BACKGROUND: To date, no study has specifically examined children with acute-onset pupillary motility disorders (APMD). Especially in the Emergency Department (ED), it is crucial to distinguish benign and transient conditions from life-threatening or urgent conditions (UCs). The aim of the study is to describe the clinical characteristics of children with APMD and their association with an increased risk of UCs.
METHODS: We conducted a pediatric retrospective study of APMD referred to ED over a 10-year period. We described the characteristics in the overall sample and in two subgroups divided according to urgency of the underlying condition. Furthermore, we applied a logistic regression model to identify the variables predictive of LT condition.
RESULTS: We analyzed 101 patients. In 59.4%, the APMD was isolated. In patients with extra-ocular involvement, the most frequently associated features were altered consciousness, headache, and vomiting. Exposure to toxic agents was reported in 48.5%. Urgent conditions occurred significantly more frequently in older children, presenting bilateral APMD and/or other ocular or extra-ocular manifestations.
CONCLUSIONS: Our study shows that UCs most commonly occur in patients presenting with bilateral APMD and other associated features. In unilateral/isolated APMD ophthalmological examination, exclusion of toxic exposure and observation until resolution of symptoms should be recommended.

OBJECTIVE: Previous transverse and a handful of longitudinal studies have shown that the slope of the static accommodation response/stimulus curve declines as complete presbyopia is approached. Changes in pupillary miosis and ocular spherical aberration (SA) are also evident. This study further investigated longitudinal changes in the relationships between the monocular static accommodative response, pupil diameter and SA of a single adult.
METHODS: A wavefront analysing system, the Complete Ophthalmic Analysis System, was used in conjunction with a Badal optometer to allow continuous recording of the aberration structure of the dominant eye in a low myope for a range of accommodative demands (-0.83 to 7.63 D) over a period of 17 years until the age of 50. Monocular accommodative response was calculated as the equivalent refraction minimising wavefront error. The associated longitudinal changes in pupil size and SA with accommodation were also recorded.
RESULTS: A decrease in accommodation response with age was found at almost all target vergences, with the changes being greatest for higher vergences. In addition, although absolute pupil diameter decreased with age, the rate of change in pupil diameter with accommodative stimulus remained approximately constant with age. Pupil constriction occurred for near stimuli even in full presbyopia. SA changed linearly with the accommodation response at all ages.
CONCLUSIONS: The objective amplitude of accommodation declined linearly with age as complete presbyopia was approached, while the slope of the response/stimulus curve also fell. It was hypothesised that the retinal image blur associated with the larger lags of accommodation at higher accommodative stimuli was reduced by pupil constriction and the resulting lower levels of SA.

BACKGROUND: Opioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjects with untreated OSA have increased sensitivity to opioids compared with subjects without OSA, or with OSA treated with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP).
METHODS: This was a single-centre, prospective cohort study in subjects without OSA (n=20), with untreated OSA (n=33), or with treated OSA (n=21). OSA diagnosis was verified using type III (in-home) polysomnography. Subjects received a stepped-dose remifentanil infusion (target effect-site concentrations of 0.5, 1, 2, 3, 4 ng ml-1). Primary outcome was miosis (pupil area fractional change), the most sensitive opioid effect. Secondary outcomes were ventilatory rate, end-expired CO2, sedation, and thermal analgesia.
RESULTS: There were no differences in miosis between untreated OSA subjects (mean=0.51, 95% confidence interval [CI] 0.41-0.61) and subjects without OSA (mean=0.49, 95% CI 0.36-0.62) (mean difference=0.02, 95% CI -0.18 to 0.22); between treated OSA subjects (mean=0.56, 95% CI 0.43-0.68) and subjects without OSA (difference=0.07, 95% CI -0.16 to 0.29); or between untreated OSA and treated OSA (difference=-0.05, 95% CI -0.25 to 0.16). There were no significant differences between subjects without OSA, untreated OSA, and treated OSA in ventilatory rate, end-expired CO2, sedation, or thermal analgesia responses to remifentanil. There was no relationship between OSA severity and magnitude of opioid effects.
CONCLUSIONS: Neither obstructive sleep apnoea nor obstructive sleep apnoea treatment affected sensitivity to the miotic, sedative, analgesic, or respiratory depressant effects of the opioid remifentanil in awake adults. These results challenge conventional notions of opioid effects in obstructive sleep apnoea.
BACKGROUND: NCT02898792 (clinicaltrials.gov).

Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities remain poorly understood. This study tested the hypothesis that IV morphine and hydromorphone differ in onset, magnitude, duration, and variability of analgesic and ventilatory effects.
The authors conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-h IV infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1 to 2 weeks apart. The authors measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discrete preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired carbon dioxide, and respiratory rate for 12 h after dosing.
For morphine and hydromorphone, respectively, maximum miosis was less (3.9 [3.4 to 4.2] vs. 4.6 mm [4.0 to 5.0], P < 0.001; median and 25 to 75% quantiles) and occurred later (3.1 ± 0.9 vs. 2.3 ± 0.7 h after infusion start, P < 0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs. 50 ± 2°C, P < 0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P < 0.001); maximum end-expired CO2 was 47 (45 to 50) and 48 mmHg (46 to 51; P = 0.007) and occurred later (5.5 ± 2.8 vs. 3.0 ± 1.5 h after infusion start, P < 0.001); and respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P < 0.001), and occurred at similar times. The area under the temperature tolerance-time curve was less for morphine (1.8 [0.0 to 4.4]) than hydromorphone (5.4°C-h [1.6 to 12.1] P < 0.001). Interindividual variability in clinical effects did not differ between opioids.
For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of a disposable uniplanar pupil expansion device in small-pupil cataract surgery.
METHODS: This is a feasibility study carried out at the Rothschild Foundation, Paris, France. Patients undergoing routine cataract surgery with a dilated pupil size < 6 mm, and who agreed to participate in the study were included. The trial enrolled 25 patients, of whom 21 proceeded to cataract surgery using the pupil expansion device to be evaluated. The pupil diameter was measured at defined stages during the cataract surgery, which was performed by a single surgeon, in a single center setting. The 1st generation Bhattacharjee pupil expansion ring was used if the preoperative pupil size was < 6 mm. Intraoperative and postoperative adverse events were recorded.
RESULTS: Pupil size immediately after the Bhattacharjee ring implantation was ≥ 6 mm for 15 eyes (71.4%). The mean dilated pupil size before ring insertion was 4.5 ± 0.8 mm (range 2.5-5.8 mm), and the mean pupil size after ring insertion was 6.1 ± 0.3 mm (range 5.9-6.8 mm). Mean pupil size following removal of the ring was 4.2 ± 0.8 mm (range 2.5-5.4 mm). Two adverse events occurred during the surgeries: 1 Bhattacharjee ring broke prior to implantation, and 1 implanted Bhattacharjee ring was unstable and removed before the end of the surgery. No postoperative adverse event was recorded.
CONCLUSIONS: The Bhattacharjee ring is an effective pupil expansion device, which facilitates stable pupil expansion during cataract surgery. This study was registered as a clinical trial at clinicaltrials.gov under the number NCT02434588.

UNASSIGNED: To compare accidental pediatric poisoning from methadone vs. buprenorphine in terms of clinical indicators and in-hospital morbidity.
UNASSIGNED: A matched observational study conducted on children aged ≤12 years admitted to our center between March 2018 and March 2019 with acute poisoning from methadone or buprenorphine. Data were extracted from the electronic patient files of the pediatric methadone poisoning cases, and buprenorphine poisoning cases were followed from ED, during the study period. Cases were compared regarding rates of bradypnea/apnea (primary outcome), the need for antidote therapy and intubation, duration of hospital stay, miosis, loss of consciousness, blood gas analyses, and mortality (secondary outcomes).
UNASSIGNED: A total of 90 methadone- and 30 buprenorphine-poisoned children were evaluated. Methadone cases had significantly higher rates of apnea (20/90 methadone vs. 0/30 buprenorphine; OR = 17.7, 95% CI 1.1, 302.8; p = 0.047), but there was no group difference in bradypnea (39/90 methadone vs. 10/30 buprenorphine; p = ns). 28 (31%) methadone and 3 buprenorphine (10%) cases had been referred to as fully awake (p = 0.013). Methadone cases required higher median naloxone doses for initial bolus (0.4 vs. 0.02 mg; p = 0.014) and maintenance infusion (14.4 vs. 2.4 mg; p < 0.001). 20 apnea cases (all from the methadone group) had miotic pupils, and miotic pupils were seen in 44 (90%) cases with bradypnea (OR = 3.2, 95% CI 1.1, 9.3; p = 0.026). Intubation was needed in only 5 methadone cases (5.5%; p = ns). All patients survived.
UNASSIGNED: Compared to children poisoned with methadone, buprenorphine cases had higher rates of loss of consciousness on admission but subsequently experienced fewer complications during hospital treatment, which is likely due to the buprenorphine partial antagonist effect. Our findings suggest that methadone exposure is more toxic than buprenorphine in pediatric populations.

