by Dan Roberts
with additional material
by Wendy Strouse Watt, O.D.
Originally Published October 26, 2005
Acuity Medical has successfully completed a proof of concept, double-masked trial of its TheraMac™ device for the treatment of dry age-related macular degeneration (AMD). The therapy developed from early studies of microcurrent stimulation, with improvements in the science and application.
Since the late 1980’s, practitioners have been marketing microcurrent stimulation devices that have not been approved for treatment of the retina by the Food and Drug Administration (FDA). Acuity Medical, however, has been working with the FDA, and successful completion of the trials will allow legal marketing of TheraMac™ for use in biocurrent therapy. This is good news for patients with dry macular degeneration, as it is one of the few studies currently underway for treatment of that form of the disease. This article gives complete information as provided to MD Support by lead researcher John Jarding, O.D., in an Internet conference on October 12, 2005. Also present were Wendy Strouse Watt, O.D. (MD Support Professional Advisor), and Thomas McColley, President of Acuity Medical, Inc.
Background
In 1985, Leland Michael, O.D. (Rapid City, South Dakota) and Merrill Allen, O.D. (Purdue University, Indiana), began a ten-year study of the treatment of age-related macular degeneration (ARMD) using biocurrent. They found that biocurrent, originally designed as a treatment for pain, seemed to stabilize the degenerative process of the retinal cells.
When Dr. Michael passed away in 1995, his work was taken over by John Jarding, O.D., who began to determine which microcurrent frequencies and waveforms would be most therapeutic for the macula. That research led him to the development of TheraMac™.
“I have felt,” Dr. Jarding told MD Support, “that it was only appropriate to follow FDA protocol when treating patients. Until we prove the benefits of biocurrent therapy to the FDA, it is not appropriate to sell instruments or advertise the benefits of biocurrent for the treatment of macular degeneration. These are FDA rules. These are things we plan to prove or disprove to the FDA through the trials.”
“Because there are significant differences in micro current instruments,” he explained, “none of which are FDA approved for the treatment of macular degeneration, appropriate research in current amounts, current frequencies, and frequency of use must be studied. Through my work with electrical engineers and a cell biologist, the TheraMac™ instrument has passed these items to the FDA’s satisfaction, allowing it to be used in clinical trials. I have had a continued fear that uncontrolled use of microcurrent and unapproved instruments would shed unfair and negative light on my work. My open clinical studies have shown very positive results using the appropriate current, frequency levels and frequency of use with TheraMac™ and biocurrent. 62% of the eyes treated have gained 2 or more lines of best-corrected visual acuity.”
When asked to compare results of his recent research with the 10-year study in which he participated with Drs. Michael and Allen, Dr. Jarding said that comparison is difficult. The earlier research simply collected data from patients in open label studies. Also, the studies included use of vitamins in tandem with biocurrent therapy (aka microcurrent stimulation), which the recent study did not. The feasibility study also used current levels at the lower end of the therapeutic range to ensure not breaking the double masked status. “Yet,” said Dr. Jarding, “all studies showed an improvement in vision in well over half of the patients treated.”
Possible Mechanisms
Electrical currents in the wound healing range increase ATP concentrations, promote the absorption of amino acids in tissue, stimulate protein synthesis, and assist membrane transport of amino acids. Nordenstom discussed the effects of relatively low-level electric fields on the permeability of capillaries.
A review of the literature showed that the time frames associated with minutes to one hour per treatment). The short duration of the treatment times indicated that the healing effects tended to favor mechanisms associated with short-term metabolic events, such as ATP synthesis, cyclic AMP and protein kinase C activity, and calcium transport. Other possible electrotherapy effects included: vascular dilation, changes in capillary permeability, vascular conditioning, protein filtering, tissue cell membrane polarization, and nervous system conditioning. It is possible that electrotherapeutic treatments could affect cell proliferation, cell differentiation, and tissue regeneration.
Biocurrent stimulation appears to improve the membrane permeability of the blood vessels and the cells and allows better oxygen and nutrition delivery to the cells and removal of by-products from the cells. An improvement in circulation improves the functioning of the cells and enables improved vision. There may be an improvement in cell metabolism, ATP levels, and protein synthesis.
