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Back to Journal »Clinical Ophthalmology» Volume 15

Minimally Invasive Glaucoma Surgery: A Review of Schlemm Root Canal Surgery

Authors Konopińska J, Lewczuk K, Jabłońska J, Mariak Z, Rękas M 

Published on March 11, 2021, the 2021 volume: 15 pages 1109-1118

DOI https://doi.org/10.2147/OPTH.S293702

Single anonymous peer review

Editor who approved for publication: Dr. Scott Fraser

Supplementary Video 1: "Ab Endoplasty (ABiC)" [ID293702].

Joanna Konopińska, 1 Katarzyna Lewczuk, 2 Joanna Jabłońska, 2 Zofia Mariak, 1 Marek Rękas 2 1 Department of Ophthalmology, Bialystok Medical University, Bialystok, Poland; 2 Ophthalmology Newsletter from the Institute of Military Medical Research in Warsaw, Poland: Joanna Konopińska Department of Ophthalmology, Javistok Medical University, Jana Kilińskiego 1 STR, Białystok, 15-089, Poland Tel 48 857468372 Fax protected 4468 Abstract: Minimally invasive glaucoma surgery has become more and more popular in the past decade. It can be executed using three different mechanisms. In this review, we focus on Schlemm tube (SC)-based surgery, which increases the flow of aqueous humor (AH) into the aqueous vein by removing the trabecular meshwork (TM) or increasing the tension of the TM. In primary open-angle glaucoma (POAG), TM is the area most likely to increase the resistance to AH outflow. In theory, removing TM can improve AH outflow; therefore, glaucoma experts focus on the microsurgical anatomy of TM. In this review, we analyzed the existing literature to examine SC-related microsurgery based on histopathological evidence of AH outflow resistance location. First, we considered the role, anatomy and physiology of TM and SC. We refer to studies describing the mechanisms and potential pathways associated with POAG intraocular pressure elevation, which are the targets of microsurgical interventions using SC. Next, we carefully studied the gonioscopic tools required for the ab-interno method, and explored incision tube surgery: ab-interno trabeculectomy using different instruments (Trabectome®, Kahook Dual Blade) and technical changes . After that, we discussed ab-interno canaloplasty, explained the technique and reviewed its effectiveness. Finally, we propose the scope of future research in this field. Although iStent also targets the SC by bypassing the SC, the device has been extensively reviewed elsewhere. Keywords: microsurgery, trabecular meshwork, trabeculoplasty, trabeculectomy, Kahook Dual Blade, Schlemm's canal

Glaucoma remains the most common cause of blindness worldwide. It is estimated that 13.5-42.0% of glaucoma patients are blind on one side and 4.0-16.0% are blind on both sides. 1 The only treatment proven to slow the progression of glaucoma and related field loss is to reduce intraocular pressure (IOP). 2,3 Although trabeculectomy is still considered the gold standard for glaucoma surgery, it may cause many short-term and long-term side effects. 4 After one year, the success rate is about 80%. 5 This success is burdened with a 1% annual risk of endophthalmitis and other frequent and vision-threatening adverse events (such as persistent hypotonia and choroidal detachment). 6 According to reports, the success rate of glaucoma drainage devices within 5 years is about 50-75%, but it may also cause major complications such as dyskinesias, hypotonia, corneal decompensation and tube erosion, 7-9 to name a few . Such complications usually delay surgery until extensive loss of vision.

Due to the increase in life expectancy, individuals have a higher lifetime risk of glaucoma, and they usually live longer when they have glaucoma. 10 Therefore, it is important to perform glaucoma surgery at an early stage and focus on reducing intraocular pressure from the beginning. For more than ten years, in-depth research has been conducted on the use of minimally invasive glaucoma surgery (MIGS) to reduce intraocular pressure and its fluctuations, while reducing the risk of side effects that affect the quality of life of patients, and reducing the burden of intraocular pressure drugs. From an anatomical point of view, there are different types of MIGS. In this review, we focus on surgery based on Schlemm's Canal (SC), because the possible underlying mechanism for increased intraocular pressure is the magnified resistance of the trabecular meshwork (TM) to the outflow of aqueous humor (AH). 11-13

Goniotomy and trabeculectomy are effective in the treatment of children's glaucoma; the incision causes the elastic scleral spurs to shrink back, stretch and separate TM. These techniques have been improved by removing adult TM strips; otherwise, the front and rear TMs may re-approach and block the collector channel (CC) entrance. Goniotomy and trabeculotomy are classified as MIGS when they are modified to be performed through the anterior chamber access. The difference between SC-based MIGS is the method of TM removal or bypass. TM can be removed using plasma-mediated TM ablation14 or physical TM with or without irrigation and aspiration; 15 TM can also be bypassed with a stent 16-18.

