Clinical Trial to Improve the Magnetic Levator Prosthesis (MLP) Including the Development and Testing of a Novel Adjustable Force System
Phase: NA
Conditions: Blepharoptosis, Ptosis, Eyelid, Myasthenia Gravis, Stroke, Traumatic Brain Injury
Sponsor: Massachusetts Eye and Ear Infirmary

 
 
 
 
 
CLINICAL TRIAL TO IMPROVE THE MAGNETIC LEVATOR PROSTHESIS  
     
NCT03818204 
 
DOCUMENT DATE:  3/17/2020 
 
 

ii 
 
Clinical Trial to improve the magnetic levator prosthesis (MLP) including the development and testing of 
a novel adjustable force system 
Principal Investigator: Kevin Houston, OD 
Draft or Version Number:  version 2.0 
March 17, 2020 

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Table of Contents 
LIST OF ABBREVIATIONS ............................................................................................................................... 1 
STATEMENT OF COMPLIANCE ...................................................................................................................... 1 
PROTOCOL SUMMARY .................................................................................................................................. 1 
SCHEMATIC OF STUDY DESIGN ...................................................................... Error! Bookmark not defined. 
1 
KEY ROLES .......................................................................................................................................... 2 
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ................................. 2 
2.1 
Background Information .......................................................................................................... 2 
2.2 
Rationale .................................................................................................................................. 4 
2.3 
Potential Risks and Benefits..................................................................................................... 5 
2.3.1 
Known Potential Risks ............................................................................................ 5 
2.3.2 
Known Potential Benefits ...................................................................................... 6 
3 
OBJECTIVES AND PURPOSE ............................................................................................................... 7 
4 
STUDY DESIGN AND ENDPOINTS ....................................................................................................... 7 
4.1 
Description of the Study Design .............................................................................................. 7 
4.2.1 
Primary Endpoint ................................................................................................... 7 
4.2.2 
Secondary Endpoints .............................................. Error! Bookmark not defined. 
4.2.3 
Exploratory Endpoints ............................................ Error! Bookmark not defined. 
5 
STUDY ENROLLMENT AND WITHDRAWAL ........................................................................................ 7 
5.1 
Participant Inclusion Criteria ................................................................................................... 7 
5.2 
Participant Exclusion Criteria ................................................................................................... 7 
5.3 
Strategies for Recruitment and Retention............................................................................... 7 
5.4 
Participant Withdrawal or termination ................................................................................... 7 
5.4.1 
Reasons for Withdrawal or Termination ............................................................... 7 
5.4.2 
Handling of Participant Withdrawals or termination ............................................ 8 
5.5 
Premature Termination or Suspension of Study ..................................................................... 8 
6 
STUDY AGENT .................................................................................................................................... 8 
6.1 
Study Agent(s) and Control Description .................................................................................. 8 
6.1.1 
Acquisition ............................................................................................................. 9 
6.1.2 
Formulation, Appearance, Packaging, and Labeling .............................................. 9 
6.1.3 
Product Storage and Stability ................................................................................ 9 
6.1.4 
Preparation ............................................................................................................ 9 
6.1.5 
Dosing and Administration ..................................... Error! Bookmark not defined. 
6.1.6 
Route of Administration ......................................... Error! Bookmark not defined. 
6.1.7 
Starting Dose and Dose Escalation Schedule .......... Error! Bookmark not defined. 
6.1.8 
Dose Adjustments/Modifications/Delays ............... Error! Bookmark not defined. 
6.1.9 
Duration of Therapy ............................................................................................... 9 
6.1.10 
Tracking of Dose ..................................................... Error! Bookmark not defined. 
6.1.11 
Device Specific Considerations .............................................................................. 9 
6.2 
Study agent Accountability Procedures ................................................................................... 9 
7 
STUDY PROCEDURES AND SCHEDULE ............................................................................................. 10 
7.1 
Study Procedures/Evaluations ............................................................................................... 10 

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7.1.1 
Study specific procedures .................................................................................... 10 
7.1.2 
Standard of care study procedures......................... Error! Bookmark not defined. 
7.2 
Laboratory Procedures/Evaluations ......................................... Error! Bookmark not defined. 
7.2.1 
Clinical Laboratory Evaluations ............................... Error! Bookmark not defined. 
7.2.2 
Other Assays or Procedures .................................... Error! Bookmark not defined. 
7.2.3 
Specimen Preparation, Handling, and Storage ....... Error! Bookmark not defined. 
7.2.4 
Specimen Shipment ................................................ Error! Bookmark not defined. 
7.3 
Study Schedule ...................................................................................................................... 10 
7.3.1 
Screening ............................................................................................................. 10 
7.3.2 
Enrollment/Baseline ............................................................................................ 11 
7.3.3 
Follow-up ............................................................................................................. 11 
7.3.4 
Final Study Visit .................................................................................................... 11 
7.3.5 
Early Termination Visit ......................................................................................... 11 
7.3.7 
Schedule of Events Table ..................................................................................... 11 
7.4 
Justification for Sensitive Procedures ....................................... Error! Bookmark not defined. 
7.5 
Concomitant Medications, Treatments, and Procedures ...................................................... 12 
7.5.1 
Precautionary Medications, Treatments, and Procedures .................................. 12 
7.6 
Prohibited Medications, Treatments, and Procedures.......................................................... 13 
7.7 
Prophylactic Medications, Treatments, and Procedures ......... Error! Bookmark not defined. 
7.8 
Rescue Medications, Treatments, and Procedures .................. Error! Bookmark not defined. 
7.9 
Participant Access to Study Agent At Study Closure ............................................................. 13 
8 
ASSESSMENT OF SAFETY ................................................................................................................. 13 
8.1 
Specification of Safety Parameters ........................................................................................ 13 
8.1.1 
Definition of Adverse Events (AE) ........................................................................ 13 
8.1.2 
Definition of Serious Adverse Events (SAE) ......................................................... 14 
8.1.3 
Definition of Unanticipated Problems (UP) ......................................................... 14 
8.2 
Classification of an Adverse Event ......................................................................................... 14 
8.2.1 
Severity of Event ..................................................... Error! Bookmark not defined. 
8.2.2 
Relationship to Study Agent ................................................................................ 14 
8.2.3 
Expectedness .......................................................... Error! Bookmark not defined. 
8.3 
Time Period and Frequency for Event Assessment and Follow-Up ....................................... 14 
8.4 
Reporting Procedures ............................................................................................................ 15 
8.4.1 
Adverse Event Reporting ..................................................................................... 15 
8.4.2 
Serious Adverse Event Reporting......................................................................... 15 
8.4.3 
Unanticipated Problem Reporting ....................................................................... 15 
8.4.4 
Events of Special Interest ........................................ Error! Bookmark not defined. 
8.4.5 
Reporting of Pregnancy .......................................... Error! Bookmark not defined. 
8.5 
Study Halting Rules ................................................................... Error! Bookmark not defined. 
8.6 
Safety Oversight ........................................................................ Error! Bookmark not defined. 
9 
CLINICAL MONITORING ...................................................................... Error! Bookmark not defined. 
10 
STATISTICAL CONSIDERATIONS ....................................................................................................... 16 
10.1 
Statistical and Analytical Plans .............................................................................................. 16 

