William Freeman, MD: Creating Treatments with Compliance in Mind


William Freeman, MD, of UCSD and Shiley Eye Institute, discusses the importance of creating treatments for eye diseases that make compliance easier for patients.

Treatment compliance is an issue that physicians, particularly ophthalmologists, have been dealing with for decades. As new treatments are developed, researchers must always keep in mind how easy it is for patients to remain compliant for the duration of the treatment.

We sat down with William Freeman, MD, director of the Jacobs Retina Center at the Shiley Eye Institute and distinguished professor at UCSD, to discuss the importance of making treatments that are easily adherable and make compliance easier for their patients.

MD Magazine®: What is the importance of creating treatments that are easily compliable for patients with diseases of the eye?

Freeman: I work with companies in drugs, trying to develop it into a pill —that's easy, it's once a day. You should be able to assure compliance but the problem is if you do anything systemically you're going to have side effects, there's no doubt, and certainly some of the drugs were using, like anti-VEGFs, if you gave it systemically, you’d end up killing these patients. So, most of us feel that local therapy is the answer. We are now doing it, very crudely. We take as much drug as we can squeeze into the eye by its molecular weight, and all these things, and get a very high level. That level actually might cause side effects but you have to have a very high level, as it decays exponentially every few days. The drug level is half and half and half and half. So, most of the drugs we have last for a month or two and the companies try to analyze the data to get approval for as long as they can. So, for example, Eylea replaced Lucentis by and large because it can be given every other month. Our experience is that at first have to give it every month 3 times then you back off to every other month and in some patients that works, but in some patients you have to go back to monthly.

So, we're now in the world of still doing intravitreal injection of a very high concentration of drug frequently. Whether it be every month, every 6 weeks, every 8 — it varies by the patient. It's not ideal and when you look at every study of the real-world outcomes in wet macular degeneration as opposed to what the clinical trial says, the outcomes are not as good and it’s because the doctor do not send the bus to bring the patient in exactly 4 weeks or whatever. The patient thinks they’re doing okay, the patient may come in when the vision drops and you may not be able to get it all back.

Now in this disease, geographic atrophy, once the vision drops you can’t get it back. You can show them images that you are giving them a treatment that will reduce the risk of this enlarging and wiping out the central vision but, you know the patient comes every 3 months, 3 or 4 times and things look the same to them. They may just say you know I don't notice anything and the compliance problem is important as they will not notice, by and large, any improvement. So, they have to trust the doctor is doing what is best for them. It’s like hypertension, the patient feels fine if their pressure is 160 over 90, they’re at an increased risk of stroke and myocardial infarction but they don’t feel any different. So, it’s an issue of communication with the patient, showing them images. A lot of my patients will come every week if I ask them, but that’s not the rule in the real world. So, compliance is critical. So, an every 3-month drug is a lot better than a monthly.

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