What can TES therapy offer my patients?
In Germany, around 20,000 to 30,000 people are affected by retinitis pigmentosa (RP) and are therefore starting to go blind. As a rare retinal disorder it is less in the public’s focus and funds to research the disease and possible treatments are generally directed towards diseases with more common indications, such as age-related macular degeneration (AMD).
With transcorneal electrical stimulation (TES) therapy, Retina Implant now offers a scientifically proven outpatient therapy option for patients with early and middle-stage RP. In this way, people with residual vision can benefit in particular by positively influencing the course of their RP.
The RI OkuStim system uses weak electrical impulses to activate neuroprotective growth factors in the retina. These factors can generate a protective effect on the dying retinal cells, thus maintaining sight for longer.
After receiving instruction from medical personnel, patients can carry out the TES therapy themselves at home with the RI OkuStim system.
Offer your patients the opportunity to slow the progression of their disease now.
Modes of action
Basic research into transcorneal electrical stimulation
The effects of transcorneal electrical stimulation (TES) in retinitis pigmentosa (RP) and other types of retinal degeneration have been investigated using various animal models. One widely used animal model for RP is Royal College of Surgeons (RCS) rats. The electrical stimulation in this model resulted in a deceleration of what is otherwise a fast-progressing degenerative process for the RCS rats, compared with sham stimulation (Morimoto et al., 2007). Rabbits carrying the rhodopsin P347L gene, as well as photodamaged rats, showed lower loss of photoreceptors and retained their outer nuclear layer for longer with retinal degeneration following electrical stimulation (Schatz et al., 2012; Ni et al., 2009; Morimoto et al., 2012). Furthermore, rats with optic nerve neuropathy also showed an induction of regenerative processes and reacquisition of sight following electrical stimulation (Miyake et al., 2007; Morimoto et al., 2005).
Influencing factors for the neuroprotective effect of TES
According to Fu et al., the positive effects are due to the modulation, elevation and release of neuroprotective substances by the Müller cells (Fu et al., 2015). Numerous trials have proven the positive effects on growth factors and apoptosis regulators, such as:
- Insulin-like Growth Factor 1 (IGF-1; Sato et al., 2008a; Tagami et al., 2009)
- Fibroblast Growth Factor-2 (FGF-2; Sato et al., 2008c; Ciavatta et al., 2009; Pardue et al., 2005)
- Ciliary Neurotrophic Factor (CNTF; Ni et al., 2009)
- Brain Derived Neurotrophic factor (BDNF; Ni et al., 2009; Sato et al., 2008b)
- Anti-apoptotic Gene B-cell-lymphoma-2 (Bcl-2; Ni et al., 2009)
- Bax Gene (Ni et al., 2009).
It has also been shown that TES can lead to changes in the transcriptome with a neuroprotective effect (Willmann et al., 2011). In 2011, Wang et al. observed the increased secretion of glutamine synthetase by the Müller cells, which resulted in the alleviation of the neuro-excitotoxicity caused by glutamate. The neural cell depolarisation caused by TES (Ca2+ influx) appears to contribute to an increase in intracellular adenosine monophosphate (cAMP), which thus promotes the survival of retinal cells (Morimoto et al., 2002). Furthermore, TES has been shown to contribute to improved chorioretinal circulation (Kurimoto et al., 2010).
Numerous studies show that TES activates neuroprotective systems and induces regeneration processes that slow or even prevent retinal degeneration. This also reduces the degradation of affected cells, which helps to maintain the function of existing cells for longer.
Suitability for therapy
Transcorneal electrical stimulation (TES) therapy with the RI OkuStim system is suitable for patients over the age of 18 who are affected by the retinal degeneration disorder retinitis pigmentosa (including as a symptom of another illness such as Usher syndrome) and who are still at least able to perceive light. It may offer the chance to slow down the progression of the disease. Young people and people of working age in particular can benefit from maintaining their vision for longer (for more details, see the section entitled “Use”).
According to the AKF, the clinical issues working group of the Scientific Medical Board of PRO RETINA Deutschland e.V., there are no objections to treating retinal dystrophies such as rod-cone dystrophy or choroideremia with TES. However, this would constitute off-label use.
- Diseases that could be triggered or worsened by negative growth processes of the retina following TES therapy, e.g. ocular neovascularisation, macular oedema, arterial or venous occlusion, diabetic retinopathy or age-related macular degeneration. Because the TES therapy promotes growth processes and chorioretinal circulation, these processes are contraindicated for the above-named diseases.
- Severely acute or chronic diseases (medical, psychiatric, other abnormal findings) that could worsen as a result of the therapy. Any disease that may have a negative impact on the therapy, or vice versa (e.g. epilepsy), must be carefully evaluated before any treatment takes place.
- Pregnancy or breastfeeding.
- Other active implants, because reciprocal effects cannot be ruled out. One exception is a cochlea implant, provided it is deactivated and the external components are removed.
How can your patient start the therapy?
Your patients can access TES therapy with the RI OkuStim system at our certified RI Competence Centres. These are specialised in degenerative retinal disease and are usually university hospitals with a wealth of experience in diagnosing RP and caring for affected patients. These clinics usually have special retina or even RP consultations in order to be able to adequately address the needs of the patient.
