Comparison Eciency of Combined Trabeculectomy with MMC and Gonioscopy-Assisted Transluminal Trabeculotomy

Purpose: To compare the ecacy of gonioscopy-assisted transluminal trabeculotomy combined with cataract surgery (PGATT) and trabeculectomy combined with cataract surgery (PTRAB) in open-angle glaucoma patients. Methods: A multicentered, retrospective, non-randomized study included 67 PGATT patients and 70 PTRAB patients. We compared preoperative intraocular pressure (IOP), best-corrected visual acuity (BCVA) compared with early and nal IOP, medication numbers, and BCVA levels. Success was determined as IOP reduction >20% from baseline, IOP between 5-21 mmHg, preoperative IOP of higher than 21 mmHg with medication and postoperative IOP of less than 21 mmHg without medication for surgeries performed for intolerance to medication, postoperative IOP <21 mmHg as well as <18 mmHg separately without medications, and no need for further glaucoma surgery. Results: Preoperative IOP values were 28.61 ± 6.02 mmHg in PTRAB group and 23.99±8.00 mmHg in PGATT group (P<0.0001). Early postoperative IOP values were found lower in PTRAB group as 12.19 ± 3.41 mmHg and as 15.69 ± 4.67 mmHg in PGATT group (P<0.0001). Last follow-up IOP reading were lower in PGATT group (P=0.009). IOP difference values were found higher both in early and last postoperative periods in PTRAB group (respectively, P<0.0001, P=0.018). Success rates were found higher in both at lower than 21 and 18 mmHg levels in PGATT group (respectively, P=0.014, P=0.010). Conclusion: We found the PGATT combined procedure to be a well-tolerated, effective procedure that can lower IOP both early and late in the postoperative period with different rates of IOP success compared with the combined PTRAB procedure.


Introduction
Glaucoma is one of the world's leading causes of irreversible blindness and is expected to affect 76 million people worldwide. [1] Whereas trabeculectomy remains the most commonly performed glaucoma surgery worldwide, minimally invasive glaucoma surgery (MIGS) is rapidly gaining ground, chie y due to its safer surgical pro le. Even though very low target intraocular pressure (IOP) may be necessary for advanced glaucoma and achievable with trabeculectomy, a considerable number of sightthreatening complications may occur, including hypotonia, retinal detachment, and endophthalmitis. By contrast, MIGS is easily combined with surgery for cataract [2], which among older adults is frequently associated with glaucoma requiring surgical intervention. [3] Even so, Schlemm's canal surgeries offer a less invasive approach and an improved out ow pathway by either bypassing or removing diseased trabecular meshwork. [4] As a novel clear corneal approached gonioscopy-assisted transluminal trabeculotomy (GATT) technique provides alternative bleb-less glaucoma treatment option for anterior segment surgeons. [5] Since its rst introduction this new modality reported successful outcomes on numerous open angle glaucoma types.
However, there are still lacks of studies comparing and searching the surgical outcomes to long-standing known techniques such as trabeculectomy. In our study, we aimed to compare the e ciency of trabeculectomy combined with phacoemulsi cation (PTRAB) and gonioscopy-assisted transluminal trabeculotomy combined with phacoemulsi cation (PGATT).

Material And Methods
In a multicentered, non-randomized, comparative, observational retrospective study, we collected, analyzed, and followed up on data of eyes undergoing PTRAB and PGATT surgery. All patients who were Patients with normal-tension glaucoma, neovascular glaucoma, pigmentary glaucoma, steroid-induced glaucoma, glaucoma associated with ocular dysgenesis, congenital glaucoma, history of ocular trauma, or previous glaucoma surgery, including laser trabeculoplasty, in the study eye, were excluded from this study. The patients with a history of previous ocular surgery, eye trauma, uveitis, or any systemic disease such as diabetes mellitus, thus carrying an increased risk of postoperative in ammation following surgery, were excluded from the study.

