Treatment Plan

Recent Developments in IOP-Lowering Medications

BY LEO SEMES, OD, FAAO

They say there’s more than one way to skin a cat; fortunately, this is true when managing intraocular pressure (IOP). The following two IOP-lowering therapies deserve particular attention.

New Combination Drop

I recently challenged my interns to design a two-component topical “glaucoma drop” that did not contain a β-blocker. Most in the group wanted to base a new fixed-combination (FC) drop on a prostaglandin analog (PGA). This would make sense for efficacy, but the PGA component would be limited to once-daily dosing while the other component would require multiple doses.

Eventually our discussion came around to combining a topical carbonic anhydrase inhibitor with an α-adrenergic agent. This would allow t.i.d. dosing. The first new medication I will discuss features this very combination.

On April 19 of this year, Alcon announced the FDA approval of Simbrinza (1.0% brinzolamide, 0.2% brimonidine). Those fluent in glaucoma management will recognize the brinzolamide component as Azopt (Alcon) and brimonidine as the original Alphagan (Allergan) product. Clinical trials including more than 1,200 patients have shown significant efficacy of this FC over either of the individual components at four time points throughout the day, sustained for up to six months (Katz et al, 2013; Nguyen et al, 2013). As with any combination drug, the precautions and side effects of each component must be accounted for, so be sure to review the package insert.

This combination also provided enhanced IOP-lowering efficacy at each of the four measured time points (800, 1000, 1500, and 1700 hrs) compared to either individual component. Quantitatively, this translates into an IOP decrease of an additional 1mmHg to 3mmHg.

Another favorable attribute is that Simbrinza is approved to lower IOP in patients who have open-angle glaucoma (OAG) (broadly all forms of OAG, not just POAG) and ocular hypertension (OHT), so it can be used as primary or adjunctive therapy. Additivity studies have yet to be performed.

Previously Approved Drop, New Mechanism of Action

Rescula (unoprostone isopropyl ophthalmic solution) 0.15% (Sucampo Pharmaceuticals) was initially FDA-approved in August 2000 for Ciba Vision. While some would classify that date as last-century, new FDA approval was granted to Sucampo on Dec. 12, 2012. The current approval is for b.i.d. dosing to lower IOP in patients who have OAG or OHT.

Unoprostone is the first docosanoid derivative for glaucoma therapy. At the molecular level, it activates the so-called big potassium (BK) channels (Tsuruma et al, 2011). Mechanistically, it enhances trabecular outflow without influencing aqueous production. It is approved for primary monotherapy or as an additive to other IOP-lowering drops.

Because its indications include OAG and OHT, one of its main attributes is as an alternative to a β-blocker. In addition, the advantages for this topical drop lie in its versatility as a primary, adjunctive, or alternative therapy. Finally, in normal-tension glaucoma, unoprostone has been shown to increase blood flow to the optic nerve head compared to normal controls (Kimura et al, 2005).

More Options, More Success

It is an exciting time for options to lower IOP among our glaucoma patients. We will undoubtedly be seeing more from clinical studies on the efficacy of these two new medications. CLS

For references, please visit www.clspectrum.com/references.asp and click on document #213.

Dr. Semes is a professor of optometry at the UAB School of Optometry. He is a stock shareholder of H.P.O. and is a consultant or advisor to Zeiss, B+L, Arctic Dx, Merck, Sucampo, Alcon, and Allergan.