A Study of Uveitis in Children <18 Years of Age
Conditions: Uveitis
Sponsor: Jaeb Center for Health Research

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PEDIATRIC UVEITIS STUDY  
 
A Study of Uveitis in Children <18 Years of Age 
 
Protocol Identifying Number: UV1 
 
 
 
Version Number: 1.2 
 
January 30, 2026 
 

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KEY ROLES 
 
Protocol Co-Chair 
 
Name, degree 
Kara C. LaMattina, M.D. 
Title 
Director of Uveitis and Pediatrics Services  
Institution Name 
Department of Ophthalmology, Boston University School of Medicine 
Boston Medical Center 
85 E. Concord Street, 8th floor 
Boston, MA 02118 
Email: Kara.lamattina@gmail.com 
 
Protocol Co-Chair 
 
Name, degree 
Virginia Utz, M.D. 
Title 
Professor of Pediatric Ophthalmology 
Institution Name 
Cincinnati Children’s Hospital Medical Center 
Abrahamson Pediatric Eye Institute 
3333 Burnet Avenue | MLC 4008 | Cincinnati, OH 45229 
Email: Virginia.utz@cchmc.org 
 
JCHR Principal Investigator 
 
Name, degree 
Julianne Zawadzki, M.S.P.H. 
Title 
Epidemiologist 
Institution Name 
Jaeb Center for Health Research 
15310 Amberly Drive, Suite 350 
Tampa, FL 33647 
Phone: 1-888-797-3344 
Email: jrobinson@jaeb.org 
http://www.pedig.net 
 
 

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VERSION HISTORY 
VERSION
NUMBER 
AUTHOR 
APPROVER 
EFFECTIVE 
DATE 
REVISION DESCRIPTION 
1.0
J. Zawadzki
R.Kraker
16Dec2025
Initial version. 
1.1 
J. Zawadzki 
R. Kraker 
1Jan2026 
Updated to reflect proxy questionnaire now 
administered to all parents regardless of 
child’s age. 
1.2 
J. Zawadzki 
R. Kraker 
30Jan2026 
Updated protocol to provide clarification on 
study definition of uveitis and steroid 
control.  
Added section 2.4.1 to note questionnaire 
administration procedures.  
Typographical errors corrected throughout. 
 
   *Version in effect at study initiation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
KEY ROLES .................................................................................................................................................. 2 
VERSION HISTORY ....................................................................................................................................... 3 
TABLE OF CONTENTS .................................................................................................................................. 4 
LIST OF ABBREVIATIONS ............................................................................................................................ 7 
PROTOCOL SUMMARY ................................................................................................................................. 8 
STUDY SUMMARY FLOW CHART .............................................................................................................. 10 
STUDY PROCEDURES ................................................................................................................................. 11 
CHAPTER 1: 
BACKGROUND INFORMATION .......................................................................................... 12 
1.1 
Epidemiology .............................................................................................................................. 12 
1.2 
Classification ............................................................................................................................... 12 
1.3 
Clinical Characteristics ............................................................................................................... 12 
1.4 
Signs and Symptoms ................................................................................................................... 12 
1.5 
Current Practice........................................................................................................................... 13 
1.6 
Visual Acuity Outcomes and Complications .............................................................................. 13 
1.7 
Rationale for Present Study ......................................................................................................... 15 
1.8 
Study Objective ........................................................................................................................... 15 
1.8.1 
Specific Aims .......................................................................................................................... 15 
1.9 
Potential Risks and Benefits ....................................................................................................... 15 
1.9.1 
Known Potential Risks ............................................................................................................ 15 
1.9.2 
Known Potential Benefits ....................................................................................................... 16 
1.10 
Risk Assessment ......................................................................................................................... 16 
1.11 
General Considerations ............................................................................................................... 16 
CHAPTER 2: 
STUDY ENROLLMENT ....................................................................................................... 17 
2.1 
Participant Recruitment and Enrollment ..................................................................................... 17 
2.1.1 
Informed Consent .................................................................................................................... 17 
2.2 
Eligibility Criteria ....................................................................................................................... 17 
2.2.1 
Participant Inclusion Criteria .................................................................................................. 17 
2.2.2 
Exclusion Criteria ................................................................................................................... 18 
2.3 
Screening Procedures .................................................................................................................. 18 
2.3.1 
Demographic and Historical Information ............................................................................... 18 
2.3.2 
Systemic Disease..................................................................................................................... 19 
2.3.3 
Clinical Testing ....................................................................................................................... 19 

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a. 
Slit lamp exam by investigators usual method: ....................................................................... 19 
b. 
Indirect ophthalmoscopy: ........................................................................................................ 19 
2.4 
Questionnaires ............................................................................................................................. 20 
2.4.1 
Questionnaire Administration ................................................................................................. 20 
2.5 
Uveitis Classification .................................................................................................................. 20 
2.5.1 
Etiology ................................................................................................................................... 20 
2.5.2 
Localization ............................................................................................................................. 21 
2.5.3 
Disease Course ........................................................................................................................ 21 
2.5.4 
Disease Duration ..................................................................................................................... 21 
2.5.5 
Disease Activity – Anterior Chamber ..................................................................................... 21 
2.5.6 
Disease Activity – Vitreous .................................................................................................... 22 
2.5.7 
Disease Control ....................................................................................................................... 22 
2.5.8 
Ocular Complications ............................................................................................................. 23 
2.6 
Treatment .................................................................................................................................... 23 
2.7 
Medical Record Review .............................................................................................................. 23 
CHAPTER 3: 
UNANTICIPATED PROBLEM / ADVERSE EVENT REPORTING ......................................... 24 
3.1 
Unanticipated Problems .............................................................................................................. 24 
3.2 
Adverse Events ........................................................................................................................... 24 
3.3 
Stopping Criteria ......................................................................................................................... 24 
CHAPTER 4: 
MISCELLANEOUS CONSIDERATIONS ............................................................................... 25 
4.1 
Contacts by the Jaeb Center for Health Research and Sites ........................................................ 25 
4.2 
Participant Compensation ........................................................................................................... 25 
4.3 
Participant Withdrawal ............................................................................................................... 25 
4.4 
Confidentiality ............................................................................................................................ 25 
CHAPTER 5: 
STATISTICAL CONSIDERATIONS ...................................................................................... 26 
5.1 
Sample Size ................................................................................................................................. 26 
5.2 
Primary Analysis ......................................................................................................................... 26 
5.3 
Descriptive Data (Specific Aims 1–5) ........................................................................................ 26 
5.4 
Recruitment potential (Specific Aim 6) ...................................................................................... 27 
5.5 
Questionnaires (Specific Aims 7-8) ............................................................................................ 27 
5.5.1 
Rasch Analysis ........................................................................................................................ 27 
5.5.2 
Missing Data ........................................................................................................................... 27 
CHAPTER 6: 
DATA COLLECTION AND MONITORING .......................................................................... 28 
6.1 
Case Report Forms and Other Data Collection ........................................................................... 28 
6.2 
Study Records Retention ............................................................................................................. 28 

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6.3 
Quality Assurance and Monitoring ............................................................................................. 28 
6.4 
Protocol Deviations ..................................................................................................................... 28 
CHAPTER 7: 
ETHICS/PROTECTION OF HUMAN PARTICIPANTS .......................................................... 29 
7.1 
Ethical Standard .......................................................................................................................... 29 
7.2 
Institutional Review Boards ........................................................................................................ 29 
7.3 
Informed Consent Process .......................................................................................................... 29 
7.3.1 
Consent Procedures and Documentation ................................................................................ 29 
7.4 
Participant and Data Confidentiality ........................................................................................... 29 
7.5 
Future Use of Data ...................................................................................................................... 30 
CHAPTER 8: 
REFERENCES ..................................................................................................................... 31 
 
 
 
 

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LIST OF ABBREVIATIONS 
 
ABBREVIATION 
DEFINITION 
AC
Anterior chamber
AUS
American Uveitis Society 
BCVA
Best corrected visual acuity
CFR
Code of Federal Regulations 
CGRN
Childhood Glaucoma Research Network
CME
Cystoid macular edema
CMV
Cytomegalovirus
CRF
Case report form
DMARDs
Disease-modifying antirheumatic drugs
eCRF
Electronic case report form
FA
Fluorescein angiogram
FIPS
Federal information processing system
GCP
Good clinical practice
HSV 
Herpes simplex virus 
ICH 
Intracranial hypertension
IOP
Intraocular pressure
IRB
Institutional Review Board
JIA
Juvenile idiopathic arthritis
JXG
Juvenile xanthogranuloma
LP
Light perception 
mmHg
Millimeters of mercury 
MTX
Methotrexate
MUST 
The Multicenter Uveitis Steroid Treatment
NIU
Non-infectious uveitis 
OCT 
Optical coherence tomography 
QA
Quality assurance 
QC
Quality control 
SUN 
Standardization of Uveitis Nomenclature 
TNF
Tumor necrosis factor 
UBM
Ultrasound biomicroscopy
VA
Visual acuity
VZV
Herpes zoster

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PROTOCOL SUMMARY 
1 
PARTICIPANT AREA 
DESCRIPTION 
Title 
A Study of Uveitis in Children <18 Years of Age (UV1) 
Précis 
The rarity of pediatric uveitis creates a pressing need for a 
multicenter cross-sectional observational study to collect data in 
children regarding the prevalence of uveitis subtypes, current 
treatment approaches, and patient-reported outcome measures.  
 
