Glaucoma is one of the leading causes of blindness worldwide. It was estimated that in 2010, 60.5 million people had glaucoma and this was projected to increase to 79.6 million by 2020.1 Glaucoma is not considered a single disease, but rather a group of diseases associated with three major characteristics: optic neuropathy with excavation of the opticcup and associated loss of the neuroretinal rim; retinal nerve fiber layer thinning; and a resultant loss of visual field.
Advancing age, family history, race, and elevated intraocular pressure (IOP) are the major risk factors for optic nerve degeneration in glaucoma. Currently, the only risk factor that may be modified is the IOP: this can beachieved by either reducing the production of or increasing the outflow of aqueous humor.
An understanding of the complex mechanisms that regulate aqueous humor circulation is essential for the management of glaucoma. Aqueous humor leaves the eye via two pathways: the trabecular meshwork and the uveoscleral pathway, with 75 % of the resistance to aqueous humor outflow beinglocated within the trabecular meshwork and 25 % located beyond Schlemm’s canal. The latter possesses internal collector channels and is connected to episcleral and conjunctival veins through the external collector channels, the intrascleral venous plexus, the deep scleral plexus, and the aqueous veins.2 These findings form the basis of the surgical treatment of glaucoma.
There are a variety of drugs that lower IOP, as well as surgical techniques that alter the flow dynamics of the eye. These include laser surgery and filtering microsurgery. The latter creates a drainage fistula interconnecting the anterior chamber to the subconjunctival space that creates a route for aqueous humor to exit the eye and results in a filtration bleb. The long-term success of the procedure depends on the capacity of the subconjunctivaltissue to absorb this fluid and allow absorption into the capillary network, without generating excessive scar tissue that will impede fluid flow.3
Trabeculectomy has been the standard surgical treatment for glaucoma4 and can provide long-term reductions in IOP.5 However, some ophthalmologists may avoid the operation due to a potential risk for postoperative complications, a perceived lack of a fully standardized surgical procedure, and intersurgeon variation. Short-term complications after trabeculectomy include anterior chamber shallowing, hypotony, and choroidal detachment. Long-term complications include bleb leaks, blebitis, bleb-related endophthalmitis, overhanging blebs, bleb fibrosis and encapsulation, corneal endothelial cell loss, dellen, and aqueous misdirection.6,7 Trabeculectomy presents challenges in terms of creating a reproducible sclerostomy although many surgeons are able to overcome this and achieve reliable results. At the time of surgery, physicians may attempt to estimate the size of the opening needed via the number of bites with a Kelly punch or by removing sclera freehand, both of which introduce a source of variability from patient to patient. Use of a Kelly punch is associated with complications, including iris prolapse and rapid evacuation of aqueous from the anterior chamber, which causes the chamber to shallow. In addition, patients undergoing the traditional trabeculectomy also have surgical iridectomies. There are inherent risks with iridectomies that include intraoperative bleeding, postoperative hyphema formation,monocular diplopia, and, if zonular dialysis is present, potentially vitreous prolapse through the iridectomy.
Glaucoma implants, known as aqueous shunts or glaucoma drainage devices, were initially developed for use in complex glaucoma patients,many of whom had failed medical, laser, and prior surgical treatments. Many drainage devices include a tube through which the aqueous fluid passes. Others are solid and promote the flow of fluid along the surface of the implant. However, their use has its own litany of complications and failures. Glaucoma drainage devices with valves or flow regulators may not always provide low enough postoperative IOP and in some cases have been associated with complications.8 A 2005 literature review of five commonly used implants reported that surgical failure occurred in ~25 % of cases.9 The EX-PRESS® Glaucoma Filtration Device (Alcon, Fort Worth, TX) represents an advance in glaucoma drainage device technology. This article will describe the flow dynamics of the EX-PRESS device and review clinical studies in support of its use.
The EX-PRESS Glaucoma Filtration Device
The EX-PRESS Glaucoma Filtration Device is intended to reduce IOP in glaucoma patients where medical and conventional surgical treatments have failed. The device is a miniature (<3 mm long) aqueous shunt composed of medical-grade stainless steel10 and is fully biocompatible with the eye10 (see Figure 1). It has a spur to prevent extrusion and an end-plate to prevent intrusion into the anterior chamber. The trans-scleral miniature tube delivers aqueous from the anterior chamber to the subscleral and subconjunctival spaces, to form a filtration bleb in a similar manner to trabeculectomy. Postoperative outflow is controlled by the flow-modulating design.11 Its standardized ostium size allows a more reproducible channel for fluid to drain out of the anterior chamber into the subconjunctival space.
