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HomemiophthalmologyDevices Expanding Horizons: Minimally Invasive Glaucoma Surgery

Devices Expanding Horizons: Minimally Invasive Glaucoma Surgery

In a comprehensive report of minimally invasive glaucoma devices that are currently available, sitting in the wings, and emerging, Dr Sartaj Sandhu reports that minimally invasive glaucoma surgery (MIGS) is anything but minimal.

Glaucoma is the leading cause of irreversible blindness worldwide.1 Initially, as with any disease, medical or ‘conservative’ therapy is applied, including eye drops and the more recently popular selective laser trabeculoplasty. Both options lower eye pressure, which is the only modifiable risk factor in glaucoma.

Minimally invasive glaucoma surgeries can be performed at the same time as cataract surgery, which works well to reduce the number of surgeries that a patient may be subject to

Traditionally, when these therapies fail, incisional surgery, such as trabeculectomy or a glaucoma drainage device, is required to control the eye pressure. Surgical intervention can result in variable intraocular pressures (IOPs) with a wide range of complications, both early and late. Frequent follow-up, as well as prolonged recovery time and vision fluctuation, can be factors that may put patients and surgeons ‘off ’. Hence, the surgical options were traditionally delayed until later in the disease course. Even with medical treatment there are barriers to use, such as non-compliance, poor technique, intolerance of medication side effects, as well as financial burden, and physical conditions (such as arthritis).

Since the early 2000s, glaucoma as a subspecialty has experienced an explosion of options to fill the treatment gap that exists between patients who require more than medication but are not quite ready to commit to complex filtration or tube surgery.

The potential complications and higher rate of surgical failure seen with traditional incisional glaucoma operations have led to the need for better procedures, which are minimally invasive and effective, to target mild-to-moderate glaucoma.2 The term ‘minimally invasive glaucoma surgery’ (MIGS) was coined by Dr Ike Ahmed in 2009.3 To qualify as a MIGS device or procedure, the surgical intervention generally shares the following five characteristics:4

1. A high safety profile: compared with traditional incisional surgeries, there is a lower risk of low IOP (hypotony), or choroidal complications (such as effusions or haemorrhage),

2. Minimal disruption of normal anatomy: the intended effect is to enhance existing anatomy rather than alter it in a major way,

3. Ab interno approach: it can be performed through a (mostly) temporal incision used as part of cataract surgery with direct visualisation of the angle structures,

4. Efficacy: there is an expected reduction in IOP, or at least the medication burden (reduction of number of eye drops), and

5. Rapid recovery and easily incorporated into phacoemulsification surgery: this allows for a more favourable uptake by surgeons and patients alike.

Minimally invasive glaucoma surgeries can be performed at the same time as cataract surgery, which works well to reduce the number of surgeries that a patient may be subject to during their lifetime. The skills required to perform this set of surgeries involve an intimate knowledge of, and experience with, angle structure and anatomy. Angle anatomy can be highly variable between patients and sometimes even between the two eyes in the same person. The safety profiles are generally favourable between devices and are less invasive than traditional incisional operations,5 to varying degrees.

Broadly speaking, MIGS procedures can either bypass or enhance the conventional aqueous outflow.6 The currently available MIGS target one of three regions of the anterior segment anatomy:5

1. Trabecular outflow pathway or ‘angle based’: redirection of aqueous humour flow towards the Schlemm’s canal,

2. Subconjunctival space: diverting the aqueous humour to the subconjunctival space (not discussed in this review), or

3. Suprachoroidal space: diverting the aqueous humour to the uveoscleral outflow pathway via the suprachoroidal space.

It is estimated that up to 75% of the resistance to aqueous outflow is at the trabecular meshwork and the inner wall of Schlemm’s canal.7 Angle-based MIGS take advantage of the lower resistance within the Schlemm’s canal and divert aqueous flow to the canal, overcoming most of the resistance. Patients with advanced glaucoma, however, usually have a significant amount of aqueous outflow resistance, which makes these devices inadequate on their own. Within, I will attempt to summarise the pertinent points on currently available MIGS – both in Australia and elsewhere – but will not discuss any bleb-forming devices.

Categories of MIGS devices:2
1. Trabecular bypass implant,
2. Ab-interno canaloplasty,
a. Combined with viscodilation,
3. Ab-interno trabeculotomy,
a. Combined with viscodilation,
4. Goniotomy,
5. Suprachoroidal shunt.

