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MIGS alone or combined?

RCTs and the FDA say ‘no’ to standalone MIGS; experience may say ‘yes’.

Howard Larkin

Posted: Saturday, June 6, 2020


Keith Barton MD

Minimally invasive glaucoma surgery techniques (MIGS), including trabecular bypass procedures as well as suprachoroidal and, potentially, subconjunctival shunts, offer surgeons a wide range of options for treating mild to moderate glaucoma and ocular hypertension. But should they be used alone or only in combination with cataract surgery?

The answer is simple, said Keith Barton MD, FRCP, FRCS, in a debate at ESCRS Glaucoma Day 2019 in Paris, France. “MIGS are only fit for combined surgery. Why? Because the only randomised clinical trial evidence is in combined surgery.”

It’s a matter of risk vs benefit, explained Dr Barton, of Moorfields Eye Hospital, London, UK. So far, the proven efficacy of MIGS procedures of all types is modest, he noted. For patients already undergoing cataract surgery the risk is reasonable. “For a standalone procedure, you have a much higher bar … [and] there is no real standalone evidence,” he argued.

Dr Barton cited several studies in support of his argument. For example, a prospective randomised study involving 240 patients with primary open-angle glaucoma and cataract implanted with the iStent (Glaukos, Laguna Hills, California, USA) trabecular bypass device with cataract surgery found 72% of iStent eyes reached a target IOP of 21mmHg or less compared with 50% for cataract surgery only eyes one year after surgery, and 66% and 48% respectively saw IOP reduction of 20% or more. The results are statistically significant, but the gains over cataract surgery alone are not huge. (Samuelson TW et al. Ophthalmology 2011;118:459-467.)

Similarly, before it was removed from the market, a two-year study of the CyPass (Transcend Medical, Menlo Park, California, USA) supraciliary microstent involving 505 patients found mean unmedicated IOP 2.0mmHg lower in the CyPass group than the cataract surgery group, with medication use 67% lower in the Cypass group – once again significant, but modest, gains. (Vold S et al. Ophthalmoloy 2016;123:2103-2112.).

The US FDA agrees that MIGS should be limited to use with cataract surgery, Dr Barton said. “The FDA obviously does not apply in Europe, but it is noteworthy that the US FDA believes [MIGS] are only fit for combined surgery. … it’s because the only evidence is with combined surgery.”

Are subconjunctival devices MIGS?
One exception is the Xen Gel Stent subconjunctival drainage device, which the FDA has cleared for implantation as a standalone procedure or in conjunction with cataract surgery, Dr Barton said. However, the manufacturer does not refer to it as a MIGS device, he added.

While there has been much debate about what qualifies as MIGS, “it’s interesting that the device that has been out there the longest that is most appropriate for standalone surgery doesn’t call itself ‘MIGS’”, Dr Barton noted.

Similarly, Santen steers away from describing its Preserflo MS as a MIGS device “because the term MIGS seems to be associated with only modest efficacy”, Dr Barton said.

In summary, the only randomised clinical trial evidence for MIGS efficacy is in combined surgery; one major licensing agency has only licensed MIGS for combined surgery; and the devices with the strongest arguments for standalone usage shy away from calling themselves “MIGS”, Dr Barton said.


Julian Garcia Feijoo MD, PhD


Standalone MIGS

Arguing for MIGS use in both standalone and combined procedures, Julian Garcia Feijoo MD, PhD, of San Carlos Hospital, Complutense University, Madrid, Spain, first sought to clarify MIGS as a concept. He subdivided it into true MIGS, including Schlemm’s canal stents and suprachoroidal shunts, and MIGS involving blebs and use of mitomycin C shunting to the subconjunctival space.

These differing devices clearly involve varying levels of risk, have different suitable patient profiles, and differing efficacy, Dr Garcia Feijoo said. “We have many surgical procedures. That way we can find the patients who can benefit from the different glaucoma devices and MIGS.”

Therefore, Dr Garcia Feijoo believes that the decision to use MIGS or MIGS involving blebs should be taken in the context of other medical and surgical options based on the patient’s condition and circumstances.

Factors to consider include diagnosis, stage and rate of progression, ocular characteristics and pathologies, age and life expectancy and other factors, such as topical medication tolerance and adherence. “When making the decision consider the patient needs and preferences and tailor the treatment accordingly,” Dr Garcia Feijoo said.

The real question, though, is whether MIGS can be effective as standalone treatments, or do they need cataract surgery to be effective, Dr Garcia Feijoo said. Many papers suggest they can be.

Dr Garcia Feijoo agreed with Dr Barton that bleb-forming devices such as the Xen Gel Stent (Allergan, Curr Clin Opthalmol 2018. Stalmans. ICGS 2016) and Preserflow (SANTEN, Batlle JF et al J Glaucoma 2016. Garcia Feijoo. AAO 2018) have proven standalone efficacy (Curr Clin Opthalmol 2018. Stalmans. ICGS 2016) and may be considered as an alternative to trabeculectomy for moderate to severe cases.

For trabecular bypass and Schlemm’s stenting MIGS approaches, Dr Garcia Feijoo believes these may be appropriate for patients needing high to mid-teens intraocular pressure control. Studies suggest complication rates are similar to or lower than cataract procedures, and the chances of controlling IOP for two-to-five years without medication is 60-to-75% in suitable patients with early disease, which can be very helpful for patients with low medication tolerance, he said.

Several prospective studies have demonstrated efficacy of trabecular bypass stents for open-angle glaucoma patients. These include a prospective study showing 36-month efficacy (Hengerer FH et al. Adv Ther 2019 Jul;36(7):1606-1617.) and a second series out to 42 months (Katz J et al. Clin Ophthalmol in press.), Dr Garcia Feijoo said. “Do they work? Yes. For how long, we don’t know.”

Suprachoriodal devices may be useful for more advanced cases, slowing progression and the need for topical medications for more than four years in a pseudophakic patient (Garcia Feijoo et al. J Ocul Pharmacol Ther 2018;34(7):538-542.).

In summary, standalone MIGS provide efficacy – though not to the level of trabeculectomy – as well as improved quality of life and reduced medication burden for many patients. “These things are true for both standalone and combined surgery,” Dr Garcia Feijoo said.

Rebuttal
Still, FDA clinical trial guidelines and AAO technology assessments question the use of standalone MIGS procedures, Dr Barton countered. These patients typically need more than the moderate IOP lowering MIGS provides, he added.
He noted that a 2011 AAO technology assessment found “it is not possible to conclude whether these novel procedures are superior, equal to, or inferior to surgery such as trabeculectomy or to one another. The studies provide the basis for future comparative or randomized trials of existing glaucoma surgical techniques”.

“In other words, we really don’t know where we are. Are we really going to do these procedures on people who need a standalone procedure?” Dr Barton asked.

In addition, FDA trial guidelines for MIGS studies explicitly rule out patients with advanced glaucoma, ocular hypertension or vision-threatening visual field defects – “basically anyone you’d want to do standalone surgery on”, Dr Barton said. He contended that both the financial and opportunity costs of standalone MIGS are not worth the benefit.

While conceding long-term studies are needed to better understand the effects of MIGS procedures, Dr Garcia Feijoo believes surgeons should use their judgment, and use MIGS in standalone surgery when it will benefit specific patients, specially pseudophakic patients with early glaucoma. Trabecular bypass surgery can be useful early on and suprachoroidal approaches may be useful for intermediate glaucoma. “