Ten randomised controlled trials (RCTs) were included in meta-analyses (n=1,226 patients). The sample size ranged from 40 to 450. None of the patients permanently lost vision. Methodological quality varied between trials. Concealment allocation was inadequate in most trials. The follow-up duration of RCTs ranged from one to 4.6 years.
When the trials were pooled, radioiodine therapy was associated with a significantly increased risk of developing or worsening ophthalmopathy compared with antithyroid drugs (relative risk 4.23, 95% confidence interval (CI): 2.04 to 8.77; two RCTs), and an increased risk of severe ophthalmopathy (relative risk 4.35, 95% CI: 1.28 to 14.73; two RCTs). There was no statistically significant increased risk when radioiodine was compared with thyroidectomy and radioiodine with adjunctive antithyroid drugs.
Prednisolone prophylaxis was associated with a significant effect on the prevention of worsening of eye disease in patients with pre-existing ophthalmopathy (relative risk 0.03, 95% CI: 0.00 to 0.24; two RCTs), but not in patients without pre-existing ophthalmopathy. There was no significant effect of betamethasone on the prevention of ophthalmopathy.
Statistically significant heterogeneity was only observed in the outcome of ophthalmopathy for the comparison between radioiodine with prophylactic steroids and radioiodine therapy alone (I2 =62.2%, p=0.02).