Objective, Prospective Measurement of Anterior Chamber Cell Grading Using Anterior Chamber Ocular Coherence Tomography
Phase: NA
Conditions: Uveitis
Sponsor: Rutgers, The State University of New Jersey

Department of Ophthalmology and Visual Science
Rutgers New Jersey Medical School
David S. Chu, M.D.
90 Bergen Street
Newark, NJ 07103
NJMS.Rutgers.edu
chuda@njms.rutgers.edu
p. 973-972-2064
RESEARCH PROTOCOL
Version 1.5
Date 10/6/2016
Research Title: Objective, Prospective Measurement of Anterior Chamber Cell Grading Using 
Anterior Chamber Ocular Coherence Tomography
Short Title: Prospective OCT Measurement of AC Cells
Purpose: 

To determine the feasibility of objective measurement of anterior chamber (AC) cell count 
utilizing 
o
the SPECTRALIS (Heidelberg Engineering, Franklin, MA) spectral domain optical 
coherence tomography (OCT) system
o
the iSCAN (Optovue, Fremont, CA) spectral domain OCT system

To develop algorithms that automatically differentiate between cells and “noise” in the anterior 
chamber OCT (AC-OCT) images and objectively measure the cell density

To correlate the objective AC cell density measurement and the subjective clinical AC cell 
grading 

To compare the objective AC cell density measurement with subject treatment outcomes
Introduction:
Treatment decisions for patients with uveitis are currently formulated largely on subjective clinical exam 
data with high interobserver variation.1 The most used and most accurate of these subjective clinical 
data is anterior chamber (AC) cell grade, a measure of intraocular inflammation.1 AC cell grade is 
measured by experienced clinicians who manually count the number of leukocytes in a 1mm by 1mm 
beam of light in the AC visible through a slit lamp stereoscope. The result is a “grade” for AC cells on a 
nonlinear, ordinal scale as follows: grade 0 is <1 cell, grade 0.5+ is 1-5 cells, grade 1+ is 6-15 cells, grade 
2+ is 16-25 cells, grade 3+ is 26-50 cells, and grade 4+ is >50 cells.2 The wide range of cells included in 
the higher grades means that a large change in anterior chamber inflammation might go unnoticed. For 
example, a patient with 28 cells at their last visit (grade 3+) but 48 cells at their current visit (still grade 
3+) would have their 71% increase in intraocular inflammation go unnoticed, as they are still grade 3+.  
This has concerning implications for both the treatment of patients with intraocular inflammation and 
the evaluation of interventions that target intraocular inflammation (such as pharmaceuticals). 
People with uveitis and people who recently underwent cataract extraction surgery often have 
intraocular inflammation on clinical exam. Those with uveitis are generally given anti-inflammatory 
medication to resolve their inflammation. Inflammation after cataract extraction surgery is generally 
self-resolving. 
Optical Coherence Tomography (OCT) uses infrared light with a central wavelength of 840 - 870 nm from 
a superluminescent diode to scan ocular structures and produce cross sectional and three dimensional 
images.3,4 It is considered a Class 1 laser product that, “does not pose any safety hazard whatsoever.”3,5 
Pro20160000585
           10/24/2016
           7/19/2017

