Purpose: A prospective study to evaluate the macular structural and functional effects of pars plana vitrectomy (PPV) for persistent diffuse clinically significant macular oedema (CSMO). Method: A total of 12 patients with persistent diffuse CSMO were recruited and underwent assessment including best-corrected visual acuity, fundus fluorescein angiography, optical coherence tomography (OCT) and fine matrix mapping (FMM)at baseline and over a period of a year poststandard three-port PPV. Results: The median baseline ETDRS letters score for all 12 patients was 52 (range 41-63) while at 12 months it had increased to 65 (range of 27-68), an improvement of two complete ETDRS lines (P=0.037). Similarly, there was an improvement in the perifoveal cone thresholds (P=0.02). The foveal thickening for all 12 patients ranged from a median of 183 to 751μm (normal range 126-180 μm) and the macular volume ranged from a median of 2.13 to 6.42mm3 (normal < 1.66 mm3). After surgery, both the median foveal thickness (from 334 to 280μm) and median macular volume (from 3.24 to 2.61mm3) demonstrated decreases over 12 months (P=0.01). On baseline OCT, the patients fell into two anatomically distinct groups: Group 1 (n=4) had a dome-shaped thickened macula with a partial posterior hyaloid separation and a significantly higher foveal thickness and macular volume than Group 2 (n=8)which had a diffuse low-elevation profile of the thickened macula (P=0.007). Conclusions: In this prospective study of PPV for persistent fovea-involving CSMO there was structural and functional improvement. Purpose: A prospective study to evaluate the macular structural and functional effects of pars plana vitrectomy (PPV) for persistent diffuse clinically significant macular odema (CSMO). Method: A total of 12 patients with persistent diffuse CSMO were recruited and underwent assessment including best- corrected visual acuity, fundus fluorescein angiography, optical coherence tomography (OCT) and fine matrix mapping (FMM) at baseline and over a period of a year poststandard three-port PPV. Results: The median baseline ETDRS letters score for all 12 patients was 52 (range 41-63) while at 12 months it had increased to 65 (range of 27-68), an improvement of two complete ETDRS lines (P = 0.037). Similarly, there was an improvement in the perifoveal cone thresholds (P = 0.02). The foveal thickening for all 12 patients ranged from a median of 183 to 751 μm (normal range 126-180 μm) and the macular volume ranged from a median of 2.13 to 6.42 mm3 (normal <1.66 mm3). After surgery, both the median fo On baseline OCT, the patients fell into two anatomically distinct groups: Group 1 (n = 4) and the median macular volume (from 3.24 to 2.61 mm3) had a dome-shaped thickened macula with a partial posterior hyaloid separation and a significantly higher foveal thickness and macular volume than Group 2 (n = 8) which had a diffuse low-elevation profile of the thickened macula (P = 0.007). Conclusions: In this prospective study of PPV for persistent fovea-involving CSMO there was structural and functional improvement.