Newsome 1988.

Methods	Parallel group RCT Method of allocation: computer‐generated table of random numbers Masking: participant ‐ yes; provider ‐ yes; outcome ‐ yes Losses to follow‐up: 23 (10 treatment, 13 placebo)
Participants	Country: USA Number of people randomised: 174 (eyes unknown) Number (%) of people followed up: 151 (87%) (258 eyes) Average age (range): unknown (42 to 89 years) Percentage women: 65% Ethnic group: unknown Baseline visual acuity: unknown Comorbidities affecting the eye: unknown Percentage current smokers: unknown Inclusion criteria: macular degeneration: clinically visible drusen with varying degrees of pigmentary change with visual acuity in 1 eye of 20/80 or better Exclusion criteria: cataract reducing vision more than 1 line other known serious eye disease; diabetes mellitus other known systemic or metabolic disease or congenital condition, which might interfere with results
Interventions	Intervention: zinc sulfate 200 mg (daily) 1 x 100 mg twice daily 90 people randomised (eyes unknown) 80 (89%) people followed up (134 eyes) Comparator: placebo 84 people randomised (eyes unknown) 71 (85%) people followed up (124 eyes) Duration: 1 to 2 years Similarity between intervention and comparator: Quote: "Identical appearing tablets containing lactose and fructose served as the placebo." Analyses were also stratified according to number of eyes per person.
Outcomes	Primary: not specified Secondary: not specified Outcomes reported in paper: Pinhole corrected visual acuity using ETDRS charts changes in visible pigment, drusen or atrophy from grading of macular photographs adverse effects of zinc including copper deficiency anaemia Follow‐up: 6, 12, 18, and 24 months Eyes: Some people had one eye enrolled in the study and some had two eyes: "To analyze the results of two eyes of the same participant, the individual eye data were averaged and that value was used."
Notes	Source of funding: Research Fund, Department of Veterinary Science, Utah State University, Logan; James L Shupe, DVM; Mary Katherine Peterson Foundation, Houston Declaration of interest: unknown Date study conducted: unknown Trial registration number: unknown
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects were randomly assigned [...] using a computer‐generated table of random numbers."
Allocation concealment (selection bias)	Low risk	Quote: "Subjects were randomly assigned to receive either zinc or placebo [...]. The individual who recorded the zinc‐treated or placebo group assignment maintained personal control over the randomization sheet and participated in no other phases of the study. This individual also handed the study tablets to subjects. All other personnel were masked to the study."
Blinding of participants and personnel (performance bias) Visual acuity	Low risk	Quote: "All other personnel were masked to the study." Quote: "Zinc sulfate was prepared as white tablets containing 100 mg of United States Pharmacopeia‐graded material. Identical‐appearing tablets containing lactose and fructose served as the placebo. All tablets were bottled in identical containers."
Blinding of participants and personnel (performance bias) Progression AMD	Low risk	Quote: "All other personnel were masked to the study." Quote: "Zinc sulfate was prepared as white tablets containing 100 mg of United States Pharmacopeia‐graded material. Identical‐appearing tablets containing lactose and fructose served as the placebo. All tablets were bottled in identical containers."
Blinding of outcome assessment (detection bias) Visual acuity	Low risk	Quote: "All visual acuities were determined by one of two masked observers throughout the study"
Blinding of outcome assessment (detection bias) Progression AMD	Low risk	Quote: "Two independent observers masked as to patient identity,..."
Incomplete outcome data (attrition bias) All outcomes	Low risk	"A total of 90 subjects [...] were randomised to zinc and 84 subjects [...] to placebo. [......]. A total of ten subjects were lost to follow‐up from the zinc‐treated group and 13 subjects from the placebo group. [...] This figure represents dropout rates of 11.1% and 15.4% from the zinc‐treated and placebo groups, respectively." Reasons for loss to follow‐up zinc/placebo Stopped taking pills 5/6 Started taking zinc 1/2 Gastrointestinal symptoms 1/0 Died 2/1 Poor compliance 0/1 Developed diabetes mellitus 0/1 Unavailable 1/2
Selective reporting (reporting bias)	High risk	"Other ocular functions assessed included ocular vision and photostress recover tests (These observations are being analysed and will be reported later)"