Infant Aphakia Treatment Study (IATS)
Phase: NA
Conditions: Congenital Cataract
Sponsor: Stanford University

Infant Aphakia Treatment Study 
(IATS) 
Phase 3 Study Protocol for the 10Y Visit 
 
NCT00212134 
04.29.2015 
Scott Reed Lambert, Principal Investigator 
Stanford University 
Stanford, California 94305 
 

1 
 
Ver. 04.29.2015 
 
 
Infant Aphakia Treatment Study 
 
(IATS) 
 
 
 
 
Phase 3 
 
 
Study Protocol 
 
for the  
 
10Y Visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
Ver. 04.29.2015 
 
 
TABLE OF CONTENTS 
 
 
 
 
Chapter 1.  Introduction 
 
 
 
 
 
      
 
     pg 3 
 
 
 
Aims and Background 
Procedures 
 
Chapter 2.  Research Design and Methods 
 
 
     
 
    pg 10 
 
Informed Consent and Assent 
Examination Schedule 
Retention 
 
Chapter 3.  Clinical Assessments  
 
 
 
   
 
     pg 12 
 
 
Discontinuation of Contact Lens and/or Spectacles 
 
Manifest Refraction 
 
Reading Test 
Ocular Alignment and StereoAcuity 
Biomicroscopy 
Tonometry 
Pupils 
Cycloplegic E-ETDRS Acuity Assessment 
 
Assessment of Light Perception 
 
Pachymetry 
Optical Biometry 
- 
Axial length 
- 
Keratometry 
- 
Corneal Diameter 
 
Indirect ophthalmoscopy 
 
Quality of Life Measures 
 
Chapter 4.  Imaging  
 
 
 
 
 
     
 
       pg 17 
            Anterior Chamber OCT 
Optic Nerve stereo photography 
 
Nerve Fiber Layer OCT 
 
 
Chapter 5.  Statistical Considerations and Data Capture and Management            pg 18 
 
   Data Capture and Management 
 
   Statistical Analysis 
 
Chapter 6.  Study Administration    
 
 
 
   
 
         pg 24 
 
        Certification of Personnel 
        Study Organization 
 
Bibliography  
 
 
 
 
 
 
      
 
         pg 28 
 

3 
 
Ver. 04.29.2015 
 
 
CHAPTER 1   INTRODUCTION 
 
The original purpose of the Infant Aphakia Treatment Study (IATS) was to assess the safety and 
the efficacy of IOL implantation in the rapidly growing eye of infants with a unilateral congenital 
cataract; children were randomized to either intraocular lens implantation (IOL) or contact lens 
(CL) correction following cataract surgery.  Enrollment of the target sample size of 114 patients 
began in December 2004 and was completed in January 2009.  Grating acuity was assessed at 
12 months of age during Phase 1 of IATS and was completed in January 2010.  Phase 2 began 
in March 2009.  The optotype visual assessment was assessed during Phase 2 of the IATS 
when these children were age 4½ years using the ATS HOTV test. Phase 2 also included an 
ocular examination performed at age 5 years to evaluate:  axial length, refractive error, 
keratometry, endothelial cell count, intraocular pressure, central corneal thickness and ocular 
alignment.  At both the 1 Year and 4½ Year assessments, the visual acuity was found to be 
equal between the two groups.  However, many more complications requiring additional surgery 
occurred in the IOL group, mostly in the first year after the initial surgery. 
 
Glaucoma is one of the most serious adverse events that can develop after infantile cataract 
surgery.  We did not find a significant difference in the cumulative incidence of glaucoma 
between the two treatment groups at age 5 years.   We now postulate that newly diagnosed 
cases of glaucoma will occur more frequently between the ages of 5 and 10 years in the study 
eyes randomized to the CL group resulting in a higher cumulative incidence of glaucoma at age 
10 years in this group.  This hypothesis is based on a trend noted in the IATS between ages 1 
and 5 years (new cases of glaucoma/glaucoma suspect: IOL group, 7 eyes (12%); CL group, 16 
eyes (28%) and a study by Trivedi (Trivedi, 2006). 
 
One of the unique challenges associated with primary IOL implantation during infancy is to 
select an IOL power that will optimize vision during infancy while not requiring an IOL exchange 
later in childhood.  In the IATS, pseudophakic eyes were undercorrected by 8D (at 4-6 weeks of 
age) and 6D (at more than 6 weeks old) at the time of primary IOL implantation.  At age 5 years, 
3 eyes had undergone an IOL exchange because of a larger than expected myopic shift in the 
pseudophakic eye.  We now postulate that additional pseudophakic eyes will require an IOL 
exchange after a longer follow-up.  Following eyes randomized to IOL implantation to age 10 
years, will allow us to identify risk factors for a large myopic shift and to determine the ideal 
undercorrection to optimize visual acuity while minimizing the need for IOL exchange.  Phase 3 
of this study intends to examine these children one additional time when they are 10 years of 
age. Longer follow-up will allow us to compare the long-term incidence and later onset of 
glaucoma in the study eyes in the two treatment groups and the rate of myopic shift so that risk 
factors for a larger than expected myopic shift can be identified in young children. 
 
Study Aims: 
 
1. Compare the cumulative incidence of glaucoma between the two treatment groups at 
age 10 years to determine which initial treatment is associated with the lowest long-term 
risk of glaucoma or glaucoma suspect.  
2. Characterize myopic shift between the ages of 5 and 10 years in the IOL group. 
 
3. Examine the impact of Unilateral Congenital Cataract on reading (speed, accuracy and 
comprehension), self-esteem and Health Related Quality of Life i 

4 
 
Ver. 04.29.2015 
 
 
Background 
 
At the time of our original proposal in 2003, IOLs were the accepted treatment following cataract 
surgery in older children and were being used increasingly in younger children (Wilson, 1996).  
However, among infants CLs were still the standard treatment since little was known about the 
safety of IOLs or the optimal IOL power to implant in a rapidly growing eye (Beller et al., 1981; 
Lorenz et al., 1991).  Available data suggested that a fair-to-good visual acuity outcome could 
be more consistently obtained in infants with a unilateral congenital cataract who underwent IOL 
implantation at the time of cataract surgery (BenEzra, 1996; Dahan et al., 1997), but the 
methods used to assess the visual outcome in these series were non-standardized and may 
have overestimated the visual acuity of the pseudophakic eyes (Birch et al., 2005).  Moreover, 
these series generally reported more complications in pseudophakic than aphakic eyes (Plager 
et al., 2002). Therefore, the question—What is the best way to treat infants with unilateral 
aphakia?—remained unanswered.  The objective of IATS was to compare the visual outcome of 
two treatments for infants with a unilateral congenital cataract.  The control group would receive 
the conventional treatment with a CL and later coupled with spectacle treatment.  The 
experimental group would also undergo cataract surgery but in addition, would have an IOL 
implanted during the same surgery.  The IOL would serve as the primary optical treatment.  Any 
residual refractive error would then be corrected immediately with spectacles.   
 
Given the expected 75-80 year life span of infants after cataract surgery and the impact that 
vision has on the quality of life, good vision in the cataractous eyes of children has the potential 
to have a major impact on their lives.  Good vision in both eyes of these patients will allow them 
to pursue a broader range of professional and vocational opportunities and will give them the 
assurance that if they lose vision in their better seeing eye that they can continue to function as 
a sighted person.  Reducing the incidence of glaucoma will also eliminate the discomfort and 
risks of having to undergo additional surgeries and/or daily medical therapy and the possible 
loss of vision in this eye later in life.   While the prevalence of many complications can be 
established after a 5 year follow-up, the true prevalence of glaucoma following infantile cataract 
surgery cannot be established until after a longer follow-up.  We chose a follow-up of age 10 
years because most cases of glaucoma following infantile cataract surgery are diagnosed by 
this age.  Thus, a 10-year follow-up of a well-characterized cohort should provide a more robust 
estimate of the impact of glaucoma on children treated for congenital cataract.  In our own 
retrospective review of 62 eyes that underwent cataract surgery when <7 months of age, we 
found the 10-year risk of developing glaucoma or glaucoma suspect to be 63%.   
 
The proposed research is expected to establish the optimal means of treating an infant following 
unilateral congenital cataract surgery to achieve the lowest incidence of glaucoma.  In addition, 
exchanging an IOL requires that a child undergo general anesthesia with all of the attendant 
risks and costs.  There are also ocular risks associated with additional intraocular surgeries.  
Accurately predicting the myopic shift after primary IOL implantation should reduce the need for 
IOL exchange.  
Finally, the anesthesia associated with the standard care and treatment of surgical 
complications may result in a decrease in cognitive abilities. Children exposed to anesthesia 
before three years of age had lower scores in receptive and expressive language and cognitive 
ability than their peers (Ing et al.). Wilder et al, noted that children who had multiple anesthesia 
exposures prior to age 5 had significantly elevated risks of learning disabilities (Wilder). Another 
study noted that children who had surgery using general anesthesia within the first two years of 
life exhibited more behavior problems as teenagers. 

5 
 
Ver. 04.29.2015 
 
 
 IATS is a randomized clinical trial evaluating a large cohort of children who all underwent early 
cataract surgery using the same surgical protocols.  After surgery, the children were examined 
at fixed time intervals using the same follow-up protocols.  We had a 100% follow-up rate at age 
12 months and a 99% follow-up rate at 5 years.  In addition, the IATS developed a uniform 
definition of glaucoma with strict criteria.  Intraocular pressure (IOP) was measured in all 
patients during an examination-under-anesthesia (EUAs) at age 12 months and at 4½ and/or 5 
year examinations.  Measuring IOP at follow-up examinations was made easier by the approval 
of ICare rebound tonometry (ICare Finland Oy, Helsinki, Finland) by the FDA in 2007.  ICare 
rebound tonometry has been widely used in the IATS and it has greatly enhanced our ability to 
measure IOP in these young children in a clinic setting (Lambert, 2012).  Previous studies 
reporting IOL implantation in infants have been small, retrospective case series (Autrata et al., 
2005; Lundvall et al., 2006; Ram et al., 2011) with relatively short follow-up intervals and low 
follow-up rates.  Finally, these other studies did not use a uniform definition of glaucoma and 
many relied exclusively on an elevated IOP to diagnose glaucoma.   We expect the 10Y IATS 
visit to provide a more accurate assessment of the long-term effects of primary IOL implantation 
versus CL correction after unilateral cataract surgery during infancy on the cumulative incidence 
of glaucoma, the rate of axial length elongation, and the assessment of visual function. 
 
In the Infant Aphakia Treatment Study (IATS), children with unilateral cataracts were exposed to 
anesthesia a minimum of two times in the first year of life as part of their standard of care.  
Many of these children had multiple other surgeries during this time period as a result of 
adverse events.  For example, three-quarters of children in the IATS study had at least one 
additional surgery beyond the prescribed exam under anesthesia at twelve months of age, and 
over 90% of children who were randomized to receive an IOL at the time of cataract extraction 
had more intraocular surgeries as a result of adverse events, most commonly lens re-
proliferation (68%) (Lambert et al, 2014).  Before their fifth birthday, 44% of the IATS 
participants had had at least one additional surgery, not including surgery for strabismus (23-
75%) and, to date, 3 of the 57 children  randomized to remain aphakic had surgery to implant an 
IOL (Lambert et al, 2001).   
 
Inclusion Enrollment Report 
 
We enrolled 114 children in IATS between 12/04 and 1/09.  All study patients were between the 
ages of 28 and 210 days at the time of enrollment.  The patients all had a unilateral congenital 
cataract and the fellow eyes were normal.  Only infants were enrolled in the study because our 
goal was to compare two optical treatments for infants following infantile cataract surgery. The 
ethnicity and gender of the patients enrolled in IATS is shown in Table 7.  The clinical trial is 
being conducted at 12 clinical sites.  The DCC and the chairman’s office are located at Emory 
University. 
 
 
Table 7:  Ethnicity and Gender of Children Enrolled in IATS 
Gender 
White 
Black 
Am Indian/ 
Alaska 
Native 
Asian 
Other 
Total 
Female  
48 
5 
1 
2 
4 
60 
Male  
49 
3 
0 
1 
1 
54 
Total 
97 
8 
1 
3 
5 
114 
 

6 
 
Ver. 04.29.2015 
 
Procedures 
 
Glaucoma Evaluation 
 
The incidence of glaucoma and the best surgical approach to minimize its occurrence after 
infantile cataract surgery are not known.  The objective of this hypothesis is to compare the 
cumulative incidence of glaucoma after unilateral congenital cataract surgery with or without IOL 
implantation after a much longer follow-up.  Glaucoma is one of the most serious complications 
occurring after infantile cataract surgery. A wide range of incidences of glaucoma has been 
reported following infantile cataract surgery (9% – 32% in 7 studies).   
 
