Main topic: “Minimally Invasive Glaucoma...

Glaucoma Now – Issue No 3, 2016. www.glaucomanow.com 1

I S S U E 3

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Main topic:

“Minimally Invasive Glaucoma Surgery”

TARGET AUDIENCEThis educational activity is aimed at general ophthalmologists, glaucoma specialists and ophthalmo logy resi-dents.

Glaucoma Now is published and adminis-tered by the editorial board and supported by an unrestricted grant from Alcon Labo-ratories Inc., Pfizer Inc and Santen Oy

Copyright 2010 Editorial Board. All rights reserved. No responsibility assumed for injury or damage to persons or property arising from the use of informa-tion or ideas contained in this publication.

Special Focus:

Current techniques in MIGS, the theory behind the techniques, relevant data on efficacy and safety

What’s New:

Recent advances in MIGS, ab interno and ab externo approach-es, data on products in development

Practical Tips:

Key factors for suc-cessful implantation of MIGS

Inside this issue:

EDITORIAL BOARDIvan Goldberg MBBS, FRANZCO, FRACS. Head, Glaucoma Unit, Sydney Eye Hospital & Discipline of Ophthal-mology, University of Sydney.

Remo Susanna MD, Professor and Head of Department of Ophthalmology, University of São Paulo, Brazil.

Glaucoma Now is a continuing medical education publication. Distributed worldwide, our goal is to educate and update general ophthalmologists, glaucoma specialists and ophthalmology resi-dents. International leaders in the field of glaucoma are invited to contribute to this journal, sharing their most recent insights.

Supported by an unrestricted educational grant, the publication is non-promotional and has a fully independent Editorial Board. Glaucoma Now is published 3 times per year. For each issue CME credits can be obtained by registering on our website www.glaucomanow.com and answering the uploaded questions.

A newsletter is sent out to participants registered to the program.

Executive officer: Patricia Buchholz RPh, PhD Karlsruhe, Germany [email protected] Production by Phosworks www.phosworks.com

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Clinical Issues:

MIGS used in clinical practice. Which product for which patient type?

PAGE 8 PAGE 10PAGE 5

LEARNING OBJECTIVES• Special Focus: A comprehensive overview of the current techniques in MIGS, including the coverage of the theory behind the techniques, discussion of relevant data on efficacy and safety.

• What’s New: A summary on recent advances in MIGS, both on ab interno and ab externo approaches, with a focus on state of play in product development and clinical trial data.

• Clinical Issues: A review on MIGS most commonly used in clinical practice. An approach to differentiating mechanisms of action and discussing potential patient target populations.

• Practical Tips: The description of key factors for a successful implantation of MIGS

2 Glaucoma Now – Issue No 3, 2016. www.glaucomanow.com Glaucoma Now – Issue No 3, 2016. www.glaucomanow.com 3

Special Focus:

Minimally Invasive Glaucoma SurgeryMichael Stone, MD, Iqbal Ike K Ahmed, MDDepartmentof Ophthalmology, University of Toronto, Toronto, Canada

1) IntroductionMinimally (or Micro) Invasive

Glaucoma Surgery (MIGS) is a term that was introduced over 4 years ago. Questions remain as to what is MIGS? What is the role of MIGS in the cur-rent glaucoma treatment paradigm? And how is MIGS evolving?

MIGS is a new genre of devices and techniques that aim to lower IOP in a safer and typically more physiological manner. The development of these new

surgical options stemmed from the large gap that existed between topical medications on one hand, and tradi-tional glaucoma surgery on the other side. The goal of MIGS procedures is often not just IOP reduction, but re-duction and/or elimination of topical

glaucoma medications. This is impor-tant considering the poor adherence that most studies have shown with glaucoma patients.1 Many of these procedures are combined with cataract surgery, while others have been pegged as a possible standalone procedure.

2) DefinitionsMIGS has been defined as procedures

that have an ab-interno approach, are minimally atraumatic, with at least

modest efficacy, extremely high safety, and rapid recovery.2 MIGS procedures can be classified based on their outflow mechanism – whether Schlemm’s ca-nal, suprachoroidal, or subconjunctival (Table 1). We prefer to subdivide these procedures into those that are blebless

and strictly internal (iMIGS = internal MIGS), and MIGS “plus” or external MIGS which are bleb-forming, exhib-it greater potency with slightly more risks and require more postoperative management. Considering that MIGS procedures are designed to be placed in the angle, proper gonioscopic visu-alization is key. This includes optimal patient and microscope positioning, with the use of a gonioprism or goni-omirror.

3) Procedures and devicesSchlemm’s canal procedures are

located in one of the safest places to enhance outflow and to do so physi-ologically. The concept is to bypass the trabecular meshwork, thereby remov-ing the primary point of resistance to aqueous outflow and the site of disease in most glaucomas. However, episcler-al venous resistance – while protective against hypotony – limits the amount with which IOP may be lowered. This approach is likely the most technical of all the MIGS techniques. With con-ventional outflow, location of collector channels and aqueous veins are likely important to reduce outflow resis-tance. Considering the canal as a 360 degree vessel, it appears that once we get past 4 clock hours, the resistance to outflow tends to flatten out.3 Further-more, the ability to place the bypass or remove resistance in the vicinity of major collector channels and/or aque-ous veins is likely to further enhance the amount of resistance reduction and IOP-lowering. These procedures can be considered as either micro-stenting, micro-cutting, or micro-ablative pro-cedures.