Such information will be instrumental for the planning of future 
randomized clinical trials. 
Objective 
Over a one-year period, to enroll children diagnosed with uveitis 
and collect data regarding clinical features and current and past 
treatments at time of enrollment.  
 
A medical record review will be conducted 12 months after 
enrollment for any children with new onset non-infectious uveitis 
(onset within 6 months prior to enrollment). 
Study Design 
Multicenter observational study.  
Number of Sites 
The study is open to Pediatric Eye Disease Investigator Group 
(PEDIG) sites and sites affiliated with the American Uveitis 
Society (AUS).   
Specific Aims 
The specific aims of this observational study are to:  
 
1. Describe the frequency of uveitis subtypes in children 
<18 years of age, including new onset uveitis (<6 months 
duration).  
2. Describe clinical and demographic characteristics overall 
and within each type of uveitis. 
3. Compare characteristics between uveitis subtypes.  
4. Describe current and previous treatment history by type 
of uveitis.  
5. Describe clinical measures done as part of usual care.  
6. Determine recruitment potential overall and by site for 
different disease sub-types (new-onset vs. established 
disease, localization, etiology) for future randomized 
clinical trials.  
7. Evaluate relationships between demographic, treatment, 
and clinical characteristics and quality of life as measured 
by the EYE-Q (current version) questionnaire.  
8. Develop a comprehensive PEDIG Uveitis Quality of Life 
questionnaire by administration and calibration of EYE-Q 
plus additional uveitis-specific and treatment related 
items. 

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PARTICIPANT AREA 
DESCRIPTION 
Population 
Key Inclusion Criteria:  
 
Age: 
o 
Incident cases (onset ≤ 6 months) <17 years  
o 
Established cases (onset > 6 months) <18 years 
 
Diagnosis of any type of uveitis in any location except 
traumatic and post-operative uveitis 
 
Active or inactive uveitis with any treatment status 
(current / prior / none [but under surveillance]) 
 
Key Exclusion Criteria: 
 
Bilateral uveitis with differing etiologies  
 
Traumatic uveitis  
 
Post-operative uveitis 
 
Coexisting ocular and systemic conditions allowed except 
retinoblastoma, Coat’s disease, retinitis pigmentosa, 
inherited retinal degeneration, juvenile xanthogranuloma 
(JXG), or leukemia/malignancy within the eye
Sample Size 
The study will recruit up to 300 participants with uveitis over a 
one-year enrollment period. 
Phase 
Observational study. 
Treatment Groups 
Not applicable. Enrollment of children diagnosed with uveitis, 
either active or inactive with or without current treatment at time 
of enrollment.   
Participant Duration 
Single enrollment only followed by a chart review 12 months after 
enrollment for children with new onset non-infectious uveitis 
(onset within 6 months of enrollment). 
Protocol Overview/Synopsis 
The protocol establishes an observational study to collect data on 
children and teenagers who have been diagnosed with uveitis in at 
least one eye. 
 
Informed consent, screening for eligibility, and enrollment into the 
study occurs after uveitis diagnosis in at least one eye has been 
confirmed as part of usual care. Current and past history data will 
be collected from medical record review at the time of enrollment 
followed by a medical record review 12 months after enrollment 
for children with new onset non-infectious uveitis (onset within 6 
months prior to enrollment). Clinical assessment will mimic usual 
care.   

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STUDY SUMMARY FLOW CHART 
2 
ENROLLMENT  
 Medical & treatment history (including prior surgical procedures) 
 Classification of uveitis type 
 Current treatment (systemic and ocular) 
 Weight  
 Clinical measures: 
 
Best corrected visual acuity 
 
Intraocular pressure 
 
Pupil exam 
 
Slit lamp exam by investigator’s usual method 
o 
Primary location(s) of uveitis as determined by SUN1    
o 
Grading of cell count and flare per SUN criteria pre-dilation.1   
o 
Grading of vitreous cell post-dilation 
 
Dilated fundus exam with indirect ophthalmoscopy  
o 
Vitreous haze  
o 
Retinal exam  
 Additional clinical measures (if done as usual care) 
 
Strabismus Exam 
 
Refraction 
 Ancillary testing (Y/N) (if done as usual care) 
 Ocular complications present (Y/N) 
 Quality of life questions (EYE-Q with additional items from literature review) 
 
Child Questionnaire completed by children 8 to <18  
 
Parent Proxy Questionnaire completed by parent for all children 
 
Parent Questionnaire completed by parent for all children 
MAJOR ELIGIBILITY CRITERIA 
 
Age: 
o 
Incident cases (onset ≤ 6 months) <17 years  
o 
Established cases (onset > 6 months) <18 years 
 
Diagnosis of any type of uveitis in any location (except traumatic and post-operative uveitis) 
 
Active or inactive uveitis with any treatment status (current / prior / none [but under surveillance]) 
 
Coexisting ocular / systemic conditions allowed except retinoblastoma, Coat’s disease, retinitis 
pigmentosa, inherited retinal degeneration, juvenile xanthogranuloma (JXG), or leukemia/malignancy 
within the eye 
MEDICAL RECORD REVIEW – 12 MONTHS POST-ENROLLMENT 
 
Only for children with new onset non-infectious uveitis onset within 6 months prior to enrollment. 
 
Follow-up visits after enrollment will be performed according to the clinical center’s usual routine. 
 
No procedures will be performed specifically for the study except that for children with new onset non-
infectious uveitis (onset within 6 months prior to enrollment), participating sites will be asked to 
perform a medical record review 12 months after enrollment to collect clinical data that is part of usual 
care. 
 
Data collected will include medical, medication, and eye treatment history; and ocular examination data 
including best corrected visual acuity in each eye. 
 

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STUDY PROCEDURES 
3 
 
Enrollment  
12-Month 
Chart 
Review*  
Informed Consent / Assent (if needed) 
X 
 
Demographics  
X 
 
Medical and Treatment History (including prior surgical procedures) 
X 
X 
Classification of Uveitis (type, location, severity, control) 
X 
X 
Weight  
X 
X 
Clinical Measures:  
 
 
Best Corrected Distance Visual Acuity (investigator’s usual method) 
X 
X 
Intraocular Pressure 
X 
X 
Pupil Exam 
X 
X 
Slit Lamp Exam (Grading of cell count and flare per SUN criteria1)  
X 
X 
Dilated fundus exam  
(Grading of vitreous cell by Slit Lamp Exam, vitreous haze by indirect ophthalmoscopy)
X 
X 
Additional Clinical Measures (by investigator’s usual method, if done as usual care) 
- 
Strabismus Assessment 
- 
Refraction
X 
X 
Ancillary imaging (If done as usual care, Yes or No only): 
- 
OCT retina/macula   
- 
OCT optic nerve  
- 
Color photos  
- 
Fluorescein angiogram (oral or IV) 
- 
Visual field   
- 
Brain MRI 
- 
Ultrasound UBM or B-scan 
- 
Indocyanine Green angiography 
- 
Autofluorescence 
- 
A-scan (axial length for glaucoma) 
- 
Electroretinogram
X 
X 
Ocular Complications for Each Eye (Yes or No): 
- 
Band keratopathy  
- 
Synechiae  
- 
Cataract 
- 
Ocular hypertension 
- 
Glaucoma/Glaucoma Suspect 
- 
Ocular hypotony 
- 
Optic disc edema 
- 
Macular edema 
- 
Epiretinal membrane formation 
- 
Vasculitis/vascular leakage 
- 
Other
X 
X 
Current Treatment (systemic and ocular) 
X 
X 
EYE-Q questionnaire with additional quality of life questions 
 
 
- 
Child Questionnaire completed by children 8 to <18  
X 
 
- 
Parent Proxy Questionnaire completed by parent for all children 
X 
 
- 
Parent Questionnaire completed by parent for all children 
X 
 
*For children with new onset non-infectious uveitis (onset within 6 months of enrollment): Data will be collected 
4 
12-months following enrollment from data collected at standard care visits since enrollment When applicable, if 
5 
more than one element is available for a report field, the most recent element will be reported. 
 
