Microinvasive Glaucoma Surgery: A Review of Schlemm’s Canal-Based Procedures
Received 6 December 2020
Accepted for publication 18 February 2021
Published 11 March 2021 Volume 2021:15 Pages 1109—1118
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Scott Fraser
Joanna Konopińska,1 Katarzyna Lewczuk,2 Joanna Jabłońska,2 Zofia Mariak,1 Marek Rękas2
1Department of Ophthalmology, Medical University of Bialystok, Białystok, Poland; 2Department of Ophthalmology, Military Institute of Medicine, Warsaw, Poland
Correspondence: Joanna Konopińska
Department of Ophthalmology, Medical University of Białystok, Jana Kilińskiego 1 STR, Białystok, 15-089, Poland
Tel +48 857468372
Fax +48 857468604
Email [email protected]
Abstract: Microinvasive glaucoma surgery has gained popularity over the past decade. It can be performed using three different mechanisms. In the present review, we focused on Schlemm’s canal (SC)-based surgery, which increases aqueous humor (AH) outflow into the aqueous veins by either removal of the trabecular meshwork (TM) or an increase in the tension in the TM. In primary open-angle glaucoma (POAG), the TM is the most likely region for increased AH outflow resistance. Theoretically, removal of the TM can improve the AH outflow; hence, glaucoma specialists focus on microsurgical dissection of the TM. In this review, we analyzed the available literature to examine SC-related microsurgical modalities based on the histopathological proofs of the localization of resistance of the AH outflow. First, we considered the role, anatomy, and physiology of the TM and SC. We referred to studies that describe the mechanisms and potential pathways, related to increased intraocular pressure in the POAG, that are targeted using the SC-related microsurgical interventions. Next, we took a closer look at the gonioscopic tools necessary for an ab-interno approach and explored incision canal surgery: ab-interno trabeculectomy using different instrumentation (Trabectome®, Kahook Dual Blade) and variations of the technique. Thereafter, we discussed ab-interno canaloplasty, explaining the technique and reviewing its effectiveness. Finally, we presented the scope for future research in the field. Although the iStent also targets SC by bypassing it, this device has been reviewed extensively elsewhere.
Keywords: microsurgery, trabecular meshwork, canaloplasty, trabeculotomy, Kahook Dual Blade, Schlemm’s canal
Glaucoma is still the most common cause of blindness worldwide. It is estimated that 13.5−42.0% of glaucoma patients are blind unilaterally, and 4.0−16.0% bilaterally.1 The only treatment proven to slow progression of glaucoma and the related visual-field loss is the reduction of intraocular pressure (IOP).2,3 Although trabeculectomy is still considered to be the gold standard in glaucoma surgery, it may cause many short- and long-term side effects.4 It has an approximate success rate of 80% after 1 year.5 This success is paired with the burden of a 1%-per-year risk of endophthalmitis and other frequent, sight-threatening adverse events, such as persistent hypotony and choroidal detachments.6 Glaucoma drainage devices are reported to have a success rate of approximately 50–75% at 5 years, but can also precipitate major complications such as motility disturbances, hypotony, corneal decompensation, and tube erosion,7–9 to name a few. Such complications often result in the postponement of surgery until visual-field loss is extensive.
Due to increasing life expectancy, individuals have a higher lifetime risk for glaucoma development and generally live long when they do have glaucoma.10 Therefore, it has become essential to operate glaucoma at an early stage and lower IOP intensively from the beginning. For over a decade, intensive research has been conducted on the use of microinvasive glaucoma surgery (MIGS), aiming to reduce IOP and the fluctuations thereof, while posing a low risk of side effects that influence the patients’ quality of life, and decreasing the burden of medications. There are different types of MIGSs from an anatomical viewpoint. In this review, we focused on procedures based on Schlemm’s canal (SC), since the likely underlying mechanism of IOP increase is an amplified resistance to aqueous humor (AH) outflow by the trabecular meshwork (TM).11–13
Goniotomy and trabeculotomy are effective in treating glaucoma in children; the incisions made cause the elastic scleral spur to retract posteriorly, stretching and separating the TM. These techniques are improved by removing a strip of the TM in adults; otherwise, the anterior and posterior TM may reapproximate and occlude the collector channel (CC) intakes. Goniotomy and trabeculotomy are categorized as MIGSs when they are modified to perform via an anterior chamber access. The difference between the SC-based MIGSs is in the method of the TM removal or bypass. The TM may be removed using plasma-mediated TM ablation14 or physical TM removal with or without irrigation and aspiration;15 the TM may also be bypassed using stents.16–18
Trabecular Meshwork Function and Structure
Drainage of the AH from the trabeculum to the CCs takes place via SC. Cells of SC vary depending on their location, as the inner and outer walls can be distinguished in the canal’s microanatomy. Each wall is lined with an endothelium: a continuous, single layer of cells that differ in terms of morphology, expression of markers, organelles, and function.19,20 The TM is a connective tissue without any vessels, which lines the inner SC.21 The TM has three regions. 1) The anterior chamber borders the uveal meshwork contains a system of fenestrated collagen-elastin fiber lamellae concealed by the TM cells. 2) The corneoscleral meshwork contains the TM, which covers the perforated collagen and elastin plates. This structure borders the sclera and the cornea. 3) The juxtacanalicular connective tissue (JCT) borders the inner wall of SC and consists of loose connective tissue, with the TM cells encircled by an irregular extracellular matrix (ECM).21 The inner wall is linked to the ciliary muscle with elastin fibers that extend from the terminal part of the longitudinal fibers via the corneoscleral meshwork and the JCT.22 The above three regions are considered to function as a filter, as they are positioned directly over SC. The terminal part of the TM, the “insert,” is considered “non-filtering,” as it abuts Schwalbe’s line rather than SC.21,22
