AbstractThe natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p < 0.01) and the location of exudation was co-localised with soft drusen but not with pachydrusen. There was a higher rate of increase in soft drusen area compared to pachydrusen area (27.7 ± 31.9%/year versus 8.7 ± 12.4%/year respectively, p < 0.01). We found no difference in the proportion of eyes that developed exudative MNV in this study however characterisation of drusen evolution patterns revealed a strong association with exudative MNV subtype.