I spoke to a couple of old friends from Harvard Medical School at ARVO in Baltimore today about my idea of injecting stem cells into the Meibomian Glands. To my surprise, they were both excited about the idea. One is a professor at Harvard and the other a professor at Bascom Palmer (he was my fellow during his rotation on my service when I was a brand new attending at MEEI).
One warned against the unknown in this field in general and noting the terrible, devastating case where three women in Florida went blind when a Physician’s Assistant (not an MD, not an RN, but a PA) injected Stem Cells into these women’s vitreous: totally malpractice. A write up of this tragic event is below.
She noted that the risk of blindness with injecting stem cells into the meibomian glands is likely 0% but there still may be unknowns for the future. Is there a risk the glands scar more? Is there a risk of cancer? No one knows. No one has tried it yet.
The other friend has been working with stem cells for almost a decade in animals and in petri dishes. He found the idea fascinating. He thinks it is a good idea.
Still, it was clear speaking to others MDs and phD at ARVO that there are 2 camps:
1. Very Cautious
2. We will not know if this works until we try it.
The “Very Cautious” Camp view stem cell research where MDs and researchers charge the patient for the treatment as the “dark side.” I totally understand this as this is how I was trained. Most research at Harvard was paid by grants. But all to often now, even at Harvard, research is paid by the drug companies or the MDs are paid by the drug companies (on the side). Objective outcomes are at times, in question when the company, whose product a researcher is studying, is paying for the study. I have never been a consultant for a drug company. The issue of seeing my patient’s meibomian glands die away, make me wonder if I should find a company to pay for the study.
The “We will not know if this works until we try it” Camp are more likely to see the issue at hand: the FDA and pure Academia (non-adulterated with drug company money) will take years to really prove stem cells work or do not work compared to controls. It will take millions of dollars and there may be some papers that show it does not work and others that show it does. It will take years for the truth to come out. In the meantime, many people who may have been helped, who have ALS, Alzheimer’s, etc will have since died.
By putting this technology in practicing MD’s hands, we are more likely to get an answer faster, they say. Likely results will show that Stem Cells do work in certain conditions and in certain patients with certain genetic profiles (and certain proteins on their cell surface and no mutations pre-programmed in their stem cells), but not in others. For now, we have no idea if the chance is 50/50% it will work or 70/30% it will work. Still, many patients are coming forward saying that Stem Cells Injections prevented them from shoulder surgery, knee surgery, cured their Lyme disease, etc, etc.
What are we to make of these testimonies? Is this a placebo effect or a true effect of Stem Cell Injection: we do not know for sure in many disease states as the outcome is subjective: did the patient really improve on cognitive tests for Alzheimer’s or was it a “good day” for the patient? Do we have any objective outcomes on Stem Cell Injections published? There have been papers reporting it to be safe (except for these cases below which are devastating), but many of the papers saying stem cell injections work have a great deal of bias or the MD, nurses, or researchers are not blinded to treatment versus control (see below excellent BMJ paper by Pas, et.al.)
With Stem Cell Injections into the Meibomian Glands, there are 2 Options:
1. Join one of the Stem Cell Centers that already has an IRB for Ophthalmology.
This will also cost about $35,000-$40,000 or a micro-liposuction machine, a study-approved centrifuge, and an incubator as the stem cells have to be maintained at a particular temperature. Each patient requires collagenase enzymes and surgical packs to be used for the procedure. Plus there is the cost of the time of the staff and surgeon for each procedure.
Most MDs who do this pass on the cost to the patient. Most MDs charge $5000-20000 depending on where the injection is planned. The positive of this option is that there is already a network of MDs using Stem Cells in their practice. They already have an IRB. You can collect your data from the database to publish in the future. They also offer cell banking to patients for the future which an academic IRB study would not be able to do privately.
The negatives are: charging patients for a procedure which is still experimental.
Also, if it turns out the Stem Cell Injection does not work, the practice is stuck with purchased machines, supplies, etc: I suspect this could be a reason why negative studies have not be forthright in coming as there is a big financial investment to use Stem Cells in a practice.
