Identification of Optimum Spectacle Prescriptions for Patients With Down Syndrome
Phase: NA
Conditions: Vision, Low
Sponsor: University of Houston

 
 
 
 
Spectacles for Patients with 
Down Syndrome 
NCT03367793 
 
Study Protocol as defined in the Data and Safety Monitoring Plan 
 
October 16, 2015 
 
 
 

5R01 EY024590-02 (Anderson, H.) 
  
DSM Plan October 16, 2015 
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Data and Safety Monitoring Plan 
 
For 
 
Identification of Optimum Spectacle Prescriptions  
for Patients with Down Syndrome 
 
 
 
 
 
 
 
 
 
 
PI: Heather A. Anderson OD, PhD 
Institution:  University of Houston 
 

5R01 EY024590-02 (Anderson, H.) 
  
DSM Plan October 16, 2015 
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Table of Contents 
Summary of the protocol .............................................................................................................................. 3 
•         Primary and secondary outcome measures................................................................................... 4 
•         Inclusion/exclusion criteria ............................................................................................................ 5 
•         Power calculation and sample size ................................................................................................ 5 
Trial Management ......................................................................................................................................... 5 
•         List of participating enrolling clinics ............................................................................................... 5 
•         Projected timetable ....................................................................................................................... 6 
•         Target population distribution (e.g, women, minorities, etc) ....................................................... 6 
Data Management and Analysis ................................................................................................................... 7 
•         Data acquisition and transmission ................................................................................................. 7 
•         Data entry methods ....................................................................................................................... 8 
•         Data analysis plan ........................................................................................................................... 8 
Quality Assurance ......................................................................................................................................... 8 
•         Procedures in place to ensure the validity and integrity of the data ............................................ 8 
•         Procedures to guarantee the accuracy and completeness of the data, during data collection, 
entry, transmission, and analysis. ............................................................................................................. 8 
•         Reporting of IRB actions to NEI ...................................................................................................... 9 
•         Report of changes or amendments to the protocol ...................................................................... 9 
•         Trial stopping rules ......................................................................................................................... 9 
•         Disclosure of any conflict of interest in the DSM ........................................................................... 9 
Trial Safety .................................................................................................................................................. 10 
•         Potential risks and benefits for participants ................................................................................ 10 
•         Collection and reporting of AEs and SAEs .................................................................................... 11 
•         Management of SAEs or other study risks ................................................................................... 11 
Trial Efficacy ................................................................................................... Error! Bookmark not defined. 
•         Are there plans for Interim Analysis of efficacy data? .................... Error! Bookmark not defined. 
DSM Plan Administration ............................................................................................................................ 11 
•         Responsibility for data and safety monitoring ............................................................................. 11 
•         Frequency of DSM ........................................................................................................................ 12 
References .................................................................................................................................................. 13 
 
 
 

5R01 EY024590-02 (Anderson, H.) 
  
DSM Plan October 16, 2015 
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Summary of the protocol 
 
•         Brief description of the protocol (Study design) 
 
The purpose of this study is to test the hypothesis that metric-derived spectacle prescriptions based on 
wavefront aberration measurements of the eyes of individuals with Down syndrome can provide an 
improvement in visual acuity over that obtained with spectacle prescriptions based on standard clinical 
prescribing techniques.  Aim 1 is designed to collect wavefront aberration measurements from a sample 
of 30 individuals with Down syndrome to refine the process of determining metric-derived spectacle 
prescriptions from wavefront data.  Up to 30 control subjects without Down syndrome will validate the 
algorithm to identify metric-derived corrections by performing visual acuity measures while viewing 
projected acuity charts simulating the retinal image quality of participants with Down syndrome.  Aim 2 
consists of a phase II clinical trial to test this hypothesis by dispensing spectacle prescriptions (1 clinically 
derived and 2 metric-derived) to participants with Down syndrome in random order for 2 months each.  
Aim 3 will assess the ability to predict on-eye visual acuity performance of individuals with Down 
syndrome wearing metric-derived spectacles by comparing visual acuity measures obtained from 5 
control observers without Down syndrome viewing charts simulating retinal image quality of individuals 
with Down syndrome to actual acuity measures obtained from participants with Down syndrome during 
Aim 2.  In addition to these 3 aims, a pilot study will be included to validate the use of a temperature 
sensor data logger to monitor spectacle wear time, a device that will be utilized during the Aim 2 clinical 
trial.  This DSM Plan is written in reference to Aim 2.  
 
