The post-illumination pupil respOnse and its relation with Sleep quality and skin temperature in patients with a history of optic Chiasm Compression

A history of optic chiasm compression is associated with altered circadian
rhythmicity with complaints of disturbed sleep and daytime fatigue, despite
adequate hormonal substitution in case of hypopituitarism. Compression of axons
of special intrinsically photosensitive retinal ganglion cells (ipRGCs) that
form the retinohypothalamic tract (RHT) and mediate photoentrainment of the
suprachiasmatic nucleus (SCN) could be a causal factor. Similar ipRGCs control
the pupillary light reflex through projections to the olivary pretectal nucleus
(OPN). The post-illumination pupil response (PIPR) after blue light is regarded
as an unique indicator of melanopsin-mediated ipRGC function. We hypothesize
that hypopituitarism patients with a history of optic chiasm compression due to
a sellar tumour have a reduced PIPR as a result of dysfunctional ipRGC
transduction, and that a reduced PIPR is related to disturbed sleep and altered
thermoregulation in these patients.

Our main objective is to assess the difference in PIPR after a blue-light
stimulus between hypopituitarism patients with and without a history of CC.
Secondary objectives include differences in subjective and objective sleep
quality, sleep-wake disturbances and skin temperature between groups and
correlations between these parameters and to the PIPR.

Observational study, comparing two predefined groups from one historical cohort
of patients suffering from pituitary insufficiency. Duration: 8 days per
patient, 1 or 2 study visits.

A medical and ocular history is taken through an interview. Several
questionnaires on sleep, fatigue and chronotype are filled out at home (60-75
minutes). For most patients there will be only one study visit. Visual acuity
and colour vision are evaluated and then the PIPR assessment is performed using
pupillometry. After dilatation of the pupil to achieve maximal illumination of
the retina, the right eye is exposed to bright red and blue light stimuli with
intensities well below safety recommendations. The pupil diameter of the left
eye is continuously measured using an infrared camera. After the pupillometry
the left pupil is dilated as well and an evaluation by an ophthalmologist
follows, using slit-lamp biomicroscopy. The visit, including waiting time and
explanation, will last half a day. Tropicamide side-effects are minor and
include transient stinging and a dry mouth. The induced mydriasis affects
visual acuity for several hours, so patients cannot drive during that time. The
risk of inducing acute angle closure glaucoma with tropicamide is extremely low
(0.006-0.03%). In the unlikely event of it occurring, rapid treatment is at
hand. If the ophthalmological evaluation is unremarkable, ambulant study
procedures follow. Patients receive an actigraph, to be worn continuously on
the wrist for 7 days and causing no more discomfort than a wristwatch. They
will also keep a sleep diary during this week. Furthermore, 5 small
water-resistant temperature sensors are placed on different locations on the
skin for 3 days with either Velcro or adhesive tape. These can cause some minor
discomfort. A 6th sensor is attached to the actigraph strap to record
environmental temperature, causing no discomfort. The last procedure is an
ambulant polysomnography during one night. Various electrodes and sensors are
administered by a trained nurse on the head, chest and legs. The wires are
connected to a portable recorder that is worn on the body with an elastic band.
Patients can therefore move around normally. The various sensors and wires can
be somewhat inconvenient during eating, drinking and other activities. After
waking up the next day, they can remove the equipment return it by mail in a
specially provided box.
The risks associated with participation in this study are negligible, and the
burden is limited. The results of the study will aid in the understanding of
ipRGC function and the association with disturbed sleep and thermoregulation
after optic chiasm compression. This will lead to better information for
patients and guide future research on the consequences of chiasm compression
and on interventions to alleviate symptoms.