Title: Prospective OCT Measurement of AC Cells
PI: David S. Chu, MD
2
Version 1.5, 10/6/2016
OCT machines are used widely in ophthalmology clinics to image the retina and objectively measure 
glaucoma progression. It can also be used to image the anterior chamber. 
A few studies have evaluated the feasibility of imaging the AC to objectively measure intraocular 
inflammation using optical coherence tomography (OCT). Many of these have used older, time domain 
OCT (TD-OCT) devices, with resolutions larger than most leukocytes.6-8 One has used newer, spectral 
domain OCT (SD-OCT) technology with promising results.9  No study that we are aware of, however, has 
either used the SPECTRALIS or iSCAN SD-OCT systems for these measurements, or correlated these 
measurements against clinical outcomes. We plan to use the SPECTRALIS and iSCAN SD-OCT systems to 
image the AC of subjects with intraocular inflammation, automate the objective reading of AC cell count 
from these images, correlate the objective count with the subjective clinical grade, and observe if the 
correlation is strong enough to guide treatment decisions. 
Hypothesis:
Automated, objective measurement of anterior chamber cell count with the SPECTRALIS (Heidelberg 
Engineering, Franklin, MA) and iSCAN (Optovue, Fremont, CA) spectral domain optical coherence 
tomography systems cannot be used to guide the treatment of patients with intraocular inflammation.
Methods:
This is a prospective clinical imaging study. Treatment and follow up of subjects will not be altered 
through this study. Subjects will be selected from the pool of patients in the Doctors Office Center (DOC) 
at New Jersey Medical School/University Hospital who attend the Wednesday Uveitis clinic. The clinic is 
staffed by two staff physicians (David Chu, MD and Ronald Rescigno, MD) and a rotating staff of NJMS 
ophthalmology residents. Non-patient control subjects may also have an opportunity to participate in 
this study; this group will include friends and relatives of enrolled subjects and any person who 
volunteers for the study (such as those who saw the study registered on clinicaltrials.gov). Up to 300 
subjects will be enrolled. 
Three groups of subjects will be enrolled: one “uveitis imaging” group, one “cataract imaging” group, 
and one “control” group. The uveitis imaging group will include subjects with uveitis. The cataract 
imaging group will include subjects who have just undergone cataract extraction surgery within the 
previous 30 days. The third group will function as a control. Inclusion criteria for both imaging groups 
will include an age over 18 years old and active anterior chamber inflammation in at least one eye as 
diagnosed by clinical exam. Inclusion criteria for the uveitis imaging group will also include a diagnosis of 
uveitis. Inclusion criteria for the cataract imaging group will also include having recently undergone 
cataract extraction surgery within the previous 30 days. Inclusion criteria for controls will include an age 
of 18 years old in subjects with and without uveitis who do not have active intraocular inflammation 
based on clinical exam. Exclusion criteria for all three groups will include corneal opacities in the 
affected eye that would limit objective measurement by OCT and anyone judged unable to understand 
or consent to study participation. The two staff physicians will identify eligible subjects for inclusion. 
Controls will be recruited from the same clinic described above. Controls will include patients who meet 
the inclusion criteria above, and also non-patient control subjects who meet the inclusion criteria above. 
Pro20160000585
           10/24/2016
           7/19/2017

Title: Prospective OCT Measurement of AC Cells
PI: David S. Chu, MD
3
Version 1.5, 10/6/2016
Prior to the scan, non-patient control subjects will also undergo a brief, non-contact ocular exam by 
either David Chu, MD or Ronald Rescigno, MD, to ensure that they meet inclusion and do not met 
exclusion criteria (e.g. they have no intraocular inflammation and no corneal opacities); this exam will 
not require any eye drops. 
The study will be thoroughly explained to any potential subjects identified by the two staff physicians. 
Subjects recruited will be patients of the investigators or non-patient control subjects (such as the 
relatives and friends of those patients who attend the clinic with them).  Any potential subject will be 
asked to participate and will have the study thoroughly explained to them. They will have the 
opportunity to ask questions and will be given ample time to decide on participation or 
nonparticipation. They will also have the opportunity to discuss the study and their participation with 
relatives or friends.  They will be notified that their participation is completely optional and that 
participation or nonparticipation in this study will not alter or affect their relationship with their doctor 
or any of their healthcare providers. To avoid coercion, the study risks will be carefully explained to 
subjects and it will be emphasized that participation is completely optional and not required for their 
medical care or for their relationship with their physician. A subject’s participation or nonparticipation in 
this study will not alter or affect their medical care in any way. Treatment of subject’s uveitis will still be 
based on clinical examination, and not on any information obtained from the OCT imaging. The consent 
process will be administered by any of the following study staff (“study personnel obtaining consent”): 
Elliot Crane, study coordinator and NJMS medical student; David Chu, MD and uveitis specialist; and 
Ronald Rescigno, MD and uveitis specialist. 
The study personnel obtaining consent will ensure each subject has verbal fluency of the English 
language and is well able to understand the study procedures and consent form. People of all economic 
classes and educational levels will be invited equally to participate in the study. Minority status will also 
not be a factor in participation. Children, prisoners, and pregnant woman will not be included in this 
study. Pregnant woman will not be included due to the majority of expected eligible patients being non-
pregnant. 
The study personnel obtaining consent will assess capacity. Only subjects who have capacity to consent 
will be allowed to participate. The study personnel obtaining consent will also assess subjects’ 
comprehension of the study.  Only subjects who fully comprehend their role in the study will be allowed 
to participate. Subjects who do not understand their role and the risks and benefits will be ineligible to 
participate. This includes subjects with significant cognitive impairments and who do not speak English. 
Subjects with hearing impairments will be allowed to participate as long as they can understand their 
role in the study and understand explanations from the study personnel obtaining consent. Subject’s 
continued capacity for consent will be monitored by the study personnel who obtain consent. They will 
be reminded before each image acquisition that they do not have to participate and that they can drop 
out of the study whenever they want to. The principal investigator may discontinue the study with any 
subjects who are unfit to participate.
The OCT scan will be taken by either the SPECTRALIS or iSCAN OCT systems, or both. The SPECTRALIS is 
owned by Rutgers University, and it is stored in a locked room in DOC 6136. The iSCAN is owned by 
Pro20160000585
           10/24/2016
           7/19/2017

