circle AIM: To investigate the prevalence and clinical implications of hyperreflective walls (HRW) in foveal cystoid spaces in patients with cystoid macular edema (CME) caused by retinal diseases and noninfectious uveitis (NIU). circle METHODS: This retrospective cross-sectional study included 443 eyes with CME secondary to diabetic macular edema (DME), retinal vein occlusion (RVO), retinitis pigmentosa (RP), neovascular age-related macular degeneration (nAMD), and NIU. Demographic data, HRW features, and other spectral domain optical coherence tomography (SD-OCT) biomarkers were analyzed. circle RESULTS: HRW was observed in 40.9% of DME eyes (present, n=77, 38 males, 58.30 +/- 12.04y; absent, n=111, 50 males, 55.95 +/- 10.56y), 32.5% of RVO eyes (present, n=49, 22 males, 64.53 +/- 11.90y; absent, n=102, 42 males, 60.67 +/- 11.73y), 31.4% of nAMD eyes (present, n=16, 8 males, 70.13 +/- 7.75y; absent, n=35, 13 males, 73.91 +/- 9.11y), 57.1% of RP eyes (present, n=12, 4 males, 40.50 +/- 12.06y; absent, n=9, 4 males, 44.11 +/- 14.32y), and 18.8% of uveitic macular edema (UME) eyes (present, n=6, 3 males, 30.83 +/- 16.23y; absent, n=26, 12 males, 43.46 +/- 17.58y). HRW was significantly associated with vitreoretinal abnormalities [odds ratio (OR), 2.202; 95% confidence interval (95%CI), 1.342-3.61 3; P=0.002], hyperreflective foci (OR, 3.33; 95%CI, 1.884-5. 883; P<0.001), inner retinal layer disorganization (OR, 1.816; 95%CI, 1.087-3.035; P=0.023), external limiting membrane disruptions (OR, 3.476; 95%CI, 1.839-6.574; P<0.001), and disrupted ellipsoid zone length (OR, 1.001; 95%CI, 1.000-1.002; P=0.04), and a high HRW height in the foveal cystoid spaces (OR, 1.003; 95%CI, 1.001-1.006; P=0.003). circle CONCLUSION: HRW in foveal cystoid spaces is a common OCT finding in CME and is associated with more severe retinal structural damage and worse visual acuity. HRW may be utilized as a prognostic OCT biomarker for disease severity and treatment response in patients with CME. This study suggests that early detection of HRW and optimization of treatment strategies may improve patient prognosis.