The drainage of AH from trabecula to CC is carried out through SC. The cells of the SC vary according to their location, because the inner wall and outer wall can be distinguished in the microscopic anatomy of the canal. Each wall is lined with endothelium: a continuous monolayer of cells that differ in morphology, expression of markers, organelles, and function. 19, 20 TM is a connective tissue without any blood vessels, arranged inside SC. 21 TM has three areas. 1) The boundary between the anterior chamber and the uveal mesh contains a porous collagen-elastin fiber sheet system hidden by TM cells. 2) The corneoscleral mesh contains TM, which covers the perforated collagen and elastin plates. This structure borders the sclera and cornea. 3) The proximal connective tissue (JCT) borders the inner wall of the SC and is composed of loose connective tissue. TM cells are surrounded by irregular extracellular matrix (ECM). 21 The inner wall is connected to the ciliary muscle through elastin fibers and extends from the end portion of the longitudinal fibers through the corneoscleral mesh and JCT. 22 The above three areas are considered a filter because they are directly on the SC. The terminal part of the TM, the "insertion", is considered "non-filtered" because it abuts the Schwalbe line instead of SC.21,22

The inner wall is the most frequently analyzed area because it provides the main resistance to the drainage of AH. 23,24 The inner wall is characterized by the close connection of vascular endothelium-cadherin with giant vacuoles and pores. The JCT and the inner wall structure together play an important role in regulating the outflow of AH. 25

The space between ECM and SC lining cells is called "giant vacuole". 26 These are dynamic, and as IOP increases, the number and size will also increase. 27-29 Giant vacuoles mainly appear near the CC exit. 26,30 This indicates that there are high water currents that cause high pressure gradients at these locations. 26

The pore size of the inner wall is 0.6-3 µm, and 31 accounts for 10% of the AH outflow. 32,33 AH flows in the inner wall mainly through these holes. Such pores may appear in the walls of giant vacuoles or other areas. 34 The giant vacuole forms a preferential AH drainage pathway through the endothelium through the one-way valve mechanism. When the pressure of the extrascleral vein increases, the pressure in the SC also increases; subsequently, the number of vacuoles and holes in the inner wall of the SC decreases, preventing blood flow from the SC to the anterior chamber. 35 Some drugs that stimulate the polymerization of cytoskeletal proteins (ie, glucocorticoids) 36 may hinder the development of vacuoles, thereby increasing the resistance to AH outflow. 37 Reduced pore density is a typical feature of glaucoma patients. This fact indicates that the inner wall plays a key role in maintaining the steady state of AH. The AH outflow resistance is significantly amplified by the interaction of pores and subendothelial cells (basement membrane of SC cells and JCT ECM). 38

The second main role of TM cells is to act as a biological filter. Interestingly, TM cells exhibited macrophage-like activity. 21 They quickly engulf the pigment epithelial cell debris carried by the AH flow before reaching the TM 39, where it can collect and change the AH flow. 40 To fulfill this role, TM cells produce large amounts of antithrombotic substances, such as heparin or tissue plasminogen activator. 41 Similar to endothelium, TM lining cells promote antigen presentation and inflammation by releasing histocompatibility proteins and inflammatory cytokines. twenty one

AH is not evenly distributed across the inner wall of the SC. As mentioned in the previous section, the water flow mainly occurs near the CCs. 26 Compared with the rest of the inner wall, twice as many giant vacuoles were found there. This shows that the movement of fluid through the inner wall depends on the pressure gradient. 42 AH flows through multiple curved veins, from the deep blood vessels called the deep scleral plexus, through the limbus and the inner scleral plexus, to the extrascleral veins. 43 SC’s MIGS is based on Grant’s research. 44 It was observed in this study that removal of the TM or SC outer wall in the enucleated human eye reduced the AH outflow resistance under normal intraocular pressure by 49%. When the IOP is higher than the normal value, 71% of the outflow resistance is eliminated. 33 Schuman et al.45 also noted that under normal IOP, the use of excimer laser for TM ablation can reduce the outflow resistance by 35%. These studies indicate that up to 50% of the outflow resistance occurs at the distal end of the SC, depending on the IOP. The fact that IOP decreases after removing part of TM means that AH can be discharged through downstream pathways other than SC.

This residual outflow resistance beyond the SC may exist in the AH pathway from the CC to the intrascleral venous plexus or the aqueous vein. 46 The complete mechanism of the formation of this residual resistance is not yet fully understood. However, it is known that segmental AH outflow, 47 marginal tissue biomechanics, 48 ​​and aqueous venous are factors that contribute to this mechanism. 49

In a healthy eye, the IOP is close to 16 mmHg, while the pressure in the extrascleral vein is 7-8 mmHg. 50 Therefore, the pressure difference across the TM is approximately 8 mmHg. Grant et al.32 managed to maintain IOP at 25 mmHg in their early in vitro experiments, which is higher than the average IOP of healthy eyes. Subsequent studies have shown that under the conditions of an isolated 5 mmHg IOP (estimated in vivo 13 mmHg), trabeculotomy allows only about 14% of the resistance to be eliminated. 51 The same procedure at 10 mmHg in vitro IOP (equal to in vivo 18 mmHg), and in the range of 20-50 mmHg in vitro IOP, it eliminates as much as 62-82% of resistance. 52 Subsequent experiments confirmed these findings.53 Trabeculotomy reduced resistance by 49% at 7 mmHg and 71% at 25 mmHg. The conclusion of these studies is that removing TM at low IOP results in minor improvements.

Ab-interno trabeculotomy (AIT) is performed under goniolens, several of which are commercially available. These lenses are improved versions of Swan Jacob lenses, and they differ in terms of field of view, handle length, image magnification, and corneal contact range. Some of the goniolenses are specifically designed to improve eye stability. Recently, a two-mirror corner mirror with a static field of view of 45° was demonstrated, namely Ocular Upright 1.3× Surgical Gonioprism (Ocular Instruments, Bellevue, WA, USA). 54 It redirects the tilted gonioscope image to the coaxial "cataract" surgery view, reducing the need for tilting the microscope.

