Multiple avenues of investigation combining medications and MIGS are just beginning, but possible benefits have been suggested. In some cases, pharmacological medications may be found to assist MIGS, but more data are needed.
In the previous 10 to 15 years, a number of new therapies have come through the pipeline to lower IOP in glaucoma, i.e., microinvasive glaucoma surgeries (MIGS) and new medical therapies. The latest effort is combining medicines and MIGS, which may prove to be a positive option with potentially additive effects.
A number of the new therapies, according to Alex Huang, MD, PhD, target the conventional trabecular pathway, and aqueous angiography is one technique which can visualize the impact of MIGS and pharmacological agents on aqueous humor outflow patterns.
Dr. Huang, a clinician-scientist and assistant professor, University of California, Los Angeles, and Doheny Eye Institute, Pasadena, CA, described a research collaboration with Lilit Voskanyan, MD, in which indocyanine green (ICG) was introduced into the eye showing regions of poor aqueous outflow.
With placement of two aqueous bypass stents (iStent Inject; Glaukos Corporation) in that location, the angiography was able to demonstrate improved aqueous outflow (Figure 1).
Dr. Huang performed a study with Christopher Girkin, MD, in which they injected ICG into an eye to view the aqueous outflow pattern; after Miochol-E (acetylcholine chloride intraocular solution, Bausch + Lomb) was added, improved outflow was again visualized.
Looking to the future
Based on these observations, researchers questioned whether MIGS and medications could be combined.
“There are no high-volume, high-quality clinical trials to support combining therapies,” Dr. Huang said. “There is a lot of retrospective, preclinical, and basic translational work that provides a lot of promise.”
Dr. Huang subdivided investigations into three areas: proximal outflow (trabecular meshwork), distal outflow (post-TM), and steroid response concepts.
Proximal outflow pathway
Regarding the trabecular meshwork, he described picrosirius red staining of the collagen in the sclera to demonstrate how the scleral spur lies under the trabecular meshwork and above the ciliary muscle.
“The cross-sectional view teaches how the conventional system works,” Dr. Huang said. “The ciliary muscle grabs the scleral spur and can pull it down or raise it like a lever to control the opening of the trabecular meshwork.”
Dr. Kuang pointed out that this biological mechanism became relevant with procedures that were developed to ablate the trabecular meshwork, such as Trabectome (NeoMedix).
Some data have indicated that there is no good evidence to continue the use of pilocarpine after trabecular ablations. A retrospective study by Hamed Esfandian et al. showed that extended muscarinic activation with pharmacologic agents after trabecular ablation made no difference to intraocular pressure lowering or surgical success.
Distal outflow pathway
New drugs, i.e., netarsudil (Rhopressa, Aerie Pharmaceuticals) and latanoprostene bunod (Vyzulta, Bausch + Lomb), a nitric-oxide donating drug, are cytoskeletal relaxing agents that affect the TM and the distal outflow pathway.
Dr. Huang also questioned if the trabecular MIGS work by opening the proximal region and these drugs can impact the distal outflow, would there be a synergistic additive effect. He pointed out that preclinical data on this subject have suggested that there might just be an additive effect.
With Dan Stamer, PhD, they investigated an eye model in which the trabecular meshwork was removed by a 360º trabeculotomy and where changes in outflow facility were measured in response to various drugs with concomitant constriction and relaxation of distal outflow pathway collector channels and aqueous veins. These results opened the idea that drugs could be added after MIGS for positive results.
Anecdotal information exists indicating that after trabecular MIGS an aggressive steroid response can still be observed. Thus, despite a lack of carefully performed clinical characterization, the recommendation is to taper the steroid relatively quickly, according to Dr. Huang.
Unlike systemic steroid use or application after cataract surgery, steroid response after glaucoma surgery can be difficult to appreciate. Elevated IOP could be due to steroid response or failure of the glaucoma surgery. Stopping the steroid is the only way to know. When the IOP decreases, this suggests a steroid response.
Related: Looking behind IOP when managing glaucoma patients
Dr. Huang concluded that the future ahead is bright.
“In some cases, pharmacological medications may be found to assist MIGS, but more data are needed,” he said. “This is already well-known with combining glaucoma medications targeting different pathways although the additive effect may be only 2 + 2 = 3. For medications and MIGS, hopefully the synergy can be greater where 2 + 2 becomes 4 or even 5.”
Alex Huang, MD, PhD
This article is based on Dr. Huang's presentation at the American Academy of Ophthalmology 2019 annual meeting. Dr. Huang is a consultant/advisor for Aerie Pharmaceuticals, Allergan, and Santen, and receives grant support form Diagnosys LLC, Glauoks Corp., and Heidelberg Engineering, National Eye Institute, Research to Prevent Blindness, and the National Aeronautics and Space Administration Human Research Program.