The inner wall is the region most frequently analyzed since it provides major resistance to the drainage of the AH.23,24 Characteristic features of the inner wall are tight junctions of vascular endothelial-cadherin and giant vacuoles and pores. Together, the JCT and the inner wall structures play important roles in the regulation of the AH outflow.25
The spaces between the ECM and the inner wall cells of SC are called “giant vacuoles.”26 These are dynamic and increase in quantity and size as IOP increases.27–29 Giant vacuoles are mostly found near the CC outlets.26,30 This indicates the presence of a high aqueous flow resulting in a high-pressure gradient at these sites.26
The pores of the inner wall, with sizes of 0.6–3 µm,31 account for 10% of the AH outflow.32,33 The AH flow in the inner wall mainly takes place via these pores. Such pores may occur in the walls of giant vacuoles or in other areas.34 Giant vacuoles form the preferential AH drainage pathways across the endothelium via a one-way valve mechanism. When the pressure increases in the episcleral veins, it also rises in SC; subsequently, the number of vacuoles and pores in the inner wall of SC reduces, preventing reverse blood flow from SC to the anterior chamber.35 Some medications (ie, glucocorticoids) that stimulate the polymerization of cytoskeleton proteins36 may hinder vacuole development, thereby increasing the resistance to the AH outflow.37 Reduced pore density is typical for eyes with glaucoma. This fact reveals that the inner wall plays a critical role in maintaining the AH homeostasis. The AH outflow resistance is amplified markedly by the interaction of the pores and the subendothelium (the basement membrane of SC cells and the JCT ECM).38
The second main role of TM cells is to act like biological filters. Interestingly, TM cells exhibit macrophage-like activity.21 They rapidly phagocytize cellular fragments of pigmented epithelia carried by the AH flow39 before it reaches the TM, where it may collect and alter the AH outflow.40 To fulfill this role, the TM cells produce a significant amount of anti-thrombogenic substances, such as heparin or tissue-plasminogen activator.41 Similar to endothelia, cells of the inner wall of the TM contribute to the antigen presentation and inflammatory reaction by releasing histocompatibility proteins and inflammatory cytokines.21
AH is not distributed uniformly throughout the inner wall of SC. As noted in the previous section, aqueous flow takes place mostly near CCs,26 where double the number of giant vacuoles are found compared to the rest of the inner wall. This shows that the fluid movement through the inner wall depends on the pressure gradient.42 AH flows through multiple curved veins, from the deep blood vessels known as the deep scleral plexus, through the limbal and intrascleral plexus, to the episcleral veins.43 SC-based MIGS builds on Grant’s study,44 in which it was observed that the excision of the TM or the external wall of SC in enucleated human eyes lowered the AH outflow resistance by 49% at normal IOP. When IOP was higher than normal, 71% of the outflow resistance was eliminated.33 Schuman et al45 also noticed that at normal IOP, TM ablation with an excimer laser allowed for a 35% reduction in the outflow resistance. These studies suggest that up to 50% of the outflow resistance occurs distally to SC, depending on the IOP. The fact that the IOP was reduced after removal of parts of the TM implies that the AH was able to drain through the downstream pathways beyond SC.
This residual outflow resistance beyond SC may reside in the AH pathway from the CCs to the intrascleral venous plexus or aqueous veins.46 The complete mechanism of the formation of this residual resistance is not fully known. What is known, however, is that the segmental AH outflow,47 perilimbal tissue biomechanics,48 and the aqueous veins are factors contributing to this mechanism.49
In a healthy eye, the IOP is nearly 16 mmHg, while pressure in the episcleral veins is 7–8 mmHg.50 The pressure differential across the TM is, therefore, ~8 mmHg. Grant et al32 managed to maintain an IOP of 25 mmHg in their early ex vivo experiments, which was higher than the mean IOP in a healthy eye. Consequent research revealed that trabeculotomy allowed for the elimination of only ~14% of the resistance under the condition of 5 mmHg IOP ex vivo (which is estimated as 13 mmHg in vivo).51 The same procedure eliminated up to 27% of resistance at an ex vivo IOP of 10 mmHg (equal to 18 mmHg in vivo), and at an ex vivo IOP in the range of 20–50 mmHg, it eliminated as much as 62–82% of the resistance.52 Subsequent experiments confirmed these findings53 as trabeculotomy decreased the resistance by 49% at an IOP of 7 mmHg and by 71% at an IOP of 25 mmHg. The conclusion of these studies is that the removal of TM at a low IOP results in minor improvements.
Ab-interno trabeculotomy (AIT) is performed under a goniolens, of which several kinds are commercially available. These lenses are modified versions of the Swan Jacob Lens, and they differ in the field of view, handle length, image magnification, and extent of corneal contact. Some of these goniolenses have been designed specifically to improve eyeball stability. Recently, a two-mirror goniolens with a static 45° field of view, the Ocular Upright 1.3× Surgical Gonioprism (Ocular Instruments, Bellevue, WA, USA), was presented.54 It redirects the oblique gonioscopy image to the coaxial “cataract-surgery” view, reducing the need for tilting the microscope.
The lens should be docked gently onto the corneal surface to avoid compression on the cornea and forming Descemet’s folds, which preclude visualization. To facilitate this, manufacturers provide additional equipment. The Volk Transcend Vold Gonio (TVG) Surgical Lens (Accutome, Malvern, PA, USA) consists of a main handle, a fixation ring, and a balancing lens, which is suspended by a separate pendular handle that endures the compression. The Ocular Hill Surgical Gonioprism (Ocular Instruments) has a marginal lip at the base of the lens for fixating the eyeball. The disposable iPrism Clip view stabilizer (Glaukos Corp., San Clemente, CA, USA) is an accessory made specifically to snap onto the lens base; it possesses atraumatic surface protrusions and an extended base, which are designed to stabilize the globe effectively.
