The Conventional Outflow System
The major physiologic outflow pathway of the eye, and the pathway possessing the autoregulatory capacity of “pressure sensitivity,” is known as the conventional, trabecular, or canalicular pathway. It can be conceptually divided into the proximal system, consisting of the trabecular meshwork, and the distal system, including Schlemm's canal, the collector channels, and the aqueous venous system. By virtue of its pressure sensitivity, the conventional outflow pathway regulates the IOP in a normal eye. That is, when the IOP increases, outflow through the conventional pathway also increases, thus normalizing IOP. A reduction in the outflow of aqueous through the conventional pathway is a long-recognized abnormality in patients with glaucoma.2,3
In the normal eye, approximately half of the resistance to outflow is derived from the proximal system (trabecular meshwork), and the other half is from the distal system (Schlemm's canal and the collector channels).4 In glaucomatous eyes, the bulk of the pathologically increased resistance is derived from the juxtacanalicular portion of the trabecular meshwork.4 For this reason, one of the most compelling strategies in the search for a better glaucoma operation is to bypass the trabecular meshwork to gain access to Schlemm's canal and the distal system in order to restore physiologic outflow through the conventional outflow pathway.
The advantages of this approach are numerous. Such a procedure would theoretically correct the pathologic defect in the system—namely, an abnormally high resistance to outflow. It would also keep the aqueous in the subscleral space and therefore obviate the need for a filtering bleb and all the problems inherent to transscleral filtration. Further, hypotony would be virtually eliminated, theoretically, owing to the innate resistance of the distal system and the episceral venous pressure.
Blebless Glaucoma Surgery
Viscocanalostomy is an example of a blebless, nonpenetrating procedure designed to eliminate the need for transscleral filtration. One of the advantages to this strategy would be eliminating the dependence of surgical success on the healing whims of the conjunctiva. Stegmann et al led a resurgence of interest in viscocanalostomy in the late 1990s.5 Although theirs is a truly blebless procedure, most versions of nonpenetrating deep sclerectomy rely on the presence of a filtering bleb.
Both viscocanalostomy and nonpenetrating deep sclerectomy unroof Schlemm's canal and rely on the flow of aqueous through an exquisitely thin “trabeculo-Descemet's” window. Such procedures are technically difficult to perform and may be prone to late scarring. Accordingly, they have not been widely adopted. Nevertheless, both forms of nonpenetrating surgery are safe and effective, and they may have some advantages in certain clinical situations. Perhaps more importantly, these procedures have paved the way for new, more technologically sophisticated devices that bypass the trabecular meshwork and facilitate the flow of aqueous directly into the canal.
Trabecular Bypass Devices
Trabecular bypass stents and shunts are investigational devices that represent the most recent efforts toward blebless glaucoma surgery. These procedures facilitate the flow of aqueous into Schlemm's canal by shunting (Eyepass Glaucoma Implant; GMP Companies, Inc., Fort Lauderdale, FL) or by stenting the canal itself (iStent; Glaukos Corp., Laguna Hills, CA). Other devices such as the Solx Gold Micro-Shunt (OccuLogix, Inc., Mississauga, Ontario, Canada) divert aqueous into the suprachoroidal space. During excimer laser trabeculostomy, an excimer laser ablates trabecular tissue and provides a direct communication of aqueous into Schlemm's canal. Because the investigations of these devices and procedures are ongoing, there is unfortunately little published data or long-term results. For example, no data are available for the Eyepass Glaucoma Implant, and studies in the US have been suspended. The device is available in Europe, however, and studies are ongoing in Germany.
A recent report summarized the theoretical considerations as well as the results of the European clinical experience with the iStent device placed concurrently with cataract surgery in 47 patients6 (Figure 1). In this small, uncontrolled series, the IOP decreased on average from a baseline of 21.5 mm Hg to 15.8 mm Hg 6 months after the iStent's implantation, and the reduction in glaucoma medications was statistically significant (Figure 2).
Figure 1. The iStent may be placed in an ab interno fashion via a microdelivery system through a 1- to 2-mm clear corneal incision. (Courtesy of Glaukos Corp.)
Figure 2. The surgeon placed an iStent in combination with clear corneal phacoemulsification and IOL implantation.
Although the concept of trabecular bypass is intriguing and indeed promising, much work remains to be done. Johnstone has suggested that Schlemm's canal may not be entirely pristine in many patients with glaucoma.7,8 Moreover, the trabecular meshwork itself may become sclerotic, effectively obliterating the canal in some regions. Other investigators have expressed concern over the lack of circumferential flow within Schlemm's canal.9 That is, even if the trabecular meshwork is successfully bypassed with a stent or shunt, there is evidence to suggest that the enhanced outflow may be limited to several clock hours surrounding the bypass or perhaps a single quadrant.9 In such cases, multiple stents or shunts may be needed to lower the IOP adequately.
