A New Hero in the VEGF Fight

The most exciting thing at this year’s American Academy of Ophthalmology’s Retina Subspecialty Day was the data on the brolucizumab (Novartis) studies presented by Pravin Dugel, MD. In my opinion, this is going to be a molecule with the most impact long-term.

The exciting thing about this molecule is that it’s showing 22 times the power of ranibizumab to block vascular endothelial growth factor (VEGF).

What that means is that the molecule is substantially smaller than aflibercept or ranibizumab. In fact, its molecular size is 26 kDa, compared to 48 kDa for ranibizumab, 115 kDa for aflibercept and 149 kDa for bevacizumab. So the massive 6.0 mg brolucizumab dose is essentially delivering 22 times more drug per dose than 0.5 mg ranibizumab and 11 fold larger dose than 2.0 mg aflibercept.   This is probably the main reason brolucizumab appears to be a stronger drying agent in macular degeneration compared to aflibercept. At the only true head-to-head 16-week visit in the HAWK and HARRIER clinical trials, that appears to be the case. As the majority of U.S. retina specialists treat with a treat and extend regimen, this will lead to longer extension intervals and less injections per year for wet AMD patients. This was a very large study that went directly against the current best drying agent on the market, aflibercept. This will translate into fewer patient visits, which is going to be really appreciated by our patients and their families. If all goes well, the drug should be approved by the end of 2019.

Through week 56, brolucizumab had a similar safety profile to aflibercept.

Some other comments on brolucizumab - if it proves to continue to be stronger at blocking VEGF than aflibercept, brolucizumab will be a tremendous agent for other diseases with high VEGF loads, like diabetic macular edema (DME) and vein occlusion. We know our current pharmacologic treatments are not always enough. This has the potential to be a fantastic DME drug.

If real-world evidence shows we really can extend treatment intervals longer with brolucizumab, that’s going to completely change how we treat our patients.

- David M.  Brown, MD

Surgical Retina Back in the Spotlight

This year’s American Academy of Ophthalmology meeting saw the “resurgence” of surgical retina equipment and techniques. I think we’ve concentrated on medical therapies for the past few years; we haven’t paid as much attention to the surgical aspects of managing retina diseases. That pendulum swung a little bit back towards techniques.

The massive breakthroughs we’ve had lately in medical retina with ranibizumab and aflibercept had more-or-less relegated the other aspects of retina to the background, so I was happy to see that pattern reverse itself this year.

Several of the highlights for me included faster, better vitrectomy cutters with the port much closer to the tip. That’s going to allow us to have better dissection with these cutters.

Also, the use of internal limiting membrane (ILM) flaps was also highlighted at this meeting. We saw ways to use ILM flaps to treat very large macular holes, optic nerve pits, and other retina diseases that have been very difficult to manage before. It looks like we've got some new tools in our tool chest to help us out.

Usually, most surgeons peel a small circle of ILM around the macular hole, which is a basement membrane layer on the surface of the retina. That works really well for the average presenting macular hole, and that’s a procedure that is 95% successful at sealing macular holes. But for very large macular holes, and holes that are more chronic or have failed previous surgery, we’ve had less success. Typically the closure rate of those is about 50%. What we saw with ILM flaps is a technique to peel a large area of ILM and place it surgically over the macular hole to provide a scaffold for the hole to seal. It’s really pretty cool, and it’s a fun surgery on top of it.

Surgical vitrectomy has advanced in the mechanical cutters invented by Machemer that cut literally 100-200 cuts per minute range. But the current high-speed cutters are more like 1500-2000 cuts per minutes. DORC, Alcon, and Bausch + Lomb are all introducing cutters that are over twice that speed and the most advanced cutters are approaching tens of thousands of cuts per second.

What that provides is the ability to cut smaller and smaller pieces of vitreous, which produces less traction on the peripheral retina, which makes it safer to trim very close to the retina. In cases of diabetic dissection, to be able to do that dissection with just the cutter instead of having traditional tedious bimanual techniques that are technically more difficult to perform.

- David M. Brown, MD