The lens should be placed gently on the surface of the cornea to avoid compressing the cornea and forming Descemet folds, which would hinder visualization. To facilitate this, the manufacturer provides additional equipment. The Volk Transcend Vold Gonio (TVG) surgical lens (Accutome, Malvern, PA, USA) consists of a main handle, a fixed ring and a balance lens, which is suspended by an independent swing handle that can withstand compression. Ocular Hill Surgical Gonioprism (Ocular Instruments) has a marginal lip at the bottom of the lens to fix the eyeball. Disposable iPrism Clip View Stabilizer (Glaukos Corp., San Clemente, CA, USA) is an accessory specially designed to snap into the lens base; it has a non-damaged surface protrusion and an expansion base designed to effectively stabilize the earth.

Due to recent developments, trabeculotomy is usually performed using the ab-externo method, but it can also be performed using the clean corneal method (AIT). AIT was first introduced in 2014 by Grover et al. 55,56 In this method, a 360-degree incision is made that destroys the first layer of TM. The operation is an ab-interno operation performed under a gonioscope, and is performed through temporal and upper nasal/intranasal puncture using microcatheters or sutures. 57,58 It is better known as gonioscope-assisted transluminal trabeculotomy (GATT), which makes it possible to perform trabeculectomy or scleral incision without the need for conjunctiva. In short, a temporal corneal incision is made and direct gonioscopy is used to observe the structure of the nasal angle. A goniotomy was performed in the nasal quadrant, and a suture or catheter (ie, iScience Interventional Corp., Menlo Park, CA, USA) was introduced into the SC using microsurgery forceps. Thereafter, advance the microcatheter or suture along the circumference to the SC until the distal end reaches the angle of the anterior chamber, and then remove it. Thereby, a 360° trabeculectomy is performed. In the two previous studies, the reported GATT success rate was 68% and 100% in infants and infants with congenital glaucoma, respectively. 56 Grover et al.56 reported that in adolescent glaucoma cases, the intraocular pressure dropped from 27.3 mmHg to 14.8 mmHg after 12 months of GATT, and the drug burden dropped from 2.6 to 0.86. In a study of adult patients, Grover et al.57 reported that 12 months after GATT treatment, primary open-angle glaucoma (POAG) decreased the intraocular pressure by 11.1 mmHg and glaucoma medication by 1.1. In patients with secondary open-angle glaucoma (SOAG; pseudoexfoliative, pigmented, uveitis, and steroid-induced glaucoma) in the same study, the average drop in IOP and glaucoma drugs was 19.9 mmHg and 1.9 mm, respectively Mercury at 12 months. Two years after GATT, POAG patients’ intraocular pressure was observed to drop by 9.2 mmHg (37.3%), and the drug burden decreased by 1.43. 57 SOAG patients at 24 months, the intraocular pressure was observed to drop by 14.1 mmHg (49.8%), and a decrease of 2.0 Drug administration. 57 Rahmatnejad et al59 did not observe a difference in IOP drop between POAG and SOAG patients. In this study, 66 patients were followed up for an average of 11.9 months. The overall success rate (intraocular pressure <21 mmHg) was 63.0%. One year after GATT, the intraocular pressure dropped from 26.1 ± 9.9 mmHg to 14.6 ± 4.7 mmHg (44%), and the drug burden was reduced from 3.1 ± 1.1 to 1.2 ± 0.9. Baykara et al.58 reported that in POAG patients at 6 months after GATT phacoemulsification, the average IOP decreased from 34.2 ± 10.6 mmHg to 24.3 ± 11.7 mmHg (65.9% ± 10.7%). The drug burden was also reduced from 3.8 ± 0.4 to 0.3 ± 0.7. Aktas et al60 examined 65 POAG patients and 39 SOAG patients who underwent GATT during an average follow-up period of 19.4 ± 8.1 (range, 6 to 37) months. The effect of GATT in their study was contrary to the results observed by Grover et al. Compared with SOAG patients, 55-57 POAG participants had a greater drop in intraocular pressure during the 18-month observation period (40.1% vs. 27.6%). ). There was no difference in the drug burden between POAG and SOAG patients at the end of follow-up, 87 of 104 patients (83.7%) achieved overall surgical success (IOP <21 mmHg). The most common postoperative complication in all the above studies was anterior chamber hemorrhage; in Grover et al.56, the anterior chamber hemorrhage rate was 38% after the first week and 6% after 1 month.

