Methods
The University of Arkansas for Medical Sciences (UAMS) IRB approved this
prospective, single-center study. Male and female patients ages 2-21
years were approached at Arkansas Children’s Hospital Sickle Cell clinic
during their outpatient visits. Patients with sickle cell disease (SS,
SC, SBº-thalassemia, SB+-thalassemia) were considered
for the study and screened for enrollment. Patients were eligible if
they were afebrile for 48 hours (fever defined as temperature
>101°F), had vital signs within normal limits, had not
received any narcotics in the last 24 hours, and were not currently
experiencing any pain based on a patient-reported, age-appropriate pain
scale. Additionally, patients were excluded if they had a prior history
of stroke or neurological deficits.
After consent was obtained, each child was tested using the NeurOptics
PLR-2000 Pupillometer. The handheld device includes a rubber cup that is
placed over the child’s eye in order to block any outside light sources.
The device then locates the pupil and measures the resting (maximum)
pupil diameter (mm). Next, an infrared light briefly flashes and the
pupillometer measures the average and maximum pupil constriction
velocity (mm/s), minimum pupil diameter (mm), % change in pupil size in
response to light, and the pupil dilation velocity after exposure to
infrared light stimulus (mm/s) (Fig. 1). The testing takes <2
minutes, is noninvasive, and is associated with little to no risk for
the patient. Patient data was excluded if a reading could not be
obtained after 4 measurement attempts.
After data collection, the measurements were divided across different
age groups as well as male vs. female study participants for analysis.
Maximum and minimum pupil sizes were reported as means with standard
deviations across six age groups (range 2-21 years old). Maximum and
minimum pupil sizes, maximum and average constriction velocity, and
dilation velocity were reported as means with standard deviation and p
values as overall, male, and female results.
Data were evaluated for assumptions of normality and equal variances
using the Shapiro–Wilk W test and Levene’s tests, respectively. To
determine if pupillometry measures differed between gender, independent
sample t-tests were conducted. Minimum and maximum pupil sizes were
presented as means and standard deviations. The GPLOT procedure,
incorporating linear regression, was utilized to create scatter plots
and regression lines for pupil size and velocity by patient age. All
data were analyzed using SAS software version 9.4 (SAS Institute, Cary,
NC, USA).