Benefit Persists After Prostaglandin Stopped in Glaucoma

Fran Lowry

March 07, 2016

FORT LAUDERDALE, Florida — When people with primary open-angle glaucoma discontinue treatment with a prostaglandin analog, the reduction in intraocular pressure remains.

This finding has implications for medical and surgical decision-making, as well as for research trials evaluating new drugs and devices, said Cindy Hutnik, MD, PhD, professor of ophthalmology and pathology at Western University in London, Ontario, Canada.

"I do a lot of clinical-trials research, and one of the first things you do if you are testing a new drug or device in your glaucoma patients is to discontinue prostaglandin and then bring them back after the conventional washout period, which is 4 weeks," she told Medscape Medical News.

"I found that after that washout period, for many of my patients, their pressures weren't high, they had not gone back up, despite being off the drugs for weeks. I thought this might have implications, not only for clinical-trial research, but for how I treat my patients," Dr Hutnik said here at the American Glaucoma Society 2016 Annual Meeting.

Dr Cindy Hutnik

In their 6-week study, Dr Hutnik and her colleagues assessed 214 people 18 years and older with primary open-angle glaucoma who were treated with a prostaglandin analog for more than 6 months. The 124 patients randomly assigned to discontinue treatment served as the washout group. The 90 patients who continued with current medication served as the control group.

The investigators compared intraocular pressures measured at randomization and at 1, 3, and 6 weeks after randomization with baseline pressures, measured before the initiation of the prostaglandin analog.

In the washout group, mean baseline intraocular pressure was 26.6 mm Hg. After chronic treatment with a prostaglandin analog, mean pressure had decreased to 14.5 mm Hg in these patients (P < .001). After 6 weeks without treatment, mean pressure was 20.3 mm Hg, which was significantly lower than the baseline pressure (P < .05).

 
It is also interesting on a basic science level. How is this drug working for such a sustained period of time?
 

As expected, intraocular pressure continued to decrease in the control group, and values did not change during the 6-week study period, Dr Hutnik reported.

In the washout group, the decrease in intraocular pressure at 6 weeks "was less than what it was when the patients were on treatment, but still lower than it was at baseline," she said.

The "big surprise" was that pressures stayed significantly lower after discontinuation. "In fact, we have some patients we have been following for 1 year, and the intraocular pressure is still staying there," Dr Hutnik added.

That this effect can persist for so long has raised some important questions.

"I don't know if it means that it's bound to the receptor. I don't know if it means that it has altered the tissue. One thing I have noticed in patients who have been on these prostaglandin analogs is that when I subsequently do laser procedures on them, something about being on the medication alters the effect of the laser. I think it's at the tissue or cell level. There is a lot more research that we can do," Dr Hutnik explained.

Dr Sarwat Salim

"This is a very important clinical and practical study," said Sarwat Salim, MD, professor of ophthalmology and chief of the glaucoma service at the Medical College of Wisconsin in Milwaukee.

"In our clinical practices, often if one medication is not achieving the target intraocular pressure, we would like to try another one," she told Medscape Medical News. "But how do we know if the previous one is still working, and for how long that effect is sustained?"

The implications for surgery are also important, she added.

"Dr Hutnik brought up a good point. If a patient is booked for cataract surgery or cataract surgery and one of the minimally invasive glaucoma surgeries (MIGS), and right afterward you see a mild reduction, not a significant reduction, in intraocular pressure, you don't really know if it's the surgery that did it or if it is the sustained effect of the medication. That is why knowing the washout timeframe is very important clinically," said Dr Salim.

Dr Shuchi Patel

The findings also indicate that missing the occasional eye drop may not be catastrophic, said Shuchi Patel, MD, from the West Palm Beach Veterans Affairs Medical Center in Florida.

"In terms of practical use for our patients, that message is very interesting," Dr Patel said. "If you are changing patients off of drops and using another kind of drop, you may need to give a longer washout period for prostaglandins to see which kind is more efficacious."

"It is also interesting on a basic science level. How is this drug working for such a sustained period of time?" she asked. It "would be interesting to see if the prostaglandin analogs are causing some other structural changes or have another mechanism of action than we had assumed," she added.

This study was funded in part by the Canadian National Institute for the Blind. Dr Hutnik reports that she is a consultant for Alcon Laboratories, Allergan, Merck, and Bausch + Lomb. Dr Salim and Dr Patel have disclosed no relevant financial relationships.

American Glaucoma Society (AGS) 2016 Annual Meeting: Abstract 65. Presented March 4, 2016.

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