PGATT Operations
In all PGATT operations, the same surgeon (E.B.) began with cataract extraction. A combination of phenylephrine 2.5% and tropicamide 1% was given for mydriasis before surgery. After a standard sterile preparation, the surgical eye was draped, and an open wire nasal lid speculum was inserted to hold the eyelids open. Under sub-Tenon's anaesthesia, phacoemulsi cation was performed. A 2.4-mm temporal clear corneal incision was created, and sodium hyaluronate-chondroitin sulphate (Viscoat, Alcon Inc., Fort Worth, TX, USA) was injected into the anterior chamber. A 5.0-5.5-mm anterior curvilinear capsulorhexis and coaxial phacoemulsi cation with irrigation-aspiration (Centurion Vision System, Alcon Inc., Fort Worth, TX, USA) were performed. After the capsular bag was lled with sodium hyaluronate 1% (Healon AMO Inc., Abbott Park, IL, USA), a one-piece hydrophobic acrylic intraocular lens (IOL) was implanted in the bag. The intraocular viscoelastic was completely cleaned to ease its removal, after which the miotic agent Miochol-E (i.e. acetylcholine chloride intraocular solution) and 1.4% sodium hyaluronate (Healon GV; AMO Inc., Abbott Park, IL, USA) were administered in the anterior chamber. Once the nasal angle was displayed with a Swan Jacob goniolens, using the same clear corneal main incision a 1-to 2-mm goniotomy was created in the nasal angle with a microvitreoretinal (MVR) microsurgical blade through the temporal site ( Fig. 1). A 6/0 Prolene suture was rounded by hand cautery (Fig. 2), after which a blunted suture was introduced through the paracentesis and retrieved intracamerally. The microsurgical forceps were used to guide the tip of the 6/0 Prolene suture through the goniotomy cleft into Schlemm's canal and to advance the tip approximately 360° (Fig. 3). After the suture was coursed through the entire canal, the tip appeared on the opposite side of the goniotomy cleft, and the leading tip was grasped with the forceps and pulled to the center of the anterior chamber (Figs. 4). The suture was externalized from the temporal corneal incision, thereby creating the 360° ab interno trabeculotomy. Last, the anterior chamber was washed with a 2-handed irrigation aspiration system to remove viscoelastic material and blood, and the wounds were checked to ensure watertight closure.

PTRAB Operations
In all PTRAB operations, performed by the same surgeon (A.O.) under general anaesthesia, a limbusbased conjunctival-Tenon ap and a scleral ap 4 × 4 mm were opened for all patients who received trabeculectomy. Next, sponges impregnated with 0.02 mg/ml mitomycin-C were kept under the conjunctival and scleral aps for 2 min, after which a second transparent corneal incision at the superotemporal area 2.75 mm wide was made on patients who received phacotrabeculectomy. Sodium hyaluronate-chondroitin sulphate (Viscoat, Alcon Inc., Fort Worth, TX, USA) was injected into the anterior chamber, followed by the installation of a dispersive ocular viscosurgical device (OVD) to protect the corneal endothelium during surgery. After capsulorhexis, hydro-dissection, and hydro-delineation, phacoemulsi cation was performed (In nity Vision System with Ozil IP, Alcon Inc., Fort Worth, TX, USA).
Once the capsular bag was lled with OVD, a one-piece hydrophobic acrylic IOL was implanted in the bag. An excision 3 × 1 mm was made in the trabecular tissue, after which peripheral iridectomy was performed. Last, the OVD was removed from the anterior chamber by bimanual irrigation and aspiration, and the scleral ap was sutured with 3 separate 10/0 nylon. A balanced salt solution was used for anterior chamber reformation in all surgeries.

Postoperative Assessment and Success Criteria
We followed up on patients postoperatively on the rst day and during the rst week, as well as in the rst, 3rd, 6th, and 12th months. We analyzed as early postoperative IOP on the rst week and as late postoperative IOP on last recorded visit. We compared preoperative IOP values with nal IOP values, the latter de ned as the value of at least 12 months postoperative. Patients' BCVA, IOP values, and anterior and posterior segment ndings were recorded. Anti-glaucoma medications were also administered as needed based on a target IOP of less than 21 mmHg at 2 weeks after surgery.
The primary outcome measures were success rate, IOP, and the number of glaucoma medications. Success was de ned according to four criteria: 1) IOP reduction of greater than 20% from baseline, 2) postoperative IOP 5-21 mmHg as well as 5-18 mmHg separately, 3) preoperative IOP of higher than 21 mmHg with medication and postoperative IOP of less than 21 mmHg without medication for surgeries performed for intolerance to medication, and 4) lack of need for further glaucoma surgery.
Failure, by contrast, was de ned in light of necessary reoperation to control IOP, a postoperative IOP not at least 20% lower than preoperative levels at last follow-up, or an IOP exceeding 21 mmHg at last followup.

