Long Term Outcome of Combined Phacoemulsication and Excisional Goniotomy with the Kahook Dual Blade in Different Subtypes of Glaucoma

Purpose: To characterize changes in intraocular pressure (IOP), IOP-lowering medications, and visual acuity (VA) through 3 years of follow-up in patients undergoing combined phacoemulsication and excisional goniotomy with the Kahook Dual Blade (phaco-KDB), with simultaneous goniosynechialysis in cases of angle-closure glaucoma, by a single surgeon (A.H.) in Hospital of Methods: Prospective, non-comparative, uncontrolled, non-randomized interventional case series. Consecutive patients with medically-treated glaucoma and visually-signicant cataract underwent combined surgery. Subgroup analysis of glaucoma subtypes was performed. Results: Fifty-seven eyes (48 patients) including 29 eyes with primary open-angle glaucoma, 15 with pseudoexfoliation glaucoma, and 13 with angle-closure glaucoma, were enrolled. Mean (standard error) baseline IOP was 20.3 (0.7) mmHg and through up to 36 months of follow-up (minimum 12 months, mean 26.2 [1.0] months) ranged from 13.5-14.0 mmHg (13.7 mmHg at Month 36); signicant reductions (p<0.0002) of 23.6-29.9% were achieved at every time point. Medications were reduced from a mean of 3.3 (0.1) to 0.2-1.9 (reduction 51.4-94.7%; p<0.0001 at every time point). Mean logMAR VA improved from 0.97 (0.11) preoperatively to 0.25 (0.04) by Month 6 (p<0.0001), remaining stable thereafter. Outcomes were similar in POAG, pseudoexfoliation, and ACG subgroups. Hyphema occurred and resolved spontaneously in 6 eyes; 1 eye had elevated IOP on postoperative day 1. Conclusions: Phaco-KDB signicantly improved VA, lowered IOP ~25-30%, and lowered medications by >50% through 36 months. This combined procedure provides meaningful long-term reductions in IOP and need for IOP-lowering medication without compromising visual rehabilitation in eyes with cataract and glaucoma. IOP and/or medication burden, combined with goniosynechialysis in cases of angle-closure glaucoma. Patients undergoing any other combined procedures, active uveitis, coexisting retinopathy that limits visual acuity potential, active neovascularization, angle dysgenesis and those with less than 12 months of follow-up, were excluded.


Introduction
Cataract is the world's most common cause of blindness, 1 and glaucoma represents an important cause of blindness worldwide as well. 2 Effective and safe intraocular pressure (IOP)-lowering treatments appropriate for patients with all types and severities of disease would help to halt progression of glaucomatous optic nerve damage and subsequent decline in quality of life. 3 Conventional surgical techniques for the treatment of glaucoma typically provide greater IOP reductions than more conservative medical and laser therapies, 4,5 but trabeculectomy and tube shunts have a higher risk of visionthreatening complications, including early postoperative complications such as hypotony and lifetime risk of bleb or devicerelated complications. 6,7 Longer visual recovery times, activity limitations, need for frequent follow-up, and secondary o cebased or surgical interventions in the early postoperative phase also compromise the patient's quality of life as well as healthcare costs.
In recent years, a series of novel and less-invasive surgical techniques have been developed to provide meaningful IOP reductions with lower risk of complications compared to conventional glaucoma surgery. Most of these procedures avoid the formation of a ltering bleb-and its complications-by shunting aqueous humor across the obstructed trabecular meshwork (TM) into Schlemm's canal (SC) or into the suprachoroidal space, although a few techniques rely on subconjunctival ltration. 8,9 These procedures are considered safe and effective options that can be combined with cataract extraction and may prevent or delay the need for more invasive and higher-risk ltering or shunt surgeries, especially when used in early or moderate stages of the disease. 10,11 The Kahook Dual Blade (KDB; New World Medical, Rancho Cucamonga, CA, USA) is an ophthalmic knife which is used to perform surgical ab interno trabeculectomy (commonly referred to as excisional goniotomy or gonioectomy). 12 Since the development of the KDB in 2015, a rising number of studies have established its e cacy and safety in reducing IOP and medication burden. 13,14 Unlike conventional goniotomy, which is frequently implemented in congenital glaucoma, the KDB's design allows complete resection of diseased TM on the inner wall of SC, allowing the ow of aqueous from the anterior Page 3/10 chamber to the distal out ow system. 12 The KDB also has a favorable safety pro le. 13,14 The most common complication is intraoperative or early postoperative blood re ux that is to be expected with the unroo ng of several collector channels and is generally transient. 15 The newer glaucoma procedures are most commonly utilized in mild-to-moderate glaucoma, due to moderate e cacy compared to subconjunctival ltering procedures. [8][9][10][11] Therefore, most studies of these procedures have been limited to these populations. However, a previous study on stand-alone KDB goniotomy has shown promising e cacy and safety in severe glaucoma patients. 15 Another study demonstrated the e cacy of KDB combined with phacoemulsi cation (Phaco-KDB) in glaucoma patients across the spectrum of disease severity, of whom 22 had severe glaucoma. 14 To our knowledge, no study has speci cally examined the long-term e cacy of KDB goniotomy combined with cataract surgery in patients with different types of glaucoma in our region of the world. In this study, we describe long-term (up to 36 months) outcomes of phacoemulsi cation and excisional goniotomy using the KDB, combined with goniosynechialysis in cases of angle-closure glaucoma, in patients with cataract and different types and stages of glaucoma.

