Novel glaucoma therapy report

A review of the most recent devices, medications, and drug delivery methods to help lower intraocular pressure.

Glaucoma is the leading cause of irreversible blindness in the world. More than 3 million Americans are living with the disease, a number expected to double by 2050, according to a 2016 JAMA Ophthalmology article by Varma, et al.

The only approved glaucoma treatment options are designed to lower IOP by either increasing the outflow or decreasing the production of aqueous humor. Medical therapy remains the most common mode of treatment, while laser and surgical options also play a role depending on disease severity (for more on novel IOP-lowering drugs, see

In recent years, we have seen a surge of innovation in both the medical and procedural realms, providing a broader scope of treatment options that can be tailored to the individual patient. The purpose of the article is to educate ophthalmic staff on the most recent advances in glaucoma therapy.


Rho kinase inhibitors, also known as ROCK inhibitors, are a new class of medication. These medications, Rhopressa and Roclatan (Aerie Pharmaceuticals) are the first to target the outflow of aqueous at the level of the trabecular meshwork. It has also been demonstrated in some studies to reduce the episcleral venous pressure (the venous pressure system surrounding the eye).

Rhopressa (netarsudil ophthalmic solution) became available to patients in spring 2018. It is a once-daily therapy.

Roclatan is a combination drop therapy consisting of netarsudil and latanoprost. Also dosed once daily, it has demonstrated a synergistic effect on IOP lowering in the Phase 3 Mercury 1 and 2 trials compared to its individual components. Pending FDA approval, this product would be the first fixed-dose combination product containing a prostaglandin analog in the United States.

Another newer medication, Vyzulta (latanoprostene bunod ophthalmic solution, Bausch + Lomb), is a nitric oxide-donating prostaglandin analog with a dual mechanism of action. Aqueous humor drainage increases as the latanoprost affects the uveoscleral outflow pathway and the nitric oxide affects the conventional outflow pathway. Vyzulta became available in late 2017.

Drug delivery

Patient compliance with prescribed medications is one of the biggest challenges in treating glaucoma. Some barriers to compliance include the inability to correctly and reliably instill eye drops, adverse effects associated with taking eye drops, and patient forgetfulness. These obstacles could be lessened by alternative modes of drug delivery.

Some exciting options currently in Phase 2 and 3 trials include:

  • Bimatoprost Ring (Allergan), a bimatoprost-laden polymer-matrix insert embedded in a pliable ring. The ring is positioned under the upper and lower eyelids and rests on the conjunctiva. A physician replaces it every six months. A Phase 2 trial of the ring found high retention rates, favorable tolerability, and a low incidence of adverse events.
  • Bimatoprost SR (Allergan), a sustained-release, prostamide-loaded, bioerodible implant injected into the anterior chamber. It can be performed in the office, ensuring patient compliance. In the Phase 3 clinical study of 594 subjects with open-angle glaucoma or ocular hypertension, Bimatoprost SR reduced IOP by approximately 30% over the 12-week primary efficacy period, meeting the criteria for non-inferiority to timolol. A new drug application filing to the FDA is expected in the second half of 2019.
  • OTX-TP (Ocular Therapeutix), a sustained-release travoprost-loaded punctal plug that demonstrated a robust IOP reduction and clinically significant results at three months in its Phase 2b study. After therapy is complete, the hydrogel resorbs and exits the nasolacrimal system.
  • iDose (Glaukos), an anterior chamber implant made of titanium. The device elutes travoprost and is nondegradable, requiring removal and replacement at an expected interval of every 6 to 12 months. Available performance data has been limited thus far.


In addition to new drug advances, the continued development of minimally-invasive surgical procedures provides additional options to lower IOP with nominal tissue disruption. Micro-invasive glaucoma surgery (MIGS) has helped to fill the gap between medical and laser management and more invasive surgical procedures. Performed both with and without cataract surgery, these procedures offer a safer alternative to surgical lowering of IOP and thereby can reduce the patient’s dependence on topical glaucoma medication.

Several FDA-approved MIGS procedures have been utilized in recent years, including: Trabectome (Neo-Medix), iStent (Glaukos), Kahook Blade (New World Medical) for goniotomy and XEN Gel Stent (Allergan). Of note, the previously FDA-approved CyPass Micro-Stent (Alcon) was voluntarily withdrawn from the global market based on an analysis of five-year post-surgery data from the COMPASS-XT long-term safety study that demonstrated increased endothelial cell loss.

In the past two years, a few new devices have also become available. The OMNI Surgical System (Sight Sciences) is indicated for the delivery of controlled volumes of viscoelastic fluid in the anterior segment, including Schlemm’s canal, and the cutting of trabecular meshwork tissue. This device combines the technology of Sight Sciences’ original Visco 360 and Trab 360 systems into one disposable unit.

Also, the iStent inject (Glaukos) is the next-generation model of trabecular micro-bypass technology. It is designed to optimize the natural physiological outflow of aqueous humor by creating two patent bypasses through the trabecular meshwork with the use of a single injector. The device is believed to be the smallest medical device ever approved by the FDA, according to Glaukos.

Additional MIGS options with expected availability in the near future include the Hydrus Microstent (Ivantis) and InnFocus MicroShunt (Santen). Hydrus recently received FDA approval based on results of the HORIZON trial. Hydrus not only “stents” the canal with a direct inlet from the anterior chamber, but also expands the canal via tension on the meshwork and inner wall. With its 8-mm length, it extends nearly 3 full clock hours of the angle when deployed.

The InnFocus MicroShunt drainage implant consists of an extremely small micro-tube that shunts aqueous fluid from the anterior chamber of the eye to a sub-conjunctival/sub-Tenon flap. The device is made of SIBS, a biostable thermoplastic elastomeric material. It currently is in the final phase of clinical study at 29 centers in the United States and Europe.


Advancements in the surgical and medical treatment of glaucoma have provided practitioners with a larger armamentarium. New classes of medications and delivery mechanisms may help to improve patient compliance with therapeutic regimens. Also, innovative surgical devices allow for lower risk alternatives to control IOP in mild-to-moderate disease.

As technology continues to evolve, we can hope that the glaucoma treatment paradigm may shift further towards sustainable and consistent IOP lowering with an increasingly favorable safety profile. OP