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December 22, 2020
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Rate of reperfusion varies after anti-VEGF injection for DME

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Varying degrees of reperfusion after anti-VEGF injection for diabetic macular edema have been observed using advanced optics and perfusion mapping software, according to a presentation at the virtual OSN New York Retina meeting.

The rates of observed reperfusion in capillaries not completely scarred down in patients with diabetic macular edema who received anti-VEGF injections are variable and may not represent a significant overall increase, Richard B. Rosen, MD, said.

Results have been mixed, Rosen told Healio/OSN, in that injections may restore some areas of nonperfusion, but overall amount may not be significant or may even add up to less overall perfusion.

“Certain kinds of vessels, such as neovascular vessels that seem to be more sensitive, may close completely and resist reopen. There are also stable vessels that don’t seem to be affected at all. Finally, there’s a group in between that aren’t irreversibly damaged and may open or may close. Overall, it’s not a definitive yes or no,” Rosen said.

Richard B. Rosen

Adaptive optics imaging

Using adaptive optics, Rosen and colleagues examined patients with diabetes or vein occlusion soon after receiving anti-VEGF injections. The researchers observed microaneurysms shrink and a “certain amount of plasticity” in vessels that appeared to be closed but actually reopened, he said. However, the specific features to predict which vessels would reopen have yet to be identified.

Rosen and colleagues next evaluated differences in OCT angiography (OCTA) over time and developed software to measure the areas of reperfusion or nonperfusion.

“It was very interesting that we found areas that closed and areas that opened within the same fundus. There seems to be a redistribution of flow, and that may account for some of the earlier reports that there were consistent improvements in anti-VEGF therapy. It’s very hard to measure a global amount of flow,” Rosen said.

Rosen and colleagues developed a reference-based perfusion density mapping technique, which subtracts perfusion density maps and shows small areas of nonperfusion and reperfusion that are otherwise difficult to identify with OCTA comparisons.

“When you’re measuring areas of flow, you have to account for multiple underlying layers of capillaries at any point in the macula. The capillary density maps we use with our Optovue look at the full depth of vascular flow and measure the volume of flow in a particular cubic millimeter of tissue. It’s an optical estimation of how much change is taking place in that particular volume in the few seconds the measurement is being taken,” Rosen said.

No significant reperfusion

Previous research gave hope that significant reperfusion was occurring through the use of anti-VEGF injections in patients with diabetic macular edema, but more granular data suggest that this may not be the case, Rosen said.

Researchers need also to consider diabetic macular ischemia vs. diabetic macular edema, he said.

“Ischemia is marked by significant areas where there is no flow. The question is, can you reopen some of those at any point? It’s early, but some of the new targets beyond VEGF may address this. That’s the hope,” he said.

The use of adaptive optics has shown possible natural remodeling and restoration of flow in capillaries occurring in patients who have improvements in their diabetic conditions. As a patient’s HbA1c levels improve, there appears to be remodeling with natural reopening of the vessels, Rosen said.

“There definitely seems to be a capacity within the tissue to produce a lot of these changes,” he said.

The progress in this field has been tremendous but is still in its infancy. As research progresses, the solution for restoration may not lie in just one therapy, but perhaps a combination of agents that target the capillary endothelium may lead to full restoration and reperfusion, Rosen said.

For more information:

Richard B. Rosen, MD, can be reached at New York Eye and Ear Infirmary of Mount Sinai, 310 E. 14 St., Suite 319SB, New York, NY 10003; email: rrosen@nyee.edu.