Ординатура / Офтальмология / Английские материалы / Glaucoma Surgery_Bettin, Khaw_2012

towards each other analogous to ‘closing a sling’ as correctly performed in canaloplasty [27]. However, if these vector components act mainly tangential to the TM axis when only one thread end is pulled causing friction stress as intentionally done in suture trabeculotomy [1, 56], the thread cuts the TM very easily. A newly developed implant like the Stegmann Canal Expander® (Ophthalmos GmbH, Schaffhausen, Switzerland) may make canaloplasty easier and more reproducible, and may eliminate all the drawbacks and risks inherent to the tensioning suture. It has the shape of a fenestrated hollow cylinder and is designed to create a permanent distension of SC and TM.

During surgery, it is possible that the microcatheter cannot be passed 360° at first try. The most common reason is that the tip of the microcatheter becomes stuck in the ostium of a large collector channel as the microcatheter slides along the outer wall of the SC. In such situation, a slight counter-pressure over the distal tip of the catheter on the limbus might be helpful. If this is unsuccessful, the catheter should be retracted and passed from the opposite side for complete 360° cannulation. Passage of the microcatheter into the suprachoroidal space or anterior chamber should be excluded early by careful observation of the illuminated tip. In any case, further injection of OVD should absolutely be avoided as it may cause detachment of DM which is a rare but potentially vision-threatening complication [27, 44, 45]. Detachment of DM is more likely to happen in the case of canal adhesions between the inner and outer wall, when the intracanalicular resistance exceeds the strength of the junction to DM at Schwalbe’s line. Most studies have reported a low incidence of DM detachment between 1.6 and 6.1% [6, 27, 44, 45, 47–49], but bilateral detachments of DM have been described [57].

Limitations

Despite the high safety profile, ab externo SC surgery has several drawbacks. The ability of IOP reduction is limited by the physiologic pressure gradient of the outflow system mainly by the EVP. Postoperative IOP below 12 mmHg is virtually not achieved. Another disadvantage, which is the same for all ab externo techniques, is that the conjunctiva is harmed, and subsequent filtering surgery if required will be compromised. Further, SC surgery is not indicated in eyes with angle recession, neovascular glaucoma, and aphakic glaucoma. In eyes with chronic angle closure, and steep inlets with plateau iris, canaloplasty should be performed in combination with cataract surgery. Another limitation of SC surgery is the current lack of knowledge of proper suture tension, which is understood to be crucial for the success of canaloplasty. Distension of inner wall is thought to increase trabecular permeability and aqueous outflow. A loose suture may not provide adequate tension required to lower outflow resistance, whereas a too tightened suture may close off the inter-trabecular space potentially increasing that resistance [27]. Furthermore, the ideal suture tension

may vary among individuals, and reference values have not yet been determined. It also remains to be investigated whether high-resolution UBM, if available to the surgeon, may be helpful in the judgment of the canal distension being predictive for IOP reduction as longitudinal assessments have not been conducted [45].

Concept and Mechanism

Ab externo SC surgery is proven to produce substantial and sustained IOP reduction, but little is known regarding its mechanism. In an experimental study on primate and human autopsy eyes, Smit and Johnstone [12, 58] demonstrated that injecting OVD into SC resulted not only in marked dilation of the canal (about ten times to 230 μm from its usual diameter 25–30 μm), and associated collector channels but also lead to microdisruption of the inner and outer wall of SC [59]. This provides direct communication between the anterior chamber and the lumen of SC as well as choroidal tissue, increasing conventional and uveoscleral outflow. Further, it has been postulated that the hemostatic properties of OVD may avoid bleeding and fibrin clot formation, and reduce healing process and scar formation at the ostia [28]. However, as OVD is washed out after 48–72 h, it is unable to retard healing of the ostia in the long run.

The rationale for enlarging a greater part of SC is to improve transtrabecular outflow remote from the exposed TDM giving aqueous direct access to collector channels, and to restore circumferential canalicular flow [12]. This also allows for the anatomical distribution of the collector channels which are more numerous in the lower and nasal quadrant [10, 11, 60]. In a pilot study on human perfused cadaver eyes, 180° expansion of SC by means of the microcatheter showed a significant increase in outflow facility which was related to the amount of dilation [61]. The first clinical study investigating the dilation of the entire SC with OVD demonstrated a substantial reduction in IOP with few postoperative complications [13].

Experimental studies on canaloplasty have not yet been published, so its mechanism still needs to be investigated. It is understood that the permeability of the inner wall region is increased by viscodilation and maintained by the suture distension, which may also improve circumferential flow and reduce the risk of re-collapse of SC (fig. 7). However, it is unclear to what extent each of the postulated factors contributes to an increase in aqueous outflow and IOP reduction: creation of scleral lake and TDM window, 360° viscodilation, and placement of the suture stent.

