Glaucoma’s most successful molecule is arguably latanoprost. This drug was the dream of Carl Camras, who partnered with Dr. László Z. Bito to develop Xalatan¹ with Pharmacia, and the drug was FDA approved 27 years ago. Despite it efficacy, initially it was used as an adjunct therapy, and doctors began by adding it to timolol (see the OHTS trial for an example of this).² We should keep this in mind because many therapies we may consider to be adjunctive today will likely take their rightful place as primary therapies.

Latanoprost also is the only topical therapy proven to slow glaucoma progression. In the UKGTS, a sensitive measure of visual field progression showed that 25% of newly diagnosed glaucoma patients treated with placebo progressed over 2 years compared to 15% with latanoprost.³ I still wonder what we would find if we studied timolol in this manner, but that probably will not happen.

Latanoprost has found its way into a remarkable number of formulations. In this way, latanoprost has seen the best that ophthalmic pharma has to offer. While I remain bitter that the FDA did not approve the latanoprost-timolol fixed combination therapy, I was happy to see the Rho kinase (netarsudil) latanoprost combination (Roclatan; Aerie Pharmaceuticals) approved. Furthermore, with the nitric oxide–donating latanoprostene bunod modification, latanoprost seemingly found a way to become one of the most powerful single-agent therapies while maintaining its great tolerability. Finally, over the past few years, latanoprost has found a way to shed the eye drop’s mortal coil, benzalkonium chloride (BAK). We now have non-BAK latanoprost (Xelprost; Sun Pharma), as well as the recently approved Iyuzeh (preservative-free latanoprost 0.005%; Thea Pharma). TearClear recently developed a BAK-preserved latanoprost that is packaged with a BAK-snatching bottle tip that delivers a preservative-free drop, and clinical studies are under way to evaluate it. Latanoprost has even found its way into a multitude of drug delivery device candidates, many of which are delivered externally to the eye, a testament to the drug’s excellent surface tolerability.

The story of latanoprost could be a metaphor for the challenges and transformation glaucoma physicians must embrace. We should be data driven. We must evolve our paradigms to find the best treatments. We must understand the side effects of our therapies and adjust accordingly. We must adapt new drug-delivery systems and preservative-free and combination therapies. In short, we have to use all of the tricks in our bag, and we invite you to read this issue of Glaucoma Physician to learn just a little more about the capabilities of our field. GP

Dr. Radcliffe is a clinical associate professor of ophthalmology at the New York Eye and Ear Infirmary of Mount Sinai and a surgeon at the New York Eye Surgery Center.

References

1. Camras CB, Bito LZ, Eakins KE. Reduction of intraocular pressure by prostaglandins applied topically to the eyes of conscious rabbits. Invest Ophthalmol Vis Sci. 1977;16:1125-1134.
2. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-830. doi:10.1001/archopht.120.6.701
3. Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial [published correction appears in Lancet. 2015 Jul 11;386(9989):136]. Lancet. 2015;385(9975):1295-1304. doi:10.1016/S0140-6736(14)62111-5