Cases From the Real World: 65-Year-Old Woman With DME and Considering Cataract Surgery

Dr. Borkar:  
I have a 65-year-old woman with diabetic macular edema and moderate NPDR who's considering cataract surgery. Hear how I've adjusted her perioperative management with the use of second-generation agents. This is CME on ReachMD. I'm Dr. Durga Borkar, and joining me today is Dr. Katherine Talcott.  
 
Dr. Talcott:  
Thanks so much for having me.  
 
Dr. Borkar:  
So for this case, this is a 65-year-old phakic woman who has moderate NPDR with DME, and she has persistent center-involving DME with monthly bevacizumab treatment for 3 injections every 4 weeks. She would really like to consider cataract surgery in the next year, is very much bothered by the subjective symptoms from her cataract. She has hypertension and type 2 diabetes, and is active, retired, able to come to appointments on her own.  
 
On presentation, she's 20/50, and you can see on her OCT that she has significant center-involving diabetic macular edema. As required by her insurance company, I gave her 3 monthly bevacizumab injections, and you can see that she's very marginally improved. She's improved from 20/50 to 20/40. Some of the subretinal fluid has resolved, but she very much still has uncontrolled diabetic macular edema. Kat, are you surprised by this result looking at that presentation OCT? 
 
Dr. Talcott:  
To be honest, I'm a little surprised she did as well as she did on these 3 injections. She has a number of things on her OCT that would make me concerned that her diabetic macular edema would be hard to treat. That includes the subretinal fluid that you mentioned. She's also got hyperreflective foci and some very large cysts that are present. So to be honest, I'm actually a little impressed that she was able to get at least resolution of the subretinal fluid and some improvement of vision after just 3 of these injections. 
 
Dr. Borkar:  
Yeah, that's a great point. When you look at this presentation OCT, it certainly says this is probably going to be a very refractory case. So now she's done the 3 bevacizumab injections, and I'm able to switch her to aflibercept 2 mg. And she does 2 of those injections every 4 weeks. And while her vision stays stable, she's still 20/40, she does see some improvement in that edema, particularly temporally. And now it's February of 2022, she really wants to proceed with cataract surgery.  
 
Kat, at this point, what would you do? Do you typically like patients to have controlled diabetic macular edema before referring them back to their cataract surgeon? And would you consider switching to another agent, potentially steroids, a second-generation anti-VEGF agent? What are your thoughts at this point? 
 
Dr. Talcott:  
Yeah, ideally we love—and certainly the cataract surgeons even maybe more than we do, really want their diabetic macular edema to be controlled before having cataract surgery. As we know with the more inflammation following cataract surgery, that can make diabetic macular edema worse. But to be honest, I think if we wait for a lot of our patients with diabetic macular edema to have resolved fluid completely, they might not ever have cataract surgery. And I would hate for these patients to not be able to undergo a procedure that would improve their vision. So to be honest, especially for a patient like this who's been getting regular injections, I'm fine with them having cataract surgery, and I'll let the cataract surgeons know that it's fine from my perspective for them to sort of go ahead. And I just tell the patients it's really important that we continue to monitor you through this and that you continue to get injections around the time of the cataract surgery.  
 
The OCT definitely looks better after getting 2 of the aflibercept, like 2 mg, but there still is persistent fluid. I think you could make the case for just continuing on aflibercept, like 2 mg every 4 weeks, but I don't think it's unreasonable to think about switching agents either. Especially with those hyperreflective foci, this patient might do well sort of with the steroid injection. But there's that risk of the pressure going up afterwards. So I think it's also very reasonable to consider a second-generation anti-VEGF agent, either sort of switching to faricimab. You could also switch to aflibercept 8 mg, but I would be a little bit concerned that after the loading dose if you would be able to get this patient to 8 mg right away, in line with the aflibercept 8-mg label. 
 
Dr. Borkar:  
Yeah, these are all great points. Regarding the cataract surgery, in this case, the cataract surgeon really wanted the edema to be better controlled. And I think part of our sort of multidisciplinary care is sometimes working with what our colleagues' preferences are. So it’s definitely thinking about how I could better control this.  
 
I do think there are situations, particularly in patients that have very significant cortical cataracts, which we see a lot in these diabetic patients, where we get to a point where even though the edema isn't controlled, I can no longer really monitor the peripheral retinopathy as well as I'd like to. And if they got proliferative diabetic retinopathy, and I needed to do PRP, for example, I don't know that I would be able to see in some of those cases. So then I really try to discuss with the cataract surgeon whether we might be able to take the cataract out sooner.  
 