Title: Prospective OCT Measurement of AC Cells
PI: David S. Chu, MD
4
Version 1.5, 10/6/2016
Rutgers University, and it is stored in a locked room in DOC 6100A. The image for both OCT systems will 
be taken by Elliot Crane, the study coordinator and NJMS medical student, who has extensive 
experience operating various OCT machines and has been trained in operating the SPECTRALIS and 
iSCAN. 
Subjects who meet inclusion criteria, do not meet exclusion criteria, and who agree to participate in the 
study will be asked to sign a consent form. Non-patient control subjects will then be given a non-contact 
ophthalmic exam by either David Chu, MD or Ronald Rescigno, MD. All subjects will then be taken to 
one of two OCT imaging rooms (DOC 6136 or DOC 6100A), where the process of imaging will be 
explained and carried out. The scan itself will take less than one minute. After consent is obtained, the 
entire imaging process will take approximately 10-20 minutes. The consent and imaging process will 
occur at the end of the subject’s normal exam visit. The consent, exam, and imaging process for non-
patient control subjects will occur at pre-scheduled times arranged individually by the subjects and 
study staff. 
Choice of which OCT system to use (SPECTRALIS or iSCAN) will depend on OCT and subject availability. 
Subjects will generally be asked to use the SPECTRALIS OCT system. If the SPECTRALIS is being used for 
clinic patients, subjects will be asked to instead use the iSCAN system. If they have time and agree, some 
subjects will be asked to use both systems to ensure similar results can be obtained from each system. 
The system used on a subject’s first visit will determine which system they use for their entire 
enrollment. Subjects will use the same OCT system for the duration of their enrollment in this study. 
Each enrolled subject will be scanned a total of between one and eight times over a period of two to 
eight weeks, depending on the dates of their scheduled follow up visits in clinic. The scans will only 
occur on their regularly scheduled clinic visits. The first scan will occur on the first visit where they are 
identified as eligible and they agree to participate. Patients with active intraocular inflammation in the 
uveitis clinic are generally prescribed anti-inflammatory medications and asked to return within a few 
days to weeks to evaluate resolution of the inflammation. Patients who recently underwent cataract 
extraction surgery are also asked to return within a few days to weeks to follow up the surgery. On 
these follow up visits, the subjects will be reminded that participation is optional and they will be asked 
to undergo another OCT scan. Subjects who agree will be scanned again on these follow up visits with 
the same procedure described above. This will allow us to identify both inflammation and resolution of 
inflammation on the study images and analyze the data as described in the last paragraph of this 
protocol.  Non-patient control subjects will have the option of only undergoing one scan or individually 
scheduling follow-up visits for repeat scans for up to eight total scans over a period of two to eight 
weeks. No subject will be scanned more than eight times in total for this study. 
The scans performed by the SPECTRALIS and iSCAN OCT machines are non-contact procedures that use 
safe, infrared light. The subject rests their chin and forehead into plastic rests that are cleaned with 
alcohol between each use. The SPECTRALIS or iSCAN OCT can then image the subject’s eye. The subject’s 
eye will not be touched for this scan or for any part of this study. No eye drops will be used for this 
study, as none are required for these high quality, non-contact scans. 
Pro20160000585
           10/24/2016
           7/19/2017

