Efficacy of suprachoroidal-transretinal stimulation in a rabbit model of retinal degeneration.
ABSTRACT Purpose. To develop a middle-sized animal model of outer retinal degeneration and to evaluate the effectiveness of suprachoroidal-transretinal stimulation (STS) in eliciting cortical potentials from this model. Methods. Twelve rabbits were intravenously injected with 0.47 mg/kg verteporfin and the retinas were irradiated with a red light for 90 minutes. Fluorescein angiography and full-field and focal electroretinography (ERG) were performed at 7 and 28 days after the irradiation. Electrically evoked potentials (EEPs) were elicited by electrical stimulation, with the STS electrode implanted over the irradiated region, 1 month and 1 year after the irradiation. EEPs were also recorded from three rabbits before and after retinotomy of the normal retina surrounding the degenerated area, to eliminate the influence of stray currents. The retina beneath the site of the STS electrode was examined histologically at 1 month (group 1) and 1 year (group 2) after the irradiation. Results. An extensive area of degeneration was detected histologically, mainly in the outer retina after the irradiation. Focal ERGs were not recorded when the stimulus was confined to the irradiated area; however, EEPs were successfully elicited by STS of the same area 1 month and 1 year after the irradiation. The 360 degrees retinectomy did not significantly alter the amplitudes, the implicit times, or the thresholds of EEPs evoked by STS. Conclusions. Verteporfin with light irradiation induces degeneration predominantly in the outer retinal layers in rabbits. The elicitation of EEPs by STS from the degenerated area suggests that the STS system may be useful in patients with retinitis pigmentosa.
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ABSTRACT: PURPOSE: To characterize electrically elicited visual evoked potentials (eVEPs) in Argus II retinal implant wearers. METHODS: eVEPs were recorded in four subjects and analyzed by determining amplitude and latency of the first two positive peaks (P1 and P2). Subjects provided subjective feedback by rating the brightness and size of the phosphenes. We established eVEP input-output relationships, eVEP variability between and within subjects, the effect of stimulating different areas of the retina, and the maximal pulse rate to reliably record eVEPs. RESULTS: eVEP waveforms had low signal-to-noise ratios, requiring long recording times and substantial signal processing. Waveforms varied between subjects, but showed good reproducibility and consistent parameter dependence within subjects. P2 amplitude was overall the most robust outcome measure and proved an accurate indicator of subjective threshold. Peak latencies showed small within-subject variability, yet their correlation with stimulus level and subjective rating were more variable than that of peak amplitudes. Pulse rates of up to (2)/3 Hz resulted in reliable eVEP recordings. Perceived phosphene brightness declined over time, as reflected in P1 amplitude, but not in P2 amplitude or peak latencies. Stimulating-electrode location significantly affected P1 and P2 amplitude and latency, but not subjective percepts. CONCLUSIONS: While recording times and signal processing are more demanding than for standard VEP recordings, the eVEP has proven to be a reliable tool to verify retinal implant functionality. eVEPs correlated with various stimulus parameters and with perceptual ratings. In view of these findings, eVEPs may become an important tool in functional investigations of retinal prostheses.Investigative ophthalmology & visual science 04/2013; · 3.43 Impact Factor
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ABSTRACT: A rhodopsin P347L transgenic (Tg) rabbit, a model of retinitis pigmentosa, has been generated in our laboratory. The purpose of this study was to determine the properties of focal areas of the retina in this rabbit model during the course of retinal degeneration. To accomplish this, we recorded focal ERGs from wild-type (WT) and Tg rabbits at ages 3, 6, and 12 months. A 15° stimulus spot was used to elicit the focal ERGs from the center of the visual streak and from four surrounding areas. We found that the amplitudes of the focal cone ERG b-waves and oscillatory potentials (OPs) of the Tg rabbits in the five areas decreased progressively with increasing age and became almost non-recordable at 12 months. There were no significant regional differences in the b-waves of Tg rabbits recorded from the 5 areas. The amplitudes of the OPs were better preserved than the b-waves and the OPs/b-wave ratio was higher than that in WT rabbits at every recording area. The summed OPs amplitudes, which most likely originate from the amacrine and/or ganglion cells, recorded from the area superior to the optic disc was significantly larger than that from other areas at 3- and 6-months-old. This indicated that the inner retinal neurons were not altered equally after photoreceptor degeneration in this rabbit model.Vision research 08/2013; · 2.29 Impact Factor
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ABSTRACT: To characterize the effects of intravitreal injections of iodoacetic acid (IAA) in comparison to its systemic application as a measure to induce unilateral photoreceptor degeneration. Seven-week-old C57BL/6 J mice received either intravitreal injections of IAA or systemic treatment (intraperitoneal vs intravenous) and were observed in the following 5 weeks using ERG, OCT, and histology. Systemic treatment with IAA induced high toxic effects and a high mortality in contrast to the intravitreal injection. Intraperitoneal application had no effect on the retina. Intravenous application of 2 × 30 mg/kg BW IAA (time between injections 3.5 h) resulted in an extinction of the ERG and a thinning of the retina, in particular of the outer nuclear layer (ONL) indicating photoreceptor degeneration. Animals receiving intravitreal injections developed cataracts already at low concentrations (up to 100 % at 0.25 mg/kg BW). Higher intravitreal IAA doses led to extinguished ERGs. In histology, a thinning of the entire retina was observed that was most prominent in the inner part of the retina. In contrast to intraperitoneal administration, intravenous application of IAA led to a selective photoreceptor degeneration. After intravitreal injection, dense cataracts were already observed at concentrations lower than those needed to induce changes in the ERG. ERG results must be interpreted carefully. A thinning of all retinal layers rather than a specific outer retinal degeneration was observed upon intravitreal injection. IAA is not a useful model to induce outer retinal degeneration in mice.Albrecht von Graæes Archiv für Ophthalmologie 05/2014; · 1.93 Impact Factor