Trabectome: Microsurgical Management of Adult and Infantile Glaucoma by MediConcept

Trabectome: Microsurgical Management of Adult and Infantile Glaucoma

EDITORS: BRIAN FRANCIS, MD SAMEH MOSAED, MD STEVEN VOLD, MD MASAHIRO MAEDA, MD SEYED JAVAD HASHEMIAN, MD

A Special Supplement of

CSO

Clinical Surgical Ophthalmology

Library and Archives Canada Cataloguing in Publication Trabectome: microsurgical management of adult and infantile glaucoma / contributors, Brian Francis, Seyed Javad Hashemian, Masahiro Maeda, Sameh Mosed, Steven Vold. Each author contributed a separate essay. Includes bibliographical references. Electronic monograph in PDF format. ISBN 978-1-896825-32-8 (pdf) 1. Glaucoma--Surgery. I. Francis, Brian A., author RE871.T73 2015

617.7'41059

C2015-904692-0

These articles have all been previously published in Clinical & Surgical Ophthalmology, ISSN: 1705-4842. A serial clinical publication of Mediconcept. Cover Photo George Baerveldt, MD Courtesy of: John D McMahon Application and Usage The authors and publishers have extended every effort to ensure that the application and use of all medical drugs and devices mentioned in this publication are in accord with current recommendations and practices. However, in view of ongoing research, changes, in regulation, and the constant flow of information relating to ophthalmology, the reader is cautioned to consult the package insert of any product for changes, warnings, or precautions prior to usage. This is particularly important when the product is either new or infrequently used. All Rights Reserved No part of this publication may be translated into any other language, reproduced, or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, micro copying, or by any information storage and retrieval system without prior written permission from the publisher. Prepared, printed and published in Canada by: Mediconcept Inc. 3484 Sources Blvd. Suite 518 Dollard des Ormeaux, Quebec H9B 1Z9 Canada Tel.: (514) 447-1110 Copyright ÂŠ 2015 Mediconcept Inc.

Contributors

Contents Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Don Minckler, MD, MS Trabectome Implantation: Surgical Steps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 The First Decade of Global Trabectome Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Sameh Mosaed, MD Trabectome Outcomes in Adult Open-Angle Glaucoma Patients: One-Year Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Sameh Mosaed, MD; Douglas J. Rhee, MD; Theodoros Filippopoulos, MD; Helen Tseng, MD; Sunil Deokule, MD; Robert N. Weinreb, MD Trabectome Combined with Phacoemulsification versus Phacoemulsification Alone: A Prospective, Non-Randomized Controlled Surgical Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Brian A. Francis, MD, MS Impact of Preoperative Intraocular Pressure on Trabectome Outcomes: A Prospective, Non-Randomized, Observational, Comparative Cohort Outcome Study. . . . . . . . . . . . . . . . . . . . . . 28 Steven D. Vold, MD Trabectome versus Trabeculectomy in Open-Angle Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Brian A. Francis, MD, MS Comparison of the Outcomes of Trabectome with Trabeculotomy with Deep Sclerectomy: Ab Interno vs. Ab Externo Trabeculotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Masahiro Maeda, MD; Natsu Kondo, MD; Kazunori Onuki, MD; Rina Noritake; Asato Hasegawa, MD Combined Trabectome and Cataract Surgery versus Combined Trabeculectomy and Cataract Surgery in Open-Angle Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Brian A. Francis, MD, MS; Jonathan Winarko, MD Combined Cataract Extraction and Trabeculotomy by the Internal Approach for Coexisting Cataract and Open-Angle Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Seyed Javad Hashemian, MD; Arezoo Miraftabi, MD; Mohammad Ebrahim Jafari, MD; Mohsen Rezaei Hemami

Foreword

Don Minckler, MD, MS

My first awareness of Trabectome® occurred during a visit from the CEO of NeoMedix, the manufacturer of this then in-progress instrument when I was still Glaucoma Chief at USC –Doheny in Los Angeles. One of the inventors, George Baerveldt, MD, had been a former glaucoma colleague at USC before moving to Cleveland, and subsequently back to UCI in Irvine, California where he and Roy Chuck, an MD/PhD engineer along with NeoMedix bioengineers planned and built the prototype instrument. I was completely unaware of the instrument when initially asked by the development group as an outside glaucoma specialist to give an assessment of the potential value of this instrument for surgical management of open-angle glaucoma prior to their anticipated major investments of time and money to move it beyond the development stage into clinical use. At this time, no FDA approval process or application to patients had been initiated. Importantly Dr. Baerveldt had developed an autopsy eye model, an inverted donor corneal ring with ciliary body removed, still in use for clinical training at wet-lab courses for Trabectome nationally and internationally. This model allowed essential demonstrations of the micro-incisional nature of the device, by light and scanning electron microscopy, demonstrating selective simultaneous removal of the meshwork and inner wall of Schlemm’s canal without damage to the back wall of Schlemm’s canal or adjacent structures. D. Minckler — Professor Emeritus of Ophthalmology and Glaucoma Service Director; Clinical Professor of Laboratory Medicine (Ophthalmic Pathology), University of California, Irvine, CA Correspondence to: Dr. Don Minckler, Gavin Hebert Eye Institute, 850 Health Sciences Road, Irvine, CA 92697-4375; E-mail: minckler@uci.edu Dr. Don Minckler is a Trabectome Trainer since 2005 and is not a shareholder of NeoMedix.

I concluded after my initial wet lab and interactions with the developers that this novel surgery had great potential as an ab interno angle procedure, to remove approximately 60% of the barrier to aqueous access to Schlemm’s collector channels, the meshwork and inner wall of the canal. Following two visits to the FDA and several meetings with AAO and AMA representatives, US FDA 510 clearance for Trabectome use in adult and pediatric open-angle glaucoma was granted in April 2004 with the eventual CPT code designation as “trabeculotomy ab interno – 65850.” NeoMedix’s approach to marketing this device was, in my view, appropriately initially targeted at academic glaucoma thought leaders in major US and international centers. After providing didactic and wet lab training at the NeoMedix factory in Tustin, CA, I organized and directed the first large AAO skills transfer course in 2007, which continues in the 2015 Annual Meeting. Trabectome continues to be presented at national and international CME-granting meetings, many including wet lab options, as a desirable alternative among the growing list of micro-incisional glaucoma surgeries (MIGS). Again wisely in my view, NeoMedix has required attendance at a didactic, a wet-lab session, and observation of live surgery before issuing their individual certification of training. They provide an additional certificate indicating Trainer status once the surgeon has returned data on his/her first 20 cases. The self-reporting of all subsequent cases to NeoMedix is strongly recommended and all surgeons have access to their own data with any requested analysis for use in academic meetings or practice marketing. NeoMedix’s representatives attend and provide technical in-service at all new surgeons first cases worldwide. The first interventional case series including 37 adult eyes done in Mexico was reported in Ophthalmology in 1995. Subsequently through 2015 some 52 peer reviewed publications on Trabectome in both adult and pediatric age groups have been published worldwide for over 3500 eyes including clinical data and outcomes, some with 6.5 years follow-up, including Trabectome only and combined with phacoemulsification. The total number of Trabectome certified surgeons world-wide has reached 1509 with 139 now designated as being Trainers. In my personal experience of 100 cases, this procedure far more often than not normalized IOP and decreased the use of adjunctive topical medications far more safely than in my much larger experience with Trabeculectomy and Glaucoma Drainage Devices over several prior decades. In spite of my loathing of self-promotion by physicians, I am distinctly proud of my contributions to the ongoing success of Trabectome as an elegant and safe alternative to traditional filtering surgery.

Foreword

Trabectome Implantation: Surgical Steps

The First Decade of Global Trabectome Outcomes Sameh Mosaed, MD

ABSTRACT

INTRODUCTION

Purpose: To present available primary outcome results of global Trabectome experience for patients receiving Trabectome procedure including cases with up to 90 months of follow-up. Method: A total of 4,659 cases were included in the study. Baseline demographics were collected and outcome measures included intraocular pressure, number of glaucoma medications and secondary glaucoma surgery, if any. Survival analysis was performed and success was defined as IOP ≤ 21 mmHg, at least 20% of IOP reduction from baseline, and no additional glaucoma surgery. Results: At 90 months, IOP was reduced from 23.1±8.0 mmHg to 17.2±3.0 mmHg (26%) and number of glaucoma medications was reduced from 2.6±1.3 to 1.1±1.3 (58%). At 90 months, the survival rates were 66% for all cases and 56% for Trabectome alone cases. The survival rate was 85% for Trabectome combined with cataract removal at 60 months (limit of available outcome data for this subgroup). Discussion: These results are generally consistent with previously published outcome results for patients receiving the Trabectome procedure. Conclusion: Considering this outcome analysis of the available global Trabectome experience in combination with outcome data surveyed from the literature, patients receiving Trabectome on average have about a 30% reduction in IOP and 60% reduction in glaucoma medication. The Trabectome procedure can be considered for initial glaucoma therapy, as well as for end-stage patients that have been refractory to other surgical and medical treatments.

Glaucoma is a disease that results in degeneration of the optic disc and can lead to reduced vision and even blindness if left untreated. The purpose of this study is to provide summary results of Trabectome procedures performed between 2004 to 2013. Glaucoma remains one of the leading causes of blindness worldwide. Globally, 60.5 million people were estimated to have glaucoma in 2010, and the number is expected to increase to 79.6 million by 2020.1 Based on population-based surveys, it is indicated that one in 40 adults older than 40 years of age has glaucoma with loss of visual function, equating to about 8.4 million being bilaterally blind.2 Intraocular pressure (IOP) is considered to be one of the main risk factors for optic nerve damage. Hence, one of the goals of glaucoma treatment is to lower and maintain IOP control.3-6 Available treatments for glaucoma include surgical procedures and topical eye drops. Traditional filtering surgeries such as trabeculectomy and aqueous tube shunt are associated with potential complications. Complications associated with trabeculectomy include hypotony, hypotony maculopathy, bleb leaks, late blebitis, choroidal effusion and hemorrhage, bleb-related endophthalmitis, peripheral anterior synechiae formation, posterior synechiae, and cataract formation.7-8 The complication rates are increased when antifibrotics are used, but the short-term failure rate of trabeculectomy in the absence of antifibrotics is relatively high.8-10 The rate of endophthalmitis is 1% per year. Aqueous tube shunt surgery has the risk of early hypotony, choroidal effusion, suprachoroidal hemorrhage, shallow anterior chamber, diplopia, tube obstruction, conjunctival erosion, tube migration, corneal decompensation, plate encapsulation and late failure.7-8 Due to these high complication rates associated with filtering surgeries, the Trabectome surgical device was developed in attempt to lower IOP while minimizing the risks typically associated with filtering surgeries.11 The Trabectome device was cleared by Food and Drug Administration (FDA) in 2004. It is designed to address the outflow resistance problems in open-angle glaucoma (OAG). The device ablates a strip of trabecular meshwork and the inner wall of Schlemm’s canal and thus reestablishes outflow to the natural pathway.12 Since the

S. Mosaed — Associate Professor - Cataract and Glaucoma Surgery, Ophthalmology; Director of Glaucoma Services, Department of Ophthalmology; Director of Glaucoma, Long Beach Veterans Hospital; Director of Glaucoma Fellowship, Department of Ophthalmology; Gavin Herbert Eye Institute University of California at Irvine, School of Medicine, Department of Ophthalmology, Irvine, CA Correspondence to: Dr. Sameh Mosaed, Department of Ophthalmology, University of California at Irvine, 118 Med Surge I, Irvine, CA 926974375; E-mail: smosaed@uci.edu This article has been peer reviewed and was subsequently accepted for publication on February 28, 2014.

The First Decade of Global Trabectome Outcomes — Mosaed

Supplement: Clinical & Surgical Ophthalmology, June 2015

Year

2005

2006

2007

2008

Minckler D, Mosaed S, Dustin L, et al

Nguyen Q

Francis B, Minckler D, Dustin L, et al

Filippopoulos T, Rhee D

Gunderson E

Mosaed S

Francis B, See R, Rao N, et al

Minckler D, Baerveldt G, Ramirez M, et al

Minckler D, Baerveldt G, Ramirez M, Francis B

Author

Table I Peer-reviewed journals

Trabectome (Trabeculectomy-Internal Approach): Additional Experience and Extended Follow-Up

Trabectome: A Novel Approach to Angle Surgery in the Treatment of Glaucoma

Combined Cataract Extraction and Trabeculotomy by the Internal Approach for Coexisting Cataract and Open-Angle Glaucoma: Initial Results

Novel Surgical Procedures in Glaucoma Advances in Penetrating Glaucoma Surgery

Trabeculotomy Ab Interno, Using the Trabectome: A Promising Treatment for Patients with Open-Angle Glaucoma

Ab Interno Trabeculotomy with the Trabectome Surgical Device

Ab Interno Trabeculectomy: Development of a Novel Device (Trabectome) and Surgery for Open-Angle Glaucoma

Clinical Results with the Trabectome, A Novel Surgical Device for Treatme of Open-Angle Glaucoma

Clinical Results with the Trabectome for Treatment of Open-Angle Glaucoma

Title

TA: ~35% TP: ~42%

~36%

12M: 16% 21M: 25% 21M: 7

6M: 29% 12M: 34% 24M: 30% 48M: 30%

40%

42%

~40%

~31%

IOP Reduction (%)

TA: ~83% TP: ~30%

~67%

12M: 36% 21M: 32%

~67%

~75%

~90%

Meds Reduction (%)

up to 60M

up to 56M

up to 21M

up to 52M

52M

36M

30M

12M

Follow-up Period

TA: 738 at baseline and 2 at 60 M TP: 366 at baseline and 2 at 30M

679 at baseline 106 at 6M 65 at 12M 30 at 24M 13 at 48M

304 at baseline 12M: 34

679 at baseline 106 at 6M 65 at 12M 30 at 24M 13 at 48M

434 at baseline 52M: NA

201 at baseline 5 at 30M

101 at baseline 11 at 30M

37 at baseline 15 at 12M

Total # of Cases

The First Decade of Global Trabectome Outcomes â&#x20AC;&#x201D; Mosaed

Francis B

18 2010

Vizzeri G, Weinreb R

15 2010

Mosaed S, Rhee D, Filippopoulos, et al

Mosaed S, Dustin L, Minckler D

14 2009

17 2010

Liu J, Jung J, Francis B

13 2009

Vold S, Dustin L

Minckler D, Hill R

12 2009

16 2010

Patel S, Sit A

11 2009

Author

Godfrey D, Fellman R, Neelakantan A

Year

10 2009

Table I Peer-reviewed journals

Trabectome Combined with Phacoemulsification versus Phacoemulsification Alone: A Prospective, Non-Randomized Controlled Surgical Trial

Trabectome Outcomes in Adult Open-Angle Glaucoma: One Year Follow-Up

Impact of Laser Trabeculoplasty on Trabectome Outcomes

Cataract Surgery and Glaucoma

Comparative Outcomes Between Newer and Older Surgeries for Glaucoma

Ab Interno Trabeculotomy Trabectome Surgical Treatment for Open-Angle Glaucoma

Use of Novel Devices for Control of Intraocular Pressure

A Practice Model for Trabecular Meshwork Surgery

Canal Surgery in Adult Glaucomas

Title

TP: 28% PCE: 12%

TA: 31% TP: 18%

~32% ~39%

~37%

~30%

IOP Reduction (%)

40%

TA: 28% TP: 33%

~55% ~29%

~48%

~64%

Meds Reduction (%)

Up to 24M

Up to 12M

Up to 36M

Up to 60M (graph only)

Up to 60M

Follow-up Period

TP 114 at baseline 24M: 67 PCE 145 at baseline 24M: 41

TA 538 at baseline 12M: 363 TP 290 at baseline 12M: 266

No LTP 852 at baseline 36M: 47 LTP 493 at baseline 36M: 3

102 at baseline 12M: NA

1688 at baseline 60M: NA

Total # of Cases

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Author

Vold S

Jea S, Mosaed S et al

Francis B, Singh K, Lin S et al

Francis B, Winarko J

Ting J, Damji K et al

Iordanous Y, Kent J et al

Maeda M, Watanabe M, Ichikawa K

Year

19 2010

20 2011

21 2011

22 2011

23 2012

24 2013

25 2013

Table I Peer-reviewed journals

Evaluation of Trabectome in Open-Angle Glaucoma

Projected Cost Comparison of Trabectome, iStent, Endoscopic Cyclophotocoagulation versus Glaucoma Medication in the Ontario Health Insurance Plan

Ab Interno Trabeculectomy: Outcomes in Exfoliation vs Primary Open-Angle Glaucoma

Combined Trabectome and Cataract Surgery versus Combined Trabeculectomy and Cataract Surgery in Open-Angle Glaucoma

Novel Glaucoma Procedures

Effect of a Failed Trabectome on Subsequent Trabeculectomy

Impact of Pre-Operative Intraocular Pressure on Trabectome Outcomes: A Prospective, Non-Randomized, Observational, Comparative Cohort Outcome Study

Title

31%

POAG TA: ~34% POAG TP: ~22% PEX TA:: ~44% PEX TP: ~35%

TP: 30% TLE+PCE: 52%

Study Group: 47.1% Control Group: 52.1%

Group 1: 7% Group 2: 20% Group 3: 33% Group 4: 48%

IOP Reduction (%) Up to 6M

Follow-up Period

43%

POAG TA: ~21% POAG TP: ~31% PEX TA: ~28% PEX TP: ~38%

TP: ~46% TLE+PCE: ~81%

Up to 12M

Study Group: 75% Control Group: 81% Up to 24M

Group 1: 35% Group 2: 28% Group 3: 28% Group 4: 25%

Meds Reduction (%)

80 at baseline 12M: 27

POAG TA 450 at baseline 12M: 293 POAG TP 263 at baseline 12M: 247 PEX TA 67 at baseline 12M: 53 PEX TP 45 at baseline 12M: 42

TP 89 at baseline 12M: 85 TLE+PCE 23 at baseline 12M: 20

Study Group 34 at baseline 24M: 15 Control Group 42 at baseline 24M: 22

Group 1: 293 at baseline Group 2: 428 at baseline Group 3: 379 at baseline Group 4: 301 at baseline

Total # of Cases

NA Kaplowitz K, Loewen N 29 2013

PATIENTS AND METHODS

Note: TA = Trabectome Alone, TP = Trabectome+Phaco

Jordan J, Wecker T et al 28 2013

Trabectome Surgery for Primary and Secondary Open Angle Glaucomas

Pantcheva, Kahook M 27 2010

Ab Interno Trabeculectomy

Oterrendorp C, Ness T et al Trabectome as Treatment Option in Secondary Glaucoma Due to Intraocular Lymphoma 26 2012

Techniques and Outcomes of Minimally Invasive Trabecular Ablation and Bypass Surgery

POAG 261 at baseline 40M: 76 PEX 173 at baseline 40M: 46 POAG: 50% PEX: 40% POAG: 25% PEX: 32%

Up to 40M

34 at baseline 6M: 25 ~67% 38%

Up to 6M

NA NA NA

Total # of Cases Follow-up Period Meds Reduction (%) IOP Reduction (%) Title Author Year #

Table I Peer-reviewed journals

procedure does not involve manipulation of the conjunctiva, Tenon or external eye wall, the typical complications seen in filtering surgeries are not observed after Trabectome procedures.13 In addition, the procedure is minimally invasive and performed through a clear-corneal incision and thus can be combined with phacoemulsification and intraocular lens implantation.14-15 A number of peer reviewed Trabectome publications16-38 are summarized in Table I representing different comparative analyses of Trabectome outcomes. For each cited study, the parameters shown in the Table include: year of publication, journal, author(s), title, average IOP reduction (%), average glaucoma medication reduction (%), duration of follow-up and total number of cases. This paper is a summary of the first twenty cases of Trabectome surgeons who chose to contribute their initial cases on a voluntary basis globally. Some surgeons continued to provide additional cases that are also included but the majority of the data is based on the first twenty cases of Trabectome surgeons. Each Trabectome surgeon was Trabectome trained consisting of didactic, wet-Lab and surgical observation prior to performing Trabectome surgery. Therefore, this report represents the Trabectome Surgeon’s experience and Trabectome outcomes of their initial cases (generally the first 20 cases).

A total of 4,659 eyes in which patients received the Trabectome procedure were included in the total study group. Of these, 2,566 eyes (55%) received the Trabectome procedure alone, 1,993 eyes (43%) received the Trabectome procedure combined with cataract extraction (phaco), and 69 eyes (1%) received Trabectome combined with other surgical procedures. Data were obtained from the Trabectome Study Group Database. The database consists of de-identified data submitted by Trabectome surgeons on standardized forms. Data collected include patient demographics and baseline measures such as pre-operative IOP, glaucoma medication use, surgical history of operative eye, as well as intraoperative details and complications. Outcome measures include IOP, number of glaucoma medications, and secondary glaucoma surgery, if any. All research was conducted with local institutional review board approval and in accordance with the Declaration of Helsinki and the U.S. Health Insurance Portability and Accountability Act. Details of the device and surgical procedures have been published.12,16 In brief, a 1.6 to 1.8 mm temporal corneal incision is made, the Trabectome handpiece is inserted into the anterior chamber and advanced nasally. Under gonioscopic view, the handpiece tip is inserted through the trabecular meshwork and into Schlemm’s canal. Once in appropriate position, approximately a 60- to 120-

The First Decade of Global Trabectome Outcomes — Mosaed

Fig. 1 Trabectome device ablates and removes a 600 to 1200 strip of trabecular meshwork in order to expose the anterior chamber aqueous directly to Schlemm’s canal and the collector channels.

Fig. 2 Steps involved in Trabectome surgery.

degree arc of trabecular meshwork and inner wall of Schlemm’s canal is ablated. Remnants of ablated tissue are removed via the handpiece’s aspiration flow. In most combined cases, Trabectome is generally performed first and followed by phacoemulsification. Figure 1 shows the device, and Figure 2 indicates the basic surgical steps. Survival curves were generated using Kaplan-Meier analysis. Success was defined as IOP less than 21 mmHg, at least 20% reduction from baseline on any 2 consecutive

Supplement: Clinical & Surgical Ophthalmology, June 2015

visits after 3 months and no secondary glaucoma surgery. Analysis was performed using R statistical software (R Project).

RESULTS Table II shows the baseline demographics of the study group. The average age of the study group was 70 years with the gender majority being female (53%). The largest racial cohorts were Caucasians (46%) and Japanese (23%). The diagnosis of the majority of patients was

Table II Demographics Age

n = 4659 Mean ± SD Range

70±14 0 - 97

Gender Female Male

2479 (53%) 2044 (44%)

Race African-American Asian Caucasian Japanese Hispanics Other

274 (6%) 179 (4%) 2125 (46%) 1078 (23%) 154 (3%) 849 (18%)

Diagnosis POAG Pseudoexfoliation Glaucoma Juvenile ACG Myopic Degeneration Steroid Pigment Dispersion Uveitic Glaucoma Ocular Hypertension Normal Tension Glaucoma Traumatic Glaucoma Secondary Glaucoma Other

3159 (68%) 583 (13%) 37 (1%) 65 (1%) 8 (0%) 52 (1%) 136 (3%) 76 (2%) 20 (0%) 160 (3%) 14 (0%) 127 (3%) 222 (5%)

Pre-Op Snellen Acuity 6/6 (20/20) – 6/12 (20/40) 6/15 (20/50) – 6/21 (20/70) 6/24 (20/80) – 6/30 (20/100) 6/60 (20/200) – 6/120 (20/400) <6/120 (<20/400) NR

2306 (49%) 748 (16%) 235 (5%) 308 (7%) 153 (3%) 909 (20%)

POAG (68%), followed by pseudoexfoliation glaucoma (13%). The pre-op Snellen acuity of the largest cohort ranged from 20/20-20/40 (49%). Measured visual fields were relatively evenly distributed among patients ranging from mild to advanced. Cup to disc ratio of the largest cohort was 0.7-0.8 (32%), followed by >0.8 (26%). Shaffer grade of IV represented the largest cohort of 1,753 eyes (38%), followed by Shaffer grade III in 1,306 eyes (28%). The largest cohort with respect to lens status was phakic in 3,079 eyes (66%). 1,533 eyes (33%) had received argon laser trabeculoplasty (ALT) or selective laser trabeculoplasty (SLT) prior to receiving the Trabectome procedure. Table III shows average IOP and number of glaucoma medications at baseline and at different follow-up time periods. Figures 3 and 4 provide a graphical representation of this data. IOP was reduced from a baseline of 23. 1±8.0 mmHg to 17.2±3.0 mmHg at 90 months, while number of glaucoma medications was reduced from 2.6±1.3 to 1.1±1.3 at 90 months. Postoperative observations are presented in Table IV. 337 eyes (7%)

VF Mild Moderate Advanced MD/Other Disc C/D <0.7 0.7 – 0.8 >0.8 NR Shaffer Grade I II III IV NR Lens Status Phakic Pseudophakic Aphakic NR Prior Surgeries SLT ALT Shunt Trabeculectomy Trabectome Combined Surgeries Trabectome + Phaco Trabectome + Goniosynechialysis Trabectome + Shunt Trabectome + Penetrating Keratoplasty Trabectome + ECP Trabectome + Bleb Revision Trabectome Only Trabectome + Other Surgeries

1145 (25%) 1107 (24%) 1166 (25%) 1241 (26%) 1002 (22%) 1494 (32%) 1196 (26%) 967 (20%) 54 (1%) 474 (10%) 1306 (28%) 1753 (38%) 1072 (23%) 3079 (66%) 1169 (25%) 38 (1%) 373 (8%) 1024 (22%) 509 (11%) 42 (1%) 269 (6%) 31 (1%) 1993 (43%) 18 (0%) 6 (0%) 1 (0%) 3 (0%) 3 (0%) 2566 (55%) 69 (2%)

required secondary glaucoma surgery. Of the 337 eyes, most underwent additional trabeculectomy or tube shunt. None of the sight-threatening complications associated with traditional filtering surgeries were observed. The survival curves are presented in Figure 5. At 90 months, the survival rates were 66% for all cases and 56% for Trabectome alone cases. For cases combining Trabectome and phaco, the survival rate was 85% at 60 months, the maximum time period reported because combined procedures were not performed until 30 months after Trabectome alone cases were started.

