The attenuation coefficient of the retinal nerve fiber layer derived from spectral domain optical coherence tomography AND diplopia in Parkinson*s disease

An clinical diagnosis of Parkinson*s disease (PD) is still challenging, in
particular in the early stages. A quarter of patients is initially
misdiagnosed, even when seen by movement disorder specialists.1 An accurate
diagnosis is a prerequisite for adequate patient counseling and the start of
therapy. PD is now known to be a multisystem disorder that includes retinal
pathology and visual complaints like diplopia.2,3 With the development of
Optical Coherence Tomography (OCT) in vivo visualization of the retina is
possible and recent studies using this technique have shown that the Retinal
Nerve Fiber Layer (RNFL) in PD is significantly thinner than in healthy
subjects.4,5 However, since the observed differences are small with overlapping
confidence intervals, it is unlikely that regular RNFL measurements will prove
useful as an (early) diagnostic tool.
A possible solution comes from research in glaucoma patients, in whom atrophy
of the RNFL reflects disease progression.6 In glaucoma patients, measurement of
the RNFL attenuation coefficient (RNFL-ac), which reflects the scattering
properties of the retina, proved to be a sensitive measure of RNFL changes in
addition to the usual RNFL-thickness,7 see figure 1. Whether this novel method
of measuring RNFL properties is also useful in patients with PD has never been
investigated.
In this pilot study we want to study the differences in RNFL-ac between PD
patients and healthy controls. When RNFL-ac proves to be a sensitive measure
of retinal pathology in PD it would have great potential as a powerful and
non-invasive diagnostic tool to differentiate between PD patients and healthy
subjects. If it proves to be highly sensitive it might be able to differentiate
between PD patients and healthy subjects in a very early stage, maybe even
before motor symptoms of PD are present. Furthermore it might be a biomarker
for disease progress in PD patients, which can be valuable in monitoring the
effect of future protective therapy.
In addition we will investigate visual complaints in PD patients and
investigate the difference with healthy controls. PD patients have impaired
mobility and visual compensation is important to prevent falling.3 Many PD
patients complain about dubbel vision which is poorly understood. To the
authors knowledge there is never been a study with orthoptistic investigation
of PD patients. We want to perform a orthoptistic investigation in PD patients
to objectivate the dubbelvision and compare these findings to those in healthy
controls

Part 1: The primary objective is to investigate if the RNFL-ac in PD patients
differs significantly from the RNFL-ac in healthy controls.
Secondary Objectives are:
1) to investigate if the RNFL-ac can be used to differentiate PD patients from
healthy controls.
2) to compare the sensitivity of the RNFL-ac with RNFL thickness in
differentiating PD patients from healthy controls.
3) to investigate local differences in the RNFL-ac of the retina.

Part 2: The primary objective of the second part of the study is to objectivate
dubbelvision in PD patients and compaire its occurrence to healthy controls
Secondary objectives of the second part of the study are
1) Investigate visual acuity in PD patients and compare this tho the visual
acuity in healthy controls
2) Investigate astigmatism in PD patients compared to astigmatism in healthy
controls

This pilot study is an observational, cross-sectional study in PD-patients and
healthy control subjects. The study duration is 1 year and the study will take
place in the OLVG in Amsterdam.
The study protocol starts with a clinical examination and a visual acuity test
(with a Snellen chart) by a neurologist with experience in movement disorders
(AMMV, JLMvHH or HCW) to confirm the clinical diagnosis of PD. This will take
up to 20 minutes.
After an optional 10-minutes break patients and controls will undergo the
Ophtalmologic examination. This consists of an ocular pressure examination,
slit lamp examination, fundoscopy and OCT, and will take another 70 minutes. In
total (including the break) the protocol takes 1 hour and 40 minutes.

An information letter of this study (see METC protocol, Appendix D) will be
given or sent to PD patients attending the out-patient clinic of the OLVG.
After informed consent eligible patients will be invited to participate in the
study protocol.

The study protocol begins with a clinical examination: a regular neurological
examination including a MMSE, and a visual acuity test (with a Snellen chart),
performed by a movement disorder specialist (AMMV, JLMvHH or HCW). The clinical
examination will take place in the ophthalmology outpatient clinic of the OLVG
and will take 20 minutes.
After an optional 10-minute brake the ophthalmologic examination will start.
Both eyes of the subject will be examinated. First ocular pressure will be
measured by non-contact tonometry. For this the subjects will be seated in a
chair and rest their chin on a holder. They will be asked to look at a green
light and will feel a puff of air in their eyes, one by one. This is not
painfull and there will be no direct contac with the eyes of the subjects.
After this an OCT scan of the retina will be done, with the Spectralis OCT
system (Heidelberg Engineering, Dossenheim, Germany). For this subjects will
also be seated in a chair and rest there chin on a holder. They will be asked
to look at a red infrared light, again there will be no direct contact with the
subject eyes and there is no potential harm of this test. The reflection of the
infrared light in the subject eyes will be processed by the OCT machine. In the
second part of the study an orthoptist will investigate the subject which wil
take 20 minutes. The subject will be seated in a chair again and will be asked
to look at a screen on eye level.The subject will be asked to wear glasses with
one green and one red glass and to hold a green flashlight. Then there will be
a red light projected on the screen and the subject is asked to point the green
fleshlight exactly on the red light on de screen. The accuracy with which the
subject is able to do this will be measured.
The next step in the study protocol is to giveAfter this the subject will get
eye dorrps to achieve mydriasis. Every subject will get one drop of
tropicamide 1%, and in case of dark eyes, an additional drop of fenylefrine 5%.
These eye drops may give transient side effects: tropicamide may give a
prickling feeling, a raised ocular pressure, blurring of vision, dry mouth,
headache, tachycardia, allergic reaction and although rare and mainly in
children, a psychotic episode. Side effects of fenylefrine are rare (<0,01%)
and consist of a allergic conjunctivitis, tearing, blurring of vision,
prickling feeling, glaucoma, headache, subarachnoid haemorrhage, high blood
pressure, tachycardia, arrhythmia, myocardial infarction.
After 10 minutes mydriasis will be achieved and subjects will undergo the slit
lamp examination. For this the subject will have to sit in a chair, rest their
chin on a holder and look straight ahead. The examiner, an ophtalmologic
resident, will look with a bright light in the subject eyes. Additionally
fundoscopie will take place. The subject keeps seated and will be asked to look
straight ahead again. The examiner will look in the subjects eyes with the slit
lamp and a special lens. During these tests there will be no direct contact
with the eyes of the subjects and these tests bare no harm to subjects.
However, the mydriasis with concomitant blurring of vision caused by the eye
drops, may last for four to eight hours (followed by complete recovery).
Therefore we advise subjects to arrange someone to take them home after the
study visit. The ophthalomologic tests wilt take 70 minutes in total an the
total study protocol takes one hour and 40 minutes.
If during neurological and/or ophthalmologic examination any symptoms that
require further investigation or treatment are discovered, the participant will
be informed and will receive a referral letter with our findings for his or her
general practitioner.