*The CORIMAP study - A comparison study between a prototype retinal handheld oximeter (CORIMAP camera) and the Oxymap T1*

This study protocol is part of the ROPOXYMAP study, which has as a main goal to
make retinal oximetry available for children with vascular retinal diseases.
Retinal oximetry is an imaging technique, which utilizes the difference in
light absorption of hemoglobin bound and unbound to oxygen at different
wavelengths of light, to determine the relative oxygen saturation of the blood
in the retinal vessels.

The Compact Retinal Mapper (CORIMAP) camera has been developed to make retinal
oximetry available for the use in infants, in order to gain knowledge about the
oxygen metabolism of the retina in premature born children with a risk of
developing ROP. The available Oxymap T1 oximeter is only suitable for oxygen
saturation measurements in adults. Currently, there is no objective way to
measure the relative oxygen saturation in the retinal vessels in this
vulnerable group of patients. With the introduction of the CORIMAP, this
imaging technique will provide an increase in the insight of the oxygen
metabolism of the retina. There are creating possibilities for improving the
management, treatment and even prevention of ROP.

A second beneficial advantage of this newly developed device, is its
non-invasive approach to acquiring the fundus images in supine infants without
making contact to the superficial layer of the eye (cornea). This is in
contrast to the current standard camera for neonatal screening (RetCam,
Clarity, USA), which needs to make contact to the cornea to acquire images.
Additional advantage that exceeds from neonatal care into adult care is the
possibility to capture images in supine position, which is beneficial to
patients who cannot be seated in front of a conventional fundus camera, such as
severely ill or (sub)comatose patients.

With this study protocol, we wish to introduce a prototype handheld camera with
oximetry abilities, called the CORIMAP camera. Before making the transition to
an infant/child population, this study aims to validate and calibrate the
CORIMAP camera in comparison to the current Oxymap T1 in a healthy adult
population.

The primary objective of this study is to determine the Optical Density Ratio
(ODR) for the prototype CORIMAP camera and compare the ODR values with the
Oxymap T1 mounted on a regular fundus camera in a healthy adult population. For
comparison, it is paramount to determine the ODR of both oximeter cameras in
normoxia and hyperoxia conditions. With this study protocol, we wish to
introduce a prototype handheld camera with oximetry abilities, called the
CORIMAP camera. This study aims to validate and calibrate the CORIMAP camera in
a healthy adult population.

The study design is a prospective intervention study of healthy volunteers. The
volunteers will be recruited during a period of a year at the outpatient clinic
of the department of ophthalmology of the Leiden University Medical Centre.

For this study, a prototype handheld fundus camera with retinal oximetry
functionality will be used to acquire retinal images. The oximetry
functionality will be tested and compared to the validated Oxymap T1
(commercial available oximeter) with in normoxia oxygen breathing and in
hyperoxia condition by the supplication of oxygen. The validation study of the
Oxymap T1 used a study design, similar for the current study for the validation
of the CORIMAP camera. The prototype camera will be the first handheld
oximeter; therefore the repeatability will be tested in the handheld mode
(supine) as well as mounted in an ophthalmologic chin rest for seated patients.

The purpose of a retinal oximeter is the measure the relative oxygen saturation
in the retinal vessels. Therefore, measuring oxygen saturation in different
oxygen conditions (normoxia / hyperoxia) is paramount determining the
sensitivity of the measurements of the CORIMAP camera.
In one of the three phases of the photo session, participants will be supplied
with 100% oxygen, isocapnic until hyperoxia is reached. This procedure will be
repeated for both oximeter cameras. During this stage, an arterial line wil be
inserted in the participants for monitoring the bloodgas values. During the
recovery phase, retinal images will be captured every 15s during a period of 3
min. The pupil of one of the eyes of the participants will be dilated with 1
drop Tropicamide 0.5% during the ophthalmological examination for the duration
of the study procedure/

The volunteers participating in this study will visit the outpatient clinic of
the department of ophthalmology, the LUMC once for this study. The visit will
take between 90-120 minutes. During this visit, the participants will undergo
an ophthalmological examination and a photo session. This photo session
consists of three phases (sitting up right (both oximeters)), supine position
(CORIMAP camera) and hyperoxic 100% (both oximeters). During the hyperoxia
experiment a member of the department of Anaesthesiology will be present to
insert an arterial line, for verifying the blood gas values to ensure that
hyperoxia has been reached and to monitor the subjects during the experiment.
The benefits of the arterial line for collecting data from blood gas values
outweighs the small risk of complications.

The risk of the instilment of the mydriatic drops is equal to the minimal risks
of a regular visit to the ophthalmologist. As for the prototype camera, all
technical specifications are well within the NEN*EN-ISO 15004-2-2007
guidelines, therefore risks should be equal to regular ophthalmological fundus
cameras. The oximetry functionality of the CORIMAP camera will be beneficial
for adults in supine position and young children, especially for premature born
children. This latter fragile population is at risk of developing retinopathy
of prematurity. Present study will precede a study in infants, with as goal to
perform retinal oximetry in (premature) infants. These studies individual and
combined will provide a better understanding in the physiology of the retinal
metabolism and understanding of pathophysiology in retinal diseases to create
possibilities for early detection, treatment, management and even prevention.