Microcurrent Stimulation in the Treatment of Dry and Wet Macular Degeneration

Authors: Laurie Chaikin¹, Kellen Kashiwa², Michael Bennet², George Papastergiou³, Walter Gregory⁴

¹Private practice, Alameda, CA, USA
²Retina Institute of Hawaii, Honolulu, HI, USA
³California Retinal Associates, San Diego, CA, USA
⁴Clinical Trials Research Unit, Faculty of Medicine and Health, University of Leeds, Leeds, UK

Originally published in Clinical Ophthalmology 2015:9 2345–2353

Abstract

Purpose: To determine the safety and efficacy of the application of transcutaneous (transpalpebral) microcurrent stimulation to slow progression of dry and wet macular degeneration or improve vision in dry and wet macular degeneration.

Methods: Seventeen patients aged between 67 and 95 years with an average age of 83 years were selected to participate in the study over a period of 3 months in two eye care centers. There were 25 eyes with dry age-related macular degeneration (DAMD) and six eyes with wet age-related macular degeneration (WAMD).

Frequency-specific microcurrent stimulation was applied in a transpalpebral manner, using two programmable dual channel microcurrent units delivering pulsed microcurrent at 150 µA for 35 minutes once a week. The frequency pairs selected were based on targeting tissues, which are typically affected by the disease combined with frequencies that target disease processes. Early Treatment Diabetic Retinopathy Study or Snellen visual acuity (VA) was measured before and after each treatment session. All treatment was administered in a clinical setting.

Results: Significant increases were seen in VA in DAMD (P<0.012, Wilcoxon one-sample test), but in WAMD, improvements did not reach statistical significance (P=0.059). In DAMD eyes, twice as many patients showed increase in VA (52%) compared to those showing deterioration (26%), with improvements being often sizeable, whereas deteriorations were usually very slight. In WAMD eyes, five of six (83%) patients showed an increase and none showed deterioration.

Conclusion: The substantial changes observed over this period, combined with continued improvement for patients who continued treatment once a month, are encouraging for future studies. The changes observed indicate the potential efficacy of microcurrent to delay degeneration and possibly improve age-related macular degeneration, both wet and dry. However, this study has no control arm, so results should be treated with caution. Randomized double-blind controlled studies are needed to determine long-term effects.

Keywords: microcurrent, macular degeneration, transpalpebral, transcutaneous, retinal disease

Introduction

Low-intensity micro-amperage current has been applied to retinal conditions for several decades under various circumstances. Henry Dor, MD, an ophthalmologist in Germany, used electrical currents to help individuals with amblyopia, retinochoroiditis, glaucoma, and optic atrophy in 1873.

Historical Context

A summary paper by Gekeler and Bartz-Schmidt stated that subthreshold visual stimulation in inactive retinal implants leading to improvements in residual areas of vision was the result of a release of neurotrophic factors. Twenty peer-reviewed publications in PubMed over the last 5 years reflect renewed interest in microcurrent therapy.

Since then, transcorneal electrical stimulation (TES) and transpalpebral electrical stimulation (TPES) placement of the electrodes over the closed lid has been used.

Previous Research Findings

A study by Shinoda et al in 2008 applied this approach to 16 patients with wet age-related macular degeneration (WAMD) and to five with dry age-related macular degeneration (DAMD). They used four frequencies of 290 Hz, 31 Hz, 8.9 Hz, and 28 Hz delivered via a monophasic pulse at 800 µA.

Key Results:

• Subjects with both WAMD and DAMD showed statistically significant log of the minimum angle of resolution (logMAR) improvements
• WAMD: from 29.5 logMAR units to 31.8 logMAR units (P<0.04)
• DAMD: from 39.8 logMAR units to 42.9 logMAR units (P<0.04)

In 2013, Anastassiou published results from a randomized placebo-controlled exploratory trial with 22 patients using a TPES approach with variable frequencies of 5–80 Hz at 150–220 µA twice a day treatment to eight spots around the eyes for 40 seconds per spot for 1 week. Seven out of 12 patients had an improvement in visual acuity (VA) of more than five letters (P<0.001). Similarly contrast sensitivity improved with an increase of 4.4 optotypes (P<0.006). Placebo controls had no statistically significant change in VA.