One of the most commonly dis-cussed and published MIGS device is the iStent (Figure 1). This titanium 1mm stent has a snorkel in the anterior chamber and an open half-pipe that resides in Schlemm’s canal thereby allowing aqueous to bypass the tra-becular meshwork. Early randomized prospective studies compared phaco

(phacoemulsification cataract extrac-tion with intra-ocular lens insertion) combined with a single iStent with phaco alone; they showed a greater proportion of patients reached an IOP <=21 on no medications with the iS-tent than without (73% vs 50%) with a very high safety profile comparable with phaco alone at 1-year.4 Subse-quent studies comparing the use of two iStents with phaco versus phaco alone found IOP-lowering from 24.2 to 17.6 mmHg on no postoperative medica-

tions versus 23.6 to 19.8 mmHg on 0.7 medications.5 This same study found a significant difference in improvement of outflow facilty on fluorophotometry in the iStent/phaco group vs phaco alone. Most studies with the use of the iStent have been done in combination with phaco, and have found postopera-tive IOPs typically in the mid-to-high

teens; with medications this may be brought down to low-to-mid teens.6 Recently, there has been a 2nd genera-tion iStent which enables a more con-sistent and easier insertion technique.7 Many iStent users have been implant-ing two devices to facilitate a larger area of aqueous outflow with the intent to lower IOP further.8

A recent Schlemm’s canal stent with trimodal mechanism of outflow enhancement is the Hydrus micro-stent (Figure 2). This device is a lon-ger 3-clock hour device with a bypass inlet and 3 windows designed to en-hance trans-TM flow into the canal by stretching the inner wall. Further, this device significantly scaffolds the Schlemm’s canal, maintaining dila-tion. A randomized study comparing phaco and hydrus versus phaco alone found a greater proportion of phaco/hydrus eyes attained 20% IOP reduc-tion off medications at 24 months ver-sus phaco alone (80% vs 46%) with an excellent safety profile.9

The Trabectome™, an ab-interno trabeculotomy technique using mi-cro-ablation is another approach to enhancing Schlemm’s canal outflow. This procedure has been found to low-er IOP to the mid-teens (again, often with some medications) with a 30-40% IOP drop, either combined with cataract surgery or as a standalone pro-cedure, as well as having an excellent safety profile.10,11 A comparative study of phaco+iStent vs phaco+trabectome

Core Concepts• MIGS procedures are high-lighted by their enhanced safety, enabling their usage earlier in the treatment paradigm and condu-cive to combining with cataract surgery.• Schlemm’s canal MIGS pro-cedures have the highest safety profile of all glaucoma surgeries, but are limited by episcleral ve-nous resistance and downstream resistance.• Suprachoroidal MIGS devices are designed to provide a more controlled cleft procedure, with potentially significant lowering de-pendent on the size of the supra-choroidal lake.• Subconjunctival MIGS devices produce external filtering blebs and approach IOP targets similar to trabeculectomy (trab) with a safer and more controlled proce-dure.• Selection of MIGS procedures is dependent on benefit-to-risk ratio, as well as intraoperative and postoperative intensity, cost-ben-efit, and reimbursement.

Figure 1. iStent.

Internal MIGS MIGS Plus

Schlemm’s Canal Suprachoroidal Subconjunctival

Stenting Dilation Cutting Ablation

CypassiStent Supra

XenInnFocus*

iStentiStent injectHydrus

Visco360ABiC (Ab-interno Canaloplasty)

GoniotomyGATT (Gonioscopic -Assisted Transluminal Trabeculotomy)Trab360Kahook Dual Blade

Trabectome

Figure 2. Hydrus microstent.

Table 1.Figure 3. Cypass micro-stent.

A


2015;122(7):1283-1293. doi:10.1016/j.oph-tha.2015.03.031.

10. Ahuja Y, Ma Khin Pyi S, Malihi M, Hodge DO, Sit AJ. Clinical Results of Ab Interno Trabeculotomy Using the Trabectome for Open-Angle Glaucoma: The Mayo Clinic Series in Rochester, Minnesota. 2013;156(5):927–935.e2. doi:10.1016/j.ajo.2013.06.001.

11. Jea SY, Francis BA, Vakili G, Filippopoulos T, Rhee DJ. Ab interno trabeculectomy versus trabeculectomy for open-angle glaucoma. Oph-thalmology. 2012;119(1):36-42. doi:10.1016/j.ophtha.2011.06.046.

12. Khan M, Saheb H, Neelakantan A, et al. Ef-ficacy and safety of combined cataract surgery with 2 trabecular microbypass stents versus ab interno trabeculotomy. J Cataract Refract Surg. 2015;41(8):1716-1724. doi:10.1016/j.jcrs.2014.12.061.

13. Grover DS, Godfrey DG, Smith O, Feuer WJ, Montes de Oca I, Fellman RL. Gonioscopy-assisted transluminal trabeculotomy, ab interno trabeculotomy: technique report and preliminary results. Ophthalmology. 2014;121(4):855-861. doi:10.1016/j.ophtha.2013.11.001.

14. Vold S, Ahmed IIK, Craven ER, et al. Two-Year COMPASS Trial Results: Supraciliary Mic-rostenting with Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts. Ophthalmology. August 2016. doi:10.1016/j.ophtha.2016.06.032.

15. Sheybani A, Dick B, Ahmed IIK. Early Clinical Results of a Novel Ab Interno Gel Stent for the Surgical Treatment of Open-angle Glaucoma. J Glaucoma. November 2015. doi:10.1097/IJG.0000000000000352.

16. Sheybani A, Lenzhofer M, Hohensinn M, Reitsamer H, Ahmed IIK. Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: Pilot study. J Cata-ract Refract Surg. October 2015. doi:10.1016/j.jcrs.2015.01.019.

17. Batlle JF, Fantes F, Riss I, et al. Three-Year Follow-up of a Novel Aqueous Humor Micro-Shunt. J Glaucoma. 2016;25(2):e58-e65. doi:10.1097/IJG.0000000000000368.

References1. Patterns of Glaucoma Medication Adherence over Four Years of Follow-Up. 2015;122(10):2010-2021. doi:10.1016/j.ophtha.2015.06.039.

