AACS 2003.

Methods	Method of randomization: Not clearly described - “randomization schedule generated by the biostatistics department of Alcon Research”. Method of allocation concealment: Study medication and supplies for posterior juxtascleral administration were placed in sealed, opaque, sequentially numbered boxes identified by participant number only. Masking of participants and care-givers: Adequate. Masking of outcome assessment: Adequate. Losses to follow-up: At 6 months, 6.25%, 24.2%, 3% and 13.3% participants were lost to follow-up in the 3 mg, 15 mg, 30 mg Anecortave acetate and placebo groups respectively. At 1 year, however, 37.5%, 48.5%, 36.4% and 40% participants were not analysed in the 3 mg, 15 mg, 30 mg Anecortave acetate and placebo groups respectively. Intention-to-treat analysis: The 6 month analysis was by intention-to-treat with the last observation carried forward to impute missing values. However, the 12 month analysis was not. Reported sample size calculation: Assuming a standard deviation of 0.285 logMAR lines in visual acuity, the study reported a 80% power to detect a difference between treatment means of approximately 2 logMAR lines in a 2-tailed t-test with a 0.05 level of significance with 30 patients per group Unusual study design: The patients were examined by a masked ophthalmologist at 6 months who determined whether the patient was likely to benefit with further treatment. Patients judged as unlikely to benefit from further treatment were excluded from further follow-up.
Participants	# randomized in treatment arm: 3 mg (n = 32), 15 mg (n =33), and 30 mg (n=33) # randomized in control arm: n=30 Inclusion criteria: Age greater than or equal to 50 years. Exudative AMD and primary/recurrent subfoveal CNV less than or equal to 30.48 mm2 in size. Angiographic evidence that CNV occupies at least 50% of the total lesion area. The area of CNV must be composed of at least 50% classic CNV, or the area of the classic CNV must be at least 1.6 mm2. Best-corrected ETDRS visual acuity of 0.3 (20/40 Snellen equivalent) to 1.2 (20/320 Snellen equivalent) in the study eye at the eligibility visit with clinical evidence of macular degeneration in the fellow eye,with a visual acuity of 1.6 (20/800 Snellen equivalent) or better. Willing to sign informed consent and attend regular follow-up. Exclusion criteria: Pre-existing ophthalmic disease in the study eye. Myopic retinopathy or a refraction greater than -8 diopters. Intraocular surgery in study eye in the 2 months preceding enrollment. History of previous experimental treatment for AMD in the study eye other than laser photocoagulation. Scleral buckling or scleral thinning in the study eye. Use of any investigational drug or treatment within 30 days before enrollment. Medical history of a bleeding disorder. Age: Mean age was 78.1, 75.8, 75.7 and 78.3 years in 3 mg, 15 mg, 30 mg Anecortave acetate and placebo groups, respectively. Gender: 46.9%, 54.5%, 54.5% and 60% were females in 3 mg, 15 mg, 30 mg Anecortave acetate and placebo groups, respectively Equivalence of baseline characteristics: All groups were similar at baseline with respect to age, race, composition of lesions, logMAR visual acuity, sizes of choroidal neovascularization and classic component of the lesions.
Interventions	Treatment: Juxtascleral depot injection of three doses of acetonide anecortave acetate: 30 mg, 15 mg, and 3 mg. At each month 6 visit, a masked ophthalmologist decided if the patient might benefit from retreatment. Retreatment was performed by an unmasked ophthalmologist using the assigned treatment as originally randomized. Control: Placebo injection in the same fashion.
Outcomes	Primary outcome: Mean change in logMAR visual acuity from baseline. Secondary outcomes: Percentage of all participants exhibiting stabilized vision (< 3 lines lost). Percentage of participants with clinically significant worsening of vision defined as loss of at least 3 lines vision. Percentage of participants with severe vision loss (at least 6 logMAR lines lost). Percentage of participants that demonstrated reduced lesion growth (percent change from baseline).
Notes	Country: 18 centers across United States and Europe. Time period of study: April 1999 to May 2001.
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A-Adequate