6 

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Chapter 1: 
Background Information 
7 
 
8 
1.1 
Epidemiology 
9 
Uveitis is an ocular inflammatory disease affecting the uvea, which is anatomically composed of 
10 
the iris, ciliary body, and choroid. Uveitis in children is rare with reported annual incidence 
11 
estimates in those <16 years of 4.3/100,000 in a UK population,2 14/100,000 person-years (95% 
12 
CI, 11.3–16.5) in a Finnish population,3 and 6.9/100,000 person-years in Northern California.4 
13 
Annual incidence is reported to increase with age, with estimates of 3.15, 3.84, and 6.06 per 
14 
100,000 in patients from < 5, 6 to 10, and 11 to 15 years old, respectively.2 
15 
 
16 
1.2 
 Classification 
17 
Uveitis is classified as non-infectious or infectious depending on etiology. In the US, the 
18 
majority of pediatric uveitis cases are noninfectious. A retrospective analysis based on insurance 
19 
claims estimated the prevalence of non-infectious uveitis [NIU] in children to be 29/100,000 
20 
(95% CI, 26.1-33.2).5 The pathogenesis of NIU is presumed to be autoimmune or 
21 
autoinflammatory. The most common systemic disease associated with pediatric NIU is juvenile 
22 
idiopathic arthritis (JIA), present in 50-80% of uveitis cases.6-8 Pediatric NIU in the US is 
23 
commonly bilateral (75%), anterior, chronic, and is often challenging to diagnose and treat.9  
24 
 
25 
Infectious uveitis is much less common in the US, accounting for 3.4-24.3% of pediatric cases.8-
26 
10 Causes of infectious uveitis include toxoplasmosis, toxocariasis, Lyme disease, herpes simplex 
27 
virus (HSV), cytomegalovirus (CMV), herpes zoster (VZV), syphilis, Bartonella, rubella, and 
28 
tuberculosis.6,9  
29 
 
30 
Cases with no known associated systemic disease are referred to as undifferentiated (previously 
31 
termed idiopathic) uveitis. In the US, up to 27-51% of children with uveitis have undifferentiated 
32 
uveitis,9 signifying no identifiable associated systemic or ocular disease. 
33 
 
34 
1.3 
Clinical Characteristics 
35 
Uveitis is characterized by inflammation of the iris, ciliary body, and/or choroid and is classified 
36 
anatomically, histopathologically, and by descriptors of onset, duration, and clinical course using 
37 
the definitions developed by the Standardization of Uveitis Nomenclature Working Group.1  
38 
 
39 
Anterior uveitis is characterized by white blood cells generally with concomitant protein (flare) 
40 
in the anterior chamber. Intermediate uveitis is characterized by inflammation primarily located 
41 
in the vitreous cavity. Intermediate uveitis is further subclassified into pars planitis and non-pars 
42 
planitis type.1,11,12 
43 
 
44 
Posterior uveitis is characterized by primary retinal or choroidal inflammation. Panuveitis is 
45 
defined as inflammation of the anterior, intermediate, and posterior segments of the eye.1 
46 
 
47 
1.4 
Signs and Symptoms 
48 
The clinical presentation varies depending on the anatomic location and phenotype. For example, 
49 
the onset of JIA-associated chronic anterior uveitis is often insidious with few symptoms.13 
50 
However, children with other forms of uveitis may have eye redness, decreased vision, floaters, 
51 
pain, and photophobia.9,14 Visual acuity (VA) may be significantly impaired even at presentation: 
52 

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one US-based study15 (n=469 eyes; tertiary referral center) reported 20% of eyes were 20/50 to 
53 
20/200 and 8% had 20/300 to light perception (LP) vision at presentation with no LP in 1%. A 
54 
study of 527 eyes8 reported 9.23% were 20/200 or worse at presentation, and in a review of 196 
55 
eyes with JIA-associated uveitis,16 18% of eyes were “legally blind” (20/200 or worse) at 
56 
presentation. 
57 
 
58 
Complications may be present at the time of NIU diagnosis, including cataracts, band 
59 
keratopathy, synechiae, hypotony, glaucoma, and cystoid macular edema (CME).17-19 Stroh et 
60 
al.16 found 79 of 196 eyes (40.3%) with JIA-associated uveitis had ocular hypertension or 
61 
secondary glaucoma at presentation to a tertiary care center.  
62 
 
63 
1.5 
Current Practice 
64 
The primary goal of treatment for NIU is to control inflammation and prevent ocular 
65 
complications. A stepwise treatment approach is adopted to reduce the risk of potential local and 
66 
systemic side effects. Typically, topical or oral glucocorticoids are initiated as first-line 
67 
treatment, with the addition of other therapies as dictated by clinical disease and course. 
68 
Prolonged use of topical steroids can lead to the development of cataracts and glaucoma,16,20 
69 
with systemic steroids attributing additional risks of weight gain, mood disorders, and growth 
70 
retardation. Inadequate response to glucocorticoids, the development of new or worsening 
71 
complications, and failure to successfully taper steroids without recurrence of uveitis are all 
72 
indications to escalate to disease-modifying antirheumatic drugs (DMARDs) to improve vision 
73 
outcomes. If non-biologic DMARD treatment fails, biologic DMARD therapy (typically with 
74 
tumor necrosis factor inhibitors [TNFi]) may be initiated. Both a non-biologic DMARD and 
75 
biologic DMARD may be initiated early in the disease course for severe, vision-threatening 
76 
complications, rather than non-biologic DMARD monotherapy.21  
77 
 
78 
Methotrexate (MTX) is the first-line, non-biologic DMARD used to treat NIU, and it is preferred 
79 
for its efficacy, safety, and tolerability. Estimates of the proportion of patients with NIU treated 
80 
with MTX range from 45%22 to 85%.23 Nevertheless, MTX treatment has been estimated to fail 
81 
as monotherapy in at least a third of patients;24 other estimates of failure exceed 50%.25,26 In 
82 
addition, it can take at least 3-4 months27 for MTX treatment to have full effect during which 
83 
time children remain at risk of incurring additional complications such as cataract or glaucoma 
84 
from ongoing inflammation or concurrent corticosteroid use. Characteristics of children likely to 
85 
fail MTX and require biologic DMARD therapy and whether earlier initiation of biologic 
86 
therapy might confer greater treatment benefit are unknown.  
87 
 
88 
1.6 
Visual Acuity Outcomes and Complications 
89 
Even with aggressive treatment, the frequency of vision loss and ocular complications remains 
90 
high. There are few reliable estimates but some from larger studies are summarized below. 
91 
 
92 

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Table 1 – Visual Acuity Data from Larger Studies: 
93 
 
94 
 
Smith et al8 
(n=527 eyes 
baseline; 
n=63 eyes at 
3 yrs; n=22 
at 5 yrs; 
n=13 at 10 
yrs) 
Kump et 
al15 
n=469 eyes 
Tekin et al23 
n=83 eyes 
Gregory et al28 
 N=596 eyesa 
Markomichelakis et al29 
(n=533 eyes at baseline; 
n=315 eyes at 2 yrs; 
n=283 eyes at 3 yrs; n= 
230 at 5 yrs) 
VA 20/50 or worse 
21% at 3 yrs 
36% at 5 yrs 
31% at 10 yrs 
17% at last 
follow-up 
 
43% (best eye) 
at last follow-up 
3.5% at 2 yrs 
3.6% at 3 yrs 
5.6% at 5 yrs 
VA 20/200 or 
worse 
3% at 3 yrs 
15% at 5 yrs 
8% at 10 yrs 
5%a at last 
follow-up 
Worse than 
20/200 
1% at last 
follow-up 
20/400 or 
worse 
27% (best eye) 
at last follow-up 
4.7% at 2 yrs 
4.3% at 3 yrs 
5.9% at 5 yrs  
Length of 
Follow-up 
Median 3 yrs 
(range: 1 to 10 
yrs) 
Median 22 
months 
(range 1 day 
to 221 
months) 
Median 49 
months 
(range 6 to 
141 months)  
Median 2.62 yrs 
(range 0-24 yrs) 
 