Study Design
This was a prospective, non-comparative, uncontrolled, non-randomized interventional case series of consecutive patients undergoing combined Phaco-KDB, with simultaneous goniosynechialysis in cases of angle closure glaucoma. All the surgeries were performed by a single surgeon (A.H.) at King Fahd Hospital of the University, Dammam, Saudi Arabia over the course of three years. The protocol was reviewed and approved by Imam Abdulrahman Bin Faisal University IRB. Approval was given on the understanding that the "Guidelines for Ethical Research Practice" were adhered to, and all patients provided written informed consent to participate. Participating patients were adults 18 years or older with medically-managed glaucoma and visually signi cant cataract undergoing Phaco-KDB for reduction of IOP and/or medication burden, combined with goniosynechialysis in cases of angle-closure glaucoma. Patients undergoing any other combined procedures, active uveitis, coexisting retinopathy that limits visual acuity potential, active neovascularization, angle dysgenesis and those with less than 12 months of follow-up, were excluded.

Surgical Technique
The combined Phaco-KDB procedure has been previously described. 9,11 Brie y, following standard phacoemulsi cation and intraocular lens implantation, the anterior chamber was lled with ophthalmic viscosurgical device (OVD). The KDB was inserted into the anterior chamber and under intraoperative gonioscopy advanced to the nasal TM. In eyes with angleclosure glaucoma, goniosynechialysis was performed rst, as described by Dorairaj. 16, 17 The KDB's pointed tip engaged the peripheral iris at the base of each peripheral anterior synechia (PAS) and dissected the PAS with gentle radial pressure within the iris plane toward the pupillary center to reveal the trabecular meshwork. The excisional goniotomy was then performed as previously described. 13, 14 The instrument's tip engaged TM until the heel of the device rested within SC. The blade was then advanced along the TM, which became elevated and stretched as it was guided up the ramp to the two parallel cutting blades that removed an intact TM strip. Using the dip and strip technique in which the TM is punctured with the KDB at one end of the intended excision, the KDB then entered TM at the opposite end of the intended excision and was advanced to the rst puncture site. The KDB was then removed from the eye and the excised strip of TM removed from the eye with forceps.

Statistical Analysis
Data collected in this study included baseline demographic information as well as visual acuity (VA), IOP, and IOP-lowering medications at every time point. Intraoperative and postoperative adverse events were also recorded. Postoperative data were collected at Day 1, Weeks 2, 4 and 6, and Months 2-3, 6, 9, 12, 18, 24, and 36 post-surgery. VA was best-corrected VA (BCVA) preoperatively and beginning 4-6 weeks postoperatively. IOP was measured with Goldmann applanation tonometry.
In determining the number of IOP-lowering medicines used at each time point, combination products were counted by the number of constituents and oral carbonic anhydrase inhibitors were also included in the count. The co-primary outcomes of this analysis were the reductions of both IOP and IOP-lowering medications from baseline at each postoperative time point.
These outcomes were assessed using paired t-tests. Secondary outcomes included change in BCVA from baseline (also assessed using paired-tests), as well as the proportion of patients with >20% IOP reduction, with IOP <18 mmHg and <15 mmHg, with >1 medication reduction, and medication-free at each time point beginning at Month 2-3 (after postoperative stabilization). Subgroup analysis was undertaken to evaluate the co-primary endpoints separately in eyes with open-angle and closed-angle glaucoma; these outcomes were evaluated through 24 months of follow-up; the last time point at which sample sizes were adequate to characterize results. No speci c hypotheses were tested and formal power and sample size calculations were not undertaken. The level of signi cance was taken to be 0.05. Means are reported with standard errors.
Data were analyzed using SAS version 9.4 (SAS Institute Inc, Cary, NC)

