Leveling Access in Retinal Care: Driving Equity with Innovative Therapies

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Leveling Access in Retinal Care: Driving Equity with Innovative Therapies

Speakers: 
Jennifer I. Lim, MD, FASRS, FARVO
Jeremiah Brown Jr, MD, MS, FASRS
Rahul N. Khurana, MD, FASRS

Topics: Disparities in the access to care, treatment adherence, and treatment outcomes in patients with retinal disease

Dr. Lim:

Good evening and welcome to our program on Leveling Access in Retinal Care: Driving Equity with Innovative Therapies. This is a CME activity sponsored by Evolve. Our faculty includes Dr. Jeremiah Brown from the Retina Consultants of Texas, Dr. Rahul Khurana from Northern California, Retina Vitreous Associates and Clinical Associate Professor of Ophthalmology at UCSF. And I'm Jennifer Lim from the University of Illinois, where I serve as a chair of Ophthalmology, Vice Chair for Diversity, Equity and Inclusion, Director of the Retina Service and UIC Distinguished Professor of Ophthalmology. Thank you so much for being here tonight with us. And thank you, Dr. Brown and Dr. Khurana, for helping me on this program tonight. So, without further ado, we'll jump right in and we'll discuss patient presentations to the clinic and access to care. 

So, what is health equity? Well, health equity is a condition that exists when all people, regardless of their race, their sex, their sexual orientation, presence of disability, socioeconomic status, geographic location, or other societal contracts have fair and just access, opportunity and resources to achieve their highest potential for health. And it's extremely important, obviously, that this exists in the United States. Unfortunately, the reality is that it does not, and specifically it really involves eyecare. And we've seen this in the AAO IRIS registry. So, for instance, if we just look at diabetic retinopathy, diabetic macular edema, we can see that the prevalence of DR and DME is greater in the US Black and Hispanic patients compared to White patients. And furthermore, the risk of sustained visual loss is also higher in groups such as the Black patients, Asian patients, female patients as compared to White and male patients. Now, we know in the United States that the Hispanic population is the largest minority, and this group has the highest rate of diabetes. It's 80% higher in adults and five times higher in children compared to patients who are non-Hispanic White.

And we really need to address this. In addition, Hispanic individuals have a 66% greater risk of developing type 2 diabetes, and once diagnosed, they have a worse health outcome than non-Hispanic Whites. We also know that there are higher rates of diabetic retinopathy found in patients who do not have a high school-level education or who are at lower income levels. In addition, for those patients who are in lower socioeconomic status, they also present with more advanced stages of disease, such as age-related macular degeneration in the first eye, but not in the second eye because they're already in the health care system at that point. So, really this is a big problem in the United States, and we need to find some solutions to this. We need health equity to exist for ophthalmology and specifically for retinal diseases. So, now let's look at diabetes and diabetic retinopathy.

We know in the US that the diabetic retinopathy screening rates are low. And in fact, in a cohort study of youth who have diabetes and were eligible for diabetic retinopathy screening, it was found that those who had not had a previous diabetic eye exam were more likely to be non-white, have type 2 diabetes, be on Medicaid or public insurance, have a lower household income with an annual income less than or equal to $25,000, and to have parents with a high school diploma or less. So, this is our group at risk. In addition, if we look at patients and we adjust for household income, we adjust for presence of insurance or absence of insurance, and we adjust for parental educational level, we still see that minority youths remain less likely to have had a previous eye exam and more likely to have diabetic retinopathy. So, this shows us that there are some other reasons, perhaps there are some cultural or community-related access to health issues that we need to address.

In addition, minority populations between the ages of 18 to 64 years of age were less likely to receive eye exams compared to White counterparts. So, for some reason, these minority patients are less likely to perhaps access care and to utilize the care. So, these low diabetic retinopathy screening rates in our minority patients are associated with poor education surrounding diabetes-related complications. So, that's one area where we can have some impact by educating with regards to the disease and the possibility of diabetic retinopathy. In terms of access to care, when we look at the secondary analysis of the 2012 to 2014 US National Ambulatory Medical Care surveys, we see that Black patients had poorer diabetes control than White patients. We also see that the racial gap was significantly larger in rural areas compared to urban areas. And these patients in rural areas were found to have longer travel times to appointments, lower distribution of practitioners and facilities available to them, and access to barriers to healthy food.

They also were more likely to have less than a high school-level education and a lower household income. And we also found that health care practitioners in these rural settings are less likely than those who practice in urban locations to discuss the prevention of diabetes and risk reduction, including dietary care and physical activity recommendations. So, these are some areas that perhaps we can target when we see these patients, and we can educate our colleagues and our patients to these issues. So, now we're just going to discuss perhaps some effective strategies for overcoming these access to care issues, particularly amongst these marginalized populations. So, I'd like to ask both Dr. Brown and Dr. Khurana for your opinions on these issues. So, Jeremiah, you want to lead us off here and perhaps what are some effective strategies to overcome these access to care issues in this population?