A clinical examiner (who will later serve as the masked examiner) will first perform a complete eye 
examination on participants with Down syndrome to include presenting distance and near visual acuity, 
measures of binocular function (depth perception, eye alignment), and pupil size measurements with an 
infrared camera in both normal and dim room illumination. The examiner will use any clinical techniques 
indicated to determine what she believes to be the best clinical refraction for each individual 
participant. This may include the prescription of a bifocal, given evidence that the majority of individuals 
with DS do not have adequate accommodation (Anderson, 2011; Cregg, 2001; Woodhouse, 1993) and 
may benefit from bifocal prescriptions (Nandakumar, 2010; Stewart, 2005). Participants will then select 
frames for their new spectacle prescriptions from the University Optical Services.  Throughout the 
examination, the parent/guardian of each participant will complete the Vineland Behavioral Assessment 
survey about the participant’s adaptive abilities.  In the case of participants who have self-consented 
due to the lack of a parent/legal guardian (e.g. the individual is their own legal representative), the 
participant will be asked to identify an individual who knows them well and interacts with them on a 
routine basis, preferably a family member, to attend a study visit to complete the survey.  This survey 
will be scored by study personnel to assign an adapted age to the patient as an indication of their 
developmental ability.  Data will later be analyzed with this adapted age as a predictor variable to 
identify associations between acuity improvement and developmental ability. 
 
After completion of the examination, an unmasked study investigator will perform a minimum of three 
repeated, dilated wavefront measurements with the Discovery System. From these measures, 
calculations of image quality metrics will be performed within 1 week following the eye examination 
using the methodology defined previously from the work conducted in Aim 1. From this analysis, two 
alternative metric-derived prescriptions will be selected. For a metric-derived prescription to be 
considered, it must increase retinal image quality (as determined by comparison of computed metric 
values to the clinically-derived correction), and it must differ from the clinically determined prescription 
by an amount greater than the ANSI Z80.1 standards for prescription spectacle verification. 
 

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DSM Plan October 16, 2015 
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Three identical spectacle frames will be ordered, and each filled with a different prescription: 1) 
clinically derived, 2) metric-derived #1, and 3) metric-derived #2. If a bifocal was prescribed for the 
clinically derived prescription, the same add power will be included for each of the metric-derived 
corrections to maintain an equal shift in the image plane for near viewing with each prescription. 
Participants will return for a dispensing visit when the spectacles are ready.  
 
At the initial dispensing visit, an unmasked examiner will verify the power of each pair of spectacles and 
label them according to the randomization order for dispensing.  A masked examiner will then perform 
both distance and near visual acuity, as well as binocularity testing (cover test and near stereoacuity) for 
each of the three pairs of spectacles. These values will be compared to the presenting measures from 
the initial eye examination as a precaution to ensure that participants are not dispensed spectacles that 
provide worse visual function than they had when presenting to the study. Any experimental 
prescription which causes visual acuity to degrade more than 1 line from presenting acuity at either 
distance or near, depth perception to decrease more than 2 levels from presenting, or results in the 
manifestation of an eye-turn that was previously not observed, will not be dispensed to the patient. All 
remaining prescriptions (up to 3) will be dispensed to the participant one at a time in random order for 
two month wearing intervals with a SmartButton data logger placed in a mount on the temple of the 
spectacles. The data logger will provide an objective assessment of spectacle wear time for each 
prescription. The decision to select a two month wear interval was based on clinical experience related 
to patient adaptation time to new spectacle corrections, scientific evidence for perceptual adaptation 
time to previously uncorrected astigmatic refractive error (Vinas, 2012), and a desire to allow adequate 
time for assessment of the wearing profile of each individual. Although each prescription will be 
dispensed for two months, participants will be asked to return at one-month intervals to perform 
adapted visual acuity measures, download data logger readings, and complete a brief survey regarding 
their opinion of the spectacles. Monitoring patients at monthly intervals will allow us to evaluate the 
cumulative effects of spectacle correction on visual acuity and identify any treatment order effects. 
 
