Mixing MIGS and meds

The wide range of surgical and medical glaucoma treatments developed over the past 15 years provide new options for combining therapies. Technologies including aqueous humour outflow imaging are helping identify combinations that may improve outcomes, Alex Huang MD, PhD, told the Glaucoma Subspecialty Day at the annual meeting of the American Academy of Ophthalmology (2019) in San Francisco, USA. However, the efficacy and safety of such combinations must be verified by clinical trials, and few combining the two have yet been conducted, added Dr Huang, Assistant Professor, Doheny Eye Institute, Department of Ophthalmology, University of California – Los Angeles, USA. He reviewed three areas in which MIGS-Med combinations are being investigated. Fundamental aqueous humour outflow biology (long known from histological staining of outflow anatomy) suggests that muscarinic agonist miotics, such as pilocarpine and acetylcholine, work by stimulating contraction of the ciliary muscle, pulling the scleral spur, which acts as a lever opening the trabecular meshwork, Dr Huang said. Therefore, combining them with MIGS canal procedures such as the trabectome (NeoMedix) and the Kahook Dual Blade (New World Medical) was originally hypothesised to keep the angle open, further enhancing outflow and preventing peripheral anterior synechiae. However, a large 12-month retrospective study found no difference at all in IOP reduction, complications or PAS formation between eyes undergoing trabectome with and without postoperative pilocarpine, whether done alone or with phacoemulsification cataract surgery, Dr Huang said. (Esfandiari et al. F1000Research 2018, 7:178.) “This is a case where [combining MIGS and meds] didn’t work.” In addition to relaxing the trabecular meshwork, cytoskeletal relaxing agents including netarsudil (Rhopressa, Aerie) and nitric oxide-donating drugs (Vyzulta, Bausch + Lomb) may enhance the efficacy of trabecular bypass or ablation by relaxing distal collector channels and reducing episcleral venous pressure, Dr Huang said. Preclinical research he has conducted with Dan Stamer PhD of Duke University shows increased distal outflow in response to such drugs. OCT imaging also has shown them to increase outflow pathways size in distal channels still blocked after 360-degree trabeculotomy, suggesting a synergistic effect, Dr Huang said. “While the clinical data is not there, there is promise to use distally targeting IOP-lowering drugs combined with trabecular MIGS.” Steroids after MIGS is vexing as it can be impossible to tell if failure to reduce IOP is due to steroid effect or procedure failure without stopping steroids, Dr Huang said. Steroid-response after MIGS is real and can be profound. His research shows that steroids cause distal pathway scleral to proliferate, get larger and change morphology, just as do trabecular meshwork cells, suggesting a similar IOP-raising mechanism of action. The solution is to quickly taper steroids after trabecular MIGS. Dr Huang concluded that the future is bright for combined MIGS-meds procedures, but more research is needed. Alex Huang: ahuang@doheny.org