Trabectome® electrosurgical equipment (MicroSurgical Technology, Redmond, WA, USA) was approved by the U.S. Food and Drug Administration in 2004.61 for use with compatible electrosurgical instruments for low-power microsurgery applications to remove, destroy and coagulate tissues. . It can be used for AIT, using bipolar 550-kHz electrodes for ablation of 30-180° TM, thereby irrigating during double-blade angular angiotomy. 62 trabectom includes a disposable handpiece connected to the console to provide irrigation, aspiration and electrocautery. Similar to modern phacoemulsification machines, a foot pedal is used to control these actions. The trabeculectomy device is designed to permanently ablate and remove the inner wall of a TM and SC, leaving the rest of the outflow system (SC, CC and the outer wall of the aqueous vein) intact. It also aims to minimize the development of anterior adhesions that can lead to fissure closure. The No. 19.5 tip is designed to pass through corneal incisions of 1.6 mm or larger. A foot pedal insulated with a proprietary multilayer polymer is located at the tip of the phone, designed to prevent thermal and electrical damage to surrounding tissues. The distal tip of the device points to allow insertion of the SC, and the foot pedal connects the tissue with the bipolar electrode. The suction port near the tip is used to remove ablated tissue and debris, while the irrigation port is used to maintain intraocular pressure and dissipate the heat generated during the cauterization process. 63 The inner wall of a TM and SC spans from 80° to 100°°, and is then ablated and aspirated. During the operation, the surgeon temporarily sat beside the eyes of the operation and started ablation at 0.8 mW. Up to 90° of tissue can be ablated on both sides. After the tissue is removed, a viscous substance can be injected into the anterior chamber to minimize blood reflux from the SC. Studies comparing the ablation area and postoperative IOP reduction did not find any statistically significant differences. 64 During AIT, intraoperative anterior chamber hemorrhage was required, and it was confirmed that the SC successfully "opened the top". In traditional goniotomy or trabeculectomy, particles of broken tissue will remain after the operation. Use trabecome to remove tissue fragments at the same time, thereby reducing the risk of inflammation and scarring.

The overall average success rate in a study by Khan et al. 67 (defined as intraocular pressure <21 mmHg, 20% reduction, no need for reoperation) was 61 ± 17% at 1 year and 46 ± 34% at 2 years . According to the authors of the review and meta-analysis, 15 the surgical success rate of using trabecome to combine phacoemulsification with AIT was 85±17% after 1 year (n=6) and 85±7% after 2 years (n= 2 ). They found that the intraocular pressure dropped by 27% (21 ± 1.31 mmHg) after surgery, and by the last follow-up, the drop was even greater (6.24 ± 1.98 mmHg); the average post-operative medication needed was reduced by 0.76 ± 0.35. After AIT with the trabeculectomy, the intraocular pressure was reduced by an average of 31%, and the postoperative intraocular pressure was 15 mmHg. This reduces the number of drugs needed to lower intraocular pressure to less than one. After 2 years of follow-up, the average success rate was 66%. 15

In previous studies, the AIT of trabeculectomy was compared with traditional filtering surgery (mitomycin C trabeculectomy); the IOP of the latter was reduced by 52-76%, but the former only reduced 30-35%. 65,66 In another study, combined phacoemulsification and AIT were compared with phacoemulsification and insertion of two iStents; after 12 months, 14% of the patients' intraocular pressure dropped below 18 mmHg after the previous operation. After an operation, 39% of patients' intraocular pressure drops below 18 mmHg. 67

Finally, the complication rate of using trabecome to threaten vision is <1%. 66,68 To date, there are no randomized controlled trials involving trabecome. The largest available data set comes from a study sponsored by the device. 69 In conclusion, AIT using trabecome is estimated to reduce IOP by about 36% to a final average of about 16 mmHg Value, and reduce the drug burden to less than 1.

Gallardo et al. in 2018 70 studied the safety and effectiveness of ab endovascular angioplasty (ABiC). The Ab outer tube angioplasty was modified to provide the SC with an ab inner tube method through a 1.8 mm clear corneal incision. ABiC is capable of access, catheterization, and viscous expansion of all aspects of outflow resistance-TM, SC, and distal outflow system, starting with CC (Video 1). The main modification is that there is no tension suture, which is inserted into the SC during classic angioplasty, and if necessary, the conjunctiva is preserved for subsequent surgery. 71,72 Injection of viscoelastic materials (Healon® or Healon GV®, Johnson & Johnson Surgical Vision, Inc., Santa Ana, CA, USA) was used to insert the iTrack™ 250A tubuloplasty microcatheter (Ellex Medical Lasers Ltd., Adelaide, Australia) allowed the compressed and prominent tissues of TM to be removed from the CC separately. The indications for ABiC are mild to moderate glaucoma, and contraindications include neovascular glaucoma, angle-closure or narrow-angle, peripheral anterior adhesions, and narrow-angle glaucoma. ABiC can also be combined with phacoemulsification. 73 Davids et al. 74 observed a statistically significant reduction in intraocular pressure during all follow-ups at 12 months, and no major perioperative complications were reported; however, the amount of glaucoma medication required at 12 months was significantly lower than that of surgery. There is no difference in the previous quantity. Therefore, this technique does not seem to reduce reliance on glaucoma treatment, which should be considered.

Kahook Dual Blade® (KDB; New World Medical, Inc., Rancho Cucamonga, CA, USA) is designed to remove TM while minimizing collateral damage. It is composed of sharp blades and can enter the SC smoothly. Once inserted into the root canal, the device can remove the TM with minimal damage. 75 KDB was introduced into the anterior chamber through the ab-interno method. The incision of the TM can be performed using a variety of techniques: marking and meeting, from the outside to the inside or from the inside to the outside. The first technique is outlined below (Video 2).

Under the gonioscope, the tip is used to join the TM at a 10° angle to the SC to mark the end of the resection. After that, the KDB was disengaged, rotated 180°, and re-engaged 3 to 4 clock hours from the initial incision site, and the tip was again at a 10° angle to the SC. Thereafter, the foot pedal is in place, and the double blade advances through the planned resection point to the initial mark point. The slope at the distal end of the KDB lifts the TM tissue and guides it to the blades on both sides of the device to achieve clean incision, easy removal, and minimal damage to adjacent structures. This is possible due to the angle of the distal cutting surface and the design of the shaft size of the device.

