Exploring electrical stimulation therapy: A promising approach to vision loss in optic neuropathies

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Glaucoma is one of the leading causes of blindness in the world and is commonly known as a “silent thief of sight,” given its deceptive nature. It is characterized as a chronic optic neuropathy, often associated with elevated intraocular pressure (IOP).

Though IOP is the only known modifiable risk factor, it is not the sole culprit leading to the damage of retinal ganglion cells (RGCs). Apoptotic damage of RGCs at the lamina cribrosa extends upstream to cortical networks, and this is what ultimately leads to visual field (VF) loss. Medical/surgical IOP management is the mainstay of treatment, but this merely slows and, at best, halts the progression of the disease.

Currently, there are no proven clinical therapies that predictably and reproducibly prevent damage to or restore RGC function. However, the concepts of neuroplasticity and neuroprotection have been evaluated as possible forms of intervention. Neuroprotection attempts to prevent optic nerve damage, but various agents that have been evaluated have yielded mixed results. Neuroplasticity, on the other hand, may be a more viable avenue to pursue, with the goal of treatment being to activate residual neuronal capabilities in the areas of reduced vision or visual field loss.

Electrical stimulation therapy (EST) has recently emerged as a therapy designed to influence neuroplasticity and potentially enhance visual function. Bechtereva and colleagues began using EST in 1985, and it has advanced over the last few decades. rtACS is thought to influence neuronal physiology through the synchronization of neuronal networks via low-intensity sinusoidal waveforms.

Endogenous oscillating elements of neuronal networks are tuned over time to match exogenous stimuli. The efficacy of rtACS on VFs has been evaluated in various trials in a variety of optic neuropathies. In a large retrospective data analysis of 446 patients with optic nerve damage, patients demonstrated a significant increase in VFs by 7.1% and 9.3% in the right and left eyes, respectively (p < 0.001), as measured by kinetic perimetry. In a multicenter masked RCT comparing rtACS versus sham treatment in an undifferentiated group of patients with optic neuropathy primarily from glaucoma and anterior ischemic optic neuropathy (AION), there was a significant mean improvement in VFs over baseline detection in the rtACS group compared to the sham group (24% change vs. 2.5% change, respectively, p = .011).

A study by Fedorov and colleagues looked at patients 6 to 9 months after treatment with rtACS and demonstrated insignificant decreases in VF performance, suggesting a possible lasting neural-adaptive process in the absence of an exogenous stimulus. While improvements in VFs are promising, data on quality-of-life (QoL) measurements need to be explored further. Gall and colleagues evaluated a randomized pooled analysis comparing pre- and post-QoL measurements between rtACS and sham groups in a group of patients with undifferentiated causes of optic neuropathy.

Subjective vision-related QoL measures were characterized with the National Eye Institute Visual Function Questionnaire (NEI-VFQ), while other health QoL measures were characterized by the Short Form Health Survey (SF-36). Although composite NEI-VFQ scores did not significantly differ between groups, there was a significant improvement in NEI-VFQ measures for subdomains including general vision, distance activities, and social functioning for the rtACS group compared to the sham. The rtACS group showed significant improvement in SF-36 measures of mental health and mental competency scores.

The aim of our multisite RCT, currently being conducted at NYU, Stanford, Wills Eye Hospital, and in Germany with Bernhard Sabel, is to explore the potential benefit of rtACS versus sham stimulation on neuronal morphology and physiology. This collaborative study should provide valuable insight into rtACS as a potential treatment for those with vision loss from various optic neuropathies.

Dr Panarelli is an ophthalmologist at NYU Langone Health. He specializes in the treatment of adult and pediatric glaucoma. Panarelli is certified by the American Board of Ophthalmology, and he is a member of the American Glaucoma Society as well as the American Academy of Ophthalmology. He currently serves as the Associate Residency Program Director at the New York Eye and Ear Infirmary of Mount Sinai as well as Glaucoma Fellowship Director.

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