DISCUSSION Previous studies with the Trabectome procedure have been very promising with the data available at various durations of follow-up. The purpose of this paper is focused on further providing global Trabectome outcomes, biased toward reflecting initial surgeon experience. The data presented herein are provided on a voluntary basis by surgeons performing Trabectome procedures at centers around the world. Data are compiled based on

The First Decade of Global Trabectome Outcomes — Mosaed

Fig. 3 IOP Trend

Fig. 4 Number of Medications Trend Table III Intraocular pressure and number of medications Baseline 12M 24M 36M 48M 60M 72M 84M 90M

Fig. 5 Survival plots for all cases, Trabectome+phaco and Trabectome alone Table IV Postoperative observations Trabeculectomy Post-Trabectome Shunt Post-Trabectome Diode Cyclo Photo Coagulation SLT Post-Trabectome Express ECP Post-Trabectome Trabectome Post-Trabectome Tube Ligature Release on Combined Tube and Trabectome Total Secondary Surgery Sustained Hypotony (IOP < 5 mmHg) 1 month Postop Hypotony (IOP < 5 mmHg) 1 Day Postop Aqueous Misdirection Infection Bleb Formation Wound Leaks Problematic Pain Choroidal Effusion Choroidal Hemorrhage

179 (4%) 80 (2%) 8 (0%) 1 (0%) 19 (0%) 14 (0%) 35 (1%) 1 (0%) 337 (7%) 10 (0%) 49 (1%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0%)

Supplement: Clinical & Surgical Ophthalmology, June 2015

Intraocular Pressure

Number of Meds

23.1 ± 8.0 16.2 ± 4.0 16.4 ± 4.5 16.2 ± 4.3 16.1 ± 3.2 16.4 ± 2.6 16.6 ± 2.2 16.5 ± 2.3 17.2 ± 3.0

2.6 ± 1.3 1.9 ± 1.3 2.0 ± 1.3 2.0 ± 1.3 1.8 ± 1.3 1.5 ± 1.3 1.4 ± 1.1 1.3 ± 1.2 1.1 ± 1.3

receipt of de-identified data on standardized forms. There are no pre-defined exclusion criteria imposed for inclusion of cases into this analysis. This is an important factor. As such, this data reflects real-world use of Trabectome for the treatment of glaucoma patients as determined by their physician providers. As indicated in the demographics presented in Table II, patients receiving the Trabectome procedure in this study include various stages of glaucoma progression, with varying diagnoses, across a broad range of races, 1,875 (40%) of which having undergone previous surgical procedures for glaucoma that had failed to provide sufficient management of IOP. Furthermore, the database is biased toward inclusion of the first twenty Trabectome cases performed by starting surgeons, so results as presented would certainly include any early “learning curve” impact without prejudice. Considering the summary of outcomes for Trabectome patients previously published (Table I), it is apparent that most of these studies applied certain exclusion criteria for the purposes of performing certain defined comparative subgroup analyses. However, the intent of this paper is to analyze all available data without exclusion to provide insight into international observed Trabectome outcomes on a more universal and all-inclusive basis.

With respect to the primary outcome measures reported in this paper, average IOP was reduced from a baseline of 23.1 mmHg to 17.2 mmHg (26%) at 90 months, and average number of glaucoma medications was reduced from 2.6 to 1.1 (58%) at 90 months. These results are generally consistent with previously published outcome results as presented in Table I.

CONCLUSION Considering this compilation and analysis of available data, as well as all of the outcome data surveyed from the literature, patients receiving Trabectome on average have about a 30% reduction in IOP and a reduction in glaucoma medication use of about 60%. Given the American Academy of Ophthalmology preferred practice pattern guidelines for at least 25% initial IOP lowering, the procedure can be considered for initial therapy, as well as for end-stage patients that have been refractory to other surgical and medical treatments.39 ❏

REFERENCES 1. 2. 3. 4.

5. 6.

7. 8. 9. 10. 11. 12. 13. 14.

15.

Quigley H and Broman A. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006; 90: 262-207. Quigley H. Glaucoma. Lancet 2011; 377(9774): 1367-1377. Heijl A, Leske M, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from The Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120: 1268-1279. Lichter P, Musch D, Gillespie B, et al. Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology 2001; 108(11): 1943-1953. Mao L, Stewart W, Shields M. Correlation between intra-ocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am J Ophthalmol 1991; 111(1): 51-55. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000; 130(4): 429-440. Liu J, Francis B, Jung J. Ab interno trabeculotomy: Trabectome surgical treatment for open-angle glaucoma. Expert Rev. Ophthalmol 2009: 4(2): 119-128. Gedde S, Herndon L, Brandt J, et al. Surgical complications in the Tube Versus Trabeculectomy Study during the first year of follow-up. Am J Ophthalmol 2007; 143(1): 23-31. Greenfield D, Suñer I, Miller M, et al. Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol 1996; 114: 943-949. Law S, Nguyen A, Coleman A, et al. Severe loss of central vision in patients with advanced glaucoma undergoing trabeculectomy. Arch Ophthalmol 2007; 125: 1044-1055. Mosaed S. Ab interno trabeculotomy with the Trabectome surgical device. Techniques in Ophthalmology 2007; 5(2): 63-66. Francis B, See R, Rao N, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for openangle glaucoma. J Glaucoma 2006; 15: 68-73. Mosaed S, Dustin L, Minckler D. Comparative outcomes between newer and older surgeries for glaucoma. Trans Am Ophthalmol Soc 2009; 107: 127-135. Francis B, Minckler D, Dustin L, et al. Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: Initial results. J Cataract Refract Surg 2008; 34: 1096-1103. Francis B, Winarko J. Combined Trabectome and cataract surgery versus combined trabeculectomy and cataract surgery in open-angle glaucoma. Clinical & Surgical Ophthalmology 2011; 29(2/3): 4-10.

16. Minckler D, Baerveldt G, Ramirez M, et al. Clinical results with the Trabectome for treatment of open-angle glaucoma. Ophthalmology 2005; 112: 962-967. 17. Minckler D, Baerveldt G, Ramirez M, 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. 18. Gunderson E. Trabeculotomy ab interno, using the Trabectome: a promising treatment for patients with open-angle glaucoma. The Journal of the American Society of Ophthalmic Registered Nurse 2008; VolXXXIII, No.1 19. Filippopoulos T, Rhee D. Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery. Current Opinion in Ophthalmology 2008; 19: 149-154. 20. Nguyen Q. Trabectome: a novel approach to angle surgery in the treatment of glaucoma. International Ophthalmology Clinics 2008; 48(4): 65-72. 21. Minckler D, Mosaed S, Dustin L, et al. Trabectome (trabeculectomyinternal approach): additional experience and extended follow-up. Trans Am Ophthalmol Soc 2008; 106: 149-160. 22. Godfrey D, Fellman R, Neelakantan A. Canal surgery in adult glaucomas. Current Opinion in Ophthalmology 2009; 20: 116-121. 23. Patel S, Sit A. A practice model for trabecular meshwork surgery. Arch Ophthalmol 2009; 127(3): 311-313. 24. Minckler D, Hill R. Use of Novel devices for control of intraocular pressure. Experimental Eye Research 2009; (88): 792-798. 25. Vizzeri G, Weinreb R. Cataract surgery and glaucoma. Curr Opin Ophthalmol 2010; 21: 20-24. 26. Vold S, Dustin L. Impact of laser trabeculoplasty on Trabectome outcomes. Ophthalmologic Surgery, Laser & Imaging 2010; 41(4): 443-451. 27. Mosaed S, Rhee D, Filippopoulos, et al. Trabectome outcomes in adult open-angle glaucoma: one year follow-up. Clinical & Surgical Ophthalmology 2010; 28(8): 5-9. 28. Francis B. Trabectome Combined with phacoemulsification versus phacoemulsification alone: a prospective, non-randomized controlled surgical trial. Clinical & Surgical Ophthalmology 2010; 28(10): 1-7. 29. Vold S. Impact of preoperative intraocular pressure on Trabectome outcomes: a prospective, non-randomized, observational, comparative cohort outcome study. Clinical & Surgical Ophthalmology 2010; 28(11): 1-7. 30. Jea S, Mosaed S, Vold S, et al. Effect of a failed Trabectome on subsequent trabeculectomy. J Glaucoma 2012; 21(2): 71-75. 31. Francis B, Singh K, Lin S et al. Novel glaucoma procedures. Ophthalmology 2011; 118: 1466-1480. 32. Ting J, Damji K et al. Ab interno trabeculectomy: Outcomes in exfoliation vs primary open angle glaucoma. J Cataract Refract Surg 2012; 38: 315-323. 33. Iordanous Y, Kent J, Hutnik M, et al. Projected cost comparison of Trabectome, iStent, Endoscopic Cyclophotocoagulation versus glaucoma medication in the Ontario Health Insurance Plan. J Glaucoma 2014; 23(2): 112-118. 34. Maeda M, Watanabe M, Ichikawa K. Evaluation of Trabectome in open-angle glaucoma. J Glaucoma 2013; 22: 205-208. 35. Oterendorp C, Ness T, Illerhaus G, et al. The Trabectome as treatment option in secondary glaucoma due to intraocular lymphoma. J Glaucoma 2012. 36. Pantcheva M, Kahook M. Ab interno trabeculectomy. Middle East Afr J Ophthalmol 2010; 17(4): 287-289. 37. Jordan J, Wecker T, Oterendorp C, et al. Trabectome surgery for primary and secondary open angle glaucomas. Graefes Arch Clin Exp Ophthalmol 2013; 251(12): 2753-2760. 38. Kaplowitz K, Schuman J, Loewen N. Techniques and outcomes of minimally invasive trabecular ablation and bypass surgery. Br J Ophthalmol 2013; 1-7. 39. American Academy of Ophthalmology Preferred Practice Patterns, 2013.

The First Decade of Global Trabectome Outcomes — Mosaed

Trabectome Outcomes in Adult Open-Angle Glaucoma Patients: One-Year Follow-Up Sameh Mosaed, MD; Douglas J. Rhee, MD; Theodoros Filippopoulos, MD; Helen Tseng, MD; Sunil Deokule, MD; Robert N. Weinreb, MD ABSTRACT Purpose: To present the experience with Trabectome for the treatment of adult open-angle glaucoma. Methods: The main outcome measures were intraocular pressure (IOP), glaucoma medications, and secondary surgery in patients that were followed for at least one year. Success is IOP < 21 mmHg and 20% reduction of IOP compared to preoperative levels, and no secondary surgery. Results: The success rate following Trabectome (n=538) at one year alone was 64.9% with 31% IOP reduction (from 26.3±7.7 mmHg to 16.6±4.0 mmHg) and there was 28% drop in medication usage (from 2.88±1.30 to 2.09±1.35) in successful cases. The success rate following Trabectome combined with phacoemulsification (n=290) was 86.9% with a 18% reduction in IOP (from 20.2±6.0 mmHg to 15.6±3.7 mmHg) and a 33% drop in medication usage (from 2.54±1.07 to 1.69±1.33) in successful cases at one year. There were no complications that resulted in long-term visual impairment. Conclusion: Trabectome surgery offers significant long-term IOP reduction while maintaining a favorable safety profile.

INTRODUCTION The lowering and stabilization of intraocular pressure (IOP) is the proven treatment of glaucoma.1-4 The trabecular meshwork is the anatomic location of the greatest resistance to aqueous outflow.5-6 The widely accepted mainstays of incisional surgery, trabeculectomy, and glaucoma drainage implants (GDIs, also known as ‘tube shunts’), lower IOP by creating a direct communication between the anterior chamber and subconjunctival space

S. Mosaed — Assistant Professor, Department of Ophthalmology, University of California, Irvine, CA; D.J. Rhee, T. Filippopoulos — Department of Glaucoma, Massachusetts Eye and Ear Infirmary, Boston, MA; H. Tseng — Department of Ophthalmology, University of California, Irvine, CA; S. Deokule, R.N. Weinreb — Hamilton Glaucoma Center at the Shiley Eye Center, La Jolla, CA Correspondence to: Dr. Sameh Mosaed, Department of Ophthalmology, University of California at Irvine, 118 Med Surge I, Irvine, CA 926974375; E-mail: smosaed@uci.edu

Supplement: Clinical & Surgical Ophthalmology, June 2015

to completely bypass the conventional route of aqueous drainage through the trabecular meshwork, Schlemm’s canal, and collecting channels. The subconjunctival fluid collects focally, known as a “bleb,” and the aqueous resorbs into the episcleral venous system. The bleb from a trabeculectomy is prone to a significant long-term risk of infection while GDIs are prone to corneal decompensation, erosion of overlying conjunctiva with subsequent exposure, and ocular motility problems.7 A recent comparative study between trabeculectomy and tube shunts indicate that the cumulative probabilities of failure during the first year of follow-up are approximately 13.5% and 3.9%, respectively.8 Ab interno trabeculectomy using the Trabectome surgical device has been used in the United States since January 2006. This procedure involves the removal of a small sector, typically between 90-120 degrees of circumference of the trabecular meshwork and inner wall of Schlemm’s canal. This then provides a direct communication between the collecting channels and anterior chamber,9 and largely bypasses a sector of aqueous outflow resistance. This procedure does not create a subconjunctival bleb, thus offering the theoretical advantage of improved long-term safety. Previous reports of Trabectome outcomes have described the results of a consecutive case series with follow-up ranging between one day and five years.9 In this study, we report the experience of Trabectome in a cohort of patients who underwent the Trabectome procedure and had at least one-year follow-up.

METHODS All adult subjects with uncontrolled open-angle glaucoma on maximally tolerated medical therapy who received Trabectome procedure (538 eyes) or Trabectome combined with cataract extraction (290 eyes) with one-year follow-up are compared and presented in two cohorts. Success was defined as a final IOP < 21 mmHg and a 20% reduction of IOP in two consecutive visits after three months postoperatively and no secondary glaucoma incision surgery. Trabectome procedures were from academic surgical centers where three surgeons performed the majority of the procedures (SM, RNW, DR).

Fig. 1 Average IOP levels following Trabectome procedure alone. “IOP Baseline” is the overall average preoperative IOP of all 538 patients.

Fig. 2 Average medication usage in Trabectome single procedure. “# Meds Baseline” is the overall average preoperative medication usage in the 538 patients.

All research was conducted with local institutional review board approval and in accordance with the Declaration of Helsinki and the U.S. Health Insurance Portability and Accountability Act. The eye is prepped for surgery with perioperative topical antibiotic, 1% to 2% pilocarpine for Trabectomeonly cases, and topical NSAID. Anesthesia is achieved using the surgeon’s preference of topical, peribulbar or retrobulbar anesthetic. Combined phaco-Trabectome cases were performed using the surgeon’s preference of Trabectome followed by phacoemulsification, or phacoemulsification followed by Trabectome. Power settings are adjusted based on intraoperative responses judged by the surgeon, but varied between 0.5 and 1.0 watts. The steps of the ablation procedure have been described in prior reports, but briefly, a strip of 90120 degrees of trabecular meshwork and inner wall of Schlemm’s canal are removed utilizing a microelectrosurgical device through a 1.7-mm clear corneal incision under gonioscopic visualization. The removal of over 120 degrees of ablation requires two incisions. The incision is closed with a single 10-0 suture and the patient is placed on pilocarpine for one to two months postoperatively and prednisolone acetate 1% for one month. Postoperative IOP, number of glaucoma medications, and complication rates were analyzed. All IOP recordings were performed by Goldmann applanation tonometry, at the institution where the surgery was performed. All readings were made at the following postoperative intervals: day 1, week 1, month 1, month 2-4, month 4-6, and month 9-12.

290 of the patients received combined Trabectome with phacoemulsification. During this first year of postoperative follow-up, 199 (26%) of the eyes required secondary glaucoma surgery. Of the failed cases with subsequent surgery, 57 cases had shunt, 117 cases had trabeculectomy, 10 had repeat Trabectome and 7 had diode cyclophotocoagulation.

RESULTS Of the 828 patients that completed 12 months of postoperative follow-up, 538 received Trabectome alone and

Trabectome Alone at One Year The average age of the 538 patients was 68±15 years and 62% were Caucasian. 296 were female and the predominant diagnosis was primary open-angle glaucoma (POAG). At one year, 175 (32%) of the patients required a secondary glaucoma surgery. At one year, the average IOP was 16.6±4.0 mmHg representing a 31% drop in IOP from the average preoperative levels (p<0.0001) and a decrease to 2.09±1.35 medications from 2.88±1.30 (p<0.0001). The average IOP does not include the results of the IOPs after secondary surgeries. In Figure 1, “IOP Baseline” is the overall average preoperative IOP of all 538 patients. In Figure 2, “# Meds Baseline” is the overall average preoperative medication usage in the 538 patients. Combined Trabectome with Phacoemulsification A total of 290 cases were analyzed. Within the first year, 24 (8%) subjects required secondary glaucoma surgery. The summary of the IOP and medication usage are illustrated in Figures 3 and 4. In Figure 3, the “IOP Baseline” is the overall average preoperative IOP of all 290 patients. In Figure 4, “# Meds Baseline” is the overall average preoperative medication usage in 290 patients. The survival analyses of the two data sets are presented in Figure 5. The success rate is defined as:IOP < 21 mmHg and a 20% reduction of IOP compared to

Trabectome Outcomes in Adult Open-Angle Glaucoma Patients — Mosaed et al

Fig. 3 IOP of Trabectome + phacoemulsification cases with at least one-year follow-up. “IOP Baseline” is the overall average preoperative IOP of all 290 patients.

Fig. 5 Survival curves of Trabectome and Trabectome combined with phacoemulsification procedures. The success rate at one year for the Trabectome alone was 64.9%with a 31% IOP reduction (from 26.3±7.7 mmHg to 16.6±4.0mmHg) and 28% drop in medication usage (from 2.88±1.30 to 2.09±1.35). For the combined Trabectome with phacoemulsification, there was an 86.9% success rate with an 18% reduction in IOP (from 20.2±6.0 mmHg to 15.6±3.7mmHg) and 33% drop in medication usage (from 2.54±1.07 to 1.69±1.33). Failure = IOP > 21mmHg OR IOP not reduced by 20% compared to preoperative levels in two consecutive visits 3 months after surgery, OR re-operation for glaucoma. (log rank test p<0.001 for Trabectome only vs. combined procedure cases at 12 months after surgery).

pre-IOP and no secondary surgery. The result of this analysis is illustrated in Figure 5. The success rate at one year for the Trabectome alone was 64.9% with a 31% IOP reduction (from 26.3±7.7 mmHg to 16.6±4.0 mmHg) and 28% drop in medication usage (from 2.88±1.30 to 2.09±1.35). For the combined Trabectome with phacoemulsification, there was an

Supplement: Clinical & Surgical Ophthalmology, June 2015

Fig. 4 Medication usage in Trabectome + Phacoemulsification cases with at least one-year follow-up. “# Meds Baseline” is the overall average preoperative medication usage in 290 patients.

86.9% success rate with an 18% reduction in IOP (from 20.2±6.0 mmHg to 15.6±3.7 mmHg) and 33% drop in medication usage (from 2.54±1.07 to 1.69±1.33). In terms of complications, there was one reported case of aqueous misdirection following the procedure and there was one case report of a presumed cyclodialysis cleft which closed spontaneously. Although blood often refluxed into the anterior chamber from Schlemm’s canal, there were no cases of sustained hyphema beyond five days postoperatively. There were also no reports of sustained hypotony beyond one day postoperatively, infections, cases of reduced Snellen acuity greater than two lines, choroidal effusions, or maculopathy. Transient corneal epithelial defects occurred in less than 5% of subjects.

DISCUSSION Traditional incisional glaucoma surgery is associated with numerous short- and long-term complications.8 Trabeculectomies and GDIs have an approximate success rate of 80% at one year.8 This success is paired with the burden of a 1% per year risk of endophthalmitis and other frequent vision-threatening outcomes, such as persistent hypotony, choroidal detachments, and others.10 Glaucoma drainage devices have been reported to have a success rate of approximately 50% to 75% at five years, but also can precipitate major complications such as motility disturbances, hypotony, corneal decompensations, and tube erosions, to name a few.7 The Trabectome surgical device was cleared in January 2006 for the treatment of adult and juvenile glaucoma. Since then, over 3000 cases have been performed nationwide.

Previous studies with the Trabectome device have been very promising with short-term success rates reported at 84% for Trabectome single procedure cases11 and similar success rates with greater than 20% longer term IOP reduction in combined Trabectome-cataract extraction with intraocular lens implantation. These reports established that the short-term complication rates with the Trabectome procedure were minimal, with the most frequent complication being transient hyphema with one day postoperative elevated IOP. This study shows a more modest success rate than prior publications of results with the Trabectome,11-12 There are several possible explanations for the differences between our results and earlier ones. First, success criteria in this study were more rigorous than some prior reports, and we followed the subjects for a longer minimum period of time then most prior studies. All incisional procedures for glaucoma, such as trabeculectomies and GDIs, show a decrease in success over time.13-14 This phenomenon has been attributed to progressive wound healing and remodeling.15 Likewise the ablated trabecular meshwork may undergo some scarring and closure of the cleft over time, making the results less dramatic. Also, this report represents the first experience of the surgeons with the device and does not include more recently operated patients in whom postoperative and intraoperative protocols have since been adjusted with experience to gain better results. For example, the power used to create the arc of ablation has been increased by 40% to 8 watts for a more complete ablation. In addition, it is now recommended that pilocarpine be used for at least two months postoperatively to put the cleft on stretch and minimize fibrosis and closure. These steps were not exercised in the early months of use with the device. The patient selection process has also evolved as we gain more experience with the device. Prior to having a better understanding of what range of postoperative IOP was likely to be achieved, many of us were performing the procedure on patients with advanced glaucoma with target IOP in the 8-10 range. We now know that the range of IOP to be expected postoperatively with the Trabectome is usually in the mid teens, as has been reported in the literature. Hence, patients that may have obtained a substantial IOP reduction from baseline, but still had IOP above 8 to 12, went on to have further incisional surgery and were thus included in the failure category. Our results also represent data from patients in whom the arc of ablation was much smaller than that currently performed as the surgeons were in the early stages of the learning curve. A recent study by Sit et al showed that the larger arc of ablation was associated with a lower final IOP.16 Future studies analyzing more recent Trabectome procedures followed long term may better determine the expected IOP reduction rates achievable with the procedure.

The success rate of the combined Trabectome and phacoemulsification group in this study supports the findings of Francis et al who reported a 78% success rate at 6 months and 67% at 12 months with several subjects followed out past one year.17 The reasons that the procedure has a more profound effect when paired with the cataract extraction are likely several-fold. First, it is well established in the literature that the phacoemulsification procedure itself often results in a moderate IOP reduction on its own. It is possible that the ablation created in these combined procedures is less likely to develop peripheral anterior synechiae as the angle tends to be wider after cataract extraction. In addition, the extensive irrigation and aspiration performed during the phacoemulsification following the Trabectome results in a more complete removal of any red blood cells or inflammatory mediators liberated during the procedure. The IOP reduction seen in these cases is much more marked and consistent than that seen in Trabectome alone, and has not resulted in any additional complications. Given that it is performed through the same incision, and that the postoperative medication regimen and follow up is similar to what would be performed in the glaucoma patient, the Trabectome may represent an opportunity to better control the glaucoma or reduce medication usage in a cataract surgery patient with no additional risk to the patient. In conjunction with substantially lowering IOP in a large proportion of subjects in this study, the postoperative glaucoma-lowering medication usage was also significantly reduced. As multiple publications have established, compliance with glaucoma medications is a serious problem. Many patients cannot afford their medications, even with drug-coverage insurance, given their high deductibles and co-payments. Many patients are also noncompliant due to the inability to use medications properly from the physical difficulty of administering drops, memory deficits, and so forth. Our results indicate that this procedure may be a useful option to perform even in the setting of well-controlled glaucoma, in an attempt to reduce medication reliance. Considering the lack of compliance to glaucoma medications and the lack of postoperative complications, Trabectome may be a reasonable consideration for these patients and especially with patients who are undergoing phacoemulsification procedures due to its compatibility with this procedure. Our results demonstrate that the Trabectome device compares favorably to other incisional procedures in that it results in moderate IOP reduction with low complication rates. Further prospective investigations with larger numbers of subjects are necessary to better define long-term outcomes in specific patient populations.

Trabectome Outcomes in Adult Open-Angle Glaucoma Patients â&#x20AC;&#x201D; Mosaed et al

Acknowledgements/Disclosure: Funding/Support: None; Financial Disclosures: S. Mosaed — Consultant, Neomedix Inc; Lecture fees, Allergan; Grant Support, Alcon; D.J. Rhee — Lecture fees, Allergan and Alcon; Grant Support, Allergan, Pfizer, National Eye Institute, Research to Prevent Blindness, American Glaucoma Society; Statement about Conformity with Author Information: Name of IRB is University of California, Irvine.

REFERENCES 1.

5. 6. 7.

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: 1268-1279. Lichter PR, Musch DC, Gillespie BW, Guire KE, Janz NK, Wren PA, Mills RP. Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmology 2001; 108(11): 1943-1953. Mao LK, et al. Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. Am J Ophthalmol 1991; 111(1): 51-55. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 2000; 130(4): 429-440. Bill A. Experimental aqueous humor damage-reply. Arch Ophthalmol 1962; 68: 151-152. Brubaker R. Adler’s Physiology of the eye. Arch Ophthalmol 1976; 94(7): 1239-1240. Minckler DS, Vedula SS, Li TJ, Mathew MC, Ayyala RS, Francis BA. Aqueous shunts for glaucoma. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD004918. DOI: 10.1002/14651858.CD004918.pub2.

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10.

11.

12.

13.

14.

15.

16.

17.

Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL. Treatment outcomes in the tube versus trabeculectomy study after one-year of follow-up. Am J Ophthalmol 2007; 143(1): 9-22. Minckler D, Mosaed S, Dustin L, Francis B. Trabectome (Trabeculotomy internal approach): Additional experience and extended follow up. Trans Am Ophthalmol Soc 2008; 106: 149-160. Greenfield DS, Suñer IJ, Miller MP, Kangas TA, Palmberg P, Flynn HW FJr. Endophthalmitis after filtering surgery with mitomycin. Arch Ophthalmol 1996; 114(8): 943-949. Minckler D, Baervedlt 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. Minckler DS, Baerveldt G, Alfaro MR, Francis BA. Clinical results with the Trabectome for treatment of openangle glaucoma. Ophthalmology 2005; 112(6): 962-967. Minckler DS, Francis BA, Hodapp EA, Jampel HD, Lin SC, Samples JR, Smith SD, Singh K. Aqueous shunts in glaucoma: a report by the American Academy of Ophthalmology. Ophthalmology 2008; 115(6): 1089-1098. Nouri-Mahdavi K, Brigatti L, Weitzman M, Caprioli J. Outcomes of trabeculectomy for primary open-angle glaucoma. Ophthalmology 1995; 102(12): 1760-1769. Georgoulas S, Dahlmann-Noor A, Brocchini S, Khaw PT. Modulation of wound healing during and after glaucoma surgery. Prog Brain Res 2008; 173: 237-254. Review. Sit AJ, Khaja H. Relationship between ablation arc length and IOP with Trabectome surgery. AAO Scientific Poster 102; 2008. Francis B, Minckler D, Dustin L, et al. Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: initial results. J Cataract Refract Surg 2008; 34(7): 1096-1103.

Trabectome Combined with Phacoemulsification versus Phacoemulsification Alone: A Prospective, Non-Randomized Controlled Surgical Trial Brian A. Francis, MD, MS

ABSTRACT Purpose: To provide a comparison of the effects on intraocular pressure of phacoemulsification cataract extraction (PCE) combined with Trabectome versus phacoemulsification alone. Methods: This is a prospective, non-randomized, controlled, comparative trial cohort analysis of 259 eyes that underwent Trabectome or PCE by a single surgeon. The main outcome measures were intraocular pressure (IOP) and complications. A secondary outcome measure was glaucoma medications in the combined group. Results: Trabectome and PCE: The mean IOP was 22.2±5.9 mm Hg preoperatively (n=114), 15.4±3.1 mm Hg at 1 year (p<0.01) and 15.3±3.5 mm Hg at 2 years (p<0.01). The mean number of glaucoma medications decreased 40% from baseline at the end of 2 years. Subsequent secondary glaucoma procedures were performed in 5 patients. PCE: The mean IOP preoperatively was 16.2±4.2 mm Hg (n=145), at 1 year was 14.5±3.3 mm Hg (p<0.01) and at 2 years it was 14.3±3.6 mm Hg (p<0.01). Conclusions: Although the baselines were different, the mean IOP showed a greater decrease of 28% in combined Trabectome PCE versus 2% in PCE alone at the end of 2 years. The matched-pair analysis also indicates that IOP at 1 year is significantly lower in combined surgery group.

INTRODUCTION Glaucoma continues to represent a significant healthcare issue, affecting approximately 1% to 2% of the U.S. population and an estimated 67 million people worldwide. Glaucoma management has evolved during the past decade with the introduction of new medications and surgical techniques. In the aging population, glaucoma and cataract frequently are seen in the same patient. The management of coexisting glaucoma and cataract depends on the severity of the respective diseases and the requirements Francis B.A. — Associate Professor of Ophthalmology, Doheny Eye Institute, Keck School of Medicine, University of Southern California Correspondence to: Dr. Brian Francis, 1450 San Pablo Street, Los Angeles, CA 90033-4682; E-mail:bfrancis@usc.edu Dr. Brian Francis is a Trabectome Trainer and receives honorarium for Surgeon Training Sessions.

for control of intraocular pressure (IOP). There are three main surgical options for treatment of visually significant cataract and glaucoma. The first is cataract surgery alone, which may be augmented by medication use or laser trabeculoplasty after surgery if needed. The second is combined glaucoma surgery and cataract extraction. Lastly, staged surgery can be employed with either the glaucoma or cataract procedure performed initially. Standard glaucoma external filtering surgery, such as trabeculectomy, may be performed in combination with cataract extraction with excellent success in long-term IOP control.1,2 Adjunctive mitomycin-C (MMC) during trabeculectomy in combined cases has significantly improved IOP outcomes. However, use of this antifibrotic agent is also associated with a significant increase in sight-threatening complications such as hypotony, choroidal effusion and hemorrhage, leaking blebs, late blebitis and endophthalmitis.3-5 These postoperative complications associated with trabeculectomy are especially problematic for the treatment of cataract and glaucoma in cases that glaucoma is not severe or uncontrolled. The desire for improved therapy in combined cataract and glaucoma has led to interest in alternative glaucoma procedures with a favorable risk profile relative to traditional combined filtering surgeries. Examples of these techniques are: endoscopic cyclophotocoagulation6 (ECP, Endooptiks, Little Silver, NJ), excimer laser trabeculotomy7 (ELT, AIDA, Glautec AG, Nurnberg, Germany), SOLX Gold Shunt8 (SOLX Ltd, Boston, MA), non-penetrating deep sclerectomy with viscocanalostomy,9 circumferential viscodilation and tensioning of Schlemm’s canal with a flexible microcatheter10 (canaloplasty, iScience, Menlo Park, CA), trabecular microbypass stent (iStent, Glaukos Corporation, Laguna Hills, CA), and trabeculotomy by internal approach (Trabectome, Neomedix, Inc, Tustin, CA). The Trabectome has been evaluated in several earlier studies11-18 describing the instrument, histopathology and the outcomes of IOP and medications after Trabectome as a stand alone procedure or combined with cataract phacoemulsification. This surgical approach offers the opportunity to combine surgical cataract and glaucoma treatment with more favorable risk profiles while also sparing conjunctiva should traditional external filtering surgery be deemed appropriate for future care.

Trabectome Combined with Phacoemulsification vs Phacoemulsification Alone — Francis

Fig. 1 Trabectome device ablates and removes a 60º-120º strip of trabecular meshwork in order to expose the anterior chamber aqueous directly to Schlemm’s canal and the collector channels.

In this study, the outcomes of combining Trabectome with cataract extraction for the treatment of adults with open-angle glaucoma and visually significant cataract are compared with cataract extraction alone.

PATIENTS AND METHODS A prospective, non-randomized, controlled, comparative trial cohort analysis of patients treated by a single surgeon (BAF) at Doheny Eye Institute (Department of Ophthalmology, Keck School of Medicine at University of Southern California), was performed. Cohort comparison was studied between patients receiving Trabectome combined with phacoemulsification cataract extraction (PCE) and intraocular lens (IOL) insertion and patients receiving cataract extraction and IOL insertion alone. All research was conducted with local institutional review board approval and in accordance with the Declaration of Helsinki and the U.S. Health Insurance Portability and Accountability Act. The inclusion criteria for the combined Trabectome PCE group were: primary or secondary open angle glaucoma (as defined by glaucomatous optic nerve appearance with or without glaucomatous visual field damage), an unobstructed view of the angle, age greater than or equal to 18 years, a visually significant cataract, and ability to follow up for 6 months. Exclusion criteria were: angle closure, uveitic, pediatric or neovascular glaucoma, previous glaucoma surgery (not including laser trabeculoplasty) or corneal pathology preventing a clear view of the nasal angle. Inclusion criteria for the PCE alone group were: visually significant cataract, age greater than 18 years, and ability to follow up for 6 months. All patients who received either combined Trabectome and cataract extraction or cataract extraction alone from 2007 to 2009 were included. A total of 259 patients met the criteria and were included for analysis. 114 patients underwent combined

Supplement: Clinical & Surgical Ophthalmology, June 2015

Fig. 2 Steps involved in Trabectome surgery.

Trabectome with cataract extraction and 145 patients underwent cataract extraction alone. In each group, patient demographics, preoperative, intraoperative, and postoperative details including gonioscopy, and complications were compiled. Patient data were recorded onto standardized reporting forms. Postoperative data at 1 day, 1 week, 1 month, and every 3 months thereafter were collected. An additional matched-pair analysis (age and IOP) was performed by searching the database for eyes from each group with identical preoperative IOPs, age, and at least 12 months of postoperative follow up data. A total of 10 matched pairs met these criteria. For statistical analysis, 2-tailed Student t-tests were used to determine the statistical significance of changes in IOP within each of the groups. Both paired sample t-test and signed rank test were performed on the paired data. Two-proportion z-test was used to determine difference in complications after surgery between the two groups. Kaplan-Meier survival curves are presented for cumulative

Close-up: Removal of angle tissue barrier reestablishing natural outflow of aqueous humor.

1 mm

Trabectome® handpiece inside glaucoma damaged eye during a minimally invasive procedure.

Fig. 3 Trabectome hand-piece surgical approach inside the anterior chamber viewing through a gonioscopic surgical lens.

Fig. 4 View of this minimally invasive surgical device.

Fig. 5 Schlemm’s Canal congested with blood showing a red hue of trabecular meshwork after the clear cornea incision and depressurization of anterior chamber.

Fig. 6 Trabectome hand-piece inside Trabecular Meshwork.

probability for success based on the success criteria presented in Tube versus Trabeculectomy (TVT) publications19,20 as follows: no additional glaucoma surgery and IOP <21 mm Hg and IOP reduced by 20% below baseline on the last two consecutive follow-up visits after three (3) months postoperative.

in bursts with a high peak power and low duty cycle. An aspiration port is located adjacent to the bipolar electrode, and irrigation is more distal to the surgical site to keep the anterior chamber formed. The irrigation is controlled by a foot pedal that actuates a pinch valve for turning the irrigation on and off. The aspiration pump is peristaltic and allows flow rates up to 4 ml/min. The fluidics and electro-surgical functions are controlled by the surgeon via a 3-position foot pedal (position 1, irrigation; position 2, aspiration; position 3, electro surgery pulse).

Trabectome Instrumentation The Trabectome system which has been described in detail11 consists of a single-use bipolar electro surgical instrument with irrigation and aspiration, powered by a high frequency electro-surgical generator and a peristaltic irrigation aspiration console. The single-use hand-piece is a 19.5-gauge instrument with a tip that incorporates a purpose-designed insulated footplate pointed for ease of insertion through the trabecular meshwork into Schlemm’s canal and a protective member that isolates the collector channels and the drainage system of the eye (Fig. 1). The trabecular meshwork is selectively vaporized and aspirated using high-frequency electro-surgery pulses

Surgical Technique In most combined surgeries, Trabectome was performed first, followed by cataract extraction using phacoemulsification. Standard dilating drops comprising phenylephrine hydrochloride (Neo-Synephrine 2.5%) and tropicamide (Mydriacyl 0.5%) were instilled in the preoperative area, with application of antibiotic and nonsteroidal anti-inflammatory drops as per institution protocol. Preservative free lidocaine gel 1% was instilled

Trabectome Combined with Phacoemulsification vs Phacoemulsification Alone — Francis

Table I Average IOP in Trabectome and PCE group vs PCE group Trabectome and PCE group

p values

PCE group

p values

Preoperative

22.2±5.9(n=114)

————

16.2±4.2(n=145)

———-

1 day

17.6±8.1(n=114)

<0.01

20.0±7.9(n=145)

<0.01

1 mth

15.9±4.6(n=114)

<0.01

15.2±3.8(n=145)

0.034

3 mth

15.4±3.7(n=112)

<0.01

14.6±3.6(n=136)

<0.01

6 mth

15.5±3.2(n=101)

<0.01

14.8±3.1(n=112)

<0.01

12 mth

15.4±3.1(n=85)

<0.01

14.5±3.3(n=76)

<0.01

24 mth

15.3±3.5(n=67)

<0.01

14.3±3.6(n=41)

<0.01

p values compare each follow-up to preoperative value

Fig. 7 Average IOP levels after Combined Trabectome and Phacoemulsification procedures: “IOP Baseline” is the average IOP of 114 patients before Trabectome combined with cataract extraction.

Fig. 8 Average glaucoma medication levels after Trabectome combined with cataract extraction procedures: “#Meds Baseline” is the overall average preoperative medications of 114 patients before Trabectome combined with cataract extraction.

Fig. 9 Survival curves of Trabectome combined with cataract extraction and cataract extraction only procedures. Success = no secondary surgery and IOP<21mm Hg and IOP reduced by 20% in last two consecutive visits 3 months afer surgery. Log rank test gives p<0.001.

Fig. 10 Average IOP levels after cataract extraction only: “IOP Baseline” is the average IOP of 145 patients before cataract extraction only.

Supplement: Clinical & Surgical Ophthalmology, June 2015

Table II Comparison of average IOPs in the Trabectome and cataract extraction, and cataract extraction alone matched-pair patients. Matched pair Analysis Trabectome and PCE group PCE group Preop IOP 14 16 17 17 18 20 23 29 18 20 19.2±4.2 (mean+std)

12 mth IOP 11 12 13 10 12 17 14 17 20 18 14.4±3.37 (mean+std)

Preop IOP 14 16 17 17 18 20 23 29 18 20 19.2±4.2 (mean+std)

12 mth IOP 20 24 18 21 17 19 23 26 18 16 20.2±3.26 (mean+std)

in the inferior cul-de-sac and the bulbar conjunctival surface. Pilocarpine was not given before combined surgeries, as is typical when Trabectome is performed as a stand-alone procedure. Once the surgical area was prepped and draped, the head and microscope were tilted to enhance the gonioscopic view of the angle. The combined tilt of microscope and patient head was approximately 70 to 80 degrees to optimize the view of the angle under gonioscopic view. The surgical steps are shown in Figure 2. The Trabectome gonio-surgical lens (a modified Swann-Jacobs lens) was placed on the cornea to verify the angle landmarks. A 1.7 mm keratome blade was used to make a near-limbal, temporal corneal incision. Preservative-free lidocaine 1% was injected into the anterior chamber for anesthesia. A small de-pressurization of the anterior chamber can be used to congest Schlemm’s canal and to provide a red hue of the trabecular meshwork for easy visualization (Figs. 3, 4, 5, 6). Variably, an ophthalmic viscosurgical device (OVD) such as hydroxypropyl methylcellulose (Ocucoat) or sodium hyaluronate 1% (Healon) was injected to form the anterior chamber. The Trabectome handpiece was inserted and advanced nasally across the anterior chamber with the infusion on. A surgical gonioscopy lens was used to visualize the target trabecular meshwork nasally as the instrument tip was advanced across the anterior chamber. The pointed tip of the footplate was inserted through the trabecular meshwork into Schlemm canal, and a footswitch activated the aspiration and electro-surgical elements. The instrument was advanced along the meshwork, first in a counterclockwise, then in a clockwise direction using the limbal corneal incision as a fulcrum, ablating and removing a strip of trabecular meshwork and the inner wall of Schlemm’s canal. The initial power setting was 0.7 to 0.8 W, and the power was titrated up or

Fig. 11 Average IOP levels after treatment from matched pairs analysis comparing outcomes for n=10 pairs of patients with matching preoperative IOP values. “IOP Baseline” is the average IOP of 10 patients from each group before treatment (note that the value is the same for both groups based on matching criterion).

down depending on the desire to ablate a wider strip of trabecular meshwork or to minimize charring of tissue, respectively. Verification of the cleft was performed, and the angle was viewed for evidence of blood reflux from Schlemm canal as the handpiece was removed. The anterior chamber was then filled with an OVD, and the head and microscope were returned to the straight up-and-down position. A paracentesis was created and the corneal incision enlarged with a phacoemulsification keratome. Phacoemulsification and IOL implantation were then performed using the surgeon’s preferred technique. At the conclusion of the procedure, depending on pupil size, acetylcholine chloride (Miochol) or carbachol intraocular solution (Miostat) was instilled. The amount of blood in the anterior chamber was assessed. Additional irrigation and aspiration was performed to remove any remaining OVD, blood or debris. If active bleeding was present, an air-bubble tamponade was injected into the anterior chamber. The corneal incision was then closed with 10-0 nylon or vicryl. For patients receiving phacoemulsification and IOL implantation alone, surgeries were performed using the surgeon’s same preferred technique for phacoemulsification and IOL implantation.

RESULTS Patient Demographics The mean age in the Trabectome group combined with cataract extraction was 77±9 years with 62% female

Trabectome Combined with Phacoemulsification vs Phacoemulsification Alone — Francis

patients. The mean age in the cataract extraction only group was 74±12 years with 68% female patients. Trabectome Combined with Cataract Extraction Group The mean preoperative IOP in this group was 22.2±5.9 mm Hg (n=114). At 12 months, the average IOP dropped by 27% to 15.4±3.1 mm Hg (n=85, p<0.01). At 24 months, the IOP was 15.3±3.5 mm Hg (n=67, p<0.01) which was a 28% drop from baseline IOP (Table I). Figure 7 indicates the trend in IOP in this group of patients. Glaucoma medications dropped by 40% during the study period as shown in Figure 8. There were 5 patients that underwent secondary surgery by the end of second year. The success at 24 months was 80% (Fig. 9). Phacoemulsification Cataract Extraction Only Group The preoperative IOP in this group was 16.2±4.2 mm Hg (n=145). At 6 months, the average preoperative IOP dropped by 5% to 14.8±3.1 mm Hg (n=112, p<0.01). At 12 months, the average preoperative IOP dropped to 14.5±3.3 mm Hg (n=76, p<0.01) (Table I). At 24 months, the average preoperative IOP dropped to 14.3±3.6 mm Hg (n=41, p<0.01). Figure 10 indicates the trend in IOP after PCE only. The success at 24 months was 46% (Fig. 9). The change in IOP at 1 year when compared to preoperative IOP level was statistically significant in both the groups (p<0.01, Table I). Analysis of Matched Pairs Based on Preoperative IOP For the Trabectome combined with cataract extraction group as well as the PCE only group, average preoperative IOP was 19.2±4.2 mm Hg (n=10 each group). The preoperative IOP levels were the same for both groups as a result of the matching criterion. At 12 months for the combined Trabectome PCE group, the average preoperative IOP dropped to 14.4±3.4 mm Hg (n=10, p=0.01) which was a 25% drop from baseline IOP (Table II). At 12 months for the PCE only group, the average pre-operative IOP increased to 20.2±3.2 mm Hg (n=10, p=0.55) which was a 5% rise from baseline IOP (Table II). Comparing the IOP results between groups at 12 months postoperative, the p-value from the paired t-test was 0.0057 and from the signed rank test was 0.0137; thus, IOP was significantly lower in the Trabectome combined with cataract extraction group compared with the cataract extraction only group. Figure 11 compares the trend in IOP in these groups of patients.

DISCUSSION Various studies of the changes in intraocular pressure after phacoemulsification have been published21-24 and reviewed.1,25 In an extensive evidence-based review of available published literature,1 evidence was weak (but

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consistent) that long-term IOP is lowered by 2 to 4 mm Hg after cataract extraction alone in glaucoma patients. However, there was strong evidence for better long-term control of IOP in glaucoma patients with combined glaucoma surgery (trabeculectomy) and cataract extraction compared with cataract surgery alone.1 However, among glaucoma specialists, there remains a lack of consensus as to the best approach to surgical management of coexisting cataract and glaucoma, as available evidence remains limited and is often conflicting. In the present study, the mean IOP in patients treated with both Trabectome and cataract extraction is lowered 28% from a preoperative baseline of 22.2±5.9 mm Hg to 15.3±3.5 mm Hg at 24 months (p<0.01) (Table I). Concurrently, these patients have about a 40% reduction in average use of glaucoma medicines relative to preoperative usage (Fig. 8). In comparison, the average IOP in patients treated with cataract extraction was lowered from a preoperative baseline of 16.2±4.2 mm Hg to 14.3±3.6 mm Hg at 24 months (p<0.01) (Table I). Although this IOP lowering effect of cataract extraction reached statistical significance relative to the preoperative IOP level, the magnitude of the drop is relatively smaller (~ 2 mm Hg) and represents a 2% reduction from baseline IOP level in this group. These results are consistent with those reported by others for the IOP-lowering effects of cataract extraction alone.1,22,23,26 Applying the same success criteria used in Tube versus Trabeculectomy (TVT) publications,19,20 the group treated with Trabectome combined with cataract extraction has a survival of 80% at 24 months, compared with a survival of 45% for the group treated with cataract extraction only (Fig. 9). The primary contributing factor for the greater success achieved in the combined group was the higher degree of IOP-lowering that resulted from adding use of Trabectome to these cataract extraction surgeries relative to that achieved by cataract extraction only. It has been reported that IOP reduction may be proportional to preoperativeerative IOP levels following phacoemulsification.27 In our study, the baseline IOP was significantly higher in the combined Trabectome PCE group than in the PCE alone group, which may account in part for the greater IOP lowering in the former. In the present study, an additional analysis was performed by selecting matched pairs of patients from each group with identical preoperative IOP values and age. As a result of the matching criterion, both groups had the same mean preoperative IOP baseline of 19.2±4.2 mm Hg. In the matched-pair group treated with combined Trabectome PCE, the average IOP is lowered 25% from the preoperative baseline to 14.4 mm Hg at 12 months (p=0.01) (Table II). In the matched-pair group treated with cataract extraction only, the average IOP is elevated 5% from the

same preoperative baseline to 20.2 mm Hg (p=0.55) at 12 months (Table II). These results are consistent with others that have reported postoperative IOP levels that were slightly elevated relative to baseline at 12 months following cataract surgery.24 Results of the present study support the conclusions of others that have reviewed the published literature on cataract surgery and glaucoma.1,25 For eyes with open angle glaucoma, glaucoma surgery combined with cataract extraction may be used to achieve clinically significant IOP reduction, while cataract surgery alone may be inconsistent in lowering IOP. The effectiveness of Trabectome in reducing IOP and lowering medication use in combination with cataract removal has been reported previously.14,17 In the present study, use of Trabectome in combination with cataract surgery likewise results in clinically significant reductions in IOP and medication use, while cataract surgery alone results in a significant, but more limited reduction in IOP by comparison. As newer surgical alternatives for glaucoma such as Trabectome offer a favorable risk profile relative to traditional combined filtering surgeries, its use in combination with cataract surgery offers a sensible approach to the surgical management of coexisting cataract and glaucoma for patients requiring reduction in and control of IOP. For surgical management of coexisting cataract and glaucoma, Trabectome in combination with phacoemulsification cataract surgery results in clinically meaningful reductions in both IOP and glaucoma medication use, while cataract surgery alone results in a more limited reduction in IOP by comparison. ❏

REFERENCES

3. 4. 5. 6. 7.

10.

11.

12. 13.

14.

15. 16. 17.

18.

CONCLUSION

Friedman DS, Jampel HD, Lubomski LH, et al. Surgical strategies for coexisting glaucoma and cataract: an evidence based update. Ophthalmology 2002; 109: 1902-1915. Jampel HD, Friedman DS, Lubomski LH, et al. Effect of technique on intraocular pressure after combined cataract and glaucoma surgery: an evidence-based review. Ophthalmology 2002; 109: 2215-2224. Bindlish R, Condon GP, Schlosser JD, et al. Efficacy and safety of mitomycin-C in primary trabeculectomy; five-year follow-up. Ophthalmology 2002; 109: 1336-1341. Soltau JB, Rothman RF, Budenz DL, et al. Risk factors for glaucoma filtering bleb infections. Arch Ophthalmol 2000; 118: 338-342. DeBry PW, Perkins TW, Heatley G, et al. Incidence of late-onset bleb-related complications following trabeculectomy with mitomycin. Arch Ophthalmol 2002; 120: 297-300. Gayton JL, Van Der Karr M, Sanders V. Combined cataract and glaucoma surgery: trabeculectomy versus endoscopic laser cycloablation. J Cataract Refract Surg 1999; 25: 1214- 1219. Babighian S, Caretti L, Tavolato M, et al. Excimer laser trabeculotomy vs 180° selective laser trabeculoplasty in primary open-angle glaucoma. A 2-year randomized, controlled trial. Eye (London) 2010; 24(4): 632-638.

19. 20. 21.

22. 23.

24.

25. 26. 27.

Minckler DS, Hill RA. Use of novel devices for control of intraocular pressure. Exp Eye Res 2009; 88(4): 792-798. Cheng JW, Xi GL, Wei RL, Cai JP, Li Y. Efficacy and tolerability of nonpenetrating glaucoma surgery augmented with mitomycin C in treatment of open-angle glaucoma: a meta-analysis. Ophthalmologica 2010; 224(3): 138-146. Lewis RA, von Wolff K, Tetz M, et al. Canaloplasty: circumferential viscodilation and tensioning of Schlemm’s canal using a flexible microcatheter for the treatment of open-angle glaucoma in adults; interim clinical study analysis. J Cataract Refract Surg 2007; 33: 1217-1226. Francis BA, See RF, Rao NA, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma 2006; 15: 68-73. Minckler DS, Baerveldt G, Alfaro MR, Francis BA. Clinical results with the Trabectome for treatment of open-angle glaucoma. Ophthalmology 2005; 112: 962-967. 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. Available at: http://www.aosonline.org/xactions/2006/15456110_ v104_p040.pdf. Francis BA, Minckler D, Dustin L, et al. Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: initial results. J Cataract Refract Surg 2008; 34(7): 1096-1103. Liu J, Jung J, Francis BA. Ab interno trabeculotomy: Trabectome surgical treatment for open-angle glaucoma. Expert Rev Ophthalmol 2009; 4(2): 119-128. Mosaed S. Ab interno trabeculotomy with the Trabectome surgical device. Techniques in Ophthalmology 2007; 5(2): 63-66. Minckler D, Mosaed S, Dustin L, Francis B, and the Trabectome Study Group. Trabectome (trabeculotomy – internal approach): additional experience and extended follow-up. Trans Am Ophthalmol Soc 2008; 106: 149-160. Godfrey DG, Fellman RL, Neelakantan A. Canal surgery in adult glaucomas. Curr Opin Ophthalmol 2009; 20(2): 116-121. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol 2007; 143(1): 9-22. Gedde SJ, Schiffman JC, Feuer WJ, et al. Three-year follow-up of the tube versus trabeculectomy study. Am J Ophthalmol 2009; 148(5): 670-684. Ferrari E, Bandello F, Roman-Pognuz D, Menchini F. Combined clear corneal phacoemulsification and ab interno trabeculectomy: three-year case series. J Cataract Refract Surg 2005; 31: 1783-1788. Hayashi K, Hayashi H, Nakao F, Hayashi F. Effects of cataract surgery on intraocular pressure control in glaucoma patients. J Cataract Refract Surg 2001; 27: 1779-1786. Shingleton BJ, Gamell LS, O’Donoghue MW, et al. Long-term changes in intraocular pressure after clear corneal phacoemulsification: Normal patients versus glaucoma suspect and glaucoma patients. J Cataract Refract Surg 1999; 25: 885-890. Merkur A, Damji KF, Mintsioulis G, Hodge WG. Intraocular pressure decrease after phacoemulsification in patients with pseudoexfoliation syndrome. J Cataract Refract Surg 2001; 27: 528-532. Vizzeri G, Weinreb RN. Cataract surgery and glaucoma. Curr Opin Ophthalmol 2010; 21: 20-24. Fea AM. Phacoemulsification versus phacoemulsification with micro-bypass stent implantation in primary open-angle glaucoma. J Cataract Refract Surg 2010; 36: 407-412. Poley BJ, Lindstrom RL, Samuelson TW, Schulze R. Intraocular pressure reduction after phacoemulsification with intraocular lens implantation in glaucomatous and nonglaucomatous eyes: evaluation of a causal relationship between the natural lens and open-angle glaucoma. J Cataract Refract Surg 2009; 35; 1946-1955.

