Table 15:

Study Characteristics of Treat-and-Extend PRN Re-treatment Protocols for n-AMD in A-VEGF Trials

Study, Author, Year, Country	Study Design and Follow-Up	Sites, Patients, Trial Arms	Maintenance and Follow-Up	Re-treatment Criteria
Ernst et al, 2010 (76) United States	Single-arm prospective study 1 year	1 site, 22 Ps 0.5 mg of ranibizumab monthly until OCT-based CRT failed to decrease followed by treat-and-extend PRN	Maximum 3-month visit interval with OCT and Snellen VA testing	Any recurrence of fluid on OCT, such as retinal cysts, SRF, or increase in CRT > 100 μm
LAST, Fung et al, 2012 (77) United States	Single-masked prospective RCT 6 months	1 site, 9 Ps Low- (0.5-mg) vs. high- (2.0-mg) dose 3MoLD of ranibizumab followed by treat-and-extend PRN	Maximum 2-month visit interval with SD-OCT and ETDRS BCVA testing	After a 4-week post–loading dose phase, patients were reinjected if SRF or IRF were present on SD-OCT and then reviewed again in 4 weeks. If no SRF or IRF was present, patients were re-evaluated at 2-week intervals or if SRF or IRF was present patients received treatment at 6 weeks or at 8 weeks regardless of fluid present. Any recurrence of fluid required a review shortened to 4 weeks following an injection. Recurrence or increase in vascularized PED was also re-treatment indication
Oubraham et al, 2011 (78) France	2 parallel cohorts 1 year	1 site, 90 Ps Group 1: 3MoLD of ranibizumab followed by PRN re-treatment Group 2: 3MoLD of ranibizumab followed by treat-and-extend PRN	Maximum 3-month visit interval with SD-OCT, fundus photography, and EDTRS BCVA	In the PRN treatment group, subsequent injections were given with VA decreased > 5 letters, persistent subfoveal or perifoveal fluid, macular IRF on OCT, or new hemorrhage In the treat-and-extend group, patients were examined at 6 weeks post–loading dose and treated regardless of OCT. The next visit was scheduled 8 weeks later if OCT and fundus photography did not show exudative manifestations (subfoveal or perifoveal fluid or macular edema) or new macular hemorrhage—or at 4 weeks if they did. Those with no signs of active disease at week 8 were examined and re-treated 10 weeks later and, in absence of active CNV, at week 10. Follow-up for any interval was not extended beyond 12 weeks

Abbreviations: BCVA, best corrected visual acuity; CNV, choroidal neovascularization; CRT, central retinal thickness; IRF, intraretinal fluid; 3MoLD, 3-month loading dose; OCT; optical coherence tomography; P, patient; PED, pigment epithelium detachment; PRN, pro re nata (as needed); RCT, randomized controlled trial; SD-OCT, spectral domain optical coherence tomography; SRF, subretinal fluid; VA visual acuity.