For 50 years ophthalmologists have known about resistance to the flow of aqueous through Schlemm’s canal and the cascade of events resulting in glaucoma. “We don’t know exactly where all the outflow resistance is,” said Michael S. Berlin, MD, clinical professor of ophthalmology, University of California, Los Angeles, and yet Dr. Berlin and others are creating devices that overcome that resistance and deliver aqueous into the outflow system. These devices may also help unlock the mystery of what goes on inside the canal of Schlemm.
This new concept in trabecular surgery attempts to make Schlemm’s canal more accessible to aqueous by altering the canal’s anatomy through ablation, dilation or bypass. “We’re not filtering anymore,” Dr. Berlin said. “We’re altering the anatomy and bypassing the major outflow resistance that occurs.” These procedures are in various stages of testing, but they have the potential to relegate trabeculectomy, the current gold standard for surgical treatment of glaucoma, to the back of the armamentarium.
“All these surgeries are designed to reduce the complications [hypotony, bleb leaks, late blebitis and bleb-related endophthalmitis] from trabeculectomies and other filtering surgeries,” said Brian A. Francis, MD, associate professor of ophthalmology, University of Southern California. “We’ll see in the next few years which one will gain the most acceptance,” he said. “There will always be a place for trabeculectomy, but the number of trabeculectomies will decrease with these kinds of procedures.”
Go With the Flow
Schlemm’s canal, named for the 19th- century German anatomist Friedrich Schlemm, is an endothelium-lined channel running contiguously along the trabecular meshwork. Aqueous humor ordinarily seeps through the meshwork into the canal and then drains out the canal into the general venous circulation.
The theory behind the new trabecular surgeries is that IOP elevation may be caused by inordinate resistance to aqueous migrating through the meshwork/ canal system. The main site of resistance is thought to be at the juxtacanalicular connective tissue and adjacent inner wall of the canal.
Unlike trabeculectomy, which shunts the aqueous from the anterior chamber to the subconjunctival space, these minimally invasive procedures attempt to restore the natural, physiologic mechanisms of aqueous drainage through Schlemm’s canal. In other words, they enhance outflow without external filtration. “It’s more physiologic [than trabeculectomy], and enhances the existing outflow state,” Dr. Francis said. “It relies on your normal outflow pathways.”
What’s more, these procedures avoid external fistulization under the conjunctiva and eliminate the risk of hypotony and infection. And since there is no conjunctival scarring, the possibility for trabeculectomy or tube shunt surgery remains open.
Some wind out of those sails? The downside is that the pressures achieved with these procedures are not as low as with trabeculectomy, Dr. Francis said. And there are some ophthalmologists who simply don’t agree with the assumption that resistance is all juxtacanalicular.
Thomas W. Samuelson, MD, attending surgeon at Minnesota Eye Consultants, has been involved in the testing of a number of Schlemm’s canal devices, and said there is a school of thought that contends Schlemm’s canal itself “may not be as pristine in some glaucoma patients as classic teaching would lead us to believe.” Rather, some think that sclerosis of the trabecular meshwork can extend into and block the lumen, in which case a juxtacanalicular bypass would simply transport aqueous to an already clogged exit.
In any event, Dr. Samuelson believes the current round of investigations has led to a new generation of devices that will further our understanding of Schlemm’s canal. Dr. Berlin agrees. “We don’t know exactly where all the outflow resistance is, but techniques like these will help us learn more about resistance.” At the same time, he said, “We’re learning we can eliminate some of the resistance and enhance outflow.”
A page from cardiology. As more is learned, Dr. Berlin predicts that ophthalmologists will treat glaucoma the way cardiologists treat arteriosclerosis. Angiograms reveal the obstruction, then angioplasty fixes it. “In glaucoma, we’ll do canalograms to see where the obstruction is. Then we’ll do canaloplasty to fix them. So we’ll be doing more precise surgeries.”
George Titus, vice president of GMP, a medical device company, agrees. “What’s going on now is a very miniaturized version of the interventional cardiology work that started 25 years ago. This is smaller, but the devices and imaging capabilities are very much a parallel to what went on in cardiology.”