Scientific Foundation

Basic Research Evidence

Basic research both in vitro and in vivo demonstrating the safety and neuroprotective effects of electrical current stimulation has been done in numerous areas:

Neurological Benefits:

• Motor axonal regeneration
• Sensory nerve regeneration
• Growth-associated gene expression significantly enhanced by brief periods of micro-amperage stimulation
• Increased survival of retinal ganglion cells in rats following crushed optic nerve
• Significant delay of posttraumatic cell death
• Increased visual evoked potential amplitude following optic nerve crush

Retinal Protection:

• Electroretinogram measurements showed amelioration of progressive photoreceptor degeneration following light-induced retinal damage
• Neuroprotection through proinflammatory effects
• Alteration in gene expression with close to 500 transcriptome changes measured
• Retinal photoreceptor protective effects demonstrated in rhodopsin P347L-deficient rabbits
• Neuroprotection from ischemic damage
• Increase in cerebral blood flow in rats following TES

Frequency-Specific Microcurrent (FSM)

FSM has been used extensively in the field of physical medicine and rehabilitation for pain relief and accelerating tissue recovery. This approach proposes that it is not only the microcurrents that have a positive effect on biological tissue but also the frequencies themselves.

How FSM Works:

• Frequencies are delivered via a square-wave pulse train
• Square-wave pulse trains contain a wide range of harmonics, which can stimulate a resonance effect in target tissues
• One well-known resonance effect is in sound acoustics breaking down the binding of lead atoms in crystal glass enabling it to shatter
• In tissue pathology, the resonance could potentially break molecular bonds responsible for inflammation

Clinical Evidence for Anti-Inflammatory Effects

An animal model was used to test the anti-inflammatory effect in the immune system. Arachidonic acid was painted on mouse ears to create inflammation. The frequency combination of 40 Hz and 116 Hz for inflammation in the immune system was run through the ears immediately afterward.

Results:

• Treatment group showed a 62% reduction of lipoxygenase-mediated inflammation
• 30% reduction of cyclooxygenase-mediated inflammation at 4 minutes
• Sham group showed no change
• Treated ear thickness reduced by 62% compared to controls

A human case study published in 2010 showed successful treatment of herpes zoster on ophthalmic branch of CN V with FSM using 190-minute treatment at 230 Hz and 430 Hz.

In a clinical study of pain in 77 fibromyalgia patients, statistically significant subjective improvements in pain were associated with reductions in inflammatory cytokines by a factor of 10–20 times in 90 minutes:

• Interleukin (IL)-1 from 392 pg/mL to 21 pg/mL
• TNF-α from 299 pg/mL to 21 pg/mL
• IL-6 from 204 pg/mL to 15 pg/mL

Methods

Study Design and Participants

Seventeen patients aged between 67 and 95 years with an average age of 82.9 years were tested and treated in two eye care centers located at the Retina Institute of Hawaii in Honolulu and a private practice in Castro Valley, CA, USA. There were 25 eyes with DAMD and six eyes with WAMD.

All patients were screened for inclusion after providing written informed consent. The research followed the tenets of the Declaration of Helsinki, and an independent review board application was completed and approved by Sterling Independent Review Board (Atlanta, GA, USA) prior to subject selection. The trial was registered with number NCT01790958.

Inclusion and Exclusion Criteria

Inclusion Criteria:

• 50 years of age or older, male and female
• History of retinal disease involvement
• No anti-vascular endothelial growth factor treatments for at least 3 months prior to the study
• No new antioxidant/vitamin supplementation for at least 6 months prior to the study
• Subjects with WAMD were placed in the study only after they were medically cleared as having no active bleeding

Exclusion Criteria:

• History of noncompliance with regular medical visits
• Significant media opacities that might interfere with assessing VA
• Presence of pigment epithelial tears or rips
• Diabetic retinopathy
• Any known serious allergies to fluorescein dye
• Presence of retinal neovascularization
• Any treatment with investigation agents in the past 30 days

Treatment Protocol

Equipment Setup: FSM stimulation was applied in a transpalpebral manner, with flat carbon electrodes placed into chamois-type fabric, which was moistened with water and placed over the closed eyes; another electrode was placed at the base of the skull.

