Should MIGS be considered first-line therapy over eye drops?
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Eye drops, laser trabeculoplasty are typical first-line choices for new glaucoma diagnosis
In a 2020 position statement on microinvasive glaucoma surgery, the American Glaucoma Society said:
“It is essential for researchers and industry to continue developing innovative therapeutic options that are effective at lowering IOP, possess a good safety profile, and are well tolerated by patients.”
While MIGS procedures can fulfill many of these goals, they are not the universal first-choice management option for patients with a new diagnosis of glaucoma.
MIGS procedures are divided by their anatomical targets: the trabecular meshwork and Schlemm’s canal, the subconjunctival space and the suprachoroidal space. Each procedure and region are associated with varying efficacy outcomes, although there are only a few high-quality studies on MIGS. Regardless of the procedure chosen, there is no guarantee that patients will not require IOP-lowering medications after surgery. Regarding trabecular meshwork bypass stents, in the COMPARE study, only 47% of Hydrus microstent (Alcon) eyes and 24% of iStent (Glaukos) eyes were medication-free at 12 months. Additionally, even after MIGS in this study, 18% of Hydrus eyes and 39% of iStent eyes needed medication escalation or had no medication reduction. Regarding subconjunctival MIGS, the need for additional surgery (needling or reoperation) for Xen gel stent (Allergan) has been reported at between 32% to 47% and 10%, respectively, and concerns about the efficacy of the PreserFlo microshunt (Glaukos) have prevented its FDA approval.
While the safety profiles of MIGS can be more favorable relative to traditional glaucoma surgery, MIGS are not without risk. Postoperative complications include early events (corneal edema, inflammation, epithelial defect, discomfort) in 13%, stent malposition or obstruction in 7%, IOP spike greater than 10 mm Hg from baseline in between 4% and 21%, transient hyphema in between 1% and 24%, uveitis in 6%, and hypotony in between 3% and 35%. While these unfavorable outcomes are considered within the spectrum of expected postoperative events, safety concerns related to corneal decompensation were so substantial that they led to the voluntary withdrawal of the CyPass microstent (Alcon).
Not every patient is a suitable surgical candidate. Patients with glaucoma are often elderly and have other comorbid systemic conditions. Some have undergone prior surgery that may scar their angles and conjunctiva, preventing the use of canalicular and subconjunctival MIGS devices, respectively. Others may be wary of surgery and would rather choose medications. This may especially apply to monocular patients, who know that the stakes for their “good eye” are higher and may want to pursue low-risk options.
For a patient with a new diagnosis of glaucoma, the first-line treatment options generally are eye drops and laser trabeculoplasty. These have decades of high-quality clinical trials substantiating their safety and efficacy outcomes, while such evidence for MIGS is limited.
With this information in mind, who is an appropriate candidate for MIGS as a first-line procedure before medication use? Patients with evidence of mild to moderate glaucomatous damage or ocular hypertension and open angles who are considering cataract surgery deserve a discussion about MIGS. In this scenario, they are already planning to undergo a procedure with a different goal — improvement of vision — and MIGS offers them the option of also better controlling IOP. The general risks of surgery — infection, intraocular hemorrhage, anesthesia complications — would have been present with cataract surgery alone, and most MIGS procedures likely do not substantially increase these risks. Additionally, patients who do not need cataract surgery but will almost certainly face challenges with medication adherence — those who have physical limitations (eg, rheumatologic disease, tremors) that prevent them from instilling drops or neurocognitive conditions that prevent them from remembering to use their drops — may benefit with a procedural intervention as a first therapeutic option instead of topical medication use. My first choice in these cases is selective laser trabeculoplasty as it is lower risk, has more evidence supporting its efficacy and is less costly than stand-alone MIGS. However, for patients in this category who do not respond to laser, MIGS remains a suitable choice.
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Aakriti Garg Shukla, MD, is the Leonard A. Lauder assistant professor of ophthalmology at Columbia University Irving Medical Center and attending ophthalmologist at New York Presbyterian Hospital.
MIGS may be considered early over chronic eye drops for certain patients
MIGS may not always be a good first choice therapy for all patients with a new diagnosis of any type of glaucoma.
However, there are certain specific clinical scenarios in which performing MIGS first, or at least soon after medications have been used to temporarily stabilize the IOP, may be appropriate. In many ways, gonioscopy-assisted transluminal trabeculotomy (GATT) can be considered to be the biggest and most physiologic MIGS because it achieves a 360° goniotomy/trabeculotomy. In the absence of postoperative scarring, GATT can theoretically eliminate all resistance to outflow at the level of the trabecular meshwork, making IOP results after successful GATT limited only by the episcleral venous pressure.
The concept of MIGS first has been a mainstay in the treatment philosophy of childhood glaucoma. Instead of recommending surgery after medical therapies, which has proven to be inadequate, angle surgery is often the first-line therapy in various types of childhood glaucoma in which the obstruction to aqueous outflow is primarily at the trabecular meshwork. Grover and colleagues previously described GATT to be an effective treatment option for primary congenital glaucoma and juvenile open-angle glaucoma, and this option can be offered before the IOP becomes uncontrolled on chronic medical therapy.
Similarly, in a variety of secondary open-angle glaucomas (SOAG), in which the obstruction is primarily at the level of the trabecular meshwork and the presenting IOP can be profoundly elevated, angle surgery can be offered soon after the IOP is stabilized in acute setting with medical therapy. In steroid-induced glaucoma, the resistance to aqueous outflow is thought to be due in part to physical changes at the trabecular meshwork. Boese and colleagues described GATT to be an effective surgical option for steroid-induced glaucoma. Rather than tapering down steroids or keeping the patient on multiple IOP-lowering medications, GATT can be offered early for IOP control, while keeping the steroid dose as high as needed by the prescribing service. Chen and colleagues also described GATT to be an effective treatment option for steroid-induced glaucoma and uveitic glaucoma in eyes without peripheral anterior synechiae. Others have also described GATT to be an effective intervention in eyes with uveitic glaucoma. In patients like these, instead of keeping eyes on chronic medical therapy and waiting for the IOP to become uncontrolled, GATT can be offered earlier in the treatment timeline. Pseudoexfoliative glaucoma (PXG) and pigmentary glaucoma are other SOAGs in which the obstruction is primarily at the trabecular meshwork. Sharkawi and colleagues reported excellent 2-year outcomes of GATT in PXG, and while there are no reports to date focusing on GATT in pigmentary glaucoma, large GATT series in the literature do include some patients with pigmentary glaucoma.
Eye drops have historically been considered the first-line therapy in patients with glaucoma. However, the chronic use of topical eye drops, especially those containing the preservative benzalkonium chloride, can lead to severe ocular surface toxicity. In recent years, selective laser trabeculoplasty (SLT) has grown in popularity due to results from the LiGHT trial, which only included patients with ocular hypertension or primary open-angle glaucoma. While short-term outcomes of SLT in SOAG can also be promising, the longevity of SLT may not be as favorable compared with GATT, although there are no head-to-head comparisons in the literature.
Some patients may prefer to move directly to a surgical treatment rather than trying medications or SLT first, then GATT, then traditional glaucoma surgery. Offering GATT early for a variety of SOAGs, rather than trying chronic medical therapy or SLT first, may be a great middle ground for achieving maximal efficacy with a big angle-based MIGS procedure while minimizing the risk for more serious complications that would be associated with traditional glaucoma surgery.
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Mary Qiu, MD, is an assistant professor of ophthalmology and visual science at the University of Chicago.
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