The scientific community knows that vascular endothelial growth factor (VEGF) causes increased, vascular permeability, resulting in diabetic macular edema (DME) in the ischemic retina, but how to stop the VEGF drive remains the challenge.
“It makes sense, then, if we could obliterate the ischemic peripheral retina, that we could decrease the VEGF drive, and thus decrease the need for anti-VEGF injections,” said Rosa Kim, MD. Several published papers seem to suggest the benefit, “but none of these papers had a control group.”
Unfortunately, “with the information that we have, we would not–at this time–recommend targeted laser photocoagulation” as a means to reduce treatment burden in patients being treated with an anti-VEGF, said Dr. Kim, who is in private practice in Houston.
The Efficacy & Safety Trial of Intravitreal Injections Combined with PRP for CSME Secondary to Diabetes Mellitus (DAVE) study is an FDA-approved, randomized control trial with the following inclusion criteria:
Patients had to have center-involving DME, with a visual acuity between 20/32 and 20/400, and at least 50 disc areas of capillary non-perfusion. (Of note, neovascularization was not an exclusion criterion.) Patients were randomized to receive intravitreal ranibizumab 0.3 mg (Lucentis, Genentech) PRN (n = 20) or in combination with ultrawide 200° field angiography panretinal photocoagulation (PRP) (n = 20).
The monotherapy group received 4 monthly injections, was evaluated monthly, and received additional PRN injections only if the presence of DME on exam or through optical coherence tomography (OCT) confirmed. In the combination arm, patients received the same loading doses, but received targeted PRP at day 3, and possibly at month 6 and 18, if there were additional areas of ischemia on wide-angle angiography.
The primary outcome measures were the mean best-corrected visual acuity (BCVA) change from baseline and the difference in total number of intravitreal injections between the cohorts.
Baseline demographics were not different in either group. Mean age of the enrolled subjects was 55 years (ranging from age 31 to 75), the mean BCVA was 20/63 (Snellen equivalent on the ETDRS scale), and the mean central retinal thickness was 530 µm.
“There are two pertinent baseline points,” Dr. Kim said. “Patients’ mean hemoglobin A1c was 8.0 in the ranibizumab-only group and 8.8 in the combination group, which is an average test in diabetic population. These patients had significant DME, ranging from 496 µm in the combined group to 579 µm in the ranibizumab-only group.”
Dr. Kim said the investigator was initiating therapy based upon the DME, but not really determining how much non-perfusion there was. If the protocol did not specify foveal-involving DME as a criterion for re-treatment, it is possible more patients would have required injections.