Ab-Externo and Ab-Interno Trabeculotomy
Trabeculotomy, classically performed using an ab-externo approach, can also be performed using a clean corneal approach (AIT), owing to recent developments. AIT was first introduced in 2014 by Grover et al.55,56 In this method, a 360-degree incision that disrupts the first layer of the TM is made. The procedure is performed ab-interno under gonioscopy and via temporal and superonasal/inferonasal paracentesis with a microcatheter or a suture.57,58 Better known as gonioscopy-assisted transluminal trabeculotomy (GATT), this method makes performing trabeculotomy possible without the need for conjunctival or scleral incisions. Briefly, a temporal corneal incision is made and the nasal-angle structures are visualized using direct gonioscopy. A goniotomy is performed in the nasal quadrants, and microsurgical forceps are used to introduce a suture or a catheter (ie, iScience Interventional Corp., Menlo Park, CA, USA) into SC. Thereafter, the microcatheter or suture is circumferentially advanced into SC, until the distal end reaches the goniotomy point, following which it is retrieved. Thereby, a 360° trabeculotomy is performed. In two previous studies, the reported success rates of GATT was 68% and 100% in young children and infants with congenital glaucoma.56 Grover et al56 reported that in cases of juvenile glaucoma, the IOP dropped from 27.3 to 14.8 mmHg 12 months after GATT, and the medication burden declined from 2.6 to 0.86. In a study of adult patients, Grover et al57 reported an IOP drop of 11.1 mmHg and 1.1 fewer glaucoma medications administered at 12 months after GATT for primary open-angle glaucoma (POAG). In patients with secondary open-angle glaucoma (SOAG; ie, pseudoexfoliative, pigmentary, uveitic, and steroid-induced glaucoma) in the same study, the average decreases in IOP and glaucoma medications were 19.9 mmHg and 1.9, respectively, at 12 months. Two years after GATT, an IOP drop in patients with POAG of 9.2 mmHg (37.3%) and a decline in medication burden of 1.43 were observed.57 In patients with SOAG, at 24 months, an IOP decline of 14.1 mmHg (49.8%) was observed and 2.0 fewer medications were administered.57 Rahmatnejad et al59 did not observe a difference in the decrease in IOP between patients with POAG and SOAG. In that study, 66 patients were followed up for 11.9 months, on average. The overall success rate (IOP < 21 mmHg) was 63.0%. One year after GATT, the IOP dropped from 26.1 ± 9.9 mmHg to 14.6 ± 4.7 mmHg (44%), and the medication burden lessened from 3.1 ± 1.1 to 1.2 ± 0.9. Baykara et al58 reported a statistically significant average decrease in IOP from 34.2 ± 10.6 mmHg to 24.3 ± 11.7 mmHg (65.9% ± 10.7%), 6 months after GATT with phacoemulsification for patients with POAG. The medication burden was also reduced from 3.8 ± 0.4 to 0.3 ± 0.7. Aktas et al60 examined 65 patients with POAG and 39 with SOAG who had undergone GATT over a mean follow-up of 19.4 ± 8.1 (range, 6 to 37) months. The effect of GATT in their study was contrary to that observed by Grover et al,55–57 in that participants with POAG had a larger decrease in IOP versus patients with SOAG at the 18-month observation period (40.1% vs 27.6%). The medication burden at the end of follow-up did not differ between patients with POAG and SOAG, and overall surgical success (IOP < 21 mmHg) was achieved in 87 of 104 (83.7%) cases. The most frequent postoperative complication in all the above-mentioned studies was hyphema; in Grover et al,56 the rate of hyphema after the first week was 38%, and after 1 month it was 6%.
The Trabectome® electrosurgical device (MicroSurgical Technology, Redmond, WA, USA) was approved “for use with compatible electrosurgical instruments in low power microsurgical applications for the removal, destruction and coagulation of tissue” by the US Food and Drug Administration in 2004.61 It can be used for AIT, using a bipolar, 550-kHz electrode to ablate 30–180° of TM, which enables irrigation during dual-blade goniotomy.62 The trabectome comprises a disposable handpiece attached to a console that provides irrigation, aspiration, and electrocautery. Similar to the modern phacoemulsification machines, a foot pedal is used to control these actions. The trabectome is designed for the permanent ablation and removal of a strip of TM and the inner wall of SC, leaving the rest of the outflow system (the outer wall of SC, CCs, and aqueous veins) intact. It is also designed to minimize the development of anterior synechiae that would result in closure of the cleft. The 19.5-gauge tip is designed to fit through a 1.6-mm-or-larger corneal incision. A footplate, insulated with a proprietary multilayered polymer, is located at the tip of the handpiece, which is designed to prevent thermal and electrical damage to surrounding tissues. The distal tip of the device is pointed to allow for insertion into SC, and the footplate connects the tissues with the bipolar electrodes. An aspiration port near the tip is used to remove the ablated tissue and debris, while the irrigation port is used to maintain the IOP and dissipate heat generated during cauterization.63 A strip of TM and inner wall of SC, straddling from 80° to 100°, is ablated and aspirated afterwards. During the procedure, the surgeon is seated temporally to the operated eye and the ablation is initiated at 0.8 mW. Up to 90° of tissue can be ablated in both sides. Following removal of the tissue, a viscoadaptive substance can be injected into the anterior chamber to minimize blood reflux from SC. Studies that compared the relationship between the area of ablation and postoperative IOP decrease did not reveal any statistically significant differences.64 Intraoperative hyphema is desired during AIT and confirms the successful “unroofing” of SC. In traditional goniotomy or trabeculotomy, particles of the ruptured tissue remain after the procedure. Using the trabectome, tissue debris is simultaneously removed, which reduces the risk of inflammation and scarring.
The overall average success rate (defined as IOP < 21 mmHg, a 20% decrease, and no reoperation needed) in a study by Khan et al67 was 61 ± 17% at 1 year, and 46 ± 34% at 2 years. According to the authors of a review and meta-analysis,15 combining phacoemulsification with AIT using the trabectome yielded a surgical success rate of 85 ± 17% after 1 year (n=6) and 85 ± 7% after 2 years (n=2). They found a 27% drop in the IOP postoperatively (21 ± 1.31 mmHg), and an even larger drop to the final follow-up (6.24 ± 1.98 mmHg); 0.76 ± 0.35 fewer medications were required, on average, following the surgery. After AIT with the trabectome, IOP was lower by an average of 31%, for a postoperative IOP of 15 mmHg. This allowed for a reduction in the number of IOP-lowering medications required to less than 1. After 2 years of follow-up, the average success rate was 66%.15
In previous studies, AIT with the trabectome was compared to the conventional filtration surgery (trabeculectomy with mitomycin C); the IOP decreased 52–76% in the latter, but only 30–35% in the former.65,66 In another study, combined phacoemulsification and AIT was compared with phacoemulsification and the insertion of two iStents; after 12 months, the IOP dropped to less than 18 mmHg in 14% of patients following the former procedure and in 39% following the latter.67
Finally, the rate of vision-threatening complications using the trabectome is < 1%.66,68 To date, there have been no randomized controlled trials involving the trabectome, and the largest available data set is from a study that was sponsored by the device manufacturer.69 In summary, AIT using the trabectome is estimated to decrease the IOP by approximately 36% to a final average of around 16 mmHg and enables a decrease in the medication burden to less than 1.