Conclusions and Future Prospects

The common goal of all surgical procedures for glaucoma is to lower IOP – the main risk factor for the development and progression of glaucoma. Ideally, surgery should target exclusively the pathological site of aqueous outflow resistance without harming

Fig. 7. Slit-lamp gonioscopy after canaloplasty illustrates the distension of the inner wall. Note the knot of the suture stent.

other structures of the eye. Ab externo SC surgery comes close to this goal; it aims to correct the abnormally high resistance to outflow in the TM and to reestablish the physiologic outflow. Viscodilation of SC leads to microperforations of the inner wall, which in turn reduces outflow resistance as demonstrated in viscocanalostomy. In canaloplasty, the additional intracanalicular tension suture keeps the canal patent and enhances the circumferential flow in the canal. In both procedures, the surgically created intrascleral space may serve as a reservoir for aqueous before leaving through the collector channel system. The main advantage of SC surgery is without any doubt the independence of subconjunctival filtration. First, the problems inherent to filtering blebs are avoided. They range from mild discomfort which doctors are often not oblivious of, to refractive changes and astigmatism, and to severe infections such as blebitis and endophthalmitis. Second, the postoperative care is much less intense and arduous than after trabeculectomy. The follow-up visits are fewer and the chair time after surgery is less. There are no bleb massage, subconjunctival injection of antimetabolites, and needling procedures, all invaluable for the patient, the busy surgeon and last but not least the health care costs. Third, hypotony is practically eliminated by the intrinsic resistance of the distal physiological outflow system including EVP. The high safety profile but the limited potency of very low IOP after surgery scrutinizes the time of surgical intervention and the choice between newer and traditional procedures. The surgeon has to weigh the pros and cons for each method regarding the preset target IOP and the patient’s risk for complications. Ab externo SC surgery will likely play an important role in early glaucoma with high IOP, in patients with intolerance or poor adherence of medications, ocular surface problems, and wearing contact lenses; further, it is a valuable alternative in younger patients who may not need a very low IOP, but the risk of vision-threatening complications following trabeculectomy is too high, and in patients with high risk for infections for sanitary and climatic reasons. A frequently mentioned concern is that ab externo SC surgery is too difficult for the average glaucoma surgeon. While they are unambiguously challenging procedures, one may object, that with the advance of microsurgery, creating a filtering hole in the eye like in trabeculectomy and dealing with all the inherent drawbacks will no

longer be the state of the art. Ab externo SC surgery has the potential to become the future standard in modern glaucoma surgery because of its efficacy and high safety profile, which meet the expectations of the demanding glaucoma patient. Surgeons will be well advised to implement these procedures into their armamentarium.

Description of Devices and Procedures

Trabectome (Trabeculotomy Internal Approach)

Trabectome System

Trabeculotomy by internal approach with the Trabectome system (Neomedix Inc., Tustin, Calif., USA) is performed to remove a strip of trabecular meshwork (TM) and inner wall of Schlemm’s canal in order to create a direct pathway for aqueous from the anterior chamber to Schlemm’s canal and aqueous collector channels. The Trabectome consists of a disposable handpiece connected to a console with irrigation and aspiration as well as a bipolar electrocautery generator. The handpiece is a 19.5-gauge instrument with a tip that incorporates an insulated footplate with a pointed end for ease of insertion through the TM. The tissue between the outgoing and return electrodes is vaporized using high frequency electrocautery energy in bursts with a high peak power and low duty cycle. An aspiration port is located adjacent to the cautery electrode, and irrigation more distally to keep the anterior chamber formed and dissipate heat energy. The aspiration pump is peristaltic and allows for flow rates up to 10 ml/min, controlled by the surgeon via a 3-position foot pedal (position 1: irrigation, 2: aspiration, 3: cautery). The amount of flow is controlled by manually adjusting the bottle height on a pole above the console.

Trabectome Surgical Procedure

In preparation for the procedure, the head and microscope are tilted to give a gonioscopic view of the angle, with a combined tilt of 60–80°. The view of the angle is verified by placing the goniolens on the cornea. A 1.7-mm keratome is used to make a near limbal, temporal corneal incision. Preservative-free lidocaine 1% may be injected into the anterior chamber followed by 2% hydroxypropyl methylcellulose viscoelastic (Ocucoat, Bausch and Lomb, Rochester, N.Y., USA) in most cases.

The Trabectome handpiece is inserted and advanced nasally across the anterior chamber with the infusion on, guided by a surgical gonioscopy lens. The pointed tip of the footplate is inserted through the TM into Schlemm’s canal, and a footswitch activates the aspiration and electro-surgical elements. The surgeon advances the instrument along the meshwork using the limbal corneal incision as a fulcrum, ablating and removing the strip of TM and inner wall of Schlemm’s canal. Initial power setting is 0.7–0.9 W and is titrated up or down depending on the desire to ablate a wider strip of TM or by charring of tissue, respectively. The formation of a ‘cleft’ or unroofed Schlemm’s canal is verified, and the angle is viewed for evidence of blood reflux from Schlemm’s canal. Irrigation and aspiration of the anterior chamber is performed with a Simcoe handpiece connected to the device tubing, and the incision may be closed with a 10-0 suture.