Sieck et al. 76 studied the effect of KDB goniotomy alone or combined with phacoemulsification in reducing intraocular pressure in patients with glaucoma. At 12 months, the success rates of the CEUS-KDB group and the KDB group alone were 71.8% and 68.8%, respectively. In the phaco-KDB group, at 12 months, IOP decreased from 16.7 ± 0.4 mmHg with 1.9 ± 0.1 drugs to 13.8 ± 0.4 mmHg with 1.5 ± 0.1 drugs. In the KDB group alone, the intraocular pressure dropped from 20.4 ± 1.3 mmHg to 14.1 ± 0.9 mmHg at 12 months. At the end of the follow-up, the number of IOP medications dropped from 3.1 ± 0.2 to 2.3 ± 0.4. In a study by Dorairaj et al.,77 the effect of phaco-KDB was studied in participants with angle-closure glaucoma. The average preoperative intraocular pressure was 25.5 ± 0.7 mmHg, which decreased by 12.3 ± 0.73 mmHg at the 6th month of follow-up. Before the operation, the drug burden was 2.3 ± 0.1, which decreased by 2.2 ± 0.12 at the 6th month. At the 6th month, 92.9% of the eyes showed an IOP ≤ 18 mmHg, and 100% showed a ≥ 20% decrease in intraocular pressure.

ElMallah et al78 studied the efficacy of KDB in a multicenter study that followed patients for 12 months, most of whom (86%) had mild to severe POAG. In their study, the preoperative IOP was 21.6 ± 0.8 mmHg, and the baseline average drug burden was 2.6 ± 0.2. After 12 months, the intraocular pressure dropped by 3.9 mmHg (19.3%), and the drug burden was reduced by an average of 0.3 (12.5%). . During the 12-month follow-up period, 6 cases (14.3%) required additional glaucoma surgery.

Recently, Al Habash et al.79 reported the 12-month results of GATT combined with ABiC. The first step of GATT-ABiC is to create a port side cut towards the corner of the nose. After adjusting the patient's head, the Volk TVG surgical lens of the surgical microscope is used to identify the corners of the nose. A small (2 mm wide) partial keratotomy is performed at the level of the nasal angle to enter the SC. After that, insert an iTrack™ microcatheter with a light-emitting tip into the SC, and use microsurgery forceps to insert the catheter through 360° while injecting Healon®/Healon GV®. After the entire root canal is intubated, the distal end of the microcatheter is taken out through the lead membrane incision. The proximal part is introduced into the anterior chamber and 360° GATT is performed. The viscoelastic material is sucked by the irrigation/suction probe; however, a small amount may be left to prevent blood from flowing out of the SC. In their study of 19 patients (20 eyes)79, the success rate was 100%. The preoperative intraocular pressure was 19.75±4.68mmHg; after that, it dropped to 13.30±1.30 mmHg (a decrease of 32.7%) 12 months after the operation. The preoperative drug burden was 3.4; after 12 months, it dropped to 1.1. None of the surgical participants required additional glaucoma surgery. There were 6 cases of anterior chamber hemorrhage in the first week after surgery. In addition, the peak intraocular pressure of the three eyes returned to normal at the end of the first month after surgery.

MIGS equipment and instruments are designed to reduce IOP and are considered a safer and more effective method compared to traditional full-thickness filtration surgery. SC-based procedures can effectively reduce the IOP of eyes with different types of glaucoma. Similar to most other MIGS procedures, root canal-based surgery requires a clear corneal incision and can be combined with phacoemulsification. One of its main advantages is that it does not form blisters, thereby reducing the risk of fibrosis and endophthalmitis. When the blood pressure reduction effect is not as expected, the eyes are still naive to classic glaucoma surgery, and filtering surgery based on follicles is still an option. However, the SC-based MIGS program is not without its shortcomings. It is worth mentioning that GATT can only be used for trabeculotomy; the TM tissue is not removed during this procedure. The short-term effect of GATT in adults is probably due to postoperative regeneration, scar formation and the formation of anterior adhesions. 59 Postoperative repair of residual TM may indicate TM regeneration, which may subsequently increase AH outflow. Some authors reported that within 4 months after the operation, the angular incision area was covered with granular tissue. 80

Theoretically, using trabeculectomy, the successful removal of tissue and ablation of the incision edge can help prevent the closure of surgical fissures, postoperative fibrosis, and inflammation caused by residual tissue fragments in the anterior chamber. However, for the trabeculectomy system, an electrocautery device and a disposable handpiece are required. Therefore, its operating costs may limit its utility in resource-poor areas. In this regard, KDB is more economical to treat glaucoma. Trabeculectomy can also cause thermal damage to adjacent tissues. Using a manual "corner scraper" to remove TM can also cause damage to adjacent tissues, including the splitting of the posterior wall of the SC.

