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Optic Cup Enlargement Followed by Reduced Optic Nerve Head Circulation after Optic Nerve Stimulation

¹ From the Department of Ophthalmology, Osaka Medical College, Japan; the ² Glaucoma Group, Ophthalmic Research Division, Santen Pharmaceutical Co., Ltd., Nara, Japan; and the ³ Department of Pathology, Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.

PURPOSE. To investigate changes in optic nerve head (ONH) circulation, visual evoked potentials (VEPs), and ONH cupping after stimulation of the optic nerve.

METHODS. Electrodes were fixed above the optic chiasma in rabbits under general anesthesia. Screw-type electrodes for VEP recording were fixed on the dura. ONH circulation, intraocular pressure (IOP), and blood pressure (BP) were measured after the passage of a current of 0.1 mA for 0.1 second (weak stimulation), 1 mA for 1 second (moderate), 5 mA for 10 seconds (strong), or 25 mA for 10 seconds (severe). Normalized blur (NB), indicative of tissue blood flow and velocity, was measured in the ONH after each stimulation, by using a laser speckle circulation analyzer. Changes in VEP and ocular fundus were also recorded. The ratio of cup area (CA) to disc area (DA) was measured before and 4 weeks after stimulation. After all experiments, the ONH was histologically examined.

RESULTS. Weak stimulation increased NB in ONH for 10 minutes, whereas strong or severe stimulation significantly decreased NB for a longer time, in a dose-dependent manner. BP showed no significant change, except with severe stimulation. IOP was not significantly changed. VEP amplitude was reduced 30 minutes after strong stimulation. The CA-to-DA ratio was significantly increased 4 weeks after strong stimulation. In some rabbits, disc hemorrhage occurred, followed by enlargement of disc cupping, with slight gliosis.

CONCLUSIONS. Electrical stimulation of the optic nerve changed ONH circulation and VEPs and increased disc cupping. This technique warrants further investigation as an experimental model for normal-tension glaucoma.

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