Ask the Mito Doc – January 2025; Q&A

Ask the Mito Doc – January 2025 Q&A

 

 

All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.

A Comprehensive Vision: Understanding Chronic Progressive External Ophthalmoplegia (CPEO) from the Eyes to the Body

Clinicians:

· Zarazuela Zolkipli Cunningham, MD, Children’s Hospital of Philadelphia

· Rustum Karanjia MD, PhD, University of Ottawa Eye Institute

 

 

Q: Mitokatlyst—are there any studies planned? What therapies in trials are applicable to CPEO? Are there any supplements you suggest to help with CPEO? What medications do you recommend for dry eye?

A: Zarazuela Zolkipli Cunningham, MD: The UMDF website lists active trials in mitochondrial disease. Trials that are enrolling Mitochondrial Myopathy would be relevant to CPEO if the individual has muscle symptoms. Our standard of care on mitochondrial supplements for mitochondrial disease would be relevant to CPEO.

 

 

Q: Is Antisense Oligonucleotide Therapy for hepatitis C safe to give in Autosomal Dominant Optic Atrophy or CPEO?

A: Zarazuela Zolkipli Cunningham, MD: Oligonucleotide therapies for mitochondrial disease are not yet available. If you are wondering whether this approach to treat another disorder is safe in CPEO, that would require a discussion between the clinical trial investigators/physician for Hepatitis C and your mitochondrial physician in regard to the procedures involved to treat hepatitis C.

 

 

Q: What do you think about scleral lenses vs ptosis surgery?

A: Rustum Karanjia MD, PhD: Scleral lenses and ptosis surgery serve two different purposes. It would depend on what is being treated.

 

 

Q: Can muscles of only eye be involved and not the eyelids?

A: Rustum Karanjia MD, PhD: Not typically, genetic disease are usually bilateral when it comes to the eyes.

 

 

Q: Is there a list of neuro ophthalmologists? How would a patient find a doctor to help them?

A: Rustum Karanjia, MD, PhD: If you go to the NANOS (North American Neuro Ophthalmology Society) website, there is a directory on there that you can look up to see if there’s a local neuro ophthalmologist that might be able to assist you. Find a Neuro-Ophthalmologist | North American Neuro-Ophthalmology Society.

 

Q: Anecdotally I’ve heard people affected by CPEO complain of fluctuating eye glass prescriptions — that is, blurred vision leading to an updated prescription, but the new glasses are too strong or weak, get retested and get a different prescription. Only explanation is that first script was erroneous. This has happened to me. I’ve also had my astigmatism change. I now keep multiple old pairs of glasses and wear whichever works best at a given time. I am certain my vision fluctuates, though I don’t know why. I do not have diabetes or retinal disease. My ptosis was recently repaired. I shrugged this off until I heard others with CPEO complain of the same, some saying it got worse as they fatigued through the day. Any thoughts or explanations? None of us think we are imagining it.

A: Rustum Karanjia, MD, PhD: Patients with CPEO have a decreased blink rate. This effects the tear film which requires blinking to redistribute the tear film. The majority of refraction (focusing of light) is done by the tear film not the cornea or other parts of the eye. If the tear film is not stable the images will become blurred. Typically, fluctuating refractions are related to tear film instability. This changes from day to day or even within the same day. As such, the refraction done by the optometrist will work well only at certain times.

 

Q: Do you have suggestions to improve energy levels/reduce fatigue? What is the efficacy of NAD+, mito cocktail, or pyridostigmine (Mestinon)?

A: Zarazuela Zolkipli Cunningham, MD: Barcelos, Isabellaa,∗; Shadiack, Edwardb,∗; Ganetzky, Rebecca D.b,c,†; Falk, Marni J.b,c,†, wrote Mitochondrial Medicine Therapies: Rationale, Evidence, and Dosing Guidelines for care of mito patients. We have outlined the types of mitochondrial supplements, the individual components of a mitochondrial supplement, the types of ranges of doses that we use to prescribe, and the reasons for it. It is standard of care in the US at least, to support the empiric use of mitochondrial supplements which we consider to be mitochondrial treatment. The overarching goal is to stabilize and enhance metabolism, improve your energy levels, maintain your disease stability and/or improvement, and if there is progression, to try and attenuate it. At CHOP we are big supporters of having multiple components of the supplements compounded into one liquid or one capsule.