Trabectome Combined with Phacoemulsification vs Phacoemulsification Alone — Francis

Impact of Preoperative Intraocular Pressure on Trabectome Outcomes: A Prospective, Non-Randomized, Observational, Comparative Cohort Outcome Study Steven D. Vold, MD

ABSTRACT Purpose: To evaluate the impact of preoperative intraocular pressure (IOP) on Trabectome surgery outcomes. Methods: This is a prospective nonrandomized quasi-experimental study using cohort analysis of 1401 Trabectome procedures (86.3% from US population), grouped by preoperative IOP with 6 months postoperative follow-up. Results: In eyes with preoperative IOPs of ≤17 mmHg, mean reductions in IOP and glaucoma medications 6 months after surgery were 7%, 35% (n=293). In eyes with IOPs of 18 to 22 mmHg, reductions were 20%, 28% (n=428). In eyes with IOPs of 23 to 29 mmHg, reductions were 33%, 28% (n=379). In eyes with IOPs of ≥ 30 mmHg, reductions were 48%, 25% (n=301). Secondary surgery incidence rose with increasing preoperative IOP, but was less for eyes undergoing combined cataract and Trabectome surgery. Conclusion: Higher preoperative IOP increased Trabectome IOP reduction but not magnitude of glaucoma medication reduction. Likelihood of secondary surgery increased with higher preoperative IOP, but was reduced for all preoperative IOP levels when cataract and Trabectome surgery were combined.

INTRODUCTION Trabeculotomy using an internal approach has recently emerged as a viable treatment option for patients with open-angle glaucoma.1 This procedure is generally performed using the Trabectome® (NeoMedix, Inc., Tustin, California) which was approved by the U.S. Food and Drug Administration in April 2004. The Trabectome procedure serves as an alternative to trabeculectomy, which currently serves as the gold standard for modern glaucoma surgery. The relatively long postoperative course and high rate of complications associated with trabeculectomy performed with an antifibrotic agent have served as impetus for the development of more minimally invasive procedures.2-6 S.D. Vold — Boozman-Hof Eye Clinic, P.A., Rogers, AR Correspondence to: Dr. Steven D. Vold, Boozman-Hof Eye Clinic, P.A., 3737 West Walnut, Rogers, AR 72756; E-mail: svold@cox.net Dr. Steven D. Vold is a Trabectome trainer, and receives honoraria for surgeon training sessions.

Supplement: Clinical & Surgical Ophthalmology, June 2015

In several earlier studies,1,7-14 Trabectome surgery has been reported to be effective in lowering intraocular pressure (IOP) and reducing the need for topical glaucoma medications. However, we still have much to learn regarding the importance of proper patient selection and factors impacting Trabectome outcomes. Previous laser trabeculoplasty does not appear to negatively impact Trabectome IOP outcomes, but may increase the need for glaucoma medication in some patients undergoing Trabectome surgery.15 The purpose of this study is to help elucidate the impact of preoperative IOP levels on outcomes of Trabectome surgery.

PATIENTS AND METHODS Local institutional review board approval was obtained in accordance with the Declaration of Helsinki and the U.S. Health Insurance Portability and Accountability Act. Consecutive patients undergoing Trabectome procedure with at least 6 months of followup were included in the study cohort. Trabectome patients either received Trabectome only (T) or Trabectome combined with cataract surgery by phacoemulsification (T+P). In most combined surgeries, the Trabectome procedure was performed first, and cataract surgery was performed second. Recorded preoperative data included the following: patient demographic data; type of glaucoma; prior surgeries; intraocular pressures; number of glaucoma medications; operative findings; and surgical complications. Primary outcome measures evaluated included IOP, number of glaucoma medications, and need for secondary glaucoma surgeries. The Trabectome surgical system has been described in detail1 and consists of a disposable handpiece connected to a console with irrigation and aspiration as well as an electrosurgical generator (Fig. 1). The

Fig. 1 Trabectome surgical system

Fig. 2A Make 1.7 mm clear corneal incision

Fig. 2B Inject viscoelastic into anterior chamber

Fig. 2C Insert Trabectome handpiece tip into anterior chamber

Fig. 2D Identify trabecular meshwork and begin ablation

Fig. 2E Treat 90-120 degree arc

Fig. 2F Aspirate viscoelastic and ensure wound secure

hand-piece is a 19.5-gauge instrument with a tip that incorporates an insulated footplate pointed for ease of insertion through the trabecular meshwork into Schlemm’s canal. The trabecular meshwork and inner wall of Schlemm’s canal are removed using high-frequency electrocautery heat energy in bursts with a high peak power and low duty cycle. The aspiration port is located adjacent to the microcautery electrode, and irrigation keeps the anterior chamber formed and dissipates heat energy. The irrigation/aspiration console has a pinch valve for control of gravity feed irrigation from a hanging bottle of balanced salt solution, with the height manually adjusted. The peristaltic aspiration pump allows flow rates up to 4 ml/minute. The electro-surgical functions and fluidics are controlled by the surgeon via a 3-position foot pedal (position 1, irrigation; position 2, aspiration; position 3, electro-surgery pulse). For trabecular meshwork ablation, typical electrosurgical power settings range from 0.7 to 1.0 Watt. Prior to surgery, topical antibiotic and nonsteroidal anti-inflammatory drops were generally instilled in the operative eye per each individual surgeon’s postoperative cataract surgery protocol. Topical pilocarpine was often instilled prior to Trabectome only surgeries, while dilating agents were used in combined Trabectome and cataract surgeries. In most combined procedures, Trabectome was performed first, followed by cataract extraction via phacoemulsification with intraocular lens (IOL) insertion. Local anesthesia using intraconal, peribulbar or topical approaches was used.

Once the eye is prepped and draped, the patient’s head and the surgical microscope were tilted (combined angle of about 75 degrees) to facilitate gonioscopic view of the angle. A modified Swann-Jacob goniolens (Ocular Instruments, Bellevue, Washington) was placed on the cornea to verify visualization of the angle structures. A 1.7 mm keratome was used to make a near-limbal, temporal clear corneal incision (Fig. 2A). To congest Schlemm’s canal and provide improved visualization of trabecular meshwork location, a depressurization of the anterior chamber may be utilized. Preservative-free lidocaine was typically injected into the anterior chamber in patients not receiving a retrobulbar or peribulbar block. An ophthalmic viscosurgical device (OVD) such as hydroxypropyl methylcellulose (eg., Ocucoat; Bausch & Lomb, Rochester, New York) was used to help maintain the anterior chamber (Fig. 2B). The Trabectome handpiece was inserted and advanced nasally across the anterior chamber under continuous irrigation to maintain the anterior chamber (Fig. 2C). The surgical goniolens was used to visualize the target trabecular meshwork as the tip of the instrument was advanced toward the nasal angle. Under direct visualization, the pointed tip of the instrument footplate was inserted through the trabecular meshwork and into Schlemm’s canal, and the footswitch was activated to initiate aspiration and discharge of electrosurgical energy pulses (Fig. 2D). The surgeon slowly advanced the instrument along Schlemm’s canal to ablate and remove a strip of trabecular meshwork and the inner wall of

Impact of Preoperative IOP on Trabectome Outcomes — Vold

Table I Demographic data

Number (n) Mean Age Race African-American Asian Caucasian Hispanic Other Diagnosis POAG&COAG Pseudoexfoliation JRA Myopic Degeneration Steroid Induced Pigmentary Glaucoma Uvetic Other Type of Surgery T+P T

Group 1 (≤ 17 mm Hg)

Group 2 (18-22 mm Hg)

Group 3 (23-29 mm Hg)

Group 4 (≥ 30 mm Hg)

293 73±12

428 71±13

379 68±16

301 65±18

15 38 192 7 41

20 59 292 16 41

17 47 238 30 47

20 41 166 38 36

230 25 1 1 1 6 2 27

334 42 0 0 3 14 2 33

284 22 2 3 2 14 7 45

164 49 1 1 10 15 20 41

189 104

186 242

86 293

43 258

Format for Age: Mean±Standard Deviation; T: Trabectome only; T+P : Trabectome combined with phacoemulsification surgery

Table II Postoperative IOP outcomes Group

Pre-Op IOP mm Hg

6-Month IOP mm Hg

IOP Change mm Hg (%)

p-IOP

Group 1 (n=293) (≤17 mmHg)

14.9+1.9

13.7+2.8

-1.1+2.8 (-7%)

<0.01

Group 2 (n=428) (18-22 mmHg)

19.9+1.4

15.8+3.2

-4.0+3.2 (-20%)

<0.01

Group 3 (n=379) (23-29 mmHg)

25.6+1.9

17.2+4.3

-8.4+4.4 (-33%)

<0.01

Group 4 (n=301) (≥ 30 mmHg)

35.4+5.5

17.9+5.3

-16.8+6.6 (-48%)

<0.01

p-IOP is the p value from t-test comparing IOP values before and 6 months after surgery

Table III Subgroup postoperative IOP outcomes Group

Subgroup

Pre-Op IOP mm Hg

6-Month IOP mm Hg

IOP Change (%)

p-IOP

Group 1 (<17mmHg)

T T+P

15.3±1.7 14.6±2.0

14.2±2.6 13.5±2.8

-6% -7%

<0.01 <0.01

Group 2 (18-22mmHg)

T T+P

20.1±1.3 19.6±1.4

16.4±3.3 15.2±2.9

-18% -22%

<0.01 <0. 01

Group 3 (23-29mmHg)

T T+P

25.7±1.9 25.4±1.8

17.5±4.5 16.2±3.4

-31% -36%

<0.01 <0.01

Group 4 (≥30mmHg)

T T+P

35.6+5.7 34.0+4.2

17.9±5.4 17.8±4.4

-48% -47%

<0.01 <0.01

p-IOP is the p value from t-test comparing IOP values before and 6 months after surgery.

Schlemm’s canal. Typical treatment was approximately 90 to 120 degrees of the nasal angle (Fig. 2E). A visible cleft and blood reflux emanating from collector channels located along the distal wall of Schlemm’s canal, were typically observed as the handpiece was removed (Fig. 2F).

Supplement: Clinical & Surgical Ophthalmology, June 2015

In combined surgeries, the corneal incision was generally enlarged following the Trabectome procedure to accommodate the surgeon’s preferred method of performing phacoemulsification and IOL placement. Following the surgical procedure(s), depending on

Table IV Postoperative glaucoma medication utilization Group

Pre-Op Rx #

6-Month Rx #

Rx Change %

p-IOP

Group 1 (n=293) (≤17 mmHg)

2.63±1.12

1.72±1.30

-35%

<0.01

Group 2 (n=428) (18-22 mmHg)

2.66±1.19

1.92±1.32

-28%

<0.01

Group 3 (n=379) (23-29 mmHg)

2.82±1.39

2.02±1.39

-28%

<0.01

Group 4 (n=301) (≥ 30 mmHg)

3.10±1.25

2.34±1.45

-25%

<0.01

p-Rx is the p value from t-test comparing Rx values before and 6 months after surgery

Fig. 3 Postoperative IOP reduction at 6 months T designates Trabectome only surgical subgroup T+P designates Trabectome combined with phacoemulsification surgical subgroup. Table V Glaucoma medication utilization subgroup analysis Subgroup

Preop Rx

6 month Rx

Rx change

p-Rx

Group 1 T (≤17 mmHg) T+P

2.83±1.16 2.52±1.09

2.26±1.29 1.45±1.22

-12% -42%

<0.01 <0.01

Group 2 T (18-22 mmHg) T+P

2.76±1.28 2.53±1.06

2.20±1.26 1.60±1.32

-17% -36%

<0.01 <0.01

Group 3 T (23-29 mmHg) T+P

2.91±1.44 2.49±1.19

2.11±1.41 1.79±1.29

-23% -27%

<0.01 <0.01

Group 4 T (≥30 mmHg) T+P

3.11±1.30 3.07±0.91

2.32±1.49 2.43±1.17

-27% -21%

<0.01 <0.01

p-Rx is the p value from t-test comparing Rx values before and 6 months after surgery

surgeon preference, acetylcholine chloride (Miochol; Novartis Pharmaceuticals Corporation, East Hanover, NJ) or carbachol intraocular solution (Miostat; Alcon Laboratories, Inc., Fort Worth, Texas) was instilled to induce miosis and potentially prevent postoperative IOP spikes. An air-bubble tamponade was optionally introduced into the anterior chamber to prevent intraocular bleeding in select cases. At the surgeon’s discretion, the corneal incision was closed with a single 10-0 nylon or polyglactin suture to insure a leak-tight closure of the wound. Postoperative care generally included the use of topical steroid, antibiotic and pilocarpine 1% (typically starting at four times a day for 7 days, followed by a tapering regimen over a period of several weeks). Topical non-steroidal anti-inflammatory and other glaucoma medications were instilled as needed. This prospective, non-randomized, quasi-experimental study using cohort analysis helps elucidate the impact of preoperative IOP levels on outcomes following Trabectome surgery. Eyes were categorized into four groups based on measured preoperative IOPs as follows: ≤ 17 mm Hg (Group 1), 18 to 22 mm Hg (Group 2), 23 to

Fig. 4 Postoperative drop in glaucoma medication usage at 6 months T designates Trabectome only surgical subgroup T+P designates Trabectome combined with phacoemulsification surgical subgroup.

29 mm Hg (Group 3) and ≥ 30 mm Hg (Group 4). Primary outcome measures were analyzed for each of these groups and compared between groups. In addition, within each of these groups, primary outcome measures were analyzed separately for patients receiving Trabectome only (T subgroups) and patients receiving Trabectome combined with cataract surgery (T+P subgroups). Statistical analyses include unpaired t-tests to analyze differences between outcome measures.

RESULTS Table I displays key demographic data in the 4 patient groups undergoing Trabectome surgery. No demographic statistical differences were observed between groups. Table II provides information regarding IOP outcomes for all four patient groups. Table III evaluates differences between Trabectome only and combined Trabectome and cataract surgery patients in regards to postoperative IOP outcomes at 6 months postoperatively. Figure 3 graphically illustrates the level of IOP reduction in all 4 patient groups

Impact of Preoperative IOP on Trabectome Outcomes — Vold

Table VI Secondary surgeries and complications

Number of eyes (n) Secondary Surgeries: Trabeculectomy Shunt DCP (Diode Cyclophotocoagulation) ECP Trabectome Total Secondary Surgeries Complications: Sustained Hypotony (IOP<5 mmHg) one month postop IOP @1st Day postop >10 mmHg from pre op IOP Aqueous Misdirection Infection Bleb Formation Wound Leaks Problematic Pain Choroidal Effusion Choroidal Hemorrhage Visual Acuity Decrease (>2 lines)

Group 1 (≤ 17 mm Hg)

Group 2 (18-22 mm Hg)

Group 3 (23-29 mm Hg)

Group 4 (≥ 30 mm Hg)

293

428

379

301

6 1 1 1 0 9(3%)

23 11 5 1 2 42(10%)

41 22 0 2 6 71(18.7%)

45 20 1 3 5 74(24.5%)

0 27 0 0 0 0 0 0 0 0

0 32 0 0 0 0 0 0 0 0

0 20 1 0 0 0 0 0 0 0

0 12 0 0 0 0 0 0 0 0

Table VII Secondary Surgery Subgroup Analysis

Number of eyes (n) Secondary Surgeries: Trabeculectomy Shunt DCP ECP Trabectome Total Secondary Surgeries p value within group

Group 1 (≤17 mmHg)

Group 2 (18-22 mmHg)

Group 3 (23-29 mmHg)

Group 4 (≥30 mmHg)

T 104

T+P 189

T 242

T+P 186

T 293

T+P 86

T 258

T+P 43

5 1 1 0 0

1 0 0 1 0

19 10 5 1 2

4 1 0 0 0

39 20 0 2 6

2 2 0 0 0

39 18 1 3 5

6 2 0 0 0

7 2 (6.7%) (1%) <0.01

37 5 (15.2%) (2.6%) <0.01

67 4 (22.8%) (4.6%) <0.01

66 8 (25.5%) (18.6%) 0.32

Table VIII Complications subgroup analysis

Number of eyes (n) Complications: Sustained Hypotony (IOP<5 mmHg) one month postop IOP @1st Day postop >10 mmHg from pre op IOP Aqueous Misdirection Infection Bleb Formation Wound Leaks Problematic Pain Choroidal Effusion Choroidal Hemorrhage Visual Acuity Decrease (>2 lines)

Group 1 (≤17 mmHg)

Group 2 (18-22 mmHg)

Group 3 (23-29 mmHg)

Group 4 (≥30 mmHg)

T 104

T+P 189

T 242

T+P 186

T 293

T+P 86

T 258

T+P 43

0 0 0 0 0 0 0 0

1 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0

Supplement: Clinical & Surgical Ophthalmology, June 2015

and their subgroups. Absolute IOP and percentage IOP drops were greater in patients with progressively higher IOPs. No differences were found between Trabectome only and combined surgery patients within each group. Within each patient group, the magnitude of reduction in glaucoma medication was also carefully analyzed (Table IV). Table V provides a subgroup analysis of this important outcome measure. Figure 4 illustrates the differences in glaucoma medication reduction between all 4 treatment groups and their subgroups. Trabectome surgery decreased the need for glaucoma medication in all 4 groups and their subgroups. However, statistically significant differences were noted between Trabectome only and combined patients in only groups 1 and 2. Postoperative complications were carefully evaluated in all patient groups and subgroups as well (Tables VI, VII, VIII). With increasing preoperative IOP, a trend toward progressively higher incidence of secondary glaucoma surgeries was observed. Furthermore, patients undergoing Trabectome surgery only were more likely to undergo additional glaucoma surgeries than patients undergoing combined surgeries in all 4 patients groups.

DISCUSSION The effectiveness of Trabectome as a surgical option to reduce IOP and glaucoma medication usage in open-angle glaucoma patients is now well established.7-14 In these studies, Trabectome surgery also demonstrates a very favorable safety and risk profile with relatively minimal postsurgical complications compared with those following conventional filtering surgeries.2-6 These considerations make Trabectome surgery an attractive approach for surgical management of open-angle glaucoma, particularly when a patient presents with coexisting glaucoma and cataract. Numerous studies have examined the changes in intraocular pressure following phacoemulsification cataract surgery.16-24 Based on an extensive review of available published literature and evidence-based analysis, evidence was weak but consistent that long-term IOP is lowered by about 2 to 4 mm Hg after cataract surgery alone in glaucoma patients. Evidence was stronger for better long-term IOP control in glaucoma patients with combined glaucoma and cataract surgery when compared with cataract surgery alone.17 Slightly elevated postoperative IOP levels relative to preoperative baseline values following phacoemulsification cataract surgery alone have been reported as well.21 Poley and colleagues reported that IOP changes resulting from cataract surgery alone are proportional to preoperative IOP levels, ranging from a mean increase of 0.2 mm Hg for the group of patients with preoperative IOP levels of 9 to 14 mm Hg, up to a mean decrease of 6.5 mm Hg for

the group of patients with preoperative IOP levels of 23 to 31 mm Hg.22 In this study, the degree of IOP lowering increased significantly with increasing preoperative IOP. Clearly, absolute and percentage lowering are easier to achieve when starting at a higher IOP. Trabectome surgery does seem to lower IOP more than cataract surgery alone when compared to previous cataract surgery studies. In addition, our data showed that Trabectome surgery alone lowered IOP to a similar degree as combined Trabectome and cataract surgery. In this study, all patients groups achieved in the mid-high teens independent of preoperative IOP. However, any potential differences in IOP outcomes between Trabectome alone and combined surgery patients may have been reduced because 50.1% of the patients undergoing Trabectome procedures alone in the current study already were pseudophakic prior to surgery. Trabectome surgery also reduced the need for glaucoma medication postoperatively in all 4 treatment groups and their subgroups. Interestingly, the magnitude of glaucoma reduction was similar in all patient groups and their subgroups. Given the costs associated with glaucoma medication use and challenges of medical compliance, surgical glaucoma interventions such as Trabectome surgery that reduce glaucoma medication utilization may benefit both glaucoma patients as well as the health care system.25-27 Complications and secondary glaucoma surgeries analysis comparing the 4 patient groups indicates a strong trend toward increased incidence of secondary glaucoma surgeries at six months in patients with increased preoperative IOP. Interestingly, patients undergoing combined Trabectome and cataract surgery were less likely to require a secondary procedure in this study. The author believes that the reason for this finding is linked to the severity of the glaucoma preoperatively. In patients undergoing Trabectome surgery alone, glaucoma was the driving force for surgery. In patients undergoing combined surgery, the cataract was often the primary indication for surgery. However, one cannot rule out a potentially protective effect of cataract surgery. Potential weakness of this study is the relatively short postoperative follow-up period. However, the large cohort and high quality data collection provide an excellent resource for obtaining this kind of important information.

CONCLUSION Trabectome surgery significantly reduces IOP and the need for topical glaucoma patients in open-angle glaucoma patients regardless of preoperative IOP level. However, the magnitude of IOP reduction at six months is dependent upon the preoperative IOP levels in these patients, with IOP reduction progressively increasing with increasing preoperative IOP level. Concurrently, mean

Impact of Preoperative IOP on Trabectome Outcomes â&#x20AC;&#x201D; Vold

number of glaucoma medications being used 6 months following Trabectome surgery is significantly reduced in all groups of patients regardless of preoperative IOP levels. The magnitude of glaucoma medication reduction at 6 months was similar at each preoperative IOP level. The incidence of secondary glaucoma surgery following Trabectome surgery increases substantially with increasing preoperative IOP. In addition, for all preoperative IOP levels, the incidence of secondary glaucoma surgery within 6 months following Trabectome surgery appears to be reduced if the procedure is combined with cataract surgery. Further research is necessary to validate these findings. ❏

REFERENCES 1.

Francis BA, See RF, Rao NA, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma 2006; 15(1):6873. 2. Wormald R, Wilkins MR, Bunce C. Post operative 5 fluorouracil for glaucoma surgery. Cochrane Database Syst Rev. 2001; CD001132. 3. Wilkins M, Indar A, Wormald R. Intra operative mitomycin C for glaucoma surgery. Cochrane Database Syst Rev 2001; CD002897. Review. 4. Kim YY, Sexton RM, Shin DH, et al. Outcomes of primary phakic trabeculectomies without versus with 0.5 to 1 minute versus 3–5 minute mitomycin C. Am J Ophthalmol 1998; 126(6): 755-762. 5. Bindlish R, Condon GP, Schlosser JD, et al. Efficacy and safety of mitomycin C in primary trabeculectomy: five year follow up. Ophthalmology 2002; 109(7): 1336-1342. 6. Gedde SJ, Schiffman JC, Feuer WJ, et al. Three-year follow-up of the tube versus trabeculectomy study. Am J Ophthalmol 2009; 148(5): 670-684. 7. Minckler DS, Mosaed S, Dustin L, Francis BA. Trabectome (trabeculectomy-internal approach): additional experience and extended follow-up. Trans Am Ophthalmol Soc 2008; 106: 1-12. 8. Francis BA, Minckler D, Dustin L, et al. Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: initial results. J Cataract Refract Surg 2008; 34(7): 1096-1103. 9. Vizzeri G, Weinreb RN. Cataract surgery and glaucoma. Curr Opin Ophthalmol 2010; 21: 20-24. 10. Minckler DS, Baerveldt G, Alfaro MR, Francis BA. Clinical results with the Trabectome for treatment of openangle glaucoma. Ophthalmology 2005; 112: 962-967. 11. Liu J, Jung J, Francis BA. Ab interno trabeculotomy: Trabectome surgical treatment for open-angle glaucoma. Expert Rev Ophthalmol 2009; 4(2): 119-128. 12. Mosaed S. Ab interno trabeculotomy with the Trabectome surgical device. Techniques in Ophthalmology 2007; 5(2): 63-66.