2. Saheb H, Ahmed IIK. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr Opin Ophthalmol. 2012;23(2):96-104.

3. Rosenquist R, Epstein D, Melamed S, John-son M, Grant WM. Outflow resistance of enucle-ated human eyes at two different perfusion pressures and different extents of trabeculot-omy. Current Eye Research. 1989;8(12):1233-1240.

4. Samuelson TW, Katz LJ, Wells JM, Duh Y-J, Giamporcaro JE, US iStent Study Group. Randomized evaluation of the trabecular micro-bypass stent with phacoemulsification in patients with glaucoma and cataract. Ophthal-mology. 2011;118(3):459-467.

5. Fernández-Barrientos Y, García-Feijoó J, Martínez-de-la-Casa JM, Pablo LE, Fernández-Pérez C, García-Sánchez J. Fluorophotometric study of the effect of the glaukos trabecular microbypass stent on aqueous humor dynamics. Invest Ophthalmol Vis Sci. 2010;51(7):3327-3332. doi:10.1167/iovs.09-3972.

6. Belovay GW, Naqi A, Chan BJ, Rateb M, Ahmed IIK. Using multiple trabecular micro-bypass stents in cataract patients to treat open-angle glaucoma. J Cataract Refract Surg. 2012;38(11):1911-1917. doi:10.1016/j.jcrs.2012.07.017.

7. Arriola-Villalobos P, Martinez-De-La-Casa JM, Díaz-Valle D, et al. Mid-term evaluation of the new Glaukos iStent with phacoemulsification in coexistent open-angle glaucoma or ocular hypertension and cataract. Br J Ophthalmol. 2013;97(10):1250-1255. doi:10.1136/bjoph-thalmol-2012-302394.

8. Katz LJ, Erb C, Carceller GA, et al. Prospec-tive, randomized study of one, two, or three tra-becular bypass stents in open-angle glaucoma subjects on topical hypotensive medication. Clin Ophthalmol. 2015;9:2313-2320. doi:10.2147/OPTH.S96695.

9. Pfeiffer N, García-Feijoó J, Martínez-de-la-Casa JM, et al. A Randomized Trial of a Schlemm’s Canal Microstent with Phacoemul-sification for Reducing Intraocular Pressure in Open-Angle Glaucoma. Ophthalmology.

found similar IOP-lowering but with less medications and less postoperative hyphema in the iStent group.12

Schlemm’s canal micro-cutting techniques include the Gonioscopy Assisted Transluminal Trabeculotomy (GATT) procedure, which has shown similar results to other Schlemm’s ca-nal procedures with mid-high teen IOP targets and significant IOP low-ering with high safety. 13 Recently, a plethora of similar techniques, includ-ing the ABiC (ab-interno canaloplas-ty), the Trab360 and Visco360 pro-cedures, and the Kahook Dual Blade have been introduced as Schlemm’s canal procedures that either remove a large strip of trabecular meshwork and/or create ab-interno viscodilation. Further data on these procedures are forthcoming.

Another internal MIGS approach is to enhance uveoscleral outflow by draining aqueous into the suprachoroi-dal space. These procedures follow the notion of a large resorptive area in this space with potential IOP-reduction. Previous cleft procedures were trau-matic, less-controlled, and resulted in potentially wide swings in IOP. Re-cent MIGS procedures into this space include ab-interno placed micro-stents designed to provide a more controlled access to the suprachoroidal space, with maintenance of patency using stent placement. Two such devices are the CyPass micro-stent and iStent Supra micro-stent (Figure 3). These devices have also been studied primar-ily combined with cataract surgery. A recently published large randomized control study comparing phaco + Cy-Pass versus phaco alone found 65% of phaco/CyPass patients reached a po-stop IOP between 6-18 mmHg ver-sus 44% of phaco alone.14 This study also found safety was comparable with phaco alone.

Both Schlemm’s canal approaches and suprachoroidal MIGS devices appear to be reasonably helpful when combined with cataract surgery in an effort to reduce medication burden in a safe and effective manner. Although these internal MIGS procedures lack the potency of external filtration, the attraction of a safer procedure may allow them to be considered earlier in disease and comfortably combined with phaco. There are also some in-stances where they may be performed as a standalone procedure: mostly for mild-to-moderate glaucoma where IOP targets are more modest (mid-to-high teens). Patients also must be pre-pared to use medications to reach these targets or lower.

Figure 4. XEN gel stent.

Figure 5. InnFocus microshunt.

To enable further IOP-lowering, albeit with external filtration, the Xen gel-stent is an ab-interno mic-rostent that creates a communication between the anterior chamber and the subconjunctival space (Figure 4). The ability to create a more posterior bleb that is diffuse and low-lying in nature is the goal of this procedure. The use of Mitomcyin-C is often necessary to help modulate wound healing. Early published results show a very good safety profile of this device, while ap-proaching IOP-targets and medication reduction that are closer to trabeculec-tomy standards.15,16 This enables this device to be considered as standalone procedure, or combined with phaco if needed. The ability to efficiently and effectively create an external filtering bleb through an ab-interno approach is an attractive alternative to trabeculec-tomy (trab) for many patients and may allow this device to be considered for patients with earlier disease (less dam-age) due to its enhanced comparative safety and control.

Although not strictly a MIGS pro-cedure, the InnFocus micro-shunt is delivered through an ab-externo ap-proach, and is designed to produce a posteriorly placed well tolerated bleb (Figure 5). It also is often used with Mitomycin-C, and has been found to also lower IOP to trab-like levels into the low-teens or below with a very good safety profile.17

Both the Xen and the InnFocus devices drop IOP more than iMIGS devices, although they do depend on creation of an external filtering bleb – albeit with what appears to be a more controlled, safer, and better tolerated procedure with faster recovery than often with trabeculectomy. These de-vices are thus more likely to be used a standalone procedure for patients requiring a potent IOP-lowering drop, and/or combined with phaco for lower IOP targets.

