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The group of procedures classed under the heading of minimally invasive or microinvasive glaucoma surgery (MIGS) has had a positive impact on the management of patients with glaucoma. These procedures, generally performed at the time of cataract surgery, involve implantation of one of a number of tiny devices designed to increase aqueous outflow to lower intraocular pressure (IOP).
Glaucoma is not a single disease entity, but rather a family of diseases that affect the retinal nerve fiber layer. The neuropathy associated with glaucoma is the common endpoint of these several disease entities. Because the glaucomas can stem from different etiologies, it may be that different kinds of glaucoma respond to different treatment approaches. Therefore, having an array of treatment options could provide clinicians with an increased chance of matching the right treatment to the right patient. Fom my perspective, MIGS procedures have already broadened our ability to offer treatment to glaucoma patients. However, the category is not static; it continues to evolve.
The classic treatment paradigm for the most common form of glaucoma in the Western world, primary open-angle glaucoma, has for decades been, first, topical medical therapy first to lower IOP, followed by laser trabeculoplasty for those who do not respond sufficiently to topical therapy, followed by incisional surgery. This continuum has become more fluid with the introduction of the less invasive MIGS procedures.
Glaucoma is chronic and progressive, and intervening early is beneficial. A greater emphasis has been placed in recent years on aggressive treatment of patients in mild to moderate stages of disease. Therefore, MIGS has become a viable option for patients in the mild or moderate phase if a concomitant cataract is present. Devices now in the development pipeline hold promise to expand the utility of MIGS even further.
The MIGS device that eye care providers are most familiar with, the iStent (Glaukos), is indicated for use in patients with mild to moderate glaucoma who have a cataract. In my experience, implantation of this device at cataract surgery is likely to lower IOP by about 20% to 30%, and usually patients can stop using one or two topical medications.
The success of the iStent, which received US Food and Drug Administration approval in 2012, helped create interest in early surgical management of patients and demonstrated the market potential for MIGS devices. Several other companies now have MIGS devices in various stages of clinical investigation.
Success rates with the iStent have improved over time as greater understanding has emerged with respect to patient selection. The techniques for using the device have also evolved, and there is interest in combining the iStent with other procedures, such as iStent implantation plus cataract surgery plus endocyclophotocoagulation (ECP), or ICE. The rationale for ICE is reflective of a growing appreciation for the many mechanisms of aqueous production and outflow and their relevance for glaucoma management. Indeed, the glaucoma field is moving toward an ability to affect aqueous production and outflow through multiple mechanisms that can be additive, complementary, and synergistic.
In ICE, the iStent improves trabecular outflow while the ECP portion of the procedure decreases aqueous production by the ciliary body. Cataract removal also likely contributes to IOP lowering, perhaps secondary to removing mechanical pressure on the angle.
The combination ICE technique illustrates an important concept in the MIGS class and in glaucoma as a whole. We have always used multiple mechanisms to address glaucoma (drugs, laser, and surgery). Now we can perform one procedure that addresses multiple aspects of the disease at one surgical sitting. This provides the clinician with increased ability to individualize his or her approach to patient management, something that has always been a bedrock of glaucoma care.
TREATING MULTIPLE PATHWAYS
As noted, a number of additions to the MIGS category are in various stages of development. The pipeline includes candidates that address multiple outflow pathways, including the trabecular pathway (Hydrus [ Ivantis]; iStent Inject [Glaukos]), the uveoscleral outflow pathway (iStent Supra; Glaukos), and the subconjunctival pathway (Xen45 [Allergan]; MicroShunt [InnFocus]). When and if these devices make it to market, there will be greater potential to mix and match procedures to produce more robust and potentially more durable IOP-lowering effects.
Of the three outflow mechanisms mentioned, current thinking is that the subconjuctival approach may yield the greatest effect. However, response to the implant will likely vary according to a number of factors, including individual patient characteristics and the etiology of the patient’s glaucoma.