The safety and efficacy of ab-interno canaloplasty (ABiC) was studied by Gallardo et al in 2018.70 Ab-externo canaloplasty was modified to provide an ab-interno approach to SC through a 1.8-mm clear corneal incision. ABiC enables access, catheterization, and viscodilation of all aspects of the outflow resistance—the TM, SC, and the distal outflow system, beginning with the CCs (Video 1). The main modification is the lack of a tensioning suture, which is inserted into SC in classic canaloplasty, and the conjunctiva is preserved for subsequent surgery, if needed.71,72 Injection of viscoelastic (Healon® or Healon GV®, Johnson & Johnson Surgical Vision, Inc., Santa Ana, CA, USA) during insertion of the iTrack™ 250A canaloplasty microcatheter (Ellex Medical Lasers Ltd., Adelaide, Australia) allows compressed and herniated tissue of the TM to separately withdraw from CCs. The indication for ABiC is mild-to-moderate glaucoma, and contraindications include neovascular glaucoma, a closed- or a narrow-angle, peripheral anterior synechiae, and narrow-angle glaucoma. ABiC can also be performed in conjunction with phacoemulsification.73 Davids et al74 observed statistically significant reductions in IOP at all follow-ups over a 12-month period and there were no major perioperative complications to report; however, the number of glaucoma medications required at 12 months did not differ from the preoperative number. Thus, this technique does not seem to reduce dependence on glaucoma therapy, which should be considered.
Kahook Dual Blade Device
The Kahook Dual Blade® (KDB; New World Medical, Inc., Rancho Cucamonga, CA, USA) is designed for the removal of the TM while minimizing collateral damage. It consists of a sharp blade allowing for smooth access into SC. Once inserted into the canal, the device is capable of removing the TM with minimal damage.75 The KDB is introduced into the anterior chamber via an ab-interno approach. Incision of the TM may be conducted using several techniques: mark-and-meet, outside-in, or inside-out, the first of which is outlined below (Video 2).
Under gonioscopic visualization, the tip is used to engage the TM at a 10° angle to SC, to mark the excision endpoint. Thereafter, the KDB is disengaged, rotated 180°, and re-engaged at 3 to 4 clock hours from the initial incision site, again with the tip at a 10° angle to SC. Thereafter, the footplate is seated and the dual blades are advanced through the planned excision points to reach the initial mark point. The ramp at the distal end of the KDB elevates the TM tissue and guides it toward the blades on either side of the device for clean incision, easy removal, and minimal damage to adjacent structures. This is possible thanks to the design of the angle of the distal cutting surface and shaft size of the device.
Sieck et al76 studied the IOP-lowering effect of KDB goniotomy alone or combined with phacoemulsification in glaucoma patients. At 12 months, the success rate was 71.8% versus 68.8% for the phaco-KDB group and KDB-alone group, respectively. In the phaco-KDB group, at 12 months, the IOP dropped from 16.7 ± 0.4 mmHg on 1.9 ± 0.1 medications to 13.8 ± 0.4 mmHg on 1.5 ± 0.1 medications. In the KDB-alone group, at 12 months, the IOP declined from 20.4 ± 1.3 mmHg to 14.1 ± 0.9 mmHg. The number of IOP medications dropped from 3.1 ± 0.2 to 2.3 ± 0.4 at the end of follow-up. In a study by Dorairaj et al,77 the effect of phaco-KDB was investigated in angle-closure glaucoma participants. The mean IOP was 25.5 ± 0.7 mmHg, preoperatively, and reduced by 12.3 ± 0.73 mmHg at month 6 of follow-up. Preoperatively, the medication burden was 2.3 ± 0.1, which dropped at month 6 by 2.2 ± 0.12. At month 6, 92.9% of eyes exhibited an IOP ≤ 18 mmHg and 100% exhibited an IOP reduction of ≥20%.
ElMallah et al78 studied the efficacy of KDB in a multicenter study with a 12-month follow-up in patients, most (86%) of whom had mild-to-severe POAG. In their study, the preoperative IOP was 21.6 ± 0.8 mmHg, and the mean medication burden at baseline was 2.6 ± 0.2. After 12 months, the IOP dropped by 3.9 mmHg (19.3%) and the mean reduction in medication burden was 0.3 (12.5%). In six cases (14.3%), additional glaucoma surgery was required within the 12-month follow-up period.
Combined Gonioscopy-Assisted Transluminal Trabeculotomy with Ab-Interno Canaloplasty
Recently, Al Habash et al79 reported 12-month results of GATT combined with ABiC. The first step in GATT-ABiC is the creation of a portside incision directed toward the nasal angle. After adjustment of the patient’s head, a Volk TVG Surgical Lens of the surgical microscope is used to identify the nasal-angle landmarks. A small (2 mm in width), localized goniotomy is performed horizontally in the nasal angle to gain access to SC. Thereafter, an iTrack™ microcatheter with an illuminated tip is inserted into SC and is catheterized 360° circumferentially using microsurgical forceps, with injection of Healon®/Healon GV®. After cannulation of the entire canal, the microcatheter’s distal end is removed through the main corneal incision. The proximal part is introduced into the anterior chamber and 360° GATT is performed. The viscoelastic is aspirated with the irrigation/aspiration probe; however, a small amount may be left to prevent blood outflow from SC. In their study of 19 patients (20 eyes),79 the success rate was 100%. The preoperative IOP was 19.75 ± 4.68 mmHg; thereafter, it declined to 13.30 ± 1.30 mmHg (a 32.7% reduction) at 12 months postoperatively. The medication burden before surgery was 3.4; after 12 months, it dropped to 1.1. None of the operated participants required additional glaucoma surgery. Hyphema was present in six cases in the first postoperative week. Also, three eyes exhibited IOP spikes that normalized by the end of the first postoperative month.
