Quantification of Translaminar Pressure Gradient (TLPG) With Continuous Wireless Telemetry in Nonhuman Primates (NHPs)

Abstract

Purpose: Recent retrospective clinical and animal studies suggest that cerebrospinal fluid pressure (CSFP) is important in glaucoma pathogenesis. Intraocular pressure (IOP) and CSFP are the driving components of translaminar pressure (TLP = IOP - CSFP), which acts across the lamina cribrosa (LC) thickness to create the translaminar pressure gradient (TLPG = TLP/LC thickness).

Methods: We developed an implantable wireless telemetry system based on a small piezoelectric sensor with low temporal drift. IOP, measured in the anterior chamber, and intracranial pressure (ICP), measured in the brain parenchyma (as a surrogate for CSFP) were measured at 200 Hz in three male rhesus macaques (nonhuman primates, NHPs) on a 10% duty cycle (15 seconds of every 150-second period). Three-dimensional LC thickness was autosegmented as the mean thickness of the visible hyperreflective band in 48 radial spectral-domain optical coherence tomography b-scans centered on the optic nerve head.

Results: Results indicated the rank order of IOP, ICP, TLP, and TLPG for waking, sleeping, and 24-hour periods averaged across all days. NHP 150110 had the highest IOP and ICP in all periods; however, it had the lowest TLPG in all periods due to its relatively thick LC. The other two NHPs showed similar shifts in the rank order of possible glaucoma risk factors.

Conclusions: IOP is the only modifiable and readily measurable pressure-based risk factor for glaucoma. However, other potential risk factors such as ICP, TLP, and TLPG, as well as their rank-order patterns, differed compared to IOP across subjects, demonstrating that a comprehensive view of relevant risk factors is warranted.

Translational relevance: Future studies should consider including CSFP, TLP, and TLPG in addition to IOP as potential risk factors when assessing eye-specific glaucoma susceptibility.

Keywords: intracranial pressure; intraocular pressure; nonhuman primate; translaminar pressure; translaminar pressure gradient.

Figure 1.

(A) TSE Systems Stellar IOP/ICP/BP total implant system. (B) Top view of the IOP transducer and integrated scleral baseplate for affixing the transducer to the sclera under Tenon's capsule and conjunctiva. (C) Side view of the IOP transducer and integrated scleral baseplate. (D) En face photograph of the piezoelectric IOP transducer in the anterior chamber. (E) Slit-lamp photograph of the intraocular placement of the piezoelectric IOP transducer in the anterior chamber relative to the cornea and iris. Reprinted with permission from Jasien et al.

Figure 2.

(A) Oblique x-ray of an NHP with the Stellar implant (IOP and ICP transducers) and custom indwelling titanium ICP calibration port installed. The IOP transducer is in the right eye, and the ICP transducer is in the right lobe of the brain, whereas the calibration port is in the left lobe. The IOP and ICP transducers and bottom of the screw post within the calibration port are at the same height when the animal's head is in the upright position. (B) Photograph of the custom indwelling titanium ICP calibration port, showing the bolt with central screw. Note that the screw is sealed to the bolt with a sterile medical-grade silicone washer when installed. Reprinted with permission from Jasien et al.

Figure 3.

Screenshot of the pressure telemetry signals acquired during a typical ICP transducer calibration procedure wherein the NHP is moved from the prone position to a positive 45° incline (head up) to a negative 45° decline (head down) and back to prone. Arterial BP (blue), IOP in the right eye (red), ICP from Stellar Telemetry (green), and ICP from the Codman microsensor (gold) are recorded at 200 Hz during the calibration procedure. The y-axis scale is mm Hg for all signals. Reprinted with permission from Jasien et al.

Figure 4.

(a) Unprocessed SD-OCT reflectance radial b-scan through the ONH in a NHP. (b) The original scan after custom filtering and deep tissue enhancement. (c) The original scan after principal light intensity curvature computation to enhance the different layers of the tissue; the hyperreflective band defining the LC is clearly visible, and LC autosegmentation is shown in Figure 5.

Figure 5.

Lamina cribrosa thickness (µm) in the nasal–temporal b-scans through the ONH in all eight sessions, 1 month apart, for NHP 150069 at an IOP of 10 mm Hg.