Contrast sensitivity with a subretinal prosthesis and implications

Purpose: To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic 12 subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual 13 information. Methods: We measure ex-vivo the full-field contrast sensitivity of healthy rat retina stimulated with 15 white light, and the contrast sensitivity of degenerate rat retina stimulated with a subretinal 16 prosthesis at frequencies exceeding flicker fusion (>20Hz). Effects of eye movements on retinal 17 ganglion cell (RGC) activity are simulated using a linear-nonlinear model of the retina. Results: RGCs adapt to high frequency stimulation of constant intensity, and respond transiently to 19 changes in illumination of the implant, exhibiting responses to ONsets , OFFsets , and both ON-and 20 OFFsets of light. The percentage of cells with an OFF response decreases with progression of the 21 degeneration, indicating that OFF responses are likely mediated by photoreceptors. Prosthetic vision 22 exhibits reduced contrast sensitivity and dynamic range, with 65% contrast changes required to 23 elicit responses, as compared to the 3% (OFF) to 7% (ON) changes with visible light. The maximum 24 number of action potentials elicited with prosthetic stimulation is at most half of its natural 25 counterpart for the ON pathway. Our model predicts that for most visual scenes, contrast sensitivity 26 of prosthetic vision is insufficient for triggering RGC activity by fixational eye movements. Conclusions: Contrast sensitivity of prosthetic vision is 10 times lower than normal, and dynamic 28 range is two times below natural. Low contrast sensitivity and lack of OFF responses hamper 29 delivery of visual information via a subretinal prosthesis. 30 Financial disclosure: D.P.'s patents related to retinal prostheses are owned by Stanford University 31 and licensed to Pixium Vision. D.P. is a consultant for Pixium Vision.