Purpose: To detect the presence of urotensin-2 (U-II) in the aqueous humor and evaluate the relationship between aqueous humor level and systemic diseases and pupil size. Methods: The study included 88 patients who underwent cataract surgery. Those with a pupil diameter (PD) of up to 4 mm were considered to have small dilation, those with 4-7 mm of dilatation were considered to have moderate dilation, and those with a PD of more than 7 mm considered to have large dilation. Patients with HT (hypertension) were classified as group 1, those with DM (diabetes mellitus) as group 2, and those with HT+DM as group 3, and those without any systemic disease as group 4. The U-II levels in humor aqueous samples taken from anterior chamber were measured. Results: When compared with the control group, it was observed that the level of U-II in the aqueous humor of the HT, DM, and DM+HT groups was significantly higher (P < 0.05). At the same time, when we compared the DM+HT group with the other groups, the level of U-II in the aqueous humor was significantly higher compared to the group with DM (P < 0.05). The U-II levels of the aqueous humor were higher in the patients with small pupils compared to the remaining groups (P < 0.005). Conclusion: U-II may play a role in small pupil pathophysiology. In addition, it was determined that patients with HT and/or diabetes had higher U-II levels in the aqueous humor than healthy individuals.

The Tokyo subway sarin attack in 1995 was an unprecedented act of terrorism that killed 13 people and sickened more than 6,000. The long-term somatic and psychological effects on its victims remain unknown.
We conducted analyses on the self-rating questionnaire collected annually by the Recovery Support Center (RSC) during the period from 2000 to 2009. The RSC is the only organization that has large-scale follow-up data about sarin attack victims. The prevalence of self-reported symptoms was calculated over 10 years. We also evaluated the prevalence of posttraumatic stress response (PTSR), defined as a score ≥ 25 on the Japanese-language version of the Impact of Event Scale-Revised. The multivariate Poisson regression model was applied to estimate the risk ratios of age, gender, and year factor on the prevalence of PTSR.
Subjects were 747 survivors (12% of the total) who responded to the annual questionnaire once or more during the study period. The prevalence of somatic symptoms, especially eye symptoms, was 60-80% and has not decreased. PTSR prevalence was 35.1%, and again there was no change with time. The multivariate Poisson regression model results revealed \"old age\" and \"female\" as independent risk factors, but the passage of time did not decrease the risk of PTSR.
Although symptoms in most victims of the Tokyo subway sarin were transient, this large-scale follow-up data analysis revealed that survivors have been suffering from somatic and psychological long-term effects.

OBJECTIVE: To examine ischemic neurodegeneration of the ciliospinal center on permanent miosis following subarachnoid hemorrhage (SAH).
METHODS: Nineteen rabbits were examined in this study. The animals were divided into three groups, as control (GI, n=5), sham (GII, n=5) and study group (GIII, n=9). Pupil diameters were measured after giving 0.5 mL physiological saline for sham and autologous arterial blood for the study group into the cervico-thoracic subarachnoid space. After three weeks of follow up, the cervico-thoracic cord and bilateral superior cervical sympathetic ganglia were removed. The pupil diameter values were compared with degenerated neuron volumes of sympathetic ganglia and degenerated neuron densities of thoracic sympathetic nuclei which were studied by stereological methods.
RESULTS: The mean pupil diameter was 5180 ± 370 µm and the mean degenerated neuron density of the ciliospinal center was 4 ± 1/mm3 in animals of the control group (GI). These values were 9850 ± 610 εm, 10 ± 3/mm3 in sham (GII), and 7.010 ± 440 εm and 98 ± 21/mm3 in the study (GIII) groups. There was an inverse relationship between degenerated neuron density of the ciliospinal nuclei and pupil diameters.
CONCLUSIONS: We showed and reported for the first time that ciliospinal sympathetic center ischemia-induced neurodegeneration may have been responsible for permanent miosis following SAH.

OBJECTIVE: This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8 mg/ml to intramuscular 0.8 mg.
METHODS: Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102 min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured.
RESULTS: The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference.
CONCLUSIONS: A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8 mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose.
BACKGROUND: clinicaltrials.gov : NCT02307721.