Neurostimulation for Glaucoma

Educational Objectives

The goal of this program is to improve management of glaucoma through neurostimulation. After hearing and assimilating this program, the clinician will be better able to:

1. Evaluate the efficacy of neurostimulation in enhancing neural function in glaucoma.

Summary

Glaucoma: treatments targeted toward preserving neural structure and function in glaucoma are an unmet need; neuroplasticity — defined as the brain’s ability to reorganize and rewire its synaptic connections; residual vision activation theory proposed by Sabel et al (2011) postulates that areas of damaged retina or brain tissue contains cells that are injured but not dead yet; residual cells can be engaged with rehabilitative techniques to restore visual function; in glaucoma, modifying the retinal ganglion cells (RGCs) within the window of time between functional loss and structural damage may enhance neural function; electrical stimulation therapy (EST) can modify RGC dysfunction and employs a low-level stimulus to activate injured nerves

Repetitive transorbital alternating current stimulation (rtACS): a method of applying EST to the eye; rtACS uses periorbital electrodes to apply the stimulus with the eyes closed; the strength and frequency of the current are individualized to the patient (a little above the phosphene threshold); rtACS therapy consists of 10 sessions (30-60 min each) over 2 wk; proposed mechanisms — rtACS activates neurons in the visual pathway in a synchronized manner, and the increased traffic enhances neuronal connectivity and amplifies electrical signals from injured RGCs; other mechanisms include improved blood flow and cell metabolism, and modulation of gene expression; however, rtACS cannot regenerate cells nor restore dead nerves (no complete reversal of visual field [VF] loss)

Availability of rtACS therapy: offered using a proprietary device in Europe; a commercial device (eg, Eyetronic) is also available

Clinical trials: in a large-scale study, Fedorov et al (2011) found VF improvement in 40% to 50% of eyes after rtACS in patients with optic nerve damage; randomized controlled trial (RCT) — Gall et al (2016) compared rtACS and sham therapy in patients with glaucoma or anterior ischemic optic neuropathy; in the rtACS group, suprathreshold perimetry showed a 5% increase in detection accuracy, and standard automated perimetry showed a 10% improvement in VF mean deviation; rtACS was well-tolerated, with no serious adverse events (AEs); transient AEs included vertigo, dizziness, and headache

rtACS in progressive glaucoma: in a retrospective study, Erb et al (2022) analyzed patients with progressive vision loss despite intraocular pressure-lowering therapy; ≈60% of patients had severe VF loss at baseline; after rtACS, 63% of eyes improved or had no change in mean deviation, with some patients registering a 4- to 8-dB improvement (super responders)

Vision-related quality of life (VRQOL): in an RCT, Ramos Cadena et al (2024) randomized patients with moderate-to-advanced glaucoma to rtACS or sham; at 1 mo, VRQOL improved in the rtACS group compared with sham; no improvement in visual acuity, contrast sensitivity, or VF analyses; a trend toward improvement for 24-2 parameters but an opposite trend for 10-2 parameters were observed

Take-home points: rtACS has the potential to stabilize or improve visual function; limitations of the above-mentioned literature include small sample size, heterogenous population, high variability in outcome measures, and possible placebo effect; benefits have not been replicated outside Europe; further trials are needed

Readings

Erb C, Eckert S, Gindorf P, et al. Electrical neurostimulation in glaucoma with progressive vision loss. Bioelectron Med. 2022;8(1):6. doi:10.1186/s42234-022-00089-9; Fedorov A, Jobke S, Bersnev V, et al. Restoration of vision after optic nerve lesions with noninvasive transorbital alternating current stimulation: a clinical observational study. Brain Stimul. 2011;4(4):189-201. doi:10.1016/j.brs.2011.07.007; Gall C, Schmidt S, Schittkowski MP, et al. Alternating current stimulation for vision restoration after optic nerve damage: a randomized clinical trial. PLoS One. 2016;11(6):e0156134. doi:10.1371/journal.pone.0156134; Ramos Cadena M de LA, Sohn A, Livengood H, et al. Transorbital alternating current stimulation in a double-masked randomized clinical trial: visual functional effect and quality of life. Ophthalmol Sci. 2024;5(1):100614. doi:10.1016/j.xops.2024.100614; Sabel BA, Henrich-Noack P, Fedorov A, et al. Vision restoration after brain and retina damage: the “residual vision activation theory.” Prog Brain Res. 2011;192:199-262. doi:10.1016/B978-0-444-53355-5.00013-0.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Radhakrishnan was recorded at the 29th Annual Glaucoma Symposium, held on February 8, 2025, in San Francisco, CA, and presented by The Glaucoma Research Foundation. For more information about upcoming CME activities from this presenter, please visit https://glaucoma.org/get-involved/events. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.25 CE contact hours.

Lecture ID:

OP631002

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.