Median 30 months 
(range, 6–82 months) 
a All JIA 
95 
 
96 
Table 2 - Complication Data from Larger Studies:  
97 
 
98 
 
Ferrara et al9 
N=520 eyes 
Kump et al15 N=469 
eyes 
Smith et al8 
N=926 eyes 
(rate at 3 yrs) 
Dajee et al30  
N=68 eyes 
Gregory et al28 
 N=596 eyesb 
Glaucoma 
121 (23%) 
71 (15%) 
7 (11%) 
11 (16%) 
86/281 
(31%)
Cataract 
228 (44%) 
188 (40%) 
31 (49%) 
18 (26%) 
-- 
Posterior 
synechiae 
102 (20%) 
164 (35%) 
30 (48%) 
16 (24%) 
69/232 
(30%) 
Band 
keratopathy
70 (13%) 
107 (23%) 
29 (46%) 
9 (13%) 
79/220 
(36%)
Optic nerve 
involvement 
108 (21%) 
38 (8%) 
-- 
-- 
-- 
Maculopathy 
111 (21%) 
111 (24%) 
15 (24%) 
2 (3%) 
38/309 
(12%)
Retinal 
detachment 
14 (3%) 
14 (3%) 
-- 
3 (4%) 
-- 
Hypotony 
Not reported 
18 (4%) 
6 (10%) 
-- 
44/314 
(14%)
Follow-up 
Min 5 months 
Median 22 months 
(range 1 day to 221 
months) 
Median 3 yrs 
(range: 1-10 yrs) 
Median 13.5 
months 
Median 2.62 yrs 
(range 0-24 yrs) 
b All JIA 
99 
 
100 

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1.7 
Rationale for Present Study 
101 
Despite advances in diagnosis and treatment, poor visual outcomes remain prevalent in children 
102 
with uveitis, not only from the disease process itself, but from corticosteroid-related side effects. 
103 
Therefore, there is a pressing need for a multicenter data collection study as proposed, to identify 
104 
the clinical features and prevalence of the types of uveitis in children. Collecting such data will 
105 
help design future randomized clinical trials to evaluate treatments for children with uveitis. 
106 
 
107 
Key study aims include defining specific uveitis phenotypes and etiologies and providing data on 
108 
the types of current and past treatments prescribed. Another important aim is to develop a 
109 
comprehensive Rasch-analyzed PEDIG Uveitis QoL questionnaire for use in future uveitis 
110 
studies. 
111 
 
112 
1.8 
Study Objective 
113 
Over a one-year period, to enroll children diagnosed with uveitis and collect data regarding 
114 
clinical features and current and past treatments at time of enrollment. For children with new 
115 
onset non-infectious uveitis (onset within 6 months prior to enrollment), a medical record review 
116 
will collect data 12-months after enrollment. 
117 
 
118 
1.8.1 Specific Aims 
119 
The specific aims of this observational study are to:  
120 
 
121 
1. Describe the frequency of uveitis subtypes in children <18 years of age, including new 
122 
onset uveitis (<6 months duration).  
123 
2. Describe clinical and demographic characteristics overall and within each type of uveitis. 
124 
3. Compare characteristics between uveitis subtypes.  
125 
4. Describe current and previous treatment history by type of uveitis.  
126 
5. Describe clinical measures done as part of usual care.  
127 
6. Determine recruitment potential overall and by site for different disease sub-types (new-
128 
onset vs. established disease, localization, etiology) for future randomized clinical trials.  
129 
7. Evaluate relationships between demographic, treatment, and clinical characteristics and 
130 
quality of life as measured by the EYE-Q (current version) questionnaire.  
131 
8. Develop a comprehensive PEDIG Uveitis Quality of Life questionnaire by administration 
132 
and calibration of EYE-Q plus additional uveitis-specific and treatment related items. 
133 
 
134 
1.9 
Potential Risks and Benefits 
135 
This is an observational data-collection study in children with uveitis. Participants with uveitis 
136 
will be enrolled and managed according to the investigator’s usual clinical practice. Current 
137 
clinical data and past historical data will be collected from chart review after informed consent 
138 
and again 12-months after enrollment for children with new onset non-infectious uveitis (onset 
139 
within 6 months of enrollment). 
140 
 
141 
1.9.1 Known Potential Risks 
142 
The risk to participating participants is the unlikely event of sensitive personal health 
143 
information being viewed by an unauthorized person. Efforts are being made to ensure that this 
144 
does not occur, as described in Chapter 7. 
145 
 
146 

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1.9.2 Known Potential Benefits 
147 
There are no direct benefits for study participants. Results of this study will provide important 
148 
new knowledge that will be helpful to design future randomized trials in children less than 18 
149 
years of age with uveitis. 
150 
 
151 
1.10 Risk Assessment 
152 
The protocol’s level of risk is consistent with 45 CFR 46.404 and 21 CFR 50.51, which indicates 
153 
research not involving greater than minimal risk for the individual involved in the research.  
154 
 
155 
1.11 General Considerations 
156 
The study is being conducted in compliance with the policies described in the network policies 
157 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with 
158 
the protocol described herein, and with the standards of Good Clinical Practice (GCP).
159 

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Chapter 2: 
Study Enrollment 
160 
 
161 
2.1 
Participant Recruitment and Enrollment 
162 
The study plans to enroll up to 300 participants over a one-year recruitment period for whom 
163 
parental informed consent and child assent will be obtained. 
164 
 
165 
Study participants will be recruited from PEDIG clinical sites and clinical sites affiliated with 
166 
the American Uveitis Society (AUS). All eligible participants will be included regardless of sex, 
167 
race, or ethnicity. There is no restriction on the number of participants enrolled at each site.  
168 
 
169 
As the study approaches the end of enrollment, sites will be notified of the end date for 
170 
recruitment into the study. Participants who have signed informed consent forms can be 
171 
enrolled until the end date. 
172 
 
173 
A screening log will be kept of all participants eligible for inclusion but not enrolled, along with 
174 
the reason for not enrolling. 
175 
 
176 
2.1.1 Informed Consent  
177 
A child is considered for the study after undergoing a routine eye examination (i.e., as part of 
178 
usual care) that identifies uveitis appearing to meet the eligibility criteria. The study will be 
179 
discussed with the child’s parent(s) or guardian(s) (referred to subsequently as parent(s)).  
180 
 
181 
Parent(s) and children 13 years of age or older who express an interest in the study will be given 
182 
a copy of the informed consent form to read.  
183 
 
184 
Prior to performing any study-specific procedures that are not part of the child’s routine care, 
185 
written or electronic informed consent must be obtained from the parent and child if the child is 
186 
13 years of age and older; and child assent must be obtained from a child 7 years of age and 
187 
older but less than 13 years of age. 
188 
 
189 
If informed consent and assent if required cannot be obtained, then study data collection cannot 
190 
continue.  
191 
 
192 
If the participant and/or parents are not fluent in written and spoken English, then the consent 
193 
and/or assent forms must be translated into a language of fluency for the participant/parent. 
194 
Further, a qualified interpreter must be available for the consent process and all subsequent 
195 
study-related interactions.  
196 
 
197 
A child is considered enrolled when the informed consent form and assent form (as applicable) 
198 
have been signed.  
199 
 
200 
2.2 
Eligibility Criteria 
201 
 
202 
2.2.1 Participant Inclusion Criteria 
203 
Individuals must meet all the following inclusion criteria to be eligible: 
204 
 
205 

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 Age: 
206 
o Incident cases (onset ≤ 6 months) <17 years  
207 
o Established cases (onset > 6 months) <18 years 
208 
 Diagnosis of any type of uveitis (infectious or noninfectious) in any location except 
209 
traumatic and post-operative uveitis. 
210 
 Active or inactive uveitis with any treatment status (current / prior / none [but under 
211 
surveillance]). 
212 
 
213 
2.2.2 Exclusion Criteria 
214 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from 
215 
study participation: 
216 
 
