RADIANCE 2010.

Methods	Study design: parallel group randomised controlled trial. Unit of randomisation and analysis: the participant (1 study eye per participant). If both eyes were eligible, the eye with worse VA (assessed at visit 1) was selected for the study treatment. However, if medical reasons and local ethical requirements dictated, the investigator could select the eye with the better VA as the study eye. If needed, the fellow eye was treated as per the investigator's discretion.
Participants	Country: Australia, Canada, France, Germany, Hong Kong, Hungary, India, Italy, Japan, Korea, Lithuania, Poland, Portugal, Singapore, Slovak Republic, Spain, Switzerland, Turkey, UK (76 study centres) Setting: international, multicentre (see appendix of RADIANCE 2010) Number of participants: 277 Number of men: 68 Number of women: 209 Age (mean ± SD): 54.0 ± 14.0 years in Group 1, 56.1 ± 14.4 years in Group 2 and 57.4 ± 12.8 years in Group 3 Ethnic group: white (56.6% in Group 1, 60.3% in Group 2 and 58.2% in Group 3), Asian (42.5% in Group 1, 39.7% in Group 2 and 41.8% in Group 3) and Other (0.9% in Group 1). Inclusion criteria: diagnosis of active CNV secondary to pathological myopia confirmed by complete ocular examination in the study eye using the following criteria: presence of high myopia, > ‐6 D of spherical equivalence; anteroposterior elongation of ≥ 26 mm; presence of posterior changes compatible with pathological myopia; presence of active leakage from CNV; and presence of intraretinal or subretinal fluid or increase of central retinal thickness; presence of at least 1 of the following lesion types: subfoveal, juxtafoveal with involvement of the central macular area, extrafoveal with involvement of the central macular area, and margin of the optic disk with involvement of the central macular area; BCVA ≥ 24 and ≤ 78 letters at a starting distance of 4 m using ETDRS‐like VA chart (˜ 20/32 to 20/320 Snellen equivalent); visual loss only due to the presence of any eligible types of CNV related to pathological myopia, based on clinical ocular findings, FA and OCT data. Exclusion criteria: history of stroke; panretinal or focal/grid laser photocoagulation with involvement of the macular area in the study eye at any time; intraocular treatment with corticosteroids or intraocular surgery within 3 months prior to randomisation and treatment with anti‐VEGF or vPDT at any time in the study eye, or (d) hypersensitivity to ranibizumab or verteporfin or to drugs of similar class; presence of CNV secondary to any cause other than pathological myopia; presence of active infectious disease or intraocular inflammation, active or suspected periocular infection, confirmed intraocular pressure ≥ 25 mmHg, or iris neovascularisation in either eye at the time of enrolment; pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test (> 5 mIU/mL).
Interventions	Intervention (Group 1): ranibizumab treatment guided by VA stabilisation criteria (intravitreal ranibizumab 0.50 mg on day 1 and month 1, with further treatment determined by the VA stabilisation criterion, defined as no change in BCVA as compared with 2 preceding monthly visits) (106 participants). Comparator 1 (Group 2): ranibizumab treatment guided by disease activity criteria (intravitreal ranibizumab 0.50 mg on day 1, with further treatment based on disease activity determined by OCT and FA) (116 participants). Comparator 2 (Group 3): verteporfin PDT, with ranibizumab allowed as of month 3 (verteporfin PDT on day 1, with further treatment determined by treating investigator using ranibizumab 0.50 mg guided by disease activity criteria, verteporfin PDT, or both through month 3 to 11) (55 participants).
Outcomes	Primary outcomes: mean change from baseline to month 1 through month 3 on VA of the study eye. Secondary outcomes: mean change from baseline to month 6 in BCVA; mean change from baseline to month 1 through to month 12 in BCVA; percentage of participants with BCVA ≥ 10 and 15 letters gain or reach 84 letters at month 3; percentage of participants with BCVA ≥ 10 and 15 letters gain or reach 84 letters at month 6 and month 12; percentage of participants with BCVA ≥ 10 and 15 letters loss at month 3; percentage of participants with BCVA ≥ 10 and 15 letters loss at month 6 and month 12; change from baseline in central retinal thickness by OCT; percentage of participants with CNV leakage by FA and colour fundus photography images; number of ranibizumab injections administered and the number of verteporfin PDT treatments administered over 12 months; safety assessments (incidence of adverse events). Follow‐up: 12 months VA measurement: ETDRS chart at a distance of 4 m.
Notes	Date conducted: October 2010 to August 2012 Sources of funding: Novartis Pharma AG, Basel, Switzerland Declaration of interest: SW is on advisory boards of and has served as a consultant and a speaker for Allergan, Bayer, Heidelberg Engineering, Molecular Partners, Novartis, Roche and Optos. VJB reports grants and personal fees from Novartis during the conduct of the study and personal fees and non‐financial support from Bayer, Novartis, Allergan outside the submitted work. GL, UM, KO‐M and TS have nothing to disclose. TYW reports grants, personal fees, travel support and writing/reviewing fees from Novartis and Bayer and has served as a consultant for Abbott, Allergan, Bayer, Genentech, Novartis, Roche and Pfizer. RS reports grants from Novartis during the conduct of the study and has received grants from Bayer, Allergan, Thea and Alimera outside of the submitted work. SP and MG are employees of Novartis Pharma AG, Basel, Switzerland. Novartis Pharma AG, Switzerland, sponsored the study and was involved in the study conception and design, protocol writing, study drug provision, study co‐ordination, data collection, data analysis and data interpretation. Trial registration: NCT01217944
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A randomisation list was produced by Novartis Drug Supply Management using a validated system that automates the random assignment of treatment groups to randomisation numbers in the specified ratio. At enrolment, patients received the lowest available randomisation number that then assigned them in a 2:2:1 ratio to 1 of the 3 treatment groups."
Allocation concealment (selection bias)	Low risk	Quote: "The randomisation numbers were generated using the following procedure to ensure that treatment assignment was unbiased and concealed from patients and investigator staff. A randomisation list was produced by or under the responsibility of Novartis DSM using a validated system that automates the random assignment of treatment arms to randomisation numbers in the specified ratio. The randomisation scheme for patients was reviewed and approved by a member of the Biostatistics Quality Assurance Group." (Email communication with Novartis Pharma AG, dated 10 June 2015)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quotes: "Due to the different appearances and routes of administration between the 2 treatments, all patients received either sham injection or PDT sham in conjunction with the study treatment. The PDT sham consisted of intravenous injection of 5% dextrose solution followed by light application of PDT." "The treating investigator was unmasked and administered the randomised study medication per the protocol; however, they were not involved in any other aspects of the study and could not communicate details of the treatment."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quotes: "To ensure masking, 2 investigators were involved at each study center. All study assessments were made by the evaluating investigator, VA assessor, or other site personnel who were masked to the treatment assignment." "The images (OCT) were reviewed by a central reading center to ensure standardized evaluation." "The fundus photography and FA images were independently reviewed by the central reading center (CRC) to ensure standardized evaluation."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: 10 participants (5.7% in Group 1 and 3.4% in Group 2) discontinued from the study and the reason was recorded (see Figure 2).
Selective reporting (reporting bias)	Low risk	Comment: the outcome measures were prespecified on ClinicalTrials.gov registration.
Other bias	Low risk	Comment: no other bias identified.