Proof of Concept: Histological Evidence

Histopathological analysis was performed to confirm the ability of the Trabectome device to remove the target tissue and compare it to simulated goniotomy [1]. Treated areas were examined by confocal microscopy in 20 donor human corneoscleral rims that underwent trabeculotomy with a Trabectome device and 2 specimens that received simulated goniotomy.

Twenty specimens were treated by the Trabectome at various power levels (0.3– 5.0 W) to determine the width of the TM gap created and to monitor for surrounding tissue damage. At 0.3 W, the average gap was 79.55 μm, which included one sample in which Schlemm’s canal was not cannulated by the footplate. At 0.5 W, the TM gap averaged 106.8 μm, with one sample that only demonstrated damage to the superficial TM. At 0.7 W, the average TM gap was 126.8 μm; one sample showed full-thickness TM damage, but had reapproximated ends. All samples that underwent trabeculotomy at powers greater than 0.7 W (except one sample at 1.0 W) showed disruption of the TM with separation of the severed ends. There was no evidence of thermal damage in any of the tissue samples seen deep to the TM or in the surrounding tissues. Coagulation was visible in 10 among the 20 samples treated, and commonly affected the anterior TM more than the posterior TM.

The theoretical advantages of the procedure are that it opens a large pathway for aqueous outflow from anterior chamber to Schlemm’s canal with minimal heat damage or trauma to adjacent structures. The clear corneal approach prevents conjunctival scarring or bleb formation, and also combines well with phacoemulsification. The possible disadvantages are the lack of circumferential flow in Schlemm’s canal, the possibility of cleft closure, and the limitation of IOP reduction by episcleral venous pressure and Schlemm’s canal resistance.

Trabecular Micro-Bypass Stent (iStent)

Trabecular Micro-Bypass Stent (iStent) Device

The trabecular micro-bypass stent is designed to create a permanent opening from the anterior chamber into Schlemm’s canal in order to provide a conduit for aqueous humor to bypass the TM and Schlemm’s canal inner wall and directly enter the canal to access the collector channels. The Glaukos Trabecular Micro-Bypass Stent, or iStent (Glaukos Corporation, Laguna Hills, Calif., USA) was designed to fit into and remain within Schlemm’s canal. It is made from nonferromagnetic titanium and consists of an inlet, or anterior-chamber end connected at a right angle to the implantation portion, which has a pointed end to facilitate entry into the canal and is shaped like a half cylinder at the distal end to prevent blockage or fibrosis over the tip.

iStent Surgical Procedure

A 3-mm self-sealing temporal corneal incision is made and the implant and applicator tip are rinsed with balanced salt solution. The anterior chamber is filled with viscoelastic, and the head and microscope are tilted to provide a gonioscopic view of the angle. The surgical goniolens is placed on the cornea, the applicator is inserted into the anterior chamber and advanced across to the nasal angle. The pointed tip of the device is used to perforate the TM, and the distal end is slid into the canal. The device is released by pushing the button on the applicator, and the tip of the applicator is used to gently push the device to ensure that it is seated within the canal with the tip parallel to the iris plane. The viscoelastic is then removed with irrigation/aspiration and the anterior chamber is filled with balanced salt solution to physiologic levels. The corneal incision may be closed with a 10-0 suture.

Proof of Concept: Theoretical and in vitro

Theoretical

The theory behind trabecular bypass was explored by Zhou and Smedley [2] by mathematical equations used to calculate the expected effect on the outflow facility and IOP. First, they assume that the primary resistance to outflow is in the TM, and that the collector channels are so close together and so similar in dimensions as to form a uniform leak from the canal. In a normal healthy eye, the IOP is 15 mmHg, the episcleral venous pressure is 9 mmHg and the rate of aqueous humor outflow is 2.4 μl/ min. This results in an average total resistance of conventional outflow pathway of 2.5 mmHg/(μl/min) and average outflow facility of 0.4 μl/min/mmHg. According to their geometrical model, the conventional outflow pathway is axisymmetric, the pressure in the canal is essentially uniform, and there is no circumferential flow. Thus, when the TM is intact, the resistance of the canal does not impact the outflow resistance. When the trabecular bypass is created, aqueous enters into the canal through the bypass and meshwork, and then is drained from the canal via the collector channels. Now the outflow pathway is no longer axisymmetric, and the resistance of Schlemm’s canal affects the outflow.

Based on this mathematical outflow modeling assuming a constant conventional outflow of 2.4 μl/min is assumed, the situation is the following:

With no bypass: IOP = 15.0 mmHg; flow through TM = 2.4 μl/min; flow through bypass = 0; facility of outflow = 0.40 μl/min/mmHg.

With a unidirectional bypass: IOP = 14.3 mmHg; flow through TM = 1.84 μl/min; flow through bypass = 0.56 μl/min; facility of outflow = 0.45 μl/min/mmHg.

With a bidirectional bypass: IOP = 13.8 mmHg; flow through TM = 1.40 μl/min; flow through bypass = 1.00 μl/min; facility of outflow = 0.51 μl/min/mmHg.

In vitro

The device was tested in cultured human anterior segments to assess in vitro IOP reduction by Bahler et al. [3]. In this study, the anterior segments (eyes were bisected