Acute Aminoglycoside Retinal Toxicity Alters the Optic Nerve Head Component (ONHC) of the Porcine Multifocal Electroretinogram (mfERG)

Abstract

Purpose: : Inadvertent intravitreal injection of aminoglycoside antibiotics can have devastating visual consequences. Gentamicin toxicity is well characterized and is known to damage both the neuroglial and vasculature compartments of the inner retina. This study was conducted to establish a large animal model of gentamicin toxicity in order to pursue potential neuroprotective strategies and to evaluate the effects of inner retinal damage on the ONHC of the porcine mfERG. The ONHC, a signal whose implicit time varies with distance to the optic disc, is thought to be generated by the retinal ganglion cell axons at the optic nerve head and is computationally derived from the mfERG.

Methods: : mfERG recordings were obtained from five 6-week old Yorkshire pigs. Premedication included atropine (0.1mg/kg IM) and rompun (2mg/kg IM). Anesthesia was maintained with propofol (12-20mg/kg/hr) and midazolam (0.1-0.2mg/kg/hr). Pupils were dilated with 1% atropine and Burian-Allen contact lens electrodes were used and grounded with a reference needle behind the ear. A specialized ONHC program was provided by EDI (San Mateo, CA) and consisted of 103 equal sized hexagons presented over a 9-minute stimulation period. A 0.1ml aliquot of 30mg/ml gentamicin was injected into the vitreous cavity of one eye of each animal, and 0.1ml buffered saline injected into the contralateral eye. Recordings were taken at baseline and 1, 24 and 72 hours after injection. Rings 2 and 3 implicit times (IT) and amplitudes were analyzed and the difference between the minimum and maximum IT calculated for each ring.

Results: : The two peaks of the ONHC were identified in all tracings and showed a characteristic shift in latency proportionate to distance from the optic nerve. Progressive, time dependent increases in implicit times, and decreases in peak amplitudes, were observed in all animal subjects at 24 and 72 hours compared to baseline recordings. In two animals, increased amplitudes and shortened latencies consistent with retinal hypersensitivity were noted at 1 hour only. The magnitude of the characteristic latency shift diminished as time progressed, eg from 3.0 to 2.3ms in ring 2.

Conclusions: : Gentamicin induces progressive inner retinal damage in a porcine model. The ONHC is a quantitative marker of inner retinal and optic nerve head damage, and we suggest, will be useful in evaluating neuroprotective strategies for both acute and chronic retinal toxicity.

Keywords: retina • drug toxicity/drug effects • electroretinography: non-clinical