![Patient receiving microcurrent treatment – Image shows a patient wearing protective eyewear with electrodes placed over closed eyes and microcurrent device visible]

Treatment Parameters:

• Two small dual channel programmable microcurrent units (Custom Care Manufacturing Microcurrent Technologies, Seattle, WA, USA, and Precision Distributing, Vancouver, WA, USA)
• Treatment time: 35 minutes
• Current delivered at 150 µA
• Frequency delivered via a ramped square-wave pulse train
• All treatments administered in a clinical setting

Frequency Selection: The frequency pairs selected were based on targeting tissues typically affected by the disease and combining with frequencies that target disease processes. Example frequency pairs included:

• 40 Hz with 95 Hz for inflammation in the retina and macula (137 Hz)
• Scarring and inflammation in the arteries, veins, capillaries, and retina (3 Hz and 13 Hz with 62 Hz, 79 Hz, 162 Hz, and 95 Hz)

Assessment Measures

Visual Acuity Testing:

• Early Treatment Diabetic Retinopathy Study or Snellen VA measured before and after each treatment session
• Subjective responses were recorded
• In cases of count fingers, hand motion, light perception, or no light perception, conversion values used: count fingers=1.6, hand motion=2.0, light perception=2.5, and no light perception=3.0 logMAR units

Additional Testing:

• Ophthalmic examination
• Intraocular pressure measurement
• Fluorescein angiography
• Fundus photography
• Optical coherence tomography (OCT)
• Microperimetry (when possible)

Statistical Analysis

Because treatment intervals varied slightly from patient to patient, and patients were followed-up for varying lengths of time, a linear increment method was used to calculate mean logMAR changes over time. This method involves:

1. Interpolating logMAR values between time points
2. Assuming changes follow a linear pattern
3. Extrapolating beyond individual patient follow-up using overall cohort patterns

To evaluate the significance of overall changes in VA over time, the Wilcoxon one-sample test (Wilcoxon signed-rank sum test) was used.

Results

Visual Acuity Outcomes

Dry AMD (DAMD) Results:

• Significant increases were seen in VA in DAMD (P<0.012, Wilcoxon one-sample test)
• Twice as many patients showed increase in VA (52%) compared to those showing deterioration (26%)
• Improvements were often sizeable, whereas deteriorations were usually very slight

Wet AMD (WAMD) Results:

• In WAMD, improvements did not reach statistical significance (P=0.059)
• With only six values, all six WAMD eyes would have had to show improvements for statistical significance
• Five eyes showed improvement and one showed no change
• Five of six (83%) patients showed a positive trend, while none showed deterioration

Detailed Visual Acuity Results

Table 1: VA Results for Dry AMD

(Table continues with remaining 15 eyes)

Table 2: VA Results for Wet AMD

Time Course Analysis

The study revealed consistent patterns in both dry and wet AMD:

Initial Response (First Week):

• Sharp fall in logMAR scores indicating improvement in VA
• Effect begins almost immediately
• Highly statistically significant effect observed

Continued Improvement (First Month):

• Continuing improvement throughout the first month
• LogMAR scores at 21 days showed:
  • DAMD eyes: 3.8 SEs below 0 (P<0.0001)
  • WAMD eyes: 3.9 SEs below 0 (P<0.0001)

Stabilization (2-3 Months):

• LogMAR scores appear to level off after the first month
• Some slight deterioration may occur in months 2-3
• Upper 95% confidence intervals consistently well below 0

Microperimetry Results

Of the patients who had microperimetry testing done, there was an overall increased retinal sensitivity across the board following microcurrent stimulation.

Key Findings:

• Some patients with large areas of geographic atrophy increased their sensitivity in areas of their preferred retinal locus
• Others with smaller to no areas of geographic atrophy increased their sensitivity in their fovea
• No changes in retinal thickness were measured by OCT

[Note: The original paper includes detailed microperimetry field maps showing pre- and post-treatment changes, with color-coded sensitivity maps demonstrating improvements in retinal function]

Treatment Response Patterns

Letter Change Analysis:

• Dry AMD: 52% showed improvement, 26% showed deterioration, 22% no change
• Wet AMD: 83% showed improvement, 0% showed deterioration, 17% no change
• Mean improvements often exceeded 5-10 letters
• Deteriorations, when they occurred, were typically 1-3 letters

Discussion

Clinical Implications

In this study, dual channel FSM therapy was used in a noninvasive procedure, involving transcutaneous electrical current with very low intensity. Clinically, if further studies support positive trends over time, this would be a relatively easy treatment modality for physicians to offer their patients, either as a weekly in-office treatment or a home-based therapy.