MIGS devices and instrumentation are developed to lower the IOP and are considered safer and more effective methods compared to the traditional, full-thickness filtration surgeries. SC-based procedures are effective in lowering the IOP in eyes with different types of glaucoma. Similar to most other MIGS procedures, canal-based procedures require a clear corneal incision that can be combined with phacoemulsification. One of its main advantages is the lack of bleb formation, reducing the risk of fibrosis and endophthalmitis. When the hypotensive effect is not as expected, the eye remains naive to classic glaucoma procedures, and bleb-based filtration surgery remains an option. However, SC-based MIGS procedures are not without drawbacks. It is worth mentioning that GATT can only be used for trabeculotomy; the TM tissue is not removed during this procedure. Transient efficacy of GATT in adults is most probably due to postoperative regeneration, scarring, and formation of anterior synechiae.59 Post-surgical repairing of residual TM may indicate the regeneration of TM and subsequently may increase the AH outflow. Some authors reported that the goniotomy area was covered with granular tissue within 4 months of surgery.80
Theoretically, using the trabectome, successful tissue removal, and ablation of the edges of the incision helps prevent the closure of the surgical cleft, postoperative fibrosis, and inflammation caused by residual tissue fragments in the anterior chamber angle. However, with the trabectome system, an electrocautery unit and disposable handpieces are required. Therefore, its operating cost may limit its utility in resource-poor areas. In this respect, the KDB is more economical for the treatment of glaucoma. The trabectome can also cause thermal damage to the adjacent tissues, and removal of the TM using the manual “gonioscraper” also causes injury to the adjacent tissues, including the splitting of the posterior wall of SC.
Seibold et al,75 in their research on corneoscleral rims from human donors, used the KDB for incision of the TM. Thereafter, specimens were examined histologically and compared to those obtained using goniotomy with a microvitreoretinal (MVR) blade and cautery with the trabectome. They observed a full-thickness incision through the TM caused by the MVR blade. The amount of removed tissue was minimal with large residuals of TM on either side of the incision. In addition, the procedure resulted in damage to the adjacent sclera. The trabectome produced a similar opening in the TM, but also resulted in residual TM tissue, as well as thermal damage to the residual TM leaflets. Specimens treated with the KDB exhibited complete TM-tissue removal and no substantial damage to adjacent tissues. Use of the KDB, MVR blade, and trabectome all result in a similar reduction in IOP. The number of degrees treated did not correlate with the level of decrease in IOP for any of the devices.73
Wang et al81 used anterior segment optical coherence tomography (AS-OCT) to compare the intraoperative angle stability and postoperative outflow yielded by two AIT devices, with or without active aspiration and irrigation, in enucleated porcine eyes. Angle stability was determined by measuring the degree of the nasal angle and the anterior chamber depth (ACD). For this, a passive dual blade goniectome (a KDB) and an active dual-blade goniectome (aDBG) were used. Using the aDBG, the nasal angle remained wide open during the surgery (above 90°) and did not change until surgery was completed. In contrast, using the KDB, the ACD was less stable and the angle continuously narrowed by 40 ± 12%. However, canalograms revealed a similar degree of access to SC using the two techniques. AS-OCT revealed that anterior chamber maintenance was improved due to active irrigation and aspiration. Use of aDBG in the study’s training model also improved ease of handling. The immediate postoperative outflow using each device was improved.81 One of the disadvantages is that, in theory, use of the trabectome and the KDB will not decrease the IOP under the low-teens in mmHg. On the other hand, certain procedures—such as trabecular microbypass and SC stents—are indicated for patients with mild and moderate open-angle glaucoma. The KDB is not limited to a certain severity or type of glaucoma, and its effectiveness in moderate-to-severe POAG has been demonstrated.61
One aspect that requires investigation is the impact of the elimination of the filtering role of the TM on the other eye tissues. It is important to determine the exact extent of tissue removal for the optimal balance in the IOP-lowering effect and preservation of the filtering action of the TM.
Beyond doubt, elucidation of the most effective technique for AIT requires more randomized controlled trials. This in turn will offer guidance for surgeons in the selection of the surgical intervention most suitable for each individual patient.
Future developments in the field of AIT may include intra- and postoperative imaging of SC and distal pathways using AS-OCT. Ideally, preoperative evaluation could be used to identify regions near CCs that are collapsed, and intraoperative imaging could be used to ablate TM in those regions. Canalography or AS-OCT could be used postoperatively to identify the source of obstruction to AH outflow. Finally, adjunctive use of canal-based procedures requires further research, such as for cases where trabeculectomy is unsuccessful.
We would like to thank Editage (www.editage.com) for English language editing.
The authors report no conflicts of interest in this work.
