Ask the Mito Doc – October 2022: Q&A: Ophthalmic Manifestations of Mitochondrial Disease

Ask the Mito Doc- October 2022

Ophthalmic Manifestations of Mitochondrial Disease


Clinician: Dr. Rustum Karanjia MD, PHD from the University of Ottawa

Watch the full video:
Ask the Mito Doc: October 2022 – Ophthalmic Manifestations of Mitochondrial Disease – YouTube


Q: There is research being done on LHON in Australia that is in a pre-clinical phase in a stem cell approach to LHON. What is your opinion of this science and how promising is it?

A:  Overall, the use of stem cells inside the eye is something that I’m not keen on largely because you’re talking about replacing the optic nerve in cases of optic neuropathy. So, in situations where you’re trying to replace the optic nerve not only does the cell have to start off in the right place it has to get to the right target and the right target is at the back of the brain. So being able to transfer across that entire pathway and end up in the right spot is something that we don’t even know how it happens in vitro entirely in a baby. Yet we’re trying to do it in a human by injecting stem cells in various places which doesn’t entirely make sense. The other consideration with stem cells was that there have been some case reports inside the literature including a case series of about 4 patients who got injected with stem cells and went from being able to see things not well, but to being blind and could not see anything. In some cases, they lost the eye. So, we’re always very hesitant to suggest anything with stem cells, unless there is good evidence and good support behind it.
The other thing to consider, if you are considering a clinical trial where you must pay for it. Money is a big motivation to enroll patients and good quality clinical trials should have funding and you should not have to pay for it.



Q: My son was just diagnosed. He suffers from leg and foot pain which started around the same time he lost his sight. Have you seen this?

A: This would depend on what diagnosis. There are neuropathies that can happen with a lot of mitochondrial diseases and ending up in the plus spectrum whether it would be Lebers or Dominant Optic Atrophy or CPO, they do include neuropathy as one of the features.


Q: Does loss of vision with LHON always progress quickly or could it get worse over 2-3 years. 20/30 to 20/300 over 2 years.

A:   Most patients get worse within the first 6 months or so.  There are case reports of individuals who had one eye get affected, and then the second eye was not affected for about 20 to 30 years. Why that happens in some individuals and not others, We don’t have an answer for it, but it is in the literature.

Q:  Is either anisocoria or nystagmus related to mitochondrial myopathy?

A: Not typically associated with mitochondrial myopathy. Anisocoria, is the difference in size of the 2 pupils and usually there are other explanations for it.  Melanopsin cells are typically preserved so it’s not something that we anticipate as being associated with mitochondrial myopathy.

Q Are large pupils and/or sluggish pupil responses possible manifestations of MC disease?

A: In Lebers patients there’s a type of cell in the eye called Melanopsin Cell. This cell is responsible for pupillary response. The eye has a separate circuitry system in it between the eye and the brain to allow it to respond to light and the pupil to constrict. Those cells seem to be preserved in patients who have Lebers. So, whether there’s a different energy, dynamics or energy demand for the cells we don’t entirely know. It seems like those cells are preserved and the pupil is preserved. Pupillary response is preserved in patients with Lebers.


Q: Can you speak to the connection between Sjögren’s syndrome and mitochondrial dysfunction as they relate to the eye?

A: Sjögren’s syndrome is a result of having low turnover rates of the cells that produce the tears. In any tissue or organ system that has a high energy demand you’re going to expect some deterioration in that function and as a result you end up with dryness. You end up with situations where you’re not producing enough fluid in to keep the eyes moist. If you don’t produce enough saliva it results in dryness inside the mouth. It goes back to the whole issue of energy, so if you have less energy it will manifest in different ways.

Q: If ERG’s have been consistently the same result, is it necessary to repeat them?

A: An ERG is kind of like doing a visual field. The electroretinogram (ERG) is a diagnostic test that measures the electrical activity of the retina in response to a light stimulus.  It’s another way of looking at the eyes that gives us information to be able to see how things are doing over time. Typically, most of my patients are seen every 6 months to a year. We repeat the tests in order to track out on different levels how a patient is doing over time.

Q: Is there any preventive medicine available?

A: One the best and simplest methods to try and treat is to use antioxidants to reduce the amount of reactive oxygen species. This has been tried many times, they have about three to four generations of Quinones available, which are the antioxidants we use. With the first being COQ10 had poor ability to cross into the brain and into the eye. As a result, it wasn’t very effective. Idebenone was used in the clinical study and another generation of EPI-743.

Q: Should women take estrogen to prevent onset?