After completion of all spectacle prescription dispensing periods, the clinical examiner will be unmasked 
and determine, through evaluation of acuity results and consultation with the patient and their 
parent/guardian, which pair of spectacles is recommended for continued wear. Participants will be 
asked to return for one additional follow-up after 6 months additional wear of the recommended 
prescription. At the follow-up visit, visual acuity and binocularity will be measured to determine whether 
additional improvements occur with continued spectacle wear.  
•         Primary and secondary outcome measures 
 
The primary outcome measure is: 
Adapted visual acuity - compared after two months wear time for each pair of spectacles.  Visual acuity 
will be measured monocularly by a masked clinical examiner using custom chart presentation software 
in which participants read a series of three charts from 100% seeing until 5 letters are missed.  The 
average acuity of the three charts will be recorded for each eye.  ETDRS charts will be attempted first 
with HOTV charts reserved as an alternate for participants who are unable to reliably perform ETDRS 
due to cognitive limitations. 
  
Secondary outcome measures include: 
1)  Initial visual acuity – obtained by a masked examiner at the initial dispensing visit for all three 
spectacle prescriptions.  Acuity will be obtained in the manner described above prior to any adaptation 
time to the spectacles. 
 

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2)  Spectacle wear time – obtained by a temperature sensor data logger attached to the temple of each 
pair of spectacles.  Total wear time over the two month trial for each pair of spectacles will be compared 
with the interpretation that longer wear time is indicative of better visual performance, or conversely, 
short duration wear time is indicative of poorer visual performance. 
 
3)  Spectacle Assessment Survey – administered to participants after each two month wear period for 
each pair of spectacles.  The survey consists of the following questions which will be read to the 
participants who will then respond by pointing to a picture of the facial expression that corresponds to 
their opinion (5 point frown to smile scale). 
 
 
A)  Do you like wearing this pair of glasses? 
 
B)  How well do you see with this pair of glasses when looking far away? 
 
C)  How well do you see with this pair of glasses when looking up close? 
 
D)  Do you see better with these glasses than without glasses? 
 
Responses will be tallied on a scale from1 – 5 and summed for the four questions.  Larger total scores 
will indicate greater participant preference. 
 
4)  Final participant comparison of spectacles – administered at the end of all spectacle trial periods.  
The patient will be asked to compare all three pairs of spectacles and indicate which they prefer. 
•         Inclusion/exclusion criteria 
 
Inclusion critera: 
Participants must be 18 years of age or older and have a diagnosis of Down syndrome. 
 
Exclusion criteria: 
Participants cannot have nystagmus (estimated to be 5 to 17% of the population), visually significant 
media opacities (estimated to be 13% of the population), strabismic amblyopia (estimated to be 15% of 
the population), or anisometropic amblyopia (estimated to be 7% of the population) (Berk, 1996; da 
Cunha, 1996; Tsiaras, 1999). Given that these conditions often co-exist, we expect to exclude 
approximately 30% of potential participants with Down syndrome. 
•         Power calculation and sample size 
 
We will enroll 30 individuals with Down syndrome for this trial which provides us the power to detect a 
difference as small as 1.9 letters between visual acuity measures; however, we will only consider a 
difference of greater than 5 letters to be clinically meaningful given the intra-observer test-retest 
variability of visual acuity measures (Lovie-Kitchin, 2000). 
Trial Management 
•         List of participating enrolling clinics  
 
This is a single site study with all participants enrolled at the University of Houston, College of 
Optometry in Houston, TX.  An additional site, The Ohio State University College of Optometry, will be 
included for recruitment and testing for a cold weather environment to complete the pilot study (data 
logger development) listed below, but will not be involved in the Aim 2 study discussed in this DSM Plan. 

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DSM Plan October 16, 2015 
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•         Projected timetable 
 
This trial is Aim 2 of three aims that will be sequentially pursued over the course of the grant funding.  A 
projected timetable is shown below. 
 