Proposed Mechanisms of Action

Mechanisms of possible tissue effects that may explain some of the changes in visual function by FSM are theoretical. No direct measures of tissue changes were taken. Many of the following hypotheses are derived from animal models using TES:

1. Mitochondrial Effects:

• Effects on the mitochondrial Krebs cycle increase production of intracellular adenosine triphosphate
• Transmembrane transport through voltage-gated ion channels is dependent on adenosine triphosphate
• Voltage-gated ion channels may be positively influenced by the presence of external current flow, enabling the configuration change that precedes ion flow

2. Electromagnetic Field Influence:

• Influence of extremely low-frequency electromagnetic fields has been demonstrated to have beneficial and therapeutic effects on voltage-gated calcium channels via influence on the G-protein channel through the nitric oxide-cyclic GMP–protein kinase pathway

3. Gene Expression Changes:

• Alteration in gene expression, such as upregulation of Bcl-2, ciliary neurotrophic factor, and brain-derived neurotrophic factor
• Downregulation of Bax
• Suppression or inhibition of inflammatory factors, such as IL-1β and TNF-α
• Transcriptome changes in 490 genes have been identified, including neuroprotective genes
• Upregulation of intrinsic insulin-like growth factor-1 (Mueller cell activation and diffusion into the inner retina)

4. Vascular Effects:

• Increase in choroidal vessel blood flow in normal human subjects, measured in ten healthy subjects following TES using a laser speckle flowgraphy
• Statistically significant increase in blood flow in the macular zone, which may account for the improvements in patients with ischemia

Study Limitations

Important Considerations:

• Follow-up is still relatively short and determination of long-term efficacy is as yet unproven
• Training effects of repeated VA measures are unknown
• VA testers were not blinded, adding the possibility of examiner bias
• The study has no control arm, so results should be treated with caution

Comparison to Previous Studies:

• The magnitude of changes in VA in this patient population was similar to that seen by Shinoda et al
• Perhaps less dramatic than that reported by Anastassiou, although follow-up was extremely short in the latter study
• Those patients who continued treatment once a month for at least 6 months maintained their VA gains

Future Treatment Considerations

Long-term Management: It is likely that patients would need to continue treatment for the duration of their lives, since the natural course of disease progression for age-related macular degeneration is a steady loss of vision.

Disease Progression Patterns:

• DAMD: Slow steady decline over what could be a long period (10 years or more), with the possibility of geographic atrophy occurring in a steady but more rapid decline with complete loss of central vision
• WAMD: Rapid precipitous loss of vision over a very short (days to months) time if left untreated

Safety Profile: This efficacy and safety study suggests that microcurrent stimulation can be safely administered to this population. In all human studies reviewed, there were no adverse effects aside from short-term corneal irritation from the contact electrode, and in most cases, there were notable and sometimes significant improvements in vision.

Conclusions

Key Findings

The substantial changes observed over this 3-month period, combined with continued improvement for patients who continued treatment once a month, are encouraging for future studies. The changes observed indicate the potential efficacy of microcurrent to delay degeneration and possibly improve age-related macular degeneration, both wet and dry.

Clinical Significance

Treatment Efficacy:

• Dry AMD showed statistically significant improvements in visual acuity (P<0.012)
• Wet AMD showed strong trends toward improvement (P=0.059)
• Microperimetry demonstrated improved retinal sensitivity
• No adverse effects were observed

Treatment Characteristics:

• Noninvasive procedure with very low intensity current
• Relatively easy treatment modality for clinical implementation
• Potential for both in-office and home-based therapy
• Safe administration profile

Future Research Directions

Recommended Studies:

• Randomized double-blind controlled studies are needed to determine long-term effects
• Studies could be made double-blind by including a control arm with sham treatment
• Longer follow-up periods needed to establish sustained benefits
• Investigation of optimal treatment frequencies and intervals

Clinical Applications: Interested clinicians would benefit from specialized training in FSM techniques. The approach shows promise as an adjunctive treatment for age-related macular degeneration, potentially offering patients a safe, noninvasive option for vision preservation and improvement.

Final Assessment

While this study lacks a control arm and requires cautious interpretation, the consistent improvements observed across multiple measures (visual acuity, microperimetry, patient reports) suggest that frequency-specific microcurrent stimulation represents a promising therapeutic approach for both dry and wet age-related macular degeneration. The safety profile and ease of administration make it an attractive option for further investigation and potential clinical implementation.

Disclosure: None of the authors have any financial interest in the equipment used, and report no conflicts of interest in this work.

Correspondence:
Laurie Chaikin
Private practice, 420 F Cola Ballena
Alameda, CA 94501, USA
Tel +1 510 693 8053
Fax +1 510 995 8376
Email: laurie.chaikin@gmail.com

Originally published in Clinical Ophthalmology 2015:9 2345–2353