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10.2 
Statistical Hypotheses ............................................................... Error! Bookmark not defined. 
10.3 
Analysis Datasets ...................................................................... Error! Bookmark not defined. 
10.4 
Description of Statistical Methods ........................................................................................ 16 
10.4.1 
General Approach ................................................................................................ 16 
10.4.2 
Analysis of the Primary Efficacy Endpoint(s) ....................................................... 16 
10.4.3 
Analysis of the Secondary Endpoint(s) ................................................................ 16 
10.4.4 
Safety Analyses .................................................................................................... 17 
10.4.5 
Adherence and Retention Analyses ..................................................................... 17 
10.4.6  
Baseline Descriptive Statistics ............................................................................. 17 
10.4.7 
Planned Interim Analyses .................................................................................... 18 
10.4.9 
Multiple Comparison/Multiplicity ....................................................................... 18 
10.4.10 
Tabulation of Individual Response Data .............................................................. 18 
10.4.11 
Exploratory Analyses ............................................................................................ 18 
10.5 
Sample Size ............................................................................................................................ 18 
10.6 
Measures to Minimize Bias .................................................................................................... 18 
10.6.1 
Enrollment/ Randomization/ Masking Procedures ............................................. 18 
10.6.2 
Evaluation of Success of Blinding ............................ Error! Bookmark not defined. 
10.6.3 
Breaking the Study Blind/Participant Code ......................................................... 19 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ........................................... 19 
12 
QUALITY ASSURANCE AND QUALITY CONTROL .............................................................................. 19 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ................................................................................... 19 
13.1 
Ethical Standard ..................................................................................................................... 19 
13.2 
Institutional Review Board .................................................................................................... 20 
13.3 
Informed Consent Process ..................................................................................................... 20 
13.3.1 
Consent/assent and Other Informational Documents Provided to Participants 20 
13.3.2 
Consent Procedures and Documentation ............................................................ 20 
13.4 
Participant and data Confidentiality ...................................................................................... 21 
13.4.1 
Research Use of Stored Human Samples,Specimens or Data Error! Bookmark not 
defined. 
13.5 
Future Use of Stored Specimens .............................................. Error! Bookmark not defined. 
14 
DATA HANDLING AND RECORD KEEPING ........................................................................................ 21 
14.1 
Data Collection and Management Responsibilities ............................................................... 22 
14.2 
Study Records Retention ....................................................................................................... 22 
14.3 
Protocol Deviations ................................................................................................................ 22 
14.4 
Publication and Data Sharing Policy ...................................................................................... 22 
15 
STUDY ADMINISTRATION ................................................................... Error! Bookmark not defined. 
15.1 
Study Leadership ...................................................................... Error! Bookmark not defined. 
16 
CONFLICT OF INTEREST POLICY ....................................................................................................... 22 
17  
LITERATURE REFERENCES ................................................................................................................ 22 
APPENDIX .................................................................................................................................................... 24 
 

 Clinical Trial to improve the magnetic levator prosthesis (MLP) including the development and testing of a novel adjustable 
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LIST OF ABBREVIATIONS 
 
MLP 
magnetic levator prosthesis 
IPF 
Interpalpebral fissure 
PI 
Principal Investigator 
VFQ 
visual functioning questionnaire 
IVI 
impact of visual impairment questionnaire  
MOCA 
Montreal cognitive assessment 
NEI 
National Eye Institute 
NAFL 
Sodium Fluoroscein 
IRB 
Institutional Review Board 
MEEI 
Massachusetts Eye and Ear Infirmary 
HRPP 
Human Research Protections Program 
MMSE 
Mini Mental Status Exam 
 
 
 
STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with Good Clinical Practices, the U.S. Code of Federal 
Regulations on the Protection of Human Subjects (45 CFR Part 46), the Code of Federal Regulations 
applicable to clinical studies (21 CFR 312 – Investigational New Drug Application, 21 CFR 50 – Protection 
of Human Subjects and 21 CFR 54.  The Principal Investigator at the study site Massachusetts Eye and 
Ear Infirmary will assure that no deviation from, or changes to the protocol will take place without prior 
agreement documented approval from the Institutional Review Board (IRB), except where necessary to 
eliminate an immediate hazard(s) to the study participants. All personnel involved in the conduct of this 
study have completed Human Subjects Protection Training. 
 
PROTOCOL SUMMARY 
Title: 
Clinical Trial to improve the magnetic levator prosthesis (MLP) including 
the development and testing of a novel adjustable force system 
Objectives: 
 
To improve the magnetic levator prosthesis (MLP) by development and 
testing of a novel adjustable force system. 
 
 
 
 
Endpoints 
1. Completion of the 2 visit protocol with acquisition of 
interpalpebral fissue height during resting open without the MLP, 
and with the MLP over 5 adjustable force levels.   
 
 

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Population: 
Individuals with severe unilateral or bilateral ptosis (n = 19) defined as 
occlusion of the lower pupil margin by the lid in the resting state 
Phase: 
I/II 
Number of Sites 
enrolling participants: 
1 
Description of Study 
Agent : 
magnetic levator prosthesis (MLP) with compatible spectacle frames 
Study Duration: 
2 to 3 years 
Participant Duration: 
2 visits over 2 weeks. 
\ 
1 
KEY ROLES 
Principal Investigator – Overall responsibility for all study related activities. 
Post Doctoral Fellow- Responsible for consenting, enrolling and scheduling subjects. Also will collect, 
record and report all study data. 
Reseach Technician 1 – Responsible for 3-D design and printing of prototypes.   
Research Technician 2 – Responsible for producing the MLP lid magnet array.  Also responsible for 
randomization and counterbalancing schemes.     
2  
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
 
2.1 
BACKGROUND INFORMATION  
Blepharoptosis, defined as incomplete opening of the upper eyelid, occurs due to abnormalities in the 
function or structure of the levator palpebrae superioris muscle, injury to or dysfunction of the superior 
division of the 3rd cranial nerve, or structural abnormalities.[1] Etiologies include congenital 
abnormalities, stroke, traumatic brain injury, tumors of the brain or face, viral illnesses, diabetes, 
autoimmune disorders such as myasthenia gravis, and general aging mechanisms.[1] The prevalence of 
blepharoptosis within the US general population is unknown; however, in Korean and U.K. general 
population it has been reported to be 11% [2, 3] suggesting 30 million people in the U.S. have the 
disorder. 
Severe ptosis and associated ophthalmoplegia cause low vision with negative effects on function and 
quality of life – Total bilateral ptosis causes profound yet potentially reversible visual impairment.  
Associated ophthalmoplegia results in an inability to consistently utilize the fovea, and so in many cases 

