Diabetic macular changes in the form of yellowish spots and extravasations that permeated part or the whole thickness of the retina were observed for the first time by Eduard Jaeger in 1856. This was only possible as a result of the newly developed direct ophthalmoscope that was first described in 1855. Jaeger's findings were controversial at the time and Albrecht von Graefe openly claimed that there was no proof of a causal relationship between diabetes and retinal complications. It was only in 1872 that Edward Nettleship published his seminal paper "On oedema or cystic disease of the retina" providing the first histopathological proof of "cystoid degeneration of the macula" in patients with diabetes. In 1876, Wilhelm Manz described the proliferative changes occurring in diabetic retinopathy and the importance of tractional retinal detachments and vitreous haemorrhages. In the early years of the 20th century, the debate continued whether macular changes were directly related to diabetes or whether they were due to hypertension and arteriosclerosis. It was not until the second half of the century that the work of Arthur James Ballantyne in Glasgow provided more evidence that suggested that diabetic retinopathy represents a unique vasculopathy.