Stem Cell Treatment for Optic Nerve Atrophy (ONA): What It Involves, Who It Is For, and What the Results Show

No. Stem cell therapy is not a cure for optic nerve atrophy. Nerve fibres that have died do not normally grow back, and no current treatment replaces them (2). What studies and our own follow-up data describe is improvement in specific aspects of vision for many, but not all, patients. Improvement cannot be guaranteed and differs considerably from one patient to another.

No. Stem cell therapy for optic nerve atrophy is not approved by the US Food and Drug Administration, and we do not offer it in the United States. Treatment is delivered at affiliated hospitals in Thailand and China under those countries’ regulations for cell therapy. The laboratories that prepare the cells hold CNAS, ISO and GMP accreditation, which is not the same thing as FDA approval of the treatment. More detail is on our standards and certifications page.

The optic nerve is the nerve supplying the retina – the neurological part of the eye receiving different visual images to transmit them to the brain. Optic nerves, therefore, transmit visual images from the eye (retina) to the brain to be processed and analyzed. Optic nerve atrophy (ONA) is basically the loss or gradual degeneration of the optic nerve. It could occur due to hereditary causes, endocrine/metabolic causes, brain/eye tumors (ex. pituitary tumors), neurological diseases (ex. multiple sclerosis), head trauma, glaucoma, ischemia, inflammation, toxins or due to different optic neuropathies and retinal disorders – as will be discussed below (3, 4, 5). Optic nerve atrophy is usually an irreversible chronic condition. Not all optic neuropathies have a clearly reversible stage before atrophy: acute ischemic or traumatic injury, for example, can produce permanent loss rapidly.

Retinal disorders are a separate group of diseases, although severe retinal or retinal ganglion-cell disease can sometimes be associated with secondary optic-nerve changes. The most-commonly encountered retinal disorder is age-related macular degeneration (AMD), which is a major cause of visual impairment and blindness in older adults (11). Different risk factors often increase one’s risk of developing macular degeneration including smoking and cardiovascular and metabolic factors (7, 11). Although both conditions have different causes and do not necessarily follow the same pathway of degeneration and symptoms, both can cause significant and sometimes irreversible visual impairment and will therefore be discussed together in relation to regenerative and stem cell therapy.

Symptoms vary according to the underlying disorder. Optic neuropathies may cause reduced visual acuity, impaired colour vision, visual-field defects or loss of contrast sensitivity, while macular retinal diseases more typically affect central vision and may cause blurred or distorted vision as the macula and fovea become involved. Symptoms may also include impaired night and/or light vision, and nystagmus, or abnormal involuntary eye movement (3, 4, 5, 11).

Given that optic atrophy occurs due to nerve degeneration, its treatment options are limited similar to other neurological conditions. Once the original cause of damage causes the optic nerves to atrophy, the damage is usually irreversible and doesn’t respond to conventional treatments. Therefore, current treatment usually focuses on reducing/removing the insult damaging the retina or optic nerve prior to entering the stage of actual optic atrophy. Such treatments include:

• Corticosteroids: Steroids are strong anti-inflammatory drugs that might reduce optic nerve or retinal inflammation in conditions such as optic neuritis, but they have no proven benefit in traumatic optic neuropathy and are not a general treatment for established optic nerve atrophy (5, 14).
• Lifestyle modifications: These include adopting a healthy diet, exercising, smoking and alcohol cessation…etc.
• Anti-VEGF drugs and other anti-angiogenic drugs: These drugs are beneficial mainly in neovascular or “wet age-related macular degeneration” and several other retinal vascular conditions which occur due to overproduction of “defective” blood vessels within the retina. Therefore suppressing the production of these blood vessels delays the retinal degeneration rate and the development of blindness (11). Several anti-VEGF therapies are now approved for this use, including ranibizumab, aflibercept, brolucizumab and faricimab. However, these drugs require prolonged, and maybe life-long, intraocular (within the eye) injections at close intervals; which might be inconvenient for many patients. Anti-VEGF treatment can preserve and often improve vision in neovascular AMD, although repeated injections are commonly required and it does not cure the underlying disease.
• Photodynamic therapy (Using Verteporfin dye): This treatment is also used in wet AMD to slow the progression of the disease by targeting the abnormal blood vessels within the retina. However, this therapy doesn’t improve visual outcomes and it simply delays disease progression (11).