Aims/Experiment 
9/14-
8/15 
9/15-
8/16 
9/16-
8/17 
9/17-
8/18 
9/18-
8/19 
Pilot Study - Data Logger Development 
X 
X 
 
 
 
Aim 1, Exp 1.1 – Develop Metric-Derived Correction Algorithm 
X 
X 
 
 
 
Aim 1, Exp 1.2 – Identify Most Predictive Metrics for DS Eyes 
X 
X 
 
 
 
Aim 2, Exp 2.1 – Treatment Trial Part 1: Initial Acuity Outcome 
 
 
X 
X 
 
Aim 2, Exp 2.2 – Treatment Trial Part 2: Adapted Acuity Outcome 
 
 
X 
X 
X 
Aim 3, Exp 3.1 – Control Study for Exposure to Foreign Aberrations 
 
 
 
X 
 
Aim 3, Exp 3.2 – Agreement between Predicted & Actual Acuity 
Improvement 
 
 
 
X 
X 
•         Target population distribution (e.g, women, minorities, etc) 
 
The targeted enrollment for this trial is to have an equal number of males and females and a racial 
distribution representative of the population of Houston, TX in which the research will be conducted.  
No participants will be excluded from participation based upon gender, ethnicity, or race; however, it is 
not anticipated that participants of American Indian or Native Hawaiian race will be enrolled in the study 
simply due to the small numbers of persons from these races in the population of Houston, TX.  The 
anticipated racial distribution of participants, based on the make-up of Houston, TX, is shown in the 
table below (note this only reflects anticipated enrollment for Aim 2 – the clinical trial portion of the 
grant).  We will attempt to adhere to the targeted enrollment outlined in the included table; however, 
this is a small scale study investigating a special population (participants with Down syndrome) and thus 
we will not turn away potential participants who respond to our recruitment efforts simply because of 
an effort to strictly adhere to a specific balance of gender or minority groups.  The purpose of this study 
is to investigate the use of metric-derived spectacle corrections to improve visual acuity in participants 
with Down syndrome. There is no evidence that the effectiveness of this treatment modality should be 
associated with race, ethnicity, or gender. 
 
Racial Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American Indian/Alaska Native 
0 
0 
0 
0 
0 
Asian 
1 
1 
0 
0 
2 
Native Hawaiin or Other Pacific 
Islander 
0 
0 
0 
0 
0 
Black or African American 
1 
1 
0 
0 
2 
White 
6 
6 
6 
6 
24 
More than One Race 
0 
0 
1 
1 
2 

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DSM Plan October 16, 2015 
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Total 
8 
8 
7 
7 
30 
Data Management and Analysis 
•         Data acquisition and transmission 
 
Complete Eye Examination Findings: 
Eye examination findings from the clinical masked examiner will be first documented on paper by the 
clinical examiner during the study visit.  These data will subsequently be scanned and saved with the 
participant’s unique study ID on the PI’s laboratory computer.  Data will also be entered by the clinical 
masked examiner into the University of Houston Eye Institute Electronic Medical Records system.  
Participant’s parents/guardians, or the self-consenting participant will complete a HIPAA authorization 
form prior to entry of the findings in the system.  The intent is to have clinical examination findings 
available as part of the participant’s medical records for their potential future medical care outside of 
the study. 
 
Visual acuity measures (primary and secondary outcomes): 
Visual acuity will be performed with a custom Matlab software program in which an unmasked 
examiner will key in participant responses to letter charts presented on a monitor.  Each visual acuity 
test will result in an electronic file that will be saved to the PI’s laboratory computer using the 
participant’s unique study ID. 
 
Temperature sensor data (secondary outcome): 
Temperature data indicating spectacle wear time will be recorded by a commercially available data 
logger mounted to the temples of the participant’s spectacles.  Each month, participants will return to 
the lab and the data will be extracted from the data logger into an excel file on the PI’s laboratory 
computer.  Data files will be saved by the participant’s unique study ID and the temperature data 
deleted from the sensor. 
 
Spectacle Assessment Survey: 
Participant responses to the spectacle assessment survey will be first documented on paper and later 
scanned by unmasked study personnel and saved on the PI’s laboratory computer with the 
participant’s unique study ID. 
 
Vineland Behavioral Assessment Survey: 
The participant’s parent/guardian, or other appropriate individual will complete this survey on paper 
during the initial examination visit.  The survey score sheet will then be completed by study personnel 
and all documents scanned and saved on the PI’s laboratory computer with the participant’s unique 
study ID. 
 