Development of TheraMac™
Dr. Jarding coined the name TENSMAC™ (Transcutaneous Electrical Nerve Stimulation of the Macula) in 1997. Years of research led him to more accurately name his procedure TESMAC™ (Transcutaneous Electrical Stimulation of the Macula) since not only nerves were being stimulated as the acronym suggests. Physiologically, increases in ATP (or energy) levels, increases in metabolic activity of the cells, and protein synthesis occurred. TESMAC™ became TheraMac™ in 2003 to reflect the advances in development of the therapy.
How the Biocurrent Stimulation Studies Differ From Earlier Work
The results of these earlier studies, that were neither blinded nor controlled, suggested that nutrition and electrical stimulation were beneficial in treating all types of macular degeneration. By using both types of treatment at the same time, the data was confounded. It was difficult to determine whether the nutrition or the electrical stimulation was responsible for the change in vision or how much of an effect each had on the change in vision. These studies demonstrated the need for more research, controlled and double-blinded studies, treatment with electrical stimulation only, and treating one type of macular degeneration at a time. Nevertheless, the patients achieved a meaningful improvement in visual acuity.
The results of the feasibility study (which was controlled and double-blinded) showed that treatment with biocurrent generated significant improvement in visual acuity in those in the treatment group. This was achieved while keeping the blind in place. The current used was determined to be therapeutic (at the lowest level that would be beneficial), without allowing any indications of receiving it so as not to allow the patients to know if they were using the functional or non-functional instrument. Also, the data was pure because only one treatment was used for one type of macular degeneration, and the changes in visual acuity were attributable to it.
How TheraMac™is Different from Other Devices
The only instruments that are being used for macular degeneration therapy off-label are TENS devices. These have received FDA approval for the alleviation of pain, but have not been approved and found to be safe for use in retinal therapy. The TheraMac™ device was designed specifically for the treatment of AMD. It has built-in safety measures to prevent the use of current that is too high and dangerous to the retina. It has patented current and frequency levels designed specifically for the treatment of AMD. Acuity Medical has addressed the problems of poor current control and impedance that have shown to be big problems for other micro current devices. The FDA Open Label and Feasibility studies have found the TheraMac™ device to be safe and effective.
The Science Behind Biocurrent Therapy
Microcurrent stimulation describes a broad spectrum of applications. These include TENS therapy for the alleviation of pain, cochlear implants, therapy of Parkinson’s disease, stimulation for bladder control, etc.
Acuity Medical maintains that treatment with TheraMac™ utilizes patented biocurrent ranges with very specific frequencies to stimulate the desired physiologic response at the retinal level. Researchers confirm that micro current is well controlled with good control of current impedance.
Biocurrent therapy uses very low doses of micro current. Micro current is electrical current in the one millionth of an ampere range. This low current has shown to stimulate the production of the active transport enzyme, adenosine triphosphate (ATP), which facilitates the movement of nutrition from the blood to the cell. Microcurrent also increases membrane permeability to move substrates into and out of the cell. Since AMD is a disease of poor circulation to the center of the retina, the macula, an improvement of that circulation is essential in revitalizing retinal cell function. This fact was proven in the Cheng study of 1982.
Acuity’s research has focused on determining the ideal range of current and frequencies of biocurrent. They have found that too little current is ineffective, as is too much current. Too much current can also be damaging to neural cells of the retina. When testing many of the micro current devices currently on the market for pain, Acuity researchers found them to have a poor current control and major impedance problems. All of these problems have been addressed with the TheraMac™ instrument and the treatment protocol.
Clinical Trial Objectives and Endpoints
The title of the study was: A Double-Blind, Placebo-controlled, Randomized, Feasibility Study to Evaluate the Efficacy of TheraMac™. Although previous experience provided anecdotal support for the efficacy of the TheraMac™ device, no well-controlled trials had been done prior to the feasibility study. The primary purpose was to test study procedures and conduct exploratory data analyses in anticipation of expanding to a large-scale clinical trial. The secondary endpoint was the efficacy of the TheraMac™ device to improve visual acuity in patients with Dry MD. Success was defined as a significant difference between TheraMac™ and the control group in the change in distance visual acuity from baseline to post-treatment.