217 
 Bilateral uveitis with differing etiologies  
218 
 Traumatic uveitis  
219 
 Post-operative uveitis 
220 
 Immediate family member (spouse, biological or legal guardian, child, sibling, parent) 
221 
who is an investigative site personnel directly affiliated with this study or who is an 
222 
employee of JAEB Center for Health Research. 
223 
 Ocular disease related to Retinoblastoma, Coat’s disease, retinitis pigmentosa, inherited 
224 
retinal degeneration, Juvenile xanthogranuloma (JXG), or leukemia/malignancy within 
225 
the eye. 
226 
 
227 
2.3 
Screening Procedures 
228 
After signed informed consent (and assent, if required), a potential participant will be evaluated 
229 
for study eligibility by reviewing their medical history, along with data collection and clinical 
230 
testing as below. 
231 
 
232 
2.3.1 Demographic and Historical Information 
233 
The following demographic and historical information will be collected either as part of the 
234 
clinical exam or by review of available medical records and by parental / patient interview:  
235 
 
236 
1. Age at enrollment 
237 
2. Sex 
238 
3. Race / ethnicity 
239 
4. Age at initial diagnosis 
240 
5. Weight: estimated by parent or as noted in the medical record 
241 
6. Socioeconomic factors: distance from care, socioeconomic status, highest parental 
242 
education, insurance status (private, uninsured, government) 
243 
7. Ocular and medical history: 
244 
a. Prior medical treatments 
245 
b. Current medical treatments 
246 
i. Current systemic treatment dose and frequency 
247 
ii. Current eye-drop type +/- frequency 
248 
c. Prior surgeries 
249 
d. Complications and diagnoses 
250 
 
251 

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2.3.2 Systemic Disease  
252 
Current systemic diagnoses will be recorded and will include juvenile idiopathic arthritis, 
253 
sarcoidosis, Behcet disease, Vogt-Koyanagi-Harada, Tubulointerstitial Nephritis and Uveitis 
254 
syndrome, Inflammatory bowel disease, NOD2-spectrum syndrome, and other autoimmune 
255 
and/or infectious conditions.  
256 
 
257 
2.3.3 Clinical Testing 
258 
Clinical Measures: 
259 
 
260 
1. Monocular Distance Best Corrected Visual Acuity 
261 
In each eye, using investigators usual method, noting method. 
262 
 
263 
2. Intraocular Pressure 
264 
In each eye (mmHg), noting method (iCare, applanation, tonopen). 
265 
 
266 
3. Pupillary Reaction 
267 
Including recording of whether an afferent pupillary defect is present in each eye. 
268 
 
269 
4. Slit Lamp Exam 
270 
Including evaluation of the cornea, iris, lens, anterior chamber, and posterior segment. 
271 
Grading of cell count and flare pre-dilation using SUN criteria1 (see section 2.5.5).  
272 
 
273 
5. Dilated Fundus Exam 
274 
 
275 
a. Slit lamp exam by investigators usual method:  
276 
i. 
Grading of vitreous cell post-dilation as described in the MUST trial31 (see 
277 
section 2.5.6) 
278 
ii. 
Assessment of the retina with careful attention to the macula and optic nerve 
279 
 
280 
b. Indirect ophthalmoscopy:   
281 
i. 
Grading of vitreous haze as described by Nussenblatt et al32 and adopted by 
282 
the SUN group1 (see section 2.5.6).  
283 
ii. 
Assessment of the peripheral retina with scleral depressed exam if 
284 
indicated/tolerated 
285 
 
286 
Other clinical testing, performed according to the investigator’s usual practice (if done as usual 
287 
care), will also be collected if performed at the time of enrollment or within 60 days prior to 
288 
enrollment: 
289 
 
290 
6. Ocular Alignment 
291 
Presence versus absence of manifest strabismus at distance or near with designation of the 
292 
principal direction (esotropia, exotropia, or hypertropia). Measurement of strabismus 
293 
magnitude (if strabismus present) is not required.  
294 
 
295 
7. Refraction 
296 

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Investigators preferred method with cycloplegia. 
297 
  
298 
To help understand what constitutes usual care, investigators will be asked to indicate whether 
299 
the following specific tests were performed, but test data will not be collected: 
300 
 
301 
 Slit lamp photography 
302 
 Electroretinogram 
303 
 Visual fields 
304 
 Fluorescein angiography 
305 
 Optical coherence tomography of the optic nerve 
306 
 Optical coherence tomography of the macula  
307 
 Anterior segment OCT  
308 
 Magnetic resonance imaging 
309 
 Ultrasound (UBM)  
310 
 Ultrasound (B-scan)  
311 
 Indocyanine green angiography 
312 
 Color or pseudocolor fundus images 
313 
 Fundus autofluorescence 
314 
 A-scan (axial length for glaucoma)  
315 
 
316 
2.4 
Questionnaires 
317 
At the time of enrollment, the EYE-Q plus additional uveitis-specific quality of life and 
318 
treatment questions (identified from a literature review) may be completed by children age 8 to 
319 
<18 years; parent proxy may be completed by one parent for each child <18 years; parent 
320 
questionnaires may be completed by one parent for each child <18 years.   
321 
 
322 
2.4.1 Questionnaire Administration 
323 
For each participant, questionnaires should be attempted to be completed while the patient is in 
324 
office. Questionnaires will be administered electronically with a login for each participant. For 
325 
child questionnaires, the questionnaire MUST be completed during the visit and cannot be 
326 
continued out of the office. For both the proxy and parent questionnaires, questionnaires may be 
327 
completed after the visit, as long as completed within 7 days of the enrollment visit.  
328 
 
329 
2.5 
Uveitis Classification 
330 
For each participant clinical and historical data will be used to record the following for each 
331 
affected eye: etiology, localization, course, activity, control, and complications. 
332 
 
333 
2.5.1 Etiology 
334 
Uveitis will be classified as either non-infectious or infectious. Cause (suspected or confirmed) 
335 
will be recorded as indicated on study data collection forms, grouping in the following broad 
336 
categories: 
337 
 
338 
 Non-infectious:  
339 
o JIA-associated 
340 
o other systemic 
341 
o undifferentiated 
342 

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o other  
343 
 
Infectious  
344 
 
Drug-induced 
345 
 
Other 
346 
 
347 
2.5.2 Localization 
348 
Localization will be classified as bilateral vs unilateral and using the SUN criteria1 as follows:  
349 
 
350 
 
Anterior (anterior chamber): includes iritis, iridocyclitis, anterior cyclitis 
351 
 
Intermediate (vitreous): pars planitis, posterior cyclitis, hyalitis 
352 
 
Anterior and intermediate 
353 
 
Posterior (retina or choroid): focal, multifocal or diffuse chorioretinitis, chorioretinitis, 
354 
retinochoroiditis, retinitis, neuroretinitis 
355 
 
Panuveitis: anterior chamber, vitreous and retina or choroid 
356 
 
357 
2.5.3 Disease Course 
358 
Disease course will be classified in accordance with the SUN criteria:1  
359 
 
360 
 Acute: episode characterized by sudden onset and limited (≤3 months) duration 
361 
 Chronic: persistent uveitis with relapse <3 months after discontinuing treatment 
362 
 Recurrent: repeated episodes separated by periods of inactivity without treatment for ≥3 
363 
months. 
364 
 
365 
2.5.4 Disease Duration 
366 
‘New-onset’ cases will have less than 6 months total duration of disease.  
367 
 
368 
2.5.5 Disease Activity – Anterior Chamber 
369 
Disease activity will be graded in accordance with the SUN criteria1 
370 
 
371 
Grading system for anterior chamber cells1 
372 
Grade 
Cells in field† 
0
<1
0.5+
1-5
1+
6-15
2+
16-25
3+
26-50
4+
>50
† Field size is 1mm x 1mm slit beam 
373 
 
374 
 
375 
Grading system for anterior chamber flare1 
376 
Grade 
Description 
0
None
1+
Faint
2+
Moderate (iris and lens detail clear)
3+
Marked (iris and lens detail hazy)
4+
Intense (fibrin or plastic aqueous)
 
377 

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2.5.6 Disease Activity – Vitreous 
378 
 
379 
Grading system for vitreous haze32 through indirect ophthalmology  
380 
Grade 
Description 
0
None
0.5 
Slight blurring of optic disc margin; normal striations and reflex of the nerve 
fiber layer cannot be visualized
1+
Obscured view with definition to the optic nerve head and retinal vessels
2+
Obscured view with definition to the retinal vessels
3+
Optic nerve head visualized, but with blurry borders
4+
Obscured fundal view
 
