Nathan Radcliffe, MD: Benefits of Combo Eye Drops for Glaucoma

Nathan Radcliffe, MD

A study of combination eye drops for glaucoma found that at 90 days, patients receiving the simplified eye drop regimen had a change of -4.2 mmHg from baseline intraocular pressure (IOP) compared to a change of -1.9 mmHg in those receiving the same medication as separate eye drops.

About 40% of patients with glaucoma require more than one eye drop to control their eye pressure, said Nathan Radcliffe, MD, Clinical Assistant Professor of Ophthalmology, Icahn School of Medicine, Mount Sinai.

Radcliffe, Lauren Seo, BA, and Damien Goldberg, MD, were authors of the poster presenting this data at the 2018 American Academy of Ophthalmology Annual Meeting held in Chicago, IL.

“It gets complicated,” said Radcliffe. “They're taking 1 drop at night another 3 times a day and then another twice a day and they need a schedule. It's impossible for them to keep it straight.”

Both the complexity of the multi-drop regimens and the high cost of multiple eye drops are challenges that patients face that provided an impetus for the study.

“A compounding pharmacy will typically charge something like $50 for a month's supply of these drops,” Radcliffe told MD Magazine®. “I asked most of my patients how much they're paying for their eye drops and you'll get no shortage of surprises there. Some people have very good co-pays, but some people will tell me they're paying $300 or $400 a month for their eye drops.”

(Full transcript of the video is below.)

The prospective, multi-center, observer-masked study included 60 patients with primary open-angle glaucoma who were taking at least 3 intraocular pressure-reducing medications.

Participants were randomized to either the combination drop group (IP) (n = 29) or to the control group (n = 31) where they continued their current therapy of ≥3 medications. The IP group received one combination for the morning (timolol maleate .5%, brimonidine tartrate .2%, dorzolamide hydrochloride 2%, with benzalkonium chloride .001% as a preservative) and another combination for the evening (same as AM with additional latanoprost .005%).

Participants were evaluated at baseline and on days 7±2, 30±7, 60±7, and 90±7. The primary outcome measurement was IOP change, while secondary outcomes included corneal staining and visual acuity.

The study met the primary outcome of non-inferiority as the upper limit of the 95% confidence interval for between group difference in mean change from baseline IOP was <1 at all measurements. Additionally, the upper limit was <0 at all measurements, indicating the superiority of the combined eye drops.

Total corneal staining improved for 89% and 54% of patients in the IP and control groups, respectively, by day 90. Additionally, 54% and 4% of IP and control patients improved at least 4 points from baseline to day 90.

The mean differences in corneal fluorescein staining showed that there were significant differences between IP and control groups at days 7, 60, and 90. The authors suggested that this could be explained by the lower levels of preservatives in the IP versus control regimen.

“There are many benefits to combining 4 medications into a single bottle,” wrote Radcliffe, Seo, and Goldberg. “These benefits include a lower amount of preservative exposure to patient, the use of fewer bottles, and easier dosing schedule, ad potential cost savings.”

Radcliffe also touched on the benefits the combination drops have for ophthalmologists prescribing them. The simpler regimen means that providers don’t waste time during follow-up visits repeatedly reviewing and explaining the medications with patients.

The poster, “Prospective Multicenter Trial of a Compounded Fixed Combination of Timolol Maleate 0.5%, Brimonidine Tartrate 0.2%, Dorzolamide Hydrochloride 2%, Latanoprost 0.005%, for Glaucoma,” was presented at the 2018 American Academy of Ophthalmology Annual Meeting in Chicago, IL.

What were the reasons for studying combination eye drops for glaucoma?

This transcript has been edited for clarity.The background for my research is that in the treatment of glaucoma we mainly rely upon eye drops to get the pressure down, but we're using these eyedrops—multiple bottles in some patients, about 40% of patients need more than one eye drop to control their disease, and it gets complicated. They're taking 1 drop at night another 3 times a day and then another twice a day and they need a schedule. It's impossible for them to keep it straight. Most patients can't even say some of the words on their eye drops and so there's been some confusion there.

How did you decide on a combination of eye drops to test?

What are the financial implications of your results?

What can providers expect if they begin prescribing combination eye drops?

But it's also expensive—because even generic medicines in 2018 can be really expensive. There's a lot of fluctuation in price from month to month, so one potential solution to this is to make your own eyedrops and the way you would do that is through a compounding pharmacy. A compounding pharmacy can get the individual powder for 4 common glaucoma medications and compound them into one bottle that's then taken twice a day or something like that.The way we decided on the combination to use—there are now 5 or 6 classes of pressure-lowering therapy and we picked the most commonly used molecule in its generic form from the 4 most commonly used medicines. So, most of the patients who were on their own therapy really stayed on the same molecules and just got switched to having them in a different way.One of the implications of this is actually that it may be a way to get patients on less expensive therapy. A compounding pharmacy will typically charge something like $50 for a month's supply of these drops. I asked most of my patients how much they're paying for their eye drops and you'll get no shortage of surprises there. Some people have very good co-pays, but some people will tell me they're paying $300 or $400 a month for their eye drops. Of course I’m always saying, “why didn't you tell me? This is horrible, that's too much money.” But they don't know and so for patients in that situation they can save a lot of money, get on something that's easier to use, and easier to remember. It's sad, but a lot of people just have trouble remembering the names of all their drops and if you don't know the name of your drop it's hard to take it appropriately.What's different for doctors if they choose to use a compounded therapy is their patient will probably be a little bit more clear, in terms of what medicine they're on and how they're supposed to be using it because it's in some cases it's just one bottle twice a day. There's actually a lot of time that we spend reviewing these medications, and to be honest I'll spend a lot of time, I'll take time to write it out, and then the next visit it's like we're back to square one in many cases.

I have had patients who I’ve put on this therapy and when they run out, they're coming back and asking for it again because for them it was either a lot less expensive or a lot easier to use. And again, sometimes the pressure goes down and of course that's always the main goal for treating glaucoma—to lower the eye pressure.