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Absolute Contraindications to Intravitreal Injection and Managing Patients With Contraindications

Expert ophthalmologists discuss absolute contraindications to intravitreal injections and how to manage patients with contraindications.

Nadia K. Waheed, MD, MPH: Are there any absolute contraindications that you have to not use intravitreal injections? Are there any patients that you absolutely would not inject?

David M. Brown, MD: Patients I wouldn’t inject?

Nadia K. Waheed, MD, MPH: Yes.

David M. Brown, MD: Not really. If I go through the risk of therapy, which is one in 7,000 endophthalmitis, vs the benefits, which other than a big disciform, I typically won’t inject unless it’s their only eye and they want to try. There are patients that are barely ambulatory, and if you can get some of the fluid off of those, they can move around a little bit better in the nursing home. I tend to give up on those if they’ve got another eye. In other words, if I’m just making the OCT [optical coherence tomography test] better, and they’re still hand-motions, it’s hard to imagine that that’s helping them. I do not typically do injections on those eyes, but give the patients the option. Some want to try, and some don’t.

Nadia K. Waheed, MD, MPH: You’ll stop for futility, it sounds like, but really no contraindications such as if someone’s on anticoagulation or something you would still do the injections. My general approach is to tell them, “You’re more likely to get a red eye, but it doesn’t really represent anything dangerous; it just doesn’t look good because you’re more likely to get hemorrhages.” But I still continue, and I would say a good percentage of my patients are on anticoagulants of some sort or the other. Is that pretty much your approach as well?

David M. Brown, MD: We never stopped. In the original trials, there never was a contraindication for even Coumadin. With the modern anticoagulants, it’s even less, the pars [plana] is an amazingly tolerated entry into the part of the eye we all work in. There are patients that have a big stroke and because they read, they’re concerned, and you just go over the risk/benefits. And with those patients, I typically go to ranibizumab because it’s cleared faster in the systemic circulation, and I guess the same would be said of the ranibizumab biosimilar. But I do not think it’s a contraindication. If you have a stroke and you have mobility issues or speech issues, it’s certainly not going to help you if you’re more visually impaired.

Nadia K. Waheed, MD, MPH: And I guess the other question is, what general approach do you take with these patients? Do you do treat PRN as needed, or do you do more of a treat and extend approach?

David M. Brown, MD: No. I’m for treat and extend; PRN never made sense. I call it progressive retinal neglect. I take Losartan for hypertension. I don’t check my blood pressure every morning waiting for it to spike; I don’t wait till I have a stroke till I take my antihypertensive. I want to keep the anatomy as good as I can. You try to get by with as little injections on every patient but treat and extend generally gets you there. The problem is, different eyes clear a drug faster. And if you’re an eye that clears the drug slowly, you’re an every 10-, 12-weeker with almost any drug. If you’re a quick clearance of drug, probably with every drug that’s out there, you’re a 4- or 5-weeker at the least. And thus, our clinic fills up with those fast-clearance patients. In my clinic, it’s typically over half that are monthly, just because of partly tertiary care—I’m getting the ones that are trouble for other doctors—but also just the way the bell curve works. You get more of those that need more frequent injections.

Nadia K. Waheed, MD, MPH: Now, for those patients who need more frequent injections, would you consider putting in kind of the port delivery system, for example, or something along those lines?

David M. Brown, MD: Unfortunately, in my opinion, the port delivery system, which would be fantastic, I did two yesterday, and it would be fantastic for those patients, but it doesn’t seem to elute enough drug to control them. The control of the drug is more like a 3-week 4-week delivery. It’s not like that initial spike. The patients that are every 8 weeks to 10 weeks I think do great on the port delivery, but they’re less amenable to do it, because why do an operation to get a shot every 4 to 6 months when you’re getting a shot every 3 months.

Nadia K. Waheed, MD, MPH: That is certainly—

David M. Brown, MD: I think the Brolucizumab—there’s a palivizumab that’s going to be put in a port, hopefully, we’ll see higher concentrations with that.

Nadia K. Waheed, MD, MPH: That’s very, very interesting, so interesting real-world experience with the port delivery system. If I have a patient whom I’m injecting, and I almost always do a treat and extend, and it’s a patient who has wet AMD [age-related macular degeneration] who has some underlying atrophy in addition, I actually don’t worry too much about the atrophy. I’m not too convinced about anti-VEGF [antivascular endothelial growth factor therapy] causing atrophy. I think it’s more as you dry out the retina, you unmask preexisting atrophy, but what has your approach been to patients who have a combination of wet AMD and some underlying drying?

David M. Brown, MD: I’ve never been convinced that data was worth anything. Color photographs are really hard to demonstrate geographic atrophy when you have fluid, but once the fluid’s gone, it’s easier to see it. That’s not a priori causation; certainly, you didn’t see it in the HARBOR clinical trial (NCT00891735) with 2 milligrams, we haven’t seen it in other studies. I think to let somebody go blind from wet AMD on the theoretical fear that it could maybe hurt their dry AMD is crazy, or not founded yet.

Nadia K. Waheed, MD, MPH: You’re an “inject according to schedule” kind of an injector for those patients.

David M. Brown, MD: You want to keep your fluid away…What can happen, though, is that they get central geographic atrophy. You can get concomitant choroidal and choriocapillaris atrophy that often makes the CNV [choroidal neovascularization] regress because there’s no feed for it. Sometimes you don’t have to inject, but it’s not a happy thing, because they can’t see from their central GA. Hopefully our upcoming geographic atrophy drugs will help those patients.

Nadia K. Waheed, MD, MPH: That sounds great.

Transcript Edited for Clarity

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