Ab Interno Trabeculotomy
The Trabectome (NeoMedix Corporation, Tustin, CA) employs microcautery to ablate and remove the trabecular meshwork and inner wall of Schlemm's canal. The surgical approach is transcameral, ab interno, typically through a clear corneal incision. The tip of the handheld device simultaneously irrigates and aspirates the ablated material. In a recently reported series of 37 patients treated with the Trabectome, the mean preoperative IOP following a 1-week washout period was 28.2 ±4.4 mm Hg. The mean postoperative IOPs were 18.4 ±10.9 mm Hg (n = 37) at 1 day, 17.5 ±5.9 mm Hg (n = 37) at 1 week, 17.4 ±3.5 mm Hg (n = 25) at 6 months, and 16.3 ±2.0 mm Hg (n = 15) at 12 months. As expected, a reflux of blood from Schlemm's canal and small transient hyphema were commonly observed in this series of patients, but they cleared by an average of 6 days postoperatively.10
Canaloplasty
A promising new procedure under investigation is the 360° canaloplasty in which the surgeon places a microcannula (iScience Interventional, Menlo Park, CA) in the canal via an external scleral dissection. The microcatheter is elegantly designed and measures 200 µm in diameter. Internally, the device has an optical fiber that allows transscleral visualization of the catheter's tip as it traverses the canal. A high-viscosity viscoelastic material is sequentially delivered in exquisitely controlled increments to the entire circumference of the canal, effectively viscodilating it (Figure 3). A recently described adjunct to the procedure involves placing a Prolene suture (Ethicon Inc., Somerville, NJ) within the canal. Early data suggest that the suture-augmented canaloplasty may enhance the reduction of IOP, although a randomized comparison of canaloplasty with and without the suture has not been conducted11 (also R. A. Lewis, K. von Wolff, M. Tetz, et al, unpublished data, January 2007).
Figure 3. Schlemm's canal is widely dilated after 360º canaloplasty with the microcatheter from iScience Interventional.
Potential Limitations
Devices that use Schlemm's canal for aqueous outflow will be limited in their ability to lower IOP by the resistance of the distal system and by the pressure of the espisceral vasculature. For example, Schlemm's-canal–based outflow will not be able to reduce IOP lower than episcleral venous pressure, generally believed to be in the range of 12 mm Hg. Moreover, the episcleral venous pressure may be substantially higher in some forms of glaucoma. Such limitations do not exist for procedures that completely bypass the conventional outflow system such as trabeculectomy, the placement of drainage devices such as the Baerveldt glaucoma implant (Advanced Medical Optics, Inc., Santa Ana, CA) or Ahmed Glaucoma Valve (New World Medical, Inc., Rancho Cucamonga, CA), which drain aqueous into the subconjunctival space, and the Solx Gold Micro-Shunt, which diverts aqueous into the suprachoroidal space. Thus, procedures that provide transscleral flow will likely continue to play a role in select individuals with badly damaged optic nerves and advanced glaucoma.
In the future, an ophthalmologist's selection of a glaucoma surgical procedure will probably be individualized based on target pressure. Patients who require very low IOPs may need a reservoir with inherently low resistance such as the subconjunctival or suprachoroidal space, whereas those with more modest target pressures may benefit from procedures that augment outflow into Schlemm's canal and the distal system. Ongoing clinical trials will further define the role that these procedures will play in the surgical management of glaucoma.
Thomas W. Samuelson, MD, is Adjunct Associate Professor at the University of Minnesota in Minneapolis and Attending Surgeon at Minnesota Eye Consultants/Phillips Eye Institute in Minneapolis. He is a consultant and investigator for iScience Interventional, a scientific advisor and investigator for Glaukos Corp., and an investigator for GMP Companies, Inc., and OccuLogix, Inc. Dr. Samuelson may be reached at (612) 813-3628; twsamuelson@mneye.com.
1. Parrish R, Minckler D. “Late endophthalmitis”—filtering surgery time bomb? Ophthalmology. 1996;103:1167-1168.
2. Grant WM. Further studies on facility of flow through the trabecular meshwork. Arch Ophthalmol. 1958;60:523-533.
3. Grant WM. Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol. 1963;69:783-801.
4. Johnson DH, Johnson M. How does non-penetrating glaucoma surgery work? Aqueous outflow resistance and glaucoma surgery. J Glaucoma. 2001;10:55-67.
5. Stegmann R, Pienaar A, Miller D. Viscocanalostomy for open-angle glaucoma in black African patients. J Cataract Refract Surg. 1999;25:316-322.
6. Samuelson TW, Katz LJ, Spiegel D. Exploiting Schlemm's canal to restore physiologic outflow in glaucoma. Poster presented at: The 16th Annual Meeting of the American Glaucoma Society; March 4, 2006; Charleston, SC.
7. Johnstone MA. The aqueous outflow system as a mechanical pump: evidence from examination of tissue and aqueous movement in human and non-human primates. J Glaucoma. 2004;13:421-438.
8. Johnstone MA. Biomechanics of the aqueous outflow system. The sixteenth annual AGS lecture. Paper presented at: The 16th Annual Meeting of the American Glaucoma Society; March 3, 2006; Charleston, SC.
9. Epstein DL. Journey to Schlemm's canal: roles for the MD clinician-scientist. The fifteenth annual AGS lecture. Paper presented at: The 15th Annual Meeting of the American Glaucoma Society; March 4, 2005; Snowbird, UT.
10. Minckler DS, Baerveldt G, Alfaro MR, Francis BA. Clinical results with the Trabectome for treatment of open-angle glaucoma. Ophthalmology. 2005;112:962-967; erratum in: Ophthalmology. 2005;112:1540.
11. Lewis RA, Ball S, Kearney JR, Stegmann R. 360-degree microcanalostomy of Schlemm's canal in POAG: interim results of US and center clinical trial. Paper presented at: The ASCRS/ASOA Symposium & Congress; March 19, 2006; San Francisco, CA.