Dr. Brown:

Sure. Good evening. One thing that I would really like to emphasize is the importance of education, health education. It's amazing how many patients come in not even knowing on their first visit that diabetes can cause eye complications. And so clearly that message is not getting down to all of our patients who have diabetes mellitus. When in the clinic, it's really important to be welcoming, to be friendly, to be setting the tone for a positive experience. So, patients who come in with diabetes, they've often been told, well, you are a diabetic or you are poorly controlled, or you’re this or that. To have a more open conversation about the importance of monitoring their vision, monitoring their retinal appearance, and having that eye exam every year in a more positive constructive way versus labeling, I think language is very important.

Dr. Lim:

Yes, I agree totally with that and that shared decision-making with the patients, kind of being an ally for the patient and not judging the patient. I think that is key. Rahul, do you have…?

Dr. Khurana:

Yeah, Jeremiah brought some really great points. And I think one of the parts, as retina specialists, we actually have a very unique opportunity that we often see our patients more often than their primary care doctors or their specialists. Just because of the regular nature of the treatments for diabetic treatments, our patients actually become very close to us and we actually have a really great opportunity to really impact their health even beyond their eyes. And so I think one of the things that is really important, I mean I think Jeremiah really talked about the importance of avoiding labels being open and then using this as an opportunity to further educate and also empower patients to be more empowered about their health and to be more involved in their health.

And part of that also involves conversations that I'll be honest, I don't always talk about, but access to care often we don't even assume that. We don't even think about that. And I think as you can form a better relationship with your patients, you can find some of these challenges. I mean, Jenny's done a nice description of a lot of the social determinants of health that often can be more impactful than the actual health issues on affecting care for our patients. And being aware of this is really the first step. I think education is super important, but bringing awareness of what these barriers are and acknowledging them is really the first step then to find ways to find solutions to them.

Dr. Lim:

Yeah, I agree with you, Rahul, and I think bringing in a social worker to help them with social issues, for transportation, for getting in to the clinic, being able to get time off work, I think all of these issues are very important. And then for us, for all of us who take care of these patients, we have to realize too that we have to be more available perhaps. We have to have times for when the patients who cannot afford to take time off work can see eye care practitioners. So, that's really important as well. And many other issues that social work can help us. So, thank you so much and we'll move on now to treatment adherence, which Dr. Khurana will present. And before we do that though, just again to emphasize the US diabetic treatment adherence, when we compare White patients to Black, Asian and Hispanic populations, we see that the Black, Asian, and Hispanic populations are less adherent to diabetes quality-of-care recommendations including dilated exams.

So, I'd like now to put a polling question up for our audience. And the question is, what are the greatest challenges in ensuring equitable access to retinal disease treatment in your practice? We want to know what's happening in your practice. Is it A) insurance-related barriers? Is it socioeconomic factors that affect adherence? Is it the treatment burden? Or D) is it advanced disease presentation limiting the treatment effectiveness? Or is it E) poor health literacy? What would you say is the biggest hurdle in your practice, Jeremiah?

Dr. Brown:

Yeah, it's hard. Several of these are right up there. I think that probably the biggest one is poor health literacy for those more severe patients who present with later in their course, have more severe disease, and maybe didn't realize the impact of diabetes on their eyes or the importance of glucose control, even if they're not to the point where they're actually having vision symptoms. So, I really think that education is a big part of this. And you can have insurance and you can have the ability to get to your appointment, but if you don't realize why it's important, you may not come.

Dr. Lim:

And Rahul, which one is yours in your practice?

Dr. Khurana:

They're all really important. And they're all somewhat intertwined, but I actually like Jeremiah's answer. I actually think the health literacy starts at the top because it's interesting, as retina specialists, we in view our treatments as a high-treatment burden. You see these monthly injections and it's there. And it's interesting because I have patients who are willing to come every month and who actually show up every month for their treatments, and they're amazing. Then I have some patients who can't come in every 6 months and the ones who show up every month understand the gravity of the situation, understand why it's important and are willing to do it.

And a lot of that stems from them understanding the disease, the importance of it, and are willing to do that. And so to me, the treatment burden becomes less of an issue, the more educated the patients are. And so, in some regards, education and health literacy are really almost, it's a starting point. And then, unfortunately, there are practical issues. I mean, I think insurance-related barriers definitely limit us once we have patients who are empowered and want to come in, but then we can't give the treatments we want to give. We have to wait for them to do poorly before switching on. And so I think that sometimes plays the next level that's there.

Dr. Lim:

Yeah, I agree with both of you. I really do believe it is poor health literacy and it's not necessarily even tied to poor educational level. I've had very well-educated patients who don't realize that certain diseases can affect the eye. For example, sickle cell disease. We see a lot of patients with sickle cell retinopathy and some patients are quite astounded to the fact that yes, it can actually cause bleeding in their eye and can lead to visual loss and bleeding. And I think that is probably the most significant challenge that we face because patients are unaware that these diseases can affect them. They present late. So, we get a lot of patients at the Eye and Ear Infirmary at University of Illinois at Chicago that come in with very advanced diabetic retinopathy, very advanced sickle cell retinopathy, very advanced retinal detachments because they think it's going to get better. So, I really think in this country we really need to educate across all retinal diseases.

