP-reducing efficacy of viscocanalostomy, the AquaFlow implant, or other NPDS variants may indeed be enhanced with antimetabolites, data indicating this is scarce. (The FDA trial for the AquaFlow implant prohibited the use of concurrent antimetabolites.) Dr. Stegman pioneered viscocanalostomy without antimetabolites because of their late complications; his patient population resides in remote areas that are far from medical facilities.

In fact, when the AquaFlow device is used, there may be less need for antimetabolites; the collagen AquaFlow device resorbs over 6 to 9 months and is thought to be a "space maintainer" that helps limit fibrosis under the superficial flap. Either way, now that the device is FDA-approved, some surgeons may elect to use the AquaFlow along with off-label antimetabolites. Data from their work should help to clarify whether or not antimetabolites are a useful adjunct to NPDS.

Which procedure for which patient?

Medical intervention remains the primary means of controlling IOP in the United States. If medical treatment fails to control IOP, newer laser procedures such as selective laser trabeculoplasty (which targets the pigmented trabecular meshwork) may help some patients avoid further surgery. However, most of these patients become candidates for incisional filtering surgery. The question is: When should you perform NPDS instead of trabeculectomy (with or without antimetabolites)?

Based on the available peer-reviewed literature and reports to the FDA, surgeons can expect an IOP in the mid teens following the AquaFlow procedure (without antimetabolites). For this reason, it wouldn't be appropriate to consider using NPDS when the target IOP is in the low teens or single digits.

On the other hand, when safety is paramount (especially when the patient is elderly or requires an uneventful postoperative course) NPDS may be the best option. Patients whose eyes are at considerable risk for post-op complications are also good candidates. These patients would include high myopes, those with a history of choroidal hemorrhage or effusion after trabeculectomy in the contralateral eye, and those who are likely to be noncompliant with medications or follow-up.

Combining cataract and filtering surgery is another option. This approach has been shown to lower IOP significantly compared with cataract extraction alone. (See the work of Gianoli, Schnyder and Bovey, Journal of Cataract and Refractive Surgery 1999; 25(3):340-6.) In this situation it's possible to perform a same-site scleral tunnel phacoemulsification/AquaFlow procedure, but NPDS using the AquaFlow is easier to perform as a separate site clear-cornea procedure.

A promising alternative

Today, trabeculectomy with antimetabolites remains the surgical procedure of choice for eyes requiring extremely low IOP and eyes with significant conjunctival scarring. However, NPDS increases our options and permits a safer surgical approach for other patients, such as those for whom an IOP in the mid teens is acceptable, and patients who need to minimize the likelihood of postoperative complications.

It remains to be determined whether the addition of antimetabolites or other modifications to NPDS procedures will enhance their efficacy or end up sacrificing their safety profile. Eventually, as long-term data accumulates and we develop a better understanding of these procedures, we should be able to determine whether these safer NPDS alternatives can approach the efficacy of trabeculectomy.

Dr. Bylsma practices at the Shepard Eye Center in Santa Maria, Calif. He specializes in cataract, glaucoma and refractive surgery, staying on the cutting edge of eye care by participating in numerous FDA clinical trials and investigational studies. Dr. Bylsma is also a faculty member at UCLA.