Abstract
Purpose: :
Consecutive electric stimulation of the retina can lead to fading of percepts. This study investigates the effect of temporal and spatial distance of two consecutive stimulations on fading of perception in human volunteers provided with a subretinal implant.
Methods: :
An electrode array comprising of 4x4 TiN electrodes (as separate part of the light sensitive 1500 pixel Multiphotodiode-Array) was implanted subretinally in the eye of blind retinitis pigmentosa patients. As a surrogate marker for the fading of percepts, the likelihood to perceive the second of two consecutive stimuli (biphasipc, 4ms phase duration) was tested in a paired pulse experiment in 2 patients participating in that study. Two pulses near threshold were applied and the time interval (Δt, 5-405msec) as well as the distance between sites of stimulation (Δx, 0 - 792µm) was varied. Patients were asked to indicate whether the second pulse has been perceived. Logistic regression estimated the likelihood of perceiving the second pulse in dependence on the parameters time interval (Δt) and distance (Δx).
Results: :
Fading of percepts follows a nonlinear function of both Δt and Δx. The likelihood of perceiving the second pulse decreases sharply for values of Δt < 155 msec. For Δt > 155 msec no fading was observed, independent of the value of Δx (i.e. even when stimulating at the same site). Similarly, the likelihood of perceiving the second pulse decreases with closer sites of stimulation (decreasing Δx). Only for distances > 790 µm no fading was observed irrespective of Δt. Both functions are non-linear, i.e. exhibiting a secondary local minimum at ~45 msec and ~200 µm, respectively. For the combination of those values, a chance of 85% was found to perceive subsequent stimulation.
Conclusions: :
These data suggest when stimulating the retina repetitively and synchronously a delay of ~ 155 msec (~ 6.5 Hz) avoids fading largely. If asynchronous stimulation is used sites of consecutive stimulation should be separated by >790 µm to avoid any fading. The nonlinearity in the temporal dependency of fading suggests more than one mechanism responsible for this effect (e.g. desensitization of Na+-channels and inhibitory network responses). In implants that use image receivers exactly moving with the eye, natural fixational microsaccades may help to avoid fading by constantly changing the localization and increasing the distance between two consecutive stimuli in the neuroretina.
Clinical Trial: :
http://www.clinicaltrials.gov NCT00515814
Keywords: retinal degenerations: hereditary • temporal vision • retina