And as you both know, many organizations, including the ASRS, are doing many public service announcements to educate the public about this. I think we're moving in the right direction. And I'd like now to just go over and let's see what our audience responded, because I believe the poll is now in. So, it looks like our audience said that insurance-related barriers account for the greatest challenge in 22% of them; 44%, it was socioeconomic factors that affect adherence that's the greatest challenge in ensuring equitable care; 11% said it was a treatment burden; and none said it was advanced disease presentation limiting treatment effectiveness. So, that's good. And the last response to poor health literacy, 22%. Really the top was socioeconomic factors and then insurance-related barriers and poor health literacy. And as you said, Rahul, they are all tied together. I agree. Let's go ahead now and let's learn from you about adherence issues. Dr. Khurana.

Dr. Khurana:

So, yeah, I think one of the issues that we brought up before was insurance-related barriers. And all of us who are practicing retina specialists have seen this firsthand. And we've seen issues with step therapy protocols that often have us to use certain drugs. Usually ones that are cheaper often have to "fail first" before we can go to the medicines that we may think should really be used first line. And it really, I think it's unfortunate on many levels of these protocols, because not only do they undermine the trust between both the physician and the patient, they ultimately delay the ultimate care that's there. Because if physicians come up with what they think is best for their patients, they should have the freedom, the ability to deliver these medicines instead of being constrained by certain rigid protocols. And so I think this ASRS poll really talks about what our colleagues have seen and have shown that there are a lot of adverse outcomes from step therapy protocols, which usually require starting with bevacizumab first.

And you can see these things occur from patient dissatisfaction, most importantly, lack of visual improvement, which is about 63%, worsening vision and then lack of effect on the left side. And then I think when we look at what our colleagues in the retina community have said, they do say the difficulties we have with patient outcomes. A lot of people blame step therapy, but also incomplete visits, and that's nearly 71%. They do talk about low health literacy, which Jeremiah highlighted, and a lot of the things that Jenny talked about inadequate access. And I think a lot of these things, unfortunately, are all coming together and, unfortunately, they're all going to get worse. As we've seen with the explosion of Medicare Advantage plans, which now have outnumbered Medicare fee-for-service plans, which often seem very attractive to patients because they have low costs, but, unfortunately, they often have limitation on choice for physicians and for the medicines that are there. And often many patients don't know this when they're getting signed up for these Medicare Advantage plans. And this is going to become a bigger and bigger problem as we move forward.

And something I think we all have to be really aware of, and we really need to advocate with our patients to give them the best care and also have the best options when it comes to insurance. And we're going to move on to the issues with step therapy. And I think as the previous surveys show that nearly 50% of retina specialists identify the lack of visual anatomic improvement when using some of these protocols. And this is actually not surprising. I think when we look at the DRCR protocols, we have seen that even in studies where they started off with a bevacizumab, a vast majority of these patients after 3 to 4 months had to switch to aflibercept.

I think that gives us evidence that that's there. One of the challenges of translating that into real-world practice is that often to get those switches or get the approvals, it's quite cumbersome. And many insurance plans have some arbitrary numbers where they really take away the choice of the physician to give what's best care, rather come up with some rigid protocols of having to do six treatments or three treatments, or even some protocols have advocated for losing over 15 letters of vision, which really is unacceptable if you have better options available. I mean, Jenny and Jeremiah, have you had issues with step therapy? What challenges have you guys had or what are some of the frustrations you've seen firsthand in your practice?

Dr. Lim:

Yeah, it certainly is a problem, and it's become a bigger problem as time goes by. And frequently a lot of these insurance plans, as you alluded to, make you start with say a bevacizumab when perhaps this is a patient who has a large pigment epithelial detachment and a lot of fluid that may be better served by a aflibercept or faricimab, any other drugs, some people use, brolucizumab. That's the problem, is it takes away our judgment. So, if we say, this is a situation where the biomarkers point to that this is going to be a process in say, neovascular AMD, that's going to be less likely to respond to bevacizumab based on studies that have been done. There are components of PEDs, there's very thick fluid, there's chronic fluid, polypoidal lesion, and, you know, that really you should try this.

If this is where you're at, this is what you'd want to do. And you can't get the insurance to agree with you. They tell you you have to start with this. You have to use at least three or five or sometimes even six, and you have to show there's lack of improvement. And frequently what happens, it's not just lack of improvement, it's a patient gets worse. And so then I'm writing back to the insurance through my authorization team and saying, "Look, please let them know vision's dropping, the biomarkers are worsening, this patient is clearly not responding. It's been three doses, please let me switch before further damage is done." So, that's what happens, I think, in some patients.

Dr. Khurana:

And I think one of the challenges about that is that when you have that fail and that key time when you can have a good relationship, you're building trust within your patient and you're kind of going down this path. And it's frustrating because even though you don't want to show this to the patient, you are frustrated because you're using a treatment that you know is maybe not best and it's not doing it. It doesn't build any trust with the patient. And we just talked about how a real key goal is for us to build trust, to empower them. When you have these structural constraints and needless constraints, it really makes that aspect even harder.

Dr. Lim:

Absolutely. Jeremiah, you were saying.

Dr. Brown:

That's exactly the point I was going to go to.

Dr. Khurana:

Oh, sorry.