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13. 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. 14. Godfrey DG, Fellman RL, Neelakantan A. Canal surgery in adult glaucomas. Curr Opin Ophthalmol 2009; 20(2): 116121. 15. Vold SD, Dustin L. Impact of laser trabeculoplasty on Trabectome outcomes. Ophthalmic Surg Lasers Imaging 2010; 41(4): 443-451. 16. Shingleton BJ, Pasternack JJ, Hung JW, O’Donoghue MW. Three and five year changes in intraocular pressures after clear corneal phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients. J Glaucoma 2006; 15(6): 494-498. 17. Friedman DS, Jampel HD, Lubomski LH, et al. Surgical strategies for coexisting glaucoma and cataract: an evidence based update. Ophthalmology 2002; 109: 19021915. 18. Jampel HD, Friedman DS, Lubomski LH, et al. Effect of technique on intraocular pressure after combined cataract and glaucoma surgery: an evidence-based review. Ophthalmology 2002; 109: 2215-2224. 19. Hayashi K, Hayashi H, Nakao F, Hayashi F. Effects of cataract surgery on intraocular pressure control in glaucoma patients. J Cataract Refract Surg 2001; 27: 1779-1786. 20. Shingleton BJ, Gamell LS, O’Donoghue MW, et al. Longterm changes in intraocular pressure after clear corneal phacoemulsification: normal patients versus glaucoma suspect and glaucoma patients. J Cataract Refract Surg 1999; 25: 885-890. 21. Merkur A, Damji KF, Mintsioulis G, Hodge WG. Intraocular pressure decrease after phacoemulsification in patients with pseudoexfoliation syndrome. J Cataract Refract Surg 2001; 27; 528-532. 22. Poley BJ, Lindstrom RL, Samuelson TW. Long-term effects of phacoemulsification with intraocular lens implantation in normotensive and ocular hypertensive eyes. J Cataract Refract Surg 2008; 34(5): 735-742. 23. Poley BJ, Lindstrom RL, Samuelson TW, Schulze R Jr. Intraocular pressure reduction after phacoemulsification with intraocular lens implantation in glaucomatous and nonglaucomatous eyes: evaluation of a causal relationship between the natural lens and open-angle glaucoma. J Cataract Refract Surg 2009; 35(11): 1946-1955. 24. Altan-Yaycioglu R, Canan H, Pelit A, Akova YA. Intraocular pressure after phacoemulsification in eyes with pseudoexfoliation. J Cataract Refract Surg 2009; 35(5): 952-954. 25. Vold SD, Riggs WL, Jackimiec J. Cost analysis of glaucoma medications: a 3-year review. J Glaucoma 2002; 11(4): 354-358. 26. Ryander NR, Vold SD. Cost analysis of glaucoma medications. Am J Ophthalmol 2008; 145: 106-113. 27. Schwartz GF, Quigley HA. Adherence and persistence with glaucoma therapy. Surv Ophthalmol 2008; 53(Suppl1): S57-S68.

Trabectome versus Trabeculectomy in Open-Angle Glaucoma Brian A. Francis, MD, MS

ABSTRACT

INTRODUCTION

Purpose: To compare the effects of glaucoma surgery with the Trabectome versus trabeculectomy in glaucoma patients with at least 1-year follow-up. Method: This is a prospective, non-randomized, comparative cohort study of 79 patients who underwent trabeculectomy or Trabectome® by a single surgeon. Inclusion criteria were open-angle glaucoma and at least 12 months of follow-up. The main outcome measures were intraocular pressure (IOP), medications, need for secondary surgery, and postoperative complications. Success was defined as a 20% or greater reduction in IOP from baseline, IOP <21 mmHg, and no additional surgery. Results: Forty-three Trabectome cases had a mean preoperative IOP of 25.7±7.9 mmHg and 3.07±1.33 glaucoma medications. At 12 months, there was a mean 29% reduction in IOP to 16.5±3.6 mmHg (p<0.01) and 34% reduction in medication to 1.77±1.22 (p<0.01). Thirty percent required subsequent glaucoma surgeries. There were no other complications. Thirty-six trabeculectomy cases had a mean preoperative IOP of 23.2±9.1 mmHg and 3.19±1.14 glaucoma medications. At 12 months, there was a mean 48% reduction in IOP to 10.9±4.3 mmHg (p<0.01) and 78% reduction in medication to 0.43±0.94 (p<0.01). Seventeen percent required subsequent surgeries. Seventeen percent of cases had at least one of the following complications: hypotony maculopathy, hypotony, anterior segment wound revision, and persistent corneal epithelial defects. Conclusion: Both Trabectome and trabeculectomy significantly lower IOP and glaucoma medications in the surgical treatment of glaucoma. While trabeculectomy has significantly greater IOP and medication reduction, it is also associated with significantly greater incidence of postoperative complications compared to Trabectome (p<0.01).

An estimation in 2006 predicted that open-angle glaucoma (OAG) and angle-closure glaucoma (ACG) would be prevalent in 60.5 million people in 2010, and this increasing to 79.6 million by 2020, and of these, 74% would have open-angle glaucoma.1 Glaucoma is a progressive eye disease for which elevated intraocular pressure (IOP) has been identified as the major treatable risk factor.2 Lowering of IOP has been shown in several trials to decrease the rate of progression of glaucoma.3-6 OAG is treated first with medical therapy, later followed by laser trabeculoplasty and with a filtering surgery as the final treatment method in the United States. Trabeculectomy and aqueous tube shunt have been the gold standard surgical approaches to control IOP in glaucoma patients. These procedures involve external filtration, or the passage of aqueous humor from the anterior chamber to an extraocular site (conjunctival bleb) and then into the vascular system. Because of this, these procedures carry the risks related to hypotony, choroidal effusion and hemorrhage, conjunctival scarring, and late-onset endophthalmitis.7-19 Trabectome (trabeculotomy internal approach), in contrast to external filtration surgery, relies on the augmentation of the trabecular outflow pathway without the need for a conjunctival bleb. Therefore, many of the complications of external filtering procedures may be reduced or eliminated while still providing reduction in IOP and dependence on glaucoma medications.20 In this study, the outcome of Trabectome is compared with trabeculectomy for open-angle glaucoma. Although the procedures are different in their intent and method of action, it is useful to compare the outcomes of the newer, angle based procedure with the gold standard external filtration procedure. In this manner, surgeons may gain a better understanding of which procedure may be most appropriate for an individual patient.

B.A. Francis — Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA Correspondence to: Dr. Brian Francis, Doheny Eye Institute, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, DEI 4804, Los Angeles, CA 90033; E-mail: bfrancis@usc.edu Dr. Francis is a consultant for Neomedix Corporation, the manufacturer of the Trabectome®.

PATIENTS AND METHODS Ninety participants were recruited from patients attending the glaucoma service between January 2006 and January 2010 at the Doheny Eye Institute, Keck School of Medicine, University of Southern California. Participants

Trabectome versus Trabeculectomy in Open-Angle Glaucoma — Francis

Step 1: Scleral Incision

Step 2: Viscoelastic

Step 3: Goniolens Placement

Step 4: Ablation

Step 5: Rotate Tip

Step 6: Ablation

Step 7: Irrigate and Aspirate

Step 8: Suture

Fig. 1 Trabectome (trabeculotomy internal approach) surgical steps.

were patients who underwent trabeculectomy or Trabectome for uncontrolled glaucoma. All procedures were performed by a single surgeon (BAF). The Institutional Review Board at the University of Southern California approved the study protocol, and all study procedures conformed to the Health Insurance Portability and Accountability Act and the Declaration of Helsinki for research involving human participants. All participants had provided written consent prior to their respective procedures. Inclusion criteria are patients who recieved either Trabectome or trabeculectomy and reached a minimum of 12-months follow-up. The diagnoses included primary open-angle glaucoma, exfoliation glaucoma, pigmentary glaucoma, or chronic angle-closure glaucoma. Exclusion

Supplement: Clinical & Surgical Ophthalmology, June 2015

criteria were a diagnosis of neovascular glaucoma, uveitic glaucoma or pediatric glaucoma, and concurrent surgical procedure other than those studied. Preoperative characteristics including age, gender, lens status, IOP, optic nerve cup-to-disc ratio, visual field status, and number of glaucoma medications were noted. The type of surgery to be performed was determined by the treating physician. Postoperative measurements including IOP, number of glaucoma medications, hypotony (IOP â&#x2030;¤5 mmHg), presence of choroidal effusions or hemorrhage, wound leak, infection, surgical re-intervention, and bleb formation were collected at postoperative intervals of 1 day, 1 to 2 weeks, 1 month, 3 months, 6 months, and 12 months. In the case of trabeculectomy, laser suture lysis was not considered as a postoperative surgical intervention.

Table I Demographics of patients who underwent Trabectome or trabeculectomy 1-year follow-up

Gender Male Female Age mean±st dev Disc C/D <0.7 0.7-0.8 >0.8 NR Diagnosis POAG/COAG PEX Other VF Status Minimal Moderate Advanced MD/other Preop IOP mean±st dev

Trabectome (n=43)

Trabeculectomy (n=36)

20 (47%) 23 (53%)

12 (33%) 24 (67%)

0.23 (chi-sq test)

66±18

72±11

0.07 (t-test)

5 (12%) 13 (30%) 21 (49%) 4 (10%)

1 (3%) 4 (11%) 28 (78%) 3 (8%)

35 (81%) 4 (9%) 4 (9%)

26 (72%) 2 (6%) 8 (22%)

5 (12%) 15 (35%) 15 (35%) 8 (19%)

3 (8%) 3 (8%) 20 (56%) 10 (28%)

25.7±7.9

23.2±9.1

0.20 (t-test)

TRABECTOME PROCEDURE The surgical technique employed for patient undergoing the Trabectome procedure was consistent with those previously published.21,25-29 In brief, surgical steps for the Trabectome procedure are as follows: after topical antibiotic and anti-inflammatory drops are instilled in the eye, anesthesia is then obtained with topical lidocaine gel and preservative lidocaine 1% in the anterior chamber. A 1.7-mm temporal clear corneal incision is performed with a keratome, followed by injection of viscoelastic into the anterior chamber. A surgical goniolens is placed on the cornea and the angle view is verified. The goniolens is removed, and the tip of the Trabectome hand-piece is then introduced into the eye. The goniolens is replaced and continuous irrigation is activated. The Trabectome tip is advanced across the anterior chamber and inserted through trabecular meshwork into Schlemm’s canal just anterior to the scleral spur. The trabecular meshwork is then ablated at a power of 0.8 to 0.9 watts for approximately two clock hours in a counter-clockwise direction, then two clock hours in the clockwise direction. The steps of the Trabectome surgery are shown in Figure 1.

TRABECULECTOMY PROCEDURE In brief, surgical steps for trabeculectomy are as follows. After topical antibiotic and anti-inflammatory drops are instilled in the eye, anesthesia is then obtained with

subconjunctival and subtenons injection of lidocaine 1% and marcaine 0.75%. A 7-0 vicryl suture is passed through the superior peripheral cornea as a traction suture and the eye is rotated inferiorly to reveal the superior conjunctiva. A fornix-based or limbus-based conjunctival flap is then created. A scleral flap is marked with a supersharp blade, and a half thickness dissection carried out anteriorly to the corneal surgical limbus with a 67 blade. Instrument wipe sponges are soaked in Mitomycin-C in a concentration of 0.25-0.4 mg/mL and placed under the scleral flap and in the subconjunctival or sub-Tenons space for 2 to 4 minutes. After this time, the sponges are removed and the area is profusely irrigated with balanced salt solution. A 0.75 supersharp blade is used to enter the anterior chamber beneath the sceral flap and the Kelly punch is used to create the ostium. Vannas scissors are used to create the peripheral iridectomy. The scleral flap is closed with 10-0 nylon sutures, and the knots are rotated into the sclera. The anterior chamber is filled with balanced salt solution and the flow through the scleral flap is checked. The overlying conjunctival and tenons tissue are then reapposed using 8-0 vicryl suture on a vascular needle. Mild pressure on the flap is applied to elevate a bleb, and the wound surface is checked for watertight closure with a fluorescein strip.

STATISTICAL ANALYSIS Statistical analysis included unpaired t-tests between the IOPs in the two surgical groups at each postoperative time period. Chi-square test and two-tailed z-test for proportions were also used to compare attributes of patients in the two groups. Survival analysis is based on the success criterion in which success is defined IOP <21 mmHg and IOP >5 mmHg and IOP reduced by 20% in the last two consecutive visits 3 months after surgery without the need for additional surgery.

RESULTS Seventy-nine patients met inclusion criteria, and completed a 1-year follow-up and were included in the study. There were 36 eyes in the trabeculectomy group and 43 eyes in the Trabectome group. Table I demonstrates the baseline demographics of the subjects. The percentage of male patients in the Trabectome group was 47% and in the trabeculectomy group was 33%. There was no significant difference in preoperative IOP between the two groups. There is no significant difference in the age of the two groups. Table II summarizes the pre- and postoperative IOPs for both of the study groups, and this data is presented graphically for each respective study group in Figures 2 and 3. The IOP at each postoperative follow-up interval was significantly lower than preoperative IOP in both groups. There was a significant difference between the

Trabectome versus Trabeculectomy in Open-Angle Glaucoma — Francis

Table II IOP levels before and after Trabectome and trabeculectomy surgeries. Trabectome (n=43) Preop 1 day 1 week 2 weeks 1 month 3 months 6 months 12 months

25.7±7.9 17.1±11.3 (<0.01)* 18.1±7.8 (<0.01)* 19.3±7.3 (<0.01)* 19.5±7.3 (<0.01)* 19.7±6.6 (<0.01)* 18.4±4.9 (<0.01)* 16.5±3.6 (<0.01)*

Trabeculectomy (n=36) (43) (43) (42) (42) (42) (40) (34) (30)

23.2±9.1 15.3±10.8 (<0.01)* 14.1±9.0 (<0.01)* 11.9±9.0 (<0.01)* 11.3±6.1 (<0.01)* 10.5±6.0 (<0.01)* 10.7±5.4 (<0.01)* 10.9±4.3 (<0.01)*

p value between groups

(36) (36) (36) (36) (34) (33) (32) (30)

0.20 0.47 0.04 <0.01 <0.01 <0.01 <0.01 <0.01

* p value comparing each postoperative IOP with preoperative IOP within the same surgery group.

Fig. 2 Trend in IOP in Trabectome group.

Fig. 3 Trend in IOP in trabeculectomy group

IOPs in the two groups after the 1-week follow-up interval. As indicated in Table II, after the postoperative week-1 follow-up, the trabeculectomy group had a significantly lower IOP as compared to the Trabectome group at all subsequent time intervals. At 12 months, the average IOP in the Trabectome group was 16.5±3.6 mmHg while the mean IOP in the trabeculectomy group was 10.9±4.3 mmHg. Table III summarizes the postoperative observations and complications. There were no cases of hypotony (IOP ≤5 mmHg) in the Trabectome group at the 1-month or 12-month postoperative period. In contrast, in the trabeculectomy group, 19% had hypotony at the 1-month follow-up and 8.3% of cases had hypotony at the 12-month postoperative period. In the Trabectome group, 4 patients (9%) experienced a postoperative day 1 IOP elevation of >10 mmHg above baseline, compared to 1 patient (2.8%) in the trabeculectomy group. There was no significant difference in rate of Glaucoma Surgical Intervention between Trabectome and trabeculectomy (p=0.16). The trend in the mean number of medications required in both study groups is shown in Figures 4 and 5. In both groups, there was a significant reduction in

number of medications required for IOP control after each respective procedure. In the Trabectome group, mean number of medications was reduced from 3.1 medications preoperatively to approximately 1.8 medications postoperatively at 1 year. In the trabeculectomy group, the mean number of medications was reduced from 3.2 medications preoperatively to approximately 0.5 medications postoperatively. The survival curves of the two groups are illustrated in Figure 6. At 12 months, the success in the Trabectome is 67% compared with the success in the trabeculectomy group of 83%. The log rank test for the overall success in the two groups gives p<0.01 and this indicates significant difference in the survival curves of the two groups. The occurrence of complications in the 12-month follow-up period is shown in Figure 7 with Trabectome having significantly less postoperative complications of all types compared to trabeculectomy. Seventeen percent of trabeculectomy cases had at least one of the following complications: hypotony maculopathy, persistent hypotony, anterior segment wound revision, and persistent corneal epithelial defects.

Supplement: Clinical & Surgical Ophthalmology, June 2015

Table III Postoperative observations and complications after Trabectome and trabeculectomy.

Sustained hypotony 3 months postop Sustained hypotony 12 monts postop (1 day IOP) - (preop IOP) >10 mmHg Glaucoma surgical intervention Shunt Trabeculectomy ECP Trabectome Trab/Bleb revisions Hypotony maculopathy Anterior segment wound revision (bleb suturing) Persistent epithelial defects

Trabectome (n=43)

Trabeculectomy (n=36)

p value

1 (2%)

4 (11%)

0.1

3 (8.3%)

0.05

4 (9%)

1 (2.8%)

0.2

13 (30%) 6 (13.9%) 3 (6.9%) 2 (4.6%) 2 (4.6%) 0 0 0

6 (17%) 1 (2.8%) 0 0 0 5 (13.8%) 1 (3%) 1 (3%)

0.16 0.08 0.1 0.2 0.2 0.01 0.3 0.3

1 (3%)

0.3

Fig. 4 Trend in glaucoma medications in Trabectome group. “# of Meds Baseline” is the overall average preoperative medications of 43 patients before Trabectome.

Fig. 5 Trend in glaucoma medications in trabeculectomy group. “# of Meds Baseline” is the overall average preoperative medications of 36 patients before trabeculectomy.

DISCUSSION

Mitomycin-C and 5-fluorouracil are also eliminated. Lastly, the Trabectome completely spares the conjunctiva and allows for future standard filtering procedures if necessary, as the procedure is performed through a clear cornea incision. Our study analyzed the clinical outcomes of Trabectome and trabeculectomy over a 12-month follow-up period. The findings suggest that both procedures can result in a significant reduction in IOP as well as a reduction in glaucoma medications. With regards to IOP reduction, the trabeculectomy group had a significantly lower IOP as compared to the Trabectome group during the 12-month time period. In both groups, the mean number of postoperative medications required

Trabeculectomy has been shown to significantly lower IOP with or without antifibrotic therapy.30,31 However, previous studies have shown that complications after trabeculectomy, such as wound leaks, hypotony, blebitis, and endophthalmitis, occur at significant rates and can be associated with permanent visual disability.32-35 Theoretically, Trabectome glaucoma surgery has fewer complications due to the internal filtration method of action and absence of a conjunctival bleb. Thus, serious bleb-related complications possible with trabeculectomy such as hypotony, bleb leak and endophthalmitis are avoided. Given that Trabectome does not require the use of anti-fibrotic agents, risks associated with the use of

Trabectome versus Trabeculectomy in Open-Angle Glaucoma — Francis

Fig. 6 Survival curves comparing the two groups. Survival curves of Trabectome and trabeculectomy procedures. Success = No secondary surgery and (IOP <21 mmHg and IOP >5 mmHg and IOP reduced by 20% in last two consecutive visits 3 months after surgery). Log rank test gives p<0.01

for IOP control was significantly reduced compared to the number of preoperative medications. In terms of complications, trabeculectomy was associated with prolonged hypotony, while there were no such cases in the Trabectome group. There were 14% of cases that had trab/bleb revisions while no such revisions occurred in the Trabectome group. In this study, there were three cases that had persistent hypotony even at 12 months after trabeculectomy. One patient had hypotony maculopathy at 4 months after surgery. One patient had bleb suturing at 2 months. In one patient, several postoperative complications set in, beginning with bleb leak, then bleb leak not healing, and then requiring scleral patch and tube shunt 5 months later. There was one patient that had trabeculectomy revision at 2 weeks and ECP at 7 months. In all there were five patients (14%) that underwent trabeculectomy or bleb revision (Table III). Several studies have indicated that the major concern after filtering surgeries is vision threatening complications such as hyphema, choroidal effusion, hemorrhage or bleb infection.7-18 However, in our study, no patients in either group experienced choroidal hemorrhage, or significant decrease in visual acuity. With larger groups and longer follow-up, it may be more likely to see these types of complications. We used the success criteria developed in the Tube versus Trabeculectomy Study and this revealed success at 83% in trabeculectomy versus 67% in Trabectome group.36 Since this is a standardized success definition, we felt that this would allow for comparison with other studies.

Supplement: Clinical & Surgical Ophthalmology, June 2015

Fig. 7 Complications in the two groups during postoperative period.

Several studies of trabeculectomy have previously reported a significant reduction in IOP. In a retrospective study, Mora et al studied 140 eyes and the IOP reduced from 25.7±8.6 mmHg to 12.5±5.7 mmHg.37 Studies have shown that the intraoperative use of antimetabolites such as Mitomycin-C increases the success rate of filtration surgeries. A study by Law et al showed that eyes with initial trabeculectomy and repeat trabeculectomy with Mitomycin-C had lowered their IOP but the success of the former was more than the latter.38 The IOP reduction following trabeculectomy in our study is generally consistent with the results seen in these previous studies. Trabectome has also been shown to result in significant IOP reduction.22-24,39 Minckler et al reported that for 37 patients undergoing Trabectome, baseline IOP of 28.2±4.4 mmHg decreased at 12 months to 16.3±2.0 mmHg and medications decreased from 1.2±0.6 to 0.4±0.6 at 6 months.22 Mosaed reported that for patients undergoing only Trabectome, the mean preoperative IOP of 26.3 mmHg ±7.7 and mean of 2.88±1.30 glaucoma medications were reduced to a mean postoperative IOP of 16.6 mmHg ±4.0 on a mean of 2.09±1.35 glaucoma medications at 1-year follow-up.39 The findings with regards to the Trabectome group in our study are again generally consistent with the findings of these previous studies. A retrospective comparison of trabeculectomy and Trabectome was reported by Jea et al.40 The Trabectome group included 115 patients, and the Trabeculectomy group 102 patients, with a follow-up of up to 2 years. This study also found a significant reduction in IOP for Trabectome and trabeculectomy (44% and 61% reduction, respectively), that was significantly greater for the latter. Similar to our findings, there was a higher incidence of complications in the trabeculectomy group. The strengths of this study include close monitoring of IOP, medications, and complications in a prospective

fashion of the two groups. A validated, standard success criterion was used in order to make the results comparable to other studies. Participants were required to have 1-year follow-up in order to eliminate loss of data points. This study also has important limitations. The sample size in the both groups was not large, and therefore may not be adequately powered to detect subtle findings especially in the category of postoperative complications. Additionally, the study was non-randomized, making it susceptible to selection bias. The follow-up in this series was generally short term, and future studies would ideally include longer term results. Furthermore, all procedures were performed by a single surgeon, which makes the procedures more uniform, but also may limit generalizability to the surgical community as a whole. The primary goal of any glaucoma surgery is to reduce IOP with the lowest requirement for adjunctive glaucoma medications while providing the minimal risk for complications. In summary, our data suggests that both trabeculectomy and Trabectome are effective methods to significantly lower IOP and to reduce patient medication requirements. For 12 months of follow-up, trabeculectomy appears to result in a greater reduction in IOP with a lower medication requirement as compared to Trabectome. Yet, trabeculectomy also has a higher complication rate as compared to Trabectome. Due to its favorable risk profile, Trabectome is a viable alternative to trabeculectomy in patients with mild to moderate glaucoma severity seeking lower IOP and decreased dependence on glaucoma medications. Patients requiring very low target IOP may still benefit from trabeculectomy, despite the possible increased risk. ❏

10. 11.

12.

13. 14. 15.

16. 17.

18.

19.

20.

REFERENCES 1.

HA Quigley, Broman AT. Number of people with glaucoma world wide in 2010 and 2020. Br J Ophthalmol 2006; 90(3): 262-267. Le A, Bickol NM, et al. Risk factors associated with the incidence of open-angle glaucoma: the visual impairment project. Invest Ophthalmol & Vis Sci 2003; 44(9): 3783-3789. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study (OHTS): Baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120: 714-720. Heijl A, Leske MC, Bengtsson B et al. Early Manifest Glaucoma Trial Group (EMGTS): Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002; 120(10): 1268-1279. The AGIS Investigators: The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000; 130: 429-440. Collaborative Normal-Tension Glaucoma Study Group (CNTGS). The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol 1998; 126: 498-505.

21.

22.

23.

24.

25.

26.

Watson PG, Jakeman C, Ozturk M et al. The complications of trabeculectomy (a 20-year follow-up). Eye (Lond) 1990; 4 pt(3): 425-438. Kao SF, Lichter PR, Musch DC. Anterior chamber depth following filtration surgery. Ophthalmic Surg 1989; 20(5): 332-336. Stewart WC, Shields MB. Management of anterior chamber depth after trabeculectomy. Am J Ophthalmol 1988; 106: 41-44. Brubaker RF, Pederson JE. Ciliochoroidal detachment. Surv Ophthalmol 1983; 27: 281-289. Gressel MG, Parrish RK II, Heuer DK. Delayed nonexpulsive suprachoroidal hemorrhage. Arch Ophthalmol 1984; 102: 1757-1760. Ruderman JM, Harbin TS Jr, Campbell DG. Postoperative suprachoroidal hemorrhage following filtration procedures. Arch Ophthalmol 1986; 104: 201-205. Freedman J, Gupta M, Bunke A. Endophthalmitis after trabeculectomy. Arch Ophthalmol 1978; 96: 1017-1018. Zaidi AA. Trabeculectomy: a review and 4-year follow-up. Br J Ophthalmol 1980; 64: 436-439. Akafo SK, Goulstine DB, Rosenthal AR. Long-term post trabeculectomy intraocular pressures. Acta Ophthalmol (Copenh) 1992; 70: 312-316. Mills KB. Trabeculectomy: a retrospective long-term follow-up of 444 cases. Br J Ophthalmol 1981; 65: 790-795. Molteno AC, Bosma NJ, Kittelson JM. Otago glaucoma surgery outcome study: long-term results of trabeculectomy, 1976 to 1995. Ophthalmology 1999; 106: 1742-1750. D’Ermo F, Bonomi NJ, Kittelson JM. A critical analysis of the long-term results of trabeculectomy. Am J Ophthalmol 1979; 88: 829-835. Lingam V, Panday M, Ronnie G, et al. Management of complications in glaucoma surgery. Indian Journal of Ophthalmology 2011; 59: S131-S140. Razeghinejad MR, Fudemberg SJ, Spaeth GL. The changing conceptual basis of trabeculectomy: a review of past and current surgical techniques. Surv Ophthalmol 2012; 57(1): 1-25. Francis BA, See RF, Rao NA, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma 2006; 15: 68-73. Minckler DS, Baerveldt G, Alfaro MR, et al. Clinical results with the Trabectome for treatment of open-angle glaucoma. Ophthalmology 2005; 112: 962-967. 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. Available at: http://www.aosonline.org/ xactions/2006/1545-6110_ v104_p040.pdf Minckler D, Mosaed S, Dustin L, Francis B, and the Trabectome Study Group. Trabectome (TrabeculectomyInternal Approach): Additional Experience and Extended Follow-Up. Trans Am Ophthalmol Soc 2008; 106: 149-160. Francis BA, Minckler D, Dustin L, et al. Trabectome Study Group Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and openangle glaucoma: Initial results. J Cataract Refract Surg 2008; 34(7): 1096-1103. Liu J, Jung J, Francis BA. Ab interno trabeculotomy: Trabectome surgical treatment for open-angle glaucoma. Expert Rev Ophthalmol 2009; 4(2): 119-128.