Statistical Analyses
Statistical analyses were performed using SPSS (version 20.0, Chicago, IL, USA). The variables were investigated using visual histograms, probability plots, and the Shapiro-Wilk test to determine whether they were normally distributed. A statistical power analysis was also performed. Descriptive analyses were recorded using means and standard deviations because the variables were normally distributed. The mean between-group differences in baseline demographic and clinical characteristics were compared with the independent samples t test or chi-square test as applicable. All p values less than 0.05 were evaluated as indicating statistical signi cance.

Results
Measurements obtained from all cases included in the sample were analyzed. Among the demographic data (i.e. age, gender, glaucoma type, follow-up time, preoperative IOP, pachymetry, BCVA, and number of medications), mean age, gender distribution, and preoperative IOP values differed signi cantly between the groups. In particular, the PGATT group had a statistically higher mean age than the PTRAB group (P = 0.005) and more males, whereas the PTRAB group included more females (P = 0.013). No signi cant between-group differences arose in mean preoperative IOP, pachymetry reading, and preoperative use of medication, surgical side, or type of glaucoma. Similar mean LogMAR BCVA values were observed in both groups, although mean follow-up time was signi cantly longer in the PTRAB group. Table 1 shows the demographic characteristics of the groups. Early postoperative IOP readings in the PGATT, and PTRAB group were 15.69 ± 4.67, 12.19 ± 3.41 mmHg respectively (P < 0.0001), whereas the last readings were 15.04 ± 4.26, 16.96 ± 4.11 mmHg respectively (P = 0.009). Early and nal postoperative IOP differences compared to preoperative levels were statistically higher in the PTRAB group. When the last postoperative target IOP level was lower than 18 mmHg, complete success rates were 57/10 in the PGATT group and 47/23 in the PTRAB group (P = 0.014).
However, when the last postoperative target IOP level was lower than 21 mmHg, success rates increased 64/3 in the PGATT group and 57/13 in the PTRAB group (P = 0.01). Table 2 shows the results of IOP analyses and comparisons. Apart from the surgical outcome differences, there was no early and late postoperative complication was noted on our study.