1. Moroi SE, Reed DM, Sanders DS, et al. Precision medicine to prevent glaucoma-related blindness. Curr Opin Ophthalmol. 2019;30(3):187–198. doi:10.1097/ICU.0000000000000564
2. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268–1279. doi:10.1001/archopht.120.10.1268
3. Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E. Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003;121(1):48–56. doi:10.1001/archopht.121.1.48
4. Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol. 2012;153(5):804–814.e1. doi:10.1016/j.ajo.2011.10.024
5. Saheb H, Gedde SJ, Schiffman JC, Feuer WJ. Outcomes of glaucoma reoperations in the Tube Versus Trabeculectomy (TVT) Study. Am J Ophthalmol. 2014;157(6):1179–1189.e2. doi:10.1016/j.ajo.2014.02.027
6. Soltau JB, Rothman RF, Budenz DL, et al. Risk factors for glaucoma filtering bleb infections. Arch Ophthalmol. 2000;118(3):338–342. doi:10.1001/archopht.118.3.338
7. Bailey AK, Sarkisian SR. Complications of tube implants and their management. Curr Opin Ophthalmol. 2014;25(2):148–153. doi:10.1097/ICU.0000000000000034
8. Hau S, Barton K. Corneal complications of glaucoma surgery. Curr Opin Ophthalmol. 2009;20(2):131–136. doi:10.1097/ICU.0b013e328325a54b
9. Konopinska J, Deniziak M, Saeed E, et al. Prospective randomized study comparing combined phaco-ExPress and phacotrabeculectomy in open angle glaucoma treatment: 12-month follow-up. J Ophthalmol. 2015;2015:720109. doi:10.1155/2015/720109
10. Varma R, Lee PP, Goldberg I, Kotak S. An assessment of the health and economic burdens of glaucoma. Am J Ophthalmol. 2011;152(4):515–522. doi:10.1016/j.ajo.2011.06.004
11. Dickerson JE
12. Sadruddin O, Pinchuk L, Angeles R, Palmberg P. Ab externo implantation of the MicroShunt, a poly (styrene-block-isobutylene-block-styrene) surgical device for the treatment of primary open-angle glaucoma: a review. Eye Vis (Lond). 2019;6:36. doi:10.1186/s40662-019-0162-1
13. SooHoo JR, Seibold LK, Radcliffe NM, Kahook MY. Minimally invasive glaucoma surgery: current implants and future innovations. Can J Ophthalmol. 2014;49(6):528–533. doi:10.1016/j.jcjo.2014.09.002
14. Minckler D, Mosaed S, Francis B, Loewen N, Weinreb RN. Clinical results of ab interno trabeculotomy using the Trabectome for open-angle glaucoma: the mayo clinic series in Rochester, Minnesota. Am J Ophthalmol. 2014;157(6):1325–1326. doi:10.1016/j.ajo.2014.02.030
15. Kaplowitz K, Bussel II, Honkanen R, Schuman JS, Loewen NA. Review and meta-analysis of ab-interno trabeculectomy outcomes. Br J Ophthalmol. 2016;100(5):594–600. doi:10.1136/bjophthalmol-2015-307131
16. Arriola-Villalobos P, Martínez-de-la-Casa JM, Díaz-Valle D, Fernández-Pérez C, García-Sánchez J, García-Feijoó J. Combined iStent trabecular micro-bypass stent implantation and phacoemulsification for coexistent open-angle glaucoma and cataract: a long-term study. Br J Ophthalmol. 2012;96(5):645–649. doi:10.1136/bjophthalmol-2011-300218
17. Konopinska J, Kozera M, Krasnicki P, Mariak Z, Rekas M. The effectiveness of first-generation iStent microbypass implantation depends on initial intraocular pressure: 24-month follow-up–prospective clinical trial. J Ophthalmol. 2020;2020:8164703. doi:10.1155/2020/8164703
18. Paletta Guedes RA, Gravina DM, Paletta Guedes VM, Chaoubah A. iStent inject (second-generation trabecular microbypass) versus nonpenetrating deep sclerectomy in association with phacoemulsification for the surgical treatment of open-angle glaucoma and cataracts: 1-year results. J Glaucoma. 2020;29(10):905–911. doi:10.1097/IJG.0000000000001576
19. Hamanaka T, Bill A, Ichinohasama R, Ishida T. Aspects of the development of Schlemm’s canal. Exp Eye Res. 1992;55(3):479–488. doi:10.1016/0014-4835(92)90121-8
20. Karl MO, Fleischhauer JC, Stamer WD, et al. Differential P1-purinergic modulation of human Schlemm’s canal inner-wall cells. Am J Physiol Cell Physiol. 2005;288(4):C784–C794. doi:10.1152/ajpcell.00333.2004
21. Stamer WD, Clark AF. The many faces of the trabecular meshwork cell. Exp Eye Res. 2017;158:112–123. doi:10.1016/j.exer.2016.07.009
22. Tamm ER. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res. 2009;88(4):648–655. doi:10.1016/j.exer.2009.02.007
23. Osmond MJ, Krebs MD, Pantcheva MB. Human trabecular meshwork cell behavior is influenced by collagen scaffold pore architecture and glycosaminoglycan composition. Biotechnol Bioeng. 2020;117(10):3150–3159. doi:10.1002/bit.27477
24. Ethier CR. The inner wall of Schlemm’s canal. Exp Eye Res. 2002;74(2):161–172. doi:10.1006/exer.2002.1144
25. Zhou EH, Krishnan R, Stamer WD, et al. Mechanical responsiveness of the endothelial cell of Schlemm’s canal: scope, variability and its potential role in controlling aqueous humour outflow. J R Soc Interface. 2012;9(71):1144–1155. doi:10.1098/rsif.2011.0733
26. Johnstone MA, Grant WG. Pressure-dependent changes in structures of the aqueous outflow system of human and monkey eyes. Am J Ophthalmol. 1973;75(3):365–383. doi:10.1016/0002-9394(73)91145-8
27. Sit AJ, Coloma FM, Ethier CR, Johnson M. Factors affecting the pores of the inner wall endothelium of Schlemm’s canal. Invest Ophthalmol Vis Sci. 1997;38(8):1517–1525.
28. Johnson M, Chan D, Read AT, Christensen C, Sit A, Ethier CR. The pore density in the inner wall endothelium of Schlemm’s canal of glaucomatous eyes. Invest Ophthalmol Vis Sci. 2002;43(9):2950–2955.
29. Fautsch MP, Johnson DH. Aqueous humor outflow: what do we know? Where will it lead us? Invest Ophthalmol Vis Sci. 2006;47(10):4181–4187. doi:10.1167/iovs.06-0830
30. Johnson M, Erickson K. Mechanisms and routes of aqueous humor drainage. In: Albert DM, Jakobiec FA, editors. Principles and Practice of Ophthalmology. Vol. 4. Philadelphia: Saunders; 2000:2577–2595. Chapter 193B, Glaucoma
31. Braakman ST, Pedrigi RM, Read AT, et al. Biomechanical strain as a trigger for pore formation in Schlemm’s canal endothelial cells. Exp Eye Res. 2014;127:224–235. doi:10.1016/j.exer.2014.08.003
32. Grant WM. Clinical measurements of aqueous outflow. Am J Ophthalmol. 1951;34(11):1603–1605.
33. Rosenquist R, Epstein D, Melamed S, Johnson M, Grant WM. Outflow resistance of enucleated human eyes at two different perfusion pressures and different extents of trabeculotomy. Curr Eye Res. 1989;8(12):1233–1240. doi:10.3109/02713688909013902
34. Parc CE, Johnson DH, Brilakis HS. Giant vacuoles are found preferentially near collector channels. Invest Ophthalmol Vis Sci. 2000;41(10):2984–2990.