Trabecular Bypass Implants

iStent Inject and iStent Inject W

Figure 1. The iStent inject trabecular micro-bypass stent.

The iStent inject trabecular micro-bypass stent (Figure 1, Glaukos Corporation, San Clemente, California, USA) is the second-generation iteration of the trans-trabecular device. This is one of the smallest known medical devices to be implanted in the human body. It is composed of titanium and is a third of the size of the first generation iStent (not discussed here). There are two stents within the injector. Each stent contains a central inlet and multiple outlets designed to provide multi-directional flow through Schlemm’s canal.8 There is a lower risk of hypotony and hypotony-related complications with a favourable safety profile. There is, however, a high risk of fibrosis that may lead to device obstruction. Transient microhyphaema is perhaps the most frequently encountered complication. Stent malposition and obstruction can also occur, which can be solved by laser intervention, failing which the implant can be removed and replaced. There are no reports yet of persistent hypotony, choroidal effusions or endophthalmitis.

There is a proven additive IOP lowering effect of inserting more than one implant and hence the iStent inject and iStent inject W have two implants each. The IOP reduction is modest (31% at two years),9 so it is best suited for patients with mild-to-moderate grade glaucoma. The newer generation iStent inject W (essentially similar in profile to the iStent inject but with a larger flange diameter) does not have published data available for comparison. It does, however, allow better visualisation and placement for the surgeon.

Furthermore, there is ongoing interest in implanting three devices, with studies currently underway.

Hydrus Microstent

Figure 2. Hydrus Microstent.

Hydrus Microstent (Figure 2, Alcon Laboratories, Fort Worth, Texas, USA) is a curved, flexible 8mm nitinol (a biocompatible nickel titanium alloy) implant, with an open frame-like structure to hold the Schlemm’s canal open, thus enhancing trabecular outflow. The device has three openings along its anterior surface and is wide open on its posterior surface. It is curved to match the shape of Schlemm’s canal and implanted using a preloaded hand-held injector. The implant allows dilation of the canal by four to five times its usual calibre. The device covers approximately three clock hours of the canal. The implantation of this device is considered slightly more challenging than the iStent implant, however is generally considered safe and complications are not commonly encountered. Formation of peripheral anterior synechiae has been reported at a higher rate when compared with patient groups that underwent cataract surgery alone.10

However, this has not been associated with elevated IOP. There is also minor concern about an incremental, non-statistically significant loss in mean endothelial cell count, which has been observed in the HORIZON randomised control trial.11 The latest results from the HORIZON cohort of patients show a non-statistically significant higher incidence of clinically significant (i.e., more than 30% change from baseline) endothelial cell loss in the Hydrus microstent implant with cataract surgery group (20.8%) compared with the cataract surgery alone group (10.6%) over the five-year period.11 The authors noted that none of the patients in either group developed clinically significant corneal oedema, decompensation or other clinical sequelae.

Few studies have been conducted to compare between these two MIGS devices, one such study analysed iStent versus Hydrus.11 The IOP reduction results, as well as the safety profile, were similar, however the Hydrus microstent more often reduced the need for postoperative glaucoma medications.

AB-Interno Canaloplasty

Ab-interno canaloplasty (AbiC) using the iTrack system (Figure 3, Nova Eye Medical, South Australia, Australia) is an implant free procedure using a catheter. The iTrack is designed to bypass collector channel ostia and push trabecular meshwork herniations out of the ostia with minimal tissue trauma, and with an illuminated fibre optic tip for added assurance of catheter location.12 On removal of the catheter, the viscoelastic material is injected to ensure dilation of the canal. In terms of adverse effects, hyphaema is frequently reported and occasionally, damage can occur to adjacent structures, such as Descemet’s membrane, iris, and even the posterior capsule.13

Figure 3. Ab-interno canaloplasty using the iTrack system.


Figure 4. AbiC using the Omni Surgical System.