One large population based study estimated that the cumulative incidence of glaucoma in 
children <9 months of age at the time of cataract surgery was 32% after a 10 year follow-up 
(Haargaard, 2008).   However, all of these studies had serious limitations.   All were 
retrospective and many had a selection bias.  Furthermore, some studies defined glaucoma 
solely on the basis of an elevated IOP (>25 mmHg) (Cotter, 2003; Swamy et al., 2007).  Studies 
which relied solely on an elevated IOP to diagnose glaucoma may have over-diagnosed 
glaucoma, since there can be a long “lag” phase between modestly elevated IOP and clinically 
significant optic nerve or visual field damage in eyes with healthy nerves.  In addition, the thicker 
corneas of aphakic eyes introduces a controversial but important potential source of 
measurement error in using IOP alone as a criterion for diagnosing glaucoma  (Simsek et al., 
2006; Muir et al., 2007; Lupinacci et al., 2009; Lim et al., 2011).   Lastly, some of these series 
included patients that had undergone cataract surgery using outdated surgical techniques that 
may be associated with a higher risk of glaucoma than surgery performed using modern 
surgical techniques (Phelps et al., 1977; Chen, 2004). 
 
Most studies suggest that a follow-up much longer than 5 years is necessary to determine the 
true cumulative incidence of glaucoma in eyes undergoing cataract surgery during infancy.  In a 
population based study from Denmark the median time interval between infantile cataract 
surgery and the diagnosis of glaucoma was 6.6 years (25% quartile, 1.1 years; 75% quartile, 
10.7 years) (Haargaard, 2008).   Others have reported a mean interval of 7 years or longer from 
the time of cataract surgery until glaucoma was diagnosed (Mills et al., 1994; McClatchey, 
1997).  One study reported that the cumulative incidence of glaucoma almost doubled (11% to 
19%) between the ages of  5 to 10 years (Egbert, 2006).   Most studies of aphakic glaucoma are 
limited by a relatively short follow-up and as a result likely underestimated the cumulative 
incidence of glaucoma (Swamy, 2007; Chak, 2008; Kuhli-Hattenbach et al., 2008).   
There is a debate in the literature whether primary IOL implantation following cataract surgery 
reduces the risk of glaucoma in pediatric eyes.  Two large retrospective multi-centered studies 
have reported that glaucoma rarely developed in children following cataract surgery and IOL 
implantation.  In the first study, only 1 of 377 (<1%) pseudophakic eyes developed glaucoma 
(mean follow-up, 5.1 years) compared to 14 of 124 (11%) aphakic eyes (mean follow-up, 7.2 
years) (Asrani et al., 2000).  However, none of the pseudophakic children in this study 
underwent cataract surgery during the first 12 months of life and the pseudophakic patients 
were older than the aphakic patients at the time of cataract surgery (5.06 vs 2.73 years) 
suggesting a selection bias.  In the second study, only 1 of 105 (1%) pseudophakic eyes 
developed glaucoma compared to  89 of 377 (23%) aphakic eyes (hazard ratio, 0.036; 95% 
confidence interval, 0.001, 0.914; p=.044) after a mean follow-up of 5.92 years (Mataftsi et al,In 
Press).  While all of the patients in this study underwent cataract surgery during the first year of 
life (median age, 3 months), it is likely that there was a selection bias for the children 
undergoing IOL implantation since it was a retrospective, non-randomized study.   
 

7 
 
Ver. 04.29.2015 
 
In contradistinction to the studies by Asrani (Asrani, 2000) and Mataftsi (Mataftsi,2014), Trivedi 
and coworkers (Trivedi, 2006) did not find a statistically significant difference in the cumulative 
incidence of glaucoma after infantile cataract surgery with or without IOL implantation (24% vs 
19%). However, the onset of glaucoma occurred earlier in eyes that underwent IOL implantation 
(median age of glaucoma onset, 3.5 months; range, 0.8 to 38 months) versus eyes that were 
left aphakic (median age of glaucoma onset, 90 months; range, 62 to 133 months).  Glaucoma 
may develop earlier in infantile eyes after cataract surgery coupled with IOL implantation due to 
greater trauma to the trabecular meshwork at the time of cataract surgery.  However, if 
glaucoma does not develop in the immediate postoperative period, the IOL may protect these 
eyes from developing glaucoma by mechanically supporting the trabecular meshwork or 
blocking the egress of toxic substances from the vitreous chamber to the trabecular meshwork.  
By following these children to age 10 years, we should be able to ascertain if the median age of 
onset of glaucoma is different between eyes that undergo primary IOL implantation versus eyes 
that are initially left aphakic after infantile cataract surgery.   
 
 
Phase 3 Definition and Diagnosis of Glaucoma:  
 
In Phases 1 and 2, an eye was defined as having glaucoma if the following criteria were 
present:  IOP >21 mmHg with one or more of the following anatomical changes:  1) corneal 
enlargement; 2) asymmetrical progressive myopic shift coupled with enlargement of the corneal 
diameter and/or axial length; 3) increased optic nerve cupping defined as an increase of ≥ 0.2 in 
the cup-to-disc ratio, or 4) the use of a surgical procedure for IOP control.  An eye was defined 
as glaucoma suspect if any of the following criteria were present:  1) two consecutive IOP 
measurements >21 mmHg on different dates after topical corticosteroids had been discontinued 
without any of the anatomical changes listed above; or 2) glaucoma medications were used to 
control IOP without any of the anatomical changes listed above. 
 
In Phase 3, an eye will be defined as having glaucoma if the following criteria are present: 1) 
IOP > 21mmHg; and 2) a progressive increase in cup-disc ratio, cup-disc asymmetry of ≥ 0.2, or 
focal rim thinning. An eye will be defined as glaucoma suspect if any of the following criteria are 
present: 1) IOP > 21mmHg; or 2) glaucoma medications are being used to control IOP; or 3) an 
optic disc suspicious for glaucoma (e.g. increased cup-disc ratio).  The criteria which will be 
used to diagnose glaucoma in Phase 3 will be the same as the criteria used in Phases 1 and 2 
of the IATS, with the exception of ocular enlargement criteria. Unlike infants, children aged 5-10 
years do not usually exhibit signs of ocular enlargement with elevated IOP.  The criteria which 
will be used to diagnose glaucoma suspect in Phase 3 will also be the same as the criteria used 
in Phases 1 and 2 of the IATS with the exception that two consecutive IOP measurements >21 
mmHg at two different visits will not be included in the definition since children in Phase 3 will 
only be examined once.  In addition, since optic disc photographs will be taken at the 10Y exam, 
we have added a suspicious optic disc as another criterion for Phase 3.  Since some children 
may be diagnosed as having glaucoma or glaucoma suspect between the five and 10 year 
evaluations, a review of medical records will be performed for all patients to determine who are 
classified as glaucoma or glaucoma suspect for Phase 3.  This will assist in establishing 
diagnostic criteria and the age of onset for study purposes.  
.  
Adult glaucoma studies typically include visual field criteria for the diagnosis of glaucoma. We 
have chosen not to include visual field criteria for the following reasons: 1) children usually 
cannot perform visual field testing until they are about 7-10 years of age; 2) initial visual field 
testing is unreliable in children; and 3) at least three visual field tests are needed to document a 
reproducible visual field defect. 

8 
 
Ver. 04.29.2015 
 
 
Anterior Chamber OCT 
 
Glaucoma in children is generally evaluated by measuring the intraocular pressure and 
assessing the cup-to-disc ratio of the optic disc. Gonioscopy, which is the “gold standard” in the 
evaluation of anterior chamber angles (Sharma R, 2013), is difficult to perform in children. 
Ultrasound biomicroscopy is another modality that has been used in children to assess the 
anterior segment of the eye. It uses ultrasound to image the anterior segment and studies have 
shown it to be consistent with gonioscopy. Its major disadvantage is that it requires an 
immersion shell to be placed on the eye which is generally not tolerated by young children. 
Due to its noninvasive nature, OCT may be useful for assessing the anterior segment of 
children after cataract surgery to evaluate risk factors for glaucoma as it is comparable to 
gonioscopy.  
 
Nerve Fiber Layer OCT 
 
Spectral domain optical coherence tomography (SD-OCT) has been shown to be a powerful  
tool evaluating and managing adults with glaucoma, and can even predict among glaucoma 
suspect those eyes at higher risk for developing visual field loss (Mwanza et al., 2011; Miki at al, 
2014).  In children, peripapillary retinal nerve fiber layer thickness (RNFL) assessed by either 
time domain OCT [Hess et al; Nadeau et al., 2010] or, more recently, by SD-OCT [Alasil et al, 
2013], has been shown to be effective in differentiating between normal eyes and eyes with 
glaucoma (Ghasia et al., 2013; Srinivasan et al, 2014).  RNFL measurements of both eyes will 
be taken using the Heidelberg Spectralis OCT by a trained OCT imager.  Average RNFL will be 
compared between the surgical and the normal fellow eyes for all subjects.  Average RNFL will 
be compared among study eyes with glaucoma suspect or glaucoma status, and those without 
a glaucoma-related adverse event.  Quadrant level analysis of RNFL thickness will be carried 
out to detect trend in thinning among those with glaucoma-related adverse events compared to 
normal fellow and unaffected study eyes.  Similarly, the difference in average RNFL between 
study and control fellow eyes will be compared for children with glaucoma suspect, glaucoma, 
and those with neither.  Average RNFL will be correlated with optic nerve head cupping and the 
presence or absence of glaucomatous optic neuropathy (assessed by masked review of 
stereophotographs) across all study eyes.  
 
Myopic Shift and Accuracy of IOL Calculations 
 
During childhood, the human eye elongates and the cornea and the crystalline lens flatten.  
When the biometrics of the growing eye are perfectly calibrated, the eye remains emmetropic.  
However, if the crystalline lens is removed surgically, the corneal flattening that occurs in early 
childhood cannot offset the 3-4 mm of axial elongation that occurs during the first year of life 
and the additional axial elongation that occurs in some eyes even into the teenage 
years.(Gordon et al., 1985)  While small myopic shifts after IOL implantation can be corrected 
with contact lenses or spectacles, large myopic shifts may require an IOL exchange.(Dahan et 
al., 1990)  In children with unilateral pseudophakia, a large myopic shift may contribute to the 
development of anisometropic amblyopia and impaired binocularity.  Most clinicians 
undercorrect infants after cataract surgery and IOL implantation in anticipation of a myopic 
shift.(BenEzra, 1996; Dahan, 1997; Thouvenin et al., 2003; Autrata, 2005; Gouws et al., 2006)   
However, there is no agreement regarding the optimal magnitude of this undercorrection.  While 
small cases series have reported a mean myopic shift ranging from 5 to 7 D after IOL 
implantation during infancy, these studies are retrospective with variable lengths of follow-
up.(McClatchey et al., 2000; Ashworth et al., 2007; Astle et al., 2007)  In addition, co-morbidities 

9 
 
Ver. 04.29.2015 
 
such as glaucoma and microphthalmos which may impact the magnitude of the myopic shift 
were not always exclusion criteria in these studies.   
 
In the IATS, all pseudophakic eyes had a targeted undercorrection of 6 or 8 D at the time of 
cataract surgery and primary IOL implantation (age 4-6 weeks, 8 D; age 7-28 weeks, 6 D).  
Postoperatively,  follow-up clinical examinations were performed by an IATS certified 
investigator at 1 day, 1 week, 3 months and then at 3 months ± 2 weeks intervals until age 4 
years and then at ages 4.25, 4.5 and 5 years.  The age 5 year examination, included a 
cycloplegic refraction to assess the refractive error in both the treated and untreated eyes.  The 
median (25th, 75th percentiles) refractive error in the treated eyes in the IOL group was -2.25 D 
(-7.25, 0.00) (range, -19.00 to +5.00 D). As expected, the median refractive error was larger in 
with glaucoma (-7.25 D) compared to eyes without glaucoma (-1.69 D). 
 
   
 
# Patients 
Median 
IQR* 
Range 
Without Glaucoma 
44 
-1.69 
-5.03 to 1.16 
-18.00 to 5.00 
With Glaucoma 
11 
-7.25 
-16.50 to -3.50 
-19.00 to -1.50 
 
 
Refractive Error at Age 5 Years for Patients Treated with an IOL 
 
 
 
While the median refractive error was -2.25 D in the treated eyes in the IOL group, there was a 
wide range of refractive errors in these pseudophakic eyes at age 5 years ranging from +5.00 D 
to -19.00 D.    The absolute prediction error was 1.8 D and only 41% of eyes had an absolute 
prediction error of 1 D or less.  While the inaccuracy of the targeted refractive error was one 
factor, the unpredictability of the axial elongation of these eyes was the primary reason for the 
wide range of refactive errors at age 5 years. 
 