Dr. Brown:

No, that's exactly it. And it's a little bit difficult because you're in the room with the patient and you're talking about their disease and what medication we're going to use. And you're having to look up to see, oh, what do we have to start with? And that's suboptimal as far as starting on a good note with your patient and to heighten what you said, and especially if the results aren't that great after the first few injections, I mean, that's when you'd really like to build that trust and really get them on board with, this is going to be a long-term project that we're starting together. And it'd be great to get them on board with enthusiasm. And sometimes that's hard.

Dr. Lim:

And when I go a little bit further for some of my patients who are also frustrated and I say, write to your congressperson, let them know that you as a patient don't agree with step therapy. So, just pushing it one level more.

Dr. Khurana:

Very, very important. So, yeah, so I think we kind of discussed some of these. There are some really egregious definitions of what failure is, such as requiring to lose 15 letters, which in my mind is completely unacceptable. And really, I think, as Jenny said, it really is going to involve everybody, not just physicians but our patients to also advocate to let them know that these things are unacceptable. And it's especially unacceptable for Medicare Advantage plans because by definition, Medicare Advantage plans are supposed to offer the same benefits as Medicare fee-for-service. And the fact that those patients first have to step through bevacizumab is completely unacceptable. And so I think these are all important things to kind of be aware of. 

And so we're going to shift gears a little bit here. We're going to talk a little bit about proliferative diabetic retinopathy and an issue of loss to follow-up. Really loss to follow-up was an area that became ... was an area that I was very interested in because there were reports that came out of the Wills Eye Hospital showing you really high rates. And it made me really wonder because often when in our busy clinics, if a patient doesn't show up, you're not always aware of it. The clinic is always full, and if someone is on a treatment plan and then falls off, we're not really aware of what's going on. And so in order to answer this, wanted to look, we looked at the American Academy's IRIS registry, as Jenny had talked about before, and the real beauty of the IRIS registry is this is a registry that covers nearly 70 to 75% of all ophthalmologists in the United States. And you can get really high numbers and really find out how certain disease or certain conditions that you really can't answer in single sites. And so we wanted to look at the rates of loss to follow-up specifically for PDR. We looked at 73,000 eyes of 57,000 patients with PDR who were diagnosed between 2013 and 2015 and were subsequently treated. And what we found was that we found risk factors for loss to follow-up, and we had a very broad definition.

We said, hey, you had to be seen within 12 months of your last injection or PRP, and if you received more than a year, that would be considered loss to follow-up, because that I think we all would agree, would be probably too long a follow-up that's there. And what we found was that patients that were higher risk of being lost to follow-up included our Black and African-American patients, Hispanic, Native American and Pacific Islander patients, and also patients who had unilateral disease compared to bilateral disease. So, we clearly saw those initial issues that Jenny had brought up about issues with not getting diabetic exams, things there, we're seeing it even in more advanced disease, which is not surprising. We also found that patients who had a worse baseline visual acuity of 20/50 to 20/200 and a vision worse than 20/200 were at a higher rate of being lost to follow-up than those with good vision. And we also found that patients who had Medicare fee-for-service, and even Medicare, managed plans had a lower rate to follow-up, and that's compared to private insurance.

So, patients in private insurance often had a higher rates of loss to follow-up. And finally, we found that patients who were treated in the South were more likely to be lost to follow-up than those patients treated in the Midwest and the West and even in the East. And this kind of also highlights the social determinants of health that we've kind of danced around a little bit, but unfortunately we know in the South there are also higher rates of poverty and higher rates of challenging ways of getting to access, which just further highlights and emphasizes the social determinants of health that often affect the care of our patients. And then a smaller study that looked at also risk factors for loss to follow-up, this came out of the Wills Eye Hospital and this looked at rates for PDR and looked at about 2,000 patients. And it found a lot of very interesting facts. It found that when you looked at gross incomes that were decreased, there were higher rates of loss to follow-up.

You saw that as the loss of follow-up also decreased as the age increased. And finally they found a differing rates that there's higher adherence with patients who are White compared to African-American patients, Asian patients, and Hispanic patients. Again, highlighting the social determinants of health issue and this disparity that we're seeing across many different health metrics. Finally, in another study that also looked at loss to follow-up, looked at rates in a community hospital, and here they found rates that were extremely high, nearly 61%, and they found that certain barriers were there: non-English as a primary language, living less than 20 miles away, having more than five comorbidities, all increase the rates of loss to follow-up and prevented adherence within seeing patients and following up for their care for proliferative diabetic retinopathy. And we also know that when patients with PDR who are not followed up, they're at high risk of developing really vision-threatening complications such as vitreous hemorrhage, tractional retinal detachment, diabetic macular edema, and adherence is really essential in maintaining and preventing severe vision loss.

When we look at adherence with anti-VEGF therapy, just in general, we see rates are very high from single-site studies looking from nearly 22 to 50%. And really a nice systemic review in ophthalmology showed that nearly 50% of patients stop anti-VEGF treatments within 24 months and really high rates of nonadherence. And so the challenging thing here is that we know anti-VEGF therapy for neovascular AMD has been revolutionary. We've seen these outcomes in clinical trials, but translating that into clinical practice has been challenging. There have been issues with different types of patients in the studies, but at the same time, we don't have the same adherence, we don't have the same compliance that had we had in the clinical trials in the real world. And that's why it's been very challenging to replicate the excellent results we have in the phase 3 studies when we look at our outcomes in clinical practice. And we again went back to the IRIS registry, looked at it specifically for neovascular AMD, and this was really the largest study.