Trabectome versus Trabeculectomy in Open-Angle Glaucoma — Francis

27. Mosaed S. Ab interno trabeculotomy with the Trabectome surgical device. Techniques in Ophthalmology 2007; 5(2): 63-66. 28. Gunderson E. Trabeculotomy ab interno, using the Trabectome: a promising treatment for patients with openangle glaucoma. Insight 2008; 33(1): 13-15. 29. Godfrey DG, Fellman RL, Neelakantan A. Canal surgery in adult glaucomas. Curr Opin Ophthalmol 2009: 20(2)116-21. Review. 30. Chaudhry IA, Pasha MA, Oâ&#x20AC;&#x2122;Connor DJ, et al. Randomized, controlled study of low-dose 5-floroucil in primary trabeculectomy. American Journal of Ophthalmology 2000; 130(6): 700-703. 31. Jampel HD, Friedman Bindish R, Condon GP, Schlosser JD, et al. Efficacy and safety of mitomycin-C in primary trabeculectomy; 5-year follow-up. Ophthalmology 2002; 109: 1336-1341. 32. Song A, Scott IU, Flynn Jr. HW, et al. Delayed-onset blebassociated endophthalmitis; clinical features and visual acuity outcomes. Ophthalmology 2002; 109: 985â&#x20AC;&#x201C;991. 33. Soltau JB, Rothman RF, Budenz DL, et al. Risk factors for glaucoma filtering bleb infections. Arch Ophthalmol 2000; 118: 338-342.

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34. DeBry PW, Perkins TW, Heatley G, et al. Incidence of lateonset bleb-related complications following trabeculectomy with mitomycin. Arch Ophthalmol 2002; 120: 297-300. 35. Francis BA, Hong B, Winarko J, Kawji S, Dustin L, Chopra V. Vision loss and recovery after trabeculectomy: risk and associated risk factors. Arch Ophthalmol 2011; 129(8): 1011-1017. 36. Gedde SJ, Schiffman JC, Feuer WJ etal. Three- year follow-up of the tube versus trabeculectomy study. Am J Ophthalmol 2009; 148(5): 670-684. Epub Aug 11, 2009. 37. Mora JS, Nguyen N, Iwach AG, et al. Trabeculectomy with intraoperative sponge 5-fluorouracil. Ophthalmology 1996; 103(6): 963-970. 38. Law SK, Shih K, Tran DH, et al. Long-term outcomes of repeat vs initial trabeculectomy in open-angle glaucoma. Am J Ophthamol 2009; 148(5): 685-695. 39. Mosaed S, Rhee D, Filipopoulous T, et al. Trabectome outcomes in adult open-angle glaucoma patients: one-year follow-up. Clinical & Surgical Ophthalmology 2010; 28(8/9): 182-186. 40. 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. Epub Oct 7, 2011.

Comparison of the Outcomes of Trabectome with Trabeculotomy with Deep Sclerectomy: Ab Interno vs. Ab Externo Trabeculotomy Masahiro Maeda, MD; Natsu Kondo, MD; Kazunori Onuki, MD; Rina Noritake; Asato Hasegawa, MD ABSTRACT Background/Objectives: The objective of this study is to compare the outcomes of Trabectome® versus trabeculotomy with deep sclerectomy (TDS) in Japanese patients. Methods: Twenty eyes that had undergone TDS were matched to 20 eyes that had undergone Trabectome. They were compared according to age, combined phacoemulsification and diagnosis. The outcome measures recorded are intraocular pressure (IOP), glaucoma medications, secondary surgeries, if any, and Kaplan-Meier survival (KMS) curves where success was defined as an IOP less than 21 mmHg, 20% or more reduction in IOP from baseline at the last two consecutive follow-ups after 3 months, and no secondary glaucoma surgery. Results: At 12 months, IOP reduced from preoperative mean of 27.5 ± 10.6 mmHg to 16.1 ± 2.8 mmHg (p<0.01) in Trabectome cases and glaucoma medication was reduced from 2.8 ± 1.0 to 1.6 ± 1.5 (p=0.02) with Kaplan-Meier success rate of 100%. IOP reduced from preoperative mean of 26.4 ± 7.9 mmHg to 13.5 ± 3.7 mmHg (p<0.01) in TDS cases and glaucoma medication was reduced from 3.1 ± 1.2 to 2.1 ± 1.0 (p<0.01) with Kaplan Mayer Success rate of 94%. Conclusions: Both Trabectome and TDS successfully lower IOP and decrease the need for glaucoma medications. Trabectome may be considered a viable alternative to TDS in Japanese patients.

INTRODUCTION Glaucoma refers to a group of diseases with characteristic structural and functional changes that occur over the course of the disease which, untreated, often leads to

M. Maeda, N. Kondo, K. Onuki, R. Noritake — Gifu Red Cross Hospital, Department of Ophthalmology, Gifu, Japan; A. Hasegawa — Social Insurance Chukyo Hospital, Department of Ophthalmology, Aichi, Japan Correspondence to: Dr. Masahira Maeda, Yasuma Eye Clinic, 4-10-50 Osu, Naka-ku, Nagoya, Japan; E-mail: mmaeda.eye@gmail.com The authors have no financial interest in either Trabectome or TDS. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

blindness. Increasing disc cupping and thinning of the nerve fiber layer, especially in the temporal arcades, correlating with retinal ganglion cell loss, are most characteristic. Glaucoma is among the leading causes of blindness worldwide. Increased intraocular pressure (IOP) above tolerable levels is thought to be the main pathophysiological injury.1 Currently available evidence suggests that mechanical injury to axons in the lamina cribrosa best explains acute damage as in angle closure or relatively high IOP cases of open-angle glaucoma (OAG). Chronic ischemia may cause or add injury over the many decades of typical OAG. Hence, treatments for glaucoma are generally directed toward controlling IOP by either pharmaceutical agents or surgery. Surgical procedures for glaucoma treatment include trabeculectomy,2-5 trabeculotomy ab externo,6-10 shunts,3-4 trabeculoplasty,11-12 and others. Glaucoma medications tend to be costly and are known to be associated with unwanted side effects. Hence, a desirable surgical procedure is one that can effectively control IOP and reduce dependency on medications at the same time. Today, trabeculotomy ab externo, usually without deep sclerectomy, is performed primarily on children with developmental glaucoma and can be done even in cases with opaque corneas. Trabeculotomy is thought to enhance aqueous outflow by rupturing through trabecular meshwork, which is believed to be the main initial site of resistance to aqueous outflow. Studies have shown that the rate of successful IOP control is high. Iwao et al reported that trabeculotomy is also effective in cases of steroidinduced glaucoma. Although trabeculotomy is now commonly performed only on children, it has been reported that trabeculotomy is also successful for IOP reduction in adults.6-10 Trabectome® (NeoMedix Corporation, Tustin, CA) is a micro-incisional glaucoma surgery that reduces IOP to the natural physiological level of the mid-teens, as well as reducing dependency on glaucoma medications. Several studies have shown that Trabectome is effective in lowering IOP and in reducing the need for topical glaucoma medications.13-22 The potential advantages of Trabectome compared to ab externo trabeculotomy with or without deep sclerectomy include preservation of the conjunctiva and removal of a

Comparison of the Outcomes of Trabectome with Trabeculotomy with Deep Sclerectomy — Maeda et al

Inclusion Criteria Patients with progressive nerve injury on maximal available or tolerated medications, disc or VF damage, or both, consistent with primary open-angle glaucoma or its variations and open angles (Shaffer grade 1 or above) were included in the study. The criteria also allowed inclusion of patients either with or without prior laser or cataract surgery, or vitrectomy more than six months before surgery. Exclusion Criteria Both procedures: Patients with a history of uveitis and neovascularization of the iris or angle were excluded from the study. Fig. 1 Microscope set up in Trabectome® surgery The microscope is tilted toward the surgeon, and patient’s head is tilted away from the surgeon.

strip of trabecular meshwork that likely prevents re-closure during the healing process. In addition, Trabectome preserves the option for subsequent filtering surgery if necessary. Furthermore, as with trabeculotomy ab externo, it avoids bleb formation and bleb-related complications. Both Trabectome and trabeculotomy ab externo have shown successful IOP control alone and when combined with phacoemulsification.6-10,13-22 Francis et al compared the outcomes of Trabectome with those of trabeculectomy, which is the most frequent and best studied surgical procedure. There is, however, no published data comparing Trabectome with trabeculotomy ab externo. The mechanisms of both procedures for reducing IOP are the same, but each method uses a different approach. The purpose of this study is to compare the efficacy of Trabectome with that of trabeculotomy with deep sclerectomy (TDS) in Japanese patients.

METHODS This is a retrospective, controlled, matched-pair, comparative outcome study of Trabectome and TDS in Japanese patients receiving glaucoma treatment at the Gifu Red Cross Hospital in Japan. All procedures conformed to the Declaration of Helsinki, and all patients received and signed informed consent documents approved by the hospital’s Institutional Review Board. TDS procedures were conducted from October 2005 to November 2011. Trabectome procedures were conducted from April 2009 to March 2012. Primary outcome measures evaluated included intraocular pressure, number of glaucoma medications, and secondary surgeries, if any.

Supplement: Clinical & Surgical Ophthalmology, June 2015

Trabectome procedure: In addition to the above, exclusion criteria for Trabectome patients included: corneal edema due to endothelial decompensation or opacities such as large pterygia preventing a good gonioscopic view; anterior chamber being too shallow; and anatomically confusing angles without clear definition of the scleral spur or meshwork. In addition, the potential risks, benefits, and chances of postoperative complications for both surgical procedures were explained in detail to all patients and they were given the opportunity to accept or decline either procedure. A total of 20 eyes of 16 patients that had undergone TDS were matched to 20 eyes of 19 patients that had undergone Trabectome. Matching criteria were age, if procedure was combined with phacoemulsification, and type of glaucoma. All procedures were performed by a single surgeon (MM). Baseline patient data included age, glaucoma stage, lens status, IOP as measured by applanation tonometry, any surgeries conducted before these procedures, and the number of glaucoma medications. Postoperative measurements included IOP and number of glaucoma medications. The preoperative IOP used was that measured on the day the surgeon recommended the patient for surgery. Trabectome Procedure The Trabectome system has been described in detail in a previous study.22 In brief, a 1.7-mm temporal clear corneal incision was made. The microscope was tilted, eyepieces toward the surgeon, and the patient’s head was tilted away from the surgeon in order to provide the maximum view of the angle (Fig. 1). The tip of the Trabectome handpiece was introduced into the eye and a goniolens was placed on the cornea. The area was irrigated and the tip was advanced into Schlemm’s canal anterior to the scleral spur. The trabecular meshwork was ablated about 60° in one direction, and then about 60° in the other direction, leaving the posterior wall of Schlemm’s canal exposed for approximately 120°.

canal and then rotated. Finally, the external scleral flap and conjunctiva were closed.

Fig. 2 Insertion (left) and rotation (right) of Trabeculotome probe

Both TDS and Trabectome: For all procedures combined with phacoemulsification, cataract removal was followed by IOL implantation in the capsular bag. Following IOL implantation, the anterior chamber was irrigated to remove any remaining viscoelastics as well as any blood reflux or hemorrhage, if present. Patients were examined by the physician at 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months, and every 6 months after surgery. The physician requested additional patient examinations if needed.

STATISTICAL ANALYSIS TDS Procedure First, a limbal incision was made in the inferior conjunctiva. A limbus-based superficial 4 × 3 mm triangular scleral flap of approximately one-third thickness was fashioned, and then a smaller second deep scleral flap was dissected. The base of the second deep flap was dissected such that it opened directly into Schlemm’s canal. This approach renders the canal far more easily identifiable than it would be from the scleral surface. After Schlemm’s canal was identified, the trabeculotomy probe (New trabeculotome probe HS2155B2, HANDAYA, Japan) was inserted into Schlemm’s canal and was advanced by rotating around the axis of the extension part of the arched tip. Care was taken to avoid damaging the iris and lens when breaking through the trabecular meshwork into the anterior chamber (Fig. 2). Care was taken to place the inner part of the probe horizontal to the iris with the outer part of the probe resting on the cornea. The probe was carefully removed and the external scleral flap was closed with one or more sutures using 10-0 nylon. The conjunctiva was sutured using 8-0 vicryl. The anterior chamber was irrigated thoroughly with balanced salt solution to remove as much hemorrhage as possible. Phacoemulsification Procedure Combined with Trabectome: For procedures combining Trabectome with phacoemulsification, the Trabectome procedure was performed first. Following the Trabectome surgery, the corneal incision was enlarged to 3.0 mm for the phacoemulsification procedure. Combined with TDS: For procedures combining TDS and phacoemulsification, the TDS procedure was initiated, Schlemm’s canal was found, and the scleral flap was temporally sutured. Then, the temporal clear corneal incision was made for the phacoemulsification procedure and the cataract removed. After implantation of the intraocular lens (IOL), the TDS procedure was continued. Trabeculotome probes were inserted into Schlemm’s

Wilcoxon-Mann-Whitney test and chi-square test were used to compare attributes of patients in the two groups. Wilcoxon signed rank test was used to compare IOP within each group, and Wilcoxon-Mann-Whitney test was used to compare IOP between groups. Kaplan-Meier survival analysis was used to compare the survival distributions between the two surgical groups. Success was defined as an IOP less than 21 mmHg, 20% or more reduction in IOP from baseline at the last two consecutive follow-ups after 3 months, and no secondary glaucoma surgery.

RESULTS A total of 40 cases were analyzed in this study, with 20 eyes in the TDS group and 20 eyes in the Trabectome group. Postoperative IOP and the number of glaucoma medications were compared to preoperative IOP and the number of glaucoma medications within each group and also between groups. Table I demonstrates the baseline demographics of the subjects. There were no significant between-group differences in any of the baseline characteristics. One case from the TDS group had prior laser trabeculoplasty and another case had prior vitrectomy. In the Trabectome group, one case had prior trabeculectomy. In both groups, the IOP at 12 months was significantly lower than the preoperative IOP and the standard deviation of IOP measurements decreased. Intraocular pressure decreased from 27.5 ± 10.6 mmHg at baseline to 16.1 ± 2.8 mmHg at 12 months in the Trabectome group (p<0.01). In the TDS group, IOP was reduced from 26.4 ± 7.9 mmHg to 13.5 ± 3.7 mmHg at 12 months (p<0.01). When comparing the IOP between these two groups, there was no statistically significant difference at 12 months (p=0.3). Figure 3 (top) shows the trend in mean IOP for Trabectome and TDS. Two patients in the TDS group had paracentesis shortly postoperatively as the result of high IOP.

Comparison of the Outcomes of Trabectome with Trabeculotomy with Deep Sclerectomy — Maeda et al

Table I Baseline characteristics of TDS cases and Trabectome cases 20(19) 62 ± 19 20 to 92 9 11 0.29 ± 0.39 12 2 2 4 1 14 5 5 6 9

Glaucoma Rx

9 11 27.5 ± 10.6 12 to 59

Fig. 3 Trend in mean of IOP (top) and trend in mean glaucoma medications (bottom). Both groups showed statistically significant difference in IOP and medication reductions at 12 months compared to baseline.

2.8 ± 1.0 1 to 4 14.7 ± 12.9

SD: standard deviation IOP: Intraocular pressure logMAR: log of the minimum angle of resolution

In the Trabectome group, the mean number of medications reduced from 2.8 ± 1.0 to 1.6 ± 1.5 (p=0.02). The mean number of medications reduced from 3.1 ± 1.2 to 2.1 ± 1.0 in the TDS group (p<0.01). At 12 months, both groups showed a statistically significant reduction in the mean number of glaucoma medications. When comparing the mean number of glaucoma medications, there was no statistical significant difference between Trabectome and TDS (p=0.9) at 12 months and at any other post-operative time point. Figure 3 (bottom) shows the trend in mean number of medications in the Trabectome and TDS groups. Figure 4 shows the Kaplan-Meier survival curves of the two groups. The success rate at one year was 100% in the Trabectome group and 94% in the TDS group. Log rank test gave a p-value of 0.3, which indicates that there

IOP (mmHg)

20(16) No. of eyes (patients) Age (years) Mean ± SD 62 ± 19 Range 21 to 89 Gender Male 14 Female 6 Visual Acuity (logMAR) 0.32 ± 0.76 Mean ± SD Diagnosis POAG 12 Pseudoexfoliation 4 Steroid 2 Secondary Glaucoma 2 Lens Status Phakic 2 Pseudophakic 14 Aphakic 4 Visual Field Mild 3 Moderate 5 Advanced 12 Combined Surgeries Phaco 9 Trabectome Alone 11 Pre-operative IOP (mmHg) Mean ± SD 26.3 ± 7.9 Range 15 to 40 No. of pre-operative medications Mean ± SD 3.1 ± 1.2 Range 0 to 5 Follow-up (months) Mean ± SD 13.3 ± 14.8

IOP (mmHg)

Trabectome

Mean Number of Medications

TDS

Supplement: Clinical & Surgical Ophthalmology, June 2015

was no significant difference between the two survival curves. A stricter success criterion was applied using IOP less than 18 mmHg, 20% or more IOP reduction, and no secondary glaucoma surgery, but the result remained statistically insignificant. Regarding the outcome measure of secondary surgeries, over the follow-up duration of this study, there were no secondary surgeries in the Trabectome group, and there was only one case of secondary glaucoma surgery in the TDS group. Subgroup analyses were performed comparing Trabectome combined with phacoemulsification (T+P) to TDS with phacoemulsification (TDS+P) and Trabectome only to TDS only. At 6 months, IOP was reduced from 26.6 ± 14.7 mmHg to 14.0 ± 3.1 mmHg in the T+P group (p<0.01) and 24.8 ± 7.4 mmHg to 12.8 ± 4.4 mmHg in TDS+P group (p<0.01). In both groups, the reduction in medications was not statistically significant. No statistically significant difference was found in IOP or medications between T+P and TDS+P at 6 months. In the Trabectome only group, IOP was reduced from 28.3 ± 6.3 mmHg to 15.6 ± 3.9 mmHg (p=0.01) and 27.6 ±

Trabeculotomy vs Trabectome

Survival Time in Months Fig. 4 Kaplan-Meier survival curves for Trabectome® and TDS (log-rank test: p=0.3)

8.5 mmHg to 14.7 ± 3.1 mmHg in TDS only (p<0.01) at 6 months. Glaucoma medications were statistically significantly reduced from 3.3 ± 1.1 to 2.4 ± 1.2 in the TDS only group (p=0.03), but no statistical significant difference was found in medication reduction in the Trabectome only group. IOP and medications showed no statistically significant difference between the Trabectome only versus TDS only groups at 6 months.

DISCUSSION This study compared the efficacy of Trabectome and TDS by analyzing clinical outcomes. Both Trabectome and TDS are effective in lowering IOP and glaucoma medications from baseline. The Trabectome group demonstrated 100% success rate at one year versus 94% in the TDS group. The failure in the TDS group was due to one case of secondary surgery being required. Log rank test suggested that there was no statistically significant difference between the two survival curves. The effectiveness of Trabectome as a surgical option to reduce IOP and glaucoma medication usage has been shown by several studies.5-6,14-22 For example, Jea et al reported a total of 115 patients who underwent Trabectome. The baseline IOP of 28.1 ± 8.6 mmHg was reduced to 17.4 ± 5.9 mmHg and the number of medications was reduced from 3.3 ± 1.3 to 1.8 ± 1.3 at 12 months.2 Ting et al reported 80% success at 12 months in 300 patients with pseudoexfoliation glaucoma, and over 90% success in 249 patients on Trabectome combined with phacoemulsification, where success was defined as IOP less than 21 mmHg, reduced by 20% from baseline IOP and no secondary surgery.22 Mosaed reported on 538 patients undergoing Trabectome only. The mean preoperative IOP of 26.3 ± 7.7 mmHg and mean of 2.88 ± 1.30 glaucoma medications were reduced

to 16.6 ± 4.0 mmHg and 2.1 ± 1.4 glaucoma medications at the one- year point.17 Studies have also reported the effectiveness of trabeculotomy. Mizoguchi et al have shown that trabeculotomy successfully lowered IOP.7 For a total of 51 eyes, IOP was reduced from 23.4 ± 3.6 to 17.8 ± 3.1 mmHg after one year of follow-up. The success rate at one year was approximately 75%. The obvious main advantages of both procedures are IOP control without bleb formation, hence eliminating all complications associated with bleb formation. In this study, no complications were encountered in the Trabectome group. Common complications associated with trabeculotomy include Descemet’s membrane injury, hyphema, IOP spike, cyclo-dissection, and angle recession. In our study, hyphemas were observed in the TDS cases but all were trivial and resolved quickly. Other downsides of TDS include conjunctival injury, the skill required to perform this type of angle surgery, and the time required which is substantially longer than for Trabectome alone. During TDS it is critical to find the scleral spur and Schlemm’s canal which involves anatomic layer-by layer dissection of the outflow system. In addition, rotating the trabeculotomy probe without tilt is the most critical step in performing TDS. If the device is tilted inappropriately, massive injury, including ciliary body disinsertion, vitreous prolapse, and Descemet’s injury may occur. The strengths of this study include close monitoring of the IOP and the number of glaucoma medications in both groups, the 12 months survival analysis using established TVT survival analysis, and that the surgery was performed by a single surgeon. A major difference of this study with previous studies is that this study targeted specifically Japanese patients while previous studies focused on more general patient populations. The limitations of this study include no randomization and short follow up relative to the disease’s natural history. There was no statistically significant difference in IOP between Trabectome and TDS, but post-operative IOP tended to be lower in TDS than with Trabectome. This might be due to the effect of deep sclerectomy. Studies in larger numbers of patients and a longer observation period are needed. The fact that all surgeries were performed by a single surgeon makes the generalization to the larger community of surgeons problematic; however, it removes variability in surgical techniques. Another limitation of this study is that we could not compare the preoperative IOP without medication after washout. The finding that no statistically significant difference was found in IOP and number of medications between groups may be due to the limited sample size and the low power of the analysis. In addition, Bonferroni correction was used to adjust for multiple comparisons and the method itself is conservative.

Comparison of the Outcomes of Trabectome with Trabeculotomy with Deep Sclerectomy — Maeda et al

In summary, both TDS and Trabectome are effective methods to normalize IOP and decrease the number of glaucoma medications. Although both procedures produce effective results for any stage of glaucoma, they are most suitable for the early to moderate stages of glaucoma because the expected postoperative IOP for these procedures is mid-teens, and advanced glaucoma often requires extremely low IOP. Considering that Trabectome is a micro-incisional glaucoma surgery that is minimally invasive, spares the conjunctiva, is easy to learn, and performs comparably to TDS, Trabectome may be a viable alternative to TDS in Japanese patients. â??

REFERENCES 1.

5. 6. 7.

Minckler DS, Bunt AH, Johanson GW. Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey. Invest Ophthalmol Vis Sci 1977; 16: 426-441. Jea SY, Francis BA, Vakili G, et al. Ab interno trabeculectomy versus trabeculectomy for open-angle glaucoma. Ophthalmology 2012; 119: 36-42. Gedde SJ, Herndon LW, Brandt JD, et al. Surgical complications in the Tube Versus Trabeculectomy Study during the first year of follow-up. Am J Ophthalmol 2007; 143: 23-31. Gedde SJ, Herndon LW, Brandt JD, et al. Three-year follow-up of the Tube versus Trabeculectomy Study. Am J Ophthalmol 2009; 148: 670-684. Vizzeri G, Weinreb RN. Cataract surgery and glaucoma. Curr Opin Ophthalmol 2010; 21: 20-24. Godfrey DG, Fellman RL, Neelakantan A. Canal surgery in adult glaucomas. Curr Opin Ophthalmol 2009; 20: 116-121. Mizoguchi T, Nagata M, Matsumura M, et al. Surgical effects of combined trabeculotomy and sinusotomy compared to trabeculotomy alone. Acta Ophthalmol Scand 2000; 78: 191-195. Iwao K, Inatani M, Tanihara H, et al. Success rates of trabeculotomy for steroid-induced glaucoma: A Comparative, Multicenter, Retrospective Cohort Study. Am J Ophthalmol 2011; 152: 503. Garg A, Alio J. Surgical techniques in ophthalmology: pediatric ophthalmic surgery. Delhi: Jaypee Brothers Medical Publishers 2011: 171-180.

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10. LĂźke C, Dietlein T, et al. Phaco-trabeculotomy combined with deep sclerectomy, a new technique in combined cataract and glaucoma surgery complication profile. Acta Ophthalmol Scand 2007; 85: 143-148. 11. Francis BA, Chopra V, Traudt B, Enright J, et al. Selective Laser trabeculoplasty after failed trabeculectomy in Open Angle Glaucoma. J Clin Exp Ophthalmol 2011; 2: 176. 12. El Mallah MK, Walsh MM, Stinnett SS, et al. Selective laser trabeculoplasty reduces mean IOP and IOP variation in normal tension glaucoma patients. Clin Ophthalmol 2010; 4: 889-893. 13. Francis BA, See RF, Rao NA, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma 2006; 15: 68-73. 14. Minckler DS, Mosaed S, Dustin L, Francis BA. Trabectome (trabeculectomy-internal approach): additional experience and extended follow-up. Trans Am Ophthalmol Soc 2008; 106: 149-160. 15. Minckler DS, Baerveldt G, Alfaro MR, Francis BA. Clinical results with the Trabectome for treatment of open angle glaucoma. Ophthalmology 2005; 112: 962-967. 16. Liu J, Jung J, Francis BA. Ab interno trabeculotomy: Trabectome surgical treatment for open-angle glaucoma. Expert Rev Ophthalmol 2009; 4: 119-128. 17. Mosaed S, Rhee D, Filipopoulous T, et al. Trabectome outcomes in adult open-angle glaucoma patients: one-year follow-up. Clinical & Surgical Ophthalmology 2010; 28(8/9): 182-186. 18. Vold S. Impact of preoperative intraocular pressure on Trabectome outcomes: a prospective, non-randomized, observational, comparative cohort outcome study. Clinical & Surgical Ophthalmology 2010; 28(12): 270-276. 19. Francis BA, Minckler D, Dustin L, et al. Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: initial results. J Cataract Refract Surg 2008; 34: 1096-1103. 20. Mosaed S. Ab interno trabeculotomy with the Trabectome surgical device. Techniques in Ophthalmology 2007; 5: 63-66. 21. 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. 22. Ting J, Damji K and Stiles M. Ab interno trabeculectomy: Outcomes in exfoliation versus primary open-angle glaucoma. J Cataract Refract Surg 2012; 38: 315-323.