Still, I am very interested in injecting Stem Cells in the Meibomian Glands of patients with Meibomian Gland Dysfunction. The beauty of the Meibomian Gland is that you can clearly and objectively see whether it works or not with LipiScan or Meibography. There is less of a need for subjective questionnaires and subjective assessments: either the glands grow back or they do not. Also we can use one eye’s glands as a control. We would only inject the left lower lid glands and leave the right lower lid glands as a control initially. If we see an improvement and the patients notices an improvement in symptoms, we could then inject the rest of the eye lid glands.
2. Wait to get a large grant and submit my IRB to Georgetown or Medstar in the DC area: we need about $60,000-$80,000 to study about 10 patients. This money would be allocated for a micro-liposuction machine, a study-approved centrifuge, and an incubator as the stem cells have to be maintained at a particular temperature (all of this is about $35,000 to purchase). Each patient requires collagenase enzymes and surgical packs to be used for the procedure. Plus there is the cost of the time of the staff and surgeon for each procedure. The IRB may take 4-8 months to be approved. If anyone wants to donate funds to my project, please let me know: I would obviously not to charge patients for this study.
I believe so much that this will work, I would have my glands injected myself first. I would undergo the whole protocol. The issue is that there are no surgeons in my area that do Meibomian Gland probing. The closest surgeon near me that does this is Dr. Maskin in Florida.
Like the Ideal Protocol for a Study on the Evaluation of Stem Cell Injection Into Meibomian Glands is as follows. But as you will see, some parts of this are so unappealing (ie, being assigned to the control group without knowing you are not getting stem cells but just a placebo).
1. Informed consent will be reviewed explaining risk, benefits, and alternatives, including the risk of increased risk for cancer and unknown risk we do not know about. Risk of loss of vision is extremely low but we do not know all the risks as it has not been performed yet, not even in animals. Still, stem cells have been injected in many other parts of the body with published reports regarding safety (see below). This part would be part of Option 1 and 2
2. Reports kept in line with the CONSORT (Consolidated Standards of Reporting Trials) statement. This would be part of Option 1 and 2.
3. Randomize allocation. This is hard to do but more an option with Option 2 as patients are not paying for receiving a “Placebo/Control”.
4. Blind the researcher responsible for randomization to the patient at randomization: so multiple patients will get the liposuction and stem cells isolated. But only those randomized to Cases will get their stem cells injected into the Meibomian Glands. Controls will have a “sham” injection: only steroid or BSS (ie, salty water) will be injected into the Meibomian Glands and no one except a masked researcher or outside consultant will know who gets what. Not even the MD injecting would know. This is only an option with Option 2 as patients are not paying for receiving a “Placebo/Control/Sham Probing.” But in Option 1, the other eye is the control eye which makes the study more compelling as there can be no placebo bias as the LipiScan/Meibography will show if the Stem Cell Injection into the gland worked or not.
5. Blind participants, medical personnel, outcome assessor and statistician to secure unbiased estimates of effect. This is only an option with Option 2 as patients are not paying for receiving a “Placebo/Control/Sham Probing.” But in Option 1, the other eye is the control eye which makes the study more compelling as there can be no placebo bias as the LipiScan/Meibography will show if the Stem Cell Injection into the gland worked or not.
6. Protocols would be published in trial registers before the study’s start to enable the assessment of reporting bias and outcome switching for individual trials and to enable the detection of publication bias in general. This is an done in Option 1 and Option 2.
7. Characterization of the stem cells (MSCs) should be done in accordance with international recommendations in order to provide heterogeneous samples and allowing, eventually, for dose–effect analyses to be possible. This is an option for Option 1 and Option 2
8. All treated patients will be followed for an extended period of time, to assure the safety of MSC: Cell Surgical Network and US Stem Cell Inc. do this for the researcher. This is harder to do for Option 2 as grant funds are limited.