And we found that really nearly one out of nine patients with neovascular AMD were lost to follow-up. And nearly one out of seven were nonpersistent. And our definition of being nonpersistent was simply having a follow-up within 6 months after your last anti-VEGF injection. And again, a very broad and generous category, but still found a very high rate. And when we looked at risk factors, you found that, again, increasing age, which makes a lot of sense. These patients often are older, have many comorbidities. It's hard for them to come in. We found actually male sex, unilateral involvement, diabetes, Medicaid insurance, and race and ethnicity, again playing its role in patients who are nonpersistent with anti-VEGF therapy and often are more likely to be lost to follow-up. When we talk about socioeconomic factors, we talk about social determinants of health and there's a lot of different ways this plays a role. One role is the cost of therapy.

We know that whenever there's any type of extra cost, it prevents adherence. And this can be as simple as a copay. And that's why one of the reasons why private insurances, there's actually higher rates of loss to follow-up and noncompliance because a simple copay actually can be a determinant. Now, when we talk about anti-VEGF therapy, we know that they're very effective. They're also quite expensive. And so sometimes their copays can play a big role in preventing patients from continuing or maintaining therapy. And we've seen this number to be up nearly 28%. There are copay assistance programs from private and public charities that are very helpful. And even we've seen this year with our good days nationally, which is under a little bit of a funding crunch that has affected care for our patients as that is becoming a challenging aspect. We also, there's also a cost of time away from work. Jenny's kind of alluded to this, many of our patients are working, and especially for our diabetic population, they're often working. And for them to take time off from work, that can often be a rate-limiting step. And finally, there's cost of transportation. And that's where I think involving social help, social workers to help kind of minimize these things can also help minimize it. And I think one of the first steps is really even asking the question and finding out are there barriers there? Because I think once you learn about those barriers, then you can try to come up with solutions to address them. 

Finally, there's some really good real-world evidence on diabetic macular edema therapy on how insurance and geography play roles. We've seen how across races, Medicaid insured patients have smaller gains. Any type of co-pay significantly lower the odds of receiving treatment. As I mentioned before, any type of copayment, like a copay really limits access or entry into the system and can be a determinant for adherence. We've seen that Hispanic patients were more likely to be treated with bevacizumab than White patients across all insurance types, controlling for disease severity and visual acuity. And finally, we've seen that in certain regions there are difference in how things are done.

We've shown how there are higher rates of nonadherence and loss to follow-up in the South. And often I think this really shows the interplay with social determinants of health where poverty and a lot of other things can often play a big role in care and how these patients do and what treatments they ultimately receive. So, I think as we've talked a lot about the problems of adherence, loss to follow-up, I think among my panelists, what are some effective strategies for overcoming this adherence barriers, particularly among marginalized populations or patients that may even have hesitation with the healthcare system of even coming in?

Dr. Brown:

One thing that I like to do is, especially with my patients_­—this is great for the diabetes population, patients who are making the effort and coming in and you can see their vision improving, you can see their retinas getting better—and to congratulate them for that, tell them, give them feedback. The reason you're doing so well is I see you here every time on time. That really makes a difference. And that's why we're seeing these results. It's easy to start to think that, well, I'm doing okay, maybe I don't need to go next time. And to kind of short circuit that thought process, I like to jump ahead of it and just give them that positive feedback.

Dr. Lim:

Yeah, I agree with you, Jeremiah. I do the same. I show them their OCT and they can see visually. And I always go back, I show them like what it looked like, how bad did it look, because sometimes they say, well, you're showing me last month, it doesn't look that different. I'm like, yes, but it's slightly improved. But look how far you've come from when you first presented. And I do this in front of the family and, just like you, I emphasize how important it is. And then I also tell the patient, look, this is really important for you. And I'm sure your wife or son or daughter, whoever it is, your mother, whoever it is with you, would want you to keep your vision and the family ... and of course the patient says, "Oh, but it's so hard. My daughter has," it's usually the daughter or the granddaughter, it's usually the female, let's say, "she has to drive, pick me up and bring me in, and it's such a burden."

And then I look at the family member and the family member immediately says, "No, it is my pleasure to do this for you. Of course, I want you to see." And then so you get buy-in. So, I agree, the buy-in from the family is really important. Now, if they don't have family and then they have social issues, the next thing is let me introduce you to my social worker. So, I immediately contact a social worker via chat on Epic or have somebody who can get the social worker and connect them right away. And then if cost is an issue, we are fortunate at the university to have access to some samples, limited number, but we have that ability and so we can use those in the meantime to bridge some problems with payment so that perhaps I can use this stronger drug and get the effect that I want to get and help the patient out and then get copay assistance for them while we're doing that.

