The Limits of Combining Phacoemulsification and MIGS

MIGS has taken off across the world,¹ with many viewing it as a useful tool for managing mild to moderate glaucoma. This low-risk, well-tolerated surgical approach has reported benefits that include stemming disease progression and reducing the burden of eye drops. This article explores key considerations for this increasingly popular approach to the surgical management of glaucoma and, importantly, highlights when MIGS should not be considered. Procedures that dilate Schlemm canal (SC) or excise the trabecular meshwork (TM) are not discussed in depth.

A working definition of MIGS is useful to any discussion of this area. The US FDA includes minimally invasive bleb-forming procedures in this category, whereas the European Glaucoma Society limits MIGS to ab interno, non–bleb-forming procedures.² The latter are generally minimally traumatic and have three key therapeutic targets: the TM, SC, and the suprachoroidal space. Devices stent, dilate, or disrupt tissue—or combine these mechanisms.

Stenting procedures either bypass the TM and direct aqueous into SC, ideally near the collector channels, or the devices are positioned in the supraciliary space to increase uveoscleral outflow. Dilating procedures cannulate SC to increase outflow capacity. Disruptive procedures ablate or remove the TM, effectively creating a trabeculotomy and permitting aqueous to reach SC directly.

EFFICACY AND THE BROADER GLAUCOMA SURGICAL LANDSCAPE 

Among MIGS devices, the Hydrus Microstent (Alcon) and the iStent inject (Glaukos) are supported by the strongest evidence; the Hydrus data are generally considered more robust.³

The HORIZON study was a well-designed randomized controlled trial that provided prospective 5-year Hydrus outcomes in patients with cataract and mild to moderate primary open-angle glaucoma (POAG) who were undergoing treatment with one to four topical glaucoma medications.⁴ The iStent inject pivotal trial provided robust prospective randomized controlled trial data on 2-year outcomes in similar patients, those with mild to moderate POAG who were administering one to three topical glaucoma medications.⁵

In the HORIZON study, a 20% or greater reduction in IOP without glaucoma medication was achieved by 54% of patients who underwent the combined procedure versus 33% of those who underwent cataract surgery alone (P < .001). In the pivotal trial of the iStent inject, the corresponding rates were 76% and 62% (P = .005). The greater response in both iStent inject arms likely reflects the shorter follow-up duration and may be consistent with a tendency for the trabecular bypass effect to diminish over time.

Complete elimination of the medication burden was achieved in 66% of the Hydrus group and 46% of the patients who received cataract surgery alone (P < .001). The difference was statistically significant but modest in the iStent inject trial: The mean number of glaucoma medications at 2 years was 0.4 in the combined group and 0.8 in the group that underwent cataract surgery alone (P < .001).

Montesano et al reported that Hydrus implantation reduced the apparent rate of visual field progression by almost 50%, from -0.49 dB/year with cataract surgery alone to -0.26 dB/year in the Hydrus group (P < .05).⁶ These data are clinically relevant, especially because the reduction appeared to be greatest among the patients experiencing the most rapid progression. The rate of progression in these patients, however, was not high even among those undergoing phacoemulsification alone. A problem arises when these data are used to justify combining phacoemulsification and MIGS in eyes with more advanced or rapidly progressing disease, where the modest improvement in field stability shown in the HORIZON trial is unlikely to be sufficient.

If Hydrus is taken as a reasonable representative of canal-based MIGS, phacoemulsification combined with Hydrus implantation achieved a mean IOP that was only 1 mm Hg lower than phacoemulsification alone at 5 years, with 0.4 fewer medications.² The HORIZON 5-year data showed a mean diurnal IOP of 17 mm Hg in the Hydrus group. These outcomes do not meet the needs of eyes that require a low target IOP.

The surgical standard for achieving a long-lasting IOP reduction with a robust safety profile is trabeculectomy, a procedure first described more than 50 years ago by Cairns⁷ and currently often augmented with antimetabolites.⁸ The Treatment of Advanced Glaucoma Study (TAGS) confirmed trabeculectomy’s continued importance, with 5-year outcomes demonstrating successful IOP lowering and prevention of disease progression when the procedure was performed as first-line treatment in patients presenting with advanced disease.⁹

The pivotal Tube Versus Trabeculectomy (TVT) and Primary Tube Versus Trabeculectomy (PTVT) studies demonstrated that, at 5 years, trabeculectomy achieved an IOP of approximately 12 mm Hg.^10,11 This level of IOP lowering was further validated by TAGS.⁹ In the PTVT study, complete surgical success—defined as an IOP of less than 21 mm Hg without hypotony or additional glaucoma medication—was achieved in more than one-third of patients who underwent primary trabeculectomy.¹¹

The published data support trabeculectomy as a better option than tube shunt surgery when the goal of treatment is long-term independence from glaucoma medication and when a greater magnitude of pressure reduction is required. The PTVT study also suggested that trabeculectomy is the better option in virgin eyes when the baseline IOP is low.¹¹ In eyes with a history of trabeculectomy or cataract surgery, but the TVT study found that tube shunts achieved an IOP of 14 mm Hg at 5 years and were associated with a much lower reoperation rate than trabeculectomy (< 10% vs 29%).¹⁰ The failure rate, moreover, was approximately 47% after trabeculectomy compared to less than 29% after tube shunt surgery in these nonvirgin eyes.