The EX-PRESS device also offers the advantage of being less invasive than other techniques: implantation does not require scleral or iris tissue removal and requires a small point of entry into the anterior chamber. The device is implanted under a partial-thickness scleral flap that provides additional resistance to aqueous outflow and minimizes the risk for conjunctival erosion.12 The operative time can be less than trabeculectomy and the procedure does not require the acquisition of a new skill set for many glaucoma surgeons, rather just the refinement of a few procedural steps accounting for the standardized ostium. The EX-PRESS device implantation procedure standardizes the sclerostomy. As a result of the lumen remaining constant, aqueous flow is adjusted by the number and tightness of the sutures used to close the scleral flap without having to consider a varying sclerectomy opening. Since there is no need to perform an iridectomy, the procedure should result in less inflammation.13
Flow dynamics modeling has been used to optimize trabeculectomy and glaucoma-filtration devices. The success of implantation of glaucoma filtration devices depends on the formation of an improved outflow facility from the eye. A computational model has been developed describing fluid flow in the eye after glaucoma surgery.3 According to this model, failure of IOP control is more directly related to decreases in hydraulic conductivity, resulting from scar formation, than to decreased absorption. The success of glaucoma surgery therefore depends on the hydraulic conductivity of the fibrous cap that develops around the bleb. Small, encapsulated blebs are less likely to be effective at allowing fluid to move into and be absorbed by subconjunctival tissue, and expose tissues to high pressures, particularly directly above the bleb. This is believed to initiate an ischemic tissue remodeling response, a reduction of hydraulic conductivity, and an elevation of IOP. High blebs are less likely to undergo remodeling but may lead to hypotonous eyes.3 A low, diffuse bleb is therefore the ultimate goal of glaucoma-implant surgery. The engineering of the EX-PRESS device improves flow dynamics and provides the surgeon lumenal control in their filtration surgery (see Figure 2).
Its length is designed to scan the sclera and enter the anterior chamber. The vertical slot in the end-plate is designed to direct aqueous flow posteriorly and facilitate the generation of a low-lying, diffuse bleb.11 A restrictor bar allows for the option of two sizes of internal lumens while maintaining a constant outer dimension. Two different models are available: the P-50 and P-200. They differ only in their internal lumen. In fluid dynamics, flow and resistance are inversely related to each other. The Hagen–Poiseuille equation, also known as the Poiseuille law, describes the pressure drop in a fluid flowing through a long cylindrical tube. Resistance to flow through a tube is determined by three factors: the effective radius or diameter of the tube’s internal lumen, the tube length, and liquid viscosity. According to the Hagen–Poiseuille equation, the factor with the greatest impact on resistance is the diameter of a tube’s internal lumen, i.e. a small change in diameter leads to a large inverse change in resistance.
The EX-PRESS device acts as a simple flow resistor and in a flow dynamics study, created a relatively constant resistance to flow.14 The P-200 model with the larger internal lumen gave the highest flow rate and generated the least resistance to flow. Compared with the P-50 model, the flow rates were statistically significant (p<0.0001) at all pressure levels. All models tested showed higher flow rates per unit pressure than the outflow facility of a healthy human eye. It has been postulated that the lower rate of hypotony of the EX-PRESS device compared with trabeculectomy can be explained by the resistance to flow that is offered by the 50 μm lumen of the shunt. In trabeculectomy, the smallest scleral punch available is approximately 750 μm and that is only if one punch alone is used to make the incision.15
Clinical Studies of the EX-PRESS Device
Several studies to date have demonstrated that the EX-PRESS device has equivalent efficacy to trabeculectomy, but its flow dynamics confer advantages (see Table 1). The EX-PRESS device relies on nonphysiologic subconjunctival flow as its mechanism of IOP lowering similar to that of a trabeculectomy. While the EX-PRESS device standardizes the filtration procedure, as with any surgical procedure, there are complications and adverse events. Additional glaucoma filtration surgery, device removal, bleb revision with or without antimetabolites, device-iris touch, hyphema <2 mm, shallow anterior chamber, hypotony, tenon cyst, corneal complication, anterior chamber reformation, and device exposure are listed in the EX-PRESS directions for use with an occurrence rate above 5 %. In the first large, retrospective study to compare standard trabeculectomy with the EX-PRESS device, the EX-PRESS device was implanted in 50 eyes of 49 patients and a traditional trabeculectomy performed in 50 eyes of 47 patients. After 12 months, the IOP reduction was similar in both groups, but there was less postoperative hypotony (IOP <5 mm Hg); 32 % hypotony rate in the trabeculectomy group versus 4 % in the EX-PRESS device group.16 In another study, 345 eyes underwent EX-PRESS device implantation with or without cataract surgery. At 3 years, the success rate was 95 %. Hypotony was seen in 15.6 % of the EX-PRESS device group in the first week, and 7.9 % with hypotony in the combined group. All instances of hypotony during the early postoperative period resolved spontaneously.
