Minimally Invasive Glaucoma Surgery – The Next Steps
Until recently, there were limited options for the treatment of glaucoma, which remains the leading cause of irreversible blindness worldwide and whose incidence is projected to increase to 111.8 million by 2040.1 As a first step, most patients newly diagnosed with open-angle glaucoma (OAG), the most common form, are prescribed topical medications that aim to reduce intraocular pressure (IOP). Laser trabeculectomy is often used as a second-line treatment but this is not effective over the long term.2 Minimally invasive cataract surgery offers a safer, less invasive means of reducing IOP and is one of the most exciting recent developments in ophthalmology. The first MIGS device to be approved by the US Food and Drug Administration (FDA) was the iStent (Glaukos, Laguna Hills, CA), a trabecular bypass device, and was originally used in patients undergoing concomitant cataract surgery.3,4 In addition, MIGS devices are increasingly being implanted in standalone procedures.5,6Cataract surgeons are increasingly adopting MIGS techniques, so it is important for them to establish which device is the best for their practice. Other available MIGS devices include the Hydrus microstent (Ivantis, Irvine, CA)7 ; Cypass suprachoroidal implant (Alcon, Fort Worth, TX),8,9 and subconjunctival filtration devices: the XEN gel stent (Allergan, Dublin, Ireland)10 and the InnFocus microshunt (Santen, Osake, Japan).11
The only drawback of MIGS procedures to date is that they have produced only modest IOP reductions. However, as surgeons become more familiar with MIGS, a new possibility has arisen: the implantation of multiple stents. Experience has shown us that combining drugs that target different outflow pathways can increase IOP reduction, so why not combine MIGS procedures? Several studies have shown that two stents are well tolerated and effective in providing additional IOP reduction.12,13 In a new study of 119 patients with open-angle glaucoma, implantation of one, two or three iStents achieved mean IOP reductions of 30%, 37% and 43%, respectively, at 36 months postoperative. At 42 months, 61%, 91% and 91% of eyes in the one-, two- and three-stent groups, respectively, achieved a ≥ 20% reduction in IOP without medication. No intraoperative or perioperative complications were reported; the most commonly reported adverse event was progression of pre-existing cataract. In addition, no eyes required additional glaucoma surgery.14
Glaukos is currently seeking FDA approval for five new products that involve multiple stents and different outflow pathways. The Stent inject® trabecular micro-bypass system, which is approved in the European Union, is a second generation iStent designed for use during cataract surgery and allows the placement of two stents into two trabecular meshwork locations through a single corneal entry point. A randomised controlled trial showed that the use of the iStent inject is at least as effective as two medications and is associated with an excellent safety profile.5 The iStent® SA trabecular micro-bypass system is a standalone, two-stent procedure that is designed for use in pseudophakic, mild-to-moderate OAG eyes. The iStent infinite™ trabecular micro-bypass system is a standalone, three-stent procedure, designed for refractory OAG patients. The iStent Supra® suprachoroidal micro-bypass stent is approved in the European Union, and is placed between the anterior chamber/sclera and suprachoroidal space. In an ongoing prospective study, it has been successfully implanted with two trabecular micro-bypass stents and postoperative prostaglandin, an approach that may be useful for refractory disease.15 Finally, the iDose™ travoprost is an implant containing a unique formulation of travoprost, which is continuously eluted at therapeutic levels from within the eye for extended periods of time. When depleted, it can be removed and replaced.
When choosing a MIGS device, it is important to consider its safety profile and the speed of patient recovery. Complications, while infrequent and usually transient, do occur. Intraoperative malpositioning of ab-interno microstents can result in luminal obstruction and decreased efficacy. Acutely elevated IOP has been reported with the iStent (2–4.3%), Hydrus microstent (21%), Cypass (3–10.8%) and XEN gel stent (21.5%).16 Hypotony (IOP < 6 mmHg) is also a potential complication during the first postoperative month, but typically does not require further surgical intervention, and is not associated with vision-threatening consequences.16 The mode of action might also be an important consideration; the iStent, iStent inject and Hydrus increase aqueous humour outflow into Schlemm’s canal, while other devices create new outflow pathways into the suprachoroidal space (CyPass and iStent Supra) or the subconjunctival space (XEN). The Schlemm’s canal microstents may be preferred in patients with mild to moderate glaucoma, and the suprachoroidal and subconjunctival devices for the more severe cases of glaucoma. However, there is a lack of comparative studies between the different implants, and direct comparisons of the evaluations of the different MIGS devices are difficult due to the diverse study designs, patient populations, and outcome measures. In addition, there is a need for well-designed randomised clinical trials with an extended follow-up to evaluate the long-term efficacy and late complications of these implants. In December 2015 the FDA issued guidance specifying standards which should be met by future MIGS studies.17 This is important since a number of new devices are likely to be developed over the coming years.
As the treatment options for MIGSs increases, clinicians need to determine the most appropriate approach for each patient. The first decision is whether the patient needs a glaucoma procedure. If so, the most effective aqueous outflow pathway must be determined based on patient target pressure and risk profile. Finally, within each of the pathways, there is a growing choice of optimal device.
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13. Berdahl J, Voskanyan L, Myers JS, et al., Implantation of two second-generation trabecular micro-bypass stents and topical travoprost in open-angle glaucoma not controlled on two preoperative medications: 18-month follow-up, Clin Exp Ophthalmol, 2017;45:797-802.
14. Katz LJ, Erb C, Carceller Guillamet A, et al., Long-term titrated IOP control with one, two, or three trabecular micro-bypass stents in open-angle glaucoma subjects on topical hypotensive medication: 42-month outcomes, Clin Ophthalmol, 2018;12:255-62.
15. Myers JS, Masood I, Hornbeak DM, et al., Prospective Evaluation of Two iStent((R)) Trabecular Stents, One iStent Supra((R)) Suprachoroidal Stent, and Postoperative Prostaglandin in Refractory Glaucoma: 4-year Outcomes, Adv Ther, 2018;35:395-407.
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17. FDA, Premarket Studies of Implantable Minimally Invasive Glaucoma Surgical (MIGS) Devices: Draft Guidance for Industry and Food and Drug Administration Staff. Rockville: Food and Drug Administration; 2015, http://wwwfdagov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM433165pdf Accessed 4 April 2018, .