PURPOSE. To assess the changes in hyperreflective foci (HF) by means of spectral-domain optical coherence tomography (SD-OCT) in patients undergoing anti-VEGF treatment for subfoveal choroidal neovascularization (CNV) secondary to angioid streaks (AS). METHODS. Fifteen eyes with diagnosis of AS-related CNV (8 males) and 15 control eyes with uncomplicated AS were consecutively recruited. Patients and controls underwent complete ophthalmologic examination and SD-OCT. Patients were subjected to a pro re nata treatment regimen, including monthly examinations and intravitreal aflibercept injection in case of fluid detection on SD-OCT. HF were measured on horizontal scans of the six-line radial SD-OCT, in the fovea and parafovea and the subdivided as retinal or choroidal. Specifically, HF were analyzed at the following time points: baseline, dry on SD-OCT, 1 month before its reactivation, and the time of CNV reactivation. RESULTS. HF numbers resulted higher in all CNV phases with respect to controls, except during inactive phase. Moreover, foveal and parafoveal HF were found significantly increased in active, prereactive, and reactive phases when compared with inactive phase (P <0.05). A similar trend was detected for choroidal HF. Interestingly, a subanalysis revealed that only foveal choroidal HF are significantly higher in a prereactive phase if compared with an inactive phase (P = 0.03). Our correlational analysis unveiled negative associations between intraretinal HF numbers and logMAR best-corrected visual acuity. CONCLUSIONS. Our findings suggest that HF represent useful markers to monitor CNV activity. Choroidal HF appear already increased in the fovea 1 month before CNV reactivation. Validation of our results might lead to earlier anti-VEGF reinjection and possibly better visual outcomes. © 2018 The Authors.