LONG-TERM FOLLOW-UP AND CLINICAL APPLICATION 

The best MIGS data extend to approximately 5 years, which is not long in the context of what can be a slowly progressive disease such as glaucoma. In comparison, an enormous body of evidence supports the long-term efficacy of trabeculectomy. For example, a landmark study by Landers et al showed that, even at 20 years, the complete and qualified success rates of trabeculectomy were 57% and 88%, respectively.¹²

Where does the Preserflo MicroShunt (Santen) fit into this equation? The device is inserted ab externo and augmented with mitomycin C (MMC), and it is designed to facilitate aqueous drainage directly into the sub-Tenon space, similar in principle to the flap of a trabeculectomy. This category is increasingly termed minimally invasive bleb-forming surgery.

Five-year data from Panarelli and colleagues provided insight into how the MicroShunt performs compared with trabeculectomy in adults 40 to 85 years of age with mild to severe uncontrolled POAG.¹³ Mean postoperative IOP was 14 mm Hg with the MicroShunt and 10 mm Hg with trabeculectomy (P < .0001). Mean postoperative medication use was 1.1 and 0.7 medications, respectively (P < .001), again favoring trabeculectomy. Overall success, defined as at least a 20% IOP reduction without an increase in medication use, was 35% with the MicroShunt and 53% with trabeculectomy (P = .01), consistent with the 36% glaucoma reoperation rate in the MicroShunt group. Given the relatively low concentration of MMC used (0.2 mg/mL), higher success rates and lower reoperation rates might be possible; for comparison, the PTVT study used 0.4 mg/mL MMC for 2 minutes.

Strictly speaking, these data represent a 3-year observational extension of a 2-year prospective randomized trial, but the findings are promising. Compared with canal-based procedures, the MicroShunt appears to lower IOP and reduce the medication burden more substantially out to 5 years, although the data are not directly comparable. The MicroShunt is less effective than trabeculectomy. We have found the device increasingly useful when some features of trabeculectomy, such as a low IOP, are desirable but the patient cannot commit to the intensive postoperative course that trabeculectomy requires.  

CLINICAL SAFETY 

Safety is an important consideration with any novel surgical approach, and endothelial cell loss is a key concern for any device deployed into the anterior chamber. For the Hydrus Microstent, Ahmed et al reported no difference in endothelial cell density at 5 years between treatment arms.¹⁴ Similarly, the iStent inject pivotal trial identified no difference in the rate of endothelial cell loss at 2 years.⁵

Panarelli and colleagues reported similar endothelial cell loss with the Preserflo MicroShunt and trabeculectomy at 5 years (18.5% vs 18.6%). The MicroShunt was also associated with a lower incidence of hypotony than trabeculectomy (3% vs 13%; P < .01).¹³

TAKE-HOME MESSAGES 

If a cataract surgeon is managing a patient with visually significant cataract and POAG that is well controlled on two or more medications and that patient is motivated to reduce their medication burden at the time of cataract surgery, combining phacoemulsification and MIGS could be a sensible choice if cost permits. If, however, glaucoma itself is the challenge—uncontrolled IOP, visual field progression, retinal nerve fiber layer loss, or disc hemorrhage—combined surgery is unlikely to halt disease progression in most instances but may delay a more definitive intervention. The latter is often cited as a benefit, but this is often not the case, because delaying a more definitive intervention usually implies procrastination, thereby allowing the glaucoma to get worse before a more definitive intervention is performed. 

Enthusiasm for MIGS in inappropriate situations can perpetuate two myths: (1) that glaucoma procedures do not produce long-term success and (2) that glaucoma always becomes more severe. Neither is inevitable if the correct surgical intervention is performed at the correct time.

Trabeculectomy remains the most effective first line when durable, long-term IOP control is needed, particularly in virgin eyes with advanced disease. In virgin eyes with less advanced glaucoma but uncontrolled IOP, the Preserflo MicroShunt is a less invasive and reasonably effective alternative.

Canal-based MIGS can augment cataract surgery and may offer additional IOP lowering beyond cataract surgery alone. The surgeon, however, must not miss the opportunity to arrest glaucomatous progression when a lower target pressure is required.