Dr. Khurana:

And you guys brought up good points, educating, I think the office of the patient, it always starts back to Jeremiah's education, so I think that's always there. I think getting buy-in and educating their caregiver, I think working on both sides emphasize the importance of maintaining these visits. Do you guys have any thoughts on any other strategies from a practice perspective or from a system perspective to improve adherence or things that you guys have done in your practices to help have patients to kind of come in? Or if they do not follow-up to remind them?

Dr. Lim:

We definitely…

Dr. Brown:

[inaudible 00:34:12]. Okay, go ahead.

Dr. Lim:

Okay. I was going to say yes, we have to contact them and let them know if they miss an appointment and try to find out what happened. Are they sick? Is there some other comorbidity that's preventing them from coming in? Because especially the very reliable patients, you worry about them. Did they have a heart attack? Did they have an adverse effect to something? And so we have ways of following up in contacting the patient. I think it's really important, if you will, to do contact tracing almost, if you will, that kind of mechanism. Trace, see where they are, find out what happened, get to the root cause and help solve it.

Dr. Brown:

Mm-hmm. And I also, I think offering appointments that are a little bit later in the afternoon, making that available and just having that as a possibility for some patients. I also just wanted to echo what you were saying earlier, Dr. Khurana, as kind of a clinic-wide project to actually, for each of the participants on this call, take a look at your own clinic and see what your loss to follow-up rate is. It is surprising. I mean, we just don't think it's us because our clinic is always full. I remember her, I see her, I've known her for 15 years, we've been taking care of her, but you forget the ones that aren't there. And so once you do that actual exercise, you realize, wow, this is an issue. We need to address it in our clinic.

Dr. Khurana:

I think that's a really good point, Jeremiah. And I was just going to say, we've actually done that with these papers we've done. We've actually looked internally and saying, "Hey, what are our rates?" And it's much higher than you think. And before our solution was if someone didn't show up, we would call them and then maybe send them a card. And they've shown stuff that it's better to send a card than to do nothing. But now we actually call them up. And then often, a lot of times, many of them don't show up because they had something happen. They got sick, they got hospitalized, and so they're actually, even if you call them, they can't come in.

And so we actually have a system now that if they don't show up, we call them, we call them again, and then we call them a month later and we put them on a list and we keep hounding them and keep checking on them. And it's part of our practice to make sure that's there. And we've had patients who, for whatever reason, missed a visit and then they were out for a couple of weeks. And then normally, in the past, we would lose them, but now because we follow-up a month or two later, we're able to get them back into the system. And I think every practice, every clinic's got to figure out what the right way is to identify the problem, and then find out what are some effective strategies, whether it's callbacks, reminders, all those kinds of things to make sure people come back.

Dr. Lim:

Great. Thanks so much, Rahul. That was great. And I'd like now to move on to treatment outcomes, which Dr. Jeremiah Brown will present to us today. And do you want to take it away, Jeremiah?

Dr. Brown:

Absolutely. Sounds great. So, we've been kind of talking a little bit about this, but now we'll really get into the fact that many times the outcomes we see in our clinic are different than the outcomes we see in the big clinical trials. There was a post hoc analysis of the DRCR Protocol T trial, which showed that African-American patients with DME had the largest reduction in central subfield thickness, but they had smaller visual acuity benefits than White or Hispanic patients. Looking at the IRIS registry, White patients of non-Hispanic Latino ethnicity and those with private insurance on average received more injections over a 60-month period. Those factors we know are associated with higher long-term vision. So, many times the challenge is keeping a consistent level and number of appointments and getting those injections because with fewer appointments, fewer injections, you just don't get the same visual gains. Another retrospective study looked at a cohort of Black patients and they had a lower odd of visual improvement when receiving one or three bevacizumab injections compared to White or Hispanic patients.

So, basically showing that the response in Black patients to bevacizumab was not as good as in other patient populations. If we look at the ASRS PAT survey and looking at the question, are there racial ethnic differences in diabetic retinal disease response? And do you tailor your treatment based on these factors? Only 17% thought that there were differences based on racial or ethnic differences. And actually that small number actually tailored that to their treatment approach. 29% believed that there were differences but did not tailor their approach. Now where are the data coming from? So, where do we have our data to look to help guide us? Well, if you look over a 20-year period, Black, Hispanic, Latino and other non-White participants were underrepresented in clinical trials. So, this actually led to the FDA well in the clinical trials that led to FDA drug approval suggesting that the trial outcomes may not reflect treatment outcomes across minority patients populations.

And this is so striking that actually led to the FDA making a mandate that drug companies look at this issue and make plans for how to make their populations in their drug studies reflect the population that's actually going to be using this drug if it's approved. So, let's take a look at a few studies. So, first we'll start to the PHOTON study for diabetic macular edema. In this study, patients were randomized to either get aflibercept 8 mg every 12 or 16 weeks after three monthly doses, or standard aflibercept 2 mg every 8 weeks after five monthly doses. They looked at these results and broke it down by sex, age, race, ethnicity, best corrected visual acuity and central subfield thickness. Okay, so first, let's look at this visual acuity improvement by race at week 96. And you can see for the White population, 7.9 letters, 9.3 letters, and 8.2 letters gained in the three treatment groups that we just described. Compared in the Asian population, we had 8 letters gained in the standard aflibercept group. Seven letters gained in the Q12 group and 4 letters gained in the Q16 group.