Three eyes in the IOL group underwent an IOL exchange:  one during the first postoperative 
year and 2 after the first postoperative year to correct refractive errors of -10.00, -8.50, and  
-19.00 D, respectively.  None of these eyes had glaucoma. 
 

10 
 
Ver. 04.29.2015 
 
CHAPTER 2   RESEARCH  DESIGN and METHODS 
  
The 114 patients enrolled in IATS will be examined within the year after their 10th birthday. A 
comprehensive ocular examination will be performed including tonometry and refractometry as 
well as measurements of central corneal thickness, keratometry, and axial length.  Nerve fiber 
layer Optical Coherence Tomography (OCT) will also be performed.  All data will be entered on 
standardized electronic Case Report Forms.  All key personnel will maintain or acquire IATS 
certification according to the procedure described in the Manual of Procedures. 
 
Informed Consent and Assent 
 
At the 5Y visit, all caregivers were asked to give written permission for the study staff to 
maintain contact after the closeout visit. If the parents(s) or legal guardian(s) have agreed to 
have their child return for a study visit at age 10 years, the study will be discussed with them 
and with the child.  Written informed consent must be obtained from the parent(s) or legal 
guardian(s) of the child before performing any procedures that are not part of the patient's 
routine care.  In addition, because these children are now old enough to assent to their medical 
treatment, they must give verbal assent or sign an approved Assent Form. If the child has been 
followed by a non-study ophthalmologist since the 5y visit, the caregiver will be asked to sign a 
Medical Records Release form in order to capture the interim history. 
 
The accompanying Caregiver will be asked to fill out a brief form regarding the child’s use of 
optical correction, occlusion therapy, or special education services. 
 
Retention 
 
Attrition poses a significant threat to the internal validity of the proposed study given that attrition 
has been associated with low socioeconomic status and poor treatment adherence in chronic 
pediatric illnesses.  The study group has been very successful in follow-up of the cohort and has 
experienced a very low attrition rate in both Phases 1 and 2 of the IATS.  Nearly 90% of the 
mandated study visits were completed and more importantly, 100% of the Primary Outcome 
visits at age 12 months and 99% at age 4½ years were completed.  All but 6 parents have 
signed a Permission to Contact Form allowing the Data Coordinating Center (DCC) to maintain 
contact with the participants and their parents even after they have completed the 5Y visit in 
Phase 2 of the study. Until mid 2015 the DCC will be maintaining contact with participants and 
their families in a variety of ways including:  quarterly newsletters informing the families about 
key findings of the Study as well as providing information regarding visual development and 
ocular health, the popular IATS calendar, birthday cards, and periodic telephone contact with 
the families by the Site Coordinators.  The DCC works to ensure that we have and maintain 
accurate addresses of the families, as well as contact information for other key individuals in 
each family’s life.  The Sites will begin trying to schedule the 10-year visit about 6 months in 
advance to ensure that there is adequate time to find any participants who may have moved 
and for whom there is not current address information available.  In this case, the Clinical 
Coordinating Center and the Sites will collaborate to locate and retain these participants using 
available resources such as the family contacts and electronic search databases. 
 
We will supplement our previously successful outreach programs using social media.  Social 
media will provide us with another opportunity to engage participants and other interested 
stakeholders, and to inform these individuals about the Study’s progress.  Additionally, engaging 
participants has been an important component of our success in retaining participants.   

11 
 
Ver. 04.29.2015 
 
  Recent data suggest that 90% of Americans age 18 to 39 use the internet and 73% use social 
media, and that usage does not differ by race or ethnicity 
(http://www.pewinternet.org/2013/12/30/social-media-update-2013).  The goal of including a 
social media presence in the IATS is to increase engagement with the Study and to enhance 
the sense of community among participants that was initiated through adherence phone calls, 
newsletters and calendars.  We are adding this component to the proposed follow-up because 
of its increasing importance in American culture and because we will no longer be conducting 
adherence phone calls.  Social medial will be used by IATS as a mechanism of engaging 
participants and creating a sense of community for these families, and not as a method to 
collect data or personally identifiable data.  However, we will use social media to request that 
participants contact to Study to ensure that we have accurate contact information.   
 
Because of recent trends in social media, as noted above, IATS will focus its social media 
presence on Facebook, Twitter and Pinterest which have high penetration among women aged 
30 to 49.  To ensure that these sites are used and serve the goals of the study, we will ensure 
that postings are updated at least three times each week.  The postings will provide updates to 
the Study’s progress, updates on publications related to the study, information of interest to 
parents with school-aged children and information of interest to caregivers of children with 
cataracts and other eye conditions which are prevalent among this population.  All posts will be 
reviewed by the Executive Committee prior to posting to ensure that the most relevant and 
accurate information is presented.  Additionally, best practices and guidelines developed by 
Federal agencies (i.e., CDC and NIH) will be used to govern the implementation of social media 
in IATS. 
 
To encourage participation in the study, the following steps will be taken:  1) families will be 
reimbursed for the time they invest in the study visit with monetary incentives ($250 for 
attending the scheduled study visit and a $50 gift card for the child), 2) travel costs will be 
reimbursed if it is a financial hardship for families to return for the study visit, and 3) families will 
receive IATS newsletters three times a year and an “IATS Kids” holiday calendar annually.   
 
 
Examination Schedule   
 
Clinical examinations will be performed by IATS certified physicians and visits will be scheduled 
by the IATS certified clinical coordinator.  Study visits will be scheduled for sometime in the year 
after children have reached 10 years of age and ideally around 6 months after the birthday.  
Non-study visits may be performed at the discretion of the investigator. 
 
 
10.0 Years 
 Examination Information, Interim History, Reading 
Manifest Refraction, Cycloplegic E-ETDRS Vision  
Clinical Examination: Motility/Stereo, Biomicroscopy,  Biometry/ 
keratometry, Tonometry,  Pachymetry , Cycloplegic Refraction, 
Imaging Optic Disc Photos, Nerve Fiber Layer OCT, Anterior 
Chamber OCT 
 
 
 
 

12 
 
Ver. 04.29.2015 
 
 
CHAPTER 3.   Clinical Examination 
  
Primary Outcome Examination at Age 10 Years 
 
A clinical examination will will be performed at age 10 years by the site investigator including 
biomicroscopy, retinoscopy, tonometry, and indirect ophthalmoscopy.  Optical biometry, 
keratometry, and pachymetry will also be performed.  
Visual acuity assessment using the E-ETDRS protocol will be performed by certified site 
personnel; patients should be in their best optical correction as determined by the PI either 
recently or just before the EVA test. 
 
Discontinuation of CL Use Prior to Examination 
 
If a child randomized to CL correction discontinues CL use prior to the age 10 year assessment 
and has not received a secondary IOL, then the child will wear the aphakic correction in a trial 
frame for the visual assessment or a CL with a close spherical power can be on hand and a trial 
frame can be used for residual correction.   
 
Discontinuation of Spectacles Prior to Examination  
 
If spectacles are still indicated for a child in the IOL group and the child discontinues their use 
prior to the age 10 year examination, the spectacles prescribed will be worn during the visual 
assessment.  If the refraction has changed based on recent measurement or the glasses are 
not available, then the most current prescription in a trial frame can be used. 
 
Manifest refraction 
 
A non-cycloplegic measurement of the refractive error at distance will be performed on the study 
eye using a phoropter or a trial frame.  If the child is wearing a contact lens, this refraction 
should be done over the contact lens. If the child is wearing spectacles, this refraction should be 
done without them.   
 
Reading Test 
 
We will use the ReadAlyzerTM to assess reading speed and comprehension 
(http://www.compevo.se/ReadAlyzerInfo.pdf).  The ReadAlyzer system includes specialized 
goggles that are worn over the child's usual optical near correction.  The near interpupillary 
distance is adjusted for the child's size.  To ensure that the goggles are appropriately adjusted 
to the child, the child will read a short (100-word) passage written at the 1st grade level.  If the 
child is unable to read and comprehend this short passage, the clinic staff will readjust the 
goggles to ensure proper fit.  After proper fit has been ensured, the child will read a standard, 
grade-appropriate, 800-word passage and then answer a series of 20 comprehension 
questions.  The system comes with software that provides automatic analysis of the number of 
fixations, the number of regressions, the mean fixation duration, the reading speed (words per 
minute), grade level equivalent and comprehension.  There is no need for head fixation or 
calibration.   
 
We have chosen to use the ReadAlyzer System in contrast to other standard reading systems 
such as the Gray Oral Reading Test (GORT) because it is relatively automated which should 
maximize inter-rater reliability, because it provides information on fixations and saccades 

13 
 
Ver. 04.29.2015 
 
associated with reading and because it assesses silent reading which is salient to children's 
academic reading during the later years of elementary school.   
 
Ocular Alignment  and Randot Stereo testing 
 
Ideally, testing of stereopsis should occur prior to occlusion of one eye for vision testing, motility 
evaluation, etc. 
 
The Randot Preschool Stereoacuity Test measures random dot stereoacuity from 800 to 40 arc 
seconds. The test consists of three booklets. Each booklet has two sets of four random dot 
shapes on one page. One of these images is blank; the other three are pictures that can be 
seen only when viewed through polarizing lenses. On the opposite of the booklet are non-stereo 
images of the same shapes. There are six levels of stereoacuity in the test, with two levels in 
each book. Each level has four rectangles that contain three shapes and one blank. 
 
Ocular alignment will be assessed with the child fixating on an accommodative target in the 
distance and at near using the simultaneous prism and cover test.  The test will be performed by 
simultaneously covering the fixating eye and placing a prism in front of the deviating eye.  
Increasing prism powers are placed over the deviating eye until it no longer shifts.  The power of 
the prism used when the deviating eye no longer shifts is the measure of the deviation. If the 
child cannot fixate on a target due to poor vision, increasing prism powers will be placed over 
the deviating eye until the pupillary light reflex is symmetrical with the pupillary reflex in the 
fixing eye (Krimsky test).  If the child will not tolerate a prism placed over the deviating eye, a 
point source of light will be shown on both eyes.  The angle of strabismus will then be estimated 
based on the degree that the pupillary light reflex is decentered relative to the fixing eye 
(Hirschberg light reflex test). 
 
 
Biomicroscopy 
 
An examination of the anterior segment will be performed using the slit lamp. In particular, the 
condition of the cornea, anterior chamber and, after dilation, the status of the media and IOL (if 
present) will be assessed. 
 
Tonometry  
 
Tonometry will be performed in both eyes at the 10Y study visit while the child is calm and quiet 
using Goldmann applanation tonometry preferably, but using Icare rebound tonometry (Icare 
Finland Oy, Helsinki, Finland), or Tonopen (Tono-PenXL, Medronic Solan, Jacksonville, FL), if 
necessary.  Topical anesthesia is required for performing Goldmann and Tonopen tonometry, 
but is not needed for rebound tonometry.  Rebound tonometry IOP readings on average 
measure 2 mm higher than Goldmann applanation tonometry (Lambert, 2013).  In contrast, a 
Tonopen tends to underestimate high IOPs (Kooner et al., 1992).  An alternative strategy would 
be to only assess IOP using Goldmann tonometry.  However, some 10 year olds will not tolerate 
Goldmann tonometry, but will tolerate rebound tonometry or a Tonopen.   Flemmons and 
coworkers reported that 3 of 17 children with glaucoma (mean age, 10 years) would not tolerate 
Goldmann applanation tonometry, but would tolerate IOP assessment using ICare or a 
Tonopen.   
 
When Goldmann applanation tonometry is used, a drop of topical anesthetic mixed with 
fluorescein should be placed on the cornea.  At least 2 measurements should be obtained that 

14 
 
Ver. 04.29.2015 
 
are within 3 mm Hg of each other. If the readings are more than 3 mm Hg apart, then a third 
reading should be obtained. The average of the 3 IOP readings should be used as the study 
IOP.  We anticipate that about 10% of the patients in our study will not tolerate Goldmann 
applanation and will require the IOP be measured with ICare or a Tonpen. If the IOPs obtained 
with ICare or a Tonopen are normal, no further testing will be performed.  However, if the IOP is 
elevated (>21 mmHg) with ICare and/or Tonopen another attempt will be made immediately to 
measure the IOP using Goldmann applanation.  If the child will still not tolerate Goldmann 
applanation, another attempt will be made 1-2 hours later after the child has had a lunch or 
snack and has rested.  If the child will still not tolerate Goldmann applanation, arrangements will 
be made for the child return within 30 days to have the elevated IOP verified using Goldmann 
applanation. We anticipate that this scenario will occur in fewer than 5 patients.  
 
