Blepharoptosis, Chronic Progressive External Ophthalmoplegia, Myasthenia Gravis, Ptosis, Eyelid, Stroke, Traumatic Brain Injury
Conditions
Brief summary
This clinical trial will evaluate two non-surgical devices designed to improve eye lid opening for patients with severe Blepharoptosis (incomplete opening of the eyelids).
Detailed description
Two non-surgical devices for patients with Blepharoptosis will be evaluated. The Magnetic Levator Prosthesis (MLP), is an external device that makes use of a newer class of permanent magnets (made of alloys of neodymium (Nd), iron (Fe) and boron (B)) to restore eyelid movement. The Kinesiotape Frontalis Sling (KTFS), involves the use of tape to help facilitate levator muscle contraction to open the eyelid. Video recordings of spontaneous and volitional blinks will be used to evaluate the effects of each device on eyelid reanimation. The clinical trial will employ a crossover design in which participants will try each device at home in counterbalanced order with a washout period between. In each period of the crossover, participants will receive training (during study visits at Massachusetts Eye and Ear) in how to apply the device and will then try the device at home for one week with daily follow up by video calls. At the end of the one-week period of home use there will be a study visit at Massachusetts Eye and Ear when the device will be returned and additional video recordings of eye blinks will be made. At the end of the crossover period, participants will be asked to complete a questionnaire comparing the two devices and to select their preferred device.
Interventions
Neodymium magnet embedded in a glasses frame and a polymer embedded (PDMS) micro-magnet array fitted externally to the upper lid with IV 3000 securement film. The IV 3000 is FDA approved for extended wear on the skin.
DEVICEKinesiotape Frontalis Sling (KTFS)
Kineso Tape is FDA registered as a 510K exempt class 1 device, typically used by physical and occupational therapist to support muscular healing and movement. It is sometimes used on the face in cases of facial palsy or on the eye lid to support the lid in cases of severe blepharoptosis. In such cases it may be attached near the lid margin above the lashes extending up to the forehead skin overlying the frontalis muscle. Alternatively it may be a very short piece attached only along the lid skin. The tape is easily removed.
Sponsors
National Eye Institute (NEI)
Massachusetts Eye and Ear Infirmary
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of ptosis for at least one eye which occludes the visual axis in the resting position (without frontalis drive, lifting with forehead muscles) * Moderate cognitive function or better defined as greater than or equal to 18 out of 30 on a pre-screening of the Mini-Mental State Exam (MMSE)
Exclusion criteria
* Absence of ptosis which occludes the visual axis * Presence of a corneal ulcer of any size * Age less than 5 years * Severe Cognitive impairment defined as MMSE score less than 18, behaviors consistent with delirium (combinations of disorientation, hallucinations, delusions, and incoherent speech), or lethargy. * Presence of corneal hypoaesthesia; * Orbicularis weakness on the side of the ptosis * Mechanical ptosis, including ptosis due to orbital or lid tumor, cicatricial processes affecting the movements of the upper lid, and enophthalmos. * Previous ptosis surgery less than 3 months prior to Visit 1. * Lid position affected by lid or conjunctival scarring. * History of herpes keratitis. * Periocular neurotoxin (eg, Botox, Xeomin, Dysport, Myobloc) injections on the side of the ptosis within 3 months prior to Visit 1 and during the study. * History of hyperthyroidism or thyroid eye disease (ie, exophthalmos, upper eyelid retraction, diplopia secondary to extraocular muscle involvement). Hypothyroidism that is controlled on medication is allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Interpalpebral Fissure (IPF) During Spontaneous Blink | 2 weeks | The primary outcome was objective measurement of the IPF midpoint height during maximum closing in five spontaneous blinks, captured with a Nikon mirrorless SLR video recording system (Z7II; Nikon USA, Melville, NY, USA), with a visible light source mounted just above the lens, measured manually with ImageJ (National Institutes of Health, Bethesda, MD, USA). Spontaneous blinks are normally incomplete, a behavior that is dependent upon age, gender, task, and environmental demands. Maximum closing was defined as the three points at the base of the blink. Participants were instructed to look at the camera lens and try to relax and behave normally. Recording was stopped after 1 minute or after five spontaneous blinks, whichever came first. Recording always occurred in the same windowless clinical research room with consistent lighting, temperature, humidity, and air flow. The IPF midpoint height during maximum closing in five spontaneous blinks is averaged and reported below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interpalpebral Fissure During Resting Open | 2 weeks | Resting open IPF was the median between blink-event IPF, measured automatically by a deep learning model for eyelid landmark detection. the IPF midpoint height during resting open was averaged and reported below. |
| Proportion of Non-closure During Volitional Blinks | 2 weeks | At the end of recording, participants were instructed to close their eyes completely and open completely three times, representing volitional blink trials. These were evaluated manually with ImageJ. Blinks were classified by a human rater as having complete closure, or not, and then the proportion of non-closure blinks across all subjects was calculated for each condition and reported below. |
| Proportion of Subjects Selecting Each Device | 6 weeks | Proportion of subjects selecting either the MLP, the KTFS or neither |
Countries
United States
Participant flow
Recruitment details
Data for this study were collected at Massachusetts Eye and Ear, Boston, MA. Subjects were recruited by flyer and by referral from other ophthalmology clinics, or neurology clinics.