As you can see, treatment options are limited, and none of the mentioned treatments address the issue of retinal and/or optic nerve atrophy. Current treatments only aim to reduce the damage and/or delay disease progression. This is where stem cell therapy has been emerging in the past few years as a possible hope for the treatment of retinal degeneration and/or optic nerve atrophy after its success in improving a multitude of other neurological disorders such as cerebral palsy and autism.

To date, there has not been a single study – to our knowledge – that has compared different types of stem cells, concerning safety and efficacy, particularly in patients with retinal or optic nerve disorders (1, 7). However, we can summarize different stem cell sources that have been tested in these disorders. Each form of stem cells has its own benefits and drawbacks as will be mentioned. Different stem cell sources that have been tested in ONA include:

• Mesenchymal Stem Cells: These are stem cells obtained from adipose tissues, bone marrow, or umbilical cord tissues – which we actually use at Beike. These cells can be easily produced in larger numbers to accommodate higher number of patients and allow better efficacy, have better response in neurological diseases – including ONA and retinal disorders – have better immunomodulatory, neurotrophic and paracrine properties compared to other stem cells (6, 7).
• Embryonic Stem Cells: Another type of stem cells includes embryonic stem cells. These cells can be differentiated into specific retinal cell types; yet they are difficult to obtain and have ethical concerns regarding their sources (7).
• Induced Pluripotent Stem Cells (iPSCs): These are adult cells that have been reprogrammed into a pluripotent state and can then be differentiated toward retinal or neural cell types. Their use remains primarily experimental (7).

After carefully reviewing all of the benefits and risks of each type, we have decided to use mesenchymal umbilical cord-based stem cells that have been most extensively studied; with the least reported side effects. In addition to the source of stem cells, there are also multiple routes of stem cell administration. Clinical trials testing stem cell therapy in ONA and retinal disorders have explored several routes, including (1, 8, 9):

• Intravenous (Into the blood)
• Intrathecal (Into the CSF surrounding the brain)
• Retrobulbar (Behind the eye where the optic nerve resides)
• Intraocular (Into the eye)
• Intravitreal routes (Into the vitreous of the eye)
• Sub-Tenon (Around the eye)

At Beike, we use combined intravenous and intrathecal routes; with some patients being eligible for two additional retrobulbar injections depending on different factors. We do not use intravitreal or intraocular cell injection.

At Beike, we use umbilical cord stem cells for ONA and retinal disorders, both umbilical cord-related mesenchymal/tissue and blood/hematopoietic cell samples donated from healthy mothers after normal birth. As previously mentioned, this concomitant administration of both types of stem cells provides better results.

There is no specific timing for stem cell treatment; but like many other neurological conditions, we generally recommend seeking stem cell therapy early after diagnosis. This is because the earlier the stem cell intervention, the easier it is to prevent further damage of the present cells and to be able to restore normal retinal or eye functioning before permanent damage takes place (2, 6). We still need to report that clinical benefit is not 100% guaranteed as is the case with any intervention, and consulting our specialists prior to undergoing the procedure is of utmost importance in order to gain more insight on the procedure and the estimated possibility of treatment success for your individual case.

Of course, no treatment is without complications, and stem cell therapy is the same. However, despite its novelty, stem cell therapy has limited side effects if used properly, with comparable general side effects to those experienced with regular blood transfusion or foreign organ transplantation (ex. allergic reactions, cell rejection, or fever). Additionally, across randomised trials of mesenchymal stem cells given into a vein, no increase in death, cancer, infection or blood-clot events was found (10). Injection into the eye itself is a different matter: in a 2023 trial, one of five patients lost vision through retinal detachment (9). We do not inject cells into the eye.

The following factors might influence a patient’s response to stem cell therapy, and how we at Beike Technology address each factor to ensure that we provide you with the highest efficacy using the safest procedure possible.