Title: Prospective OCT Measurement of AC Cells
PI: David S. Chu, MD
5
Version 1.5, 10/6/2016
All study activities will be performed in the Doctor’s Office Center suite 6100. Subject recruitment and 
the consent process will occur in exam rooms owned by Rutgers University in DOC 6100. Subjects who 
enroll in the study, as described above, will be brought to either DOC 6136 or DOC 6100A, where the 
SPECTRALIS OCT or iSCAN OCT, respectively, are stored and where the study scans will be performed; 
this room and the equipment are owned by Rutgers University. Data storage and analysis will take place 
on computers and in locked areas of DOC 6100 owned by Rutgers University. 
A list of participating subjects with unique identification keys will be kept in the locked room of a 
secondarily locked research area by the study coordinator.
Data taken from the medical record will include: name, date of birth, medical record number, 
inflammation status, and ocular history. The name, date of birth, and medical record number will be 
used to coordinate scans for subject’s follow-up visits. The inflammation status and ocular history will be 
used to make appropriate comparisons for the study. 
Scan data will be stored in the SPECTRALIS or iSCAN OCT systems as is standard for clinical practice. Scan 
data will be taken from the OCT system via encrypted USB drive upon each subject’s completion in the 
study. The data will then be de-identified, labeled with the unique identification key described above, 
and stored in the locked room of a secondarily locked research area. The key will remain on paper in a 
locked room in a secondarily locked research area in the DOC. Only the study coordinator and principle 
investigator will have access to the data. 
Subject risks include potential breach of confidentiality of information collected and the loss of 10-20 
minutes of time required to complete the OCT scan process. The risk of breach of confidentiality of 
information is minimal due to the lack of collection of sensitive information and will be further 
minimized by storing data in locked and password protected files, as described above. Subject benefits 
include potentially increased understanding of intraocular inflammation and the new management 
standards that may be applied to their, and others’, uveitis treatment in the future.  
All subject data obtained will be confidential. Data will only be released in aggregate and no subjects’ 
personal identifiers will be revealed. 
De-identified image data from the SPECTRALIS and iSCAN OCT systems will be analyzed two ways. The 
first analysis methodology will be the manual identification of leukocytes on the OCT image by the staff 
uveitis specialists. The second analysis methodology will be the automatic identification of leukocytes on 
the OCT image by computer algorithm. The AC cell count results of the two analysis methodologies will 
be compared to subject’s clinical AC cell grading. Statistical analysis using T-test and other statistical 
tools will be used to compare the study and the clinical AC cell count methodologies. Study AC cell count 
results will also be correlated with the actual subject treatment plans and outcomes to test the null 
hypothesis that the study results would not have been able to correctly guide subject treatment 
decisions. 
References: 
Pro20160000585
           10/24/2016
           7/19/2017

Title: Prospective OCT Measurement of AC Cells
PI: David S. Chu, MD
6
Version 1.5, 10/6/2016
1.
Kempen JH, Ganesh SK, Sangwan VS, Rathinam SR. Interobserver agreement in grading activity 
and site of inflammation in eyes of patients with uveitis. Am J Ophthalmol. 2008;146:813-818.
2.
Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of Uveitis Nomenclature for Reporting 
Clinical Data. Results of the First International Workshop. Am J Ophthalmol. 2005;140:509-516.
3.
User Manual: SPECTRALIS HRA+OCT. Heidelberg Engineering GmbH;2012.
4.
ISCAN. Optovue 2016; http://www.optovue.com/products/iscan/, 2016.
5.
Laser Safety Information. Laser Institute of America 2016; 
https://www.lia.org/subscriptions/safety_bulletin/laser_safety_information. Accessed March 
31, 2016.
6.
Agarwal A, Ashokkumar D, Jacob S, Saravanan Y. Highspeed optical coherence tomography for 
imaging anterior chamber inflammatory reaction in uveitis: clinical correlation and grading. Am J 
Ophthalmol. 2009;147:413-416.
7.
Li Y, Lowder C, Zhang X, Huang D. Anterior Chamber Cell Grading by Optical Coherence 
Tomography. Invest Ophthalmol Vis Sci. 2013;54(1):258-265.
8.
Igbre A, Rico M, Garg S. HIGH-SPEED OPTICAL COHERENCE TOMOGRAPHY AS A RELIABLE 
ADJUVANT TOOL TO GRADE OCULAR ANTERIOR CHAMBER INFLAMMATION. Retina. 
2014;34:504-508.
9.
Sharma S, Lowder CY, Vasanji A, Baynes K, Kaiser PK, Srivastava SK. Automated Analysis of 
Anterior Chamber Inflammation by Spectral-Domain Optical Coherence Tomography. 
Ophthalmology. 2015;122:1464-1470.
Pro20160000585
           10/24/2016
           7/19/2017