4) ConclusionIt is exciting to see a new era of

glaucoma interventions with MIGS procedures and devices. No doubt, much more data, longer-term results, and cost-effectiveness studies must be produced to better understand their role. The use of MIGS also requires a change in the mindset of the clinician to move towards addressing adherence in a more interventional and proac-tive way. The opportunity to combine many of these devices with phaco in a safer manner can help reduce medi-cation burden while providing mod-est IOP-lowering. External filtering MIGS procedures may approach IOP targets similar to trabeculectomy but with a more controlled, less-invasive,

and potentially safer approach. The potential synergy with advances in drug delivery and MIGS may further broaden the application of these pro-cedures. As with any therapy, the bal-ance of risk, benefit, and effort must be considered in an individualized, pa-tient-centric manner. We look forward to more developments in this growing field of interventional glaucoma.


What’s New

Update on MIGSRobert Stamper MD, PhDDepartment of Ophthalmology, University of California in San Francisco, USA

miniaturizing the older procedures or finding new aqueous drainage path-ways. While they reduce the incidence of some of the potentially devastating complications, they are less effective.

The MIGS group of operations are divided into: • miniaturized versions of trabecu-

lectomy (e.g. Xen and Midi-Arrow implants)• trabecular bypass operations (e.g.

Trabectome, Trab360, iStent) • suprachoroidal shunts (e.g. Cypass

or Glaukos shunts) and• gentler versions of laser photoco-

agulation (e.g. endocyclophotocoagu-lation and Micropulse cyclophotoco-agulation).

2) Miniaturized Anterior Filter-ing Operations

External filtering operations have been the mainstay of glaucoma surgi-cal care. The main vision-threatening complication is hypotony usually from excessive filtration. Hypotony can lead to other complications that reduce vision such as suprachoroidal

Core Concepts• Newer techniques are evolving with the promise of less risk of vision-threatening complications. • Most need more study before being placed in our range of anti-glaucoma surgical strategies. • A summary of current knowl-edge is provided in table 1. • Possible utilization of vari-ous MIGS procedures based on glaucoma severity is proposed in Table 2 – based on current knowledge; subject to change as more information and experience become available. • While no comparative studies are available yet, possibly some of these newer procedures will allow us to consider surgical treatment earlier in the glaucoma treatment paradigm. Safety and predictable effectiveness will determine this.• Enhanced interest in better surgical approaches to glaucoma portends exciting times ahead.

1) Why MIGS?The goal of glaucoma surgery is to

lower intraocular pressure (IOP) to a level that will retard or prevent further loss of ganglion cells and, thus, loss of vision. Standard glaucoma surgeries such as trabeculectomy and ExPRESS shunts, external tube-shunts like the Ahmed, Baerveldt and Molteno styles and transscleral cyclophotocoagula-tion are major surgeries.

While they are very often effective at lowering IOP and preventing pro-gression of glaucoma, they have many potential complications that can inter-fere with vision temporarily or perma-nently, such as prolonged hypotony, hemorrhage, leaking blebs and bleb related infections.

Recently, several new glaucoma procedures have emerged, designed to minimize some of the visually threat-ening complications of conventional glaucoma surgery. These new surgeries are collectively called minimally inva-sive glaucoma surgery (MIGS) because they are performed through very small incisions; they reduce complications by

PROCEDUREAP-PROACH

ALONE OR WITH CAT-ARACT SURGERY

NUMBER OF SUB-JECTS

INITIAL IOP (MMHG

LENGTH OF LAST FOLLOW UP (MOS)

IOP @ LAST F/U

% REDUC-TION

# MEDS @ LAST F/U

TRABECTOME Internal Alone 46 25.7 24 16.6 40% 1.2

ISTENT Internal With 117 18.4 24 16.0 18% 0.2

HYDRUS Internal With 50 N/A 24 16.9 N/A N/A

TRAB 360 Internal Alone 26 19.8 4 13.5 32% 0.2

EXCIMER LASER TRABECULOT-OMY

Internal With 64 19.8 12 15.3 23% 0.9

CYPASS Internal With 94 20 12 13 35% 0.8

MIDI-ARROW (INFOCUS)

External Both 21 23.9 24 11.1 54% 0.3

XEN GEL Internal Both 37 22.4 12 15.4 31% 0.9

Table 1. Some reported data for various MIGS procedures (N/A = not available)

hemorrhages, maculopathy, corneal decompensation, cataract and optical instability. Because of the adjunctive use antifibrosis agents like mitmomy-cin C, potentially devastating late bleb leaks and bleb-related infections are more common.

The newer approaches to filtration use tiny tubes whose small diameters reduce the risk of overfiltration. One such device, the MIDI-Arrow Glau-coma Device is a tiny tube made of a biocompatible polystyrene compound that has shown promising results in a multinational study of 79 patients (av-erage IOP 11.6 at two years) with a low rate of hypotony (<10%, all transient).1 IOP reduction seems to persist even into the third year in a high risk-for-failure population.2 The MIDI-Arrow is implanted ab externo under con-junctiva and into the anterior chamber. Because of its small size, the conjunc-tival incision is very small, facilitating watertight closure. Clinical trials are underway for U.S. Food and Drug Administration (FDA) approval.

A similar device made of collagen and implanted ab interno via a trans-corneal incision is the Xen Gel stent .3 While no results have been pub-lished, reports of early trials also have been promising.4 This device has a CE mark and is undergoing trials in the USA to obtain FDA approval.

3) Trabecular Meshwork Bypass Based on studies by Chandler and

Grant, aqueous outflow obstruction in open angle glaucoma is assumed to lie

in the trabecular meshwork. Removal or bypassing of the trabecular mesh-work should restore normal or near-normal outflow.