The African-American group really could not be evaluated because the sample size was so small, less than 15 patients in the Q8 and the 8 mg Q16 groups. All right, now if we look at ethnicity, Hispanic or Latino versus non-Hispanic or Latino. So, in terms of vision gained, 8 letters, 10 letters and 6 letters, respectively, in the three different groups. Non-Hispanic Latinos, 8.4 letters, 8.6 letters, and 7.8 letters. So, not a tremendous difference there in the Hispanic Latino, maybe in the Q16 group, not as many people gaining as many letters as in the non-Hispanic Latino group, but not a tremendous difference. Now let's take a look at neovascular AMD and the PULSAR study also a aflibercept 8 mg. So, patients received either 8 mg every 12 or 16 weeks, and that showed noninferior visual acuity gains compared to 2 mg every 8 weeks. In that study, a subgroup of Asian patients was analyzed at week 48 and week 96. So, if we look at the Asian subgroup, you can see gains that occurred early, you can see on the left side of the graph and then continued on throughout the study.

Now, these were all three of the different treatment groups right here, down below is where we see the comparison with the other populations. So, overall, there's a lot of data on this slide, but what I want to point you to is if we look at change from baseline, we're seeing in the Asian subgroup 7.5 letters, 9.3, 8.8 versus the overall population of 7.26 and 6. So, actually performed very well at week 48. If we jump out to week 96, once again, the Asian subgroup, 7.5 letters, 8.9, and 7.2 in those three different treatment groups. And that was the same or even better than the overall population, which gained 7, 5.5, and 5.4 letters. Any comments, Jenny, on the studies and your take-home messages?

Dr. Lim:

Yeah, I think it shows you perhaps that within the Asian subgroup there's a slight difference in the type of AMD. There are more polypoidal, there are more PEDs, and we know that some of these newer anti-VEGF or anti-placental growth factor drugs, in this case with aflibercept 8 mg, can be more effective than aflibercept 2 mg, and that'll do better. And so maybe in the other population there's a different variant of AMD that's present as well, different biomarkers that can affect that. It's not surprising that you might get a difference there. It's heartening to know, and I would like to know if the PCV was higher in this group and if it was just more sensitive to this drug. But I think it's really important because it shows that there is a biological difference in some situations based on what the pathology is.

Dr. Brown:

And it's just another example of why it's so important that we need this data. Without the data, we can't be talking about this. So, very well done. 

Now let's switch over to faricimab. So, in the ELEVATUM trial, ELEVATUM trial was to understand the use of faricimab in diabetic macular edema in underrepresented patients and look at the social health and operational barriers that might limit trial recruitment and retention in these populations. So, in the ELEVATUM trial, the goal was to achieve approximately 45% Black and African-American patients, 45% Hispanic Latino patients, and 10% Native American and Pacific Islanders patients had to have diabetes mellitus and their A1C had to be 10% or better. But up to 20% of the population was allowed to have an A1C of up to 12% to try to improve enrollment. Patients could not have had any previous treatment. So, these were all treatment naïve. You can see the visual acuity requirements, which are similar to many DME studies at 20/40 to 20/400, and the central subfield thickness had to be at least 325 µm.

This was an open-label study. So, basically it was designed to match the fixed-dosing arm of YOSEMITE and RHINE. And what was found is that faricimab was effective in all treatment groups in improving visual acuity and no new safety concerns were raised through the study. Hispanic patients overall, they had greater visual gains, better retinal drying with an overall 14 letter gain in one year. The African-American cohort gained approximately 11 letters in one year. It was also interesting that Hispanic patients tended to present with more severe disease at baseline. So, their diabetic retinopathy severity score was higher at baseline, and they had a greater average central subfield thickness compared to African-American patients, 490 µm to 467 µm. So, there were a number of things done in this trial to really try to help encourage and to keep patients going that were part of the trials.

Some of the things were having extended treatment intervals, having bilateral treatment if necessary, having later appointments, having transportation, having some assistance for childcare. If someone needed childcare assistance for 2 to 3 hours after school, they could submit receipts and get reimbursement for the childcare. So, these are some of the strategies that were used. And 87% of the patients who started the study continued and finished the study, which was much better than everyone was expecting. And the study enrolled faster than we were expecting. So, this brings us to the next question, and what are some of these strategies for personalized treatment plans to improve outcomes, particularly in these marginalized populations?

Dr. Lim:

I think, Jeremiah, you summarized beautifully there and really brought out what the effective strategies, just what you just said, having the childcare available, having the extended times, having good community engagement and so forth. And I think that really, really showed the difference in your compliance in the study. And it showed that the patients really came back for their care better than you thought, better than what would be predicted based on the known demographics of this group. And I think if we can implement that going forward, that would be really wonderful.

Dr. Brown:

Yes.

Dr. Lim:

Yes. And we are almost out of time here, and I did want to just touch upon a few things and then answer some of the audience questions that have been posed. And so we've heard about the inequities, we've heard about some potential strategies that you can do. And I'd just like to sum it up perhaps by this section called level the playing field. So, what can we do? And I think it's really important, we've heard this throughout the program today, that we have to strengthen the physician-patient relationship and it has to be patient-centric. We have to listen to our patients. Identify what's the problem. Why aren't they coming in? Why aren't they following up? We have to build trust. We've talked about that when we have drug selection and we have step care affecting that. We have to educate the patient on their disease state and the disease therapy. And we have to get buy-in. We have to do what's called shared decision-making and make the strategy work. And then when things fall apart, we have to identify what's the risk factor? What was it?