When using rebound tonometry, the child should be sitting in a chair with the instrument 
positioned vertically.   Icare rebound tonometry measurements should not be taken on a given 
eye until a long beep is heard, and the instrument panel shows a reliable IOP reading (with no 
error bar or the error bar on the bottom of the screen).  If the error bar is in the middle of the 
screen, and the IOP reading is below 21 mm Hg, then this is also acceptable as a reading.  At 
least two IOP measurements with reliable readings should be obtained within 3 mm Hg of one 
another, or a third reading should be taken and recorded.  If the error bar is in the middle (with 
IOP above 20 mm Hg) or at the top of the screen, indicating a less reliable reading, the 
measurement should be repeated until a reliable reading has been obtained.   
 
When using a Tonopen, the IOP reading should be taken with a 5% confidence interval noted 
on the instrument.  At least 2 readings should be obtained within 3 mm Hg of each other.  If the 
average IOP is > 21 mm Hg with ICare rebound tonometry or a Tonopen, a confirmatory IOP 
should be measured using Goldmann applanation tonometry.     
 
Pupils 
 
Pupils will be assessed for size (diameter in millimeters), shape (round or not), and position 
(central or eccentric). 
 
 
Cycloplegic Refraction 
 
 A cycloplegic refraction of both eyes will be performed without external correction (ie, not over 
contact lens or spectacles) and using a phoropter or trial frame. Enough dilation should be 
achieved to accommodate later fundus imaging. 
 
 
E-ETDRS Acuity Assessment after Cycloplegic Refraction 
 
Monocular Visual Acuity Testing – Recognition Acuity 
 
Visual acuity measures will be standardized at each clinical site by using the Electronic Visual 
Acuity Tester (EVAT). The EVAT runs a visual acuity testing program called E-ETDRS. This 
program was developed to provide a visual acuity letter score that is comparable to the ETDRS 
chart testing score. Visual Function Examiners (VFE) will have been certified to perform vision 
testing according to the protocol. Visual acuity will first be tested binocularly and then 
monocularly for each eye. 
 

15 
 
Ver. 04.29.2015 
 
Electronic Visual Acuity Tester (EVAT) 
 
The EVAT is an automated system that displays the acuity stimuli on a monitor. It uses a 
programmed Palm handheld device (or tablet PC) that communicates with a personal computer 
running a Linux (or Windows) operating system. This system was developed by JAEB for the 
ATS projects. Ten IATS sites use this system in their clinics; the other 2 sites have the E-
ETDRS test available on the M&S acuity tester.  VFE certification will occur via an online test at 
PEDIG sites and will be a paper test created by the JAEB Center for non-PEDIG sites. 
 
Optical Correction 
 
If the child was wearing a CL, the lens should be replaced on the study eye and any residual 
correction placed in a trial frame. Any correction needed for the fellow eye will also be placed in 
the trial frame.  If the child normally wears spectacles, the vision should not be tested using 
them as there may be imperfections in the lenses.  Instead the cycloplegic refraction should be 
placed in a trial frame. 
 
Monocular Occlusion 
 
 A translucent occluder will be used to minimize the presence of latent nystagmus under 
monocular conditions. If this type of occluder is not available, an appropriate high plus power 
(e.g., +10D) lens may be used 
 
Range of Testable Acuity 
 
If the child is unable to see the largest (20/800) stimulus at the 3M testing distance, the testing 
will be conducted at 1 meter. The same procedure will be followed at 1 meter as was used at 3 
meters. If the child is unable to detect the 20/800 stimulus at 1 meter (ie, VA < 20/2400), then 
the E-ETDRS testing will be stopped for this eye and the test for Hand Motion will be performed. 
 
Assessment of Hand Motion Vision 
 
The examiner’s hand is extended to about two feet in front of the eye being tested; the fellow 
eye is occluded. With a light shining from behind the patient onto the examiner’s hand, the hand 
is moved either up-and-down or side-to-side in front of the eye at a steady speed of about one 
cycle/second.  The patient is asked to identify the direction of motion of five separate trials. Four 
out of five correct responses indicate the presence of Hand Motion vision.  If fewer than four 
responses are correct, check for Light Perception vision. 
 
Assessment of Light Perception  
 
Children who are unable to perform E-ETDRS or Hand Motion testing in the treated eye will 
have that eye assessed for the presence of light perception (LP).  LP will be tested with an 
indirect ophthalmoscope. Testing for LP will take place in a darkened room. Because the LP 
testing needs to be done monocularly, it is necessary to block the eye not being tested from all 
possible light to preserve accuracy. Standard eye patches alone do not achieve complete 
occlusion, and for this reason the tester, parent, or helper will place the palm of his or her hand 
gently but firmly over the patched eye thereby blocking out all light.  The bright light from the 
indirect ophthalmoscope will then be directed at the uncovered eye 3 or 4 times from the front 
and sides at 18 – 24 inches from the face to avoid exposing the child to the heat of the light. The 
tester will ask the child to respond when the light is seen or to watch for consistent changes in 

16 
 
Ver. 04.29.2015 
 
behavior occurring only when the light is being presented, such as eye movement towards or 
away from the light or head turn towards or away. If the examiner is convinced that the child 
does not perceive light, the vision will be recorded as No Light Perception. 
 
Pachymetry   
 
Pachymetry will be performed using the Pachmate (DHG Technology) or similar pachymeter 
after the instillation of a topical anesthetic drop.  The probe tip will be touched to the center of 
the cornea and measurements will be taken until there is 1 with a SD <10 microns. 
 
Optical Biometry   
 
Axial Length 
  
Biometry to determine axial length will be performed on both eyes using the non-contact 
instrument, the IOLMaster (Carl Zeiss Meditec, Dublin, CA) or Lenstar (Haag-Streit USA, 
Mason, OH).  At least three measurements will be obtained for each eye and then averaged to 
hundredths of a millimeter.  Both the raw data/scan and the summary page is to be printed out 
and faxed to the DCC. 
 
Keratometry   
 
Keratometry readings will be obtained using the IOLMaster or Lenstar. The AUTO mode will 
give the average of three measurements; two such averages should be obtained for each eye 
and their average recorded.  Manual keratometry may be done if necessary. 
 
Corneal Diameter 
 
Corneal diameter will be taken from the IOLMaster or Lenstar biometry print-out. 
 
 
Indirect Ophthalmoscopy 
 
Indirect ophthalmoscopy will be performed on the dilated eyes to determine the cup-to-disc ratio 
and to assess the health of the optic nerve and retina. 
 
 
QUALITY OF LIFE MEASURES 
 
Caretakers will be given a packet of questionnaires to take home.  These are to be completed 
by either the primary caretaker or the study participant.  They will be accompanied by detailed 
instructions and a stamped, addressed envelope for returning them to the Coordinating Center.   
 
The questionnaires are: 
 
Pediatric Quality of Life Inventory (PedsQL) 
Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q)  
Child Behavior Checklist 
Self-Perception Profile for Children 
Participation and Environment Measure for Children and Youth (PEM-CY)  
Parenting Stress Index, Short Form (PSI-SF)  

17 
 
Ver. 04.29.2015 
 
 
CHAPTER  4     IMAGING 
 
 
Anterior Chamber OCT (AC OCT) 
Anterior Chamber OCT will be performed on the undilated eyes. We prefer to use the 
Heidelberg SPECTRALIS spectral domain OCT machine. Heidelberg has created an anterior 
segment analysis lens and a specialized program. The Heidelberg SPECTRALIS anterior 
segment module, ASM, was approved by the FDA in March 2012 (Heidelberg Corporation, 
2012). Leung et al. (Leung CK, 2008) found high reproducibility of results with the Heidelberg 
OCT along with agreement with gonioscopy findings. It is performed prior to instillation of any 
dilating drops. 
 
Optic Disc Photos 
Stereoscopic disc photographs are an established means of evaluating optic discs for 
glaucomatous damage.  All patients will have stereoscopic disc photographs taken after dilating 
the pupils. Dilation will be performed prior to obtaining optic disc photographs. Simultaneous 
stereo images centered on the optic disc should be performed on both eyes using a digital 
fundus camera. The resolution of the disc photos should be such that the disc margins and 
vasculature are clearly visible. Disc photographs will be reviewed independently by three 
ophthalmologists with expertise in pediatric glaucoma (Sharon Freedman, Allen Beck, and 
David Plager). Photographs will be graded as normal, glaucoma suspect, or glaucomatous optic 
neuropathy primarily by comparing the appearance of the study eye to the fellow eye. Disc 
photographs were not part of the Phase 1 or 2 protocols due to the difficulty of obtaining high 
quality photographs in very young children.  
 
Optic Nerve Fiber Layer OCT 
Spectral domain optical coherence tomography (SD-OCT) has been shown to be a powerful  
tool evaluating and managing adults with glaucoma, and can even predict among glaucoma 
suspect those eyes at higher risk for developing visual field loss (Mwanza et al., 2011; Miki at al, 
2014).  In children, peripapillary retinal nerve fiber layer thickness (RNFL) assessed by either 
time domain OCT [Hess et al; Nadeau et al., 2010] or, more recently, by SD-OCT [Alasil et al, 
2013], has been shown to be effective in differentiating between normal eyes and eyes with 
glaucoma (Ghasia et al., 2013; Srinivasan et al, 2014).  RNFL measurements of both eyes will 
be taken using the Heidelberg Spectralis OCT by a trained OCT imager, with a baseline signal 
strength of at least 25.  Average RNFL will be compared between the surgical and the normal 
fellow eyes for all subjects, the latter serving as the control group.  Average RNFL will be 
compared among study eyes with glaucoma suspect or glaucoma status, and those without a 
glaucoma-related adverse event.  Quadrant level analysis of RNFL thickness will be carried out 
to detect trend in thinning among those with glaucoma-related adverse events compared to 
normal fellow and unaffected study eyes.  Similarly, the difference in average RNFL between 
study and control fellow eyes will be compared for children with glaucoma suspect, glaucoma, 
and those with neither.  Average RNFL will be correlated with optic nerve head cupping and the 
presence or absence of glaucomatous optic neuropathy (assessed by masked review of 
stereophotographs) across all study eyes.   
 
The OCT data will be submitted digitally so that they can be reviewed remotely without 
copy/fax/scan issues. Evaluation will consist of a look at the mean NFL, the 
superior/inferior/nasal/temporal quadrant numbers, and symmetry with the fellow eye.  
 
 

18 
 
Ver. 04.29.2015 
 
CHAPTER 5  STATISTICAL CONSIDERATIONS & DATA CAPTURE AND MANAGEMENT 
 
Study Design 
IATS is a randomized controlled clinical trial with patients originally assigned to either CL or IOL 
as a correction for aphakia after cataract surgery. During Phases 1 and 2, investigators 
diligently avoided implanting a secondary IOL in patients randomized to CL correction except 
when it would be in the best interest of the child to have a secondary IOL because of lack of 
compliance with CL correction. Steering Committee approval was required before a secondary 
IOL could be implanted and documentation of the efforts to improve CL compliance had to be 
submitted before approval was granted.  No child randomized to CL received a secondary IOL 
before the vision test at 12 months of age. As of December 2013 when all 57 study participants 
who were randomized to CL completed the study, only 3 had received a secondary IOL before 
the 5Y visit. Since the 5Y visit, 16 children in the CL group have received secondary IOLs. 
 
Glaucoma 
At age 1 year we did not find a statistically significant difference in the percent of patients with 
glaucoma/glaucoma suspect between the IOL  and CL treatment groups (16% vs 9%, 
respectively, p =  0.39, 95% CI for difference = 6% - 21%). At 5 Years, those numbers were 
higher (CL 35% and IOL 28%), but were still statistically equal. We hypothesize that newly 
diagnosed glaucoma/glaucoma suspect will occur more frequently between the ages of 5 and 
10 years in the study eyes randomized to the CL group resulting in a higher cumulative 
incidence of glaucoma in this group. The percent of patients with glaucoma at 10 years of age 
will be compared between the treatment groups using Fisher’s exact test. As described above 
under the statistical considerations for visual acuity, we expect very little missing data. We will 
conduct sensitivity analyses comparing results for patients examined at 10 years of age with 
results in which patients not examined at 10 years who did not previously have glaucoma will be 
assumed to either have or not have glaucoma at 10 years of age. Patients not examined at 10 
year of age who were previously diagnosed with glaucoma will retain that diagnosis in the 
sensitivity analyses, since per the IATS protocol, once a patient is diagnosed with glaucoma the 
patient is considered to have glaucoma for the remainder of the study. 
We expect that the percentage of patients with glaucoma in treated eyes will double between 
the age 1 and 10 year examinations in the CL group whereas the percent will remain largely 
unchanged in the IOL group. 
 