Ab externo trabeculotomy was tried but found to be ineffective in adult open angle glaucoma. However, tra-beculotomy with the Trabectome, an electrocautery device that is inserted ab interno into Schlemm’s canal to ablate a 1 mm swathe of trabecular meshwork over 160 degrees or so, has been shown to be effective in many patients to reduce both IOP and de-pendence on anti-glaucoma medica-tions when performed alone or when combined with cataract extraction. 5 6 7 Complications include transient hy-phema (about 20%) and early post-op-erative pressure spikes. The procedure requires a relatively expensive console as well as a disposable hand piece.

Similar results seem to be obtained with a device that inserts a suture-like material into Schlemm’s canal under gonioscopic control and once the su-ture has been threaded 180 degrees, is pulled out of the eye tearing 180 de-grees of trabecular meshwork. The de-vice (the Trab360) can then be turned around and the other 180 degrees of trabecular meshwork torn through the same incision.8 Although the hand-piece is not reusable, since no capital equipment is required, it may be more affordable than the Trabectome.

A similar result can also be accom-plished with the ICath device (Ellex) which can be threaded 360 degrees through a small incision under go-

nioscopic control and then pulled noose-like to tear the entire tra-becular meshwork (Gonioscopic As-sisted Transluminal Trabeculotomy- GATT).9

All these procedures have the ad-vantages of a small incision, relatively low serious complication rates and us-ability with or without cataract proce-dures. When they work, they generally reduce IOP to around 16 and appear more suitable for mild to moderate glaucoma, with higher target IOPs.

Yet another strategy with the same goal is to make precise holes through the trabecular meshwork into Sch-lemm’s canal with an excimer laser.10 No pricing is available yet for the equipment,, but it is likely to be costly.

One company has adapted their Trab360 instrument to inject visco-elastic into Schlemm’s canal, dilating it to reduce IOP. No published reports are available for this procedure to date.

Another approach to bypass the tra-becular obstruction is to place ab in-terno a tiny snorkel-like device to shunt aqueous from the anterior chamber di-rectly to Schlemm’s canal. The iStent is inserted through the anterior chamber via a small (~2mm) corneal incision. The inserting instrument crosses the anterior chamber to the area of the trabecular meshwork opposite the in-cision; the leading edge engages the meshwork and slides into Schlemm’s canal leaving a small snorkel like pro-trusion in the anterior chamber. A randomized controlled trial compar-ing the iStent combined with cataract

Phase of Glaucoma Surg Rx alone Surg Rx with phaco

Early SLT, Trabectome SLT 1st, Trabectome, Istent

ModerateMultiple Istents, Trab 360, Cypass when approved, MP TCP

Trab360, ECP, Cypass when approved

AdvancedTrabeculectomy, ExPRESS, MidiArrow (Innfocus minishunt), Xen, GDD Tube, MP TCP

Trabeculectomy, Express, Xen shunt

End StageGDD tubeMicropulse TCPContinuous wave TCP

Table 2. Possible Patient Selection for MIGS procedures based on current knowledge; likely to change as more information and experience become available. (MPTCP = micro-pulse trans-scleral cyclophotocoagulation; ECP = endocyclophotocoagulation; GDD tube = glaucoma drainage device tube shunt)


10. Toteberg-Harms M, Hanson JV, Funk J: Cataract surgery combined with excimer laser trabeculotomy to lower intraocular pressure: effectiveness dependent on preoperative IOP. BMC Ophthalmol. 24:13-24.

11. SamuelsonTW, Katz LJ, et al and US IStent study group: Randomized evaluation of the tra-becular micro-bypass stent with phacoemulsi-fication in patients with glaucoma and cataract. Ophthalmology. 2011. 118:459-67.

12. Neuhann TH: Trabecular micro-bypass stent implantation during small-incision cataract surgery for open-angle glaucoma or ocular hypertension: Long-term results. . J Cataract Refract Surg. 2015 Dec;41(12):2664-71

13. Donnenfeld ED(1), Solomon KD(2), Voskan-yan L(3), et al: A prospective 3-year follow-up trial of implantation of two trabecular microby-pass stents in open-angle glaucoma. Clin Ophthalmol. 2015 Nov 3;9:2057

14. Gulatti V, Fan S, Hays, et al: A novel 8 mm Schlemm’s’s canal scaffold reduces outflow resistance in a human anterior segment perfur-sion model. Invest Ophthalmol Vis Sci. 2013 54:1698-704

15. Pfeiffer N, Garcia-Feijoo J, Martinez-de-la-Casa J et al: A Randomized trial of a Schlemm’s’s canal Microstent with Phacoemul-sification for reducing intraocular pressure in open angle glaucoma. Ophthalmology. 2015. 122:1283-1293.

16. Yablonski ME(1): Trabeculectomy with internal tube shunt: a novel glaucoma surgery. J Glaucoma. 2005 Apr;14(2):91-7.

17. Garcia-Feijoo J, Grsanti SW, Grsanti SA et al: Supraciliary micro-stent implantation for open angle glaucoma gailing topical therapy: 1 year results of multicenter study. Am J Ophthal-mol 2015; 159:1075-1081

References1. Palmberg P. Two-year follow-up data for a soft and durable minimally invasive ab interno trans-scleral implant in open-angle glaucoma subjects. Poster Presented at: World Glaucoma Congress; 2013; Vancouver, Canada.

2. Batlle JF, Fantes F, Riss Iet al.: Three-Year Follow-up of a Novel Aqueous Humor MicroS-hunt. J Glaucoma. 2016, 25: 58-65

3. Lewis RA.: Ab interno approach to the subconjunctival space using a collagen glau-coma stent. J Cataract Refract Surg. 2014. 40(8):1301-6

4. Vold S. Implantation of a minimally invasive ab interno subconjunctival implant in combina-tion with cataract surgery for the treatment of glaucoma. Poster Presented at: World Glaucoma Congress; 2013; Vancouver, Canada.