Pre-assignment details
One candidate was ruled as ineligible at a pre-screening visit due to lack of blepharoptosis.
Participants by arm
| Arm | Count |
|---|---|
| Participants Baseline characteristics were calculated for the entire group. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Participants |
|---|---|
| Age, Continuous | 61 years |
| Baseline Interpalpebral Fissure | 3.89 millimeters STANDARD_DEVIATION 2.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 0 / 15 | 3 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Interpalpebral Fissure (IPF) During Spontaneous Blink
The primary outcome was objective measurement of the IPF midpoint height during maximum closing in five spontaneous blinks, captured with a Nikon mirrorless SLR video recording system (Z7II; Nikon USA, Melville, NY, USA), with a visible light source mounted just above the lens, measured manually with ImageJ (National Institutes of Health, Bethesda, MD, USA). Spontaneous blinks are normally incomplete, a behavior that is dependent upon age, gender, task, and environmental demands. Maximum closing was defined as the three points at the base of the blink. Participants were instructed to look at the camera lens and try to relax and behave normally. Recording was stopped after 1 minute or after five spontaneous blinks, whichever came first. Recording always occurred in the same windowless clinical research room with consistent lighting, temperature, humidity, and air flow. The IPF midpoint height during maximum closing in five spontaneous blinks is averaged and reported below.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Magnetic Levator Prosthesis (MLP) | Interpalpebral Fissure (IPF) During Spontaneous Blink | 2.4 millimeters |
| Kinesiotape Frontalis Sling (KTFS) | Interpalpebral Fissure (IPF) During Spontaneous Blink | 4.1 millimeters |
| Baseline (Sham) | Interpalpebral Fissure (IPF) During Spontaneous Blink | 1.1 millimeters |
Comparison: Linear mixed-effects regression was used to determine the effect of treatment condition on the spontaneous blink and resting state open IPF, with participant as random intercept. Covariates of age, gender, blink sequence, and crossover order were investigated alone, and significant (P \< 0.05) covariates were included in the final model, from which the estimated marginal means and their 95% confidence interval were reported. Hypothesis: MLP allows a more complete spontaneous blink.p-value: <0.001Mixed Models Analysis
Secondary
Interpalpebral Fissure During Resting Open
Resting open IPF was the median between blink-event IPF, measured automatically by a deep learning model for eyelid landmark detection. the IPF midpoint height during resting open was averaged and reported below.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Magnetic Levator Prosthesis (MLP) | Interpalpebral Fissure During Resting Open | 6.8 millimeters |
| Kinesiotape Frontalis Sling (KTFS) | Interpalpebral Fissure During Resting Open | 7.0 millimeters |
| Baseline (Sham) | Interpalpebral Fissure During Resting Open | 3.9 millimeters |
Comparison: Hypothesis was that both devices (MLP and KFTS) would open the eye equally well, and that both would be better than sham treatment.p-value: 0.001Mixed Models Analysis
Secondary
Proportion of Non-closure During Volitional Blinks
At the end of recording, participants were instructed to close their eyes completely and open completely three times, representing volitional blink trials. These were evaluated manually with ImageJ. Blinks were classified by a human rater as having complete closure, or not, and then the proportion of non-closure blinks across all subjects was calculated for each condition and reported below.
Time frame: 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Magnetic Levator Prosthesis (MLP) | Proportion of Non-closure During Volitional Blinks | 0.067 Proportion of Non-closure Blinks |
| Kinesiotape Frontalis Sling (KTFS) | Proportion of Non-closure During Volitional Blinks | 0.356 Proportion of Non-closure Blinks |
| Baseline (Sham) | Proportion of Non-closure During Volitional Blinks | 0.022 Proportion of Non-closure Blinks |
Comparison: A test of proportionality was performed to determine the effect of the three treatments on the probability of the eyelid not fully closing.p-value: 0.001test of proportionality
Secondary
Proportion of Subjects Selecting Each Device
Proportion of subjects selecting either the MLP, the KTFS or neither
Time frame: 6 weeks
Population: All 15 participants were asked to chose which device they liked better, or no device. They were still masked to which was the novel/experimental treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Magnetic Levator Prosthesis (MLP) | Proportion of Subjects Selecting Each Device | 7 Participants |
| Kinesiotape Frontalis Sling (KTFS) | Proportion of Subjects Selecting Each Device | 6 Participants |
| Baseline (Sham) | Proportion of Subjects Selecting Each Device | 2 Participants |