It is hard to believe that it has been 42 years since the landmark Early Treatment Diabetic Retinopathy Study (ETDRS) began with the goal of studying whether 650-mg aspirin delayed or reduced the onset or severity of diabetic retinopathy (DR). It didn’t. Most retina specialists might not remember that a large part of ETDRS was to study aspirin. The data to support the study were good — high doses in animals could reverse diabetic microangiopathy. In fact, randomized studies have since reported that doses of 900 mg slowed the progression of microaneurysms in early nonproliferative DR. So, the jury is still out on aspirin.

Thankfully, the ETDRS also evaluated the use of focal laser photocoagulation and reported a reduction in moderate visual loss in patients with clinically significant macular edema. For generations, this mantra was the gold standard until the recent anti-VEGF studies showed better visual results with anti-VEFG injections with a new definition of center-involved diabetic macular edema. The debate over when to use laser in diabetic macular edema has raged ever since. Although certainly there are situations where laser can be considered, only a few studies have examined when in a clinically meaningful way. In this issue, we explore the evidence of when to use laser photocoagulation in our diabetic macular edema patients.

Anti-VEGF injections have also been proposed as a better treatment for DR over panretinal laser photocoagulation. In contrast to DME, the best treatment for proliferative diabetic retinopathy is less clear. Although the results from clinical trials are certainly impressive, anti-VEGF agents require regular administration to achieve results similar to those seen in clinical trials. Complications still occur. In this issue, we also explore the risk and management of diabetic traction retinal detachments after anti-VEFG therapy.

Diabetic macular edema is a multifactorial disease. Although anti-VEGF therapy is very effective, there are numerous other pathways that can be blocked or activated to improve outcomes. The recent studies with faricimab, a bispecific that blocks both Angiopoietin 2 and VEGF, open the door for other drugs that activate the tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) receptor. Longer acting agents are also being explored.

We hope you enjoy our diabetes issue. Diabetic retinopathy is one of our most treated pathologies, and we have enjoyed putting this issue together as a resource for you in your daily practice. As you can see, we have come a long way since our attempts to treat DR with aspirin. RP