381 
Grading system for vitreous cell31 
382 
Grade 
Cells in field†+ 
0
No cells
0.5/Trace
1 to 5 cells
1+
6 to 10 cells
2+
11 through 20 cells
3+
21 through 50 cells
4+
51 or more cells
† Field size is 1mm x 0.5mm slit beam 
383 
+Grade is based on number of cells in syneretic spaces 
384 
As assessed post-dilation at the slit lamp   
385 
 
386 
2.5.7 Disease Control 
387 
For each affected eye, uveitis control will be classified as either: 
388 
 
389 
1. Full control 
390 
 Grade 0 AC cell  
391 
 Grade 0 vitreous haze 
392 
 No retinal / choroidal inflammation 
393 
 If FA performed, no vascular leakage posterior to the equator 
394 
 
395 
2. Minimal activity 
396 
 <=0.5+ AC cell  
397 
 Grade 0 vitreous haze 
398 
 No retinal / choroidal inflammation 
399 
 If FA performed, no vascular leakage posterior to the equator  
400 
 
401 
3. Uncontrolled 
402 
 Criteria for full control or minimal activity are not met. 
403 
 
404 
If criteria for either full control or minimal activity are met, further classification will be made 
405 
regarding the use of topical or oral steroids:  
406 
 
407 
 Steroid-free: no systemic or topical steroids being used. No peri/intraocular 
408 
steroid injections for 6 months.  
409 

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 Steroid-limited: Topical steroids (prednisolone acetate 1%, or equal to/less 
410 
potent equivalent) - no more than 2 drops / day and no systemic steroids. No 
411 
peri/intraocular steroid injections for 3 months 
412 
 Steroid-dependent: does not meet criteria for steroid-free or steroid-safe control 
413 
 Remission: full control with no topical or systemic medications of any kind for 
414 
3 months with no disease activity  
415 
 
416 
2.5.8 Ocular Complications 
417 
Specific complications present at the time of the enrollment ocular exam will be recorded 
418 
including cataract, ocular hypertension, glaucoma, optic disc edema, band keratopathy, 
419 
hypotony, epiretinal membrane, posterior synechiae, and cystoid macular edema. 
420 
 
421 
The presence of glaucoma and glaucoma suspect will be defined according to Childhood 
422 
Glaucoma Research Network (CGRN) criteria33: 
423 
 
424 
 Glaucoma: presence of ≥2 of the following: 1) Intraocular pressure (IOP) of greater 
425 
than 21 mmHg, 2) optic nerve glaucomatous damage such as increased cupping, 
426 
focal notching, or cup to disc asymmetry of 0.2 or more between both eyes, 3) visual 
427 
field defects consistent with optic nerve glaucomatous damage 4) Myopic shift or 
428 
increased axial length  
429 
 
430 
 Glaucoma suspect: one of the following: presence of ocular hypertension (IOP of 
431 
greater than 21 mmHg; IOP elevation must be reproducible), visual field 
432 
abnormalities suspicious of glaucoma, optic nerve appearance suspicious of 
433 
glaucoma, or signs of ocular enlargement (e.g., increased corneal diameter or axial 
434 
length) with normal IOP.  
435 
 
436 
2.6 
Treatment 
437 
Participants will be managed according to the investigator’s usual clinical practice. 
438 
Documentation of current and prior treatment will include dose and frequency of each. 
439 
 
440 
2.7 
Medical Record Review 
441 
There is no study-mandated follow-up visit schedule, and no protocol related to how patients 
442 
should be managed. Visits occur as part of standard patient care. For children with new onset 
443 
non-infectious uveitis (onset within 6 months prior to enrollment), data will be collected 12-
444 
months following enrollment from standard care visits (visit window Enrollment +11 months to 
445 
Enrollment +15 months). When applicable, if more than one element is available for a report 
446 
field, the most recent element will be reported.  
447 
 
448 
Data collected will mirror data collection at time of enrollment and is summarized in the Study 
449 
Procedures Table.  
450 

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Chapter 3: 
Unanticipated Problem / Adverse Event Reporting 
451 
 
452 
3.1 
Unanticipated Problems 
453 
Given that the study is cross-sectional with data collection only, unanticipated problems are not 
454 
expected. However, if an unanticipated problem meeting the criteria below does occur, site 
455 
investigators will promptly report it to the Coordinating Center on an eCRF within seven (7) 
456 
calendar day of recognition. An unanticipated problem is an incident, experience, or outcome 
457 
that meets all the following criteria: 
458 
 
459 
 Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
460 
that are described in the protocol related documents, such as the IRB-approved research 
461 
protocol and informed consent document; and (b) the characteristics of the participant 
462 
population being studied 
463 
 Related or possibly related to participation in the research (possibly related means there is 
464 
a reasonable possibility that the incident, experience, or outcome may have been caused 
465 
by the procedures involved in the research) 
466 
 Suggests that the research places participants or others at a greater risk of harm than was 
467 
previously known or recognized (including physical, psychological, economic, or social 
468 
harm)   
469 
 
470 
The Coordinating Center also will report to the IRB all unanticipated problems not directly 
471 
involving a specific site such as unanticipated problems that occur at the Coordinating Center or 
472 
at another participating entity such as a pharmacy or laboratory.  
473 
 
474 
These instances must be reported to the JCHR IRB within seven calendar days of recognition.  
475 
 
476 
The Director of the Human Research Protection Program will report to the appropriate regulatory 
477 
authorities if the IRB determines that the event indeed meets the criteria of an Unanticipated 
478 
Problem that requires further reporting.  
479 
 
480 
3.2 
Adverse Events 
481 
The study is a passive data collection study and includes no specific intervention or use of a 
482 
device or drug as part of the protocol. Some participants may receive treatment for uveitis and 
483 
some may not. Data from any complications from past treatments will be collected at 
484 
investigator discretion but are not considered adverse events. 
485 
 
486 
The Coordinating Center will not be conducting any on-site monitoring. 
487 
 
488 
3.3 
Stopping Criteria 
489 
The study may be discontinued by the Jaeb Center for Health Research at any time. 
490 
 
 
491 

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Chapter 4: 
Miscellaneous Considerations 
492 
 
493 
4.1 
Contacts by the Jaeb Center for Health Research and Sites 
494 
The Jaeb Center serves as the PEDIG Coordinating Center. The Jaeb Center will NOT be 
495 
provided with the parent’s contact information and will not contact the parents or participant.  
496 
 
497 
4.2 
Participant Compensation 
498 
Participant compensation will be specified in the informed consent form. 
499 
 
500 
4.3 
Participant Withdrawal 
501 
Data will be collected at a single point in time after informed consent and assent if required. 
502 
Participation in the study is voluntary. 
503 
 
504 
4.4 
Confidentiality 
505 
For security and confidentiality purposes, participants will be assigned an identifier that will be 
506 
used instead of their name. Protected health information gathered for this study will be shared 
507 
with the coordinating center, the Jaeb Center for Health Research in Tampa, FL. De-identified 
508 
participant information may also be provided to research sites involved in the study. 
509 
 
510 
In addition, to help identify the study participant, the informed consent form and the assent form 
511 
(if applicable) will include permission for the PEDIG Coordinating Center to receive the child’s 
512 
initials (first, middle, and last name initial). 
513 
 
514 
Study data will be entered on the Coordinating Center’s secure website through an SSL 
515 
encrypted connection. The Coordinating Center websites are maintained on Unix and Linux 
516 
servers running Apache web server software and on a Windows server running IIS, all with 
517 
strong encryption. The registry website is password-protected and restricted to users who have 
518 
been authorized by the Coordinating Center to gain access. No identifiable health information of 
519 
an enrolled participant will be released by the Coordinating Center. 
520 

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Chapter 5: 
Statistical Considerations 
521 
 
522 
The approach to sample size and statistical analyses are summarized below. A detailed statistical 
523 
analysis plan (SAP) will be written and finalized before the first enrollment.  
524 
 
525 
5.1 
Sample Size 
526 
Up to 300 children will be enrolled over a one-year period. This sample is chosen for 
527 
convenience and not based on statistical principles. To provide estimates of precision, Table 3 
528 
below shows the expected half-width for a 95% confidence interval for various sample sizes and 
529 
proportions. Note that the half-width for 60% is identical to 40% and so-on.  
530 
 
531 
Table 3. Half-Width Table for Proportions 
532 
Sample Size 
Sample Proportion 
10% 
20% 
30% 
40% 
50% 
100
6%
8%
9%
10%
10%
150
5%
6%
7%
8%
8%
200
4%
6%
6%
7%
7%
250
4%
5%
6%
6%
6%
300
3%
5%
5%
6%
6%
 