Seibold et al.75 used KDB incision TM in their study of the edges of human donor corneas. After that, the specimens were examined histologically and compared with specimens obtained using micro vitreoretinal (MVR) blades and cautery and trabeculectomy. They observed a full-thickness TM incision caused by the MVR blade. The amount of tissue removed was minimal, and a large amount of TM remained on both sides of the incision. In addition, the operation resulted in damage to the adjacent sclera. Trabeculectomy created similar openings in TM, but also resulted in residual TM tissue and thermal damage to residual TM lobules. The samples treated with KDB showed complete TM tissue removal and no substantial damage to adjacent tissues. The use of KDB, MVR blades, and trabecome all cause similar IOP reductions. The degree of treatment has nothing to do with the IOP reduction level of any device. 73

Wang et al.81 used anterior segment optical coherence tomography (AS-OCT) to compare the intraoperative angular stability and postoperative outflow of two AIT devices in enucleated pig eyes with or without active suction and irrigation. quantity. The angle stability is determined by measuring the degrees of the nose angle and the anterior chamber depth (ACD). For this, a passive double-blade forelimb resection device (a KDB) and an active double-blade forelimb resection device (aDBG) are used. With aDBG, the nose angle remains wide open (greater than 90°) during the operation and does not change until the operation is completed. In contrast, when using KDB, ACD is not stable and the angle continues to narrow by 40 ± 12%. However, the canal map shows similar levels of access to SC using these two technologies. AS-OCT shows that the maintenance of the anterior chamber has been improved due to active flushing and suction. The use of aDBG in the researched training model also improves the convenience of operation. The outflow immediately after using each device has been improved. 81 One of the disadvantages is that, theoretically, using a trabeculectomy and KDB will not reduce intraocular pressure below 10 mmHg. On the other hand, certain procedures—such as trabecular microbypass and SC stents—are suitable for patients with mild and moderate open-angle glaucoma. KDB is not limited to a specific severity or type of glaucoma, and its effectiveness in moderate to severe POAG has been proven. 61

One aspect that needs to be investigated is to eliminate the influence of TM on the filtering effect of other ocular tissues. It is important to determine the exact degree of tissue removal in order to achieve the best balance between the effect of reducing intraocular pressure and retaining the filtering effect of TM.

There is no doubt that elucidating the most effective AIT technique requires more randomized controlled trials. This, in turn, will guide the surgeon in choosing the most suitable surgical intervention for each patient.

Future developments in the AIT field may include the use of AS-OCT for intraoperative and postoperative imaging of the SC and distal access. Ideally, preoperative evaluation can be used to identify areas near the collapsed CC, and intraoperative imaging can be used to ablate TM in these areas. Canal angiography or AS-OCT can be used after surgery to determine the source of obstruction of AH outflow. Finally, the auxiliary use of root canal surgery requires further research, such as the unsuccessful case of trabeculectomy.

We would like to thank Editage (www.editage.com) for the English editor.

The authors report no conflicts of interest in this work.

1. Moroi SE, Reed DM, Sanders DS, etc. 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 progress of glaucoma: results of early obvious glaucoma tests. Arched ophthalmology. 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 and treatment effects of glaucoma progression: early obvious glaucoma test. Arched ophthalmology. 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 and trabeculectomy (TVT) study during the five-year follow-up period. This is 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. Results of reoperation of glaucoma in the tube and trabeculectomy (TVT) study. This is J Ophthalmol. 2014;157(6):1179–1189.e2. doi:10.1016/j.ajo.2014.02.027

6. Soltau JB, Rothman RF, Budenz DL, etc. Risk factors for glaucoma filtering bleb infection. Arched ophthalmology. 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, etc. A prospective randomized study comparing the combination of phaco-ExPress and phacotrabeculectomy in the treatment of open-angle glaucoma: a 12-month follow-up. J Ophthalmology. 2015; 2015: 720109. doi:10.1155/2015/720109

10. Varma R, Lee PP, Goldberg I, Kotak S. Assessment of the health and economic burden of glaucoma. This is J Ophthalmol. 2011;152(4):515–522. doi:10.1016/j.ajo.2011.06.004

11. Dickerson JE Jr, Brown RH. Circular tube surgery: a brief history. Curr Opin Ophthalmol. 2020; 31(2): 139–146. doi:10.1097/ICU.0000000000000639

12. Sadruddin O, Pinchuk L, Angeles R, Palmberg P. Ab implantation of MicroShunt in vitro, a poly(styrene-block-isobutylene-block-styrene) surgery for the treatment of primary open-angle glaucoma Device: Overview. Eye Vis (London). 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 trabeculectomy using Trabectome to treat open-angle glaucoma: Mayo Clinic series in Rochester, Minnesota. This is 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. A review and meta-analysis of the results of ab-interno trabeculectomy. 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 opening Coexistence of angular 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 the first-generation iStent micro-bypass implantation depends on the initial intraocular pressure: 24-month follow-up-prospective clinical trial. J Ophthalmology. 2020; 2020: 8164703. doi:10.1155/2020/8164703

18. Paletta Guedes RA, Gravina DM, Paletta Guedes VM, Chaoubah A. iStent injection (second-generation trabecular micro-bypass) and non-penetrating deep sclerectomy combined with phacoemulsification for the treatment of open-angle glaucoma and cataracts: 1 year result. J Glaucoma. 2020;29(10):905-911. doi:10.1097/IJG.0000000000001576

19. Hamanaka T, Bill A, Ichinohasama R, Ishida T. All aspects of the development of the Schlemm canal. Exp Eye Res. 1992;55(3):479-488. doi:10.1016/0014-4835(92)90121-8

20. Karl MO, Fleischhauer JC, Stamer WD, etc. Differential P1-purinergic regulation of cells in the inner wall of human Schlemm’s canal. Am J Physiol Cell Physiology. 2005; 288(4): C784–C794. doi:10.1152/ajpcell.00333.2004