These centres are trained by product specialists from Retina Implant in the use of the RI OkuStim system, the suitability of patients for treatment, determining and setting individual patient therapy parameters, and in caring for patients with regular check-ups (see also “Therapy process”).
Determining the therapy parameters in the RI Competence Centre
Following the medical examination, an individual adjustment of the therapy parameters for the patient in question is necessary in order to apply the TES therapy. To do this, the RI Competence Centre has access to a special piece of software that determines the individual phosphene threshold of the patient using the RI OkuStim system. The phosphene threshold is the strength of the electric current at which a patient starts to perceive phosphenes in their field of vision. Trial results showed the positive effects of TES with stimulation above the patient’s individual phosphene threshold, ideally 200% of the threshold current.
The stimulation parameters are saved on a special memory card, which can be read by all RI OkuStim systems. The card also saves the data from each application so that the relevant competence centre can obtain an overview of the stimulation sessions carried out. The stimulation parameters cannot be changed by the patient.
Once the therapy parameters have been established by the RI Competence Centre, the patient has several options available for the therapy itself. The stimulation sessions can either be carried out independently, by a certified low-vision optician or directly in a RI Competence Centre. The TES therapy is carry out weekly with a duration of 30 minutes.The following diagram depicts the complete therapy process with all of its steps.
Therapy process for TES therapy with the RI OkuStim system:
Financing TES therapy with the RI OkuStim system
The following information outlines the possibilities for financing TES therapy in Germany. Generally speaking, patients receiving therapy with the RI OkuStim system have to pay for the treatment themselves.
If the patient is suitable for TES therapy, he or she will receive a prescription for the RI OkuStim system from the TES Competence Centre, which can be submitted to a certified low-vision optician. The optician takes care of the delivery, technical service and supports the competence centre in the one-to-one care of patients, particularly when it comes to fitting frames and with regard to technical aspects.
Because RI OkuStim therapy has not yet been added to the German statutory health insurance catalogue of services, patients have to bear the cost of the therapy themselves. The medical services can be invoiced by the doctors on the basis of the scale of fees for physicians (GOÄ). Patients have the option of applying for reimbursement by either statutory or private health insurers.
Information about the cost coverage process in Germany
If patients apply to health insurance providers for reimbursement, the health insurers can decide via a case-by-case check whether the cost of the prescription and therapy will be covered and the patient can receive the requested treatment. Prior to submitting the application, it is generally recommended for the patient to speak personally with the claim handler at the health insurer in question, or the area manager.
Necessary documents for applying for reimbursement
- An informal letter from the patient to the health insurer (“Application for reimbursement of cost”) Informal release from confidentiality for the treating physician
- Prescription for the RI OkuStim system and RI OkuEl electrodes
- Doctor’s letter with diagnosis, in-depth explanation of the disease progression and expected development, as well as the medical argument in favour of the therapy. This letter will be written by the RI Competence Centre.
- Cost estimate of the medical treatment costs. This letter will be written by the RI Competence Centre.
- Cost estimate of the material costs. This letter will be written by the certified low-vision optician.
The doctors at the RI Competence Centres support the patient after they receive their diagnosis and therapy recommendation in terms of making the application with doctor’s letters regarding their individual disease progression, the mode of action of the therapy, as well as regarding the therapy benefit as outlined by the clinical trials.
Trial process: Prospects for financing
As a manufacturer, we play an active role in championing the future inclusion of TES therapy with the RI OkuStim system in the German statutory health insurance catalogue of services, thus offering all patients a therapy option. For this reason, the German Federal Joint Committee (G-BA) has been conducting a trial according to Section 137e of the German Social Security Code (SGB V) since 2014. We are happy to provide you with in-depth information about this in the doctors’ leaflet on the trial.
Steps in the cost coverage process in Germany
Working together with the doctor at the RI Competence Centre, the patient compiles the application for cost coverage with the necessary documents.
With the assumption of approval under the Act to Protect Patient Rights, which came into force in February 2013, health insurers are forced to process applications more quickly. For this reason, patients should actively enquire about the approval of the application if:
- Either the health insurer has not responded within three weeks of the health insurer receiving the application
- Or information has been provided that the medical commission has been involved to assess the case, but no decision has been made five weeks after submitting the application.
Unfortunately, applications are often turned down at the deadline.
If no response has been received within the deadlines above, or the application is denied, we recommend finding out whether it may be useful to seek advice on social welfare law.
This information has been kindly provided by rbm gemeinnützigen GmbH, a charity promoting the rights of people with disabilities. For more information, please click on the following link: www.rbm-rechtsberatung.de.
Useful tips and pointers for RP patients submitting applications
- A conversation with the health insurer’s claim handler (e.g. at the local level) in good time is both helpful and highly recommended. Health insurers have a duty to inform people seeking advice.
- For patients whose applications are rejected, we recommended requesting a written statement of the reasons for the rejection from the health insurer. In case of an appeal procedure, this makes it easier for the lawyers to make their case in cooperation with the treating physician.
- Although cost coverage via case-by-case consideration by the health insurers can take some time and effort, we still encourage patients to attempt this step.