533 
5.2 
Primary Analysis 
534 
There is not a formal primary analysis for this study. There are 8 specific aims (see Section 
535 
1.8.1) related to demographic and clinical characteristics, recruitment potential, and quality of 
536 
life that will be addressed.  
537 
 
538 
5.3 
Descriptive Data (Specific Aims 1–5) 
539 
The following data will be summarized overall and by uveitis subtype/etiology (Section 2.5) at 
540 
enrollment and following 12-month chart review. 
541 
 Demographic and historical information (see Section 2.3.1) 
542 
 Socioeconomic factors  
543 
 Laterality at time of initial diagnosis and at time of enrollment (if not diagnosed at time 
544 
of enrollment) 
545 
 Presence of systemic disease (see Section 2.3.2) 
546 
 Clinical testing (see Section 2.3.3) 
547 
 Etiology (see Section 2.5.1) 
548 
 Localization per the SUN criteria1 (see Section 2.5.2) 
549 
 Disease course classified per the SUN criteria1 (see Section 2.5.3) 
550 
 Disease Duration (Section 2.5.4): 
551 
o New onset: onset less than 6 months prior 
552 
o Established: present for 6 months or more  
553 
 Disease Activity 
554 
o Anterior chamber cells and flare per the SUN criteria1 (see Section 2.5.5) 
555 
o Vitreous haze and vitreous cell (see Section 2.5.6) 
556 
 Disease Control (see Section 2.5.7)  
557 

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 Ocular complications (see Section 2.5.8) 
558 
 Current and past treatments (see Section 2.6) 
559 
 
560 
5.4 
Recruitment potential (Specific Aim 6) 
561 
Total and monthly recruitment will be tabulated overall and stratified by site and type of uveitis.  
562 
5.5 
Questionnaires (Specific Aims 7-8) 
563 
Responses to all questionnaire items (EYE-Q as well as additional items) from each of the 3 
564 
questionnaires (child, proxy, and parent) will be used to create scores for analysis. For each 
565 
score, univariate relationships with each factor in Section 5.3 will be evaluated using linear 
566 
regression. To address the risk of false positives due to multiple comparisons, the false discovery 
567 
rate (FDR) will be controlled at 5%. Results will be considered significant if the FDR-adjusted p-
568 
value is < 0.05.  
569 
5.5.1 Rasch Analysis 
570 
Existing EYE-Q items will be combined with uveitis-specific quality of life questions. The child, 
571 
proxy, and parent responses will be used in separate factor analyses to determine the number of 
572 
domains for each questionnaire. Each domain will be refined through the evaluation of misfitting 
573 
items and will then be Rasch scored.  
574 
 
575 
5.5.2 Missing Data 
576 
In the event of missing data, a complete case analysis will be conducted unless otherwise 
577 
specified in the SAP. The potential impact of missing data will be assessed, and sensitivity 
578 
analyses may be conducted as appropriate. 
 
579 

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Chapter 6: 
Data Collection and Monitoring 
580 
 
581 
6.1 
Case Report Forms and Other Data Collection 
582 
The main study data are collected on electronic case report forms (CRFs). When data are directly 
583 
collected in electronic case report forms, this will be considered the source data. For any data 
584 
points for which the eCRF is not considered source (e.g., lab results that are transcribed from a 
585 
printed report into the eCRF), the original source documentation must be maintained in the 
586 
participant’s study chart or medical record. This source must be readily verifiable against the 
587 
values entered into eCRF. Even where all study data are directly entered into the eCRFs at office 
588 
visits, evidence of interaction with a live participant must be recorded (e.g., office note, visit 
589 
record, etc.). 
590 
 
591 
Electronic device data files are obtained from the study software and individual hardware 
592 
components. These electronic device files are considered the primary source documentation. 
593 
Each participating site will maintain appropriate medical and research records for this trial, in 
594 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
595 
confidentiality of participants. 
596 
 
597 
6.2 
Study Records Retention 
598 
Study documents should be retained for a minimum of 3 years after completion of the final grant 
599 
reporting. These documents should be retained for a longer period, however, if required by local 
600 
regulations. No records will be destroyed without the written consent of the sponsor, if 
601 
applicable. It is the responsibility of the sponsor to inform the investigator when these documents 
602 
no longer need to be retained. 
603 
 
604 
6.3 
Quality Assurance and Monitoring 
605 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
606 
assurance (QA) and quality control (QC) systems to ensure that the clinical portion of the trial is 
607 
conducted and data are generated, documented and reported in compliance with the protocol 
608 
adhering to Good Clinical Practice (GCP) and the applicable regulatory requirements, as well as 
609 
to ensure that the rights and wellbeing of trial participants are protected and that the reported trial 
610 
data are accurate, complete, and verifiable.  
611 
 
612 
The Coordinating Center will not be conducting any on-site monitoring.  
613 
 
614 
6.4 
Protocol Deviations 
615 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
616 
requirements. The noncompliance may be either on the part of the participant, the investigator, or 
617 
the study site staff. As a result of deviations, corrective actions are to be developed by the site 
618 
and implemented promptly. 
619 
 
620 
The site PI/study staff are responsible for knowing and adhering to their IRB requirements. 
621 
Further details about the handling of protocol deviations will be included in the monitoring plan. 
622 

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Chapter 7: 
 Ethics/Protection of Human Participants 
623 
 
624 
7.1 
Ethical Standard 
625 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
626 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 
627 
21 CFR Part 56, and/or the ICH E6. 
628 
 
629 
7.2 
Institutional Review Boards 
630 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
631 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
632 
form must be obtained before any participant is enrolled. Any amendment to the protocol will 
633 
require review and approval by the IRB before the changes are implemented to the study. All 
634 
changes to the consent form will be IRB approved; a determination will be made regarding 
635 
whether previously consented participants need to be re-consented. 
636 
 
637 
7.3 
Informed Consent Process 
638 
 
639 
7.3.1 Consent Procedures and Documentation 
640 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
641 
the study and continues throughout the individual’s study participation. Extensive discussion of 
642 
risks and possible benefits of participation will be provided to the participants and their families. 
643 
Consent forms will be IRB-approved and the participant will be asked to read and review the 
644 
document. The investigator will explain the research study to the participant and answer any 
645 
questions that may arise. All participants will receive a verbal explanation in terms suited to their 
646 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
647 
research participants. Participants will have the opportunity to carefully review the written 
648 
consent form and ask questions prior to signing. 
649 
 
650 
The participants should have the opportunity to discuss the study with their parents or think 
651 
about it prior to agreeing to participate. The participant will sign the informed consent document 
652 
prior to any procedures being done specifically for the study. The participants may withdraw 
653 
consent at any time throughout the course of the trial. A copy of the informed consent document 
654 
will be given to the participants for their records. The rights and welfare of the participants will 
655 
be protected by emphasizing to them that the quality of their medical care will not be adversely 
656 
affected if they decline to participate in this study. 
657 
 
658 
7.4 
Participant and Data Confidentiality 
659 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, 
660 
and the sponsor(s) and their agents. This confidentiality is extended to cover testing of biological 
661 
samples and genetic tests in addition to the clinical information relating to participants. 
662 
Therefore, the study protocol, documentation, data, and all other information generated will be 
663 
held in strict confidence. No information concerning the study or the data will be released to any 
664 
unauthorized third party without prior written approval of the sponsor. 
665 
 
666 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
667 
regulatory agencies or company supplying study product may inspect all documents and records 
668 

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required to be maintained by the investigator, including but not limited to, medical records 
669 
(office, clinic, or hospital) and pharmacy records for the participants in this study. The clinical 
670 
study site will permit access to such records. 
671 
 
672 
The study participant’s contact information will be securely stored at each clinical site for 
673 
internal use during the study. At the end of the study, all records will continue to be kept in a 
674 
secure location for as long a period as dictated by the reviewing IRB, institutional policies, or 
675 
sponsor requirements. 
676 
 
677 
When feasible, data will be directly collected in electronic case report forms, which will be 
678 
considered the source data. Study participant research data, which is for purposes of statistical 
679 
analysis and scientific reporting, will be transmitted to and stored at the Jaeb Center for Health 
680 
Research. This will not include the participant’s contact or identifying information. Rather, 
681 
individual participants and their research data will be identified by a unique study identification 
682 
number. The study data entry and study management systems used by clinical sites and by Jaeb 
683 
Center for Health Research staff will be secured and password protected.  
684 
 
