Neil Minkoff, MD: And just to make sure we’re all on at least equal footing to discuss this, could you talk about some of the different classes of drugs that you would use in glaucoma and give some examples of why you choose those classes rather than other classes for a patient?
Nathan Radcliffe, MD: Yes. The first-line treatment is widely considered to be the prostaglandin analogue, basically 0 systemic adverse effects and mainly local adverse effects, which ophthalmologists have a good grasp of local adverse effects around the eye. They have high efficacy and good tolerance, hyperemia being the main adverse effect of these drugs. Then we move on to some of the traditional therapies. These include the aqueous suppressant class of drugs, beta-blockers, with timolol maleate being the most widely used. We also have carbonic anhydrase inhibitors, topical in this case, as well as alpha agonists. Brimonidine is mostly the only molecule in this class.
Of these 3 that I just mentioned, we have fixed combinations that are the basis of modern drug therapy. Fixed combinations are the fastest growing drug class, and the reason for this is that patients, most of whom have low health literacy in this regard and poor dexterity because they are aging, and find it difficult to juggle more than 1 or 2 bottles a day. If you can put them together, it’s a real benefit in terms of quality of life. This is also an area where most ophthalmologists disagree with the FDA. [Food and Drug Administration]. The FDA is hesitant to approve fixed combinations, and we want them all in 1 bottle. It’s a fight for us.
Recently we had a new class of drugs, our first class for a very long time called rho-kinase inhibitors. And, again, there was only one company making them and only one molecule, netarsudil [Rhopressa]. It is available in a fixed combination with a prostaglandin analogue, which is unique because it is the only fixed combination we have with a prostaglandin analogue. Interestingly, there is only one representative of the class of prostaglandin analogues that is generic and that is latanoprost [Xalatan]. It is the molecule most used for glaucoma. There are other generics, but they must be single-source generics. They are prohibitively expensive, and if it is a generic prostaglandin analog, even though we have 5 or 6 branded alternatives, we really only have one generic available.
Neil Minkoff, MD: This is probably a naive question, but why is the combination necessary? I need combinations in 1 bottle because that’s for the patient and it can be difficult to apply the drops or what have you. But what percentage of glaucoma patients ultimately require combined or multiple drug therapy?
Nathan Radcliffe, MD: It’s about 50%. It might be a little surprising, but we learned that you probably want about a 35% pressure reduction, and the prostaglandin analog class gets you 30% to 35%. If that’s average, you can imagine that half the people don’t reach that average and will need an additional agent to get the desired pressure reduction. Also, as we treat earlier and get better and better [at] recognizing the disease, we are more aggressive. We have good technology to detect progression, it’s wonderful. The downside is you have a person on 1 drop, and it progresses, well, you have to add a drop. We realize we have to be aggressive. Almost all glaucoma patients get worse over their lifetime, even when treated and even when treated well. It’s just part of the disease. We have to be aggressive and that’s where you end up using more than one therapy.
Neil Minkoff, MD: I guess my follow-up question then would be as I’m very interested in hearing both your and Dr. Pickering’s opinion on this. One of the things we love about managed care is the guidelines and pathways. You start with drug A or class A, then you go to class B, then you add class C and so on, like we do with, say, diabetes drugs or heart drugs or something like this, CHF [congestive heart failure] medications. Is there a progression that you normally follow in these patients? I guess are part A and part B, as glaucoma specialists, seeing the patient too late for that and you have to max it all out?
Terri-Diann Pickering, MD: The answer is yes and no. In theory, we would start with the most effective drops, which are prostaglandin analogues, and that’s what I’m trying to do. However, they have a particular negative effect. If your iris is hazel, which means it is a mixture of brown and green or brown and blue, 40% of these people will have a permanent change in iris color to brown. So just on that basis most of my patients with hazel eyes or even if you have light brown eyes that may turn dark brown, they won’t agree to use a prostaglandin. We can have a decision tree, but when faced with a particular patient, literally looking at their eyes, we can’t use the most effective drug.
Then you go to the second level, which could be a carbonic anhydrase inhibitor, and those are sulfa drugs, and a lot of people are allergic to sulfa drugs. Then you go to another second level drop which is brimonidine, and it’s a generic and it’s useful. But for my older patients, especially for some reason women, they can get tired with this drug. Then you have beta blockers, that’s fine, it’s been around for decades, it’s generic, you can’t use it for my patients with asthma, CHF or COPD [chronic obstructive pulmonary disease]. The problem with treating glaucoma is that we have a lot of drops, but looking at any patient we can eliminate 1, 2, 3 or even 4 whole classes of drugs leaving us with these types of drugs more recent and much more expensive. drops that, no matter how we try to appeal, are not approved. It becomes difficult.
Transcript edited for clarity.