21. Stamer WD, Clark AF. Many faces of trabecular meshwork cells. Exp Eye Res. 2017; 158: 112-123. doi:10.1016/j.exer.2016.07.009

22. Tam ER. Outflow pathway of trabecular meshwork: 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. The behavior of human trabecular meshwork cells is affected by the pore structure of the collagen scaffold and the composition of glycosaminoglycans. Biotechnology and Bioengineering. 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, etc. The mechanical reactivity of Schlemm’s duct endothelial cells: range, variability and their potential role in controlling the outflow of aqueous humor. JR SOC interface. 2012;9(71):1144–1155. doi:10.1098/rsif.2011.0733

26. Johnstone MA, Grant WG. Pressure-dependent changes in the structure of the aqueous humor outflow system of human and monkey eyes. This is 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 endothelial pores of the inner wall of Schlemm's canal. Invest in Ophthalmol Vis Sci. 1997;38(8):1517-1525.

28. Johnson M, Chan D, Read AT, Christensen C, Sit A, Ethier CR. The pore density of the inner wall of Schlemm's canal in glaucoma. Invest in Ophthalmol Vis Sci. 2002;43(9):2950-2955.

29. Fautsch Councillor, Johnson DH. Water-based humor: What do we know? Where will it lead us? Invest in Ophthalmol Vis Sci. 2006;47(10):4181–4187. doi:10.1167/iovs.06-0830

30. Johnson M, Erickson K. The mechanism and approach of aqueous humor drainage. In: Albert DM, Jakobiec FA, editor. Principles and Practice of Ophthalmology. roll. 4. Philadelphia: Sanders; 2000:2577-2595. Chapter 193B, Glaucoma

31. Braakman ST, Pedrigi RM, Read AT, etc. Biomechanical strain acts as a trigger for the formation of Schlemm tube endothelial cell pores. Exp Eye Res. 2014;127:224-235. doi:10.1016/j.exer.2014.08.003

32. Grant WM. Clinical measurement of aqueous humor outflow. This is J Ophthalmol. 1951;34(11):1603-1605.

33. Rosenquist R, Epstein D, Melamed S, Johnson M, Grant WM. The outflow resistance of the human eye was removed under two different perfusion pressures and different degrees of trabeculotomy. Curr Eye Res. 1989;8(12):1233–1240. doi:10.3109/02713688909013902

34. Parc CE, Johnson DH, Brilakis HS. Giant vacuoles preferentially appear near the collector channel. Invest in Ophthalmol Vis Sci. 2000;41(10):2984-2990.

35. Stamer WD, Braakman ST, Zhou EH, etc. The biomechanics of Schlemm’s duct 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. Glucocorticoids induce the formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest in Ophthalmol Vis Sci. 1994;35(1):281-294.

37. Sumida GM, Stamer WD. Sphingosine 1-phosphate enhances the cortical actomyosin tissue in the monolayer of cultured human Schlemm’s duct endothelial cells. Invest in Ophthalmol Vis Sci. 2010;51(12):6633–6638. doi:10.1167/iovs.10-5391

38. Johnson M. What controls the resistance of aqueous humor outflow? 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. The pluripotent stem cells from the trabecular meshwork become phagocytic TM cells. Invest in 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: regulation and imbalance of intraocular pressure in glaucoma. Exp Eye Res. 2015; 133: 112-125. doi:10.1016/j.exer.2014.07.014

41. Dismuke WM, Klingeborn M, Stamer WD. The mechanism of fibronectin binding to human trabecular meshwork exosomes and its regulation by dexamethasone. Public Science Library One. 2016;11(10):e0165326. doi:10.1371/journal.pone.0165326

42. Ma Johnstone. Water outflow system as a mechanical pump: Evidence from human and non-human primate tissue and water movement inspections. 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 involves pressure-dependent tissue movement. Exp Eye Res. 2017;158:171-186. doi:10.1016/j.exer.2016.06.007

44. Grant WM. Experimental aqueous humor perfusion with human eyes removed. Arched ophthalmology. 1963; 69: 783-801. doi:10.1001/archopht.1963.00960040789022

45. Schuman JS, Chang W, Wang N, de Kater AW, Allingham RR. The influence of excimer laser on the morphology of outflow facilities and outflow channels. Invest in Ophthalmol Vis Sci. 1999;40(8):1676-1680.

46. ​​Ethier CR, Coloma FM, Sit AJ, Johnson M. There are two types of pores in the endothelium of Schlemm's canal. Invest in Ophthalmol Vis Sci. 1998;39(11):2041-2048.

47. Chang JY, Folz SJ, Laryea SN, Overby DR. Multi-scale analysis of the segmental outflow pattern of human trabecular meshwork under changes in 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, etc. The mechanical properties of the marginal sclera: the effect on the intraocular pressure of pigs. Public Science Library 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-the continuum from the trabecular meshwork to the extrascleral vein. Prog Retin Eye Res. 2017; 57: 108-133. doi:10.1016/j.preteyeres.2016.12.004

50. Take AJ, McLaren JW. Measure the extrascleral 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 between human eye pressure and aqueous humor outflow. Invest in ophthalmology. 1971;10(6):430–437.

52. Ellingsen BA, Grant WM. Trabeculotomy and sinusotomy to remove human eyes. Invest in ophthalmology. 1972;11(1):21-28.

53. Grierson I, Lee WR. The fine structure of the trabecular meshwork at graded intraocular pressure levels. (2) Pressure beyond 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 very important for MIGS. Glaucoma Today; September/October 2016.

