To investigate retinal blood flow and oxygen saturation changes in patients diagnosed with retinopathy following plaque radiation treatment to treat choroidal melanoma. Eight patients (mean age 55.75 years, SD 12.58 years) who have developed unilateral ischaemic radiation-related retinopathy as confirmed by wide-field fluorescein angiography were recruited for the study. The fellow eye with no other ocular or retinal pathology was used as control. Both eyes underwent measurement of total retinal blood flow (TRBF) and retinal blood oxygen saturation using prototype methodologies of Doppler Spectral Domain Optical Coherence Tomography (OCT) and Hyperspectral Retinal Camera, respectively. The average TRBF in the retinopathy eye was significantly lower compared to the fellow eye (33.48 ± 12.73 μl/min versus 50.37 ± 15.26 μl/min; p = 0.013). The arteriolar oxygen saturation (SaO2 ) and venular oxygen saturation (SvO2 ) were higher in the retinopathy eye compared to the fellow eye (101.11 ± 4.26%, versus 94.45 ± 5.79%; p = 0.008) and (62.96 ± 11.05% versus 51.24 ± 6.88%, p = 0.051), respectively. The ionizing radiation seems to have an impact on the TRBF, SaO2 and SvO2 , clinically presenting similar to a rapidly developing diabetic retinopathy. The results show an altered retinal vascular physiology in patients with radiation-related retinopathy.