a Pen1-XBir3 eye-drops reduce number of hyperreflective foci (HRF) (red arrowheads) and improve DRIL (yellow dashes) 24 h post-RVO (white asterisks (*) = vein occlusions). Pen1 (n = 12), Pen1-XBir3 (n = 11), RVO + Pen1 (n = 21), RVO + Pen1-XBir3 (n = 27). b Quantification of HRF in uninjured controls (n = 6), sham laser (n = 14), and RVO + Pen1 treated eyes (n = 15, 21, 13, 16) at 4 h, 24 h, 48 h, and 8 days. One-way ANOVA with Fisher’s LSD; mean ± SEM. c Quantification of HRF in uninjured and 24 h post-RVO eyes treated with Pen1 or Pen1-XBir3 (Pen1 (n = 12), Pen1-XBir3 (n = 11), RVO + Pen1 (n = 21), RVO + Pen1-XBir3 (n = 27)), one-way ANOVA with Fisher’s LSD; mean ± SEM. d Retinal cross-section immunostained for CD45 (green), isolectin (red), and DAPI (white) (scale bar = 25 μm); Pen1-mutXBir3 (n = 7) at 24 h post-RVO. Inset depicts a leukocyte in the INL expressing CD45 and isolectin. e Quantification of HRF in OCTs from RVO + Pen1-mutXBir3 (n = 7) and RVO + Pen1-XBir3 (n = 6) at 24 h post-RVO. f Correlation between CD45+ leukocyte counts from D and HRF counts from E (linear regression). g Representative ERG traces 7 days post-RVO show reduced b wave amplitude in Pen1-treated eyes, rescued by treatment with Pen1-XBir3. h ERG b wave amplitude 7 days post-RVO is correlated to the fraction of veins occluded 48 h post-RVO, and with DRIL (linear regression, n = 14). i Quantification of DRIL in RVO-induced eyes treated with Pen1 (n = 11, 20, 13, 16) or Pen1-XBir3 (n = 12, 26, 16, 16) at 4 h, 24 h, 48 h, and 8 days. Two-tailed Welch’s t test; mean ± SEM. j Quantification of b wave amplitude in uninjured control (n = 16) and 7 days post-RVO in Pen1 (n = 16) and Pen1-XBir3 (n = 14) treated eyes; One-way ANOVA with Fisher’s LSD; mean ± SEM. Source data are provided as a Source Data file.