And I agree with you. I think there are a lot of inflammatory markers on this OCT that suggest steroids might work. We actually discussed both options. At this point, I didn't have access to aflibercept 8 mg, so we discussed faricimab and steroids. And I think she was so bothered by the cataract at that point, subjectively more the glare with nighttime driving, that the idea that I might treat her with something that could make the cataract worse, even if it was only temporary, was not appealing to her. And so we decided to go ahead and transition over to faricimab.  
 
So in this case, would you do loading doses? Or how do you manage these patients when you transition from one agent to another? 
 
Dr. Talcott: 
For patients, it depends I think on what you're sort of treating for. If it's a patient whose fluid is well controlled, and you're switching them over to another agent to sort of get increased durability, then I won't necessarily go back to every 4 weeks if they're at like 7 to 8 weeks. I'll try and keep them at the same interval after I switch and then sort of extend them. But for a case like here, where it's really recalcitrant fluid, and I'm really hoping to get that increased drying impact, then I'll definitely try and do the injections as frequently as they did. They were on aflibercept 2 mg every 4 weeks. I would definitely keep up every 4 weeks for now until the OCT is kind of as dry as I can get it, because then that gives me a better sense of what their vision potential is. And then, once I understand that, then I might extend them out.  
 
And then here, if the patient's undergoing cataract surgery too I try and keep those interval of the injections pretty close together. Now is not the time, from my perspective, to try extending the patient out or try treating the patient PRN. So I would probably keep up the injections every 4 weeks around the time of the cataract surgery.                                                                                                                                                          
 
Dr. Borkar:   
For those just tuning in, you're listening to CME on ReachMD. I'm Dr. Durga Borkar, and here with me today is Dr. Katherine Talcott. We're discussing real-world use of second-generation retina treatments in patients with diabetic macular edema who are considering cataract surgery.  
 
Dr. Borkar:  
Yeah, great point. So in this patient, I did do the 4 loading doses every 4 weeks. And she did beautifully. And she went from 20/40 to 20/25. The center-involving diabetic macular edema is well controlled, as well as all of that temporal fluid that we saw.  
 
You can see and I think we think a lot about whether we should– how important it is to get the agent right up front. And you can see that even with the edema well controlled, there is still some ellipsoid zone disruption there. And so that always feels unfortunate to me when we get the DME controlled. And I wish I could have started with this right up front, because maybe that OCT would look even a little bit better. But I completely agree with you. I got her to this point, she was ready for cataract surgery, and we said we'll stay around every 4 weeks for now. But ultimately, after she had cataract surgery, we were able to extend her out to every 8 weeks. And this is how she looks after an additional 5 injections at progressively increased intervals and cataract surgery. She's 20/20.  
 
And so with these types of patients, now, do you continue to treat the DME on more of a treat-and-extend approach? Or do you find yourself, if the DME is well controlled, treating these patients more as needed?                                                                                                                
      
Dr. Talcott:  
To be honest, I mean, this is such a great result that you got here. I never would have guessed, looking at those initial OCTs, that she would be able to sort of get to 20/20 with such a like, beautiful, like anatomic like result. Although I am definitely more likely to do sort of PRN in diabetic macular edema, as opposed to neovascular AMD, for here it took you so long to be able to sort of get to this point by doing really regular injections that I would really start off, I think, for this patient and just really sort of extending out. I would just hate to sort of start again, have fluid recur and have to sort of deal with that again. So unless the patient really felt strongly sort of against having injections, I would really try and extend them out. And then maybe once I get to more extended intervals, like every 12 weeks, maybe in every 16 weeks, maybe then I would try PRN.                                                                                                                                                                                                  
 
The other thing that you'll have to keep a watch for as you extend, or if you consider doing sort of PRN for, is that this agent has been also suppressing. If there's been any worsening or any sort of risk of like proliferative diabetic retinopathy, so you'll just have to sort of make sure that that doesn't happen as you extend out, or if you give them a break between injections.  
 
Dr. Borkar:   
These are great points, and I too prefer a treat-and-extend approach in these situations.                                                                                                                                                                                                                                     
So to summarize, many patients are often limited by step therapy but typically can consider a switch even after just 1 injection depending on the plan. And it's important to try to control DME prior to cataract surgery and maintain shorter treatment intervals in the perioperative period. And while it's possible to treat DME on an as-needed basis, many patients and also physicians prefer a treat-and-extend approach just to limit office visits. They know they're getting a treatment at every office visit. And that may be particularly useful around cataract surgery.  
 
