Table - PMC

. 2017 Jun 22;2017(6):CD007419. doi: 10.1002/14651858.CD007419.pub5

LUCIDATE 2014

Methods	Parallel group RCT One eye per person, unclear how eye selected "One eye per participant was included to avoid exposure of both eyes to the study drug. If both eyes were eligible, the eye with worse visual acuity became the study eye. Subjects were randomised with 2:1 probability to receive the intervention or standard care (ETDRS macular laser). The randomization list was created using permuted blocks of varying sizes, held by the trial statistician and concealed from the researcher who enrolled, assessed, and allocated treatment to participants." (Page 961)
Participants	Country: UK Number of people randomised: 37 (37 eyes) Average age: 66 years Sex: 36% women Inclusion criteria: adult participants with type 1 or 2 diabetes BCVA of 55‐79 ETDRS letters (Snellen equivalent, 20/30‐20/80) resulting from centre‐involving DMO , with Spectralis OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) central subfield thickness of 300 mm or more in the study eye Exclusion criteria: uncontrolled glaucoma aphakia cataract precluding fundus photography external ocular infections previous anti‐VEGF or laser treatment in the preceding 3 months in both eyes angiographic evidence of macular ischaemia defined as FAZ GLD of > 1000 mm or severe perifoveal capillary loss other causes for macular oedema, for example after cataract surgery other causes of visual loss in the study eye; other diseases that may affect the course of macular oedema in the study eye PDR, either active or treated within the previous 3 months systemic conditions that precluded trial enrolment included HbA1c > 11.0%; past medical history of chronic renal failure requiring either dialysis or kidney transplantation; BP > 170/100 mmHg; an arteriothrombotic event within 6 months before randomisation, including myocardial infarction, acute congestive heart failure or other cardiac event, and stroke or transient ischaemic attack planned surgery pregnancy or breastfeeding
Interventions	Intervention: ranibizumab (0.5 mg) n = 25 Comparator: laser photocoagulation n = 12 "Subjects were randomised with 2:1 probability to receive the intervention or standard care (ETDRS macular laser)." Page 961. "Intravitreal injections of ranibizumab (Lucentis, 0.5 mg in 0.05 mL solution for injection; Novartis Pharmaceuticals UK Ltd., Frimley, United Kingdom) at baseline, 4 weeks, and 8 weeks then every 4 weeks as required according to predefined retreatment criteria to a maximum of 12 injections. Retreatment occurred if BCVA was reduced by 5 letters or more from maximum acuity or if OCT central subfield thickness was more than 300 mm. Subjects in the laser arm received ETDRS macular laser at baseline guided by fluorescein angiography, OCT, and clinical examination. Laser retreatment occurred at 12, 24, and 36 weeks if clinically significant macular edema was still present, in accordance with standard clinical practice at the time; this was guided by the most recent fluorescein angiogram, OCT, and clinical examination results" Page 961
Outcomes	Outcomes: change in ETDRS BCVA retinal sensitivity colour vision electrophysiologic parameters macular thickness and volume change in ETDRS severity grade of diabetic retinopathy from fundus photographs Follow‐up: 48 weeks
Notes	Date study conducted: November 2010 to July 2011 Sponsor: Moorfields Eye Hospital NHS Foundation Trust Conflict of interest: "Dr Comyn receives travel support from Novartis. Dr Sivaprasad is a consult for and receives payment for lectures or speaker bureaus and travel support from Novartis, Allergan, and Bayer, and receives payment for development of educational materials from Allergan. Dr Holder is a consultant to Servier. Dr Patel receives grant support from Allergan, Heidelberg United Kingdom, and Topcon United Kingdom and is a consultant to Bayer, Novartis, and Thrombogenics. Dr Hykin is a consultant to and receives grant support from Novartis, Allergan, and Bayer. Drs Comyn, Sivaprasad, Peto, Patel, Egan, Bainbridge, and Hykin have received a proportion of their funding from the Department of Health’s National Institute for Health Research Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London, Institute of Ophthalmology. Dr Bainbridge is supported by a National Institute for Health Research Professorship. Supported by an unrestricted research grant from Novartis and the National Institute for Health Research Biomedical Research Centre based at Moorfields Eye Hospital National Health Service Foundation Trust and University College London Institute of Ophthalmology." Page 970 Trial registration: NCT01223612
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization list was created using permuted blocks of varying sizes, held by the trial statistician and concealed from the researcher who enrolled, assessed, and allocated treatment to participants." Page 96
Allocation concealment (selection bias)	Low risk	See above
Blinding of participants and personnel (performance bias) All outcomes	High risk	No sham procedure
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"The microperimetry and electrophysiologic assessors were masked to the patient treatment arm. Evaluation of OCT scans, fundus photographs and fluorescein angiograms was performed by masked Reading Centre graders. The protocol states that the visual acuity assessors were also masked to the patient treatment arm but due to a protocol deviation they had access to the source notes and were potentially unmasked."
Incomplete outcome data (attrition bias) All outcomes	Low risk	22/25 (88%) of anti‐VEGF group compared to 11/12 (92%) laser group followed up
Selective reporting (reporting bias)	Unclear risk	Unclear risk
Other bias	Low risk	No other source of bias identified
Overall risk of bias	Unclear risk	High or unclear risk of bias for nearly half the items