Myopic Shift  
In the IATS, all pseudophakic eyes had a targeted undercorrection of 6 or 8 D based on age at 
the time of cataract surgery and primary IOL implantation (age 4-6 weeks, 8 D; age 7-28 weeks, 
6 D).  However, only 41% of eyes had an absolute prediction error of 1 D or less and the mean 
absolute prediction error was 1.8 D (VanderVeen et al., 2012).  The myopic shift in these eyes 
was 0.53 D/month (95% CI; 0.42 to 0.63 D/month) until age 12 months and then 0.12 D/month 
(95% CI; 0.09 to 0.15 D/month) until age 42 months.  From age 4 to 5 years, there was a mean 
myopic shift of 0.79 ± 1.56 D (range, -8 to +3 D).  At age 5 years, the median (25th, 75th 
percentiles) refractive error in the treated eyes in the IOL group was -2.25 D (-7.25, 0.00) 
(range, -19.00 to +5.00 D). As expected, the median refractive error was larger in eyes with 
glaucoma compared to eyes without glaucoma. The variability in axial elongation was the 
primary reason for the wide range of refractive errors in these eyes at age 5 years (Lambert et 
al., 2012). Three eyes in the IOL group underwent an IOL exchange to correct a large myopic 
refractive error:  one during the first postoperative year and 2 after the first postoperative year to 
correct refractive errors of -10.00, -8.50, and -19.00 D, respectively.  None of these eyes had 
glaucoma. 

19 
 
Ver. 04.29.2015 
 
Data Capture and Management 
Data management procedures for this new phase of IATS have been designed with the 
following in mind: (1) Newly captured data will need to be integrated with the extensive IATS 
database from phases 1 and 2 in order to accommodate the scientific work needed to address 
the specific aims of the study, especially those involving longitudinal analyses; (2) many of the 
clinical center and Data Coordinating Center (DCC) staff from earlier phases of IATS will be 
working on the new phase; (3) FDA regulatory and reporting requirements will continue to apply 
to IATS, as they have in the past; (4) the development, refinement, implementation and 
maintenance of data management procedures must be efficient and streamlined, especially 
since the new phase involves just one clinical examination of each subject. 
The DCC staff, data management programming and procedures for the new phase of IATS 
have been streamlined, and leverage the experience, existing infrastructure and resources of 
the current IATS DCC. Leveraging existing resources, rather than developing, implementing, 
refining and maintaining brand new systems for data management for the new phase that are 
separate from the systems for previous phases of IATS, is the most efficient approach, and is 
likely to have a direct and positive impact on data quality and scientific work in the study.  
Data will be captured and managed using the latest, internet-based electronic data capture 
(EDC) modules that are part of Clinical DataFax Systems Incorporated’s (CDSI) client-server 
data management software, iDataFax and DataFax (hereafter referred to as iDataFax). The 
data management system used in previous phases of IATS was based on earlier versions of the 
same CDSI software system, and is currently maintained by DCC staff using the latest version 
of this system. The DCC team that is in place is smaller than in past phases, but has extensive 
experience with CDSI’s software, as is detailed in the sections below. Clinical center staff from 
the previous phases of IATS also have experience interacting with CDSI’s data management 
system, especially in terms of receiving and responding to quality control reports generated by 
the system. The main difference for clinical staff in the new phase is that their data will be 
electronically entered into and captured by the system, instead of case report forms having to 
be faxed into it. The small amount of training that is required to become proficient in the use of 
CDSI’s EDC module will be provided the DCC staff who have extensive experience in doing so. 
Strict and extensive quality control programming and procedures are in place in the existing 
data management system for IATS. The continued use of CDSI’s software, iDataFax, will allow 
for the programming and procedures to be efficiently extended into the new phase, will provide 
the best chance for maintaining the highest data quality, and will make it possible for us to 
continue to meet FDA regulatory and reporting requirements in the most efficient and rigorous 
manner.  
 
Data Capture, Flow and Handling 
A diagram of the systems for data capture, management and statistical reporting and analysis is 
shown in the “IATS Data Flow) figure below. The coordinator at each clinical site will record 
exam data on paper source document worksheets, and will then enter them into an electronic 
Case Report Form (eCRF) using the iDataFax EDC module installed on a local computer. The 
eCRF will look exactly like the source document worksheet, since the latter forms the 
background of the image on the EDC module screen into which the data are entered. The 
current drafts of the eCRFs and the source document worksheets will duplicate the eCRFs in 
format. The EDC module is able to connect to the main database on a server at the DCC, and 
will automatically store the data there in real time. Edit checks for data field validity will be 
applied at data entry time, and additional edit checks will be applied using nightly batch jobs 
running on the main server at the DCC. Any data issues will be marked by a query that 
describes the problem. Queries will be emailed to the clinical centers as a Quality Control 
Report (QC Report) on a monthly basis. Clinical coordinators fix most problems by making 
changes to the eCRF via the EDC module, which changes the query status from outstanding to 

20 
 
Ver. 04.29.2015 
 
pending central review. The DCC clinical data manager will review the eCRF edits on a weekly 
basis and the queries will be either reinstated for further clarification or marked as resolved. 
iDataFax maintains an audit trail of eCRF edits made by both clinical center and DCC 
personnel. 
 
Medical records such as clinical records related to adverse events and operative reports will 
also be submitted to the system via the EDC module as scanned images, which can be 
attached to the relevant eCRF page in the database.  
 
For the purposes of remote monitoring of clinical sites, the clinical sites will upload scanned 
source document worksheets requested by the Clinical Data Manager at the DCC. The Clinical 
Data Manager will compare source document worksheets against electronically entered data. 
Discrepancies will result in queries being marked in the system, which will be included in the 
regular QC Report. 
 
iDataFax can export data in forms that can be read by commonly used statistical analysis 
software packages. Daily exports from iDataFax will be performed by batch jobs running on the 
main server. Daily automated batch routines developed by the DCC Statistical Programmer will 
import the data into SAS data sets. These data sets will be used for standard analysis and 
reporting, performed on a weekly basis, for the purpose of providing information at regular 
executive and steering committee meetings. Department of Biostatistics and Bioinformatics 
personnel have developed a system of S-Plus functions that produce the code for making tables 
and graphs in LaTex, a mark-up language commonly used in mathematical fields for document 
processing. This system has been in use in previous phases of IATS, and will continue to be 
maintained, refined and used in this new phase for the purposes of producing standard reports 
for the FDA. 
 

21 
 
Ver. 04.29.2015 
 
IATS Data Flow 
 
Data Storage and Security 
The electronically captured study data will reside exclusively on a secure, firewall- and 
password-protected Unix server at the Rollins School of Public Health (RSPH) of Emory 
University. The server is described in detail in the Facilities and Other Resources section of this 
grant application. It is housed in the locked server room of the RSPH, to which only certain staff 
members of the RSPH information technology (IT) group have keys. RSPH IT staff maintain the 
server, and perform daily incremental, and weekly full backups. 
 
The data management system on the server will be accessed by IATS DCC staff from within the 
RSPH building via the school’s secure internal network. At clinical centers, access to the EDC 
system will be limited to authorized personnel at the clinical centers (the center coordinator and 
PI), who will have access only to the data for their centers. The EDC module of iDataFax is 
compliant with all regulatory requirements including e-signatures, audit trails, and rules for 
password complexity, aging and notification. All changes to the database, at the data record and 
individual data field level, are recorded and include the id of the user making the change and the 
date and time of the change. The transmission of entered data and pdf files over the internet 
uses 128 bit SSL encryption. 
 
 
Clinical Center Monitoring 
Regular (weekly) Quality Control (QC) reports will be issued for each clinical center detailing 
eCRF data quality issues. DCC staff will continuously monitor eCRfs to ensure that 
 
all eCRFs are completed  
SAS 
Data Merging, Edits,
Calculations 
SAS Data Sets 
S - Plus
LaTex
Standard Reports 
Statistical Analysis 
and Reports
Clinical Centers
iDataFax 
Secure Server 
eCRF & Source Document 
Acquisition and Storage; 
Edits, QC Notes, 
Remote Monitoring 
EDC 
QC Reports 
Statistical Analysis
and Reports
DCC

22 
 
Ver. 04.29.2015 
 
 
all eCRFs are up to date 
 
entered data are complete, accurate and follow study protocol and procedures.  
 
all eCRF corrections have been completed since last QC report 
 
In addition to these weekly QC reports, we will implement a centralized, risk-based plan for 
remote monitoring of site study activities that is based on the specifications included in the “FDA 
Guidance for Industry: Oversight of Clinical Investigations – A Risk-Based Approach to 
Monitoring” (US Department of Health and Human Services, Food and Drug Administration, 
2013). The DCC Associate Director and Clinical Data Manager, in collaboration with the Study 
Chairman, will identify critical data elements and study administration or regulatory processes to 
be monitored and reviewed. At the Clinical Data Manager’s request, the clinical sites will upload 
scanned source document worksheets and any other requested clinical or regulatory records 
using the EDC module of iDataFax. The Clinical Data Manager will compare source document 
worksheets against electronically entered data to review their accuracy, and will review and 
evaluate other uploaded documents as appropriate. Discrepancies will result in queries being 
marked in the system, which will be included in the regular QC Report. Remote monitoring of 
each clinical site will be performed on an ongoing basis. 
 
Statistical Analysis 
Descriptive analyses will be conducted to characterize the study population and detect potential 
selection bias as a result of missing data, dropouts or noncompliance/non-adherence. Two-
sample t-tests will be used to compare continuous variables between two treatment groups. For 
continuous variables that are not normally distributed, appropriate transformations will be 
applied before normality-based tests are used or nonparametric tests such as Wilcoxon tests 
will be used as appropriate. Chi-square tests or Fisher’s exact tests will be used to compare 
categorical variables between groups. 
All primary analyses will be intention-to-treat. The percent of patients with glaucoma/glaucoma 
suspect at 10 years of age will be compared between the treatment groups using Fisher’s exact 
test. We will also explore the role of baseline characteristics in the development of the primary 
endpoint using logistic regression and the Akaike information criterion (AIC; Akaike, 1974) will 
be used for model selection. In addition to analyzing the percent of patients who develop 
glaucoma/glaucoma suspect at any time up to age 10, we will also investigate analyzing the 
time to the primary endpoint using survival analysis methods, including the product-limit method 
to estimate the probability of developing glaucoma/glaucoma suspect versus time after surgery, 
comparing the time to developing glaucoma/glaucoma suspect between treatment groups with a 
log-rank test, and exploring the role of baseline characteristics with proportional hazards 
regression. The use of survival analysis methods may be problematic depending on how 
successfully we are able to determine the date of diagnosis, particularly for those patients who 
develop glaucoma/glaucoma suspect between 5 and 10 years of age when patients are not 
being examined within the study. Of note, patients not examined at 10 years of age who were 
previously diagnosed with glaucoma/glaucoma suspect will retain that diagnosis in all analyses, 
since per the IATS protocol, once a patient is diagnosed with glaucoma/glaucoma suspect the 
patient is considered to have glaucoma/glaucoma suspect for the remainder of the study.  
 
As secondary analyses, we will repeat the aforementioned analyses for the secondary endpoint 
of glaucoma. In addition, we will use logistic regression for a multinomial outcome (proportional 
odds models or baseline logic models) to analyze the three categories, Glaucoma, Glaucoma 
Suspect, and normal (not glaucoma/glaucoma suspect) jointly.  
 

23 
 
Ver. 04.29.2015 
 
Linear mixed models (LMMs) will be used to characterize the change in refractive error over 
time for both the treated and fellow eyes in the IOL group and to compare the changes in the 
treated eyes of the two treatment groups. In addition, LMMs will be used to identify baseline risk 
factors such as age of cataract surgery and axial length and other factors that arise during 
childhood, such as amblyopia and glaucoma, that are associated with a larger than expected 
myopic shift in the IOL group. 
 
We will use two approaches for handling missing data as needed. First, we will use the 
available-case approach (Little and Rubin, 2002), i.e., conducting the proposed analyses 
excluding patients for whom the glaucoma/glaucoma suspect status is not verified at 10 years. 
Second, we will use the approach of multiple imputation (Little and Rubin, 2002) before 
conducting the proposed analyses and we will also conduct sensitivity analysis (Little et al., 
2012). In addition, to correct for potential selection bias as a result of non-adherence to patching 
in early years and/or having a secondary IOL in the CL group, we will use approaches including 
instrumental variable and propensity scores (Little et al., 2009; Rosenbaum and Rubin, 1983). In 
addition, in case there are deviations from the target date for the outcome measurement, we will 
adjust for the time of the outcome measurement in our analyses as appropriate. 
 
In addition to development of glaucoma, other clinical outcomes will also be measured and the 
analysis methods to be used in describing those outcomes are as follows. 
 