Trial Design
Subjects were patients with dry (non-bleeding) age related macular degeneration. There were two treatment groups (active and non-active). The patient population was 50 years of age or older, were diagnosed with dry AMD, and had their best visual acuity between 20/40 and 20/100. The non-active group was the control group. The trial was double-blinded or double-masked, meaning that neither the patient nor the investigator knew who was receiving treatment and who was not receiving treatment. Patients were assigned to either the treatment or the control group randomly. The non-active TheraMac™ unit looked and worked the same as the active unit, but no current was transmitted.
Trial Results
The results were significant. 26% of the treated group gained 10 or more letters (2 or more lines on the eye chart) as opposed to 11% of the control group. 59% of the treated group gained 5 or more letters (one or more lines on the eye chart) compared to 11% of the control group.
The Future
Acuity Medical is in the process of preparing for the final FDA study, in which it will be seeking approval for the sale and use of the device by all doctors who desire to use it. The pre-market approval study will be conducted at approximately 10 sites, treating a total number of 300 patients. At this time, none of the sites can be identified. Acuity Medical will notify MD Support with a list of sites and contacts as soon as the information is ready for publication.
When asked how the approval and marketing of TheraMac™ might affect practitioners who are already using other devices that have not been FDA-approved for retinal therapy, Dr. Jarding issued this statement:
“Once the FDA approves the use of biocurrent and the TheraMac™ device, the therapy and device will be made available to any eye doctor who wishes to prescribe it. Training will be provided to the doctors and their staff on the procedure and use of the instrument. It must be understood that any use of an unapproved device is deemed by the FDA as off-label use and must not be advertised as an approved therapy for AMD. If an alternative device is used off-label, the patient must be warned that it has not received FDA approval for efficacy and safety. It would make sense that doctors would choose to use an approved device over an unapproved device.”
Dr. Jarding and Acuity Medical have followed procedures, process and standards that give credibility and credence to their research. Theirs is the only research to date that involves a double-blind, controlled trial, and it is currently being peer-reviewed for publication. Also, the safety of TheraMac™ has been established, and it complies with American and International standards. If the device is approved after the trials, it will be for treating macular degeneration. Other devices that are being used are approved only for treating pain and not for use around the head and eyes.
About Dry Macular Degeneration
Macular degeneration is a disorder affecting the macula, the central part of the retina. Bruch’s membrane separates the neural network of the circulatory network of the choroid. The retina is comprised of many layers. The Retinal Pigment Epithelium (RPE) cells make up the inner most layer of the retina. The RPE are supporting cells for the outer layers of the retina and they contain melanin that gives them their dark color and decreases light scatter within the eye. The RPE form a blood-retinal barrier, are vital to the metabolism of Vitamin A, transport nutrients and metabolites between the choroid and the retina, manufacture extracellular mucopolysaccharides and lipids (which compose drusen), remove damaged and discarded photoreceptor outer segments, and resynthesizes photosensitive pigments.
The RPE-Bruch’s membrane complex is the area of activity in the genesis of drusen. The narrowing of the capillary lumen and the atrophy of the choriocapillaris at the macula is the cause of the RPE malfunction. This causes a zone of hypoxia (decreased oxygen levels). When the RPE are not functioning properly, they produce drusen. Bruch’s membrane thickens with age, and accumulation of lipids interferes with the function of the RPE, affecting the overlying photoreceptors.
As the membrane permeability decreases and the choriocapillaris degenerates, the lack of oxygen increases. The macular circulation becomes further impaired, and there is inadequate blood flow to remove the by-products from the cells. These by-products become toxic to the photoreceptors and RPE. The circulation continues to be compromised, the membrane permeability decreases more, RPE function decreases, RPE cells migrate to areas of the macula with better circulation or the cells drop out (die), and the macular degeneration worsens. If normal retinal metabolism is not restored, more and more RPE cells will die, and geographic atrophy will occur, creating the condition called dry (atrophic) macular degeneration.
To see illustrations of the anatomy of the eye as discussed here, see www.mdsupport.org/anatomy.html
About Acuity Medical
Acuity Medical, located in Brighton, Michigan, is a therapeutic technology company that is developing treatments for all aspects of macular disease. Since 1995 the company has been focused on development of biocurrent therapy for dry AMD. With an increasing amount of data demonstrating that electrical stimulation safely improves vision, Acuity Medical has the potential with the introduction of TheraMac™ to bring much-needed treatment and relief to dry AMD patients.
For more information about Acuity Medical, contact Tom McColley at (810) 229-5828.