Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT06235346 |
Other study ID # |
2015/56 |
Secondary ID |
|
Status |
Completed |
Phase |
|
First received |
|
Last updated |
|
Start date |
March 15, 2015 |
Est. completion date |
January 15, 2016 |
Study information
Verified date |
January 2024 |
Source |
Bezmialem Vakif University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
The goal of this observational study is to evaluate the ocular effects of Bonzai (synthetic
cannabinoids) with spectral-domain optical coherence tomography.
Researchers will compare eye findings in patients who have previously used Bonzai with a
healthy control group to see if there are ocular effects.
Description:
MATERIAL AND METHODS Participants This study was designed as cross-sectional, observational,
case-control study. Upon referral from the judiciary-supervised probation unit of Alcohol and
Substance Research, Treatment and Training Centre (AMATEM) of the relevant tertiary
psychiatry hospital between March 2015 and January 2016, 60 eyes of 60 consecutive male
patients with past synthetic cannabinoids (SC) use and 30 eyes of age-matched 30 male healthy
control subjects were enrolled in the study in 3 groups: a control group (n=30) included eyes
of subjects with no history of use of any substance including tobacco, a seronegative SC
group (n=30) included eyes of patients declaring no present use of any substance, as verified
by three consecutive negative urine toxicology tests performed two weeks apart, and a
seropositive SC group (n=30), including eyes of patients with positive urine toxicology tests
proving present use of SC.
SCs and relevant metabolites in urine samples were screened with a direct ELISA kit (K2
Enzyme Immunoassay, Immunalysis Corp., Pomona, CA, USA). This kit was able to detect relevant
metabolites, such as JWH-018, JWH-073, and AM-2201, with a cut-off level of 20 ng/mL and over
for positive results. Exposures to classical cannabinoids, ecstasy, amphetamines, opioids,
and ethylene glycol were also screened.
Regarding SC use, the patients were asked about the duration and the last time of use. In
addition, the previous use of other substances was questioned in detail.
Ophthalmic Assessments All eyes underwent ophthalmic examinations, including autorefraction,
best-corrected visual acuity (BCVA) testing, biomicroscopy, non-contact IOP measurement, and
dilated fundus examination.
An experienced technician performed spectral-domain optical coherence tomography (SD-OCT)
imaging of all eyes following pupil dilatation (1% tropicamide) and systolic/diastolic blood
pressure measurements (SBP/DBP). All SD-OCT assessments were conducted between 14:00 and
16:00 to minimize the potential effect of diurnal variation. Only high-quality SD-OCT images
with a signal strength index (SSI) greater than 50 were sent for analysis. The parafoveal
retinal thickness (parafoveal RT) and central foveal thickness (CFT), CT, peripapillary RNFL
thickness, and macular GCC thickness measurements were performed with an RTVue-100 OCT device
(Optovue Inc., Fremont, US), which had a 5 µm axial image resolution with a speed of 27,000
A-scans per second.
We preferred the ONH map protocol for examining the RNFL parameters. This protocol creates a
RNFL thickness map based on measurements around a circle 3.45 mm in diameter centred on the
ONH. The protocol for the GCC scan was based on examining a square grid (7 × 7 mm) on the
central macula after centring 1 mm temporal to the macula. The average, superior, and
inferior values displayed by the device were studied for the mean GCC and mean RNFL
parameters.
Segmental divisions were recorded with the MM5 protocol of the inbuilt software,
characterized by a 5 × 5 mm2 grid of 11 horizontal and 11 vertical lines with 668 A-scans and
a 3 × 3 mm2 inner grid of 6 horizontal and 6 vertical lines with 400 A-scans for the retinal
thickness of a 1 mm diameter CFT. The CT was measured by cross-sectioning through the
foveolar centre line, characterized by an 8 mm width, with 1024 A-scans captured on the
chorioretinal mode (these settings enable enhanced depth imaging along with contrast and
brightness tuning). The line was rotated horizontally and vertically so that manual
measurements were taken first at the central foveola and then 750 µm apart in the nasal,
temporal, superior, and inferior directions with the ruler function, using a line extending
from the posterior edge of the retinal pigment epithelium to the choroidoscleral junction.
The choroidal structure was analysed using the method previously described by Agrawal et al.,
and all collected images were processed and analysed using the open-source and publicly
available ImageJ software (version 1.50a, freely available at http://imagej.nih.gov/ij/;
National Institutes of Health [NIH], Bethesda, MD). According to this method, the image was
first binarized using the Niblack auto-local thresholding function. This provided a clear
visualization of the choroidoscleral interface while also enabling the precise selection of a
region of interest, such as the total subfoveal choroidal area (TA). A fovea-centred, 1500 μm
wide, nasal-to-temporal subfoveal choroidal area was manually selected using the polygon
selection tool. The dark pixels representing the luminal area (LA) were selected using the
colour threshold tool, and the residual light pixels were considered the stromal area (SA).
The subfoveal CVI was calculated as the ratio of the LA to the TA. Manual measurements (CT
and CVI) were carried out by the same experienced investigator blinded to the groups. Each
measurement was repeated twice, and the mean of the two measurements was used in the
analysis.
Statistical analysis Statistical analysis was conducted with software (SPSS 22.0 Version, IBM
Corporation, New York, USA). Descriptive statistics were stated as the mean, standard
deviation (SD), or median (Med), the interquartile range (Q1-Q3), and the frequency and ratio
(%) values, where appropriate. The distribution of normality was evaluated for each parameter
with the Kolmogorov-Smirnov test. Parametric (for normal distribution) or non-parametric
tests were applied as appropriate. A parametric analysis of variance (ANOVA) with a post hoc
Tukey test or a non-parametric Kruskal-Wallis test with a post hoc Bonferroni-corrected
Mann-Whitney U test was used to analyse the independent variables. The chi-square test was
used to analyse the qualitative data. Correlations of choroidal thickness measurements with
parameters relevant to SC use were studied using the Spearman test.