Reaching a consensus

Minimally invasive surgical techniques that leave the sclera and conjunctiva intact, collectively known as minimally invasive glaucoma surgery (MIGS), have been increasingly adopted by eye surgeons in Europe and North America, but their place in current glaucoma practice is still being fine-tuned. “I think people are still evaluating the role of MIGS and where it stands and where it fits in glaucoma therapy. It is still a relatively new idea and is still relatively uncharted territory in terms of which patients may benefit in the long-term in terms of cost-effectiveness,” Ike Ahmed MD, University of Toronto, Ontario, Canada told EuroTimes in an interview. The MIGS techniques include a range of ab interno implants, and an electric micro-cautery device. They are designed to provide an outlet for aqueous into the venous system without dissection of the conjunctiva or sclera, and include devices introduced by way of Schlemm’s canal and the collector channels, through the suprachoroidal space, or through a subconjunctival bleb. The procedures are performed through small incisions generally in combination with cataract surgery. BETWEEN TRABECULECTOMY 
AND MEDICATION At present, the reduction of intraocular pressure (IOP) remains the only effective treatment for glaucoma, and trabeculectomy remains the most effective means for lowering IOP. The popularity of the procedure rose steadily from the time of its introduction in the mid-1960s up to the mid-1990s, but declined steeply following the introduction of prostaglandin eye drops. MAJOR ADVANCE The new medications were therefore hailed as a major advance in the treatment of glaucoma, because they appeared to delay the need for surgery and its accompanying side effects on vision, and its sight-threatening postoperative complications, such as hypotony maculopathy, and endophthalmitis. However, the new medications also present problems. They are costly, and many patients find the daily routine of instilling the drops irksome and uncomfortable. They can also cause changes in eye colour and eyelid skin, as well as stinging, blurred vision, eye redness, itching, and burning. Moreover, they must often be combined with other older IOP-lowering medications, which have their own range of local and systemic side effects. Many patients have difficulty adhering to their prescribed regimens, thereby partly negating their potential benefit. Meanwhile, various implants have been devised as a means of providing a safer and less traumatic alternative to trabeculectomy. They include the Molteno tube and the Ahmed Valve and provide an IOP reduction only slightly less than that provided by trabeculectomy, but with significantly fewer reoperations. More recently, the MIGS devices have become available as a means of reducing the medical burden in patients with well-controlled but not far advanced glaucoma. SPEEDY RECOVERY “Traditionally, surgery has been reserved for patients with very advanced disease and these new procedures are not really designed for that kind of patient. They are instead designed as an alternative to medication, something that can be used earlier and in place of traditional surgery. MIGS is predicated on the idea of speedy recovery, less impact to the structure of the eye, and less refractive and visual changes. What we’re saying is that it works well in early disease,” Dr Ahmed said. Argon laser trabeculoplasty (ALT), and later, selective laser trabeculoplasty (SLT) had already provided an almost completely non-invasive means of reducing the need for medication in glaucoma patients. Like MIGS, the treatment provides IOP reductions approximately equivalent to topical medications. However, the effect of a single SLT procedure diminishes over time. Although SLT can be repeated without reduced effect, each treatment entails the risk of anterior chamber reaction/uveitis, which occur in approximately one third to one half of patients, depending on the circumferential extent of the laser treatment. Furthermore, although current European Glaucoma Society Guidelines recommend SLT as a potential second-line treatment, the laser procedure appears to be most effective when used as a first-line treatment. Prior use of prostaglandin analogues diminishes its efficacy and when SLT is used as a second-line treatment, the subsequent use of prostaglandins has little additional effect. SUPERIOR OPTION The advent of MIGS technology may provide a superior option to SLT. Dr Ahmed and colleagues published a study comparing SLT and the intracanalicular Hydrus™ Microstent (Ivantis). At 12 months there was a significant decrease in both IOP and medications among 31 primary open-angle glaucoma (POAG) patients who underwent a stand-alone implantation of the microstent. However, in the SLT group, only the decrease in IOP was significant. There was also a threefold greater reduction in medication use in the Hydrus group compared with SLT (p=0.001). (Fea et al, Clinical and Experimental Ophthalmology 2017; DOI: 10.1111/ceo.12805) “If you look at the data and try to compare SLT with MIGS – which is difficult to do with confidence – I