AbiC using the iTrack system has shown an average of 30% reduction in IOP and a 50% reduction in medication usage.14

AbiC using the OMNI Surgical System (Figure 4, OSS, Sight Sciences, Menlo Park, CA, USA) facilitates the microcatheterization of Schlemm’s canal circumferentially, allowing ab interno canaloplasty followed by trabeculotomy, if desired, using a handheld system. This device with the ability to viscodilate, similar to the iTrack system, can address the resistance encountered at the trabecular meshwork, Schlemm’s canal, and the distal collector channels. The two-year results from the ROMEO study suggest that IOP reduced by 28% in the cohort that underwent both the canaloplasty / trabeculotomy and that medications reduced by 39% in the same group.15

Adverse events reported in the ROMEO study included inflammation (over and above that expected from cataract surgery alone), hyphaema, and IOP spike, especially during the first 12 months. However, in the second year post-procedure, no device-related adverse events were noted.15

AB-Interno Trabeculotomy

Although the ab-interno trabeculotomy can be performed using both the iTrack and Omni systems, it can also be performed using a 4-0 or 5-0 prolene or nylon suture instead of a microcatheter. In the gonioscopy assisted transluminal trabeculotomy (GATT) procedure, microsurgical forceps are used to advance the microcatheter or suture into the Schlemm’s canal circumferentially. Once it has been passed through the entire canal, the distal end of the catheter is grasped and the proximal end is retracted out of the eye, shearing the trabecular meshwork to create a complete 360º trabeculotomy.16

One study16 initially reported encouraging results having performed the GATT in patients at the same time of cataract surgery or as a stand-alone procedure. An average IOP reduction of 10mmHg, as well as medication reduction of one agent, was noted. Early hyphaema has been reported in approximately 30% of patients, however with the use of viscodilation (alongside iTrack or Omni), this may be less so. There have been further encouraging reports of the efficacy of GATT17 in primary and secondary open angle glaucoma as well as paediatric and juvenile glaucoma. This conjunctival sparing technique is promising and further data is awaited to demonstrate its longevity and efficacy.

Goniotomy

Kahook Dual Blade Goniotomy The Kahook Dual Blade (KDB) (Figure 5, New World Medical Inc, Rancho Cucamongo, CA, USA) is used to excise a strip of trabecular meshwork using a handle and a sharp blade angled at 10º. Usually, three to four clock hours can be safely removed under direct gonioscopic view. One of the advantages of the KDB is that it does not leave behind a permanent implant in the eye. The adverse effects most commonly include hyphaema and IOP spikes. In fact, hyphaema can be considered a sign of procedure success as it exposes collector channels to the anterior chamber of the eye.

Figure 5. The Kahook Dual Blade.

There are also isolated reports of corneal oedema and cystoid macular oedema.18

Studies have reported approximately 20–25% reduction in IOP in up to 70% of patients at one year.19 Thus far, good results have been observed in secondary open angle glaucoma, such as pseudoexfoliation with the removal of dysfunctional trabecular meshwork. There is even evidence to suggest some benefit in congenital glaucoma and refractory /advanced glaucoma.19

Trabectome

Figure 6. The Trabectome.

The Trabectome (Figure 6, MicroSurgical Technology, Redmond, Washington, USA) uses ablation of the trabecular meshwork with a 550-kHz bipolar electrode to facilitate irrigation, aspiration, and electrocauterisation. The 19.5-gauge-tip is designed to fit through the existing main incision wound during cataract surgery (1.6mm or wider). Simultaneous aspiration and irrigation help remove debris and maintain stability of the anterior chamber.

The Trabectome can reduce IOP by up to approximately 40%.20 It has also been shown to be effective in narrow angle glaucoma, refractory glaucoma, and even after failed trabeculectomy. Adverse effects include transient hyphaema as well as delayed onset hyphaema (greater than two months postprocedure) and IOP spikes.21

Suprachoroidal Shunts

There is great interest in exploiting the alternative or ‘unconventional’ drainage pathway for aqueous via the suprachoroidal route. Since they are performed ab-interno and ‘blebless’, the procedure can avoid serious complications associated with subconjunctival bleb creation (with anti-fibrotics) – such as hypotony, leakage, infection, and failure – as well as bleb dysthesia, which can cause pain and discomfort.22 On the other hand, fibrosis and implant failure can follow if the material is not truly biocompatible. It is therefore a delicate balance and emerging devices will need to overcome these challenges to be considered superior to the traditional gold standard glaucoma operations.

Figure 7. Cypass micro-stent.

