We see a lot of intraocular fluid fluctuations in patients with nAMD who are receiving intravitreal injections with anti-VEGF therapy. Compared with patients with less fluid fluctuation between injections, those with the greatest fluid fluctuation have worse visual outcomes and develop greater fibrosis over time, which can lead to a more permanent loss of vision. In patients who receive fixed-dosing regimens of anti-VEGF therapy, there is typically very little fluctuation. At a population-based level, if you look at patients who receive injections less frequently, you will see greater fluctuation. Some individuals may not need an injection every 12 to 16 weeks, and others might need them more frequently, like every 4 weeks, to keep their fluid fluctuations low and stable. This is where T&E regimens come into play. 

A T&E regimen is a much more personalized treatment interval. At baseline, we do not know if an individual patient will need injections every 4 weeks or at 12- or 16-week intervals. Using T&E regimens is the safest way to determine the patient’s optimum dosing interval. This has been proven in multiple randomized and real-world clinical studies. T&E visual outcomes are very similar to the outcomes that are achieved using fixed dosing, yet the number of injections and clinic visits are lower. This is what differentiates T&E from PRN treatment. 

PRN regimens are different in that, basically, you treat the patient until they are dry, and then you do not treat them again until they leak again. But you do not know when that will occur. The patient has to return at fairly frequent intervals so that you do not miss the return of the fluid. With T&E regimens, you treat until dry, just like with PRN treatments, but you extend the treatment interval when the patient becomes dry. Say the patient is on a 4-week interval and you extend the interval maybe 2 or even 4 weeks longer. So, instead of bringing them back in 1 month, you bring them back in 6 or 8 weeks. If they are still dry at that time when they come back, that means that they can inject at this visit and then go longer than that initial interval. You can then extend the interval further, and you keep doing that until the patient begins leaking again. When that happens, you then contract the interval from, for example, 12 weeks to 10 weeks and see how that works. The goal of T&E is to find the optimal interval without overtreating or bringing them in for unnecessary visits.

Some of the opponents of PRN treatment in patients with nAMD point out that when the activity in wet AMD returns, it sometimes returns with a vengeance. The patient may experience a major subretinal hemorrhage or some other major catastrophic event. However, with T&E regimens, although the risk is there, it is greatly reduced compared with PRN treatment because the patient has an amount of anti-VEGF on board throughout the entire time, which decreases the risk of that complication.