Any paper documents generated at study visits will be stored in the PI’s secure laboratory.  Electronic 
documents will be stored and accessed by study personnel in the PI’s secure network storage folder 
(only lab personnel accounts have access) maintained on the University of Houston College of 
Optometry server.  De-identified study data may be transmitted between lab personnel via email.  
There will be no transmission of data outside of the study team, all of whom are part of the University 
of Houston College of Optometry. 
 

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DSM Plan October 16, 2015 
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•         Data entry methods 
 
See section above (Data acquisition and transmission) regarding data entry methods. 
 
•         Data analysis plan 
 
Differences in adapted visual acuity will be compared across spectacle types for all participants using 
dependent t-tests to identify the prescription type(s) with best-adapted performance. Differences in 
initial (un-adapted) acuity will also be compared across spectacle types for all participants using 
dependent t-tests to identify the prescription type(s) with best initial performance. 
 
Survey scores and differences in wear-time as determined by analysis of the temperature sensor 
readings will be compared to identify prescription type(s) with best patient preference and wear time 
compliance. 
 
Developmental ability (as ranked by the adaptive age obtained by the Vineland survey) will be used as a 
predictor variable for comparisons of visual acuity to identify any relationship between developmental 
ability and acuity performance. 
Quality Assurance 
•         Procedures in place to ensure the validity and integrity of the data 
 
The primary outcome measure is visual acuity measured on a computer monitor.  Each week, the 
monitor brightness will be verified with a Minolta light meter and the test distance (chinrest to 
monitor) measured to ensure that these elements remain standardized across participants and study 
visits. 
 
Prior to dispensing temperature sensor data loggers to a patient, each sensor will be placed in a 
location of known temperature for 4 hours to verify that the readings are accurate and do not fluctuate 
over time. 
 
The masked clinical examiner will obtain the visual acuity and spectacle assessment survey data to 
guard against bias in the outcomes related to prescription type. 
 
•         Procedures to guarantee the accuracy and completeness of the data, 
during data collection, entry, transmission, and analysis. 
 
All study visits will be attended by a minimum of two study personnel (one masked to spectacle 
assignment and one unmasked).  The unmasked personnel will maintain a checklist of procedures to be 
performed to assure that the masked examiner completes all necessary study measures. 
 
A co-investigator who did not attend the study visit will review all data files generated from each study 
visit to ensure completeness.  Study findings that are documented on paper and scanned will ultimately 
be converted to Excel sheets for data analysis.  The co-investigator will oversee this process and check 
the transcription of data by unmasked study personnel from paper forms to Excel files for errors.  Any 

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DSM Plan October 16, 2015 
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errors, omissions, or suspected errors identified by the co-investigator will be returned to the 
unmasked study personnel for verification/reconciliation.  This process should be manageable within 
the grant team given the small number of participants (30) enrolled in the trial.  In addition, the 
primary outcome measure (visual acuity) is stored directly in a file generated by the acuity presentation 
software and requires no transcription, thus the risk of error in that study measure is very low. 
 
The study statistician will review all de-identified data for outliers and generate reports to the PI to 
verify data which fall outside of the observed trends of the group.  Data analysis will be a group effort 
between the PI, unmasked study personnel, and the statistician.  All data analysis files will be stored on 
the PI’s secure network storage folder (accessible only by study personnel) to ensure that the current 
files are centrally accessible and that multiple versions do not exist. 
•         Reporting of IRB actions to NEI 
 
The PI will annually provide the NEI with documentation of human subjects’ protocol approval by the 
University of Houston Committee for the Protection of Human Subjects.  Any actions by the UH CPHS 
against the PI or other study personnel will be reported to the NEI via the grant program officer. 
•         Report of changes or amendments to the protocol 
 
Changes and amendments to this protocol will be reported to the NEI via the grant program officer. 
•         Trial stopping rules 
 