A: This should be discussed with your own care provider. There are risks associated with taking estrogen. Maybe taking estrogen will help increase the mitochondrial copy number and as such might help and be preventative in terms of being converted to the affected state, but every individual is different with associated risks. Twenty years ago, many women took estrogen and 10 years ago they stopped due to an increase in risk of breast cancer, heart disease and other things. Where you fall on that spectrum depends and that is something to discuss with your gynecologist as well as your family doctor.


Q: What is the best dosing for idebenone and place to purchase?

A: In the USA and Canada this can be purchased over the internet. My typical recommendation for patients who are interested in obtaining idebenone would be to get in touch with either LHON.ORG or LHON in Canada depending on where you live, as they have the most up to date information.

Q: What are the risks/benefits of ptosis surgery in children with neuromuscular conditions?

A: The risks associated with strabismus surgery would be from anesthesia. A patient who has mitochondrial disease should talk to your anesthesiologist. In terms of the eyes themselves, the risks are relatively minimal, regardless of the age of the individual. The biggest risk associated with eye muscle surgery is when we remove the muscles, we reattach them to the eye and in some cases the needle that we use to reattach it, can enter the eye. In that situation it can cause a retinal detachment which may require some laser surgery to be able to prevent it from happening, and to treat any hole that may have occurred in the structure of the eye. But beyond that there’s very limited risk in terms of moving the eyes.  The number one risk I tell my patients before strabismus surgery is that you may see double afterwards. Now the odds of that are typically around 70% of patients see single, but 30% may end up seeing double.

The goal is to get you to the point where you can see single and in children, the idea to do that earlier is in part because if one of the eyes is deviated for too long and by too much, the brain doesn’t develop correctly in the sense that the visual information that the brain receives in that eye doesn’t get processed the same way as it does in the good eye, and as a result, you may end up with something called amblyopia, where the eye itself is not seeing as well as it should.

Q: Are there any eye exercises that mito patients can do to help slow the progression?

A: The only eye exercise that really has any evidence behind it is something called a pencil push up, which is where you look at something at a distance, and you try to bring it closer and closer and closer and try to keep it together until you get to the point where it breaks apart and you keep doing that and try and strengthen your ability to do it, and to see things that are closer and closer to your face. That exercise has a role in a condition called convergence insufficiency but that is typically not a manifestation of a lot of mitochondrial eye disease.

Q: If I’ve been diagnosed with Lebers. Is there anything that progresses the disease more quickly, like smoking or drinking?

A: So what we understand with Lebers is that the flip where you go from being a carrier to becoming affected usually has a predisposition for individuals who spent a lot of time around smoke of any type. That’s not just smoking but also vaping and tire fires and bonfires and anything that has combustion and black smoke, alcohol is another prominent feature. This ends up increasing the reactive oxygen species. So either one of those or any of them can help tip the patient over. We’ve seen an individual followed over a long period of time that if they continue to use those substances, they have a tendency to continue to decline in vision. Worse than what we would anticipate in somebody who doesn’t.
So the overall recommendation would be to avoid them whether you’re affected or not.

Q: What treatment shows the most promise for Lhon?

A: Gene therapy study is one approach that could potentially show benefit. It may be that different patients have a stronger chance of benefiting from it. Idebenone again seems to work in some individuals and not in others and that may be related to other genes. Dr. Valerio Carelli in Italy has been doing some interesting work in that regard and has found another enzyme that might show whether or not a person might respond to idebenone. There are some promising treatments for patients that are affected.  In terms of mitochondrial treatment to prevent it from happening, one way is mitochondrial donation. That’s a possibility that may prevent it in the germ line. But at this stage, where that is and what’s going to happen next – its moving.

Q: Is retinitis pigmentosa a part of mitochondrial eye diseases and are there any trials going on or supplements that will slow progression?

A: There are clinical trials for retinitis pigmentosa and there is a specific gene associated with one type for which there is an approved gene therapy. That is for RP65 which is for Lebers congenital amaurosis. This gene therapy is shown to improve vision in individuals who have it.

Q: Are there special foods that are especially good for eye health (e.g., carrots)?

A: None that have very good evidence behind them.

Q: Have there been any studies with infrared and near infrared therapies with Mito and specifically with the eye? Is this being examined?  I’ve been reading that this therapy stimulates mitochondrial generation.

A: Infrared and near red light can cause some damage, depending on what wavelengths you’re dealing with. This is typically used as a treatment for certain retinal degenerations in order to try and treat around specific areas, it’s not typically used for treatment of mitochondrial disease.