• Dose/Number of stem cells: At Beike Technology, we administer an optimum dose of around 120-340 Million Cells (depending on the person’s weight and age) for people with different eye disorders.
• Route/Method of administration: How the cells are given may affect where they travel in the body and which tissues they can reach. Combining intrathecal injection (through lumbar puncture directly within the brain’s CSF) with the traditional intravenous route may provide a better response than administering intravenous injections alone (which causes stem cells to go to other organs than the brain before reaching the brain). Other local routes, including retrobulbar and intravitreal administration, have also been investigated (1, 8, 9). Therefore, at Beike Technology, we use both intravenous and intrathecal routes concomitantly. In some selected patients, we might additionally recommend additional retrobulbar injections in order to obtain maximal efficacy; while ensuring the least possible side effects or toxicity.
• Type of Stem Cells used: The type and source of stem cells may influence how they behave after treatment. We use umbilical cord-based stem cells, which have been widely studied and have shown a favorable safety profile and encouraging clinical results in a range of neurological conditions.
• Timing of stem cell transplantation: As explained before, early intervention is crucial for people with optic diseases because more viable retinal ganglion cells may remain. Therefore, we recommend early intervention soon after diagnosis depending on the time one develops symptoms.
• Follow-up Time: Significant benefits from stem cell therapy in patients with optic nerve and retinal diseases begin appearing weeks to months after stem cell therapy, and most people reach their full potential around 6 to 12 months after treatment – where the effects then plateau (1, 8). At Beike Technology, even after discharge, we provide you with a full follow-up program beginning as early as one month and up to one year after transplantation. You have complete access to our professional team even after you leave our center.

The cause of ONA is dependent upon the type of atrophy present:

• Inflammatory/demyelinating optic neuropathy, also known as optic neuritis, occurs in conditions such as multiple sclerosis and other demyelinating or inflammatory conditions (5). Patients often present with rapid loss of vision in one eye, which may be loss in part or all of the visual field.
• Ischemic optic neuropathy results from occlusion of blood vessels supplying the optic nerve and can occur in conditions such as vasculitis, giant cell arteritis, granulomatosis with polyangiitis, and rheumatoid arthritis (16). Patients with ischemic optic neuropathy typically develop sudden, painless loss of vision, most often affecting the lower (inferior) half of the visual field (16).
• Traumatic optic neuropathy results from direct or indirect injury to the optic nerve, often from blunt force or accidents such as motor vehicle collisions (14).
• Compressive or infiltrative optic neuropathy results in the destruction of the optic nerve from locally invading tumors, infection, and autoimmune processes such as sarcoidosis (15).
• Hereditary optic neuropathy: Genetic conditions including Leber hereditary optic neuropathy and dominant optic atrophy selectively damage retinal ganglion cells and their axons (3).
• Glaucomatous optic neuropathy: Glaucoma causes progressive retinal ganglion-cell and optic nerve axon loss and is one of the most common causes of irreversible visual loss worldwide (4).

ONA is diagnosed by extensive ophthalmological investigation which may include:

• Visual field testing: visual field defects in optic neuropathies can take several patterns including central, diffuse, arcuate, and altitudinal defects (15, 16). The pattern of visual field defect is not specific to any etiology and almost any type of field defect can occur with any optic neuropathy. However, altitudinal defects are more common in ischemic optic neuropathies and central, or cecocentral defects frequently accompany toxic/nutritional and hereditary optic neuropathies.
• Electrophysiological testing: Visual evoked potential (VEP) are often abnormal in optic neuropathies (5). Although VEP is not necessary for the diagnosis of optic neuropathy, it can be useful in patients with early or sub-clinical optic neuropathy who may have normal pupillary responses and no discernible optic disc changes on clinical examination.
• Optical coherence tomography: OCT is a non-invasive imaging technique that uses low coherence light to penetrate tissue and a camera to analyze the reflected image. By performing circular scans around the optic nerve head, the peripapillary nerve fiber layer can be analyzed. It is widely used to evaluate structural loss and follow patients with glaucoma, optic neuritis, hereditary optic neuropathies and other optic nerve diseases (1, 3, 4, 5).

Symptoms of ONA may include blurred vision and central, peripheral (such as tunnel vision), or other localized visual-field defects (such as scotomas). These defects are diagnosed on further investigation using the aforementioned techniques.

The mechanisms by which stem cells deliver their regenerative action are :

• Secretion of neurotrophic factors: MSCs release certain neurotrophic growth factors including brain-derived neurotrophic factor (BDNF) which may offer neuroprotection (6).
• Anti-inflammatory and immunomodulatory effects: Injection of MSC may have anti-inflammatory and neuroprotective effects that support surviving retinal ganglion cells (6, 7).
• Anti-apoptotic effects: Factors secreted by MSCs may help reduce programmed cell death in stressed retinal ganglion cells (6).
• Support of the local cellular environment: MSC-derived signaling molecules and extracellular vesicles are being studied for their ability to support neuronal survival and endogenous repair pathways (6, 7, 12).