5. Polat J, Loewen NA.: Combined Phaco-emulsification and Trabectome for Treatment of Glaucoma.

Surv Ophthalmol. 2016. 03.012 (Epub ahead of print)

6. Kaplowitz K), Bussel II, Honkanen R, Schuman JS , Loewen NA: Review and meta-analysis of ab-interno trabeculec-tomy outcomes. . Br J Ophthalmol. 2016 May;100(5):594-600.

7. Minckler D, Mosaed S, Francis B, Loewen N, Weinreb RN:

Clinical results of ab interno trabeculotomy us-ing the Trabectome for open-angle

glaucoma: the mayo clinic series in Roch-ester, Minnesota. Am J Ophthalmol. 2014 Jun;157(6):1325-6

8. Sarkisian S: New Way for ab interno Tra-beculotomy. Presented at the annual meeting of ASCRS, San Diego, CA. April, 2015. There is as yet no published material on this device.

9. Grover DS, Godfrey DG, Smith O et al: Goni-oscopy – assisted transluminal trabeculotomy, ab interno trabeculotomy technique, report and preliminary results. Ophthalmology 2014. 121:855-61.

surgery with cataract surgery alone showed no difference in IOP at two years but a reduction in medication needs. 11 When successful, the pro-cedure seems to maintain good IOP out to three years.12 For further IOP reduction two or more stents can be inserted in the same eye. 13 The iStent is approved by the U.S. FDA and de-spite a rather high price, has become popular, especially when combined with cataract surgery.

A similar product, the Hydrus with a longer arc of metal and a scaffold structure (3 clock hours of the canal is supported) is being trialled; it seems to achieve IOP in the mid teens at two years with reduced medication needs and low complication rates.14 15

4) Suprachoroidal shuntsCyclodialysis was a relatively com-

mon procedure for glaucoma especially in aphakic eyes in the middle of the last century. A simple tube shunting fluid from the anterior chamber to the suprachoroidal space could lower IOP reliably.16

Currently, one device, the Cypass has received CE mark approval in Eu-rope with data submitted to the FDA. This is a tiny tube, made of nylon-like material, inserted ab interno across the anterior chamber under gonioscopic control into the suprachoroidal space. To date there have been few serious complications.17 IOPs have settled in the mid-teens whether performed with or without concomitant cataract surgery.

A similar device under study is the iStent SUPRA.

5) Newer approaches to Cyclo-photocoagulation

Cyclodestructive procedures wheth-er performed trans-sclerally with freezing or with laser energy have been a last gasp effort to control IOP in desperate situations. Because of a small but significant risk of phthisis and frequent chronic inflammation with a fall in vision, most surgeons have shied away from these procedures unless all else has failed.

In recent years, efforts to make cy-clophotocoagulation “kinder and gen-tler” have included an ab interno ap-proach with an endoscopic technique (Endocyclophotocoagulation) and a “micropulse” trans-scleral laser. Since these are not technically MIGS proce-dures, they are not discussed further in this article.

6) SummaryNewer techniques are evolving

with the promise of less risk of vision-threatening complications. Most need more study before being placed in our

1) IntroductionMany advances have occurred in

glaucoma surgery in the last decade. Glaucoma surgeries work in 4 ways: by creating sub-conjunctival filtration, enhancing Schlemm’s Canal outflow, creating suprachoroidal drainage or by cyclodestruction.1

MIGS are a subset of glaucoma surgeries with: an ab interno micro-incision, minimal trauma, efficacy, higher safety, and more rapid recovery (figure 1).2

Currently, some of the most used MIGS are the canal-MIGS: • Trabectome,

• iStent, • Hydrus microstent

and the subconjunctival-MIGS: • the Xen gel implant.

Various patterns of use around the world result from local government approval and availability. Some procedures are available only on a research basis and have not been commercially launched. The Hydrus, Cypass and Xen are pending FDA approval in the USA. The iStent was FDA approved in 2012, in combination with cataract surgery.

Because intraocular pressure

Clinical Issues:

Microinvasive / Minimally invasive glaucoma sur-gery (MIGS)

Ridia Lim MBBS MPH FRANZCO1, Lawrence Oh B Med MD2

1Sydney Eye Hospital, Sydney, Australia2Royal North Shore Hospital, Sydney, Australia

Core Concepts• The most commonly used MIGS are aimed to enhance Sch-lemm’s canal outflow including the Trabectome, iStent and Hydrus microstent. As intraocular pres-sure reduction is modest, these are useful for mild to moderate open angle glaucoma cases, par-ticularly combined with cataract surgery.• The newer gel stent, Xen in-creases subconjunctival filtration and acts like a trabeculectomy. Its target population may be different from canal-MIGS

Figure 1: Classification of glaucoma surgery. Modified from Shaarawy 1

range of anti-glaucoma surgical strate-gies.

While no comparative studies are available yet, possibly some of these newer procedures will allow us to con-sider surgical treatment earlier in the glaucoma treatment paradigm. Safety and predictable effectiveness will de-termine this.

Enhanced interest in better surgical approaches to glaucoma portends ex-citing times ahead.

