Toronto Support Group Meeting, Spring 2007

Dr. Noelen Pang

Dr. Pang began her talk by reviewing the location of the muscles to be injected during the study. As demonstrated by the diagram (Figure 1), the muscles around the eye are seen as three distinct sections; the very outer layer (a b c and d) are known as orbital muscle, the section immediately below that (e and f) is known as the preseptal muscle, and, finally, the section adjacent to the eyelashes (g and h) is known as the pretarsal muscle.

Dr. Pang, by way of review, outlined the aim of the study and went on to state they had devised three ways to verify the results of the study.

The first way was to develop a device to measure the contractual force of the eyelid muscles before and after the Botox injections in either chosen site. The second method was to adopt the Jankovic scale of measurement. (Dr. Jankovic is a neurologist who has done a great deal of research in the field of blepharospasm.) The third method was to ask the patients to evaluate which type of injection they felt provided the maximum benefit.

Dr. Pang went on to inform us that there were other retrospective studies regarding the effects of pretarsal versus preseptal toxin injections. The studies indicated that there was about a 14% increase in responsiveness to the drug and an overall longer lasting effect as well as a noticeable reduction in the dosage administered with the pretarsal versus the preseptal (orbicularis oculi muscle) injections sites. Overall this would mean that there would be fewer visits to the doctor and a decrease in the chance of building up a resistance to the drug. Another beneficial effect was the reduction in the incidence of ptosis (droopy eyelid). However, there have not been any real prospective randomized studies such as the one currently undertaken.

The closest study to qualify was a Japanese study that indicated an increased efficacy with pretarsal injections. In that study the researchers developed a muscle-force-generation apparatus that measured the muscle-force during contraction. Results showed that there was a decrease in muscle-force generation with a corresponding increase in the dosage of the toxin. Such a device would be required in the present study to measure the effect of different injection sites. However, Dr. Pang's group did not have such a device nor were they privy to any instructions on how to build one.

A prototype had to be devised where each arm of the device would be capable of measuring the force generated by the muscles involved. The design and testing of this appliance took approximately a year; thus, delaying the actual start of the research project. Despite the obstacles encountered a suitable prototype was built. It consists of several components that were barely potable. It was awkward to use but nevertheless did the job it was intended for.

Included in this report are the schematics of the prototype and it is hoped that the engineers reading this may be able to perfect the design and functionality of this measuring appliance. If you think that you can improve the design, please contact the Bioengineering Department of the University of Toronto. They may even name the device after you.

Each patient acts as his or her own control in that each patient receives both a preseptal and a pretarsal injection: one on each side of the face. The patient can then compare the effect of both at once and relate back to the physician his or her own comments as to the effectiveness of the injections.

Patient selection was on the basis of only those with blepharospasm as diagnosed by the oculoplastic surgery service. Also patients had to have successfully received either preseptal or pretarsal botulinum toxin injections for some time. In addition, the patients had to satisfy a Jankovic rating scale of 5 or higher to be eligible. The Jankovic scale measures the severity of the eyelid spasm as well as the frequency of the spasm: the aggregate of the two values had to equal or be greater than 5.

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Patients whose eyelid spasms were caused by some type of ocular surface disease which may be corrected by some sort of lubricating ointment or punctual occlusion were excluded from the study. Similarly, patients who previously had undergone eyelid surgery or some sort of surgical treatment for blepharospasm, such as a partial myectomy, were not included in the study.

Patients with consecutive blepharospasm are recruited from the oculoplastic practices affiliated with the University of Toronto and McMaster University in Hamilton. All patients are thoroughly informed and sign a written consent. The research Ethics Board Approval has been obtained.

At the initial visit and prior to toxin injections, a baseline data measurement with the eyelid-force device is obtained along with a Jankovic scale rating. Pretarsal and preseptal injections patterns are randomly assigned to either the right or left side of the patient’s face. In this single-blinded examination technique Dr. Pang performs the initial data measurement along with the Jankovic scale assessment. In order to eliminate the possibility of any bias Dr. Pang, at no time, is aware of the injection patterns since this function is performed by other doctors participating in the study and known only to them. The toxin dosage used is the same on both sides of the face and is the current dosage that the patient is receiving.

In the first three weeks after the patients have completed their first examination and injections the procedure is repeated. All electronic data is recorded once again and the patient relates what he or she has noted in her diary. The reason that this period was selected is because it is felt that it would take about this time for the effects of the injection to ramp up to its full potential. It is felt that the measurement would be best during this plateau, when the Botox is performing at its peak.

Since the average life span of a botulinum toxin injection is three months on average, the patient is reviewed by Dr. Pang once again at the end of this period. A further review is conducted at the six-month time. The procedure is the same each time; the measurement of the muscle contraction using the eyelid-device and rated according to the Jankovic scale. From the patient’s diary such information as the duration of the peak and total effect of the injection will be extrapolated. Included in this data will be the overall time-length of the injection and which type of injection the patient prefers. In order to continue on with the study the patient must have an overall Jankovic rating of 4 or higher.

Each patient visit will last approximately one hour. Further assessments are made at the predetermined times already mentioned or sooner if the patient is experiencing functional disability. Dr. Pang stated that she had hoped to have at least 40 patients for the study but had to settle for the 10 that qualified. Unfortunately some of these have dropped out for various reasons. She estimates that it will take about one year to complete the study with the 10 patients. Overall, the study will have taken two years to complete.

During the question period immediately following the talk Dr. Pang emphasized that none of the patients had their normal injection patterns changed. The only difference now was that if they had not been receiving a pretarsal injection previously, that is injections in the eyelids, they were receiving them now according to the devised random formula. If one of the test subjects would be a new patient the doctor performing the injections would do so on the basis of his normal assessment of any new patient. In other words, he or she would apply the injections where they were required first and then add the injections that were demanded by the study. Therefore, the only new injections would be those for the eyelids and they would be done according to the random formula established for the study.

Dr. Pang was asked what kind of side effects were noticed in the study. She answered by stating that the standard side effects for injections, such as tearing, irritation, double vision and droopy eyelids, were noticed. However, the ones they observed the most were tearing, irritation, and droopy eyelids along with the odd case of topical bruising of the injection site.

Dr. Pang asked Aileen Ohashi if she would like to comment on the study without giving away the results. Aileen reported that she did get some improvement but not a lot possibly due to the other eye conditions she has. Despite this her eyelids did open more than previously. Contrary to what she had imagined, Aileen did not find the new injections to be any more painful than those she was already getting. In summary she said that she was getting some improvement.

Dr. Pang added that, upon completion of the study, Aileen will be able to tell her doctor what type of injection patter she prefers and this in itself would be an added benefit. In response to a question concerning the 'dosage amount', Dr. Pang suggested that the next step would be a study in which the injection dosage itself is varied based on the preferred injection pattern. However, this would have to be a much larger study.