The Relationship of the Urotensin-2 Level in the Aqueous Humor with Systemic Diseases and Pupil Size: Comparative Study.

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.

Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation.

Calcium (Ca2+ ) acts as a ubiquitous second messenger, and normal cell and tissue physiology strictly depends on the precise regulation of Ca2+ entry, storage, and release. Store-operated Ca2+ entry (SOCE) is a major mechanism controlling extracellular Ca2+ entry, and mainly relies on the accurate interplay between the Ca2+ sensor STIM1 and the Ca2+ channel ORAI1. Mutations in STIM1 or ORAI1 result in abnormal Ca2+ homeostasis and are associated with severe human disorders. Recessive loss-of-function mutations impair SOCE and cause combined immunodeficiency, while dominant gain-of-function mutations induce excessive extracellular Ca2+ entry and cause tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). TAM and STRMK are spectra of the same multisystemic disease characterized by muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. To date, 42 TAM/STRMK families have been described, and here we report five additional families for which we provide clinical, histological, ultrastructural, and genetic data. In this study, we list and review all new and previously reported STIM1 and ORAI1 cases, discuss the pathomechanisms of the mutations based on the known functions and the protein structure of STIM1 and ORAI1, draw a genotype/phenotype correlation, and delineate an efficient screening strategy for the molecular diagnosis of TAM/STRMK.

Spinal Subarachnoid Hemorrhage Induced Intractable Miotic Pupil. A Reminder of Ciliospinal Sympathetic Center Ischemia Based Miosis: An Experimental Study.

AIM: To examine ischemic neurodegeneration of the ciliospinal center on permanent miosis following subarachnoid hemorrhage (SAH). MATERIAL AND 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. CONCLUSION: We showed and reported for the first time that ciliospinal sympathetic center ischemia-induced neurodegeneration may have been responsible for permanent miosis following SAH.

Opioid Sensitivity in Children with and without Obstructive Sleep Apnea.

BACKGROUND: Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to children without obstructive sleep apnea. These assumptions have not been rigorously tested. This investigation tested the hypothesis that children with obstructive sleep apnea have an increased pharmacodynamic sensitivity to the miotic and respiratory depressant effects of the prototypic µ-opioid agonist remifentanil. METHODS: Children (8 to 14 yr) with or without obstructive sleep apnea were administered a 15-min, fixed-rate remifentanil infusion (0.05, 0.1, or 0.15 µg · kg · min). Each dose group had five patients with and five without obstructive sleep apnea. Plasma remifentanil concentrations were measured by tandem liquid chromatography mass spectrometry. Remifentanil effects were measured via miosis, respiratory rate, and end-expired carbon dioxide. Remifentanil pharmacodynamics (miosis vs. plasma concentration) were compared in children with or without obstructive sleep apnea. RESULTS: Remifentanil administration resulted in miosis in both non-obstructive sleep apnea and obstructive sleep apnea patients. No differences in the relationship between remifentanil concentration and miosis were seen between the two groups at any of the doses administered. The administered dose of remifentanil did not affect respiratory rate or end-expired carbon dioxide in either group. CONCLUSIONS: No differences in the remifentanil concentration-miosis relation were seen in children with or without obstructive sleep apnea. The dose and duration of remifentanil administered did not alter ventilatory parameters in either group.

Stormorken Syndrome: A Rare Cause of Myopathy With Tubular Aggregates and Dystrophic Features.

Stormorken syndrome is a rare genetic disorder (MIM 185070) first reported in 1983 with thrombocytopenia, muscle weakness, asplenia, and miosis caused by a mutation of the stromal interaction molecule 1 ( STIM1) gene.1 The muscle weakness is caused by a myopathy with tubular aggregate formation. We report a family in which both child and mother presented with proximal muscle weakness and thrombocytopenia. Histologic, histochemical, and electron microscopy studies were performed on the muscle specimen. It documented accumulation of tubular aggregates and chronic myopathic changes with dystrophic features. Genetic testing revealed that both mother and son carried a missense mutation of c.326A>G in exon 3 of the STIM1 gene, which is novel for Stormorken syndrome. We suggest that patients with unexplained chronic idiopathic thrombocytopenia and proximal weakness have genetic testing for Stormorken syndrome.

Factors influencing pupil behaviour during femtosecond laser assisted cataract surgery.