What's the root cause for this patient? And then work to modify those risk factors, if possible. For instance, patient-assistance programs, for instance, mobile injection clinics maybe in the future or in-home monitoring, so they don't have to come in. That's going to become a real possibility with home OCT and other such devices. And give them help with social work, help them get patient copay assistance. I think all that is really important. And then also we brought up today that when a patient doesn't adhere, we've heard from Dr. Khurana, you have to find out why they didn't come in. We've heard from Dr. Brown, we have to be nonjudgmental. We have to work on solutions and enlist the family, the friends, the social workers, whoever can help them to make sure the patient comes in. And then again, emphasize the importance of the continued monitoring and treatment in order to achieve our goal, which is preservation of vision. And so frequently with my patients, when they reach their goals, when their visions improve, when the disease and they're under control, and when we can begin to extend, I high-five them, and we're really celebrating.

We're celebrating their improvement in vision. We're celebrating the fact they're coming in and that they're doing well. And so by this, we're being supportive and encouraging. And I think that is really important in engaging our patients and helping them. And then as I said, in the future, maybe there'll be some solutions for easing the treatment burden. We may have the home monitoring not only the PHP, but also the home OCT, which is currently being studied to see does it give you the same outcomes? Is it going to be as effective? And then hopefully we'll have AI systems for point-of-care screening for diabetic retinopathy. We have several systems that are FDA approved, three in fact in the United States. And we just have to get our primary care people willing to do that in their clinics. Fortunately, we have longer-acting drugs, sustained-release delivery devices, newer agents that last longer. And, in the future, perhaps tyrosine kinase inhibitors and gene therapy that can also give durable therapies.

So, overall, I think we're in a good place. We are aware of what we need to do. We've got our work cut out for us to educate our patients. We know the risk factors. We can help identify them and we can mitigate those factors. 

And so I'd like now in the last few minutes here for our audience to answer this last polling question. So, which of the following strategies do you feel may be most feasible to integrate into your practice to help reduce disparities in retinal disease care? And I'll let you read through those and you can just pick your top one. And while you're voting there, I'd like to address some of these questions here. So, there was a question of, there was a talk at ASRS last year about the economic consequences of starting with bevacizumab versus other agents. Rahul or Jeremiah, do one of you want to take that?

Dr. Khurana:

Yeah, it was a really nice talk that they did that they looked at and they actually found that you would think that if you started with bevacizumab first it would be cheaper. But when they looked at the cost and if you followed the bevacizumab protocol as seen in DRCR, it actually was more expensive because there's more visits, more fails, and then more switching. Had you just started with the drug from the beginning with a treat-and-extend approach, it actually was cheaper than going with a bevacizumab approach first. And so that's unfortunately, when these step-therapy protocols come, it's often for saving money for the insurance companies and it's a cost-cutting mechanism. So, if they could see that, you know what, it actually does not save you money, hopefully that can maybe change some plans or change some minds on bringing the choice back to the physician.

Dr. Lim:

Yeah, thank you. And then there's another question here. It says, do you find when you use samples of the newer drugs that patients can maintain those gains on bevacizumab or aflibercept? So, I've used them in a handful of patients. I have not done a study on that. I've been pleasantly surprised that when I repeat, I just basically keep using the sample until I can extend the interval for my indigent uninsured patient. And this again, it's like an N of two with this situation. They've done rather well and they've maintained their vision. But again, I'm using the sample again, I'm not trying to switch them. There have been some that we've used the sample and then we've had to switch to the other drug. I don't have enough data to give you an answer on that to give you a scientific answer. Do you either of you have more data on that?

Dr. Brown:

Well, I mean, I would say anecdotal also, but I've had that situation where I've had to switch back and many times I had to shorten the interval so I may have started with the newer generation then going back to bevacizumab and I ended up having to shorten the interval.

Dr. Lim:

Great. Thank you. And it looks like our polling results are in, and 50% of all of you said that the following strategy you feel may be most feasible to integrate to reduce disparities in retinal disease is to implement earlier screening or referral protocols for high-risk patients, 50%. A quarter of you said, to enhance the patient education and counseling to improve adherence. And then the last two that tied at 13% were to collaborate with other health care providers. And the other one was to identify financial assistance programs or alternative care pathways for uninsured patients. And nobody picked improving access to clinic, use of second-generation drugs, or they didn't feel that there was no feasible way. So, it looks like everybody's pretty engaged and positive thinking that they can impact the care. And I think we certainly have shown that. I want to thank Dr. Khurana, Dr. Brown, Rahul, and Jeremiah. You guys were great. Thank you so much for sharing your expertise and your knowledge with us tonight. Thank you to the audience for sharing your evening with us.

Dr. Brown:

Thank you.

Dr. Khurana:

Thank you so much, Jenny.

Dr. Lim:

You're welcome. Take care.