55. Grover DS, Godfrey DG, Smith O, Feuer WJ, Montes de Oca I, Fellman RL. Gonoscope-assisted transluminal trabeculectomy, ab internal trabeculectomy: technical 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 transcavitary trabeculectomy: for the treatment of primary congenital glaucoma and juvenile open-angle glaucoma ab Inner trabeculectomy. Br J Ophthalmol. 2015;99(8):1092-1096. doi:10.1136/bjophthalmol-2014-306269

57. Grover DS, Smith O, Fellman RL, etc. Gonoscope-assisted transluminal trabeculectomy: ab Medial trabeculectomy: 24 months follow-up. J Glaucoma. 2018;27(5):393–401. doi:10.1097/IJG.0000000000000956

58. Baykara M, Poroy C, Erseven C. The results of combined gonioscope-assisted transluminal trabeculectomy and cataract surgery. J Ophthalmol, India. 2019;67(4):505–558. doi:10.4103/ijo.IJO_1007_18

59. Rahmatnejad K, Pruzan NL, Amanullah S, etc. Gonoscope-assisted transluminal trabeculotomy (GATT) surgical results 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. The results of prolene gonioscope-assisted transluminal trabeculectomy 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. Phacoemulsification combined with trabeculectomy for the treatment of glaucoma. Survival ophthalmology. 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 Trabeculectomy: Development of a new device (Trabectome™) and open-angle glaucoma surgery. J Glaucoma. 2006;15(1):68-73. doi:10.1097/01.ijg.0000196653.77836.af

63. Minckler D, Baerveldt G, Ramirez MA, etc. The clinical results of Trabectome, a new surgical instrument for the treatment of open-angle glaucoma. Trans Am Ophthalmol Soc. 2006;104:40-50.

64. Bhartiya S, Ichhpujani P, Shaarawy T. Trabecular meshwork surgery: histopathological evidence. J Curr Glaucoma Practice. 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 and trabeculectomy for the treatment of open-angle glaucoma. ophthalmology. 2012;119(1):36-42. doi:10.1016/j.ophtha.2011.06.046

66. Francis BA, Winarko J. Comparison of combined trabeculectomy and cataract surgery with combined trabeculectomy and cataract surgery in open-angle glaucoma. Clinical surgery ophthalmology. 2011; 29: 4-10.

67. Khan M, Saheb H, Neelakantan A, etc. The efficacy and safety of 2 trabecular micro-bypass stents combined with cataract surgery and ab internal trabeculectomy. J cataract refractive surgery. 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 the evidence sufficient? A systematic review and meta-analysis of Trabectome as a single surgery for the treatment of primary open-angle glaucoma. J Ophthalmology. 2017; 2017: 2965725. doi:10.1155/2017/2965725

69. Mosaed S. The first decade of global trabecome results. European ophthalmology. 2014;8(2):113-119. doi:10.17925/EOR.2014.08.02.113

70. Gallardo MJ, Supnet RA, Ahmed IIK. The ab-interno method is used to increase the viscosity of Schlemm's canal to reduce intraocular pressure. Clinical ophthalmology. 2018; 12: 2149-2155. doi:10.2147/OPTH.S177597

71. Mahaimi. Angioplasty using iTrack 250 microcatheter to tighten the suture on Schlemm’s Canal. Afr J Ophthalmol, Middle East. 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 choices and perspectives. Clinical ophthalmology. 2019; 13: 2617-2629. doi:10.2147/OPTH.S155057

73. Mahaimi. Canaloplasty: minimally invasive and most effective glaucoma treatment. J Ophthalmology. 2015; 2015: 485065. doi:10.1155/2015/485065

74. Davids AM, Pahlitzsch M, Boeker A, Winterhalter S, Maier-Wenzel AK, Klamann M. Ab Endoplasty (ABiC)-12 months of new minimally invasive glaucoma surgery (MIGS) results. 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 study of ab internal trabeculectomy using a new double-blade device. This is J Ophthalmol. 2013;155(3):524–529.e2. doi:10.1016/j.ajo.2012.09.023

76. Sieck EG, Epstein RS, Kennedy JB, etc. Kahook Dual Blade angle incision with or without the results of phacoemulsification and cataract extraction. Ophthalmology glaucoma. 2018;1(1):75–81. doi:10.1016/j.ogla.2018.06.006

77. Dorairaj S, Tam MD, Balasubramani GK. 12-month results of resective goniotomy in angle-closure glaucoma using Kahook Dual Blade®. Clinical ophthalmology. 2019; 13: 1779-1785. doi:10.2147/OPTH.S221299

78. ElMallah MK, Seibold LK, Kahook MY, Williamson BK, Singh IP, Dorairaj SK. A 12-month retrospective comparison of Kahook Dual Blade angle resection and iStent trabecular bypass device implantation in glaucoma during 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. Gonoscope-assisted intracavitary trabeculotomy (GATT) and a-tubular angioplasty (ABiC) combined with phacoemulsification: 12-month results. Clinical ophthalmology. 2020; 14: 2491-2496. doi:10.2147/OPTH.S267303

80. Tanito M, Ohira A, Chihara E. Combined trabeculectomy and cataract surgery results. 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. The angular stability and outflow in double-blade ab internal trabeculectomy are managed by active and passive chambers. Public Science Library One. 2017;12(5):e0177238. doi:10.1371/journal.pone.0177238

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