Discussion
DMO, weakness, peripheral retinal ischemia, retinal ischemia
RETINAL ISCHEMIA
We found no evidence that the addition of targeted retinal laser photocoagulation to areas of retinal ischemia reduced the treatment burden of DMO compared with intravitreal aflibercept treatment alone. At 24 months, there were no significant differences in the vision gained, nor macular anatomical improvement. The 3-year DAVE trial of 49 eyes, and the 1-year UK based trial of 40 eyes by the RDP study group, found the same outcome as that of our study using ranibizumab instead of aflibercept [We found no difference in visual gains between either of the treatment arms (+4.0 letters for combination therapy and +7.8 letters for monotherapy (The DAVE trial found greater CMT reduction in the monotherapy group at both 24 (−296 ± 238 µm, −169 ± 172 µm) and 36 months (−302 ± 246 µm, −152 ± 149 µm monotherapy and combination therapy respectively). The authors hypothesised that this was because of heavy laser given at the start and again throughout the trial. In the UK RDP 2000 laser shots were given using the PASCAL laser in one session 2 weeks after the first ranibizumab treatment without further laser treatment. They found that CMT was 316 µm and 311 µm at the end of 1 year of treatment for the monotherapy and combination therapy group (The mean (SD) number of injections required for DMO in the present study was similar for the monotherapy (11.8 injections) and combination group (10.5 injections) over two years; In summary, we found no effect in TPRP in combination with anti-VEGF therapy in reducing injection load when treating DMO, which is similar to findings from the DAVE and the UK RDP studies, although using a different VEGF inhibitor. Previous 2-year DMO trials have reported a higher number of injections per year than ours, perhaps because our patients were treated with a T&E regimen from the start, whereas other studies begin with a loading course of injections followed by either T&E or pro rata (PRN). DRCR Protocol T used a PRN protocol after a fixed 4 weekly regimen to 6 months and required 15 injections over 2-years (inter quartile range 11–17) [A significant weakness of our study is the low study completion rate of 67% (32/48 eyes). Previous DMO studies have had higher rates of retention: DAVE (85%), UK RDP trial (87%), Protocol T (88%), and BEVORDEX (77%). Protocol S had 83% follow-up rates at 2 years and 61% at 5 years [Not surprisingly, we found no difference in ocular and systemic safety outcomes for patients in each arm of this study.Using a treat-and-extend treatment regimen, following an initial loading dose is a commonly used for treatment of neovascular age-related macular degeneration [In conclusion, we found no reduction in the requirement for aflibercept injections in eyes with DMO and peripheral retinal ischemia when treated with the addition of TPRP. We also found that T&E aflibercept treatment, without a loading phase, is a safe and effective treatment for DMO, leading to fewer clinic visits and a lower treatment burden.