AIM: Femtosecond laser assisted cataract surgery is associated with pupillary constriction. This study aims to look at patient and surgical factors predisposing to abnormal pupil behaviour during FLACS. METHODS: This prospective observational study included all patients undergoing FLACS in the Princess of Wales Hospital, Bridgend, UK between February and June 2017. Pupils were measured at three time points; immediately before and after laser pre-treatment, and at the start of surgery. Pupil behaviour during surgery was noted in descriptive terms, patient demographic, co-morbidities, eye measurements, suction on time, shifting time and laser energy levels were recorded. RESULTS: Seventy-three eyes were included. Average patient age was 74.84 ±â€¯9.1 years. Mean horizontal pupil sizes immediately before and after femto pre-treatment were 7.87 ±â€¯0.87 mm and 7.7 ±â€¯0.89 mm respectively (P < 0.0005). Mean horizontal pupil size at the start of surgery was 6.83 ±â€¯1.43 mm (P < 0.0005). Short capsulotomy-pupil distance (P = 0.01), shallower anterior chamber (P = 0.0012), smaller pre-operative pupil size (P = 0.045) and longer suction on time (P = 0.0019) were significantly associated with intra-operative miosis during FLACS. Sustained mydriasis was observed in eyes in whom topical diclofenac was used within 2 h of surgery. CONCLUSIONS: FLACS can result in significant pupil miosis. Eyes particularly at risk are ones with smaller pre-operative pupils and shallower anterior chambers and those subjected to longer suction on time. Well-timed NSAIDs application could be protective against this phenomenon.

[Tubular aggregate myopathy and Stormorken syndrome]. / La myopathie à agrégats tubulaires et le syndrome de Stormorken.

Calcium (Ca2+) is an essential regulator for a large number of cellular functions in various tissues and organs, and small disturbances of Ca2+ homeostasis can severely compromise normal physiology. Intracellular Ca2+ balance is mainly controlled by the reticular Ca2+ sensor STIM1 and the plasma membrane Ca2+ channel ORAI1 through a mechanism known as store-operated Ca2+ entry (SOCE). Gain-of-function mutations in STIM1 or ORAI1 cause excessive extracellular Ca2+ influx, resulting in tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK). Both disorders are spectra of the same disease and involve muscle weakness, miosis, thrombocytopenia, hyposplenism, ichthyosis, dyslexia, and short stature. Here we summarize the clinical and histological characteristics of both disorders, provide an overview on the genetic causes, and recapitulate the current knowledge on the pathomechanisms leading to the multi-systemic phenotype of tubular aggregate myopathy and Stormorken syndrome.

The Tuebingen Scotopic Threshold Test (TSTT).

Measurement of the dark-adaptation threshold plays a key role in the diagnosis and estimation of disease progression of many retinal disorders. Determining the threshold is, however, difficult to perform in young children. We present here a prototype for a dark adaptometer, the Tuebingen Scotopic Threshold Test aimed to ease measurement of photoreceptor thresholds in young subjects. The device consists of two 7 cm ×10 cm fields with either blue or yellow LEDs, for testing rod or cone sensitivity, respectively. Presentation of homogenous field patterns or a flickering stimulus is also possible. The luminance threshold is measured by the method of ascending limits and the stimulus luminance, data recording and analysis are computer controlled. Preliminary results for six adults and two older children were ascertained and the influence of pupil dilation, binocular presentation, and a flickering stimulus examined. The method provides credible and consistent evaluations of the absolute threshold.

Two Hospitalizations and One Death After Exposure to Ortho-Fluorofentanyl.

Two young males were hospitalized with miosis and respiratory dysfunction after exposure to a white powder obtained from a foreign source by mail. A few days later, one of the males was found dead at his home. A serum sample from one of the hospitalized patients and a blood sample from the deceased contained ortho-fluorofentanyl in concentrations of 2.5 and 2.4 ng/mL, respectively. It was concluded that death was caused by ortho-fluorofentanyl.

Capsule-Fixated Intraocular Lens Implantation in Small Pupil Cases.

PURPOSE: To describe a new technique for implantation of capsule-fixated intraocular lenses (IOLs) (FEMTIS; Oculentis, Berlin, Germany) in patients with small pupils. METHODS: In 4 eyes with small pupils, an anterior capsule-fixated IOL was implanted into the capsular bag after femtosecond laser treatment. The two large and two small flaps of the IOL were elevated to the front of the iris and the anterior capsule. Finally, the iris was flipped over the flaps to ensure a fixation of the capsule inside of the capsulotomy. RESULTS: In all cases, the implantation of anterior capsule-fixated IOLs was possible. No complications occurred during surgery or within the first months after surgery. CONCLUSIONS: With the described technique, capsulefixated IOLs can be implanted in eyes with small pupil easily and safely. This type of IOL has great potential to improve the refractive outcome by better prediction of the postoperative IOL position and eliminating IOL rotation after cataract surgery. [J Refract Surg. 2017;33(8):568-570.].

