Diabetic macular edema (DME) is a complex condition attributed to loss of pericytes, alterations in blood flow and perfusion, ischemia, release of vascular endothelial growth factor and many other cytokines, and inflammation. There are two prominent ways to treat DME with intravitreal injections, anti- vascular endothelial growth factor (VEGF) agents and corticosteroids. Anti-VEGF agents obviously block VEGF, but corticosteroids have many effects including decreasing the production of VEGF and numerous other factors as well as decreasing inflammation. In a comparison with laser therapy, the Diabetic Retinopathy Clinical Research Network (DRCR.net) found anti-VEGF performed better, while intravitreal triamcinolone did somewhat worse. The response to triamcinolone was robust, however.
Intravitreal injection of sustained-release, biodegradable dexamethasone implants (Ozurdex, Allergan) has been reported in many smaller studies to reduce DME, even in eyes with persistent edema following intravitreal injections of anti-VEGF agents. The dexamethasone studies showed high variability in design and outcome. Consequently, some treating physicians were enthusiastic about using dexamethasone implants and others weren’t. Of course, there were numerous continuing medical education supplements giving greater of lesser amounts of discussion on this subject. A cottage industry of speakers gave talks about the benefits of dexamethasone implants in DME. Others championed anti-VEGF agents, and a minority both treatments together. There wasn’t much real data about the combination, or even the ability of dexamethasone implants to improve the course of people with DME who seemed to have a less than ideal response.
Fortunately, the DRCR.net conducted a germane study that addressed these issues. Patients who had an incomplete response to anti-VEGF agents were given a 12-week run-in period of ranibizumab, and then those with edema were randomized to implants plus ranibizumab versus sham plus ranibizumab. The primary outcome was mean change in visual acuity letter score at 24 weeks.
The results were very interesting. There was no difference in mean visual acuity in the two groups. Addition of dexamethasone implants did not have a visual acuity benefit in patients who had persistent macular edema following anti-VEGF therapy. The patients treated with the addition of dexamethasone had greater reduction of central macular thickness. From past studies we know the correlation to change in central macular thickness is poorly correlated to change in visual acuity.
There are several possible explanations for these findings. It is intuitive to think blocking or inhibiting many potential bad actors is better than just affecting one. So intuitively corticosteroids would seem to be a desirable agent by itself or with anti-VEGF agents.
- Richard Spaide, MD