A Comparison of Management Strategies and Treatment Results for Neovascular Age-Related Macular Degeneration with a Focus on the Treat-Extend-Stop Protocol

Chaili Siyang and Adrean Sean D

Neovascular Age-Related Macular Degeneration (nAMD) is a leading cause of blindness, but the management has been revolutionized by anti-vascular endothelial growth factor (anti-VEGF) agents. Three main treatment strategies have been developed to manage nAMD. The first method is fixed interval dosing, a mainstay of randomized clinical trials (RCT), where patients receive treatments on a monthly or bimonthly interval based on the anti-VEGF agent. Shortly thereafter, the pro-re-nata (PRN) method was introduced, where patients were treated as needed based on OCT status, usually preceded by three loading doses. Another method developed was the TreatAnd-Extend regimen (TAE). Patients are treated until a dry macula is obtained and then the time interval between injections is gradually increased, usually by one to two-week intervals. A variation of the TAE protocol, termed TreatExtend-Stop (TES), extends patients to a maximum interval of 12 weeks and then stops treatments after two injections, 12 weeks apart, if a “dry macula” is maintained. These patients are then monitored in a stepwise fashion, evaluating them four weeks after treatment is stopped and then increasingly at two-week intervals until the patients are monitored quarterly. Re-initiation of the TES protocol is begun immediately if a recurrence of the choroidal neovascularization (CNV) occurs. Using this method, patients’ vision improved from 20/70 to 20/50 (p<0.001), or approximately 7.5 ETDRS letters at treatment cessation, with an average of 22 injections over three years of active treatment. True disease recurrence using the TES method in eyes that ceased therapy was observed in 29.4% of eyes, with an average of 14 months to time of recurrence. Average vision initially decreased to 20/60 during recurrence, however recovered to 20/50 after restarting TES injection protocol. Thus, the TES strategy may provide visual improvement and stability, leading to disease remission and cessation of anti-VEGF therapy without loss of vision.