Visual Acuity: For visual acuity at 10 years of age, we intend to use the Wilcoxon rank-sum test 
to compare the median visual acuities of the two treatment groups, with the patients included in 
the treatment group to which they were randomly assigned (intention-to-treat). As described in 
the section above (Status of Patients between Phases 2 and 3), among the patients randomized to 
CL who have thus far completed the 5 year of age exam, 38% have had secondary IOL 
implantation (insertion of an IOL after the initial cataract surgery). Thus, unlike in Phase 1 (1 
year of age) when none of the contact lens patients had a secondary IOL and in Phase 2 (5 years 
of age) when only 2 contact lens patients had received a secondary IOL, for Phase 3 (10 years of 
age), a substantial percent of the patients in contact lens group will have a secondary IOL. 
Therefore, for visual acuity at 10 years of age, IATS will be a comparison between one treatment 
in which patients have an IOL inserted at the time of the cataract surgery and a second treatment 
in which patients are initially treated with a contact lens with the option of implanting a 
secondary IOL after 5 years of age. Analyses that attempt to address the question of a secondary 
IOL versus no IOL would likely be fraught with bias. Although the decision to have a patient 
undergo secondary IOL implantation is largely one of physician and parental preference, the 
condition of the patient is also a factor. For example, a secondary IOL would not be implanted in 
a patient with extremely poor vision. Therefore, such comparisons will be avoided. 
 
In addition to the analysis to compare visual acuity at age 10 between the treatment groups, we 
will also investigate the relationship between baseline factors and the visual acuity at age 10. 
Since as described above we expect that visual acuity at age 10 will be skewed, for the 
multivariate analyses using linear regression, we will explore transformations of visual acuity to 
a less skewed distribution that also addresses the issue of lower threshold values for patients with 
extremely poor vision. Another approach we will investigate is categorizing visual acuity into 2 
categories depending on whether or not the patient’s vision is within normal limits (Driver et al., 
2008) and using logistic regression to evaluate the relationship with baseline characteristics. 
 

24 
 
Ver. 04.29.2015 
 
Adverse Events and Additional Ocular Surgery: The occurrence of adverse events and the 
need for additional ocular surgery will also be assessed (see the age 10 exam CRFs in Appendix 
8). For those events and surgery that are specific to the IOL group, we will provide point and 
confidence interval estimates of the percent of patients experiencing those events. For events that 
apply to both treatments, we will apply the methods described above for glaucoma. 
 
Ocular Alignment: The occurrence, type and extent of deviations will be described with basic 
descriptive statistics. Life table methods will be used to estimate the probability of being non-
orthophoric at each of the follow-up visits and the development of strabismus over time will be 
compared between the treatment groups using the log-rank test. Patients who undergo strabismus 
surgery will be classified as non-orthophoric at the time of surgery 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CHAPTER 6  Study Administration  
 
Certification Procedures 
 
All of the clinical coordinators and investigators were certified before beginning Phase 1 of the 
IATS using an online certification test administered by the JAEB center.  All but two of the 
original IATS investigators continue to participate in the IATS.  Both of these Sites had certified 
sub-Investigators who were approved to assume the role of PI. 
 
Investigators 
All of the current clinical site PIs have expressed a willingness to participate in Phase 3 of the 
IATS.  No further certification will be required for current IATS investigators.   
 
Coordinators 
Site Coordinators who have already been certified will require no further certification.  Personnel 
who will serve as new coordinators must take the certification exam administered by the JAEB 
Center. 
 
Investigator/Coordinator Training 
To accommodate the different “start” times for Phase 3, in lieu of a training meeting, we will 
have a repeatable online/conference call training session.  All are welcome to attend the first 
presentation, but the coordinators at sites that will see their 10 year old patients who are nearing 
11 years old in 2015 will be required to attend a presentation prior to the first 10Y visit.  
 

25 
 
Ver. 04.29.2015 
 
 
Visual Function Examiners (VFEs) 
Many of the IATS Sites are also PEDIG sites and have personnel who are certified to administer 
the E-ETDRS computer program (EVA) developed by the JAEB Center.  Phase 3 will use these 
vision testers as the masked examiners.  For those IATS Sites that do not have a PEDIG-
certified VFE, the JAEB Center has agreed to provide a certification exam to a designated 
person or persons at the site (see Appendix 7).  Each Site should have two (2) people 
designated as masked VFEs.   
 
 
 
Study Organization  
 
 
Projected Timeline for Phase 3 of the IATS 
 
8/22/14     Visit window opens for Age 10 year examination of oldest patient  
 
8/31/15     Funding for Phase 2 (Year 12) ends  
9/01/15     Funding for Phase 3 begins  
 
2/19/18     Age 10 year visit window opens for examination of youngest patient  
 
 
 
 
 
 
 
Numbers of Patients Enrolled in the IATS who Become 10 Years of Age by Grant Year 
 
Grant Year/Beginning Date 
Phase 3 
# (Age, 10 years)  
 
 
   Year 13   9/1/2015 
52 
   Year 14   9/1/2016 
35 
   Year 15   9/1/2017 
25 
   Year 16   9/1/2018 
  2 
 
 
Performance of Individual Sites 
 
All of the individual sites have performed well in the study.  On average, 91% of the expected 
follow-up visits have been completed to date. Most clinical sites have had patient follow-up rates 
>90%.  Three sites have had patient follow-up rates near 80%; Baylor (81%); Emory (80%); and 
Indiana University (79%).  The lower rates of expected follow-up visits at these clinical sites has 
largely been due to individual patients at these clinical sites who have been lost to follow-up or 
who have been difficult to follow. Only one patient was lost to follow-up at the 5Y visit. 
 
 

26 
 
Ver. 04.29.2015 
 
Data Sharing Plan 
 
Following NIH policy, the IATS investigators are submitting a plan for sharing final research data 
in line with the goal of making the data “as widely and freely available as possible while 
safeguarding the privacy of the participants and of protecting confidential and proprietary data” *. 
NIH policy also recognizes that “the investigators who collected the data have a legitimate 
interest in benefiting from their investment of time and effort”. 
The sharing of the IATS data will conform to the following considerations: 
 
Patient confidentiality: All subject-specific data will be de-identified in the shared data files. In 
the IATS database maintained at the DCC, study patients are identified in the database by a 
unique 5-digit IATS ID Number consisting of a two-digit center number and 3-digit sequence 
number within the center. In shared databases the IATS ID will be stripped and a randomly 
generated sequence number will be assigned to each patient. The clinical center the patient 
was enrolled at will not be identified. Specific dates will not be included in the data file; rather, 
time intervals will be provided. The DCC will not share any patient health information listed 
among the 18 categories of direct identifiers that according to HIPAA regulations must be 
absent for a dataset to be considered limited. 
 
Content and format of the data files: The content of the data files would be records, keyed by 
the randomly assigned sequence number described above, and containing the raw data values, 
subject to the privacy issues also described above. We will consider making the data available 
in a variety of formats, such as ascii files and Statistical Analysis System (SAS) transport files. 
Descriptions of the files will also be provided along with programming statements, such as the 
SAS Data Step code to input the data file.  
 
Documentation:  Documentation describing the conduct of the study such as the protocol, 
manual of procedures, and major published papers will be provided to lessen the likelihood that 
the definition of the data or how it was collected will be misunderstood or inadvertently misused. 
 
Methods for release:  At this time we are not specifying what form this will take since 
technological advances and future policy will impact our options. However, we will consider 
various possibilities including making the material available on the website of the Rollins School 
of Public Health of Emory University or submitting the material to a reputable repository for 
clinical trial data. 
 
Timing of data release: Since IATS is a relatively complex trial, a large variety of data items will 
be collected. Making all items in the database available at once in conjunction with the 
publication of the first results paper is not prudent. We plan to make the data available in a 
series of releases after the publication of papers related to the pre-specified objectives and 
analyses. The files could be linked by the randomly assigned sequence number described 
above. The timing would be intended to coincide with the NIH policy that: “NIH continues to 
expect that the initial investigators may benefit from first and continuing use but not from 
prolonged exclusive use.”  
 
Licensing: At this time we do not expect to require any license agreements or data sharing 
agreements. 
 
Responding to queries: Given the possibility that responding to queries regarding the data could 
be onerous, we do not plan to make such an offer when data is released. 

27 
 
Ver. 04.29.2015 
 
* Quotations made in the text are from the NIH Data Sharing Policy and Implementation 
Guidance (Updated March 5, 2003) on the NIH Office of Extramural Research website at the 
address: http://grants.nih.gov/grants/policy/data_sharing_guidance.htm downloaded on 1/18/07. 
 
 
 
Study Headquarters:  The IATS chair’s office is located in the Department of Ophthalmology at 
Emory University.  The chair will be responsible for the overall supervision of the study. 
 
Data Coordinating Center:  The IATS Data Coordinating Center (DCC) is located in the 
Department of Biostatistics and Bioinformatics of the Rollins School of Public Health of Emory 
University and is responsible for the statistical and data management activities of the study. The 
School of Public Health is located only a few blocks from the Department of Ophthalmology.   
 
Participating Clinical Centers: 
Emory University, Atlanta, GA —PI, Scott Lambert 
Harvard University, Cambridge, MA —PI, Deborah VanderVeen 
Medical University of South Carolina, Charleston, SC —PI, M. Edward Wilson 
Cleveland Clinic, Cleveland, OH —PI, Elias Traboulsi 
University of Texas, Southwestern, Dallas, TX —PI, David Weakley 
Duke University, Durham, NC —PI, Sharon Freedman 
Baylor College of Medicine Houston, TX —PI, Kimberly Yen 
Indiana University, Indianapolis, IN —PI, David Plager 
Miami Children’s Hospital, Miami, FL —PI, Stacey Kruger 
University of Minnesota, Minneapolis, MN —PI, Erick Bothun 
Vanderbilt University, Nashville, TN —PI, David Morrison 
Oregon Health and Science University, Portland, OR —PI, Lorri Wilson 
 
 
Executive Committee 
The Executive Committee will be responsible for the day-to-day activities of the study and will 
meet weekly. The Executive Committee will organize all other committee meetings except for 
the DMOC and will be responsible for implementing changes in the Protocol and Manual of 
Procedures as needed.  However, all substantive policy decision will be presented to the 
Steering Committee.  The Executive committee will consist of the Study chair (Scott Lambert), 
the Director of the Data Coordinating Center (Qi Long), the Associate Director of the Data 
Coordinating Center (Azhar Nizam), the Data Manager (Seegar Swanson), the Epidemiologist 
(Carolyn Drews-Botsch), and the National Clinical Coordinator (Lindreth DuBois). 
 
 
 
Steering Committee 
The Steering Committee will approve all substantive changes to the Protocol and will review the 
progress of the study.  They will ensure that there is agreement on the specifics of the Protocol 
and that it represents the clinical practice in different regions of North America.  The Steering 
Committee will hold a conference call monthly.  The Steering Committee will consist of all 
members of the Executive Committee and 3 additional clinical center Principal Investigators 
(Edward Buckley, David Plager, M. Edward Wilson), a pediatric glaucoma expert (Sharon 
Freedman), a Site Coordinator representative, and Donald Everett as an ex-officio 
representative from the National Eye Institute. 

28 
 
Ver. 04.29.2015 
 
 
Writing Committee 
The Writing Committee develops policies for the Study with regard to publication, initiates all 
primary outcome manuscripts, and participates in their authorship.  An important responsibility 
of the Editorial Committee is to prioritize the use of Study data.  This committee consists of the 
Study Chair (Scott Lambert, MD), the Director of DCC (Qi Long), the Associate Director of DCC 
(Azhar Nizam), Study Epidemiologist (Carey Drews-Botsch), and National Clinical Coordinator 
(Lindreth DuBois).   All clinical investigators will be given the opportunity to serve as the lead 
author for at least one study publication.  Approval will be obtained from the DSCM prior to 
publishing primary outcome data.  The DMOC will also be kept informed of the publication of all 
secondary outcomes. 
 
 
 
Investigators and Coordinators Group  
This group will consist of all Principal Investigators and sub-Investigators, members of the 
Executive Committee, and all Clinical Coordinators.  A group meeting will be held before the 
Phase 3 to familiarize investigators with the study protocol.  Informational on-line meetings will 
be held with coordinators to familiarize them with the specifics of the protocol and data 
collection.  An Investigator meeting will be held annually in conjunction with the annual meeting 
of AAPOS to review the IATS Phase 3 protocols and to discuss the progress of the study. 
 
