Characteristics of participants
We enrolled 1193 participants (fig ). The groups were highly comparable with no differences in baseline characteristics except for a small excess in the number with cortical lens opacities in the vitamin E group (χ2=5.6, P=0.02, table ).
Randomisation of participants for vitamin E, cataract, and age related maculopathy (VECAT) study
Table 2 Comparison of baseline characteristics between two groups of participants. Figures are numbers (percentage) of participants unless otherwise stated
The rate of compliance with the study protocol for treatment and examinations was high and similar for both groups (tables and ). In the vitamin E group eight people were excluded from final data analysis: six developed diabetic retinopathy, one had myopic degeneration, and one had missing data. Six people were excluded from the placebo group: two developed adult vitelliform macular degeneration and four had missing data.
Table 3 Reasons for withdrawal or discontinued intervention
Table 4 Annual status of study participants
Mean serum vitamin E concentrations at baseline were 39.4 (SD 20.9) μmol/l in the vitamin E group and 35.3 (6.6) μmol/l in the placebo group. At two and four years respectively, the concentrations were 63.8 (21.6) μmol/l and 58.3 (25.6) μmol/l in the vitamin E group and 32.0 (SD 8.8) μmol/l and 31.4 (SD 8.9) μmol/l for the placebo group (at two years Student's t=6.82, P>0.001; at four years t=4.98, P>0.001).
We assessed compliance by counting left over capsules, and 78% of participants had a compliance rate of 80% or higher based on intention to treat analyses. There was no difference in compliance between the two groups (χ2=3.61, df=1, P=0.46). We measured plasma concentrations in a subgroup of participants to assess compliance with treatment allocation.
We classified adverse events according to the body system affected. No serious adverse events were reported, though 678 people reported at least one adverse event. There was no significant difference between overall number and type of adverse event between the two groups (χ2=1.82, df=7, P=0.97). A total of 174 adverse events were potentially related to the use of study capsules, 91 (15%) in the vitamin E group and 83 (14%) in the placebo grpup (χ2=0.48, df=1, P=0.49). Ophthalmic adverse events were reported by 105 (18%) in the vitamin E group and 90 (15%) in the placebo group (χ2=1.44, df=1, P=0.23).
Incidence—There was no difference in the four year incidence of early AMD in the two treatment groups over the four years (table ). This was true for each definition tested and for both grading of photographs and clinical grading. Similarly, there was no difference between the incidence of the separate features of early AMD and treatment, except for hypopigmentation. Hypopigmentation was significantly less common in those on vitamin E, although the clinical significance of this is unclear. In addition, there were no differences between the groups in the prevalence of early AMD, its component features, or late AMD at baseline or at four years by either grading of photographs or clinical grading (tables and ).
Table 5 Four year incidence* of features related to early AMD, AMD, and late AMD. Figures are numbers (percentage) of participants with feature and risk ratios (95% confidence interval)
Table 6 Prevalence of early and late AMD assessed by photograph grading at baseline and at four years. Figures are numbers (percentage) of participants
Table 7 Prevalence of early and late AMD as assessed by clinical grading at baseline and at four years. Figures are numbers (percentage) of participants
Progression—According to grading of photographs 95 of 491 (19%) in the vitamin E group showed progression compared with 90 of 506 (18%) in the placebo group (relative risk=1.09, 0.84 to 1.42). By clinical grading, we observed progression in 40 of 508 (7.9%) in the vitamin E group and 31 of 514 (6.0%) in the those placebo group (1.31, 0.83 to 2.07). We saw no difference in the rate of progression of drusen types by treatment group (hard drusen being replaced by soft drusen, intermediate soft drusen being replaced by soft distinct or indistinct drusen, or the increase in area of either soft distinct or soft indistinct drusen; data not shown).
A masked “side by side” comparison of photographs from baseline and at four years showed no significant difference between the two groups (table ). There was slightly more progression in the vitamin E group, which was only marginally significant (1.26, 1.01 to 1.57).
Table 8 Progression as determined by “side by side” comparison of baseline and four year photographs. Figures are numbers (percentage) of participants
Analysis of best corrected visual acuity and visual function data showed no differences between the groups (data not shown). Similar numbers of people lost more than nine letters (two lines) of visual acuity (59 in vitamin E group, 57 in placebo group).
Further analyses included all cases of AMD, geographic atrophy alone, and neovascular AMD alone. Subgroup analyses included current smokers, those with a family history of AMD, and those with a high ocular exposure to visible light or to ultraviolet-B radiation. In none of these analyses was there a difference between the two treatment groups. Similarly, no difference was found when we repeated the analyses and controlled for the baseline presence of cortical lens opacities.
Finally, a multiple logistic regression analysis that included potential confounders of incidence or progression showed no association between the study intervention and the incidence or progression of early AMD.