Five Approaches to Clearing the Canal of Schlemm
Previous attempts to enter Schlemm’s canal to correct obstruction have failed, Dr. Berlin said. Mechanical approaches were too aggressive; laser approaches—ruby, Nd:YAG and argon—were too destructive. Now, with the advent of better tools and imaging devices, it may finally be possible for glaucoma surgeons to work in the canal. The new procedures use different means to tackle obstructions—bypass, dilation or ablation—but share two features, according to Dr. Berlin. First, they are designed to eliminate the anatomic obstruction. Second, they are intended to avoid a healing response. In other words, the area must not close again from scarring.
1. The Trabectome. This device is basically an electrocautery instrument (NeoMedix) with a special tip, said Dr. Francis. It is designed to create an opening from the anterior chamber directly into Schlemm’s canal by removing the trabecular meshwork and the inner wall of the canal.1 The mode of entry is through a clear corneal incision in the anterior chamber. Viscoelastic is applied to stabilize and deepen the anterior chamber before inserting the Trabectome. The cautery unit is advanced either clockwise or counterclockwise, in approximately a 15- to 30-degree arc.
The Trabectome is FDA-approved, but its use has been limited to a handful of surgeons, said Dr. Francis. “We’re just trying to use them and see how well they work over time.”
2. Canaloplasty with microcannula and ultrasound. This procedure is an outgrowth of viscocanalostomy, said Richard A. Lewis, MD, consultant in glaucoma, Sacramento, Calif.
The procedure begins by imaging Schlemm’s canal with a high-resolution ultrasound system, the Iview (iScience Surgical). It also employs a microcannula, 200 µm in diameter, with an atraumatic tip, that allows surgeons to dilate Schlemm’s canal a full 360 degrees. Previously, surgeons could only dilate 120 degrees of the canal. This added dilation is intended to allow flow of aqueous to pass through the entire trabecular meshwork.
A multinational study of this approach is under way in the United States, Germany, South Africa and England.
3. Excimer laser trabeculostomy (ELT). Dr. Berlin began developing this procedure in rabbit eyes some 20 years ago concurrent with the use of the Aida Excimer Laser (TuiLaser AG) for refractive surgery and coronary angioplasty. The advent of the precise, nonthermal excimer lasers made it possible to work successfully in the delicate, small spaces of the trabecular meshwork. The laser energy is applied directly to the meshwork by means of a fiber-optic delivery system (also by TuiLaser). The 308-nm wavelength allows removal of trabecular meshwork by photoablation, turning the tissue into gas and enabling flow into the canal. It also concurrently dilates the canal and the collector channels without creating thermal damage or an external filtration bleb.
The lowest pressures have been achieved when ELT is combined with cataract surgery. Dr. Berlin is collecting data from European studies and anticipates FDA approval in the near future.
4. EyePass implant. This silicone Y-shaped tube (GMP Companies) has a dual-bonded end and is small enough to fit inside Schlemm’s canal. The procedure, similar to a nonpenetrating sclerostomy, begins with the creation of a deep scleral flap and the unroofing of a portion of Schlemm’s canal. After Schlemm’s canal is defined, the two legs of the tube are inserted in opposite directions down the canal, and the main stem is inserted through a small incision into the anterior chamber. EyePass was designed to bypass the juxtacanalicular portion of the trabecular meshwork, to ensure that drained fluid stays within the eye wall, where it drains from the eye more naturally. EyePass is undergoing market trials in Germany.
5. Glaukos iStent. This microstent is used in a bypass procedure that reestablishes normal outflow by stenting open the trabecular meshwork and Schlemm’s canal. The stent is inserted in Schlemm’s canal internally through a clear corneal incision. This allows aqueous to flow directly into the canal toward the episcleral drainage system, thus avoiding the trabecular meshwork.
It may be possible to place more than one Glaukos iStent in different areas of Schlemm’s canal. In vitro studies found that a multifaceted approach may produce lower pressures.
Which of these approaches will prevail? “It may be a hybrid procedure that evolves from all of this,” Dr. Samuelson ventured. “But things have moved forward substantially.”
1 Ophthalmology, 2005;112(6):962–967.
Dr. Berlin is a scientific advisor to EyeLight and has patents on ELT technology. Dr. Francis serves on the medical advisory board of NeoMedix but has no financial interest in the product. Dr. Lewis is a consultant for iScience. Dr. Samuelson reports no related financial interests.