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"We knew ahead of time that prostaglandins were an advancement. We also knew there are three very good ones there and the differences between them are not that significant," noted moderator Douglas R Anderson MD in a debate entitled ‘War of the Prosta-somethings’.

Douglas R Anderson

Carl Cameras

Peter Netland

Carl B Camras MD was first to present the case for latanoprost, one of the world’s best selling glaucoma products. He asserted that latanoprost should be the first agent chosen, primarily because of years of experience with the drug, while the others are newer and their side-effects less known.

Dr Camras said in addition to having the edge in terms of clinical experience, latanoprost "without question" produces less hyperaemia and eyelash growth, and less pruritus compared with the other agents. He cited clinical studies indicating equal efficacy for latanoprost, travoprost and bimatoprost.
Peter A Netland MD, PhD, of the University of Tennessee, backed travoprost, saying the drug is a highly potent prostaglandin analogue with a very powerful IOP lowering effect. This effect has a long duration and the side-effect profile is also reasonable.

"The pharmacology, which I think we’ve reached a consensus on, is that travoprost more potently binds to the FP prostaglandin receptor, which is associated with the hypotensive effect. That may be one explanation for some of the differences we are seeing in clinical trials on the efficacy of the drug," Dr Netland said.

He added that the number of glaucoma patients in the United States is estimated to be between 2m and 3m. African-Americans are affected more severely than the rest of the population. Study results have suggested that travoprost is more effective than other drugs in treating African-American glaucoma patients.

Because of the long duration of the effect of travoprost, the drug still works for prolonged periods after it has been discontinued. Effects discovered in diurnal measurements show differences at longer time periods after the discontinuation of the drug dosage and Dr Netland believes they might be attributable to the differences in the potency of travoprost. Slight differences in the responder rates were also reported, along with other small discrepancies hat may have also some clinical significance.

Ronald L Gross MD took the floor for bimatoprost, calling it "the single most effective drop to lower IOP". He reported that the drug is safe and well tolerated. Its side-effects include occasional hyperaemia and iris pigmentation, along with increased eyelash growth.

Dr Gross prescribes bimatoprost to his patients with the most severe case of glaucoma, switching to it to increase the IOP lowering effect without ordering additional drops.
He has found that in individual patients, bimatoprost achieves low IOP more often than other drugs. He stressed that a short-term investment in bimatoprost pays long-terms dividends.

The panelists also looked at the potential effect of the glaucoma drugs on the uterus. Dr Anderson told EuroTimes: "That’s just a theoretical concern because prostaglandins in general are known to cause uterine contractions and they are used for that purpose.

"But it has been pointed out that the concentration that would actually reach the uterus in a human being after an eye drop is quite low and is probably not a real danger, but it is a theoretical danger. As a practical matter, just to be on the safe side, if you have another alternative, I think all the panelists agreed they may choose at least some of the other classes of glaucoma drugs."

At the end of the debate, Dr Anderson declared ‘The War of the Prosta-somethings’ a draw, since it was clear from the discussion that all of the drugs represent a major advance for glaucoma patients.

Dr Netland agreed with the moderator’s decision: "We do need a bit more information to distinguish all the different drugs. We had a draw today and I think that was a fair assessment because we are perhaps not quite at the point where we can reach consensus with enough information to be able to make all the fine distinctions we would like to between the drugs."

New three-way study released

Another study, Comparing Latanoprost, Bimatoprost and Travoprost, by Dr Parrish and Dr Palmberg, and colleagues, was not included in the ‘Battle on the Beach’ programme because it was about to be published in the American Journal of Ophthalmology. The study was subsequently released and Dr Palmberg discussed it in an interview with EuroTimes.

Conducted at 45 sites in the US, the 12-week, randomised, parallel-group study was intended to compare the IOP-lowering effect and safety of latanoprost, bimatoprost and travoprost in patients with open-angle glaucoma or ocular hypertension.
Between 130 and 140 subjects were randomly assigned to each of these prostaglandin analogues. At three months, the change in pressure achieved with each drug was virtually the same within 0.3mmHg, so that they were statistically indistinguishable.
However, Dr Palmberg says the original drug in the class, latanoprost, was better tolerated, with only half as many eyes experiencing redness or itching.

"This was expected because five previous studies including those sponsored by the companies making the competitors had also shown that it was tolerated better. During development, it was discovered that reducing a 13 to 14 double bond would make the drug more tolerable, without compromising potency. But that is a patented feature the other drugs cannot copy," he said.

The scientists then looked at the distribution of pressure-lowering responses for each drug and found they were also indistinguishable. This finding was in contrast with another study, which found a higher percentage of subjects responded worse to latanoprost than bimatoprost.

A sub-analysis determined that those subjects who had previously been on latanoprost responded the same as those who had not. In other words, the study did not appear to be biased in favour of including especially good subject responses to the drug.
"If you were to consider all the studies done so far, it is likely that there is less than 0.5mmHg difference between any of the drugs, with latanoprost clearly the best tolerated," Dr Palmberg said.

Douglas R Anderson MD
Bascom Palmer Eye Institute, Miami, Florida, US
Email: danderson@med.miami.edu

Carl B Camras MD
University of Nebraska Medical Centre, US
Email: cbcamras@unmc.edu

Peter A Netland MD, PhD
University of Tennessee Health Science Centre, Memphis, US
Email: pnetland@dellmail.com

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