Paras Gupta

Background:

Retinal degeneration is initially associated with functional deficit and neuronal network programming that progresses to structural changes and heavy photoreceptor loss. After significant photoreceptor loss, innovative solutions such as neuroprotection, gene therapy, and cell therapy are no longer useful alone.

Objectives:
We explore visual prosthetics as an approach towards generating visual perception, the mechanism of which involves direct stimulation along the visual pathway.¹ Current prosthetics are compared against functional visual acuity.

Search Methods:

Review was conducted via pubmed from 2017 to 2023, with search terms of “visual prosthetics”, “retinal prosthetics”, and “visual BMI”.

Results:

Prosthetic strategies explored were subretinal (Alpha AMS) and epiretinal (Argus II) electrode array implants. Epiretinal implants are placed along the retinal surface stimulating ganglion cells and subretinal implants are placed amongst and stimulate the phototransduction cells. Both strategies have demonstrated safety with a few insignificant adverse events such as conjunctival erosion and skin rash and with stimulation under thresholds that would cause swelling.^2,3 Current design strategies utilize flat electrode arrays, however pillar electrodes have been explored demonstrating reduced stimulation, increased cell proximity and specificity, and increased safety.⁴

In an Alpha AMS Clinical Trial, gain of function from the subretinal implant was assessed via object recognition tasks, a self-assessment mobility questionnaire and screen-based tests including Basic Light and Motion, grating acuity, and grayscale contrast discrimination. All participants reached the secondary endpoint of improved visual function via the screen-based assessments.² In an Argus II study most recipients had improvements in functional vision such as orientation and mobility tasks, resulting in improved quality of life.³  Smaller electrodes could allow for discriminate activation of retinal ganglion cells which could induce the natural optic nerve cascade and could limit cross talk. Cortical response from 55 micrometer implants, compared to the current 70 micrometer standard achieved the goal visual acuity, a range of 20/192 to 20/220.⁴ A theoretical study with randomly generated color arrays purported less stimulation, corresponding with a smaller recruitment of pixels, could allow for color perception, and may explain why current implants result in achromatic perception.⁵  In Argus II, frequency modulated electrical stimulation of the retina was tested and 5/7 of the participants perceived chromatic colors along the blue-yellow axis with higher frequency stimulation shifting perceptions blue/purple.⁶ As electrode size is miniaturized, and more studies involving electrode shape, and stimulation frequency are conducted, prosthetic visual acuity in patients with retinal degeneration will improve.

Conclusion:

Subretinal and epiretinal implants are visual prosthetics with the potential to restore visual acuity in patients with late stage retinal degeneration to functional levels. Improvements in electrode size, shape and frequency modulation will increase prosthetic visual acuity, increase implant safety, and potentially restore color vision, which will have significant impact on activities of daily living. Future studies should explore making these implants adjustable as degeneration progresses.

Works Cited:

1.  Cehajic-Kapetanovic J, Singh MS, Zrenner E, MacLaren RE. Bioengineering strategies for Restoring Vision. Nature News. https://www.nature.com/articles/s41551-021-00836-4. Published January 31, 2022. Accessed February 5, 2023.
2. Edwards TL, Cottriall CL, Xue K, et al. Assessment of the electronic retinal implant Alpha Ams in restoring vision to blind patients with end-stage retinitis pigmentosa. Ophthalmology. 2018;125(3):432-443. doi:10.1016/j.ophtha.2017.09.019
3. Gregori NZ, Callaway NF, Hoeppner C, et al. Retinal anatomy and electrode array position in retinitis pigmentosa patients after Argus II implantation: An international study. American Journal of Ophthalmology. 2018;193:87-99. doi:10.1016/j.ajo.2018.06.012
4. Ho E, Lei X, Flores T, et al. Characteristics of prosthetic vision in rats with subretinal flat and pillar electrode arrays. Journal of Neural Engineering. 2019;16(6):066027. doi:10.1088/1741-2552/ab34b3
5. Towle VL, Pham T, McCaffrey M, Allen D, Troyk PR. Toward the development of a color visual prosthesis. Journal of Neural Engineering. 2021;18(2):023001. doi:10.1088/1741-2552/abd520
6. Yue L, Castillo J, Gonzalez AC, Neitz J, Humayun MS. Restoring color perception to the blind. Ophthalmology. 2021;128(3):453-462. doi:10.1016/j.ophtha.2020.08.019