Eyeworld

4 Advanced glaucoma treatment: Diagnostics, pharmaceuticals, and surgical options Figure 1. Current treatment paradigm by Nathan Radcliffe, MD Exploring new and current glaucoma therapies: Safety, efficacy, and patient selection Current and future therapies will expand glaucoma treatment options W ith the ongoing de- velopment of glau- coma medications, clinicians have an unprecedented abil- ity to customize treatment strate- gies based on each patient's needs and disease state. Moreover, the future offers even greater promise with the potential for new drugs and drug-delivery technologies. Emerging treatments Prostaglandin analogs (PGAs) typically are first-line therapy, although selective laser trabecu- loplasty (SLT) can be used at any point (Figure 1). PGAs generally achieve a 25–30% intraocular pressure (IOP) reduction, but each has its own safety and efficacy profile. 1 Ophthalmologists often rely heavily on adjuncts. In the Ocular Hypertension Treatment Study (OHTS), which sought a 20% IOP reduction, 40% of patients required 2 or more drops; however, increasing the frequency or dosage may increase non-com- pliance. 2 Combination therapy sim- plifies administration, and the side effect profiles of approved fixed combinations are generally good. 3–6 However, generics vary significantly from brand name drops in drop volume, viscosity, surface tension, and bottle tip. 7 New PGAs are on the hori- zon. Latanoprostene bunod, a ni- tric oxide donating PGA, increases outflow through the trabecular meshwork. In the APOLLO and LUNAR studies, latanoprostene bunod administered once a day vs. timolol maleate 0.5% admin- istered twice a day reduced mean IOP 7.5 to 9.1 mm Hg in patients with open-angle glaucoma and ocular hypertension. 8,9 The effect on IOP was statistically superi- or (p<0.05) to timolol in both studies. In the CONSTELLATION trial, latanoprostene bunod administered once a day reduced IOP during a 24-hour period vs. timolol maleate 0.5% adminis- tered twice a day, which reduced daytime IOP only. 8,10 A New Drug Application has been filed for a benzalkonium chloride-free latanoprost formu- lation with proprietary swollen micelle microemulsion technolo- gy, designed for solubilizing oph- thalmic drugs with limited water solubility or insoluble ophthalmic drugs. 11 Trabodenoson is an ade- nosine mimetic optimized to selectively target the A1 recep- tor. Phase 2 trials demonstrated dose-dependent IOP reduction in subjects with primary open-angle glaucoma or ocular hyperten- sion that did not reach maximal efficacy. 12 A new class of medication, inhibiting rho kinase (netar- sudil), increases flow through the trabecular meshwork, reducing episcleral venous pressure and moderating aqueous production through norepinephrine trans- porter inhibition. In Rocket 1 and Rocket 2 phase 3 studies, netarsudil achieved its primary endpoint of non-inferiority to timolol. 13 Phase 3 trials are in progress for a sustained-release bimato- prost intracameral implant. Phase 1 and 2 data showed that all dose strengths had similar IOP reduction to bimatoprost 0.03% through week 16. 14 After this time, it continued to provide sta- tistically significant IOP reduction through 6 months of follow-up. A flexible bimatoprost sustained-release ring is being studied, which is placed in the su- perior and inferior fornix. 15 Mean IOP was reduced in phase 2 study patients treated with the device (mean decrease from baseline, –3.2 to –6.4 mm Hg) for 6 months compared with those receiving timolol 0.5% daily (mean de- crease from baseline, –4.2 to –6.4 mm Hg). Other sustained-release options also are being studied. Conclusion We have many options to reduce IOP in patients with glaucoma, and many others are expected. These will allow us to tailor treat- ment to patients' lifestyles, needs, disease stage, and velocity. Practice pearl: Be versatile with your medication choices. We now have many options (and more on the way) that fit the needs of most patients. The key is matching the right treatment approach to the right patient. –Nathan Radcliffe, MD continued on page 5 References 1. Parrish RK, et al. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, masked-evalu- ator multicenter study. Am J Ophthalmol. 2003;135:688–703. 2. Kass MA, et al. The Ocular Hyperten- sion Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–713. 3. Sherwood MB, et al. Twice-daily 0.2% brimonidine-0.5% timolol fixed-combina- tion therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular hypertension: a 12-month randomized trial. Arch Ophthalmol. 2006;124:1230–1238. 4. Higginbotham EJ, et al. Latanoprost and timolol combination therapy vs. mono- therapy: one-year randomized trial. Arch Ophthalmol. 2002;120:915–922. 5. Radcliffe NM. The impact of timolol maleate on the ocular tolerability of fixed-combination glaucoma therapies. Clin Ophthalmol. 2014;8:2541–2549. 6. Nguyen QH, et al. Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fixed-combination brinzolamide 1%/brimonidine 0.2%. J Ocul Pharmacol Ther. 2013;29:290–297. 7. Mammo ZN, et al. Generic versus brand- name North American topical glaucoma drops. Can J Ophthalmol. 2012;47:55–61. 8. Valeant company website. 9. Vittitow JL, et al. Long-term efficacy and safety of latanoprostene bunod 0.024% for

• Cover