The natural history of untreated CSME-CI is particularly poor. The ETDRS demonstrated that over a 3-year period, 33% of subjects with CSME-CI lose >15 letters of visual acuity on the standardized ETDRS Visual Acuity Chart (Ferris et al. 1982) compared with 23% of CSME subjects without center involvement (ETDRS Research Group 1987). Such a degree of visual acuity change is equivalent to doubling of the visual angle or greater. The ETDRS did not discriminate between subtypes of diabetes mellitus.