Ptosis, miosis and cats.

Horner's syndrome (HS) is caused by a disruption in the oculosympathetic pathway. Both congenital and acquired HS are unusual in children. Acquired HS can be caused by trauma, surgical intervention, tumours, vascular malformations or infection.We describe the case of a 6-year-old boy who was brought to our emergency department with ptosis, miosis, painful cervical lymphadenopathy and a cat scratch on a hand. The diagnosis of a cat scratch disease was confirmed by serology. A full recovery was observed on antibiotic treatment and cervical lymphadenomegaly reduction 3 weeks later.

Electroretinography and Pupillography in Unilateral Foveal Hypoplasia.

The authors describe a 3-year-old boy with unilateral foveal hypoplasia and an absence of other ocular or systemic findings. Electroretinography obtained predominantly affecting cones. Laterality of pupil constriction to red but not to blue light was observed. The colored-light pupil response can be used to predict the retinal state.

Effects of Femtosecond Laser-Assisted Cataract Pretreatment on Pupil Diameter: A Comparison Between Three Laser Platforms.

PURPOSE: To assess pupil diameter before and after femtosecond laser-assisted cataract surgery (FLACS) pretreatment and compare the outcomes of three laser platforms. METHODS: This prospective observational case series included consecutive patients scheduled to undergo cataract extraction using FLACS between August 2013 and February 2015. All eyes received FLACS pretreatment using three laser platforms: LenSx (Alcon Laboratories, Inc., Fort Worth, TX), Catalys (Abbott Medical Optics Inc., Santa Ana, CA), and Victus (Bausch & Lomb, Inc., Rochester, NY). The same protocol for preoperative medical mydriasis was used for all patients, and pupil diameter was assessed immediately before and 3 minutes after FLACS using a surgical ruler. RESULTS: A total of 198 eyes of 161 patients were included in the study. Mean pupillary miosis was 1.42 ± 1.26 mm for the LenSx, 0.66 ± 0.89 mm for the Catalys, and 0.14 ± 0.34 mm for the Victus groups. Furthermore, 8 of the 198 eyes (4.0%) demonstrated a pupil diameter of less than 5 mm after FLACS and 48 eyes (24.24%) demonstrated a pupil diameter of 6 mm or less. There was a statistically significant decrease in pupil diameter for all groups individually (P < .05). There was also a statistically significant difference among the three groups (P < .05), with LenSx inducing the highest degree of miosis, followed by Catalys, and finally Victus. A correlation between the pupil diameter before FLACS and degree of FLACS-induced miosis was demonstrated (P < .05), with larger pupil diameter before FLACS associated with greater miosis. CONCLUSIONS: FLACS pretreatment seems to induce significant pupillary miosis with all laser platforms assessed in this study. The decrease in pupil diameter after FLACS reached clinical significance for cataract extraction (< 5 mm) in 4.0% of cases, whereas 20.2% of eyes demonstrated small pupil diameter (≤ 6 mm) after FLACS pretreatment.

Amitraz: a mimicker of organophosphate poisoning.

Amitraz is used as an ectoparasiticide for dogs and cattle. Human poisoning due to amitraz may be misdiagnosed as organophosphate/carbamate (OPC) toxicity, since amitraz poisoning shares several clinical features (miosis, bradycardia and hypotension) encountered with OPC poisoning. A 19-year-old man with an alleged history of suicidal ingestion of a pesticide presented with drowsiness and was found to have constricted pupils, hypotension and bradycardia. He was diagnosed as a case of OPC poisoning and was treated with atropine and pralidoxime prior to presentation to our centre. Absence of a hypersecretory state, and the presence of hyperglycaemia and hypothermia along with a normal serum cholinesterase level suggested an alternate possibility. Retrieval of the poison container confirmed the diagnosis of amitraz poisoning. The patient made a rapid recovery with supportive management. Clinician awareness is key to successful management of this poisoning, which carries a good prognosis.

Small Pupil--Big Problem: A Management Algorithm.

Small pupils pose problems for cataract surgery. The pupil is dilated with topical mydriatic drugs for all cataract surgeries to improve the surgeon's access to, and visualization of, the lens nucleus, cortex, and capsular structures. Limited dilation poses a risk of surgical complications such as iris trauma or tearing of the anterior or posterior capsule. There are many ways and methods to achieve the appropriate pupil dilation, from pre-operative medications to intraoperative pharmacological and/or surgical methods. A management algorithm for small pupil will be discussed in this review. The various methods and maneuvers may work in isolation or combination to achieve adequate pupil dilation.