Prior to discussion of the devices available in this section, it is worth mentioning the Cypass micro-stent (Figure 7, Alcon Laboratories, Inc, Texas, USA). Cypass micro-stent was made of biocompatible polyimide and fenestrated along its length with pores of 76 micrometres in diameter to allow aqueous humour flow. The built-in retention rings allowed the device to be held in place via an ab-interno procedure. There was an IOP lowering effect and reduction of medications in a significant number of patients. However, the endothelial cell loss encountered was twice as much in the group that underwent cataract with Cypass micro-stent versus cataract surgery alone.23 This device was withdrawn from the market in 2018 due to concerns about the adverse effects on the corneal endothelial population from malpositioning.24

Miniject (Figure 8, iStar Medical, Wavre, Belgium) is made from a flexible silicone microporous material named ‘Star’, which is derived from NuSil med-6215 (a silicone elastomer) spanning 5mm by 1.1mm. It has a ‘porous’ structure and this promotes biointegration. The recently published Star-I prospective, multi-centre trial showed an impressive mean IOP reduction of 40% with a medication reduction of almost 50% in a small cohort of patients (21 followed over 24 months).

Figure 8. The Miniject.

This first-in-human trial was conducted in patients that were both phakic and pseudophakic (approximately 50% split) and had mild-to-moderate open angle glaucoma. It shows promise, especially as no adverse effects were reported, unlike a similar device, the Starflo (iStar Medical, Wavre, Belgium), which was associated with severe complications, such as corneal decompensation, hypotony, and choroidal haemorrhage.25 Significantly, Starflo was placed ab-externo, which differentiates it from the Miniject, which is inserted using an ab-interno procedure.

iStent Supra

Figure 9. The iStent Supra.

The iStent Supra (Figure 9, Glaukos Corporation, San Clemente, California, USA) is a biocompatible polymer with a titanium sleeve. It is a 4mm long curved stent with a heparin-coated lumen of 165 micrometres. It has received the CE mark in Europe and is awaiting approval in the United States. The iStent Supra is inserted similarly to the Cypass micro-stent via an ab-interno procedure, either at the time of cataract surgery or as a stand-alone under gonioscopic guidance. Earlier trials employed post-operative travoprost and demonstrated greater than 20% reduction in IOP in 98–100% of study patients.26

No major adverse events were reported, apart from self-limiting early hypotony and choroidal effusions which resolved by post-operative month three. There is an ongoing trial in the USA,27 which has not yet been reported.

Looking to the Future

For patients with mild-to-moderate glaucoma, MIGS devices are promising.

Their modest IOP lowering effect could lead to a reduction in the number of medications that the patient is using.

Their main advantage, however, is a lack of bleb formation, which avoids complications that the subconjunctival space can be subjected to. Preservation of the conjunctiva is an important by-product of this arrangement as it can then be used by the surgeon at a later time. Data on longevity of MIGS is emerging, however tissue reaction / fibrosis, and subsequent implant failure are frustrating endpoints. Appropriate use of biocompatible material (minimising tissue reaction /fibrosis surrounding the device) could be possible answers. The future of minimally invasive glaucoma surgery is anything but minimal.

Dr Sartaj Sandhu FRANZCO MBBS BSc (Med Sci) (Hons) MMed (Ophthal Sci) is an experienced cataract and glaucoma surgeon with a proficiency in the management of complex /advanced cataracts, minimally invasive glaucoma surgery (MIGS), glaucoma, and retinal diseases.

He completed specialist ophthalmology training at Sydney Eye Hospital and a comprehensive ophthalmology fellowship at the Concord Repatriation General Hospital before undertaking a complex anterior segment, MIGS, and glaucoma sub-specialty fellowship at Birmingham and Midland Eye Hospital in the United Kingdom.

Dr Sandhu is actively involved in research and teaching and is a Visiting Medical Officer (Glaucoma) at Royal Prince Alfred Hospital. He practises at various locations around Sydney including Northern Sydney Cataract, Gordon Eye Surgery, Northern Beaches Eye Surgery / Freedom Eye Laser.