AbInterno

AbInterno

AbExterno

AbInterno

AbExterno

AbInterno

AbExterno

SubconjunctivalFiltration

EnhancedSchlemm´s

Canal Suprachoroidal Cyclodestruction

Xen

HFDS

Trab(Express)

DeepSclerect-

omy(Class)

Arrow

GDD(Molteno,Baerveldt)

Trabectome

ELT

GATT

Trab360

Viscotrab

iStent

Hydrus

Canal-oplasty

Canal-Expanders

Cypass

iStentSupra

Goldimplant

STARFlo

Agua-shunt

ECP TS-CPC

Cryo

UC3

MIGS

MIGS withdevice

Trab- trabecuelctomyClass- CO2 laser assisted deep sclerectomy

GDD- Glaucoma drainage deviceHFDS- High frequency deep sclerotomy

ELT- Excimer laser trabeculostomyGATT- Goniscopy-assisted transluminal trabeculotomy

ECP- endoscopic cyclophotocoagulationTS-CPS- transscleral cyclophotocoagulation

Cryo- CyclocryotheraphyUC3- ultrasound circular Cyclo coagulation

AbExterno


Practical Tips:

Minimally Invasive Glaucoma SurgeryDr Colin Clement BSc(Hon) MBBS PhD FRANZCOGlaucoma Unit, Sydney Eye Hospital, Sydney, Australia. The University of Sydney, Sydney Australia, Eye Associates, Sydney Australia

Core concepts• Pre-operative gonioscopy is mandatory for selecting appropriate patients.• The irido-corneal angle view is optimised when the patients' head is tilted away and the microscope tilted toward the surgeon with a combined angle of 70-80 degrees.• Under filling the anterior chamber with visco-elastic makes intra-opera-tive gonioscopy difficult.• Avoid limbal blood vessels when positioning the corneal incision as bleeding will obscure the view.

1) IntroductionOne key factor to achieve success with

minimally invasive glaucoma surgery (MIGS) is implantation of the device of choice (eg: iStent Generation1, iStent in-ject, Hydrus, Cypass, iStent SUPRA and Xen) in the correct location. The chance of doing so is maximized by appropriate pa-tient selection and by attention to a number of factors during surgery.

2) Pre-operative Assessment:Pre-operative gonioscopy is mandatory.

Suitable eyes are those with a wide open

angle or those in whom the angle is likely to open widely following removal of cataract. Implantation in angles that are narrow may be technically difficult and lead to periph-eral anterior synechiae (PAS) and stent ob-struction or corneal decompensation if the implant touches the corneal endothelium. Eyes with evidence of elevated epi-scleral venous pressure may not be suitable for a trabecular meshwork bypass stent as there is likely to be insufficient pressure gradient to lower intra-ocular pressure (IOP).

3) Intra-operative:Optimal positioning of the patient and

microscope significantly improves the view of the irido-corneal angle. Usually the eye is approached temporally with a combined angle of 70-80 degrees (microscope 35-40 degrees towards surgeon, patient head 35-40 degrees away from surgeon). Under or over rotation will lead to a poor view of the angle and/or incorrect angle of approach (figure 1). If the surgeon does not achieve an adequate view, the positioning should be adjusted (figure 1).

When filling the anterior chamber with viscoelastic, under filling will result in a low IOP. Whilst this may aid identifica-tion of Schlemm’s canal from blood re-

flux, it makes intra-operative gonioscopy technically difficult. Application of the gonioprism when IOP is low will easily cause corneal striae and result in poor con-tact between prism and cornea (figure 2). Adding more viscoelastic to the anterior chamber will increase the IOP, thus elimi-nating the striae and poor contact. With further filling of the anterior chamber, the IOP will rise further and eventually reach a point when Schlemm’s canal collapses1. Theoretically it may be more difficult to implant some stents such as Hydrus and iStent Generation 1 under these condi-tions, whereas others such as iStent inject, Cypass and Xen may be little affected.

Consider the position of the corneal incision; this can make the difference be-tween easily performing stent implanta-tion or having great difficulty. The location determines the site of entry of the intro-ducer and the section of angle to which the surgeon has access. It may also have an unintended effect on the view through the gonioprism. The corneo-scleral limbus is vascular so too peripheral corneal incisions can cause bleeding that will track across the corneal surface and become embed-ded in the viscoelastic used to couple the lens with the cornea (figure 3). As a result, blood obscures the view and the surgeon will be frustrated by the repeated need to clear the ocular surface. This is easily avoided by positioning the incision mid-peripherally, away from peripheral corneal blood vessels.

References1. Shaarawy T. Glaucoma surgery: taking the sub-conjunctival route. Middle East Afr J Ophthalmol. 2015;22:53-58.

2. Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future direc-tions. Curr Opin Ophthalmol. 2012;23:96-104.

3. Larsen CL, Samuelson TW. Managing Co-existent Cataract and Glaucoma with iStent. Surv Ophthalmol. 2016; doi: 10.1016/j.survoph-thal.2016.01.006.

4. Richter GM, Coleman AL. Minimally invasive glaucoma surgery: current status and future prospects. Clin Ophthalmol. 2016;10:189-206.

5. Sheybani A, Dick B, Ahmed II. Early Clinical Results of a Novel Ab Interno Gel Stent for the Surgical Treatment of Open-angle Glaucoma. J Glaucoma. 2015; Nov 10:Epub ahead of print.

6. Fea A, Cannizzo PM, Consolandi G, Lavia CA, Pignata G, Grignolo FM. Managing Draw-backs in Unconventional Successful Glaucoma Surgery: A Case Report of Stent Exposure. Case Rep Ophthalmol Med. 2015;2015:847439.

5) ConclusionMIGS are a heterogenous group of

surgeries still to be placed optimally in the glaucoma treatment paradigm. As availability and experience increase, we will have the chance to choose the optimal procedure for each patient.

Fig 2. The Xen implant (Courtesy of Allergan)

reduction (IOP) is more modest, in keeping with a higher target IOP, MIGS surgeries target an earlier stage of glaucoma than incisional glaucoma surgeries; they are particularly useful when combined with cataract surgery. The procedures along with their safety and efficacy are described in detail elsewhere in this edition of Glaucoma Now.

2) Enhanced Schlemm’s Canal MIGS

Many current MIGS aim to enhance Schlemm’s canal outflow. There are variations without and with stents: the iStent, iStent inject and the Hydrus microstent (figure 1).