Results
Data from 57 eyes of 48 subjects undergoing Phaco-KDB with or without goniosynechialysis and followed for a minimum of 12 months and up to 36 months (mean 26.2 [1.0] months) were analyzed. Demographic and baseline glaucoma status data are given in Table 1. Subjects' mean age was 64.32 (1.4) years and slightly more were men (56%) than women (44%).

Visual Acuity Outcomes
Visual acuity data at each time point are given in Table 2

Outcomes in Subgroups
Mean IOP and IOP-lowering medication reductions from baseline were separately evaluated in the subgroups with POAG, PXFG, and ACG through 24 months of follow-up (Figures 1 and 2). In eyes with POAG, mean IOP reductions were 6. KDB is a novel goniotomy blade produced to create a more complete removal of TM through a minimally invasive technique without any adjacent tissue injury. 12 The design of KDB has several key features to achieve a complete goniotomy. The tip is sharp, the heel ts comfortably within SC which allows smooth advancement of the blade without any collateral injury, the ramp of the blade stretches TM gently while blade advancement and the dual blades create parallel incisions facilitating excision of a strip of TM. 12,18 An additional bene t of the KDB is that it is a single-use, disposable instrument that does not require any additional special surgical equipment, without implant-related risks as no implant is left behind with this procedure. 18 Reducing IOP or the medication burden are two main indications for combining glaucoma surgery with elective cataract surgery (as in most cases of POAG or pseudoexfoliation glaucoma) or in more urgent cases (as in acute ACG). Our prospective study is a real-world study that reveals the long experience of a single surgeon performing combined phaco-KDB demonstrates the safety, e cacy with a signi cant and persistent reduction in the IOP and the need for IOP-lowering medication throughout 36 months which is the longest reported follow up to date of which we are aware. In addition to its e cient IOP lowering and medication reduction, KDB goniotomy furthermore shows a well-tolerated and safe pro le. Overall, most complications were transient hyphemia with spontaneous resolution in only six eyes, and one eye with transient high IOP due to retained OVD as we usually intend to leave some OVD in the end of the surgery, which also resolved spontaneously and were non-sight threatening. These results correspond with prior reports in the literature. [13][14][15]20,26 Earlier studies have hypothesized that angle procedures targeting the TM may be more effective among the pseudoexfoliation glaucoma patient population as the pseudoexfoliative material may be obstructing TM out ow. 19 Only one prior study to date has compared the success rates of KDB goniotomy between POAG and PXFG. In their study, Sieck et al. reported a higher success rate among PXFG (84.6%) compared to POAG (66.0%). However, this difference did not reach statistical signi cance after . 19 Nonetheless, given the small sample sizes in this study, a de nite conclusion cannot be drawn. In our subgroup analysis, there were no clinically signi cant differences between each type of glaucoma enrolled in the study.
Strengths of this study include its length of follow-up and its patient population of Saudi Arabian glaucoma patients. The lack of a control group-common to many retrospective analyses of novel glaucoma procedure outcomes-is a limitation that precludes benchmarking our results to other procedures in a head-to-head fashion.

Conclusions
In summary, Phaco-KDB signi cantly improved VA, lowered IOP ~25-30%, and lowered medications by >50% through 36 months. This combined procedure provides meaningful long-term reductions in IOP and need for IOP-lowering medication without compromising visual rehabilitation in eyes with cataract and glaucoma.

Declarations Data Availability
The datasets analyzed during the current study are available from the corresponding author on reasonable request.