Combined Trabectome and Cataract Surgery versus Combined Trabeculectomy and Cataract Surgery in Open-Angle Glaucoma Brian A. Francis, MD, MS; Jonathan Winarko, MD

ABSTRACT

INTRODUCTION

Purpose: To compare the intraocular pressure (IOP)-lowering effect of Trabectome combined with phacoemulsification cataract extraction (PCE) and trabeculectomy combined with PCE. Methods: This is a prospective, non-randomized, comparative trial of 112 patients. There were 89 eyes in the Trabectome+PCE group and 23 eyes in the Trabeculectomy+PCE group with a minimum follow-up of 1 year. The main outcome measures were intraocular pressure (IOP) and complications, and glaucoma medications were tabulated. Results: Trabectome+PCE: The mean IOP was 22.1±5.5 mmHg (n=89) preoperatively and reduced by 27% to 15.4+3.1 mmHg at 1 year (p<0.01). Subsequent secondary glaucoma procedures were performed in 4 (4%) patients by the end of 1 year. Trabeculectomy+PCE: The mean IOP preoperatively was 23.0±10.7 mmHg (n=23) and reduced by 44% to 11.0±5.7 mmHg at 1 year (p<0.01). Subsequent procedures were performed in 3 (13%) patients. Conclusions: The reduction in IOP in both the Trabeculectomy+PCE and Trabectome+PCE groups was significant at 1 year. Applying the success criteria of the Tube vs. Trabeculectomy Study, there was no significant difference in success at 1 year between the groups. Although IOP reduction was greater at 1year in the Trabeculectomy+PCE group, the incidence of postoperative complications and surgical reintervention was also higher in this group. Trabectome+PCE are a viable alternative to Trabeculectomy+PCE due to its favorable risk profile. Data suggests that patients requiring very low target IOP may still benefit from Trabeculectomy+PCE.

Open-angle glaucoma (OAG) is prevalent throughout the world in approximately 33 million people.1 It is a slow, progressive disease which ultimately leads to blindness if appropriate therapy is not administered. The intraocular pressure (IOP) is the major treatable risk factor for OAG.2 Lowering of IOP has been shown in randomized trials to decrease the rate of progression of glaucoma in patients ranging from ocular hypertensive to advanced disease and in high pressure glaucoma as well as normal tension glaucoma.3-6 The traditional treatment paradigm in the United States has been medical therapy first, followed by laser trabeculoplasty, with filtering surgery as a last resort. Trabeculectomy and aqueous tube shunt have been the gold standard surgical approaches to control IOP in glaucoma patients. These procedures involve external filtration, or the passage of aqueous humor from the inside of the eye to an extraocular site (conjunctival bleb) and then into the vascular system. Because of this, these procedures carry the risks related to hypotony, choroidal effusion and hemorrhage, conjunctival scarring, and late-onset endophthalmitis.7-18 The advent of newer, internal filtering surgical techniques such as canaloplasty (iScience, Menlo Park CA), trabecular stent (iStent; Glaukos, Laguna Hills, CA) and trabeculotomy by internal approach (Trabectome; Neomedix, Tustin, CA) has supported the concept of earlier surgical intervention in glaucoma. These procedures, in contrast to trabeculectomy and aqueous tube shunt, rely on the augmentation of the trabecular outflow pathway without the need for external drainage of aqueous. Therefore, many of the complications of external filtering procedures are reduced or eliminated. One of the frequent indications for internal filtering surgery is in cases of combined cataract and glaucoma surgery. These procedures are offered to patients with visually significant cataract and glaucoma in order to reduce high IOP, or to reduce dependence on glaucoma medications if IOP is controlled medically. The published results on Trabectome combined with cataract extraction indicate that this procedure reduces IOP and medication usage in its patients with a favorable complication rate compared to what is traditionally seen with trabeculectomy.19-27

B.A. Francis, J. Winarko — Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA Correspondence to: Dr. Brian Francis, 1450 San Pablo Street, DEI 4804, Los Angeles, CA 90033; E-mail: bfrancis@usc.edu Dr. Francis is a consultant for Neomedix, Inc, the manufacturers of the Trabectome

Trabectome+PCE versus Trabeculectomy+PCE — Francis, Winarko

The purpose of this study is to compare the safety and efficacy of Trabectome combined with PCE versus trabeculectomy combined with PCE. To our knowledge, this is the first such report comparing combined Trabectome and PCE with any other surgical technique.

PATIENTS AND METHODS One hundred and twelve participants were recruited from patients attending the glaucoma service between January, 2007 and January, 2009 at the Doheny Eye Institute, Keck School of Medicine, University of Southern California. Participants were patients who underwent trabeculectomy with mitomycin-C combined with phacoemulsification cataract extraction (PCE) or trabeculotomy internal approach (Trabectome) combined with PCE. All procedures were performed by a single surgeon (BAF). The Institutional Review Board at the University of Southern California approved the study protocol, and all study procedures conformed to the Health Insurance Portability and Accountability Act and the Declaration of Helsinki for research involving human participants. All participants had provided written consent prior to their respective procedures. Inclusion criteria were patients who had undergone either Trabectome or trabeculectomy combined with PCE with a minimum of 12-months follow-up and diagnosis of primary open-angle glaucoma, exfoliation glaucoma, pigmentary glaucoma, or chronic angle-closure glaucoma. Exclusion criteria were a diagnosis of neovascular glaucoma, uveitic glaucoma or pediatric glaucoma, concurrent surgical procedure other than those studied, prior glaucoma surgery except laser trabeculoplasty, or corneal pathology preventing a view of the angle during surgery (in case of Trabectome), or preventing accurate applanation tonometry measurements. Preoperative characteristics including age, gender, lens status, intraocular pressure, and number of glaucoma medications were noted. The type of surgery to be performed was determined by the treating physician. Postoperative measurements including visual acuity (VA), intraocular pressure (IOP), hypotony (IOP â&#x2030;¤ 5 mmHg), presence of choroidal effusions or hemorrhage, presence of wound leak, presence of infection, surgical re-intervention, number of glaucoma medications, and bleb formation were collected at postoperative intervals of 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months, and 12 months. In the case of trabeculectomy, laser suture lysis was not considered a postoperative surgical intervention. The surgical technique employed for patients undergoing the Trabectome procedure was consistent with those previously published.19,23,24 In brief, surgical steps for the Trabectome procedure combined with PCE are as follows: after topical antibiotic and anti-inflammatory drops are instilled in the eye, anesthesia is then obtained with peribulbar, retrobulbar or topical approaches.

Supplement: Clinical & Surgical Ophthalmology, June 2015

A 1.7 mm temporal clear corneal incision is performed with a keratome, followed by injection of viscoelastic into the anterior chamber. A surgical goniolens is placed on the cornea and the angle view is verified. The goniolens is removed, and the tip of the Trabectome handpiece is then introduced into the eye. The goniolens is replaced and continuous irrigation is activated. The Trabectome tip is advanced across the anterior chamber and inserted through trabecular meshwork into Schlemmâ&#x20AC;&#x2122;s canal just anterior to the scleral spur. The trabecular meshwork is then ablated for approximately two clock hours in a counter-clockwise direction, then one to two clock hours in the clockwise direction. Once the trabectome procedure is completed, phacoemulsification is performed in the following manner. A paracentesis port is created and a viscoelastic is injected into the anterior chamber. The initial trabectome corneal incision is then enlarged using a 2.4 to 2.7 mm keratome to create a biplanar clear corneal incision. The cystotome needle and Utrata forceps are then used to create a curvilinear continuous capsulorrhexis. The cataract is hydrodissected within the capsular bag with balanced salt solution. The phacoemulsification handpiece is introduced into the eye and then the cataract is emulsified. The residual cortex is removed with the irrigation/aspiration handpiece. Viscoelastic is then injected into the capsular bag and an intraocular lens is injected into the capsular bag. The residual viscoelastic is removed with the aspiration/irrigation handpiece and the main wound is secured with one 10-0 nylon or vicryl suture. In brief, surgical steps for trabeculectomy combined with PCE are as follows. After topical antibiotic and antiinflammatory drops are instilled in the eye, anesthesia is then obtained with peribulbar, retrobulbar or topical approaches. A 7-0 vicryl suture is passed through the superior peripheral cornea as a traction suture and the eye is rotated inferiorly to reveal the superior conjunctiva. A fornix-based or limbus-based conjunctival flap is then created. A scleral flap is marked with a super sharp blade, and a half thickness scleral flap is dissected anteriorly into the peripheral cornea with a 67 blade. Instrument wipe sponges are soaked in mitomycin-C in a concentration of 0.25 to 0.4 mg/ml and placed under the scleral flap and in the subconjunctival space for 2 to 4 minutes. After this time, the sponges are removed and the area is profusely irrigated with balanced salt solution. The microscope is then rotated to approach the eye from the temporal side to perform the cataract extraction in a manner consistent with the above detailed procedure. After PCE, the microscope is again rotated to the original position, and a super sharp blade is used to enter the anterior chamber. The Kelly punch is then used to create the trabeculectomy ostium. Vannas scissors are used to create the peripheral iridectomy. The scleral flap is closed with 10-0 nylon

Table I Demographics of patients who underwent Trabectome+PCE or Trabeculectomy+PCE 1 year follow-up

Gender Age Preoperative IOP

Male Female Mean±st dev Mean±st dev

Trabectome+PCE (n=89)

Trabeculectomy+PCE (n=23)

29 60 76±10 22.1±5.5

10 13 79±7 23.0±10.7

0.3 (chi-sq test) 0.2 (t-test) 0.6 (t-test)

Table II IOP levels before and after surgery Trabectome+PCE Preoperative 1 day 1 week 2 weeks 1 month 3 months 6 months 12 months

22.1±5.5 18.0±8.1 (<0.01)* 16.2±5.2 (<0.01)* 16.0±4.8 (<0.01)* 16.0±4.8 (<0.01)* 15.5±3.9 (<0.01)* 15.6±3.3 (<0.01)* 15.4±3.1 (<0.01)*

Trabeculectomy+PCE 89 89 89 89 89 89 87 85

23.0±10.7 20.9±11.6 (0.5)* 17.3±11.6 (0.09)* 11.4±8.5 (<0.01)* 10.6±5.4 (<0.01)* 9.2±4.1 (<0.01)* 8.9±3.0 (<0.01)* 11.0±5.7 (<0.01)*

p value between surgery groups 23 23 23 23 22 21 21 20

0.6 0.17 0.5 <0.01 <0.01 <0.01 <0.01 <0.01

* is p value comparing each postoperative IOP with preoperative IOP within same surgery group.

Fig. 1 Trend in IOP in Trabectome+PCE group

Fig. 2 Trend in IOP in Trabeculectomy+PCE group

sutures, and the knots are rotated into the sclera. The overlying conjunctival and tenons tissue are then reapposed using 8-0 vicryl suture on a vascular needle. Mild pressure on the flap is applied to elevate a bleb, and the wound surface is checked for watertight closure with a fluorescein strip. Statistical analysis included unpaired t-tests between the intraocular pressures in the two surgical groups at each postoperative time period. Chi-square test and two tailed z test was also used to compare attributes of patients in the two groups. Survival analysis is based on the

success criterion in which success is defined IOP <21 mmHg and IOP >5 mmHg and IOP reduced by 20% in the last two consecutive visits three months after surgery without the need for additional surgery.

RESULTS One hundred and twelve eyes of 112 patients met inclusion criteria and were included in the study. There were 89 patients in the Trabectome+PCE group and 23 eyes in the Trabeculectomy+PCE group.

Trabectome+PCE versus Trabeculectomy+PCE — Francis, Winarko

Table III Postoperative observations

Hypotony at postoperative day 1 (IOP <5 mmHg) Sustained hypotony 1 month postoperative (1 day IOP) – (preoperative IOP) ≥10 mmHg Surgical reintervention (within 12 months after surgery) Trabeculectomy Vitrectomy Aqueous tube shunt Ptosis repair BRVO Aqueous misdirection Revision of trabeculectomy YAG capsulotomy Infection Choroidal detachment Choroidal drainage Wound leaks Choroidal hemorrhage Visual acuity decrease (>2 lines from baseline)

Trabectome+PCE (n=89)

Trabeculectomy+PCE (n=23)

p value

3 (13%)

<0.01

4 (17%)

<0.01

4 (4%)

4 (17%)

0.03

4 (4%)

3 (13%)

0.13

2 0 2 0 0 0 0 0 0 0 0 0 0 0

0 1 2 2 (9%) 1 (4%) 1 (4%) 3 (13%) 3 (13%) 0 2 (9%) 1 (4%) 0 0 0

Table I demonstrates the baseline demographics of the subjects. The percentage of male patients in the Trabectome+PCE group was 32.5% and in the Trabeculectomy+PCE group was 43.5%. There was no significant difference in the gender, mean age, or preoperative IOP between the two groups. Table II summarizes the pre- and postoperative IOPs for both of the study groups, and this data is presented graphically for each respective study group in Figures 1 and 2. The IOP at each postoperative follow-up interval was significantly lower than preoperative IOP in both groups. There was a significant difference between the IOP’s in the two groups after the one week follow-up interval. As indicated in Table II, after the postoperative week one follow-up, the Trabeculectomy+PCE group had a significantly lower IOP as compared to the Trabectome+PCE group at all subsequent time intervals. At 12 months, the average IOP in the Trabectome+PCE group was 15.4±3.1 while the mean IOP in the Trabeculectomy+PCE group was 11.0±5.7 mmHg. Table III summarizes the postoperative observations and complications. There were no cases of hypotony (IOP <5 mmHg) in the Trabectome+PCE group either in the immediate postoperative period or at the 1 month postoperative period. In contrast, in the Trabeculectomy+PCE

Supplement: Clinical & Surgical Ophthalmology, June 2015

<0.01 0.05 0.05 <0.01 <0.01 <0.01 0.05

group, 13% of cases had hypotony 1 day postoperatively and 17% had persistent hypotony at the one month follow up. In the Trabectome+PCE group, 4 patients (4%) experienced a postoperative day 1 IOP elevation of greater than or equal to 10 mmHg above baseline, compared to 4 patients (17%) in the Trabeculectomy+PCE group. The surgical re-intervention rate within 1 year of the initial procedure was 4% in the Trabectome+PCE group and 13% in the Trabeculectomy+PCE group. The main secondary surgery was aqueous tube shunt implantation in both the groups. The trend in the mean number of medications required in both study groups is shown in Figures 3 and 4. In both groups, there was a significant reduction in number of medications required for IOP control after each respective procedure. In the Trabectome+PCE group, mean number of medications was reduced from 2.3 medications preoperatively to approximately 1.3 medications postoperatively. In the Trabeculectomy+PCE group, the mean number of medications was reduced from 3.2 medications preoperatively to approximately 0.6 medications postoperatively. The survival curves of the two groups are illustrated in Figure 5. At twelve months, the success in the Trabectome+PCE group is 95% compared with the success in the Trabeculectomy+PCE

Fig. 3 Trend in glaucoma medications in Trabectome+PCE group

Fig. 4 Trend in glaucoma medications in Trabeculectomy+PCE group

“# Meds Baseline” is the overall average preoperative medications of 89 patients before Trabectome combined with cataract extraction.

“# Meds Baseline” is the overall average preoperative medications of 23 patients before Trabeculectomy combined with cataract extraction.

Fig. 5 Survival curves comparing the two groups Survival curves of Trabectome+PCE and Trabeculectomy+PCE procedures. Success = No secondary surgery and IOP <21 mmHg and IOP >5 mmHg and IOP reduced by 20% in last two consecutive visits 3 months after surgery. Log rank test gives p=0.1

group of 83%. The log rank test for the overall success in the two groups gives p=0.1 and this indicates no significant difference in the survival curves of the two groups.

DISCUSSION Given that the presence of cataract is a common co-existing condition in patients afflicted with glaucoma, there is a need for safe and effective combined glaucoma and cataract surgical procedures. Combined Trabeculectomy+PCE have been shown to yield

significant lowering of IOP.28-29 However, previous studies have repeatedly shown that complications after trabeculectomy, such as wound leaks, hypotony, blebitis, and endophthalmitis, occur at significant rates and can be associated with permanent visual disability.30-33 Theoretically, Trabectome glaucoma surgery combines well with cataract extraction. The procedure requires limited additional operating time and can be performed through the same surgical incision as phacoemulsification cataract extraction. Serious bleb-related complications such as those seen with trabeculectomy are avoided due to the lack of external filtration. Given that Trabectome does not require the use of antifibrotic agents, risks associated with the use of mitomycin-C and 5-fluorouracil are eliminated. Lastly, trabeculotomy with the Trabectome allows for future standard filtering procedures if necessary as the Trabectome procedure completely spares the conjunctiva. Our study analyzed clinical outcomes related to combined Trabectome+PCE and Trabeculectomy+PCE over a 12-month follow up period. This is the first study to compare these two combined procedures in a prospective manner. Our findings suggest that both Trabectome combined with PCE and trabeculectomy combined with PCE can result in a significant reduction in IOP as well as a reduction in glaucoma medications required for IOP control. With regards to IOP reduction, the Trabeculectomy+PCE group had a significantly lower IOP as compared to the Trabectome+PCE group at the 2 week, 1 month, 3 month, 6 month, and 12 month time intervals. In both groups, the mean number of

Trabectome+PCE versus Trabeculectomy+PCE — Francis, Winarko

postoperative medications required for IOP control was significantly reduced compared to the number of preoperative medications but with a higher mean in the Trabectome+PCE group. In terms of complications, the Trabeculectomy+PCE group had a higher incidence of postoperative hypotony compared to the Trabectome+PCE group which had no occurrences of post-procedure hypotony. In our study, the Trabeculectomy+PCE group also had a higher percentage of patients with transient IOP spike of 10 mmHg or greater. Furthermore, patients in the Trabeculectomy+PCE group had a higher surgical re-intervention rate at 13% compared with 4% in the Trabectome+PCE group. Some of these results were counter to what we hypothesized prior to the study. We had expected greater incidence of IOP spike after Trabectome+PCE than Trabeculectomy+PCE. Our results may have differed with a different surgical technique involving more aqueous flow at the time of trabeculectomy surgery, but this may also increase the hypotony rate. With regards to the success rate, there was no statistically significant difference between the two groups, despite lower mean IOP in the Trabeculectomy+PCE group. We used the success criteria developed in the Tube versus Trabeculectomy Study.34 Had we used more stringent criteria; for example IOP less than or equal to 18 mmHg and 30% reduction, there may have been a difference seen between the two groups. Several studies have indicated that the major concern after filtering surgeries is vision threatening complications such as hyphema, choroidal effusion, hemorrhage or bleb infection.7-18 However, in our study, no patients in either group experienced postoperative infection, choroidal hemorrhage, wound leak, or significant decrease in visual acuity. With larger groups and longer follow up, it may be more likely to see these types of complications. In this study, there were 4 cases that had persistent hypotony several months after trabeculectomy. Eyelid ptosis repair was done in two patients. One patient had a branch retinal vein occlusion one month after Trabeculectomy+PCE. In one patient, several postoperative complications set in, beginning with aqueous misdirection after Laser Suturelysis, then choroidal detachment, then trabeculectomy revision for bleb removal for hypotony 10 months postoperative, followed by Ahmed implant at 11 months postoperative (Table III). Combined Trabeculectomy+PCE has been previously reported to provide a significant reduction in IOP. In a retrospective study, Caporossi et al reported a reduction of IOP from a preoperative mean of 24.06 mmHg to 15.36 mmHg at 1 year of follow up using a single site phacoemulsification technique combined with trabeculectomy without the use of antimetabolites.35 Studies have shown that the intraoperative use of antimetabolites such

Supplement: Clinical & Surgical Ophthalmology, June 2015

as mitomycin-C increases the success rate of filtration surgeries.36 A study by Buys et al employed a 2 site phacotrabeculectomy technique with mitomycin-C similar to our technique and reported a reduction in IOP from a preoperative mean of 17.6 to a postoperative mean of 12.7 at 1 year of follow up.37 The IOP reduction following Trabeculectomy+PCE in our study are generally consistent with the results seen in these previous studies. Combined Trabectome+PCE have also been shown to result in significant IOP reduction. Minckler et al reported that for 45 patients undergoing Trabectome+PCE, baseline IOP of 20.0±6.2 mmHg decreased at 12 months to 15.9±3.3 mmHg (18%) and medications decreased from 2.63±1.12 to 1.50±1.36.22 Francis et al reported that for patients undergoing combined Trabectome+PCE, the mean preoperative IOP of 20.0 mmHg ± 6.3 and mean of 2.65±1.13 glaucoma medications were reduced to a mean postoperative IOP of 15.5 mmHg±2.9 on a mean of 1.44±1.29 glaucoma medications at 1 year of follow up.23 The findings in regards to the Trabectome+PCE group in our study are again generally consistent with the findings of these previous studies. The strengths of this study include close monitoring of IOP, medications, and complications in a prospective fashion of the two groups. This study also has important limitations. The sample size in the Trabeculectomy+PCE group was small, and therefore may not be adequately powered to detect subtle findings especially in the category of postoperative complications. Additionally, the study was non-randomized, making it susceptible to selection bias. The follow up in this series was generally short term, and future studies would ideally include longer term results. Furthermore, all procedures were performed by a single surgeon, which makes the procedures more uniform, but also may limit its generalizability to the surgical community as a whole. The primary goal of any glaucoma surgery is to reduce IOP with the lowest requirement for adjunctive glaucoma medications while providing the minimal risk for complications. In summary, our data suggests that both Trabeculectomy+PCE and Trabectome+PCE are effective methods to significantly lower IOP and to reduce patient medication requirements. Applying the same success criteria developed in the Tube versus Trabeculectomy Study, there was no significant difference in overall success between the two groups. For up to 12 months of follow-up, Trabeculectomy+PCE appear to result in a greater reduction in IOP with a lower medication requirement as compared to Trabectome+PCE. Yet, Trabeculectomy+PCE also have a higher complication and surgical re-intervention rate as compared to Trabectome+PCE. Due to its favorable risk profile, Trabectome+PCE is a viable alternative to Trabeculectomy+PCE in patients with visually significant

cataract and glaucoma seeking lower IOP and decreased dependence on glaucoma medications. Patients requiring very low target IOP may still benefit from combined trabeculectomy and cataract extraction, despite the possible increased risk. ❏

REFERENCES 1. 2.

10. 11.

12.

13. 14. 15.

16. 17.

18.

HA Quigley. Number of people with glaucoma world wide. Br J Ophthalmol 1996; 80: 389-393. Le A, Bickol NM, et al. Risk factors associated with the incidence of open-angle glaucoma: the visual impairment project. Invest Ophthalmol Vis Sci 2003; 44(9): 3783-3789. Gordon MO, Beiser JA, Brandt JD, et al. The ocular hypertension treatment study (OHTS): baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120: 714-720. Heijl A, Leske MC, Bengtsson B et al. Early manifest glaucoma trial group (EMGTS): reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol 2002; 120(10): 1268-1279. The AGIS Investigators: The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000; 130: 429-440. Collaborative Normal-Tension Glaucoma Study Group (CNTGS). The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol 1998; 126: 498-505. Watson PG, Jakeman C, Ozturk M et al. The complications of trabeculectomy (a 20 year follow-up). Eye (Lond) 1990; 4 pt(3): 425-438. Kao SF, Lichter PR, Musch DC. Anterior chamber depth following filtration surgery. Ophthalmic Surg 1989; 20(5): 332-336. Stewart WC, Shields MB. Management of anterior chamber depth after trabeculectomy. Am J Ophthalmol 1988; 106: 41-44. Brubaker RF, Pederson JE. Ciliochoroidal detachment. Surv Ophthalmol 1983; 27: 281-289. Gressel MG, Parrish RK II, Heuer DK. Delayed nonexpulsive suprachoroidal hemorrhage. Arch Ophthalmol 1984; 102: 1757-1760. Ruderman JM, Harbin TS Jr, Campbell DG. Postoperative suprachoroidal hemorrhage following filtration procedures. Arch Ophthalmol 1986; 104: 201-205. Freedman J, Gupta M, Bunke A. Endophthalmitis after trabeculectomy. Arch Ophthalmol 1978; 96: 1017-1018. Zaidi AA. Trabeculectomy: a review and 4-year follow-up. Br J Ophthalmol 1980; 64: 436-439. Akafo SK, Goulstine DB, Rosenthal AR. Long-term post trabeculectomy intraocular pressures. Acta Ophthalmol (Copenh) 1992; 70: 312-316. Mills KB. Trabeculectomy: a retrospective long-term follow-up of 444 cases. Br J Ophthalmol 1981; 65: 790-795. Molteno AC, Bosma NJ, Kittelson JM. Otago glaucoma surgery outcome study: long-term results of trabeculectomy – 1976 to 1995. Ophthalmology 1999; 106: 1742-1750. D’Ermo F, Bonomi NJ, Kittelson JM. A critical analysis of the long-term results of trabeculectomy. Am J Ophthalmol 1979; 88: 829-835.