685 
At the end of the study, all study databases will be de-identified and archived at the Jaeb Center 
686 
for Health Research. 
687 
 
688 
To further protect the privacy of study participants, a Certificate of Confidentiality will be 
689 
obtained from the NIH. This certificate protects identifiable research information from forced 
690 
disclosure. It allows the investigator and others who have access to research records to refuse to 
691 
disclose identifying information on research participation in any civil, criminal, administrative, 
692 
legislative, or other proceeding, whether at the federal, state, or local level. By protecting 
693 
researchers and institutions from being compelled to disclose information that would identify 
694 
research participants, Certificates of Confidentiality help achieve the research objectives and 
695 
promote participation in studies by helping assure confidentiality and privacy to participants. 
696 
 
697 
7.5 
Future Use of Data 
698 
Data collected for this study will be analyzed and stored at the Jaeb Center for Health Research. 
699 
After the study is completed, the de-identified, archived data will be made available to the 
700 
public. 
701 
 
702 

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Chapter 8: 
References 
703 
 
704 
1. 
Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for 
705 
reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 
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2005;140(3):509-516   
707 
2. 
Edelsten C, Reddy MA, Stanford MR, Graham EM. Visual loss associated with pediatric 
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uveitis in english primary and referral centers. American Journal of Ophthalmology. 
709 
2003;135(5):676-680. 
710 
3. 
Siiskonen M, Hirn I, Pesälä R, Hautala T, Ohtonen P, Hautala N. Prevalence, incidence 
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and epidemiology of childhood uveitis. Acta Ophthalmologica. 2021;99(2):e160-e163. 
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4. 
Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the 
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Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111(3):491-500; 
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discussion 500. 
715 
5. 
Thorne JE, Suhler E, Skup M, et al. Prevalence of Noninfectious Uveitis in the United 
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States: A Claims-Based Analysis. JAMA Ophthalmology. 2016;134(11):1237-1245. 
717 
6. 
Maleki A, Anesi SD, Look-Why S, Manhapra A, Foster CS. Pediatric uveitis: A 
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comprehensive review. Survey of Ophthalmology. 2022;67(2):510-529. 
719 
7. 
Angeles-Han ST, Lo MS, Henderson LA, et al. Childhood Arthritis and Rheumatology 
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Research Alliance consensus treatment plans for juvenile idiopathic arthritis-associated and 
721 
idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken). 2019;71(4):482-491. 
722 
8. 
Smith JA, Mackensen F, Sen HN, et al. Epidemiology and course of disease in childhood 
723 
uveitis. Ophthalmology. 2009;116(8):1544-1551. 
724 
9. 
Ferrara M, Eggenschwiler L, Stephenson A, et al. The challenge of pediatric uveitis: 
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Tertiary referral center experience in the United States. Ocular Immunology and Inflammation. 
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2019;27(3):410-417. 
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10. 
Rosenberg KD, Feuer WJ, Davis JL. Ocular complications of pediatric uveitis. 
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Ophthalmology. 2004;111(12):2299-2306. . 
729 
11. 
Group SoUNSW. Classification Criteria for Intermediate Uveitis, Non-Pars Planitis 
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Type. Am J Ophthalmol. 2021;228:159-164. 
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Group. SoUNSW. Classification Criteria For Pars Planitis. Am J Ophthalmol. 
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2021;228(doi):268-274. 
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Saurenmann RK, Levin AV, Feldman BM, et al. Prevalence, risk factors, and outcome of 
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uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis and Rheumatism. 
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2007;56(2):647-657. 
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Kitano M, Tanaka R, Kaburaki T, et al. Clinical Features and Visual Outcome of Uveitis 
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in Japanese Patients Younger than 18 Years. Ocul Immunol Inflamm. 2021;29(7-8):1280-1286  
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15. 
Kump LI, Cervantes-Castañeda RA, Androudi SN, Foster CS. Analysis of pediatric 
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uveitis cases at a tertiary referral center. Ophthalmology. 2005;112(7):1287-1292. 
740 
16. 
Stroh IG, Moradi A, Burkholder BM, Hornbeak DM, Leung TG, Thorne JE. Occurrence 
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of and Risk Factors for Ocular Hypertension and Secondary Glaucoma in Juvenile Idiopathic 
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Arthritis-associated Uveitis. Ocul Immunol Inflamm. 2017;25(4):503-512. 
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17. 
Wolf MD, Lichter PR, Ragsdale CG. Prognostic factors in the uveitis of juvenile 
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rheumatoid arthritis. Ophthalmology. 1987;94(10):1242-1248  
745 
18. 
Cassidy JT PR. Textbook of Pediatric Rheumatology. WB Saunders Company; 2001. 
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19. 
Kotaniemi K, Kautiainen H, Karma A, Aho K. Occurrence of uveitis in recently 
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diagnosed juvenile chronic arthritis: a prospective study. Ophthalmology. 2001;108(11):2071-
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Thorne JE, Woreta FA, Dunn JP, Jabs DA. Risk of cataract development among children 
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with juvenile idiopathic arthritis-related uveitis treated with topical corticosteroids. 
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Ophthalmology. 2010;117(7):1436-1441   
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Angeles-Han ST, Ringold S, Beukelman T, et al. 2019 American College of 
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Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of 
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Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Rheumatol. 2019;71(6):864-877   
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22. 
Yalçındağ FN, Güngör SG, Değirmenci MFK, et al. The Clinical Characteristics of 
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Pediatric Non-Infectious Uveitis in Two Tertiary Referral Centers in Turkey. Ocul Immunol 
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Inflamm. 2021;29(2):282-289.  . 
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Ekici Tekin Z, Otar Yener G, Akbulut S, Çetin EN, Yüksel S. Follow-up findings of non-
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infectious pediatric uveitis patients. Turkish Journal of Ophthalmology. 2021;51(6):351-357. 
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24. 
Wieringa WG, Armbrust W, Legger GE, Los LI. Efficacy of High-Dose Methotrexate in 
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Pediatric Non-Infectious Uveitis. Ocular Immunology and Inflammation. 2019;27(8):1305-1313. 
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25. 
Henderson LA, Zurakowski D, Angeles-Han ST, Lasky A, Rabinovich CE, Lo MS. 
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Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology 
764 
Research Alliance Registry. Pediatric Rheumatology. 2016;14(1):9. 
765 
26. 
McCracken C, Yeh S, Jenkins K, et al. Timing of infliximab and adalimumab initiation 
766 
despite methotrexate in children with chronic non-infectious anterior uveitis. Eye (Lond). 
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2019;33(4):629-639  
768 
27. 
Simonini G, Druce K, Cimaz R, Macfarlane GJ, Jones GT. Current evidence of anti-
769 
tumor necrosis factor α treatment efficacy in childhood chronic uveitis: a systematic review and 
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meta-analysis approach of individual drugs. Arthritis Care Res (Hoboken). 2014;66(7):1073-
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772 
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Gregory AC, 2nd, Kempen JH, Daniel E, et al. Risk factors for loss of visual acuity 
773 
among patients with uveitis associated with juvenile idiopathic arthritis: the Systemic 
774 
Immunosuppressive Therapy for Eye Diseases Study. Ophthalmology. 2013;120(1):186-92. . 
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29. 
Markomichelakis NN, Aissopou EK, Chatzistefanou KI. Pediatric Non-Infectious 
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Uveitis: Long-Term Outcomes and Complications. Ocul Immunol Inflamm. 2023;31(10):2001-
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Dajee KP, Rossen JL, Bratton ML, Whitson JT, He YG. A 10-year review of pediatric 
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uveitis at a Hispanic-dominated tertiary pediatric ophthalmic clinic. Clinical Ophthalmology. 
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2016;10:1607-1612   
781 
31. 
Kempen JH, Altaweel MM, Holbrook JT, Jabs DA, Sugar EA. The multicenter uveitis 
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steroid treatment trial: rationale, design, and baseline characteristics. Am J Ophthalmol. 
783 
2010;149(4)(e10):550-561. 
784 
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Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal 
785 
inflammatory activity in intermediate and posterior uveitis. Ophthalmology. 1985;92(4):467-471. 
786 
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Thau A, Lloyd M, Freedman S, Beck A, Grajewski A, Levin AV. New classification 
787 
system for pediatric glaucoma: implications for clinical care and a research registry. Curr Opin 
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789 
 
790