Discussion
The incidence of glaucoma and cataract increases during the natural ageing process of the human eye. The need for surgery depends upon the dominancy of visual deterioration and the extent to which glaucoma has progressed. If both conditions apply, then surgeries can be combined. Combining cataract and glaucoma surgeries affords several bene ts over separate operations, including reduced morbidity, lower costs, and faster recovery. Performing combined procedures also reduces the risk of postoperative IOP spikes and the need for ocular hypotensive. Cataract surgery in an eye with a lter in place poses a risk of a ltering ap; however, performing both operations at the same time can result in signi cant in ammation. Filtering procedures alone are prone to complications such as in ammation, hypotony, and hyphaemia. Beyond that, a ltering bleb can fail at any time in the postoperative period, from minutes to decades after surgery. [6] The demographic characteristics of groups in our study were statistically similar. The effects of age on wound healing are evident in ltering surgeries. Because wound healing decreases with aging, advanced age can be regarded as a positive factor in trabeculectomy surgery. [7] GATT surgery is conjunctivasparing surgery; it is not affected by wound healing or ocular surface disorder due to topical drugs.
However, the success of GATT surgery decreases in patients with advanced glaucoma due to reasons such as possible collector duct atrophy.
[8] Therefore, the age and gender distributions of the groups needed to be matched in our study to ensure their comparability.
In our study, preoperative IOP was signi cantly higher in the PTRAB group, largely because trabeculectomy surgery, a conventional ltrating surgery, is a more effective method of lowering target IOP. Likewise, preoperative IOP values were lower in the other group because GATT is preferred in patients with lower IOP, for it causes less vision-threatening complications in early-and middle-stage glaucoma.
GATT also seems to be more successful when the target pressure is in the mid-teens, because GATT provides an IOP directly proportional to the episcleral venous pressure. Early IOP was signi cantly lower in the trabeculectomy group, although its long-term success decreased due to wound healing, as commonly seen in ltrating surgeries over time. That situation increases considerably due to intense in ammatory mediator release, especially during combined phacoemulsi cation surgery. We also compared combined trabeculectomy with combined GATT and noticed that the long-term effect was more pronounced in the trabeculectomy group, most likely due to the increased in ammatory mediator release after peripheral iridectomy in trabeculectomy surgery and the fact that wound healing in the conjunctiva and scleral ap is more affected by in ammation. However, Siriwardena et al. found that anterior chamber in ammation and the breakdown of the blood-aqueous barrier are far more prolonged after uncomplicated small-incision cataract surgery than after glaucoma ltration surgery with peripheral iridectomy. [9] We thought that, in ammation might be a obstructing factor that affect surgical outcomes, especially after traditional ltration surgeries.
At present, glaucoma surgery comes in different types for different indications. The top reason for the surgery is to reduce complication rates, speci cally bleb-related complications. In particular, Schlemm's canal surgeries have the advantage of using the natural out ow route. [10] Although glaucoma surgery's effectiveness notoriously decreases in combination with cataract surgery, combined surgery sometimes needs to be performed due to the di culty of following up with the patient and the intensity of the cataract. The factors that cause PTRAB to be less successful than trabeculectomy include the disruption of the blood-aqueous barrier, the release of in ammatory mediators, the acceleration of wound healing, and secondary bleb failure. [11] In that light, minimally invasive surgery confers the bene ts of less in ammatory reaction. Even so, combined surgery should generally be avoided in interventions for glaucoma.
Epithelial cells of the human lens are released after uneventful cataract surgery, which is the principal reason for long-term in ammation and the source of in ammatory mediators. Because postoperative in ammation involves brogenesis, all ltration procedures are affected by the wound-healing effect.
Despite the lack of proof that natural IOP-reducing procedures such as GATT are affected by postoperative in ammation, we recently found that combined surgery causes shorter-term success. Our ndings herein are additional proof that the higher the in ammation following combined trabeculectomy operations other than GATT, the less the long-term complete success. However, additional preclinical studies are needed to clarify the effect of type of glaucoma surgery and in ammation on long-term IOP-reducing potency. [12] One of the best explanations for the in ammatory effect on glaucoma surgery surveillance is uveitic glaucoma surgery. Ample literature on that topic commonly acknowledges that in ammation causes the failure of interventions for glaucoma, especially if they are combined. [13] When we applied glaucoma surgery only in the case of uveitic glaucoma, as a type of surgery that is gaining ground, the effect on the failure could be better understood. [14] Bettis et al [14] found that implanting an Ahmed glaucoma valve (AGV) outperformed the trabeculectomy procedure for uveitic glaucoma, particularly in the rst year, possibly because peripheral iridectomy was applied only in the classical trabeculectomy operation. Implanting an AGV can be applied without iridectomy, and the bleb will be more posterior than the trabeculectomy, such that the in ammatory effect is less than the effect of trabeculectomy. Our study shows that amid in ammatory conditions that may affect surgery, type of surgery becomes important for long-term success.
Among our study's limitations, the long-term results of both groups were not analysed. Because trabeculectomy surgery is an older method, postoperative follow-up times were longer, and we observed that its success decreased over time. Another limitation was that the early and end-stage IOP values were approximate in the PGATT group based on their average scores at 18-month follow-up. That situation decreased e ciency, because combined surgery was signi cantly less successful in the PGATT group than in the PTRAB group.
In conclusion, we found the PGATT combined procedure to be a well-tolerated, effective procedure that can lower IOP both early and late in the postoperative period with different rates of IOP success compared with the combined PTRAB procedure.

Declarations Compliance with Ethical Standards
Funding: This study has not any nancial support.

Con ict Of Interest:
Author Ali Olgun declares that he has no con ict of interest.
Author Fatih Yenihayat declares that he has no con ict of interest.
Author Hacı Uğur Çelik declares that he has no con ict of interest.
Author Ercüment Bozkurt declares that he has no con ict of interest.
Author İbrahim Şahbaz declares that she has no con ict of interest.
Ethical approval:    The microsurgical forceps was used to guide the tip of 6/0 prolene suture through the goniotomy cleft into the Schlemm canal and to advance the tip around 360°