19. Francis BA, See RF, Rao NA, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma 2006; 15: 68-73. 20. Minckler DS, Baerveldt G, Alfaro MR, et al. Clinical results with the Trabectome for treatment of open-angle glaucoma. Ophthalmology 2005; 112: 962-967. 21. 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. Available at: http://www.aosonline.org/ xactions/2006/1545-6110_ v104_p040.pdf 22. Minckler D, Mosaed S, Dustin L, Francis B, and the Trabectome Study Group. Trabectome (Trabeculectomyinternal approach): additional experience and extended follow-up. Trans Am Ophthalmol Soc 2008; 106: 149-160. 23. Francis BA, Minckler D, Dustin L, et al. Trabectome study group combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and openangle glaucoma: initial results. J Cataract Refract Surg 2008; 34(7): 1096-1103. 24. Liu J, Jung J, Francis BA. Ab interno trabeculotomy: Trabectome surgical treatment for open-angle glaucoma. Expert Rev Ophthalmol 2009; 4(2): 119-128. 25. Mosaed S. Ab Interno trabeculotomy with the Trabectome surgical device. Techniques in Ophthalmology 2007; 5(2): 63-66. 26. Gunderson E. Trabeculotomy Ab Interno, using the Trabectome: a promising treatment for patients with openangle glaucoma. Insight 2008; 33(1): 13-15. 27. Godfrey DG, Fellman RL, Neelakantan A. Canal surgery in adult glaucomas. Curr Opin Ophthalmol 2009; 20(2): 116-121. Review. 28. Friedman DS, Jampel HD, Lubomski LH, et al. Surgical strategies for coexisting glaucoma and cataract: an evidence based update. Ophthalmology 2002; 109: 1902-1913. 29. Jampel HD, Friedman DS, Lubomski LH, et al. Effect of technique on intraocular pressure after combined cataract and glaucoma surgery: an evidence-based review. Ophthalmology 2002; 109: 2215–2224. 30. Bindish R, Condon GP, Schlosser JD, et al. Efficacy and safety of mitomycin-C in primary trabeculectomy; fiveyear follow-up. Ophthalmology 2002; 109: 1336-1341. 31. Song A, Scott IU, Flynn Jr. HW, et al. Delayed-onset bleb-associated endophthalmitis; clinical features and visual acuity outcomes. Ophthalmology 2002; 109: 985-991. 32. Soltau JB, Rothman RF, Budenz DL, et al. Risk factors for glaucoma filtering bleb infections. Arch Ophthalmol 2000; 118: 338-342. 33. DeBry PW, Perkins TW, Heatley G, et al. Incidence of lateonset bleb-related complications following trabeculectomy with mitomycin. Arch Ophthalmol 2002; 120: 297-300. 34. Gedde SJ, Schiffman JC, Feuer WJ etal. Three-year followup of the tube versus trabeculectomy study. Am J Ophthalmol 2009; 148(5): 670-684. Epub 2009 Aug 11. 35. Caporossi A, Casprini F, Tosi GM, et al. Long-term results of combined 1-way phacoemulsification, intraocular lens implantation, and trabeculectomy. J Cataract Refract Surg 1999; 25: 1641-1645. 36. Wilkins M, Indar A, Wormald R. Intra-operative mitomycin C for glaucoma surgery. Cochrane Database Syst Rev 2005;(4):CD002897. 37. Buys YM, Chipman ML, Zack B, et al. Prospective randomized comparison of one-versus two site phacotrabeculectomy two-year results. Ophthalmology 2008; 115(7): 1130-1133.

Trabectome+PCE versus Trabeculectomy+PCE — Francis, Winarko

Combined Cataract Extraction and Trabeculotomy by the Internal Approach for Coexisting Cataract and Open-Angle Glaucoma Seyed Javad Hashemian, MD; Arezoo Miraftabi, MD; Mohammad Ebrahim Jafari, MD; Mohsen Rezaei Hemami ABSTRACT Purpose: To provide efficacy and safety of Trabectome combined with phacoemulsification in primary openangle glaucoma. Methods: Thirty consecutive eyes that have had combined phacoemulsification with Trabectome were included. The main outcome measures were change in intraocular pressure (IOP), glaucoma medication use and complications. Results: Mean IOP was 18.25±3.28 mmHg preoperatively which decreased to 13.50± 2.53 mmHg at 1 year (P<0.05). There was a corresponding drop in glaucoma medications from 2.52±0.60 at baseline to 1.40±0.53 at 12 months (P<0.01). The preoperative BCVA (LogMar) was improved from 0.68±0.26 preoperatively to 0.26±0.19, 0.18±0.13, 0.17±0.13, 0.11±0.12, at 5 days and 2, 6, 12 months, respectively (P<0.01). The only frequent complication was transient blood reflux resolving spontaneously within a few days. No vision threatening complication occurred. Conclusion: Combined phacoemulsification and Trabectome significantly lowered IOP and medication use, with early visual rehabilitation in the majority of patients.

INTRODUCTION Glaucoma is the second most common cause of irreversible blindness worldwide.1 Many patients with glaucoma have concurrent cataracts. Some studies suggest that glaucoma itself is a risk factor for cataract development.2-4 They are often comorbidities that need to be managed by ophthalmologists. S. Hashemian — Assistant Professor, Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran; A. Miraftabi — Assistant Professor, Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran; M.E. Jafari — Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran; M.R. Hemami — Eye Research Center, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran Correspondence to: Dr. Arezoo Miraftabi, Eye Research Center, Rassoul Akram Hospital, Niayesh Ave, Sattarkhan St, Tehran, Iran; E-mail:arezoomiraftabi@yahoo.com The authors have no conflict of interest with any materials or products mentioned in this article. No financial support was received for this article.

Supplement: Clinical & Surgical Ophthalmology, June 2015

The benefits of combined cataract and glaucoma surgeries include possible elimination or at least reduction of glaucoma medications in glaucoma patients who desire cataract surgery but who are on multiple glaucoma medications.5,6 Phacotrabeculectomy is considered the “treatment of choice” in patients with open-angle glaucoma and cataract; however, it is associated with postoperative complications such as hypotony, choroidal effusions, suprachoroidal hemorrhages and endophthalmitis.7,8 Phacotrabeculectomy patients need intensive postoperative management even without complications.9 Combination of phacoemulsification (phaco) with an established contemporary surgical technique such as Trabectome (NeoMedix Corp., Tustin, CA) or canaloplasty may result in a lower rate of complications.10-12 These procedures, in contrast to trabeculectomy and aqueous tube shunt, rely on the augmentation of the trabecular outflow pathway without the need for external drainage of aqueous.13 Therefore, many complications associated with external filtering procedures are reduced or eliminated. Combined phaco-Trabectome has the advantage of preserving conjunctiva by performing an ab-interno trabeculotomy using electro-ablation of the meshwork and inner wall of Schlemm’s canal with continuous aspiration of tissue debris.12 The purpose of this study is to evaluate results of combined phaco and Trabectome on intraocular pressure of patients with primary open-angle glaucoma and cataract.

PATIENTS AND METHODS A consecutive series of 28 patients (30 eyes) with uncontrolled open-angle glaucoma and cataract had combined phacoemulsification and trabeculotomy by the internal approach at the Department of Ophthalmology, Iran University of Medical Sciences. Patients were in the planned phacoemulsification and trabeculotomy ab-interno group if they had cataract and mild to moderate primary open-angle glaucoma with uncontrolled IOP while receiving maximum tolerable anti-glaucomatous therapy. The target IOP was determined by the treating glaucoma specialist before the intervention according to standardized criteria such as optic nerve cupping and retinal nerve fiber layer loss, visual field loss, and clinical

course. Patients with a history of previous ocular surgery or corneal opacity that impaired angle visualization were excluded. Possible alternatives, beneficial effects, and potential complications of the surgical procedure were explained in detail to all patients. Written informed consent was obtained from all participants. Study was in adherence to the tenets of the Declaration of Helsinki. Before surgical intervention, all patients had baseline examinations including measurements of best-corrected visual acuity, visual field examination (30-2, Humphrey Field Analyzer, Model 750, Zeiss), biomicroscopy, gonioscopy, Goldmann applanation tonometry, auto kerato-refractometry, and corneal topography (KR-8100P Auto Kerato-Refractometer, Topcon). Two experienced surgeons performed all operations. IOP was compared to a group of age-matched phaco patients after two months. We did not have a parallel phaco group but we used information of 44 age-matched phaco patients by the same surgeons for comparison of IOP change. Surgical Technique In all cases, the ab-interno approach of the Trabectome was performed first, followed by cataract extraction. Standard dilating drops comprising phenylephrine hydrochloride (Neo-Synephrine 1%) and tropicamide (Mydriacyl 0.5%) were instilled 30 minute before the operation. Under topical anesthesia, after the area was prepped and draped, a 1.6 mm or 1.7 mm keratome was used to make a near-limbal, temporal clear corneal incision. Preservative-free lidocaine 2% was injected into the anterior chamber. An ophthalmic dispersive viscosurgical device (OVD) such as hydroxypropyl methylcellulose (Ocucoat) was injected to form the anterior chamber. The head and microscope were tilted to give an optimal gonioscopic view of the angle. The combined tilt was approximately 70 to 80 degrees. The Trabectome goniosurgical lens (a modified Swann-Jacobs lens) was placed on the cornea to verify the angle landmarks. The Trabectome hand-piece was inserted and advanced nasally across the anterior chamber with the infusion on. The pointed tip of the footplate was inserted through the trabecular meshwork into Schlemm’s canal, and a footswitch activated the aspiration and bipolar electrodes. Using an initial power setting of 0.7 to 0.8 watts, the surgeon slowly advanced the instrument along the meshwork first in a counterclockwise, then in a clockwise, direction using the limbal corneal incision as a fulcrum, ablating and removing a strip of trabecular meshwork un-roofing of Schlemm’s canal. The power was titrated up or down depending on the desire to ablate a wider strip of trabecular meshwork or to minimize charring of tissue, respectively. Verification of the cleft was performed, as the hand-piece was removed, and the angle was viewed for evidence of blood reflux from the newly exposed

collector channels. After filling the anterior chamber with an OVD, phacoemulsification and IOL implantation were then performed using the surgeon’s preferred technique. At the conclusion of the procedure, depending on pupil size, acetylcholine chloride (Miochol) was instilled. The amount of blood in the anterior chamber was assessed. If active bleeding was present, an air-bubble was injected into the anterior chamber. The corneal incision was then hydrated and checked for leakage. Postoperative Regimen Postoperative care varied according to clinical presentation but routinely included topical steroids (fluorometholone) 8 times daily tapered over 6 weeks, topical antibiotics 4 times daily for 5 days. Patient Evaluation Goldmann applanation IOPs and Snellen visual acuities were measured before and after surgery at each visit. Intraoperative and postoperative adverse events were tabulated, and numbers of preoperative and postoperative adjunctive medications were compared. To provide the raw data for analysis, autokeratometry and computerized corneal videokeratoscopy with the Topcon KR-8100P Auto Kerato-Refractometer were performed preoperatively and 5 day and 2, and 6 months postoperatively. Autokeratometry results and simulated K-values of corneal topography were used to analyze surgically induced keratometric and topographic astigmatism, respectively. Statistical Analysis Success was defined as a decrease in IOP of at least 20% from baseline or a decrease in glaucoma medications with maintenance of target IOP. Failure was defined as a less than 20% decrease in IOP from baseline, no decrease in medications or additional need to medications or glaucoma surgery. For statistical analysis, analysis of variance (ANOVA) was used to compare changes in IOP and medications across different baseline IOP subgroups. Paired sample t-test was performed on the pre- and postoperative data.

RESULTS Table I shows phaco-Trabectome patient demographics. The mean preoperative IOP was 18.25±3.28 mmHg with a mean of 2.52±0.60 glaucoma medications. Postoperative mean IOP and number of medications at each time point are shown in Tables II, III and Figure 1. Success (i.e., 20% or greater drop in IOP or decrease in glaucoma medications without need for additional medications or glaucoma procedures, including laser trabeculoplasty) was 46.7% at 6 months (n=30) and 59.1% at 12 months (n=22). The only significant intraoperative complication was blood reflux, which cleared within a few days after surgery. There were no complications such as hypotony, choroidal effusion or hemorrhage, aqueous misdirection, infection, bleb formation or wound leaks.

Combined Cataract Extraction and Trabeculotomy — Hashemian et al

Table I Patient demographics

Table II IOP preoperatively and postoperatively

Parameter

Value

Time

IOP (mmHg)

Reduction (%) # of Eyes (n)

Patients (# of patients / # of eyes) Age Mean ± SD Range Sex, n (%) Male Female Cup-to-disc ratio, n (%) < 0.7 0.7–0.8 > 0.8 Schaffer grade, n (%) I II III IV Visual field loss, n (%) Mild (MD 0 to -6.0 dB) Moderate (MD -6.0 to -12.0) Severe (MD > -12.0)

28/30

Preoperative 1 day 5 day 2 month 6 month 12 month 18 month 24 month

18.57±4.73 14.21±3.41 13.59±3.53 14.10±2.47 13.90±2.50 13.86±2.66 14.31±2.18 13.33±1.51

NA 20.21 22.61 20.26 21.35 24.77 19.48 28

69.90±7.5 54 – 80 17 (56.7%) 13 (43.3%) 17 (56.7%) 12 (40.0%) 1 (3.3%)

Table III Number of glaucoma medications preoperatively and postoperatively Time

0 (0.0%) 3 (10.0%) 27 (90.0%) 0 (0.0%) 2 (6.7%) 26 (86.7%) 2 (6.7%)

18 17 16 15 14

Estimated Marginal Means

Time Fig. 1 Decreasing trend of IOP with repetitive measurement

Table IV shows an analysis of IOP and glaucoma medication reduction stratified by baseline IOP level. Patients were separated into low pressure (<21 mmHg) group and high pressure (≥21 mmHg) group based on baseline IOP. The high pressure group had a statistically significant greater decrease in IOP level but less decrease in medications (Fig. 2). The visual acuity (LogMar values) level from the preoperative period was statistically significantly different throughout follow-up. The preoperative BCVA (LogMar) was 0.68±0.26 and was improved postoperatively to 0.26±0.19, 0.18±0.13, 0.17±0.13, 0.11±0.12, 0.13±.081 at 5 days and 2, 6, 12 and 24 months, respectively (P<0.01).

Mean # of Glaucoma medications

Reduction (%)

# of Eyes (n)

2.48±0.58 1.00±0.00 1.10±0.55 0.87±0.43 1.00±0.62 1.00±0.58 1.00±0.00

NA 56.41 52.47 61.73 57.02 55.56 55.56

27 26 27 27 19 12 6

Preoperative 5 day 2 month 6 month 12 month 18 month 24 month

n = # of eyes; MD= mean deviation;

30 29 29 30 30 22 13 6

Supplement: Clinical & Surgical Ophthalmology, June 2015

The mean keratometry decreased slightly 2 months postoperatively and remained stable to 6 months post operation. Changes in mean keratometry between preoperative and postoperative examinations were not statistically significant (P=0.13). The mean surgical induced astigmatism (absolute keratometric changes) was 0.38±0.28D. As mentioned before, 44 patients with only phaco surgery served as the control group for IOP comparison after 2 months. In the phaco group, mean age was 63.36±11.48 with a mean IOP of 14.73±2.49 mmHg before surgery. Mean IOP was significantly different at baseline between these two groups because all cases in phaco-Trabectome group had uncontrolled glaucoma (P<0.05). IOP was reduced to 12.3±2.5 mmHg two months after surgery, but this difference was not significant in contrast to the phaco-Trabectome group (Fig. 3). The decrease in IOP after 2 months in phaco-Trabectome group was 4.4±5.1 mmHg and 2.45±2.19 mmHg in phaco-group (P<0.04).

DISCUSSION Glaucoma is the second cause of the irreversible blindness in the world.1 Glaucoma management has evolved during the past decade by the introduction of new methods of surgical techniques and medications. Glaucoma and cataract are common in older patients.2 Although phacoemulsification in combination with trabeculectomy is effective for controlling pressure, complications such as hypotony, choroidal effusion and hemorrhage, leaking blebs and endophthalmitis tend to occur.7,8 Cataract

40.03 43.43 48.39 46.38 51.6 46.71 51 50 50 50 50 50 50

0.02 <0.01 <0.01 <0.01 <0.01 <0.01 0.04 0.42 0.86 0.33 0.61 0.65 0.31

Baseline IOP

16 10

95% CI

2 Month IOP

Trabectome+Phaco

Phaco

Group Fig. 3 Comparison of IOP reduction between two groups

surgery alone in glaucoma patients lowers IOP by 2 to 4 mmHg for a couple years.14-16 Even though phaco can reduce IOP, there is strong evidence for better long-term control of IOP in glaucoma patients with combined glaucoma surgery (trabeculectomy) and cataract extraction compared with cataract surgery alone.17,18 Combination of phaco with new surgical techniques such as Trabectome, endoscopic cyclophotocoagulation (ECP), Solx Gold shunt, canaloplasty or express shunt result in lower rate of complications.9-12 Given that Trabectome does not require the use of antifibrotic agents, risks associated with the use of mitomycin-C and 5-fluorouracil are therefore eliminated. Because the ab-interno approach of Trabectome completely spares the conjunctiva, any future standard filtering procedures remain available options if needed.19

50 25

15.04 14.46 15.88 15.1 16.88 11.32 16.5 57.25 52.78 63.19 57.84 56.67 58.33

DIOP1 DIOP5 DIOP2 DIOP6 DIOP12 DIOP18 DIOP 24 DIOP1 DIOP5 DIOP2 DIOP6 DIOP12 DIOP18 DIOP 24

p-value

-25

High Pressure (Baseline IOP ≥21mmHg)

DIOP1 DIOP2 DIOP5 DIOP6 DIOP12 DIOP18 DIOP24 DDrug2 DDrug5 DDrug6 DDrug12 DDrug18 DDrug24

Low Pressure (Baseline IOP <21mmHg)

-50

Reduction (%)

IOP Reduction (%)

Table IV Reduction in IOP and glaucoma medication stratified by baseline IOP

Pre-Op IOP Fig. 2 Dot plot with fitted lines for all of the IOP reduction

In our study, the main outcome measurement was a change in IOP after the operation. The mean preoperative IOP was reduced from18.2±3.2 mmHg to 14.5±2.3mmHg at 6 months, and 13.5±2.5mmHg at 12 months. Minckler et al reported that for 45 patients undergoing combined Trabectome and cataract extraction, the baseline IOP of 20.0±6.2 mmHg was decreased to 15.9±3.3 mmHg (18%) and medications decreased from 2.63±1.12 to 1.50±1.36 at 12 months.20 In our study, 46.7% showed an reduction in number of medications from 3 to 1 after 12 months of follow up. In a study of 538 patients that had Trabectome surgery alone and 290 patients that had phaco combined, Mosaed et al reported a 31% IOP reduction and a 28% drop in medication usage in the Trabectome only group at 1 year of follow up. In the combined group, a 18% IOP reduction and 33% drop in medication were reported.21 In a prospective case series comprised 304 eyes with open-angle glaucoma and cataract, Francis et al. reported a mean preoperative IOP 20.0±6.3 mmHg preoperatively that decreased to 15.5±2.9 mmHg at one year after combined Trabectome and phacoemulsification surgery. The glaucoma medications dropped from mean 2.56±1.13 to a mean 1.44±1.29 at one year.12 In our study, glaucoma medication decreased from 2.48±0.58 before surgery to 0.95±0.38 at 6 months. At 12 months, the number of medications was 1.14±0.53. In the phaco group, IOP decreased from baseline but the change was not significant compared to the phaco-Trabectome group. The most common complication reported in the study of Francis et al was blood reflux, which was observed in 78.4% of patients.12 Blood reflux, was observed in 90.0% our patients. Meanwhile we observed significant improvement in visual acuity and small amount of induced astigmatism after surgery. Trabeculectomy produces, during the early

Combined Cataract Extraction and Trabeculotomy — Hashemian et al

postoperative period, a reduction in the vertical corneal radius and results in with-the-rule (WTR) a change in corneal astigmatism.22,23 We observed less astigmatism in those patients who had combined phacoemulsification and ab-interno Trabectome surgeries than those in reported trabeculectomy studies using a Cairns-type technique.24,25 When considering the cost associated with glaucoma medications and challenges of medical compliance, it is certainly noteworthy that combined surgery reduced medication use by about 57% in 12 months of follow up in our study. Complications observed after surgery such as hyphema were transient, and complications such as hypotony, choroidal effusion were not observed in our study. It seems that the combination of phaco with ab-interno Trabectome may be a good option for patients with mild to moderate glaucoma and cataract. It not only decreases IOP but also dependence on glaucoma medications. The most important limitations in our study was missed data of about 26% of our patients during one year of follow up. Meanwhile, we did not have information of the phaco group in the long term as a parallel group but by considering this fact that primary goal of any glaucoma surgery is reduction of IOP with the lowest requirement for adjunctive glaucoma medications while providing minimal risk of complications, our results showed that combining phacoemulsification and Trabectome lowered IOP and medication use, with early visual rehabilitation and stable refractive outcomes in the majority of our patients. â?? Acknowledgments: Design and conduct of study: Dr. S.J. Hashemian, Dr. A. Miraftabi, Dr. M.E. Jafari; Gathering of data and analysis: Dr. M.E. Jafari, Dr. M.R. Hammami

REFERENCES 1. 2. 3. 4.

Quigley HA, Broman AT. Number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006; 90: 262-267. Xu L, Wang Y, Li Y, et al. Causes of blindness and visual impairment in urban and rural areas in Beijing: the Beijing Eye Study. Ophthalmology 2006; 113(7): 1134-1141. Hennis AJ, Wu SY, Nemesure B, et al. Nine year incidence of visual impairment in the Barbados Eye Studies. Ophthalmology 2009; 116(8): 1461-1468. Chandrasekaran S, Cumming RG , Rochtchina E, Mitchell P. Associations between elevated intraocular pressure and glaucoma, use of glaucoma medications, and 5-year incident cataract: the Blue Mountains Eye Study. Ophthalmology 2006; 113(3): 417-424. Shingleton BJ, Wooler KB, Bourne CI, O'Donoghue MW. Combined cataract and trabeculectomy surgery in eyes with pseudoexfoliative glaucoma. J Cataract Refract Surg 2011; 37(11): 1961-1970. Krupin T, Feitl M, Bishop K. Postoperative intraocular pressure rise in open-angle glaucoma patients after cataract or combined cataract-filtration surgery. Ophthalmology 1989; 96: 579-584. Zacharia PT, Schuman JS. Combined phacoemulsification and trabeculectomy with mitomycin-C.Ophthalmic Surg Lasers 1997; 28(9): 739-744.

Supplement: Clinical & Surgical Ophthalmology, June 2015

10. 11.

12.

13.

14.

15.

16.

17.

18. 19.

20.

21. 22.

23.

24. 25.

Belyea DA, Dan JA, Lieberman MF, Stamper RL. Midterm follow-up results of combined phacoemulsification, lens implantation, and mitomycin-C trabeculectomy procedure. J Glaucoma1997; 6(2): 90-98. Matlach J, Freiberg FJ, Leippi S, et al. Comparison of phacoemulsification-trabeculectomy versus phacoemulsificationcanaloplasty in the treatment of patients with concomitant cataract and glaucoma. BMC Ophthalmol 2013; 29; 13: 1. Rosdahl JA, Chen, TC. Combined cataract and glaucoma surgeries: traditional and new combinations. Int Ophthalmol Clin 2010; 50(1): 95-106. Shingleton B, Tetz M, Korber N. Circumferential viscodilation and tensioning of Schlemm canal (canaloplasty) with temporal clear corneal phacoemulsification cataract surgery for open-angle glaucoma and visually significant cataract: one-year results. J Cataract Refract Surg 2008; 34: 433-440. Francis BA, Minckler D, Dustin L, et al. Combined cataract extraction and trabeculotomy by the internal approach for coexisting cataract and open-angle glaucoma: initial results. J Cataract Refract Surg. 2008; 34: 1096-1103. Francis BA, See RF, Rao NA, et al. Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-angle glaucoma. J Glaucoma 2006; 15: 68-73. Pohjalainen T, Vesti E, Uusitalo RJ, Laatikainen L. Phacoemulsification and intraocular lens implantation in eyes with open-angle glaucoma. Acta Ophthalmol Scand 2001; 79: 313-316. Kim D, Doyle J, Smith M. Intraocular pressure reduction following phacoemulsification cataract extraction with posterior chamber lens implantation in glaucoma patients. Ophthalmic Surg Lasers 1999; 30: 37-40. Shingleton BJ, Pasternack JJ, Hung JW, Oâ&#x20AC;&#x2122;Donoghue MW. Three and five year changes in intraocular pressures after clear corneal phacoemulsification in open-angle glaucoma patients, glaucoma suspects, and normal patients. J Glaucoma 2006; 15: 494-498. Mansberger SL, Gordon MO, Jampel H, et al. Reduction in intraocular pressure after cataract extraction: the OcularHypertension Treatment Study. Ophthalmology 2012; 119(9): 1826-1831. Friedman DS, Jampel HD, Lubomski LH, et al. Surgical strategies for coexisting glaucoma and cataract: an evidence based update. Ophthalmology 2002; 109: 1902-1915. Palanca-Capistrano AM, Hall J, Cantor LB, et al. Long-term outcomes of intraoperative 5-fluorouracil versus intraoperative mitomycin-C in primary trabeculectomy surgery. Ophthalmology 2009 Feb; 116(2): 185-190. Minckler D, Mosaed S, Dustin L, Francis B. Trabectome (trabeculectomy by internal approach): additional experience and extended follow up. Am Ophthalmol Soc 2008; 106: 149-160. Mosaed S, Rhee DJ, Filippopoulos T. Trabectome outcomes in adult open-angle glaucoma patients: one-year follow-up. Clinical & Surgical Ophthalmology 2010; 28: 8. Kook MS, Kim HB, Lee SU. Short-term effect of mitomycin-C augmented trabeculectomy on axial length and corneal astigmatism. J Cataract Refract Surg 2001; 27: 518-523. Egrilmez S, Ates H, Nalcaci S, et al. Surgically induced corneal refractive change following glaucoma surgery: nonpenetrating trabecular surgeries versus trabeculectomy. J Cataract Refract Surg 2004; 30: 1232-1239 . Rosen WJ, Mannis MJ, Brandt JD. The effect of trabeculectomy on corneal topography. Ophthalmic Surg 1992; 23(6): 395-398. Dietze PJ, Oram O, Kohnen T, et al. Visual function following trabeculectomy: effect on corneal topography and contrast sensitivity. J Glaucoma 1997; 6: 99-101.

â&#x20AC;&#x153;The total number of Trabectome certified surgeons world-wide has reached 1509 with 139 now designated as being Trainers. In my personal experience of 100 cases, this procedure (Trabectome ab interno) far more often than not normalized IOP and decreased the use of adjunctive topical medications far more safely than in my much larger experience with Trabeculectomy and Glaucoma Drainage Devices over several prior decades.â&#x20AC;? from the foreword by Don Minckler, MD, MS

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