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magnification is useful.  In bilateral 3rd nerve palsy, for example, the eye is frequently permanently 
abducted 30° or more, so even if the lids are opened common low vision rehabilitation interventions are 
needed.  A similar but usually less severe situation exists in poorly controlled myasthenia gravis.  When 
ptosis is subtotal but severe, patients are symptomatic of constricted visual field reporting problems 
with mobility and inability to drive.  Inability to drive and effort of constant frontalis recruitment limits 
employability, making travel to work and sustained computer viewing very difficult.  Severe unilateral 
ptosis (CN III palsy) causes loss of binocular peripheral field (~30°), stereopsis, and binocular summation 
(which is often problematic at night or other dim environments).  All levels of ptosis have negative social 
and cosmetic impacts which are likely to affect employment and social well-being.   
Common surgical treatments - The most common method currently used to correct ptosis involves 
surgical tightening of the levator muscle, or in more severe cases, frontalis sling.[1]  While these 
procedures are a mainstay of treatment, in our experience they have disadvantages in that they do not 
always restore normal blink function and over-correction may result in exposure keratitis.  In severe 
cases of ptosis a conservative approach is needed leaving the ptosis under-corrected, and so even 
surgical candidates may benefit from magnetic correction.    
An effective easily adjustable and/or non-surgical treatment is needed - Substantially less attention 
has been given to non-surgical approaches for ptosis, which has led to lack of effective options during 
the early recovery period from neurological etiologies, in cases with daily variability in the ptosis such as 
Myasthenia Gravis, or other cases where surgery is contraindicated.  Ability for the patient to easily 
adjust the correction as the ptosis varies would be advantageous whether it were applied surgically or 
not.      
Limitations of available temporary treatments - We believe that available temporary or non-surgical 
treatments are ineffective and even contraindicated for many target populations. These include taping 
the lid(s) open and propping the lid open with a wire on the glasses (ptosis crutch).[4]  Unfortunately 
there is a paucity of data on safety or efficacy of the ptosis crutch or taping. The crutch has to be 
continually adjusted to keep the lid elevated, does not allow a complete blink,[5]  and poses a risk for 
ocular injury during adjustment or should the patient fall. We have frequently encountered use of skin 
tape to elevate the eye lid, but this has potentially damaging effects on the ocular surface from 
incomplete eye closure. 
Static magnets could provide force to elevate the eyelid while still allowing eye closure - In most types 
of ptosis, while opening of the eyelid is impaired, the neuromuscular complex for eye closure 
(Orbicularis oculi muscle/cranial nerve (CN) VII) is intact. [1]  In these cases the ptosis might be alleviated 
using a permanent static magnet system to provide the force to elevate the upper eyelid.[6]  The static 
force exerted by the permanent magnet to open the eyelid should be easily overcome by the Orbicularis 
Oculi muscle, assuming the force of the magnet is not too great, reanimating the blink.  This approach 
utilizes well-understood, widely available and inexpensive static magnetic materials.  Electromagnets 

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might seem like an attractive option for the ability to modulate force; however, they generate heat and 
would consume too much energy to be feasible for continuous use.  We had also considered electrical 
stimulation of the levator muscle; however, our mentors who have investigated the possibility of this 
approach previously indicated that repeated stimulation externally on the skin is painful in addition to 
difficulty accessing the levator non-surgically via this technique.      
Prior attempts to use magnets for ptosis - The concept of correcting ptosis with magnetic force was first 
presented in the 1970’s.[6]  Conway described attaching Mu-metal 13 x 4 x 0.5 mm to the upper lid in 3 
patients (attached with eyelash adhesive or blenderm tape), and a small bar magnet to the spectacles.  
Specifications of the ferrite spectacle magnet were not provided; however, we measured them in the 
photos to be ~20 x 5 x 10mm.  Conway’s photographs showed elevation of the eyelid when the lid and 
spectacle magnet were in contact; however, the ferrite magnet/Mu-metal would not have generated 
enough force to elevate the lid from the closed position, where there is typically 15 to 20mm 
separation.[5]  As a result the magnet glasses would have needed frequent adjustment to bring the 
materials back into direct contact after each blink offering no substantial benefit over the long available 
ptosis crutch.  It is therefore not surprising that the treatment was never commercialized.  Since 
Conway’s report, we find no publications on the use of magnets for ptosis, although they have been 
attempted for lagophthalmos via surgical implantation with only limited success.[7-10]  Problems 
related to surgical implantation highlight the benefit of first refining the approach non-surgically.  Static 
magnets are also better suited for ptosis as compared to lagophthalmos, because of the relative 
strength of the orbicularis compared to the levator.     
 
2.2 
RATIONALE  
We recently described a novel non-surgical magnetic eyewear device referred to as the Magnetic 
Levator Prosthesis (MLP) that restored blinking in patients with severe paralytic ptosis.[5, 17-19] The 
force to lift the lid was produced by a static Neodymium magnet embedded in a glasses frame and a 
polymer embedded (PDMS) micro-magnet array fitted externally to the upper lid with Tegaderm IV 
securement film (Fig 1).  The Tegaderm is FDA approved for extended wear on the skin and even as an 
eye covering.  It generated a strong bond, keeping the magnetic array affixed to the eye lid skin for a 
mean of 6 ± 4 days with good patient reported comfort when used for 2 hours per day during 
rehabilitation therapies. 
  Translational Promise – This proposed research to further improve the approach and confirm safety, 
feasibility, and relative efficacy for chronic management of ptosis is needed prior to commercialization.  
The aims of the proposed study target the clinical population of the PI who specializes in low vision 
rehabilitation with subspecialty in neurological visual impairments.  This is a large and underserved 
patient population which includes many individuals with recent neurological pathology, many of whom 

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are residing in inpatient rehabilitation facilities (IRF). IRFs provide 24 hour medical supervision and 
rehabilitation therapies to patients who are medically stable and are able to participate in a minimum of 
3 hours/day of therapy. There are 1,165 IRFs in the U.S.[20]  with an average length of stay of 16 
days.[21] If we conservatively estimate an average of 50 beds per 1,165 IRFs revolving every 16 days 
there should be approximately 1.2 million admissions and discharges per year in IRFs nationwide. Of 
that population, ~32% are recovering from stroke and 6% from traumatic brain injury.[21] Prevalence of 
CN III palsy in stroke populations has been reported at 2.5%,[22] and 4.4% in TBI (internal data).  
Therefore, the estimated national target population for temporary management of severe ptosis in IRFs 
alone is 12,000 patients annually.  In our IRF, internal review found a rate of 24 cases of severe ptosis in 
2015-2016.  No one stands to directly and immediately benefit more from this technology than patients 
with severe bilateral ptosis.  While this is presumed to be a rare situation we have encountered 8 such 
patients in the past 2 years without any active recruiting effort.  We have also encountered multiple 
patients with severe unilateral ptosis obscuring the vision in their better eye for whom surgery was 
contraindicated.  There is no available option for these patients other than taping the lids open or the 
ptosis crutch with the aforementioned problems with these approaches.     
Scientific Premise:  In summary, premise for the proposed work is that ptosis is a major public health 
concern which to this point has received less attention than it’s lagophthalmos counterpart despite the 
fact that it causes similar discomfort and disability (but without the extreme consequence of exposure 
and scarring).  Better non-surgical options are needed.  Weaknesses in prior work in the field concerning 
magnetic correction included use of ferrite magnets, inadequate adhesion methods for external 
placement, moving too soon to surgical implantation, and lack of evidence from randomized controlled 
trials to guide clinical approaches.  We will fill a significant gap in the field in terms of non-surgical 
correction while not excluding use of data and methodology to advance success with surgical 
implantation.    
 
