Introduction Ocular fluid dynamics are known to improve during hemodialysis, and the improvement of uremia after dialysis may lead to osmotic pressure changes in the retina, which eventually affect retinal edema. Recent studies using optical coherence tomography (OCT) to assess the effect of hemodialysis on macular thickness have shown variable results with a majority of them finding a decrease in retinal thickness. Paradoxical neurosensory retinal detachment (NSD) may be defined as the accumulation of subretinal fluid under the macula in patients who are on continuous HD. The purpose of the study was to find out the incidence of paradoxical neurosensory detachment in diabetic eyes undergoing hemodialysis (HD) and its management. Methods This was a cross-sectional, prospective study involving end-stage renal disease (ESRD) patients secondary to diabetes. This study evaluated the changes in macular thickness in diabetic retinopathy patients with and without diabetic macular edema (DME) by spectral-domain optical coherence tomography (SD-OCT) 60 minutes before and after HD for ESRD. Results Sixty-three eyes (36 patients) were included, with a mean age of 58.2±9.8 years. Seven eyes had paradoxical NSD at presentation with an incidence of 11.11%. Eyes with DME (Group A) showed a significant reduction in central macular thickness (CMT) by 28±2μm post HD, compared to eyes without DME (Group B) where CMT decreased by 15±2μm (p=0.003). Massive subretinal fluid accumulation (paradoxical NSD) with mean CMT 675.57±69.41μm recovered to 250.71±46.79μm at the final follow-up. Five eyes underwent an intravitreal dexamethasone implant (DEX-I, Ozurdex; Allergan, Dublin, Ireland) to achieve the resolution of SRF, whereas two eyes improved spontaneously by nine months. Conclusion Hemodialysis results in a decrease of macular thickness in diabetic eyes with or without DME. Paradoxical neurosensory detachment can develop in eyes of patients undergoing HD chronically. Intravitreal dexamethasone implant (DEX-I, Ozurdex; Allergan, Dublin, Ireland) results in early amelioration of such a complication.