The ideal patients for canal-MIGS are those with mild to moderate open angle glaucoma, either well-controlled or modestly uncontrolled on 1 to 3 medications.3 They should be avoided in angle closure, anomalous angles, most secondary glaucomas (such as uveitic and neovascular glaucomas, raised episcleral venous pressure),3,4 eyes with extremely high IOPs and eyes that require very low target IOPs.4 Canal-MIGS appears to work best when there are functioning collector channels and aqueous veins. Further research might enable us to identify these eyes preoperatively.

3) Suprachoroidal drainage MIGS

The Cypass and iStent SUPRA try to achieve suprachoroidal drain-age. Further study will determine whether target populations for the suprachoroidal-MIGS are similar to those for canal-MIGS

4) Subconjunctival filtration MIGS

The Xen gel stent is a permanent device that connects the anterior chamber to the subconjunctival space (figure 2).5 The Xen45 is the model that has been commercially launched in some parts of the world; currently it is available in EU, Turkey, Canada and Switzerland.

Being a subconjunctival-MIGS, the Xen is claimed to reduce IOP more significantly than other MIGS procedures; it might be useful for a different target population: it acts more like a trabeculectomy. Patient with higher IOPs may be suitable for the Xen as the final IOP is determined by Xen’s lumen and length (Hagen-Poiseuille equation).5 Target eyes have open angle glaucoma with indications for a trabeculectomy and have at least 2 clock hours of healthy conjunctiva in the target area.5 Xen has been used in a case of previously failed trabeculectomy.6 Secondary glaucomas should be avoided; further studies are required to refine those patients most likely to benefit from the Xen.

Figure 2. IOP Too Low - view obscured by corneal striae and poor contact between gonioprism and corneal surface.

References1. I. Grierson, W.R. Lee. Changes in the monkey outflow apparatus at graded levels of intra-ocular pressure: a qualitative analysis by light microscopy and scanning electron microscopy. Experimental Eye Research. Volume 19, Issue 1, July 1974, Pages 21–33

Figure 3. Poorly Positioned Corneal Incision - a limbal incision results in bleeding on the ocular surface (a.) that in turn obscures the view when the gonioprism is placed in position (b.).

Figure 1. Head & Microscope Position - insufficient angle results in a poor view of the angle (a.). Increasing the head/microscope tilt brings the angle structures into view (b.)

12 Glaucoma Now – Issue No 3, 2016. www.glaucomanow.com

STATEMENT OF NEED AND PROGRAM DESCRIPTIONRecent months and years have seen significant ad-

vances in our understanding of glaucoma. Much has been learned, not only about damage mechanisms and pathogenesis, but also about diagnosis and manage-ment. Treatment options – both medical and surgical – continue to expand. This program will review this new knowledge with an emphasis on incorporating recent insights into day-to-day practice.

DATE OF ORIGINAL RELEASEDate of original release: December 2016.

Approved for a period of 12 months.This issue is accredited for Continuing Medi-

cal Education (CME) by the Physicians' Chamber of Baden-Württemberg, Germany (Local Medical Re-sponsible: Andreas Buchholz, MD, PhD, ROph).

DISCLAIMERParticipants have an implied responsibility to use newly

acquired information to enhance patient outcomes and professional development. The information presented in this activity is not meant to serve as a guideline for patient care. Any procedures, medications, or other courses of di-

For each issue 3 CME credits can be obtained by successfully passing the multiple choice test on our website!

In order to maximize the learning effect, participants have the opportunity to register at our website and to an-swer a number of multiple choice questions for each of the four sections covering the key points of each section. Shortly after completion of the test participants receive electronic feedback on successful accomplishment or fail-ure. In case of failure the participant is encouraged to re-view the articles and then to retake the test.

A successful test will earn the participant valuable Con-tinuing Medical Education (CME) points needed for their continuous medical education efforts.

Accreditations:· CME approval by the Physicians' Chamber of Baden-

Württemberg, Germany has been granted for all issues since 2012, automatically implying acceptance of credits throughout the European Union and associated countries.

· Glaucoma Now is recognized by the Royal Australian and New Zealand College of Ophthalmologists as a valid Continuing Professional Development activity.

· Since 2013 the program is recognized by the Brazilian Council of Ophthalmology. Brazilian physicians success-fully taking CME tests on our website are automatically awarded CME points by CBO.

agnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications or dan-gers in use, applicable manufacturer’s product information, and comparison with recommendations of other authori-ties.

CONTRIBUTORS• Ike Ahmed, MD is Professor of Ophthalmology

at the University of Toronto, Toronto, Canada. Within the last 3 years he has acted as a consultant to Glaukos, Ivantis, Allergan, Alcon and Santen. His co-author Mi-chael Stone MD is glaucoma specialist at the University of Toronto, Toronto, Canada. He has no commercial re-lationship to disclose.

• Robert Stamper, MD PhD is Professor of Oph-thalmology at the University of California in San Fran-cisco, USA. He is, or has been within the last 3 years, a consultant to Transcend Medical and Sight Sciences.

• Ridia Lim MBBS MPH FRANZCO is a specialist at Sydney Eye Hospital, while her co-author Lawrence Oh B Med MD is specialist at the Royal North Shore Hospital in Sydney, Australia. They have no commercial relationship to disclose.

• Colin Clement MBBS PhD BSc (Hons) FRAN-ZCO, is glaucoma specialist at the Glaucoma Unit of Sydney Eye Hospital. He is also Clinical Lecturer at Cen-tral Clinical School at The University of Sydney, Sydney, Australia. He has no commercial relationships to dis-close.

DISCLOSURE STATEMENT EDITORIAL BOARD

Ivan Goldberg serves on the Faculty and Advi-sory Boards of the following com panies: Alcon, Allergan, Merck, Pfizer and Forsight Vision.

Remo Susanna serves on the Faculty and

Advisory Boards of the following compa-nies: Alcon, Allergan, Merck and Pfizer.

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