 
 
BIBLIOGRAPHY AND REFERENCES CITED/PROGRESS REPORT PUBLICATION LIST 
a.   Bibliography and References Cited 
 
Abidin, R. R. (1983). Parenting Stress Index:  Manual, Administration Booklet and Research 
Update. Charlottesville, VA, Pediatric Psychology Press. 
Akaike, H. (1974). "A new look at the statistical model identification." Automatic Control, IEEE 
Transactionss, 19(6): 716-723. 
Asrani, S., S. Freedman, V. Hasselblad, et al. (2000). "Does primary intraocular lens 
implantation prevent "aphakic" glaucoma in children?" J AAPOS 4(1): 33-39. 
Autrata, R., J. Rehurek and K. Vodickova (2005). "Visual results after primary intraocular lens 
implantation or contact lens correction for aphakia in the first year of age." 
Ophthalmologica 219(2): 72-79. 
Bailey, I. L., A. J. Jackson, H. Minto, et al. (2012). "The Berkeley Rudimentary Vision Test." 
Optom Vis Sci. 
Beck, A. D., S. F. Freedman, M. J. Lynn, et al. (2012). "Glaucoma-related adverse events in the 
Infant Aphakia Treatment Study: 1-year results." Arch Ophthalmol 130(3): 300-305. 
Beck, R. W., P. S. Moke, A. H. Turpin, et al. (2003). "A computerized method of visual acuity 
testing: adaptation of the early treatment of diabetic retinopathy study testing protocol." 
Am J Ophthalmol 135(2): 194-205. 
Beller, R., C. S. Hoyt, E. Marg, et al. (1981). "Good visual function after neonatal surgery for 
congenital monocular cataracts." Am J Ophthalmol 91(5): 559-565. 

29 
 
Ver. 04.29.2015 
 
BenEzra, D. (1996). "Cataract surgery and intraocular lens implantation in children, and 
intraocular lens implantation in children." Am J Ophthalmol 121(2): 224-226. 
Biglan, A. W. (2011). "Why is there an Infant Aphakia Treatment Study (IATS)?" J AAPOS 
15(5): 413-414. 
Birch, E. E., C. Cheng, D. R. Stager, Jr., et al. (2005). "Visual acuity development after the 
implantation of unilateral intraocular lenses in infants and young children." J AAPOS 
9(6): 527-532. 
Birch, E. E., C. Cheng, C. Vu, et al. (2010). "Oral reading after treatment of dense congenital 
unilateral cataract." J AAPOS 14(3): 227-231. 
Birch, E. E., S. F. Strauber, R. W. Beck, et al. (2009). "Comparison of the amblyopia treatment 
study HOTV and the electronic-early treatment of diabetic retinopathy study visual acuity 
protocols in amblyopic children aged 5 to 11 years." J AAPOS 13(1): 75-78. 
Bode, S. F., T. Jehle and M. Bach (2011). "Pattern electroretinogram in glaucoma suspects: 
new findings from a longitudinal study." Invest Ophthalmol Vis Sci 52(7): 4300-4306. 
Chak, M. and J. S. Rahi (2008). "Incidence of and factors associated with glaucoma after 
surgery for congenital cataract: findings from the British Congenital Cataract Study." 
Ophthalmology 115(6): 1013-1018 e1012. 
Chen, T. C., D. S. Walton and L. S. Bhatia (2004). "Aphakic glaucoma after congenital cataract 
surgery." Arch Ophthalmol 122(12): 1819-1825. 
Cotter, S. A., R. H. Chu, D. L. Chandler, et al. (2003). "Reliability of the electronic early 
treatment diabetic retinopathy study testing protocol in children 7 to <13 years old." Am J 
Ophthalmol 136(4): 655-661. 
Dahan, E. and M. U. Drusedau (1997). "Choice of lens and dioptric power in pediatric 
pseudophakia." J Cataract Refract Surg 23 Suppl 1: 618-623. 
DeVaro, J. M., E. G. Buckley, S. Awner, et al. (1997). "Secondary posterior chamber intraocular 
lens implantation in pediatric patients." Am J Ophthalmol 123(1): 24-30. 
Dobson, V., G. E. Quinn, R. M. Siatkowski, et al. (1999). "Agreement between grating acuity at 
age 1 year and Snellen acuity at age 5.5 years in the preterm child. Cryotherapy for 
Retinopathy of Prematurity Cooperative Group." Invest Ophthalmol Vis Sci 40(2): 496-
503. 
Dobson, V., G. E. Quinn, B. Tung, et al. (1995). "Comparison of recognition and grating acuities 
in very-low-birth-weight children with and without retinal residua of retinopathy of 
prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group." Invest 
Ophthalmol Vis Sci 36(3): 692-702. 
Drews, C., M. Celano, D. A. Plager, et al. (2003). "Parenting stress among caregivers of 
children with congenital cataracts." J AAPOS 7(4): 244-250. 
Egbert, J. E., S. P. Christiansen, M. M. Wright, et al. (2006). "The natural history of glaucoma 
and ocular hypertension after pediatric cataract surgery." J AAPOS 10(1): 54-57. 
El-Dairi, M. A., S. Holgado, S. G. Asrani, et al. (2009). "Correlation between optical coherence 
tomography and glaucomatous optic nerve head damage in children." Br J Ophthalmol 
93(10): 1325-1330. 
Gilbert, C. and A. Foster (2001). "Childhood blindness in the context of VISION 2020--the right 
to sight." Bull World Health Organ 79(3): 227-232. 
Haargaard, B., C. Ritz, A. Oudin, et al. (2008). "Risk of glaucoma after pediatric cataract 
surgery." Invest Ophthalmol Vis Sci 49(5): 1791-1796. 
Hiatt, R. L. (1998). "Rehabilitation of children with cataracts." Trans Am Ophthalmol Soc 96: 
475-515; discussion 515-477. 
Holmes, J. M., R. W. Beck, M. X. Repka, et al. (2001). "The amblyopia treatment study visual 
acuity testing protocol." Arch Ophthalmol 119(9): 1345-1353. 
Khan, A. O. and S. Al-Dahmesh (2009). "Age at the time of cataract surgery and relative risk for 
aphakic glaucoma in nontraumatic infantile cataract." J AAPOS 13(2): 166-169. 

30 
 
Ver. 04.29.2015 
 
Knight, O. J., C. A. Girkin, D. L. Budenz, et al. (2012). "Effect of race, age, and axial length on 
optic nerve head parameters and retinal nerve fiber layer thickness measured by Cirrus 
HD-OCT." Arch Ophthalmol 130(3): 312-318. 
Kooner, K. S., J. C. Cooksey, J. B. Barron, et al. (1992). "Tonometry comparison: Goldmann 
versus Tono-Pen." Ann Ophthalmol 24(1): 29-36. 
Kuhli-Hattenbach, C., M. Luchtenberg, T. Kohnen, et al. (2008). "Risk factors for complications 
after congenital cataract surgery without intraocular lens implantation in the first 18 
months of life." Am J Ophthalmol 146(1): 1-7. 
Lambert, S. R., E. Buckley, C. Drews-Botsch, et al. (2010). "A randomized clinical trial 
comparing contact lens with intraocular lens correction of monocular aphakia during 
infany:  Grating acuity and adverse events at age 1 year." Arch Ophthalmol(In press). 
Lambert, S. R., E. G. Buckley, C. Drews-Botsch, et al. (2010). "A randomized clinical trial 
comparing contact lens with intraocular lens correction of monocular aphakia during 
infancy: grating acuity and adverse events at age 1 year." Arch Ophthalmol 128(7): 810-
818. 
Lambert, S. R., E. G. Buckley, D. A. Plager, et al. (1999). "Unilateral intraocular lens 
implantation during the first six months of life." J AAPOS 3(6): 344-349. 
Lambert, S. R., D. A. Plager, M. J. Lynn, et al. (2008). "Visual outcome following the reduction 
or cessation of patching therapy after early unilateral cataract surgery." Arch Ophthalmol 
126(8): 1071-1074. 
Lim, Z., K. W. Muir, L. Duncan, et al. (2011). "Acquired central corneal thickness increase 
following removal of childhood cataracts." Am J Ophthalmol 151(3): 434-441 e431. 
Little, R. J., D'Agostino, R., Cohen, M. L., Dickersin, K., Emerson, S. S., Farrar, J. T., ... and 
Stern, H. (2012). "The prevention and treatment of missing data in clinical trials." New 
England Journal of Medicine, 367(14): 1355-1360. 
Little, R. J., Long, Q., and Lin, X. (2009). "A comparison of methods for estimating the causal 
effect of a treatment in randomized clinical trials subject to noncompliance." Biometrics, 
65(2): 640-649. 
Little, R. J. and Rubin, D. B.  (2002). "Statistical analysis with missing data." Hoboken, NJ: J 
Wiley & Sons. 
Lorenz, B. and J. Worle (1991). "Visual results in congenital cataract with the use of contact 
lenses." Graefes Arch Clin Exp Ophthalmol 229(2): 123-132. 
Lundvall, A. and C. Zetterstrom (2006). "Primary intraocular lens implantation in infants: 
complications and visual results." J Cataract Refract Surg 32(10): 1672-1677. 
Lupinacci, A. P., M. L. da Silva Jordao, G. Massa, et al. (2009). "Central corneal thickness in 
children with congenital cataract and children with surgical aphakia: a case-control 
study." Br J Ophthalmol 93(3): 337-341. 
McClatchey, S. K. and M. M. Parks (1997). "Myopic shift after cataract removal in childhood." J 
Pediatr Ophthalmol Strabismus 34(2): 88-95. 
Mills, M. D. and R. M. Robb (1994). "Glaucoma following childhood cataract surgery." J Pediatr 
Ophthalmol Strabismus 31(6): 355-360; discussion 361. 
Moke, P. S., A. H. Turpin, R. W. Beck, et al. (2001). "Computerized method of visual acuity 
testing: adaptation of the amblyopia treatment study visual acuity testing protocol." Am J 
Ophthalmol 132(6): 903-909. 
Muir, K. W., L. Duncan, L. B. Enyedi, et al. (2007). "Central corneal thickness: congenital 
cataracts and aphakia." Am J Ophthalmol 144(4): 502-506. 
Mwanza, J. C., J. D. Oakley, D. L. Budenz, et al. (2011). "Ability of cirrus HD-OCT optic nerve 
head parameters to discriminate normal from glaucomatous eyes." Ophthalmology 
118(2): 241-248 e241. 
Paysse, E. A., L. Camejo, M. A. Hussein, et al. (2004). "Parent-administered visual acuity 
testing: is it reliable and can it improve office efficiency?" J AAPOS 8(4): 332-337. 

31 
 
Ver. 04.29.2015 
 
Phelps, C. D. and N. I. Arafat (1977). "Open-angle glaucoma following surgery for congenital 
cataracts." Arch Ophthalmol 95(11): 1985-1987. 
Plager, D. A., M. J. Lynn, E. G. Buckley, et al. (2011). "Complications, adverse events, and 
additional intraocular surgery 1 year after cataract surgery in the infant Aphakia 
Treatment Study." Ophthalmology 118(12): 2330-2334. 
Plager, D. A., S. Yang, D. Neely, et al. (2002). "Complications in the first year following cataract 
surgery with and without IOL in infants and older children." J AAPOS 6(1): 9-14. 
Ram, J., N. Gupta, J. S. Sukhija, et al. (2011). "Outcome of cataract surgery with primary 
intraocular lens implantation in children." Br J Ophthalmol 95(8): 1086-1090. 
Rice, M. L., D. A. Leske and J. M. Holmes (2004). "Comparison of the amblyopia treatment 
study HOTV and electronic-early treatment of diabetic retinopathy study visual acuity 
protocols in children aged 5 to 12 years." Am J Ophthalmol 137(2): 278-282. 
Rosenbaum, P. R., and Rubin, D. B. (1983). "The central role of the propensity score in 
observational studies for causal effects. Biometrika, 70(1): 41-55. 
Simsek, T., A. H. Mutluay, U. Elgin, et al. (2006). "Glaucoma and increased central corneal 
thickness in aphakic and pseudophakic patients after congenital cataract surgery." Br J 
Ophthalmol 90(9): 1103-1106. 
Swamy, B. N., F. Billson, F. Martin, et al. (2007). "Secondary glaucoma after paediatric cataract 
surgery." Br J Ophthalmol 91(12): 1627-1630. 
Trivedi, R. H., M. E. Wilson, Jr. and J. Facciani (2005). "Secondary intraocular lens implantation 
for pediatric aphakia." J AAPOS 9(4): 346-352. 
Trivedi, R. H., M. E. Wilson, Jr. and R. L. Golub (2006). "Incidence and risk factors for glaucoma 
after pediatric cataract surgery with and without intraocular lens implantation." J AAPOS 
10(2): 117-123. 
Ventura, L. M., I. Golubev, W. J. Feuer, et al. (2011). "Pattern Electroretinogram Progression in 
Glaucoma Suspects." J Glaucoma. 
Webber, A. L., J. M. Wood, G. A. Gole, et al. (2008). "The effect of amblyopia on fine motor 
skills in children." Invest Ophthalmol Vis Sci 49(2): 594-603. 
Wilson, M. E. (1996). "Intraocular lens implantation: has it become the standard of care for 
children?" Ophthalmology 103(11): 1719-1720. 
 
