Central Retinal Artery Occlusions Revisited: Thoughts on TenCRAOS

But basically, it's a phase three multi-center randomized double-blind, double-dummy trial carried out in Europe, and it looked at patients with acute non-arteritic CRAO, randomized them one-to-one to IV tenecteplase versus aspirin 300 milligrams plus placebo infusion if they presented within 4.5 hours or four and a half hours of symptom onset.

They ended up recruiting 78 patients, with the primary outcome that they were looking at was meaningful visual recovery at 30 days, defined as a best-corrected visual acuity better than or equal to, uh, logMAR of 0.7, which is about t- 20/100 or better.

Um, note that there was a minimum visual acuity of 1.0 logMAR to start, so 20/200, which was required for inclusion.

Um, and then the primary endpoint reflected an improvement on chart of at least 0.3 logMAR or equivalent to at least 15 letters on the classic EDTRS chart.

Um, what they ended up finding was that there was no significant benefit of TNK versus control, even in the patients they did a sub-analysis that, um, got in and were treated within three hours.

But there was a safety concern that they found that there was increased adverse events with the TNA- TNK group versus controls.

Not super surprising there, but one of them was an intracranial hemorrhage that led to death, so that was a pretty alarming adverse event.

So the reason why I bring this up is, uh, you- we're talking about risk of benefits, and when we think about retinal artery c- occlusions, I hate to say this, but it always feels like a lost cause when I see them, either in the ED or in clinic, 'cause that ischemia has done its damage.

And I have yet to personally see one of those miracle cases where you do an ocular massage or anything and the vision improves, even though you read about it or the AC tabs that pe- some people swear by.

And so when I saw this, I guess last time we had to hope that the TPA or TNK would help, and now this feels like not so hopeful, not seeing a clear benefit, granted these are small studies, or this is a small study, and then seeing that we might actually kill someone in the process of trying something that might be futile.

So I guess I'm gonna pause there and ask: How do you feel about it, or has that changed your optimism?

Yeah.

I, you know, I think you're right.

It's a relatively small study, um, as these studies often are because getting patients enrolled in that four-and-a-half-hour treatment window is difficult.

Um, based on the study design, the study had a, uh, an 80% power to detect a 30 percentage point risk difference, so you know, one might argue that, that that could be underpowered to detect a difference.

That being said, the outcomes were, were actually pretty similar when you look at them.

And so, you know, I, I, I would e- expect that if there was a clinically significant difference, we might have seen more of a difference in the groups, even if it wasn't statistically significant.

So that's, um, uh, not, not terribly promising.

Um, yeah, I think the other thing that I would, I would bring up, which is, uh, just sort of the way the study was designed and the way all of these studies have been designed, are extrapolating the time window for, uh, for TPA or tenecteplase for, for brain strokes to the retina.

Um, and, and I think that's another limitation that may be very difficult to address.

But, you know, if we're, if we're assuming that there could be improvement within that four-and-a-half-hour window or even within a three-hour window, it may be that the window for retinaFrom what we know from animal studies, it's actually even shorter than that.

Uh, and I think that's another limitation to these studies as well and, and to this particular study.

Yeah.

I'll echo what, um, you've commented where I, I f- I really think the big limitation here is the size and therefore power of the study.

But of course, it, it is just so hard to recruit, uh, patients in a setting like this.