The Xen45, originated by AqueSys and acquired last year by Allergan, is furthest along in development. It has received the CE Mark in Europe, and there is now clinical follow-up of 3 years with the device. In June, the FDA accepted the 510(k) premarket notification filing for the device.1 The Xen45 device is made of a soft porcine gelatin, crosslinked with glutaraldehyde to enhance structural integrity. The construction of the implant offers the potential for improved safety over the iStent, as it may be less prone to induce inflammation or to migrating or eroding. It is being studied in a multicenter US trial in patients who have refractory glaucoma despite maximal medical therapy (NCT02036541).2
It is hoped that the FDA approves Xen45 as standalone procedure (ie, independent of cataract status) appropriate for patients with more advanced glaucoma. This procedure could be described as a tissue-sparing filtering surgery performed via an ab interno approach.
Watch it Now
E. Randy Craven, MD, demonstrates the implantation of the CyPass Micro-Stent immediately after cataract surgery.
The recently FDA-approved CyPass (Alcon) is interesting to surgeons because the procedure is relatively easy to perform. It is intended for implantation at the scleral spur to access the uveoscleral pathway, which may be responsible for as much as 50% of aqueous egress. This route would bypass any atrophic tissue in Schlemm canal and the collector channels that developed as a result of the disease. Use of this route suggests that the device has potential for significant IOP-lowering efficacy (Figures).
In the CyCle study (NCT01097174), in 51 patients undergoing CyPass implantation and cataract surgery, there was a 38% reduction in IOP at 24 months, and patients were able to maintain stable IOP levels with a 50% decrease in the number of medications they were taking.3,4 In the DUETTE study (NCT01166659), which enrolled 65 patients with open-angle glaucoma who were not sufficiently responding to topical therapy, there was a mean 32% reduction in IOP and 50% decrease in the number of medications needed at 1 year.4
The COMPASS pivotal trial (NCT01085357) has been completed, and study results were recently published.5 This study enrolled 505 eyes (505 subjects); 374 eyes (74.1%) received both phacoemulsification and CyPass Micro-Stent implantation (the CyPass group) and 131 eyes (25.9%) received phacoemulsification alone (the control group). Of those, 480 eyes (95%) completed the full 2-year follow-up. The study showed 73% of the CyPass group and 58% of the control group achieved at least a 20% reduction in unmedicated diurnal IOP at 24 months (P = .002). Impressively, 61.2% of the CyPass group maintained an unmedicated diurnal IOP between 6 and 18 mm Hg at 24 months, compared with only 43.5% in the control group. In addition, 93% of responders in the CyPass Micro-Stent group remained medication-free at 24 months.
Glaucoma remains a difficult clinical entity to treat and manage, but the expanding array of MIGS options will be of tremendous benefit to patients. Another trend in glaucoma management is increasing emphasis on maintaining or improving patients’ quality of life. This has refocused many conversations about cost, convenience, adherence, and safety. More important, the emphasis on quality of life reinforces the need for glaucoma caregivers to individualize therapy for patients. Response to treatment is variable and heterogeneous, and our management strategies must take this variability into account.
I look forward to continued developments in the MIGS class, and I am optimistic that the availability of yet more treatment options will only improve our ability to help patients with glaucoma save their vision while maintaining excellent quality of life. n
1. Allergan announces FDA acceptance of the 510(k) premarket notification filing for the XEN Glaucoma Treatment System [press release]. Allergan. June 15, 2016. http://www.allergan.com/news/news/thomson-reuters/allergan-announces-fda-acceptance-of-the-510-k-pre. Accessed August 18, 2016.
2. AqueSys XEN 45 glaucoma implant in refractory glaucoma. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02036541. Accessed August 18, 2016.
3. CyPass Clinical Experience Study (CyCLE). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01097174. Accessed August 18, 2016.
4. Study of CyPass implantation in patients with open angle glaucoma refractory to single or multi-agent topical therapy (DUETTE). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01166659. Accessed August 18, 2016.
5. Vold S, Ahmed II, Craven ER, et al; CyPass Study Group. two-year compass trial results: supraciliary microstenting with phacoemulsification in patients with open-angle glaucoma and cataracts. Ophthalmology. 2016;123(10):2103-2112.
Steven D. Vold, MD
• Cataract and glaucoma surgery consultant at Vold Vision in Fayetteville, Arkansas
• Chief medical editor, AOC’s sister publication, Glaucoma Today
• Financial disclosure: research support, consultant to or speaker for Alcon, Allergan, AqueSys, InnFocus, Iridex, Ivantis, Glaukos, and Transcend Medical