Patients with proliferative diabetic retinopathy (PDR) have demonstrated variable responses to panretinal photocoagulation (PRP) and anti-VEGF. Studies suggest that the location of neovascularization (NV) may be associated with outcomes—for example, those with disc NV (NVD) may have a poorer visual prognosis than those with NV elsewhere (NVE), the investigators of the CLARITY trial say. The post-hoc analysis of the trial’s findings investigated the distribution of NV in patients with PDR, as well as the NV’s topographical response to either aflibercept or PRP. The team found that NVD is more resistant to the currently available treatments for NVE.

The randomized, single-masked, multicenter, noninferiority trial included 120 treatment-naïve patients (75 male, mean age 54.8) with PDR. Patients underwent evaluation of NVD and NVE in four retinal quadrants on color fundus photography at baseline and again at 12 and 52 weeks post-treatment. Patients were randomized to receive either intravitreal aflibercept 2mg/0.05mL at baseline, four weeks, eight weeks and as needed from 12 weeks onward or PRP, which was completed in initial fractionated sessions and on an as-needed basis when reviewed every eight weeks.

The researchers observed NVD with or without NVE in 42 eyes (35%) and NVE in 78 eyes (65%) at baseline. They noted that NVE tended to occur in the nasal quadrant (64 eyes, 53.3%). Rates of regression with treatment were higher among NVE eyes (87.3%) compared with NVD eyes (53.5%) at 52 weeks. NVD demonstrated greater resistance to either treatment, with higher rates of persistence than NVE (51.3% vs. 29%).

The researchers noted that the temporal quadrant showed the lowest regression rates for NVE. Eyes that received aflibercept had higher regression rates of NVE than eyes treated with PRP (96.2% vs. 78%), but there was no difference for NVD (64.7% vs. 46.2%).

“The topographic response with regression of NVE in all quadrants except the temporal region with intravitreal aflibercept, with fewer eyes in the PRP group exhibiting similar levels of regression, supports the view that anti-VEGF therapy represents an improved form of treatment,” the researchers wrote in their paper. “This is important because the temporal retina is the watershed zone and, therefore, is most vulnerable to ischemia.”

While the exact reason for rapid regression and the smaller likelihood of NVE recurrence with aflibercept compared with PRP can only be hypothesized, the researchers noted, “The destruction of the peripheral retinal by PRP to reduce VEGF production is indirect and takes time to become established, which is in contrast to the direct suppression of VEGF by aflibercept. Alternatively, VEGF suppression by ablation of the peripheral retina may be insufficient to cause rapid regression of NV and is in accordance with clinical practice, in which supplemental PRP is required to achieve the therapeutic threshold for continued VEGF suppression.

“A further reason could be that aflibercept blocks all VEGF isoforms and the placental growth factor, and this may explain its added benefit compared with PRP,” they continued. “This possibility was substantiated by results of Protocol T, in which the regression of NV was better achieved with aflibercept than other anti-VEGF agents. However, although aflibercept doesn’t improve capillary nonperfusion, the main gritter for NV, it may stabilize progression of capillary nonperfusion.”

Overall, the investigators stated that their study builds on the results of the CLARITY trial, which demonstrated that aflibercept is superior to PRP by way of differences in rate of regression, recurrence, persistence and new occurrence between NVD and NVE. “Neither treatment is particularly effective for NVD in the short term,” they concluded. “We also observed variation in the aforementioned outcomes that was associated with both topography and treatment regimen.”