The VECAT study: methodology and statistical power for measurement of age-related macular features. Vitamin E, Cataract, and Age-related Maculopathy Study.

PURPOSES: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence. METHODS: The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye. RESULTS: Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation. CONCLUSIONS: The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.

The role of past intake of vitamin E in early cataract changes.

PURPOSE: We examined the association between prior supplementation of vitamin E and early cataract changes in volunteers currently enrolled in the cross-sectional VECAT study. The Vitamin E and Cataract Prevention Study (VECAT) is a clinical trial currently in progress, designed to assess the affect of vitamin E supplementation on the development and progression of cataract and age-related macular degeneration. METHODS: A history of vitamin E supplementation was ascertained through a self-administered questionnaire that was mailed to each of the 1,111 participants who were enrolled at the time in the prospective VECAT Study. RESULTS: With a 99% response rate, we found that 26% of participants reported prior supplementation of vitamin E. Only 8.8% of these participants took supplementation greater than the recommended daily intake (RDI) of 10 mg/day. Of these 26%, 57% took supplementation in the form of multivitamins as opposed to a vitamin E supplement on its own. The range of supplement intake ranged from as little as 0.1 mg/day to a maximum of 55 mg/day. A statistically significant association was found between prior supplementation and the absence of cortical opacity (OR = 0.47, 95%CI = 0.28-0.83), after adjusting for age. The levels of nuclear opacity (NO) were not statistically different between those who reported intake and those with no prior vitamin E supplementation. CONCLUSION: Prior vitamin E supplementation may protect VECAT participants from developing at least early cortical cataracts. No apparent protective role in terms of nuclear opacities and nuclear color was found regardless of the level, regularity or duration of intake.