The Impact of Chronic Cannabis Use on Esophageal Motility in Patients Referred for Esophageal Manometry.

BACKGROUND: Tetrahydrocannabinol, the main psychoactive compound in cannabis, binds with high affinity to the cannabinoid 1 receptor. Small randomized controlled studies using conventional manometry have shown that the cannabinoid 1 receptor can modulate esophageal function, namely transient lower esophageal sphincter relaxation frequency and lower esophageal sphincter tone. The effect of cannabinoids on esophageal motility in patients referred for esophageal manometry has not been fully elucidated using high-resolution esophageal manometry (HREM). We aimed to characterize the clinical effect of chronic cannabis use on esophageal motility utilizing HREM. METHODS: Patients who underwent HREM from 2009 to 2019 were identified at 4 academic medical centers. The study group consisted of patients with a noted history of chronic cannabis use, a diagnosis of cannabis-related disorder, or a positive urine toxicology screen. Age and gender-matched patients with no history of cannabis use were selected to form the control group. Data on HREM metrics based on the Chicago classification V3, and the prevalence of esophageal motility disorders were compared. Confounding effects of BMI and medications on esophageal motility were adjusted for. RESULTS: Chronic cannabis use was found to be an independent negative predictor of weak swallows (ß=-8.02, P =0.0109), but not a predictor of failed swallows ( P =0.6890). The prevalence of ineffective esophageal motility was significantly lower in chronic cannabis users compared with nonusers (OR=0.44, 95% CI 0.19-0.93, P =0.0384). There was no significant difference in the prevalence of other esophageal motility disorders between the 2 cohorts. In patients with dysphagia as their primary indication for HREM, chronic cannabis use was found to be independently associated with increased median integrated relaxation pressure (ß=6.638, P =0.0153) and increased mean lower esophageal sphincter resting pressure (ß=10.38, P =0.0084). CONCLUSIONS: Chronic cannabis use is associated with decreased weak swallows and reduced prevalence of ineffective esophageal motility in patients referred for esophageal manometry. In patients referred for dysphagia, chronic cannabis use is associated with increased integrated relaxation pressure and lower esophageal sphincter resting pressure, though not to levels above the normal range.

Machine Learning-Based Automated Detection of Hydroxychloroquine Toxicity and Prediction of Future Toxicity Using Higher-Order OCT Biomarkers.

OBJECTIVE: Despite guidelines for hydroxychloroquine (HCQ) toxicity screening, there are clear challenges to accurate detection and interpretation. In the current report, the feasibility of automated machine learning (ML)-based detection of HCQ retinopathy and prediction of progression to toxicity in eyes without preexisting toxicity has been described. DESIGN: Retrospective, longitudinal cohort study. SUBJECTS: Subjects on HCQ therapy. METHODS: This was an institutional review board-approved, retrospective, longitudinal image analysis of 388 subjects on HCQ. Multilayer, compartmental, retinal segmentation with ellipsoid zone (EZ) mapping was used to harvest quantitative spectral-domain (SD)-OCT biomarkers. Using a combination of clinical features (i.e., cumulative HCQ dose and the duration of therapy) and quantitative imaging biomarkers (e.g., volumetric EZ integrity and compartmental measurements), ML models were created to detect toxicity and predict progression based on ground-truth OCT-based toxicity readings by 2 masked retina specialists. Furthermore, 10-fold cross-validation was performed. MAIN OUTCOME MEASURES: The model performance was visualized using receiver operator curves and calculating the area under the curve (AUC). The corresponding sensitivity and specificity values were evaluated for the feasibility of HCQ toxicity screening and prediction. RESULTS: The prevalence of HCQ toxicity in this cohort of 388 patients was 9.8% (n = 38). Twenty-one eyes progressed to toxicity during follow-up. OCT-based features (i.e., partial EZ attenuation, EZ volume, outer nuclear layer volume, and compartmental thicknesses) and clinical features (i.e., HCQ daily dose, HCQ cumulative dose, and duration of therapy) showed significant differences between the toxic and nontoxic groups. Percentage area with partial EZ attenuation (i.e., percentage of the macula with an EZ-retinal pigment epithelium thickness of ≤ 20 µm) was the most discriminating single feature (toxic, 35.7 ± 46.5%; nontoxic, 1.8 ± 4.4%; P < 0.0001). Using a random forest model, high-performance, automated toxicity detection was achieved, with a mean AUC of 0.97, sensitivity of 95%, and specificity of 91%. Furthermore, the toxicity progression prediction model had a mean AUC of 0.89, with a sensitivity and specificity of 90% and 80%, respectively. CONCLUSIONS: This report described the feasibility of high-performance automated classification models that used a combination of clinical and quantitative SD-OCT biomarkers to detect HCQ retinal toxicity and predict progression to toxicity in cases without toxicity. Future work is needed to validate these findings in an independent dataset.

Quantitative assessment of outer retinal layers and ellipsoid zone mapping in hydroxychloroquine retinopathy.

BACKGROUND: To quantitatively assess outer retinal layers in eyes with hydroxychloroquine (HCQ) toxicity. METHODS: A retrospective case-control study was performed to identify eyes with HCQ retinopathy/toxicity at Cleveland Clinic. A clinical diagnosis of HCQ retinopathy was made based on clinical and imaging features including the presence of parafoveal ellipsoid zone (EZ) loss on spectral-domain optical coherence tomography (OCT) and visual field defects. All participants underwent macular cube scan using the Cirrus HD-OCT (Zeiss, Oberkochen, Germany). Quantitative assessment of outer nuclear layer (ONL)/Henle fibre layer complex (HFL) metrics and EZ mapping were performed with a novel software platform and compared with age-matched controls. HCQ toxicity group was divided into three subgroups based on the severity. RESULTS: There were 14 eyes from 14 patients in HCQ toxicity group (mean age 57.0±18.6 years), and 14 eyes from 14 subjects in age-matched control group (mean age 59.4±18.6 years). Multiple outer retinal parameters including ONL/HFL-EZ volume, parafoveal ONL/HFL-EZ thickness and EZ-retinal pigment epithelium (RPE) volume were significantly reduced in all HCQ toxicity subgroups (early, moderate and advanced toxicity) compared with controls. Semiautomated layer segmentation tool produced en face representation of EZ-RPE mapping and allowed unique visualisation of EZ attenuation in eyes with HCQ toxicity. The longitudinal analysis of HCQ toxicity group demonstrated progressive decline in some outer retinal parameters. CONCLUSION: HCQ toxicity resulted in significant outer retinal layer volumetric thinning compared with controls. Quantitative assessment of outer retinal parameters and EZ mapping on SD-OCT may become a useful biomarker to identify and monitor HCQ toxicity.