OBJECTIVE Perioperative visual loss (POVL) is a rare but serious complication in surgical disciplines, especially in spine surgery. The exact pathophysiology of POVL remains unclear, but elevated intraocular pressure (IOP) is known to be part of it. As POVL is rarely described in patients undergoing intracranial or intradural surgery, the aim of this study was to investigate the course of IOP during neurosurgical procedures with opening of the dura mater and loss of CSF. METHODS In this prospective, controlled trial, 64 patients fell into one of 4 groups of 16 patients each. Group A included patients undergoing spine surgery in the prone position, group B patients had intracranial procedures in the prone position, and group C patients were treated for intracranial pathologies in a modified lateral position with the head rotated. In groups A-C, the dura was opened during surgery. Group D patients underwent spine surgeries in the prone position with an intact dura. IOP was measured continuously pre-, peri-, and postoperatively. RESULTS In all groups, IOP decreased after induction of anesthesia and increased time dependently after final positioning for the operation. The maximum IOP in group A prior to opening of the dura was 28.6 ± 6.2 mm Hg and decreased to 23.44 ± 4.9 mm Hg directly after dura opening (p < 0.0007). This effect lasted for 30 minutes (23.5 ± 5.6 mm Hg, p = 0.0028); after 60 minutes IOP slowly increased again (24.5 ± 6.3 mm Hg, p = 0.15). In group B, the last measured IOP before CSF loss was 28.1 ± 5.0 mm Hg and decreased to 23.5 ± 6.1 mm Hg (p = 0.0039) after dura opening. A significant IOP decrease in group B lasted at 30 minutes (23.6 ± 6.0 mm Hg, p = 0.0039) and 60 minutes (23.7 ± 6.0 mm Hg, p = 0.0189). In group C, only the lower eye showed a decrease in IOP up to 60 minutes after loss of CSF (opening of dura, p = 0.0007; 30 minutes, p = 0.0477; 60 minutes, p = 0.0243). In group D (control group), IOP remained stable throughout the operation after the patient was prone. CONCLUSIONS This study is the first to demonstrate that opening of the dura with loss of CSF during neurosurgical procedures results in a decrease in IOP. This might explain why POVL predominantly occurs in spinal but rarely in intracranial procedures, offers new insight to the pathophysiology of POVL, and provides the basis for further research and treatment of POVL. German Clinical Trials Register (DRKS) no.: DRKS00007590 (drks.de).