Deformation of the Rodent Optic Nerve Head and Peripapillary Structures during Acute Intraocular Pressure Elevation

Abstract

PURPOSE. To evaluate the effect of acutely elevated intraocular pressure (IOP) on retinal thickness and optic nerve head (ONH) structure in the rat eye by spectral domain-optical coherence tomography (SD-OCT). METHODS. Fourteen adult male Brown-Norway rats were studied under anesthesia (ketamine/xylazine/acepromazine, 55:5:1 mg/kg intramuscularly). Both eyes were imaged by SD-OCT on two baseline occasions several weeks before and again 2 and 4 weeks after the acute IOP imaging session. During the acute IOP session, SD-OCT imaging was performed 10 minutes after IOP was manometrically set at 15 mm Hg and then at 10, 30, and 60 minutes after IOP had been elevated to 50 mm Hg (n = 8) and again 10 and 30 minutes after IOP had been lowered back to 15 mm Hg (recovery). In two additional groups, IOP elevation was set to 70 mm Hg (n = 4) or 40 mm Hg (n = 2). Acute IOP results are reported for a pattern of 49 horizontal B-scans spanning a 20° square and follow-up results for peripapillary circular B-scans. Retinal and retinal nerve fiber layer (RNFL) thicknesses were measured with custom software by manual image segmentation. Friedman and Dunn's tests were used to assess acute and longer-term effects of acute IOP elevation. RESULTS. Acute IOP elevation to 50 mm Hg caused rapid (within seconds) deformation of the ONH and peripapillary structures, including posterior displacement of the ONH surface and outward bowing of peripapillary tissue; retinal thickness decreased progressively from 10 to 30 to 60 minutes by 16%, 18%, and 20% within the area of Bruch's membrane opening (BMO; P < 0.0001) by 8%, 9%, and 11% within the central 10° (excluding the BMO; P < 0.0001) but only by 1%, 2%, and 2.4% beyond the central 10° (P < 0.0001). Recovery was progressive and nearly complete by 30 minutes. Acute IOP elevation to 40 and 70 mm Hg produced similar structural changes, but 70 mm Hg also interfered with retinal blood flow. There were no changes in peripapillary retinal or RNFL thickness (P = 0.08 and P = 0.16, respectively) measured 2 and 4 weeks after acute elevation to 50 mm Hg. CONCLUSIONS. Acute IOP elevation in the rodent eye causes rapid, reversible posterior deformation of the ONH and thinning of the peripapillary retina, with only minimal retinal thinning beyond 5° of the ONH. No permanent changes in peripapillary retinal or RNFL thickness (for up to 1 month of follow-up) were caused by 60 minutes of IOP elevation to 50 mm Hg.

Quantitative Evaluation of Factors Influencing the Repeatability of SD-OCT Thickness Measurements in the Rat

“…Thickness measurements from the manual realignment procedure were not significantly different from the combined manual þ automated realignment procedure. Similar results were published by Fortune and colleagues, 25 where they reported that manual and the Spectralis built-in automated realignment procedures yield similar thickness results. However, they did not provide details about the realignment procedures used to quantify the similarity in thickness measurements that they reported.…”

Comparison of Longitudinal In Vivo Measurements of Retinal Nerve Fiber Layer Thickness and Retinal Ganglion Cell Density after Optic Nerve Transection in Rat

“…Longitudinal measurements of peripapillary RNFLT were acquired in vivo by SD-OCT (Spectralis OCT+HRA, Heidelberg Engineering GmbH, Heidelberg, Germany) as previously described [39], [40]. After induction of general anesthesia, rats were placed on a custom-built imaging stage and kept warm with a thermostatically-controlled system (TP650, Gaymar Industries, Inc., Orchard Park, NY).…”

Retinal neurodegeneration in experimental glaucoma

“…The mechanical theory would explain the typical pie-shaped loss of RGCs and their axons that is observed in OHT models in rats and mice. Elevated IOP has been shown to cause posterior deformation of the ON head, which is more pronounced on the dorsal than in the ventral aspect, thus providing a plausible explanation for the greater susceptibility to damage in the dorsal retina (Fortune et al, 2011). In addition to this typical sectorial loss, the observation of diffuse loss could well be explained because such a constriction of axons could also affect ON fibers within the main ON head that are somehow more susceptible to pressure-induced injury.…”