So now, just to go into a little bit of the data behind some of these newer agents that we have. We’ll focus on faricimab in this case, since that's what I used for this patient. When we look at the YOSEMITE and RHINE studies, these were the phase 3 registration studies looking at faricimab for diabetic macular edema, the vision gains and CST reductions that we saw with faricimab at year 1, which is when the primary endpoint was measured, they were maintained through year 2. And so on average, patients gained about 10 letters from baseline and had an approximately 200 µm CST reduction that they were able to maintain at the end of 2 years.  
 
The RHONE-X study, which is the extension study looking at this in years 3 and 4, I think is important to think about, because a lot of times we have very, what feels like short-term data in trials, and we want to know how patients do afterward. And so this was a multicenter study in patients who completed YOSEMITE or RHINE and they didn't have discontinuation of study treatment. They were followed in this years 3 and 4 to see how they did. So the aflibercept 2-mg arm in that study did cross over to receive faricimab as well. And after week 116, there was this open-label treatment extend period.  
 
And what we saw is that patients did really well in the extension study. More than 90% of patients achieved absence of DME by the end of RHONE-X, regardless of what treatment arm they started in, which is really impressive.  
 
And when we look at these treatment intervals, when we think about my case, the patient at the end of the case was at 8 weeks but potentially could extend out much further. Almost 80% of patients, regardless of what treatment arm they started in, had at least a 12-week treatment interval at the end of 4 years.                                                                                                                                                                                                        
And this was a really well-tolerated drug. The safety signals were very similar to what we saw in YOSEMITE and RHINE when we looked at years 3 and 4. 
 
So overall, when we look at RHONE-X, patient retention was high, and the BCVA and CST improvements that we see in YOSEMITE and RHINE were maintained, and with about 80% of patients having at least q12 week dosing at the end of the study.  
 
So now turning to some real-world data. I think it's always interesting. And Kat, we've talked about this in clinical trials, we're often looking at treatment-naïve patients. In my case, this was a patient that was recalcitrant on bevacizumab and needed to switch. These often are not the patients that you're seeing in trials. So it's important to look at the real-world data.  
 
And FARETINA-DME is a retrospective, real-world study that looked at just that, using data from the IRIS Registry. And we've actually just presented 2-year data at ARVO recently, just looking at how these patients do long-term and to the point that a lot of times, real-world patients are not like what we see in clinical trials. Close to 90% of the eyes in our cohort are previously treated. About 75% switched from aflibercept 2 mg.  
But I think what's really impressive here is that we see that vision does improve in treatment-naïve eyes, as we would expect, and in previously treated eyes, actually, the vision is maintained at month 24. And at first that might not sound very impressive when you compare it to that 10-letter gain in clinical trials, but in most real-world studies, we actually see vision declining over time, especially in these previously treated eyes.                                                                                                                                                                                                                                                  
And the other thing that's important is more than 50% of patients in this study had 20/40 or better vision at baseline. So a lot of these patients wouldn't even qualify for a trial because their vision was so good. We also see CST improvements through those 2 years of faricimab treatment, and all of this is happening while there's a decrease in the number of injections. So in that first 6 months, whether treatment-naïve or previously treated, you see that patients are receiving about 4 injections. But then that quickly goes down in the second half of year 1 and then into year 2, where patients are receiving initially 2 injections in months 7 through 12, close to 3 in the previously treated group, and then about 2 injections per 6-month period in that second year, which is great to see that they're able to have these outcomes with less injections over time.  
 
And what we saw in terms of safety signals is that this was very safe in the real world with the IRIS Registry data was very similar to what we see in YOSEMITE and RHINE in terms of endophthalmitis and IOI.  
 
So just some take-home messages are to consider switching to a second-generation agent early in the treatment timeline, as insurance allows. And switching to a second-generation agent may really help improve recalcitrant fluid in patients with intraretinal fluid, although multiple injections may be needed before you see that significant reduction. We strive to maintain and control DME prior to cataract surgery. It may not always be possible, but it's an important goal. And a treat-and-extend approach may be useful, both for patients and physicians, to keep that DME well controlled.  
 
That's all the time we have for today. Thanks to our audience for tuning in, and thank you, Katherine, for being here.                                                                                        
Dr. Talcott:  
Thanks so much for having me.