 
 
 
Progress Report Publication List: 
 
1. 
Lambert SR, Buckley EG, Drews-Botsch C, DuBois L, Hartmann E, Lynn MJ, Plager DA, 
Wilson ME and the Infant Aphakia Treatment Study Group.  The Infant Aphakia Treatment 
Study:  design and clinical measures at enrollment.  Arch Ophthamol  2010;128:21-27. 
PMCID3230731. 
 
2. 
Lambert SR, Buckley EG, Drews-Botsch C, DuBois L, Hartmann E, Lynn MJ, Plager DA, 
Wilson ME and the Infant Aphakia Treatment Study Group.  A randomized clinical trial 
comparing contact lens and intraocular lens correction of monocular aphakia during 
infancy:  Grating acuity and adverse events at age 1 year.  Arch Ophthalmol 
2010;128:810-818. PMC--In process. 
3. 
Wilson ME, Trivedi RH, Morrison DG, Lambert SR, Buckley EG, Plager DA, Lynn MJ and 
the Infant Aphakia Treatment Study Group.  Infant Aphakia Treatment Study:  Evaluation 
of cataract morphology in eyes with monocular cataracts.  J AAPOS 2011;15:421-426.  
PMCID3345197. 

32 
 
Ver. 04.29.2015 
 
4. 
Morrison DG, Wilson ME, Trivedi RH, Lambert SR, Lynn MJ and the Infant Aphakia 
Treatment Study Group.  Infant Aphakia Treatment Study:  Effects of Persistent Fetal 
Vasculature on Outcome at 1 year of age.  JAAPOS 2011;15:427-431.  PMCID3223380. 
5. 
Plager DA, Buckley EG, Lynn MJ, Wilson ME, Lambert SR, and the Infant Aphakia 
Treatment Study Group.   Complications, adverse events and additional intraocular 
surgeries in the first year following cataract surgery in the Infant Aphakia Treatment Study. 
Ophthalmology 2011;118:2330-4. PMCID3230731. 
6. 
Beck AD, Freedman S, Lynn MJ, Bothun E, Neely D, Lambert SR and the Infant Aphakia 
Treatment Study Group.  Glaucoma-related adverse events in the infant aphakia treatment 
study (IATS):  One year results.  Arch Ophthalmol 2012:130;300-305. PMC--In process. 
7. 
VanderVeen DK, Nizam A, Lynn M, Bothun ED, McClatchey SK, Weakley DR, Lambert 
SR and the Infant Aphakia Treatment Study Group.  Predictability of IOL calculation and 
early refractive status in the Infant Aphakia Treatment Study.  Arch Ophthalmol 
2012;130:293-299. PMCID3329400. 
8. 
Drews-Botsch CD, Hartmann E, Celano M for the Infant Aphakia Treatment Study.  
Predictors of Adherence to Occlusion Therapy Three Months after Cataract Extraction in 
the Infant Aphakia Treatment Study.  J AAPOS  2012;16:150-155.  PMCID3336096.  
9. 
Drews-Botsch CD, Hartmann E, Kruger S, Celano M for the Infant Aphakia Treatment 
Study.  Adherence to occlusion therapy in the six months of follow up and visual acuity 
among participants in the Infant Aphakia Treatment Study (IATS).  Inv Ophthal Vis Sci 
2012;53:3368-75.  PMCID3374623. 
10. 
Russell B, Ward MA, Lynn M, DuBois L, Lambert SR and the Infant Aphakia Treatment 
Study Group.  The Infant Aphakia Treatment Study Contact Lens Experience:  One-Year 
Outcomes.  Eye & Contact lens: Science and Clinical Practice 2012;38:234-9.  PMC--In 
process. 
11. 
Carrigan AK, DuBois LG, Becker NK, Lambert, SR for the Infant Aphakia Treatment 
Study.  Cost-Analysis of Intraocular Lens versus Contact Lens Treatment for a Unilateral 
Congenital Cataract.  Ophthalmol  In press.  PMC--In process (Appendix 11). 
12. Lambert SR, Lynn MJ, Dubois LE, Cotsonis GA, Hartmann EE, Wilson ME for the 
Infant Aphakia Treatment Study Group.   Axial elongation following cataract surgery 
during the first year of life in the Infant Aphakia Treatment Study.  Inv Ophthal Vis Sci 
2012;52:7539-7545.  PMCID: PMC3493185. 
13. Bothun E, Cleveland J, Lynn MJ, Christiansen SP, Vanderveen DK, Neely DE, 
Kruger DJ, Lambert SR for the Infant Aphakia Treatment Study Group.  One-year 
strabismus outcomes in the Infant Aphakia Treatment Study.  Ophthalmology 
2013;120:1227-31.  PMCID: In process. 
14. Celano M, Hartmann EE, Drews-Botsch CD for the Infant Aphakia Treatment 
Study Group.  Parenting stress in the Infant Aphakia Treatment Study. Journal of 
Pediatric Psychology 2013; 38(5): 484–493.  PMCID: PMC3666118. 
15. VanderVeen DK, Trivedi RH, Nizam A, Lynn MJ, Lambert SR, for the Infant 
Aphakia Treatment Study Group. Predictability of Intraocular Lens Power 
Calculation Formulae in Infantile Eyes with Unilateral Congenital Cataract:  Results 

33 
 
Ver. 04.29.2015 
 
from the Infant Aphakia Treatment Study. Am J Ophthalmol 2013; 156:1252-1260. 
PMCID: PMC4140419. 
16. VanderVeen DK, Trivedi RH, Nizam A, Lynn MJ, Lambert SR, for the Infant 
Aphakia Treatment Study Group. Response to Letter to the Editor Re: 
Predictability of Intraocular Lens Power Calculation Formulae in Infantile Eyes with 
Unilateral Congenital Cataract:  Results from the Infant Aphakia Treatment Study. 
Am J Ophthalmol 2014;157:1333   
17. Trivedi RH, Lambert SR, Lynn MJ, Wilson ME. The role of preoperative biometry in 
selecting initial contact lens power in the Infant Aphakia Treatment Study. J 
AAPOS 2014:18:251-254.  PMCID: PMC4080905. 
18. Infant Aphakia Treatment Study Group.  A randomized clinical trial comparing 
contact lens to intraocular lens correction of monocular aphakia during infancy:  
HOTV optotype acuity at age 4.5 years and clinical findings at age 5 years. JAMA 
Ophthalmology 2014;132:676-682  PMCID: PMC4138810. 
19. Felius J, Busettini C, Lynn MJ, Hartmann EE, Lambert SR for the Infant Aphakia 
Treatment Study Group. Nystagmus and related fixational instabilities following 
extraction of unilateral infantile cataract in the Infant Aphakia Treatment Study 
(IATS). IOVS 2014;55:5332-5337.  PMCID:  In process. 
20. Bothun E, Lynn MJ, Lambert SR. Response to Letter to the Editor Re: One-year 
strabismus outcomes in the Infant Aphakia Treatment Study. Ophthalmology 
2014;121;e53. 
21. Wall PB, Lee JA, Lynn MJ, Lambert SR, Traboulsi EI and the IATS Group. The 
effects of surgical factors on postoperative astigmatism in patients enrolled in the 
Infant Aphakia Treatment Study (IATS). JAAPOS 2014;18:417-422 
22. Plager DA, Lynn MJ, Buckley EG, Wilson ME, Lambert SR. Complications in the 
first 5 years following cataract surgery in infants with and without IOL in the IATS. 
Am J Ophthalmol  2014;158:892-898. 
23. Lambert SR, Lynn MJ, Hartmann EE. Response to Letter to the Editor Re: A 
randomized clinical trial comparing contact lens to intraocular lens correction of 
monocular aphakia during infancy:  HOTV optotype acuity at age 4.5 years and 
clinical findings at age 5 years. JAMA Ophthalmology 2014;132:1492-1493. 
24. Kruger S, DuBois L, Becker ER, Morrison D, Wilson L, Wilson ME, Lambert SR for 
the Infant Aphakia Treatment Study.  Cost of intraocular lens vs. contact lens 
treatment after unilateral congenital cataract surgery in the Infant Aphakia 
Treatment Study:  Retrospective analysis at age 5 years. Ophthalmology 
2015;122:288-292. 
25. Plager DA, Lynn MJ, Buckley EG, Wilson ME, Lambert SR. Response to Letter to 
the Editor.  Re:  Complications in the first 5 years following cataract surgery in 
infants with and without IOL in the IATS. Am J Ophthalmol 2014;158:1361. 
26. Hartmann EE, Stout AU, Lynn MJ, Yen KG, Kruger SJ, Lambert SR and the Infant 
Aphakia Treatment Study Group. Stereopsis results at 4.5 years of age in the 
Infant Aphakia Treatment Study. Am J Ophthalmol. 2015;159:64-70. 

34 
 
Ver. 04.29.2015 
 
 
27. Hartmann EE, Lynn MJ, Lambert S. Baseline Characteristics of the Infant Aphakia 
Treatment Study Population:  Predicting Recognition Acuity at 4.5 Years of Age.  
IOVS 2015; 56:388-395. 
 
28. Weil N, Lambert SR.  Comparison of Contact Lens and IOL Correction of 
Monocular Aphakia During Infancy.  US Ophthalmic Review  2015;8:21-22. 
 
29. Lenhart PD, Courtright C, Wilson ME, Lewallen S, Taylor DSI, Ventura MC, 
Bowman R, Woodward L, Ditta LC, Kruger S, Haddad D, El Shakankiri N, Rai SK, 
Bailey TC, Lambert SR.  Global Challenges in the Management of Congenital 
Cataract: Proceedings of the International Congenital Cataract Symposium held on 
March 7, 2014 in New York City, New York.  J AAPOS 2015;19:e1-e8. 
 
30. Lambert SR, Plager DA, Buckley EG, Wilson ME, DuBois L, Drews-Botsch CD, 
Hartmann EE, Lynn MJ.  The Infant Aphakia Treatment Study:  Was the high rate 
of intraoperative and postoperative adverse events in the intraocular lens group 
preventable?  J AAPOS 2015;19:101-103. 
 
31. Freedman SF, Lynn MJ, Beck AD, Bothun ED, Orge FH, Lambert SR.  Glaucoma-
related adverse events in the first five years after unilateral cataract removal in the 
Infant Aphakia Treatment Study. JAMA Ophthalmol In press 
 
32. Celano MJ, Hartmann EE, Drews-Botsch CD.  Motor skills of children with 
unilateral visual impairment in the Infant Aphakia Treatment Study.  Submitted to 
Developmental Medicine and Child Neurology In revision 
 
33. Drews-Botsch D, Cotsonis G, Celano M, Lambert SR.  Assessment of Adherence 
to Visual Correction and Occlusion Therapy in the Infant Aphakia Treatment Study.  
J Clinical Trials Submitted 
 
PROTECTION OF HUMAN SUBJECTS:  
 
a. Study visit data will be recorded by the site coordinators on Source Document 
Worksheets which will be stored in a secure location at the site. The worksheets will 
be used by the coordinator to enter the data into the CDSI electronic data capture 
system used by the study, an FDA 21 CFR Part 11 compliant data management 
system capable of receiving data and documents via EDC, pdf email submission or 
fax. Clinical sites will be centrally monitored for protocol compliance and data quality 
by a Data Coordinating Center   
 
b. The IATS clinical trial is registered with ClinicalTrials.gov Identifer:  NCT00212134. 
 
c. All of the patients in this clinical trial are children.  Assent will be obtained from children 
and Informed Consent from parents prior to patients being enrolled in Phase 3 of the IATS 
(See Appendix 3). 

35 
 
Ver. 04.29.2015 
 
 
d. There are minimal risks involved with an ocular examination using standard procedures.  
If the patient develops complications, we will make every effort to treat the complications 
in a manner which preserves the function of the child’s eye. 
 
e. The privacy of the patients will be maintained at all times.  Assent and Informed 
Consent will be obtained before enrolling patients in Phase 3 of the IATS  
 
f. If a patient develops complications, either the investigator will treat the patient or the 
patient will be referred to the most appropriate specialist in a timely manner.  Data from 
the study are reported annually to the FDA and the DSMC.  In addition, if serious adverse 
events arise, they will be reported to the institutional IRB by the investigator.  The medical 
monitor for the IATS will also be notified and when appropriate he will then inform the 
DSMC regarding the complication. 
 
g. The knowledge gained from the IATS should provide guidance on the most appropriate 
optical treatment to be used following infantile cataract surgery.  In addition, information 
should be gained on what is the most appropriate IOL power to implant in an infantile eye 
and the likelihood of certain complications.  This information may be generalizable to 
children with bilateral congenital cataracts and to children with traumatic cataracts.