Physical exercise is important. Any movement and activity around your home is considered exercise, and it’s good for your mitochondria. It is also important to maintain proper nutrition. It does not mean just healthy eating of salads and fruit, which may not carry adequate caloric intake, it is important to eat enough. When we studied our patients and looked at their nutritional intake, it was an astoundingly new discovery to us to realize that patients, even those who were reporting that they were eating enough were, in fact, not eating enough.

 

 

Q: Are severe muscle spasms especially the day after exercise ever part of this?

A: Jean Flickinger, PT, CHOP: They can be but exercise should start slow and progress slowly to try to prevent over-doing it. If very sore 1-2 days after exercise, it may be too much. But a little soreness is expected.

 

 

Q: Does CHOP see adults?

A: Zarazuela Zolkipli Cunningham, MD: Yes, CHOP does see adults.

 

Q: What does a patient do that lives in a state where they don’t have a mito-care network center or any comprehensive mito care? What would be your 1st step?

A: Zarazuela Zolkipli Cunningham, MD: We hear this a lot, and we understand, and we sympathize, that is hard. I would say first you can speak to the UMDF, who are incredibly helpful. They can direct you to the closest center to your state. But I will state from our own experience here at CHOP, most of our patients come from out of state and they come for that exact reason. They come from states that do not have mitochondrial centers and that do not have physicians with great expertise in mitochondrial disease. But they may have a neurologist who’s willing to help, who’s seen or understands mitochondrial disease, but may not have extensive experience. That’s already a big help. There you would follow the same model we do, and I’m sure Dr. Cohen does the same, and Dr. Haas does the same where you would travel to the mitochondrial center and be seen there perhaps once a year. But in between, you would be seen by your other physicians who can help conduct the surveillance assessments and the ongoing systemic assessments and everything else that is needed based on your symptoms. So the village that you accrue is really important.

 

Q: My daughter has POLG and had a couple of metabolic strokes. It affected her eyesight. She has been seen by various eye doctors- all of which say there is nothing wrong with her eyes. Our neurologist states that her eyes and brain are not communicating. Is there anything we can do to help this improve? It has improved some with time, however, we are wondering if there are any exercises, or vitamins that may help.

A: Zarazuela Zolkipli Cunningham, MD: The same approach to management of all other organs would apply here, optimized nutrition, mitochondrial supplements, multidisciplinary care. Please consult with your eye doctor for the possibility of eye exercises, light stimuli, etc.

 

Q: If there is no extraocular manifestation, can the diagnosis be made clinically? Does the patient need to undergo muscle biopsy for the diagnosis? Also, for the biopsy, which muscles do you use?

A: Zarazuela Zolkipli Cunningham, MD: The spectrum of single mtDNA deletion disorders is a genetic diagnosis. Although the term CPEO is a description of the eye manifestations, other organ systems can be involved. I would recommend a mitochondrial evaluation to discuss the genetic testing approach. Muscle biopsies are obtained from the thigh muscle.

 

Q: Is the information presented today applicable to patients with Kearns Sayre Syndrome? My son is 23 and has confirmed KSS and may be interested in participating in clinical trials.

A: Zarazuela Zolkipli Cunningham, MD: Yes, all the information shared today would be relevant to any patient with a single mtDNA deletion disorder – which extends to CPEO, CPEO-plus and Kearns Sayre Syndrome patients.

 

Q: Do keto diets have positive effects on mitochondrial disorders?

A: Zarazuela Zolkipli Cunningham, MD: The keto diet may be poorly tolerated by many mitochondrial patients but has been used with good effect to treat a seizure disorder. Please consult with your Mitochondrial physician.