References
1. Tham, Y., Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology, 121, 2081–90. 2014.
2. Wagner, I., Updates on the diagnosis and management of glaucoma. Mayo clinic proceedings: Innovations, quality and outcomes, 6(6), 618–35. 2022.
3. Ahmed, I., A brief history of MIGS. The Ophthalmologist. 15 August 2017.
4. Saheb, H., Ahmed, I.I.K., Micro-invasive glaucoma surgery: current perspectives and future directions. Current Opinions in Ophthalmology, 23(2), 96–104. 2012.
5. Pereira, I., Conventional glaucoma implants and the new MIGS devices: a comprehensive review of current options and future directions. Eye (London), 35(12), 3202–21. 2021.
6. Lusthaus, J., The effects of trabecular bypass surgery on conventional aqueous outflow, visualized by hemoglobin video imaging. Journal of Glaucoma, 29(8), 656–65. 2020.
7. Johnson, M., What controls aqueous humour outflow resistance? Experiments in Eye Research, 82(4), 545–57. 2006.
8. Le, K., iStent trabecular micro-bypass stent for open-angle glaucoma. Clinical Ophthalmology, 8, 1937–45. 2014.
9. Samuelson, T., Prospective, randomized, controlled pivotal trial of an ab interno implanted trabecular microbypass in primary open-angle glaucoma and cataract: two-year results. Ophthalmology, 126(811–21). 2019.
10. Pfeiffer, N., A randomised trial of a Schlemm’s canal microstent with phacoemulsification for reducing intraocular pressure in open-angle glaucoma. Ophthalmology, 122, 1283–93. 2015.
11. Ahmed, I., A prospective randomized trial comparing Hydrus and iStent microinvasive glaucoma surgery implants for standalone treatment of open-angle glaucoma: the COMPARE study. 2020 Ophthalmology, 127(52–61).
12. Gallardo, M., 24-month efficacy of viscodilation of Schlemm’s canal and the distal outflow system with iTrack ab-interno canaloplasty for the treatment of primary open-angle glaucoma. Clinical Ophthalmology, 15, 1591–99. 2021.
13. Gillman, K., Combined ab interno viscocanaloplasty (ABiC) in open-angle glaucoma: 12-month outcomes. International Ophthalmology, 41, 3295–301. 2021.
14. Gallardo, M. Viscodilation of Schlemm’s canal for the reduction of IOP via an ab-interno approach. Clinical Ophthalmology, 12, 2149–55. 2018.
15. Williamson, B., Canaloplasty and trabeculotomy with the OMNI system in patients with open-angle glaucoma: Two-year results from the ROMEO study. Clinical Ophthalmology, 17, 1057–66. 2023.
16. Grover, D.S., Godfrey, D.G., Smith, O., et al., (2014). Gonioscopy-assisted transluminal trabeculotomy, ab interno trabeculotomy: technique report and preliminary results. Ophthalmology, 121(4), 855–861.
17. Grover, D.S., Smith, O., Fellman, R.L., et al., (2018). Gonioscopy-assisted Transluminal Trabeculotomy: An Ab Interno Circumferential Trabeculotomy: 24 Months Follow-up.Journal of glaucoma, 27(5), 393–401.
18. Ventura-Abreu, N., Twelve-month results of ab inferno trabeculectomy with Kahook dual blade: An interventional, randomised, controlled clinical study. Graefes Archives of Clinical and Experimental Ophthalmology, 259, 2771–81. 2021.
19. Sieck, E., Outcomes of Kahook dual blade goniotomy with and without phacoemulsification cataract extraction. Ophthalmology: Glaucoma, 1(1), 75–81. 2018.
20. Minckler, D., Clinical results with the trabectome, a novel surgical device for treatment of open-angle glaucoma. Transactions of the American Ophthalmological Society, 104, 40–50. 2006.
21. Ahuja, Y., Clinical results of ab interno trabeculotomy using the Trabectome for open-angle glaucoma: The Mayo Clinic series in Rochester, Minnesota. American Journal of Ophthalmology, 156, 927–35. 2013.
22. Gigon, A., & Shaarawy, T., (2016). The suprachoroidal route in glaucoma surgery. Journal of current glaucoma practice, 10(1), 13–20.
23. Reiss, G., Safety and efficacy of CyPass supraciliary micro-stent in primary open-angle glaucoma: 5-year results from the COMPASS XT study. American Journal of Ophthalmology, 208, 219–225. 2019.
24. Lee, R., Translating minimally invasive glaucoma surgery devices. 13, 14–25. 2020.
25. Fili, S., The STARfloTM glaucoma implant: a single-centre experience at 24 months. Graefe’s Archives of Clinical and Experimental Ophthalmology, 257, 2699–706. 2019.
26. Myers, J., Prospective evaluation of two istent trabecular stents, one istent supra suprachoroidal stent, and postoperative prostaglandin in refractory glaucoma: 4-year outcomes. Advances in Therapy, 35(3), 395–407. 2018.
27. Clinicaltrials.gov NCT no. 01461278.

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