Implantation of the EX-PRESS device is also a safe procedure when combined with cataract surgery. In a prospective series of 40 consecutive eyes, patients treated with combined phacoemulsification and EX-PRESS device implantation were compared with those who underwent combined cataract and glaucoma surgery with trabeculectomy. The complications rate in the early postoperative period was significantly higher in the trabeculectomy group. No significant differences were objectified in success between both groups after the first week.17 In an evaluation of the EX-PRESS device in refractory postpenetrating keratoplasty glaucoma, the complete success rate was 86 %. After implantation of the EX-PRESS device, clear grafts remained clear and edematous grafts became clearer.18
In a five-year extension of a randomized study (n=78),19 only 41.0 % of the patients in the EX-PRESS device arm required IOP-lowering drugs, compared with 53.9 % of the 39 patients in the trabeculectomy arm and patients required fewer IOP medications and fewer surgical interventions during the 5-year study period. More patients required bleb needling in the trabeculectomy group compared with the EX-PRESS device group (nine versus three, respectively) and more patients required cataract extraction in the trabeculectomy group than in the EX-PRESS device group (eight versus five, respectively).20
A retrospective, consecutive case-control series (n=70) focused on the health and integrity of the postoperative bleb. The pressure reduction achieved with the EX-PRESS device was found to be similar to that of a trabeculectomy but visual recovery to the preoperative baseline was significantly quicker in the EX-PRESS group being achieved 1 week after implantation compared with 1 month for trabeculectomy. Evaluation of bleb morphology by the Moorfields Bleb Grading System revealed less vascularity and height, but more diffuse area associated with the EX-PRESS device blebs, although these differences were not seen at study completion. The EX-PRESS device group had fewer cases of postoperative hypotony, fewer post-operative visits, and underwent a quicker visual recovery.21
In a recent prospective, randomized study (30 eyes of 15 patients), each patient underwent trabeculectomy in one eye and EX-PRESS device implantation under a scleral flap in the other eye. (see Figure 3) At the last follow-up visit (mean 23.6 months), IOP decreased from 31.1 to 16.2 mmHg in the trabeculectomy group, and 28.1 to 15.7 mmHg in the EX-PRESS device group.22 Complications were generally mild and less common in the EX-PRESS device group (20 % versus 33 %), as were complications requiring surgical intervention (0 % versus 27 %). In addition, one eye in the trabeculectomy group had a postoperative hyphema and an eye in the EX-PRESS group had a wound leak—these mild complications both resolved spontaneously within a week. The most common complication was hypotony (7 % EX-PRESS device group; 33 % trabeculectomy group), but all resolved spontaneously and without serious complications within 1 month of surgery. The major weakness of this study was its small sample size: only 30 eyes were studied (15 patients), due to the difficulty in enrolling primary open angle glaucoma patients who were willing to undergo trabeculectomy in one eye and EX-PRESS device implantation in the other eye in a randomized manner. However, despite the small group size, a statistically significant difference was seen between procedures, particularly in terms of success rates and complication rate. Comparing the two interventions in fellow eyes of the same patient further strengthened the validity of these findings.
The EX-PRESS device also has superior visual outcomes compared with trabeculectomy. A recent prospective, randomized study (n=64), found that although there was no difference in mean visual acuity (VA) between the EX-PRESS device and trabeculectomy groups at any time point, trabeculectomy eyes were more likely to lose ≥2 Snellen lines. Furthermore, the study showed that VA recovers to a preoperative baseline more quickly following EX-PRESS device surgery than trabeculectomy. At the 6-month follow up, 47 % of patients in the trabeculectomy group and 16 % (p=0.01) in the EX-PRESS device group had lost ≥2 Snellen lines (see Figure 4).23
There is also evidence from previous studies of quicker VA recovery following EX-PRESS implantation: Good and Kahook found that VA returned to baseline by 1 week in the EX-PRESS device group compared with 1 month in the trabeculectomy group.22 The Sugiyama study found that VA was significantly poorer from 1 week to 3 months in the trabeculectomy group while it was stable in the EX-PRESS device group for 12 months of follow up.24
Summary and Concluding Remarks
There is a need for improved surgical treatment options in glaucoma patients, especially those in which a procedure and medications have already failed. The strategy for managing patients who have experienced a failed trabeculectomy or corneal scarring can be challenging. The EX-PRESS device offers another option for these glaucoma patients. Implanting the device in the correct location and entering at the iris plane are important to reach optimal outcomes.
Results of retrospective and prospective clinical studies demonstrate that implantation of the EX-PRESS device has similar success rates as trabeculectomy, but lower rates of hypotony and choroidal effusions. The EX-PRESS device provides a more consistent flow of aqueous than trabeculectomy, and the bleb is low and diffuse, perhaps related to the fact that the egress of aqueous is more posterior with the EX-PRESS than with a manually created sclerostomy (see Figures 1 and 2). Furthermore, implantation of the EX-PRESS device in patients with previous glaucoma surgery, allows faster visual recovery to preoperative baselines compared with trabeculectomy, and can be combined successfully with more complex surgical procedures, including cataract surgery.
Implantation of the EX-PRESS device incurs additional costs compared with trabeculectomy, similar to that of tube shuts. However, for many doctors and patients the cost of the EX-PRESS device is outweighed by its benefits in terms of proven IOP lowering, fewer hypotony and choroidal effusions, quicker recovery of VA to the preoperative baseline VA, and fewer postoperative visits. In summary, the EX-PRESS device offers a step toward the standardization of aqueous outflow that is consistent with the trend in ocular surgery toward smaller incision microsurgery, and is associated with less inflammation,greater predictability with less hypotony, and more rapid visual recovery.