Mendelian Randomization Shows a Causal Effect of Low Vitamin D on Non-infectious Uveitis and Scleritis Risk.

PURPOSE: To investigate a causal relationship between Vitamin D levels and non-infectious uveitis and scleritis using Mendelian randomization (MR) techniques. DESIGN: Two-sample Mendelian randomization case-control study. METHODS: The study setting was a biobank of an academic, integrated health care system. The patient population comprised 375 case patients with a non-infectious uveitis and/or scleritis diagnosis and no diagnosis of infectious, trauma-related, or drug-induced uveitis/scleritis. In addition, there were 4167 controls with no uveitis or scleritis diagnosis. Causal effect estimates of low 25-hydroxy Vitamin D (25OHD) on uveitis/scleritis risk were calculated. RESULTS: We found an association of genetically decreased 25OHD with uveitis/scleritis risk (odds ratio [OR] = 2.16, 95% CI = 1.01-4.64, P = .049, per SD decrease in log25OHD). In a first sensitivity MR analysis excluding the genetic variants that are unlikely to have a role in biologically active 25OHD, effect estimates were consistent with those from the primary analysis (OR = 2.38, 95% CI =1.06-5.36, P = 0.035, per SD of log25OHD). Furthermore, in a second sensitivity analysis using only the 6 variants within the CYP2R1 locus (which encodes 25OHD hydroxylase, the liver enzyme responsible for converting Vitamin D to 25OHD), genetically decreased 25OHD was strongly associated with increased uveitis/scleritis risk (OR = 6.42, 95% CI = 3.19-12.89, P = 1.7 × 10-7, per SD of log25OHD). CONCLUSIONS: Our findings suggest a causal relationship between low Vitamin D levels and higher risk of non-infectious uveitis and scleritis. Vitamin D supplementation may be a low-cost, low-risk intervention to mitigate non-infectious uveitis and scleritis risk, and should be explored in a prospective trial.

A Pilot Study of Automated Pupillometry in the Treatment of Opioid Use Disorder.

INTRODUCTION/BACKGROUND: A rough, visual estimate of pupil size is used in grading the severity of opioid withdrawal. Few studies have examined the clinical utility of more precise automated pupillometry measurements. METHODS: This prospective cohort study enrolled 27 patients receiving opioid agonist therapy (OAT) to treat cravings or withdrawal during an acute hospitalization. Six sets of automated pupillometry measurements were obtained at regular intervals before and after administration of OAT. Clinical Opiate Withdrawal Scale measurements were performed pre and post OAT. Primary outcomes included pupil size in dark and bright illumination (mm). Latency of the pupillary light response (s), constriction and dilation velocity (mm/s), and percent constriction (%) were secondary outcomes. RESULTS: The mean predosing pupil size in dark and bright illumination was 4.33 ±â€Š1.40 mm and 2.96 ±â€Š0.79 mm, respectively. A significantly decreased mean pupil size was first detected at 15 minutes postdosing (4.01 ±â€Š1.34 mm, P = 0.0115 for dark illumination; 2.71 ±â€Š0.72 mm, P = 0.0003 for bright illumination) and this reduction in pupil size persisted at later postdosing timepoints. Those with Clinical Opiate Withdrawal Scale <5 after dosing had a greater decrease in dark pupil size (10.6% ±â€Š13.2 vs 3.2% ±â€Š3.2, P = 0.043). There was no significant change in the remaining pupil reactivity parameters. CONCLUSIONS: Automated pupillometry demonstrated a small but significant change in mean pupil size that occurred within 15 minutes of OAT dosing and was associated with low withdrawal scores. This pilot may inform future work to incorporate pupillometry measurement into OAT dosing assessments.

Association of Low Vitamin D Levels with Noninfectious Uveitis and Scleritis.

Purpose: To determine whether an association between Vitamin D and noninfectious ocular inflammation exists. Methods: Retrospective case-control study with 765 patients (333 uveitis cases, 103 scleritis cases, 329 controls). Logistic regression models examined the relationship between hypovitaminosis D and ocular inflammation. Results: The odds of having uveitis were 1.92 times higher for patients with hypovitaminosis D compared to patients with normal Vitamin D levels in the multivariate analysis [odds ratio (OR) = 1.92, 95% Confidence Interval (CI) = 1.36-2.72, p = 2.32 × 10-4]. A secondary analysis demonstrated that the odds of developing uveitis or scleritis were 5% lower and 4% lower, respectively, for every unit increase in Vitamin D level (uveitis: OR = 0.95, 95% CI = 0.94-0.97, p = 9.87 × 10-6; scleritis: OR = 0.96, 95% CI = 0.93-0.99, p = 0.009). Conclusion: Hypovitaminosis D was associated with increased risk of ocular inflammation in this retrospective study.