Identifying the Critical Factors Governing Translaminar Pressure Differential Through a Compartmental Model.

The effective management of glaucoma is hindered by an incomplete understanding of its pathologic mechanism. While important, intraocular pressure (IOP) alone is inadequate in explaining glaucoma. Non-IOP-mediated risk factors such as cerebrospinal fluid (CSF) pressure have been reported to contribute to glaucomatous optic neuropathy. Due to the difficulty associated with experimental measurement of the salient variables, such as the retrobulbar CSF pressure, porosity of the subarachnoid space (SAS), and especially those concerned with the perioptic SAS, there remains a limited understanding of the CSF behavior contributing to the translaminar pressure gradient (TLPG), hypothesized to be a critical factor in the development of glaucoma. An integrated compartmental model describing the intracranial and orbital CSF dynamics, coupled with intraocular dynamics, is developed based on first principles of fluid mechanics. A sensitivity analysis is performed to identify anatomic characteristics that significantly affect the retrobulbar subarachnoid space (RSAS) pressure and, consequently, the TLPG. Of the 28 parameters considered, the RSAS pressure is most sensitive to CSF flow resistance in the optic nerve SAS and the potential lymphatic outflow from the optic nerve SAS into the orbital space. A parametric study demonstrates that a combination of resistance in the range of 1.600 × 1012 - 1.930 × 1012 Pa s/m3 (200.0 - 241.3 mm Hg min/mL) with 5% to 10% lymphatic CSF outflow yields RSAS pressures that are consistent with the limited number of studies in the literature. The results suggest that a small percentage of lymphatic CSF outflow through the optic nerve SAS is likely. In addition, flow resistance in the orbital CSF space, hypothesized to be a function of patient-specific optic nerve SAS architecture and optic canal geometry, is a critical parameter in regulating the RSAS pressure and TLPG.