Purpose: Assessing changes in foveal photoreceptor microstructure (FPM) following intravitreal anti-VEGF treatment may serve as a prognostic marker in patients with macular edema (ME). Methods: Sixteen eyes belonging to newly diagnosed patients with ME were included in this prospective longitudinal study. FPM integrity was evaluated at baseline and at the end of a series of anti-VEGF injections. Results: Treatment led to a significant improvement in mean visual acuity (VA) and central macular thickness. A larger FPM defect was associated with lower VA, both before and after treatment. Patients with larger FPM defects at baseline had smaller VA improvements, and the improvement in FPM integrity was associated with VA improvement (every 100-µm FPM recovery contributed to a gain of 0.04 logMAR). Conclusions: Recovery of FPM after anti-VEGF treatment was significantly associated with a VA improvement. Direct measurement of photoreceptor integrity might provide an additional tool for the assessment of retinal function and treatment response in patients newly diagnosed with ME.