35. Stamer WD, Braakman ST, Zhou EH, et al. Biomechanics of Schlemm’s canal endothelium and intraocular pressure reduction. Prog Retin Eye Res. 2015;44:86–98. doi:10.1016/j.preteyeres.2014.08.002
36. Clark AF, Wilson K, McCartney MD, Miggans ST, Kunkle M, Howe W. Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1994;35(1):281–294.
37. Sumida GM, Stamer WD. Sphingosine-1-phosphate enhancement of cortical actomyosin organization in cultured human Schlemm’s canal endothelial cell monolayers. Invest Ophthalmol Vis Sci. 2010;51(12):6633–6638. doi:10.1167/iovs.10-5391
38. Johnson M. What controls aqueous humour outflow resistance? Exp Eye Res. 2006;82(4):545–557. doi:10.1016/j.exer.2005.10.011
39. Du Y, Roh DS, Mann MM, Funderburgh ML, Funderburgh JL, Schuman JS. Multipotent stem cells from trabecular meshwork become phagocytic TM cells. Invest Ophthalmol Vis Sci. 2012;53(3):1566–1575. doi:10.1167/iovs.11-9134
40. Vranka JA, Kelley MJ, Acott TS, Keller KE. Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma. Exp Eye Res. 2015;133:112–125. doi:10.1016/j.exer.2014.07.014
41. Dismuke WM, Klingeborn M, Stamer WD. Mechanism of fibronectin binding to human trabecular meshwork exosomes and its modulation by dexamethasone. PLoS One. 2016;11(10):e0165326. doi:10.1371/journal.pone.0165326
42. 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(5):421–438. doi:10.1097/01.ijg.0000131757.63542.24
43. Xin C, Wang RK, Song S, et al. Aqueous outflow regulation: optical coherence tomography implicates pressure-dependent tissue motion. Exp Eye Res. 2017;158:171–186. doi:10.1016/j.exer.2016.06.007
44. Grant WM. Experimental aqueous perfusion in enucleated human eyes. Arch Ophthalmol. 1963;69:783–801. doi:10.1001/archopht.1963.00960040789022
45. Schuman JS, Chang W, Wang N, de Kater AW, Allingham RR. Excimer laser effects on outflow facility and outflow pathway morphology. Invest Ophthalmol Vis Sci. 1999;40(8):1676–1680.
46. Ethier CR, Coloma FM, Sit AJ, Johnson M. Two pore types in the inner-wall endothelium of Schlemm’s canal. Invest Ophthalmol Vis Sci. 1998;39(11):2041–2048.
47. Chang JY, Folz SJ, Laryea SN, Overby DR. Multi-scale analysis of segmental outflow patterns in human trabecular meshwork with changing intraocular pressure. J Ocul Pharmacol Ther. 2014;30(2–3):213–223. doi:10.1089/jop.2013.0182
48. Man X, Arroyo E, Dunbar M, et al. Perilimbal sclera mechanical properties: impact on intraocular pressure in porcine eyes. PLoS One. 2018;13(5):e0195882. doi:10.1371/journal.pone.0195882
49. Carreon T, van der Merwe E, Fellman RL, Johnstone M, Bhattacharya SK. Aqueous outflow - A continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res. 2017;57:108–133. doi:10.1016/j.preteyeres.2016.12.004
50. Sit AJ, McLaren JW. Measurement of episcleral venous pressure. Exp Eye Res. 2011;93(3):291–298. doi:10.1016/j.exer.2011.05.003
51. Ellingsen BA, Grant WM. The relationship of pressure and aqueous outflow in enucleated human eyes. Invest Ophthalmol. 1971;10(6):430–437.
52. Ellingsen BA, Grant WM. Trabeculotomy and sinusotomy in enucleated human eyes. Invest Ophthalmol. 1972;11(1):21–28.
53. Grierson I, Lee WR. The fine structure of the trabecular meshwork at graded levels of intraocular pressure. (2) Pressures outside the physiological range (0 and 50 mmHg). Exp Eye Res. 1975;20(6):523–530. doi:10.1016/0014-4835(75)90219-5
54. Shareef S Gonioscopy is essential for MIGS. Glaucoma Today; September/October, 2016.
55. Grover DS, Godfrey DG, Smith O, Feuer WJ, Montes de Oca I, Fellman RL. Gonioscopy-assisted transluminal trabeculotomy, ab interno trabeculotomy: technique report and preliminary results. Ophthalmology. 2014;121(4):855–861. doi:10.1016/j.ophtha.2013.11.001
56. Grover DS, Smith O, Fellman RL, Godfrey DG, Butler MR, Montes de Oca I. Gonioscopy assisted transluminal trabeculotomy: an ab interno circumferential trabeculotomy for the treatment of primary congenital glaucoma and juvenile open angle glaucoma. Br J Ophthalmol. 2015;99(8):1092–1096. doi:10.1136/bjophthalmol-2014-306269
57. Grover DS, Smith O, Fellman RL, et al. Gonioscopy-assisted transluminal trabeculotomy: an ab interno circumferential trabeculotomy: 24 months follow-up. J Glaucoma. 2018;27(5):393–401. doi:10.1097/IJG.0000000000000956
58. Baykara M, Poroy C, Erseven C. Surgical outcomes of combined gonioscopy-assisted transluminal trabeculotomy and cataract surgery. Indian J Ophthalmol. 2019;67(4):505–558. doi:10.4103/ijo.IJO_1007_18
59. Rahmatnejad K, Pruzan NL, Amanullah S, et al. Surgical outcomes of Gonioscopy-assisted Transluminal Trabeculotomy (GATT) in patients with open-angle glaucoma. J Glaucoma. 2017;26(12):1137–1143. doi:10.1097/IJG.0000000000000802
60. Aktas Z, Ucgul AY, Bektas C, Sahin Karamert S. Surgical outcomes of prolene gonioscopy-assisted transluminal trabeculotomy in patients with moderate to advanced open-angle glaucoma. J Glaucoma. 2019;28(10):884–888. doi:10.1097/IJG.0000000000001331
61. Polat JK, Loewen NA. Combined phacoemulsification and trabectome for treatment of glaucoma. Surv Ophthalmol. 2017;62(5):698–705. doi:10.1016/j.survophthal.2016.03.012
62. Francis BA, See RF, Rao NA, Minckler DS, Baerveldt G. Ab interno trabeculectomy: development of a novel device (Trabectome™) and surgery for open-angle glaucoma. J Glaucoma. 2006;15(1):68–73. doi:10.1097/01.ijg.0000196653.77836.af
63. Minckler D, Baerveldt G, Ramirez MA, et al. Clinical results with the Trabectome, a novel surgical device for treatment of open-angle glaucoma. Trans Am Ophthalmol Soc. 2006;104:40–50.
