Stur 1996.

Methods	Parallel group RCT Method of allocation: sponsor‐prepared coded bottles Masking: participant ‐ yes; provider ‐ yes; outcome ‐ yes Losses to follow‐up: 6 withdrawn due to adverse gastrointestinal effects (4 treatment, 2 control); 14 withdrawn when developed neovascularisation (9 treatment, 5 control); 14 lost to follow‐up (6 treatment, 8 control)
Participants	Country: Austria Number of people randomised: 112 (112 eyes) Number (%) of people followed up: 92 (82%) (92 eyes); 78 (70%) (78 eyes) included the analyses because eyes that developed CNV were excluded Average age (range): 71 years (50 to unknown) Percentage women: 57% Ethnic group: unknown Baseline visual acuity: average 0.075 logMAR Comorbidities affecting the eye: unknown Percentage current smokers: 21% Inclusion criteria: exudative AMD in 1 eye (defined as angiographic evidence of classic or occult choroidal neovascularisation or RPE detachment) and early ARM with visual acuity 20/40 or better in other eye (early ARM: macular drusen with no angiographic evidence of exudative lesion) Exclusion criteria: dense senile cataract any other eye disease that could produce significant and permanent loss of visual acuity during follow‐up physical status that could prevent follow‐up; history of serious systemic or metabolic disease
Interventions	Intervention: zinc sulfate 200 mg (daily) 1 tablet 56 people randomised (56 eyes) unknown number (%) people followed up but 37 (37 eyes) included in the analyses, excluding eyes that developed CNV Comparator: placebo 1 tablet people randomised (eyes unknown) unknown number (%) people followed up but 41 (41 eyes) included in the analyses, excluding eyes that developed CNV Duration: 24 months Similarity between intervention and comparator: Intervention was lemon flavoured effervescent tablet made of citric acid containing saccharine and sorbitol and placebo was as treatment, but without the zinc sulfate
Outcomes	Primary: not specified Secondary: not specified Outcomes reported in paper: Best‐corrected logMAR visual acuity measured using Bailey‐Lovie chart contrast sensitivity incidence of choroidal neovascularisation progression of disease (Wisconsin Age‐related Maculopathy Grading System) copper deficiency anaemia Follow‐up: 6, 12, 18, and 24 months Eyes: one eye per person, CNV in one eye and not in the fellow eye. The fellow eye was the "study eye."
Notes	A priori sample size estimate was 500 participants, but trial stopped early because interim analysis showed no detectable trend Funders: Astra, Linz, Austria; Austrian Foundation for the Propagation of Scientific Research Source of funding: "Supported in part by the Austrian Foundation for the Propagation of Scientific Research (Ostetreichischer Fonds zur Forderung der xuissenschaftlichen Forschung), Project 7215‐MED." and "The authors thank the staff at Astra GmbH, Linz, Austria, for providing the coded doses of zinc sulfate and placebo." Declaration of interest: "Proprietary interest category: No" Date study conducted: March 1990 to June 1992 Trial registration number: unknown
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "This was a double‐masked, randomised, placebo‐controlled study conducted at a single center. The randomization between zinc and placebo was performed in a ratio 1:1" Judgement comment: No details provided of method of sequence generation, however, since coding provided by sponsor, this is unlikely to be a source of bias.
Allocation concealment (selection bias)	Low risk	Quote: "Coded doses of zinc sulfate and placebo were prepared by the sponsor (Astra, Linz, Austria). All doses were lemon‐flavored effervescent tablets made of citric acid that provided improved gastrointestinal absorption and contained saccharine and sorbitol. Treatment group doses contained an additional 200 mg of zinc sulfate. (This preparation is identical to a zinc sulfate preparation registered in Austria and other European countries under the name Solvezink; Astra, Wedel, Germany.) Tablets were bottled in identical containers."
Blinding of participants and personnel (performance bias) Visual acuity	Low risk	Quote: "Coded doses of zinc sulfate and placebo were prepared by the sponsor (Astra, Linz, Austria). All doses were lemon‐flavored effervescent tablets made of citric acid that provided improved gastrointestinal absorption and contained saccharine and sorbitol. Treatment group doses contained an additional 200 mg of zinc sulfate. (This preparation is identical to a zinc sulfate preparation registered in Austria and other European countries under the name Solvezink; Astra, Wedel, Germany.) Tablets were bottled in identical containers."
Blinding of participants and personnel (performance bias) Progression AMD	Low risk	Quote: "Coded doses of zinc sulfate and placebo were prepared by the sponsor (Astra, Linz, Austria). All doses were lemon‐flavored effervescent tablets made of citric acid that provided improved gastrointestinal absorption and contained saccharine and sorbitol. Treatment group doses contained an additional 200 mg of zinc sulfate. (This preparation is identical to a zinc sulfate preparation registered in Austria and other European countries under the name Solvezink; Astra, Wedel, Germany.) Tablets were bottled in identical containers."
Blinding of outcome assessment (detection bias) Visual acuity	Low risk	Quote: "Coded doses of zinc sulfate and placebo were prepared by the sponsor (Astra, Linz, Austria). All doses were lemon‐flavored effervescent tablets made of citric acid that provided improved gastrointestinal absorption and contained saccharine and sorbitol. Treatment group doses contained an additional 200 mg of zinc sulfate. (This preparation is identical to a zinc sulfate preparation registered in Austria and other European countries under the name Solvezink; Astra, Wedel, Germany.) Tablets were bottled in identical containers."
Blinding of outcome assessment (detection bias) Progression AMD	Low risk	Quote: "Coded doses of zinc sulfate and placebo were prepared by the sponsor (Astra, Linz, Austria). All doses were lemon‐flavored effervescent tablets made of citric acid that provided improved gastrointestinal absorption and contained saccharine and sorbitol. Treatment group doses contained an additional 200 mg of zinc sulfate. (This preparation is identical to a zinc sulfate preparation registered in Austria and other European countries under the name Solvezink; Astra, Wedel, Germany.) Tablets were bottled in identical containers."
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "One hundred twelve patients were enrolled between March 1, 1990 and June 30, 1992. Six patients (four in the treatment group, two in the placebo group) could not tolerate the medication because of gastrointestinal side effects and had to be withdrawn from the study. Fourteen patients did not return for the scheduled follow‐up visits or decided to withdraw from the study because of personal reasons. The withdrawal of these 14 patients was not connected to any side effects of the study medication. The rest of the recruited patients (92 patients) returned for all required visits." Quote: "During the treatment period, a CNV developed in the study eye in 14 patients (nine in the treatment group, five in the placebo group). Ten of these patients underwent laser treatment and were withdrawn from the study."
Selective reporting (reporting bias)	Unclear risk	Difficult to assess with the information available