This trial is anticipated to be conducted over the course of 3 years, enrolling 30 participants for 1 year 
total follow-up each.  Over the course of the first 6 months of the trial, all participants are expected to 
receive the opportunity to wear the experimental treatment (metric-derived spectacle prescriptions) – 
the only barrier to this being the acuity and binocularity criteria that may preclude dispensing a metric-
derived prescription to a given participant (e.g. initial acuity with the metric derived prescription is too 
poor to dispense).  Given the small size of the trial, short duration, and fact that all individuals will 
receive the experimental treatment if it meets the visual acuity and binocularity criteria, it is not 
anticipated that the trial will stop prematurely.  Safeguards are already in place to ‘stop the trial’ for a 
given participant as mentioned already – metric-derived spectacles that reduced visual acuity or impair 
binocularity will not be dispensed and tested at all.  The PI will monitor the number of spectacle 
prescriptions that fail to meet the performance criteria for dispensing throughout the duration of the 
trial.  If this is found to be the case for the first 5 of 30 participants (i.e. no metric-derived prescriptions 
reach the threshold to be dispensed), then the trial will stop and the study team will re-evaluate the 
work from Aim 1 to determine whether the algorithm to identify the metric-derived spectacles is faulty.  
With regards to stopping the trial early due to an overwhelming benefit of the experimental treatment 
to the participants – given the small sample size of the study, it is not expected that such overwhelming 
evidence will exist prior to completion of the full sample.  In addition, all participants will be given the 
opportunity to evaluate the experimental treatment (if it meets initial acuity and binocularity criteria) 
and ultimately offered to keep this treatment (if it performs best of the three prescriptions), and thus 
no participant will ultimately be denied the experimental treatment if it does indeed perform best for 
them individually. 
•         Management of conflict of interest (COI) 
 
The data and safety monitoring of this trial will ultimately be the responsibility of the PI.  Any COI, by 
virtue of being the PI, in data and safety monitoring will be managed by the PI reporting directly to the 

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DSM Plan October 16, 2015 
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IRB of record and by keeping NEI fully informed.  The DSM Plan will be submitted to the IRB and any 
adverse events or unexpected problems will also be reported to the IRB.   In addition, the DSM Plan 
will be submitted to the NEI program officer for approval.  The final detailed DSM Plan will also be 
submitted via the grant signing official to NEI. The PI will also submit an annual progress report to NEI 
that includes a summary of any data and safety monitoring issues, especially those that may affect level 
of risk.  The PI will also provide NEI with IRB approvals.  
Trial Safety 
•         Potential risks and benefits for participants 
 
Potential risks: 
Risks of confidentiality will be minimized by maintaining the link between participant IDs and personally 
identifying information in the PI’s locked, limited access laboratory. All other data will be de-identified 
and stored with a unique identifier that cannot be linked back to the participant without the link 
maintained by the PI. 
 
Risks of adverse events from dilation drops will be minimized by screening the participants in advance 
for medical and ocular conditions which contraindicate the use of dilation drops.  Common side effects 
of dilation drops (Tropicamide and Phenylephrine) include blurred vision, headache, sensitivity of eyes 
to light, and stinging of the eye when the medicine is applied.  A rare side effect of dilation drops is 
acute increased intraocular pressure which can largely be avoided by pre-screening patients for 
indications of increased risk (such as slit lamp examination to identify narrow anterior chamber angles 
and measurement of pre-dilation intraocular pressure).  Any participants who do experience adverse 
events from dilation drops will receive care from one of the licensed optometrists at the College of 
Optometry, including the potential for care from the after-hours resident on-call at no cost. Risks of 
discomfort and boredom when performing the study measures will be minimized by allowing 
participants to take frequent breaks during study measurements. 
 
Risks of poor vision while wearing study spectacle prescriptions will be minimized by only dispensing 
those prescriptions which do not decrease visual acuity (greater than 1 line) or binocularity (2 level 
reduction in depth perception, or manifestation of new eye-turn) from the way participants presented 
to the study. Participants with Down syndrome are considered a vulnerable population due to their 
intellectual disability. These participants will be protected in that informed parental / guardian 
permission will be obtained first and then informed participant assent obtained. Both informed parental 
permission and informed participant assent will be required for enrollment in the study with the 
exception of individuals who do not have parents or legal guardians.  In these specific cases, individuals 
will provide informed consent after it is determined that the participant has capacity to consent by 
demonstrating comprehension of the requirements of the study and the study purpose.  The inclusion of 
participants with Down syndrome is necessary to address the problem of visual impairment in this 
specific population. Risks for this population are no greater than would be experienced from a routine 
eye examination and subsequent spectacle treatment and the findings that result from this work may 
lead to future treatment options that will directly benefit persons with Down syndrome. 
 
