Table 6:

Study Characteristics of PRN Re-treatment with Combination A-VEGF and Photodynamic Intervention Trials for n-AMD

Study, Author, Year, Country	Study Design and Follow-Up	Sites, Patients, Trial Arms	Maintenance Follow-Up	Re-treatment
DENALI, Kaiser et al, 2012 (52) United States and Canada	3-arm double-masked sham-controlled multicentre Phase III non-inferiority RCT 1 year	Various sites, 321 Ps Verteporfin half-fluence PDT + 0.5 mg 3MoLD + PRN ranibizumab vs. verteporfin standard fluence PDT + 0.5 mg 3MoLD ranibizumab + PRN vs. sham verteporfin PDT + 0.5 mg 3MoLD ranibizumab followed by monthly injections	Monthly visits included OCT, ophthalmic examination, VA assessment. FA was performed as needed	OCT-defined criteria including 1) SRF or 2) cystoid macular edema or 3) increased PED > 100 μm or 4) retinal thickness increased by 100 μm over the best prior value. Also if new hemorrhage developed or VA decreased by ≥5 letters and if FA indicated CNV leakage
Krebs et al, 2013 (53) Austria	2-arm single-masked RCT 1 year	3 sites, 51 Ps 3MoLD ranibizumab + PRN vs. combined therapy 3MoLD ranibizumab and next-day standard fluence PDT + PRN	Monthly examinations including biomicroscopy of the anterior and posterior segment, VA, OCT, IOP, and evaluation of adverse events. FA at baseline and at 12 months	Signs of lesion activity in OCT, FA, or biomicroscopy
MONT BLANC, Larsen et al, 2012 (54) 12 European countries	2-arm double-masked non-inferiority RCT 1 year	45 sites, 255 Ps Verteporfin standard fluence PDT + 0.5-mg 3MoLD ranibizumab + PRN vs. sham verteporfin PDT + 0.5-mg 3MoLD ranibizumab + PRN	Monthly visits included VA and OCT. Digital FA and colour fundus photography were performed at screening, months 3 and 12, and month between on basis of re-treatment criteria	Functional and anatomic criteria included 1) ≥ 100-μm CRT (from lowest previous) 2) presence of SRF or hemorrhage 3) BCVA decrease > 5 letters 4) or leakage on FA
Rudnisky et al, 2010 (55) Alberta Canada	Retrospective parallel cohorts 1 year	Group retinal practice, 347 Ps Group 1: 1.25 mg bevacizumab vs Group 2: same-day 1.25 mg bevacizumab and half-fluence PDT. Assignment at retinal specialist's discretion	Visits at approximately 3-month intervals including OCT	Presence of SRF or IRF on clinical exam or on OCT or if VA was reduced from VA at prior visit
Soderberg et al, 2012 (56) Sweden	2-arm double-masked sham-controlled RCT 2 year	1 site, 100 Ps ranibizumab + sham TTT + PRN ranibizumab vs. ranibizumab 1MoLD + fixed quarterly TTT and PRN ranibizumab	Monthly visits included ETDRS BCVA, slit-lamp biomicroscopy, IOP, OCT, and FA at 12 and 24 months	Re-treatment on basis of any of the following: 1) loss of ≥5 BCVA ETDRS letters 2) increase OCT CRT ≥100 μm 3) new classic CNV 4) new submacular hemorrhage 5) persistent IRF or SRF
Williams et al, 2012 (57) United States	2-arm unmasked RCT 1 year	Multicentre, 60 Ps ranibizumab 3MoLD + PRN vs. PDT and 1MoLD ranibizumab + PRN	Monitored monthly	Based on clinical discretion using ETDRS BCVA, clinical findings, and OCT

Abbreviations: BCVA, best corrected visual acuity; CNV, choroidal neovascularization; CRT, central retinal thickness; ETDRS, Early Treatment Diabetic Retinopathy Study; FA, fluorescein angiography; IOP, intraocular pressure; IRF, intraretinal fluid; 1MoLD, 1-month loading dose; 3MoLD, 3-month loading dose; OCT, optical coherence tomography; P, patient; PDT, photodynamic therapy; PED, pigment epithelium detachment; PRN, pro re nata (as needed); RCT, randomized controlled trial; SRF, subretinal fluid; TTT, transpupillary thermotherapy; VA, visual acuity.