think that with MIGS we do see less medication use postoperatively and pressure drops,” said Dr Ahmed. He added that a study by Glaukos is under way comparing SLT and dual implantation of the newer collar-button designed iStent, the iStent inject, in a cohort of 500 patients. Another of the implants, the XEN® Gel Stent (AqueSys) implant is a subconjunctival filtration device. However, unlike trabeculectomy and other filtration surgeries, it creates a filtration pathway from inside the eye without dissection of the sclera or conjunctiva. It is composed of a soft pliable collagen-derived gelatin material. It is inserted using a 27-gauge needle and visualising the meshwork with a gonio mirror. The results in 216 open-angle glaucoma patients from the still ongoing APEX study showed that, at 24 months following cataract surgery and implantation of the XEN device, mean IOP was reduced from 21.4mmHg on a mean of 2.6 medications to 13.1mmHg, with a mean use of 0.7 medications. The results were therefore similar to those achieved with trabeculectomy. However, the needling rate was much higher than that seen with trabeculectomy. LESS INVASIVE “Due to its less invasive nature, XEN may be considered as a surgical step prior to other filtering techniques such as trabeculectomy or seton tubes. After a superonasal XEN implantation, other filtering surgeries can still be performed as a subsequent step if needed,” said Ingeborg Stalmans MD, PhD, University Hospitals UZ Leuven, Belgium, who participated in the study. She added that, although bleb-related complication can occur after any filtering procedure, they are expected to be less frequent in procedures without conjunctival incisions and with lower doses of mitomycin C. Long-term comparative studies will be necessary to prove whether that is true. “The bleb morphology is different between XEN and trabeculectomy, presumably in part due to the fact that the conjunctiva has not been surgically dissected during XEN implantation and the outflow of aqueous is slow. Optical coherence tomography studies by Prof Herbert Reitsamer in Salzburg have shown that the blebs after XEN implantation are often less elevated and more diffuse,” she added. Keith Barton MD, FRCP, FRCS, Moorfields Eye Hospital, London, UK, told EuroTimes that although the XEN implant and trabeculectomy achieve similar IOP reductions, trabeculectomy has a better record in terms of elimination of the need for medications. “If you do a trabeculectomy you get probably 65% of patients off medications completely; if you do a XEN implant it is more like 30% to 40%. Overall, this means that you get a good chance of good IOP control with or without medications,” he said. He added that this type of procedure may be less appropriate for surgeons whose main focus is on cataract surgery, because of its bleb-management issues. STAND-ALONE PROCEDURE The majority of studies involving MIGS have involved patients who were also undergoing cataract surgery, which itself lowers IOP to a small extent. However, there are a limited number of studies that describe the use of MIGS devices as a solo, or stand-alone procedure. “The first cases that we've been looking at have been in cataract surgery, because since the surgeon is already in the eye we can also do something for their glaucoma and their IOP control. And that is really where MIGS has made an impact. I will say that that’s just the surface of it - there is a whole other opportunity for patients who have either had cataract surgery or don't need cataract surgery where we can use it as a stand-alone procedure,” said Dr Ahmed. Dr Barton concurred, but noted that the bar for efficacy and cost needs to be set higher for stand-alone MIGS than for MIGS combined with cataract surgery. “Combined cataract surgery and MIGS is much more of a no-brainer than stand-alone MIGS. You get the patients off the medications and the only additional requirement is five more minutes of surgery and the cost of the implant. But I think if we can prove a sustained five-year reduction of IOP with MIGS as a stand-alone procedure, that will be a real worthwhile benefit for patients,” he said. At the same time he cautioned against using MIGS in patients with advanced disease. “If you get very advanced glaucoma you really need to fix the problem. Rather than trying something and seeing if that’ll work and then trying something else, I go straight for trab,” he said. STRENGHTS AND WEAKNESSES Dr Ahmed noted that it will take time to develop a consensus as to when and in which patients to use MIGS devices. The evidence for that consensus will come as people use it and realise its pros and cons, its strengths and weaknesses. “If you look at the trends around the world, certainly in the US there has been a big uptake of MIGS and it’s continuing to grow. And around the world in different pockets we see an increase. It will take time. But in my opinion, there is no immediate need to rush into anything – it’s a matter of how the technology evolves,” he added. Ike Ahmed: ike.ahmed@utoronto.ca Ingeborg Stalmans: 
ingeborg.stalmans@mac.com Keith Barton: keith@keithbarton.co.uk