 
2.3 
POTENTIAL RISKS AND BENEFITS  
 
2.3.1 KNOWN POTENTIAL RISKS  
Risk 1:  Dryness or sorness in the eye or on the lid skin from prolonged use of the MLP has been 
reported a prior study of the MLP (Singh et. al 2016).  In that study (n = 6), “total usage time was 32 
weeks, 3 weeks, 1 week, 8 weeks, 2 weeks, and 2 weeks, in each patient respectively.  The average wear 
time of the device was 5 (±2) hrs/d. Patients 1,2,4,5-6 continued to use the device at the end of the study 
period while P3 recovered negating further need.  There were no adverse events (as predefined). Mild 
(2/10) skin irritation and worsening in superficial inferior corneal staining (from 0 to 2) occurred in P1’s 

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first week after 8 hrs/d of wear.  Reducing wear time to 4 hrs/d and starting artificial tears every 4 hrs 
reversed SPK & prevented further complications.”    
Singh NK, Paschalis EI, Tomasi M, Rizzo JF, Houston KE. The boston blink-netic project: preliminary 
outpatient feasibility results (abstract). Optom Vis Sci 2016;93: E-abstract 16118. 
There have not been any cases of irreversible damage to the ocular surface occurring during use of the 
MLP and this would be extremely unlikely because the MLP is easily disengaged by removing the glasses 
and the lid magnet is easily removed with nylon tweezers.  We include the remote possibility of 
irreversible effects of extended exposure in the consent materials, which is meant to refer to any 
permanent ocular surface manifestation that may result from exposure ranging from minor dry 
sensation to scarring of the cornea.   
 
Risk 2, reduced blink reflex:  If the fitting of the MLP is not ideal, it is possible that participants (children 
and adults) would experience slowed or incomplete blink reflex.  There is the potential that this could 
cause reversible ocular surface drying and discomfort.  Participants, parents, and involved caregivers will 
be given specific instruction on how identify problems and when to remove the MLP.  To summarize, 
they will be instructed to ask themselves at regular intervals “what is my level of comfort on a scale of 1-
10” and if it is lower than 5 to remove the MLP and contact the study staff to schedule a visit to 
investigate.   
IT IS ALSO POSSIBLE THAT A REDUCED BLINK REFLEX COULD ELEVATE THE RISK OF 
FOREIGN BODY IN THE CASE OF PROJECTILES.  ALL PARTICIPANTS WILL BE FITTED WITH 
SAFETY GRADE OR POLYCARBONATE LENSES, IN THEIR PRESCRIPTION (OR NON-
PRESCRIPTION PLANO IF THEY REQUIRE NONE).  PARTICIPANTS WILL BE INSTRUCTED TO 
WEAR ADDITIONAL PROTECTIVE EYEWEAR AND TO AVOID PLACES LIKE MACHINE SHOPS 
WHERE THERE COULD BE METAL SHAVINGS.  THE LID MAGNETS ARE NOT STRONG ENOUGH 
TO PROPEL A MAGNETIC/METAL OBJECT TOWARDS THE EYE AND THE MAGNETS SHOULD 
ACTUALLY REDUCE THE RISK FOR METALLIC FOREIGN BODY PROJECTILE ENTERING THE EYE 
BY REDIRECTING IT TOWARDS THE SPECTACLE MAGNET; HOWEVER, THERE IS RISK THAT 
METAL SHAVINGS COULD ACCUMULATE AROUND THE MAGNETS IF THE DEVICE IS USED IN 
A SITUATION SUCH AS A WORKSHOP WHERE SHAVINGS ARE PRESENT.  WHILE THESE 
WOULD NOT BE PROJECTED INTO THE EYE, MINOR INJURY MAY RESULT IF THE SHAVINGS 
GET AROUND THE EYE AND THEN ARE RUBBED INTO OR SPRINKLE INTO THE EYE(S).  
STANDARD SAFETY GOGGLES WILL FIT OVER THE SPECTACLES AND PARTICIPANTS WILL BE 
INFORMED THAT THEY SHOULD BE WORN AS THEY NORMALLY WOULD.  2.3.2
 
KNOWN POTENTIAL BENEFITS  
Possible treatment for restoration of eyelid motility in subjects who wear the device comfortably.  

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3 
OBJECTIVES AND PURPOSE 
To improve the magnetic levator prosthesis (MLP) by development and testing of a novel adjustable 
force system. If endpoints are met and the device is determined to be feasible the study will continue to 
a randomized clinical trial comparing the MLP against the predicate treatment of taping the lids (future 
IRB application). 
4 
STUDY DESIGN AND ENDPOINTS 
 
4.1 
DESCRIPTION OF THE STUDY DESIGN 
A blinded study to perform measurements and experiments to improve the magnetic levator prosthesis 
(MLP) including the development and testing of a novel adjustable force system. 
4.2.1 PRIMARY ENDPOINTS 
Completion of the 2 visit protocol with acquisition of interpalpebral fissue height during resting open 
without the MLP, and with the MLP over 5 adjustable force levels.   
5 
STUDY ENROLLMENT AND WITHDRAWAL 
 
5.1 
PARTICIPANT INCLUSION CRITERIA 
1.  Presence of Blepharoptosis for at least one eye which occludes the visual axis in the resting state (no 
frontalis drive), 2.  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. 3.  Age 5 or older.   
5.2 
PARTICIPANT EXCLUSION CRITERIA 
 1.  Absence of ptosis which occludes the visual axis or presence of a corneal ulcer of any size.  2.  Age 
less than 5, Severe Cognitive impairment defined as MMSE score <18, behaviors consistent with delirium 
(combinations of disorientation, hallucinations, delusions, and incoherent speech), or lethargy. 
5.3 
STRATEGIES FOR RECRUITMENT AND RETENTION 
The aims of the proposed study target the clinical population of the PI who specializes in low vision 
rehabilitation with subspecialty in neurological visual impairments.   
5.4 
PARTICIPANT WITHDRAWAL OR TERMINATION 
 
5.4.1 REASONS FOR WITHDRAWAL OR TERMINATION 

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Subjects have a right to withdraw from the study at any time. Additionally, the subject may be 
withdrawn from the study for any reasons: if it is in the best interest of the subject, intercurrent illness, 
adverse events, or worsening condition.  The site investigators may request the withdrawal of a subject 
because of protocol violations, administrative reasons, or any other valid and ethical reasons.   
Reasons for subject discontinuation may include, but are not limited to, the following: 
• 
Investigator determination that it is not in the best interest of the subject to continue 
participation 
• 
Serious adverse events 
• 
Any other safety concerns 
 
5.4.2 HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION 
If a participant needs to withdraw early, they will be asked to accept a final telephone call at the end of 
the study to confirm vital status.  Participants who are withdrawn due to an adverse event, serious or 
not, will be followed until the resolution of the event.   
 
5.5 
PREMATURE TERMINATION OR SUSPENSION OF STUDY 
If the study is terminated or suspended prematurely, all enrolled participants will be notified and asked 
to attend a final safety visit.  If there are participants with ongoing adverse events at the time of 
premature termination those participants will be followed until resolution of the event.   
 
6 
STUDY DEVICE 
 
6.1 
STUDY DEVICE DESCRIPTION 
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.  Tegaderm, which is essentially the same adhesive, is even FDA approved as 
an eye covering (we used Tegaderm in early studies but switched to IV 3000 for its superior ease of 
handling based on packaging technique).  It generates a strong bond, in a prior study keeping the 
magnetic array affixed to the eye lid skin for a mean of 6 ± 4 days with good participant reported 
comfort when used for 2 hours per day during rehabilitation therapies.  In order to allow doctors and 
patients to easily adjust the force of the MLP in the interest of maximizing their comfort and blink 

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quality while accommodating variability in ptosis or lid magnet positioning, we propose to further 
develop and test a novel approach where the force is adjusted by manually rotating the spectacle 
magnet with a small dial on the side of the spectacle frame.  The MLP is FDA exempt as a Class 1 Device.  
An Investigational Device Exemption (IDE) application was not required in prior studies approved by the 
MEEI IRB HSC and should not be required in order to carry out this study.  MLP status as a device was 
reviewed extensively by Leila Foster and her team as well as by legal (Maureen Kelley), last reviewed in 
fall 2017.    
6.1.1 ACQUISITION 
Magnets will be acquired from SM Magnetics, Pelham AL or similar supplier.  PDMS supplies will be 
acquired from Fisher Scientific.  Frame supplies will be acquired from Designs For Vision Rokokam, NY , 
Michelle Moretti Eyeware and Skelmet, Boston MA. 
6.1.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Arrays will be labeled with lot and batch numbers.   
6.1.3 PRODUCT STORAGE AND STABILITY 
Only the arrays have an expiration date.  Neodymium magnets are highly stable and resistant to 
demagnetization.  The spectacle magnets will have an expiration of 5 years.  The PDMS arrays will have 
an expiration of 1 year.  They are stored at room temperature.   
6.1.4 PREPARATION 
Magnets are prepared by the manufacturer and coated in nickel.  They will be embedded in PDMS at 
Schepens Eye Research Institute using a mold produced onsite with a 3-D printer.   
6.1.9 DURATION OF THERAPY 
see other sections 
6.1.11 DEVICE SPECIFIC CONSIDERATIONS 
 The MLP is FDA exempt as a Class 1 Device and therefore an Investigational Device Exemption (IDE) 
application was not required in prior studies approved by the MEEI IRB HSC and should not required in 
order to carry out this study.  MLP status as a device was reviewed extensively in the fall of 2017 by Leila 
Foster and her team as well as by legal (Maureen Kelley).  Mass Eye and Ear has submitted a patent 
application for the technology, and so status was also reviewed by Ojas Mehta and his team in the 
Intellectual Property department.        
6.2 
STUDY AGENT ACCOUNTABILITY PROCEDURES 

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The devices will be stored and dispensed from the lab offices at Schepens Eye Institute.  Logs will be 
keep by the Research Assitant to keep account of which devices where used for the specific subjects.  If 
devices are returned that will also be noted on the device logs.   
7 
STUDY PROCEDURES AND SCHEDULE 
 7.1 
STUDY PROCEDURES/EVALUATIONS 
7.1.1 STUDY SPECIFIC PROCEDURES  
A cognitive pre-screening to guide the consent process will be administered as described in section 
13.3.2. After consent, participants will have their acuity measured (refraction as needed), slit lamp with 
Nafl & NEI scale.  Next, the MLP will be placed on the patient and video recordings made for 1 minute 
(comfort monitored with a 10-point scale during this period).  Next, the effect of force adjustment via 
magnet rotation on lid position will be measured.  The spectacle magnet will be rotated (settings labeled 
1-4, counterbalanced), and videos recorded for another minute at each rotational increment.  For video 
recording we will have 2 cameras: 1 straight on and the other angled up (to capture upper lid apposition 
to globe, Fig 5d&e).  Recording will be done with a blue filter and NaFl to simultaneously document tear 
film.  Additional NaFl will be added over the trial at the clinical staff discretion as needed. Once optimal 
rotational increment is found, a 20 minute trial at that setting will be performed with repeat of video 
recording with comfort and efficacy scale.  Afterwards, the array will be removed and an array with the 
alternative polarization will be applied.  We will then record for 1 min getting comfort and efficacy data 
and repeating the rotation experiment followed by another 20-minute trial.  At the end of the study visit 
we will repeat visual acuity, slit lamp with Nafl & NEI cornea scale, and video recordings with comfort 
scale will be repeated.  As this is a fitting and optimization process, it is possible that additional visits will 
be necessary in order to make modifications, but these will be optional.   
7.3 
STUDY SCHEDULE 
 
7.3.1 SCREENING 
 Pre-Screening:  In order to guide the consent/assent process, the approved study staff will administer a 
pre-consent cognitive screening using the Mini-Mental State Exam (MMSE).  If score is 18-23 (maximum 
of 30) representing mild cognitive impairment (Tomburgh et al 1992), candidates will be asked return 
with a caregiver (if one is not present).  If score is <18, they will not be eligible.  Screening/Study Intake:  
Participants will have their acuity measured (refraction as needed), slit lamp with Nafl & NEI scale.  
Inclusion Criteria:  Presence of Blepharoptosis for at least one eye which occludes the visual axis in the 
resting state (no frontalis drive), 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, age 5 or older.  Exclusion Criteria:  
Absence of ptosis which occludes the visual axis or presence of a corneal ulcer of any size.  Age less than 
5, Severe Cognitive impairment defined as MMSE score <18, behaviors consistent with delirium 
(combinations of disorientation, hallucinations, delusions, and incoherent speech), or lethargy.  These 
individuals must be excluded since participation requires competent self-care, reliable responses and 

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cooperation during fitting of the device.  Children need to be included because they represent an 
important target population (pediatric neuro-muscular conditions), and because facial structure and skin 
characteristics may result in a different response than adults   
 
7.3.2 
Enrollment/Baseline 
See 7.1.1 above7.3.3 
 
 
7.3.3 Follow-up 
 See 7.1.1 above 
7.3.4 FINAL STUDY VISIT 
At the final study visit a clinical decision will be made as to whether or not the MLP is recommended for 
continued use, and which version of the device was best.  Because the MLP is not regulated by the FDA 
as a spectacle device (similar to low vision aids), and because there is no comparable alternative for 
non-surgical management, participant will be allowed to take the MLP and continue wearing it, and 
transferred to the clinical practice of the PI.   
7.3.5 EARLY TERMINATION VISIT 
  In the event a participant is terminated from the study due to an Adverse Event, the study PI will follow 
the participant for at least 30 days after termination to confirm the event has resolved or the patient is 
receiving appropriate treatment.  
7.3.7 SCHEDULE OF EVENTS TABLE 
 
Procedures 
VISIT 1 (ASSESSMENTS 
WILL BE REPEATED IF 
PARTICIPANT AGREES ) 
Visit 2 (1 week +/-2 days 
Visit 1 assessments will 
be repeated if 
participatne agrees and 
and the clinical staff will 
determine if this is 
clinically appropriate  
Follow Up Phone Call 
 
X 
Visual Acuity (refraction if needed) 
X 
X 
Slit Lamp Exam 
X 
X 
NEI corneal staining scale 
X 
X 
 
 
 
Baseline Video Recording 
X 
X 
Eye Lid Prep 
X 
 

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Procedures 
VISIT 1 (ASSESSMENTS 
WILL BE REPEATED IF 
PARTICIPANT AGREES ) 
Visit 2 (1 week +/-2 days 
Visit 1 assessments will 
be repeated if 
participatne agrees and 
and the clinical staff will 
determine if this is 
clinically appropriate  
Measurement of force to open the 
ptotic lid 
X 
 
 Polarity experiment, case 1 (apply lid 
magnet array) 
X 
 
Video recording 
X 
X 
10 point comfort and efficacy scale 
X 
X 
spectacle magnet rotation experiment 
X 
 
20 minute trial at optimum rotation 
X 
 
Repeat Video Recording 
X 
 
Repeat 10 point comfort and efficacy 
scale  
X 
 
Polarity experiment, case 2 (apply lid 
magnet array) 
X 
 
spectacle magnet rotation experiment 
X 
 
20 minute trial at optimum rotation 
X 
 
Video recording 
X 
 
10 Point Comfort and Efficacy Scale 
 
X 
Repeat visual acuity 
X 
 
Repeat Slit Lamp Exam 
X 
 
Repeat NEI Nafl scale 
X 
 
Clinical Decision 
 
X 
<Insert text> 
7.5 
CONCOMITANT MEDICATIONS, TREATMENTS, AND PROCEDURES  
 
Oral and ophthalmic concomitant medications will be reviewed and recorded to confirm the patient 
does not have any systemic disease that would interfere with the study assessments and or data. 
7.5.1 PRECAUTIONARY MEDICATIONS, TREATMENTS, AND PROCEDURES 
none 

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7.6 
PROHIBITED MEDICATIONS, TREATMENTS, AND PROCEDURES  
Ophthalmic ointment or skin ointment applied near the eyes interferes with adhesion of the lid magnet 
and will need to be discontinued at least 1 day prior to the study.  Patients may continue with artificial 
tears.     
7.9 
PARTICIPANT ACCESS TO STUDY AGENT AT STUDY CLOSURE  
Because the MLP is not regulated by the FDA as a spectacle device (similar to low vision aids), and 
because there is no comparable alternative for non-surgical management, participants will be allowed to 
take the MLP and continue wearing it after completion of the study.  MEEI has already approved 
provision of the MLP to non-research subject patients under the Humanitarian Devices rules.  
8 
ASSESSMENT OF SAFETY 
 
8.1 
SPECIFICATION OF SAFETY PARAMETERS 
The safety of the study device will be evaluated at every visit following the enrollment visit and will be 
defined by the incidence of related adverse events. Specifically, we will evaluate:  
• 
Systemic safety: Incidence and severity of systemic adverse events during the study (adverse 
events spontaneously reported or observed by the Research Assistant).  
• 
Ocular safety: Incidence and severity of ocular adverse events during the study (ophthalmic 
examination, adverse events spontaneously reported).  
• 
SAFETY CUTOFFS:  Should visual acuity decrease more than 2 lines, worsening of corneal rating 
of more than 1.5 points or other ocular surface ratings more than 2 points, and comfort rating 
lower than 5/10; study activities will cease for at least 1 week and an adverse event report to 
the IRB.  Serious adverse events which will result in immediate dismissal from the study (and 
treatment) include: 1) development of a corneal epithelial defect or infiltrate without 
epithelial defect or 2) broken skin on the eyelid.   
 
8.1.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse Event (AE): Any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the subject’s participation in the research, whether or not considered 
related to the subject’s participation in the research.  
 

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8.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE) 
Serious Adverse Event (SAE): Any event temporally associated with the subject’s participation in 
research that meets any of the following criteria:  
• 
Results in death  
• 
Is life threatening  
• 
Requires hospitalization/prolongation of hospitalization  
• 
Results in congenital anomaly  
• 
Results in persistent or significant disability/incapacity  
• 
Required intervention to prevent permanent impairment/damage  
 
8.1.3 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
Any incident, experience, or outcome (including data loss) that is unexpected (in terms of nature, 
severity, or frequency) given (a) the research procedures described in the protocol and the 
characteristics of the subject population being studied. Unanticipated problems may include protocol 
deviations that are not adverse events 
8.2 
CLASSIFICATION OF AN ADVERSE EVENT 
The Investigator will promptly review documented adverse events and abnormal findings to determine 
1) if the abnormal finding should be classified as an adverse event: 2) if there is a reasonable possibility 
that the adverse event was caused by the study device(s); and 3) if the adverse event meets the criteria 
for a serious adverse event. 
 
8.2.2 RELATIONSHIP TO STUDY DEVICE 
If an adverse event or serious adverse event is recorded the study PI will determine the relationship to 
the study device.   
8.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
Adverse events or abnormal findings thought to be associated with the study device will be followed 
until the event (or its sequel) or the abnormal finding resolves or stabilizes at a level acceptable to the 
Investigator.  Events that have not resolved or stabilized will be followed for 30 days post study 
completion. Subjects will be encouraged to follow up with their physician for the treatment of any 
events beyond 30 days post study completion. 

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8.4 
REPORTING PROCEDURES 
 
8.4.1 ADVERSE EVENT REPORTING  
All adverse events will be reviewed by the principal investigator within 24 hours of notification and 
reported to the Mass Eye and Ear IRB on the following schedule: 
• 
Possibly, Probably, or Definitely Related Expected AE – Report to IRB on annual basis 
• 
Possibly, Probably, or Definitely Related Expected Serious AE – Report to IRB on annual basis 
• 
Possibly, Probably, or Definitely Related Unexpected AE – Report to IRB within 30 days of event 
• 
Possibly, Probably, or Definitely Related Unanticipated Problem – Report to IRB within 7 days of 
event (24 hours for death of data loss) 
• 
Possibly, Probably, or Definitely Related Unexpected Serious AE – Report to IRB within 7 days of 
event 
 
8.4.2 SERIOUS ADVERSE EVENT REPORTING  
Any adverse events that are serious, unexpected and related or possibly related to the study will be 
reported to the Mass Eye and Ear IRB within 7 calendar days from the time the PI becomes aware of the 
event.  
Any unexpected and study-related death will be reported to the Mass Eye and Ear IRB within 24 hours of 
the PI’s knowledge of the event by e-mail or telephone.  
 
8.4.3 UNANTICIPATED PROBLEM REPORTING  
All UAPs involving risks to subjects or others will be reported in writing to the Mass Eye and Ear IRB 
within 7 calendar days from the time the PI becomes aware of the event. If a UAP or an unexpected SAE 
results in a subject’s death or was potentially life-threatening, the PI will notify the Mass Eye and Ear IRB 
through e-mail or phone within 24 hours from the time the event is identified. A follow-up report will be 
submitted if applicable, at a later date when more information is available.  For UAPs that result in data 
loss the PI will notify the Mass Eye and Ear IRB through e-mail or phone within 24 hours from the time 
the UAP is identified.   

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10 
STATISTICAL CONSIDERATIONS  
 
10.1 
STATISTICAL AND ANALYTICAL PLANS 
Statistical Analysis:   
Primary Outcome:  The effect of angular position on interpalpebral fissure during the resting open phase 
will be modeled using linear mixed-effects (multiple regression) models. The five angular (rotation) 
angles will be randomly mapped over the arbitrary labels of 1 to 5 to mask the participant and study 
staff and treated as categorical variables.  Because repeated measurements will be performed on each 
eye and each participant might respond differently to each angular position, participant and angular 
position within participant-eye will be included as random effects.  Demographic covariates, such as age 
and gender, will be evaluated to determine if they have a meaningful effect on interpalpebral fissure or 
comfort. 
Sample Size Calculation:  Data was originally not available to perform a sample size calculation for the 
mixed effects analysis.  Instead we categorized the data for success versus failure defined as a clinically 
meaningful change of >1mm in interpalpebral fissure across the range of rotation forces.  Based on this 
it was estimated that with 30 subjects we will have 80% power to show that the success rate 
significantly exceeds 50% with a one-sided alpha=0.025 exact binomial test of one proportion if the true 
success rate is 75% or greater.  Therefore we originally aimed to enroll 30 subjects.  Interim analysis was 
conducted after 11 subjects were enrolled and sample size calculation was adjusted down to 19 
subjects.    
 
10.4 
DESCRIPTION OF STATISTICAL METHODS 
 
10.4.1 GENERAL APPROACH 
Linear mixed-effects will be used for the primary outcome.  
10.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
Analyses will be performed by the study staff using statistical software (STATA 14 or similar).  Primary 
outcome is the change in interpalpebral fissure with versus without MLP, and change in interpalpebral 
fissure across the 5 rotation angles.   
10.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 

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The effect of the five angular (rotation) angles on interpalpebral fissure during the spontaneous blink 
will be modeled using linear mixed-effects model, identical to that described for the primary outcome.  
Dependent variable will be the measured interpalpebral fissure during the 3 minima of each 
spontaneous blink event.   
The effect of MLP compared to baseline without device will be modeled with another linear mixed 
effects model.    
To model comfort level, we will treat the reported Likert-type data as interval data and use a linear 
mixed-effect model with angular position number as the fixed effect and participant and angular 
position number within participant-eye as random effects.  
To statistically determine whether there are between-participant differences in response to angular 
position, we will employ profile analysis which is a multivariate statistical technique that uses multiple 
analyses of variance for repeated measures to test piecewise parallelism.  
 
10.4.4 SAFETY ANALYSES 
Clinical study staff will acquire high resolution magnified images of the ocular surface and eyelid skin 
which will bereviewed by the PI and his study team weekly during project meetings.  On-site monitoring 
of participant safety will be utilized by the PI or other study personnel.  This is appropriate since 
problems can be immediately detected and addressed by research staff experienced in examination of 
the eye.  A monitoring log of expected and unexpected events will be kept.  Events will be documented 
on paper and sent to the PI (if he is not the one examining the participant) who will place a follow-up 
call to the participant that day and the next day as needed.  Paper documentation will be kept in the 
study binder and then transferred to a worksheet in the study master spreadsheet.  Non-compliance 
with protocol (e.g. failure to use the study checklist or properly document or report in a timely manner 
adverse events) will be documented.  Once identified, minor issues will be addressed by the PI by special 
meeting or at weekly study meetings.  Special meetings will be called depending on the seriousness of 
the issue.  Repeated offenses will result in removal of that study staff from the protocol. Adverse events 
will be documented and reported to the IRB and NEI per protocol.  
  
10.4.5 ADHERENCE AND RETENTION ANALYSES 
DATA SUMMARIES WILL BE PRODUCED (INCLUDING DATA ON SUBJECT ENROLLMENT, 
WITHDRAWALS, PRIMARY OUTCOME MEASURES, AND ANY SAFETY ISSUES) ON A PERIODIC 
BASIS AND REVIEWED BY THE PI AND OTHER STUDY PERSONNEL. 
 
10.4.6  BASELINE DESCRIPTIVE STATISTICS 
 

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10.4.7 PLANNED INTERIM ANALYSES  
Conduct after 11 subjects are enrolled. 
 
10.4.7.1 
SAFETY REVIEW 
The summaries will be reviewed by an internal committee comprising the PI and members of the 
research team to monitor data quality, study progress and determine whether the study should change 
in any way or be stopped. Serious (expected or unexpected) adverse events will be reported 
immediately to the PI (by a subject or member of the research team).  
Minor adverse events (e.g. mild discomfort of the lids) will be recorded on a subject’s data sheet at the 
time of occurrence; they will subsequently be reported  internally for that study.  Minor adverse events 
will also be reported on an annual basis to the relevant IRB committees, as part of the annual IRB review 
of each approved study. 
10.4.7.2 
EFFICACY REVIEW 
Preliminary data analyses will occur periodically.   
10.4.8 ADDITIONAL SUB-GROUP ANALYSES 
Subgroup analysis is not part of the analysis plan 
10.4.9 MULTIPLE COMPARISON/MULTIPLICITY 
P-values used to indicate significance will be corrected where appropriate.   
10.4.10 
TABULATION OF INDIVIDUAL RESPONSE DATA 
Individual response data will be recorded on data sheets and input into Excel spreadsheets. 
10.4.11 
EXPLORATORY ANALYSES 
 No exploratory analyses are planned. 
10.5 
SAMPLE SIZE 
19 subjects will be enrolled into this study. 
10.6 
MEASURES TO MINIMIZE BIAS 
 
10.6.1 MASKING PROCEDURES 

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Only masked/blinded clinical staff will apply the lid magnets polarized either through thickness or 
through height (counterbalanced) to the study subjects.   
10.6.3 BREAKING THE STUDY BLIND/PARTICIPANT CODE 
The PI will determine if for safety reasons, the study staff needs to be unblinded on a subject by subject 
basis and/or during a specific study visit  
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Data collection sheets will be completed for each subject enrolled into the clinical study.  Data Collection 
sheets will be study visit specific and the PI will review, approve and sign/date each subject visit. 
Investigator’s signature or record locking serving as attestation of the responsibility for ensuring that all 
clinical data entered on the data collection sheets are complete, accurate and authentic.   
All computer generated data will be stored on internal MEEI servers located on encrypted, password 
protected MEEI computers. Only the PI and researchers specific to this study who have been granted 
access to the data by the PI will be able to view the data in the MEEI network protected folder. If data is 
sent out to be analyzed the data will be de-identified. The data will contain subject identification 
numbers, which are linked to identifiers on a separately secured spreadsheet. The data will be coded by 
assigning each participant a subject identification number and removing any identifiable information. 
The code will be secured by the PI and Study staff in the drive located on encrypted, password protected 
computers at Schepens. The code that links information that can identify the participant to the data 
collected for this research will be kept separate from their health information, which will be destroyed 
once this study is complete and the manuscript has been published. 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
The Principal Investigator will be responsible for quality assurance during this study.  The Principal 
Investigator will confirm that the study device is stored correctly.  The Principle Investigator will also 
train study staff on the protocol procedures and will confirm staff can confidently complete the study 
related assessments.   
 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS  
 
13.1 
ETHICAL STANDARD  

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All staff designated to work on this trial will have CITI certification for confirmation of GCP training and 
their CV’s, licenses and other forms of certifications related to conducting research will be kept with the 
study regulatory binder. 
 
13.2 
INSTITUTIONAL REVIEW BOARD  
The IRB of record for this study will be the MEEI review board, The Human Research Protections 
Program.  The protocol will be approved by the HRPP office prior to subject enrollment and will be 
reviewed yearly after initial approval.  Any adverse events or serious adverse events will be reported to 
the HRPP office; however this is not expected to occur because this is a minimal risk protocol.     
 
13.3 
INFORMED CONSENT PROCESS  
Subjects are required to sign an informed consent before participating in the study. The consent will be 
signed in front of a study member (witness). The witness and investigator will sign and date the consent 
form. A note will be made on the study record that the informed consent was signed by the participant. 
The informed consent will follow the guidelines set by the MEEI IRB. A copy of the consent form will be 
given to the participant. A member of the study team will review the study procedures, visit schedule, 
risk and benefits, alternative treatments and rights to withdraw and ask questions with all potential 
subjects before signing the consent. Every participant has a right to withdraw at any time from the study 
without affecting their care or relationship with the treating physician and participating institution. The 
financial responsibilities of the participant will be discussed. All participants are required to sign a Health 
Insurance Portability and Accountability Act (HIPAA) form before participating (unless this is combined 
with the consent). A study member will explain and discuss with the participant their confidentiality 
rights as described in the HIPAA form. 
 
13.3.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
 
13.3.2 CONSENT PROCEDURES AND DOCUMENTATION 
Participants who are determined by their clinical specialist to have Blepharoptosis will 
receive a recruitment packet from the services’ administrative assistant.  If subjects are 
identified by a pre-screening (i.e. chart is prescreened and tagged by the clinical res earch 
office) and they are interested in the study they will schedule another appointment in 
the SERI vision rehab lab at 20 Staniford st.  The scheduler/study coordinator /research 
assistant will inquire about any prior diagnosis of dementia or significant cognitive 
impairment, and if so coordinate the primary caregiver to also attend the visit.  Pre -

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Screening:  Approved study staff will administer a short cognitive pre-screening (mini-
mental state exam, MMSE) to determine if there is any cognitive impairment.  The MMSE 
will not be linked to a study identifier and will be retained for aggregate analysi s only.  If 
score is <18, the individual is not eligible.  If score is 18-23, an assent process will occur, 
and consent obtained from the primary caregiver (the health care proxy (if one has been 
named), or the spouse or family member (in that order of preference)).  If the study 
candidate is a child, one parent will sign the consent and children under 14 will sign the 
assent and children over 14 and older will sign the consent (unless decisionally impaired 
as determined with the same MMSE criteria).  Dr. Houston, the PI, has approximately 5 
years experience in providing informed consent to patients with neurological disorders, 
and >10 years providing eye care for this population.  He will perform the informed 
consent in a private room at Schepens Eye Research Institute.  The study will be 
explained to the potential participant and they will be asked to read (or have read to 
them) and sign the approved informed consent (or assent) form before participation in 
the study.  Alternatives to participating will be explained.  They will be given ample 
opportunity to discuss all aspects of the study before signing the form.  A detailed 
explanation of the interventions and how they work will be given, including showing 
them the device and allowing them to ask questions.  Dr. Houston will leave the room 
allowing the prospective participant and any family members to discuss in private.  
Prospective participants will be specifically offered the opportunity to discuss the 
interventions and the study with Dr. Houston, their ophthalmologist, and family 
members/caregivers prior to consenting.  A copy of the consent form will be given to the 
participant.                                                                                                                       
13.4 
PARTICIPANT AND DATA CONFIDENTIALITY  
Safeguards will be employed to protect the confidentiality of participant data including the following:  Each 
member of the study team has completed privacy training and information security training at Mass Eye and Ear, 
paper files will be locked in cabinets when not in use, paper files will be protected from inappropriate access when 
in use, mobile computing devices and storage media will be locked in cabinets when not in use, computing devices 
will be protected from inappropriate access when in use, research data will be coded using a study identification 
number that does not include the participant’s initials and is not derived from the participant’s identifiable 
information, the key linking the study ID to the participant’s info is available only to the study team, the key will be 
stored in a locked password protected network with access limited to the study members who require access to 
this information, electronic data will be stored on folders only available to the study team.  Devices for video 
recording components of the study will be encrypted and/or password protected where possible and data will be 
promptly transferred and deleted from the device.  All video/image and other data will be de-identified prior to 
publication.  We will attempt to capture video/image data so as to only include the eyes, which will therefore not 
be identifiable.  In situations where this is not possible (ie participant moves), video/image data will be cropped to 
reduce the image to eliminate other facial features.  Audio will ultimately be removed from the video files, but 
may be needed during processing to determine if blinks are reflexive or the experimenter has asked the participant 
to volitionally blink.  De-identified cropped videos with sound removed will be published as supplementary data or 
on a public site such as YouTube, and will be used in lectures presenting results of the work.  Participants will be 
informed that their de-identified video recordings may be shared in this manner and ask to check a box on the 
consent form.  Those who decline will not be excluded from participation and this will be emphasized in the 
consent form and verbally by the PI during the consent process.         
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DATA HANDLING AND RECORD KEEPING  

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14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data management and collection will be monitored by the PI.  Study staff involved in data collection will 
maintain all training and certifications required  by the MEEI/IRB.   Paper data forms will be stored in a 
locked file cabinet in or near the PI’s office at Schepens Eye Research Institute, 20 Staniford St.  Boston 
MA, 02114.  
14.2 
STUDY RECORDS RETENTION  
IDENTIFIERS WILL BE DESTROYED AFTER PUBLICATION OF THE RESULTS.  THE PROJECTED 
TIME FRAME IS 3 YEARS FROM THE BEGINNING OF THE STUDY.  STUDY RECORDS IN 
DEIDENIFIED FORM WILL BE KEPT INDEFINITELY.   
 
14.3 
PROTOCOL DEVIATIONS  
Protocol deviations and unanticipated problems will be reported to the IRB upon knowledge of the 
occurrence.  Reporting of deviations and problems will be done following the MEEI HRPP office policy.   
14.4 
PUBLICATION AND DATA SHARING POLICY 
Study results will be published at scientific conferences and peer-reviewed journals. Study participants 
will not be identifiable by the data presented within the publications. 
 
 
16 
CONFLICT OF INTEREST POLICY 
Per MEEI Human Protection Program policy, the Principal Investigator and Sub Investigators will 
complete the MEEI IRB Conflict of Interest In Research Project Specific Discloser Forms before 
participating in the Study.   
17  
LITERATURE REFERENCES  
• Houston KE, Tomasi M, Yoon M, Paschalis EI.  A Prototype External Magnetic Eyelid 
Device for Blepharoptosis.  Translational Vision Science & Technology. 2014; 3(6):9. 
• Houston KE, Tomasi M, Yoon M, Batalha G, Paschalis EI. An external magnetic device for 
severe bilateral blepharoptosis: proof of concept (abstract). Optom Vis Sci 2015; E-abstract 
15092. 
• Lawrence G, Paschalis EI, Tomasi M, Finch N, Houston KE. A non-invasive magnetic 
system for temporary management of lagophthalmos- proof of concept (abstract). Optom 
Vis Sci 2016;93: E-abstract 16091. 

 Clinical Trial to improve the magnetic levator prosthesis (MLP) including the development and testing of a novel adjustable 
force system 
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23 
 
• Singh NK, Paschalis EI, Tomasi M, Rizzo JF, Houston KE. The boston blink-netic project: 
preliminary outpatient feasibility results (abstract). Optom Vis Sci 2016;93: E-abstract 
16118. 
• Houston KE, Pachalis EI, Angueira DC, Bronstad PM, Barrett AM, Iaccarino MA. 
Restoration of Vision After Brain Injury Using Magnet Glasses. Am J Phys Med Rehabil 
2017 Apr;96(4):e70-e74.  
• 
Houston KE, Tomasi M, Armaral C, Finch N, Yoon MK, Paschalis EI.  The Magnetic 
Levator Prosthesis for Temporary Management of Severe Blepharoptosis: Initial 
Safety and Efficacy. Transl Vis Sci Technol, 2018. 7(1): p. 7. 
 
 
 

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force system 
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APPENDIX 
 
Version 
Date 
Significant Revisions