Potential benefits: 
Participants with Down syndrome will receive a complete eye examination, as well as up to three pairs 
of spectacles.  At the conclusion of the study, participants will be permitted to keep the pair of 
spectacles that performed the best, as well as the frames from the other two pairs.  Our hypothesis is 
that some of these spectacles may provide significant improvements in visual acuity over what 

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DSM Plan October 16, 2015 
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participants currently experience with their habitual corrections. These benefits outweigh the risks in 
this study, which are no different than those associated with a routine eye examination. 
 
•         Collection and reporting of AEs and SAEs 
 
Adverse Events: 
Given the strict criteria to dispense a pair of spectacles, anticipated adverse events are expected to be 
few and primarily related to eye strain from adaptation to a new spectacle prescription.  To identify 
these AEs, parents/guardians of participants, or another appropriate individual who is in close, regular 
contact with the participant, will be contacted both one day and one week after each new spectacle 
prescription is dispensed by a clinical study examiner.  During these calls, examiners will ask if the 
participant is having any difficulty with the prescription.  If concerns are great enough to warrant a 
study visit, participants will be seen by the unmasked examiner to address the concerns.  All AEs as a 
result of these phone interviews will be documented in the participant’s file, along with their 
resolution.  In addition to planned solicitation of participant difficulties with prescriptions, any 
unsolicited participant complaints or findings discovered at scheduled study follow-ups will be 
managed in the same fashion. 
 
Serious Adverse Events: 
The risk for SAEs in this study is limited and primarily related to the rare possibility for an acute 
increase in intraocular pressure after instillation of dilation drops during the study visit.  This SAE would 
most likely occur in the few hours post-dilation, and thus participants and their family members will be 
advised to contact the investigator immediately if symptoms such as headache and nausea develop.  
The management of this, and other, SAEs is detailed below.  All SAEs will be documented in the 
participant’s files, along with their resolution.  All SAEs will also be reported to the University of 
Houston Committee for the Protection of Human Subjects via their online reporting system (SAE Time 
Frame: 24 hours), as well as the NEI via the Program Officer.   
•         Management of SAEs or other study risks 
 
Any SAE or other study risk will be managed by the unmasked clinical examiner, or the PI, both of 
whom have Clinical Licenses.  If a participant needs intervention of an ocular nature when either of 
those individuals are unavailable, care to resolve the acute event will be provided at no-cost to the 
participant by the on-call doctor at the University of Houston University Eye Institute, as stated above 
under risks.  If the adverse event is not of an ocular nature, the participant will be referred to the 
appropriate professional at the expense of the participant’s parent/guardian/responsible party. 
DSM Plan Administration 
•         Responsibility for data and safety monitoring  
 
The PI (unmasked) will monitor the data and any adverse events, which will in turn be reported to the 
University of Houston Committee for Protection of Human Subjects and the NEI Program Officer.  This 
collective body of individuals will ultimately be responsible for monitoring the trial. 
 
 

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•         Frequency of DSM  
 
There will be no formal review of the data over the course of the trial, but the PI will be continuously 
involved in verifying the completion and accuracy of data entry, as well as the occurrence of adverse 
events. 
 

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References 
 
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in individuals with down syndrome. Invest Ophthalmol Vis Sci. 2011;52(1):310-7. PMCID: 
PMC3053281. 
 
Berk AT, Saatci AO, Ercal MD, Tunc M, Ergin M. Ocular findings in 55 patients with down's syndrome. 
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Cregg M, Woodhouse JM, Pakeman VH, Saunders KJ, Gunter HL, Parker M, et al. Accommodation and 
refractive error in children with down syndrome: Cross-sectional and longitudinal studies. Invest 
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da Cunha RP, Moreira JB. Ocular findings in down's syndrome. Am J Ophthalmol. 1996;122(2):236-44. 
 
Lovie-Kitchin JE, Brown B. Repeatability and intercorrelations of standard vision tests as a function of 
age. Optom Vis Sci. 2000;77(8):412-20. 
 
Nandakumar K, Leat SJ. Bifocals in children with down syndrome (bids) - visual acuity, accommodation 
and early literacy skills. Acta Ophthalmol. 2010;88(6):e196-204. 
 
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