64. Bhartiya S, Ichhpujani P, Shaarawy T. Surgery on the trabecular meshwork: histopathological evidence. J Curr Glaucoma Pract. 2015;9(2):51–61. doi:10.5005/jp-journals-10008-1184
65. Jea SY, Francis BA, Vakili G, Filippopoulos T, Rhee DJ. Ab interno trabeculectomy versus trabeculectomy for open-angle glaucoma. Ophthalmology. 2012;119(1):36–42. doi:10.1016/j.ophtha.2011.06.046
66. Francis BA, Winarko J. Combined Trabectome and cataract surgery versus combined trabeculectomy and cataract surgery in open-angle glaucoma. Clin Surg Ophthalmol. 2011;29:4–10.
67. Khan M, Saheb H, Neelakantan A, et al. Efficacy and safety of combined cataract surgery with 2 trabecular microbypass stents versus ab interno trabeculotomy. J Cataract Refract Surg. 2015;41(8):1716–1724. doi:10.1016/j.jcrs.2014.12.061
68. Chow JTY, Hutnik CML, Solo K, Malvankar-Mehta MS. When is evidence enough evidence? A systematic review and meta-analysis of the Trabectome as a solo procedure in patients with primary open-angle glaucoma. J Ophthalmol. 2017;2017:2965725. doi:10.1155/2017/2965725
69. Mosaed S. The first decade of global trabectome outcomes. Eur Ophthalmol. 2014;8(2):113–119. doi:10.17925/EOR.2014.08.02.113
70. Gallardo MJ, Supnet RA, Ahmed IIK. Viscodilation of Schlemm’s canal for the reduction of IOP via an ab-interno approach. Clin Ophthalmol. 2018;12:2149–2155. doi:10.2147/OPTH.S177597
71. Khaimi MA. Canaloplasty using iTrack 250 microcatheter with suture tensioning on Schlemm’s canal. Middle East Afr J Ophthalmol. 2009;16(3):127–129. doi:10.4103/0974-9233.56224
72. Byszewska A, Konopinska J, Kicinska AK, Mariak Z, Rekas M. Canaloplasty in the treatment of primary open-angle glaucoma: patient selection and perspectives. Clin Ophthalmol. 2019;13:2617–2629. doi:10.2147/OPTH.S155057
73. Khaimi MA. Canaloplasty: a minimally invasive and maximally effective glaucoma treatment. J Ophthalmol. 2015;2015:485065. doi:10.1155/2015/485065
74. Davids AM, Pahlitzsch M, Boeker A, Winterhalter S, Maier-Wenzel AK, Klamann M. Ab interno canaloplasty (ABiC)-12-month results of a new minimally invasive glaucoma surgery (MIGS). Graefes Arch Clin Exp Ophthalmol. 2019;257(9):1947–1953. doi:10.1007/s00417-019-04366-3
75. Seibold LK, Soohoo JR, Ammar DA, Kahook MY. Preclinical investigation of ab interno trabeculectomy using a novel dual-blade device. Am J Ophthalmol. 2013;155(3):524–529.e2. doi:10.1016/j.ajo.2012.09.023
76. Sieck EG, Epstein RS, Kennedy JB, et al. Outcomes of Kahook Dual Blade goniotomy with and without phacoemulsification cataract extraction. Ophthalmol Glaucoma. 2018;1(1):75–81. doi:10.1016/j.ogla.2018.06.006
77. Dorairaj S, Tam MD, Balasubramani GK. Twelve-month outcomes of excisional goniotomy using the Kahook Dual Blade® in eyes with angle-closure glaucoma. Clin Ophthalmol. 2019;13:1779–1785. doi:10.2147/OPTH.S221299
78. ElMallah MK, Seibold LK, Kahook MY, Williamson BK, Singh IP, Dorairaj SK. 12-month retrospective comparison of Kahook Dual Blade excisional goniotomy with iStent trabecular bypass device implantation in glaucomatous eyes at the time of cataract surgery. Adv Ther. 2019;36(9):2515–2527. doi:10.1007/s12325-019-01025-1
79. Al Habash A, Alrushoud M, Al Abdulsalam O, Al Somali AI, Aljindan M, Al Ahmadi AS. Combined gonioscopy-assisted transluminal trabeculotomy (GATT) with ab interno canaloplasty (ABiC) in conjunction with phacoemulsification: 12-month outcomes. Clin Ophthalmol. 2020;14:2491–2496. doi:10.2147/OPTH.S267303
80. Tanito M, Ohira A, Chihara E. Surgical outcome of combined trabeculotomy and cataract surgery. J Glaucoma. 2001;10(4):302–308. doi:10.1097/00061198-200108000-00010
81. Wang C, Dang Y, Waxman S, Xia X, Weinreb RN, Loewen NA. Angle stability and outflow in dual blade ab interno trabeculectomy with active versus passive chamber management. PLoS One. 2017;12(5):e0177238. doi:10.1371/journal.pone.0177238
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF]