Urinary retention and mydriasis secondary to topical glycopyrronium for axillary hyperhidrosis.

PURPOSE: Glycopyrronium, also known as glycopyrrolate, is an antimuscarinic competitive inhibitor of acetylcholine widely utilized topically for its anticholinergic properties in dermatology. A single topical glycopyrronium tosylate (GT) formulation is available on the market, and prescription of this medication has become increasingly popular among dermatologists. This medication has a relatively notable adverse effect profile and carries risks that patients need to be counseled on before initiation. SUMMARY: A 22-year-old female presented to our emergency department (ED) with a chief complaint of difficulty urinating for 48 hours and blurred vision for 2 weeks. Over the course of a week, she visited the ED once and urgent care multiple times due to complications associated with combination use of GT and cetirizine. Although these clinical effects were reversible, the patient impact in our case was profound given the time, cost, and invasive nature of these visits. CONCLUSION: The notable adverse effects of GT should be considered when prescribing this agent.

Mydriasis and anisocoria in a pediatric hyperhidrosis patient with interesting findings in the family cat.

Here, we report a case of unilateral ocular mydriasis in a pediatric patient with longstanding hyperhidrosis, as well as similar findings in her cat. The patient had been undergoing treatment of her hyperhidrosis with topical glycopyrrolate. This case highlights the potential side effect profile of topical antimuscarinics and the importance of counseling patients on proper precautions.

Margin of safety of extended-duration transdermal buprenorphine solution following multiple-dose administrations to cats.

Transdermal buprenorphine solution (TBS) is approved for the control of postoperative pain in cats where a single preoperative dose provides 4 days of analgesia. It is administered as a unit dose of 8 mg to cats weighing 1.2-3 kg and 20 mg to cats weighing to >3-7.5 kg, which is equivalent to a dosage on a bodyweight basis of 2.7-6.7 mg/kg. In this safety study, the 1X dose was defined as 6.7 mg/kg. Thirty-two cats (16 males and 16 females) were randomly allocated to placebo, 1, 2, and 3X TBS administered topically to the dorsal cervical skin every 4 days for 3 doses. Clinical observations, behavioral scores, mydriasis score (yes/no), and physiological variables were assessed or measured prior to each dose administration (0 h) and at 1, 2, 4, 8, 12, 24, 36, 48, and 72 h following each treatment and prior to euthanasia on Day 12 or 13. Blood samples for clinical pathology were collected on Days - 1, 4, 8, and prior to euthanasia. There was little evidence of respiratory, cardiovascular, or gastrointestinal effects. Respiratory rates were above the reference range in all groups and lower by 10 breaths/min in the 3X group during the third dosing interval compared to placebo. There were no differences in heart rates. Constipation was transiently observed in approximately equal numbers in placebo- and TBS-treated cats. Behavioral scores showed sedation or euphoria was transient in the first dosing interval but became more prolonged with each dosing interval. Mydriasis was prolonged in the first dosing interval and diminished by the third dosing interval consistent with accommodation. Mean body temperatures in TBS-treated cats were up to 0.6°C (1.8°F) greater than placebo-treated cats. There were no clinically relevant changes to serum chemistry, hematology, or urinalysis outcomes nor gross or microscopic observations attributable to TBS. These data demonstrate that TBS is safe and well-tolerated when administered to 16-week-old cats at multiples of the approved dose and duration and supports clinical safety in the event of delayed buprenorphine metabolism, medication errors, or alterations in the dosing regimen.

Pharmacologic Mydriasis Secondary to Topical Glycopyrronium Tosylate Cloths: Clinical Characterization From a Multicenter Analysis.

BACKGROUND: Topical glycopyrronium tosylate (GT) is an anticholinergic medication for treatment of axillary hyperhidrosis. Pharmacologic mydriasis and anisocoria from topical GT has been reported and may be underrecognized. This study aims to clinically characterize patients presenting with pharmacologic mydriasis from exposure to this medication. METHODS: This study is a retrospective observational case series. A multicenter chart review of 16 patients diagnosed with pharmacologic mydriasis secondary to topical GT was performed. RESULTS: Eight patients (50.0%) were age 18 years and younger, and 14 patients (87.5%) were female. Unilateral mydriasis (anisocoria) occurred in 14 patients (87.5%). Fourteen patients (87.5%) did not initially volunteer topical GT as a "medication," and the history of topical GT exposure needed to be elicited with further questioning. Hand hygiene details were known for 12 patients, and all reported that they did not wash their hands after GT application. Six patients (37.5%) were soft contact lens users. One patient had possible exposure through a family member's use of the medication. Ocular symptoms were common (blurry vision [11 patients, 68.8%] and eye dryness [7 patients, 43.8%]), but systemic anticholinergic symptoms were uncommon (such as constipation [1 patient, 6.3%] and urinary symptoms [3 patients, 18.8%]). CONCLUSIONS: Mydriasis associated with topical GT seems to be a consequence of local exposure rather than systemic toxicity. Because patients may not volunteer topical GT as a medication, eliciting a history of exposure often requires further specific questioning. Soft contact lens wear and poor postapplication hand hygiene seem to be associated with mydriasis in GT use.

Seguridad del uso combinado de lidocaína y fenilefrina como midriáticos intracamerales en la cirugía de catarata / Safety of the combined use of lidocaine and phenylephrine as intracameral mydriatics in cataract surgery

Objetivo: Evaluar la seguridad ocular y sistémica de una combinación de lidocaína 2 por ciento y fenilefrina 1 por ciento administrada por vía intracameral para provocar midriasis intraoperatoria en la cirugía de catarata. Métodos: Se realizó un estudio prospectivo de serie de casos en 70 ojos de igual número de pacientes sometidos a facoemulsificación con implante de lente intraocular. El grupo midriasis intraoperatoria en la cirugía lo conformaron 35 pacientes dilatados con una inyección intracameral de lidocaína y fenilefrina antes de la cirugía, mientras otros 35 ojos se dilataron de manera tradicional, con un colirio midriático previo. Para la seguridad ocular se evaluaron múltiples parámetros del examen oftalmológico pre- y posoperatorio. Resultados: La presión intraocular, el espesor corneal central, la densidad celular del endotelio corneal y el edema corneal posoperatorio como hallazgo del segmento anterior se comportaron de manera similar en ambos grupos de estudio. Se reportó una complicación transoperatoria en el grupo de manera tradicional y un caso con edema quístico macular posoperatorio en el grupo midriasis intraoperatoria en la cirugía que no representaron diferencias significativas. Conclusión: La inyección de lidocaína más fenilefrina intracameral es una opción segura tanto ocular como sistémica para provocar midriasis durante la facoemulsificación(AU)

Objective: Evaluate the ocular and systemic safety of a combination of 2 percent lidocaine and 1 percent phenylephrine administered intracamerally to achieve intraoperative mydriasis in cataract surgery. Methods: A prospective study was conducted of a case series of 70 patients (70 eyes) who underwent phacoemulsification with intraocular lens implantation. The intraoperative mydriasis group was composed of 35 patients dilated with an intracameral injection of lidocaine and phenylephrine before surgery, whereas another 35 eyes were dilated by the conventional method, with mydriatic eye drops. Ocular safety evaluation was based on the analysis of a wide variety of pre- and postoperative ophthalmological examination parameters. Results: Intraocular pressure, central corneal thickness, corneal endothelial cell density and postoperative corneal edema as an anterior segment finding, behaved in a similar manner in both study groups. An intraoperative complication was reported in the conventional method group and a case with postoperative cystoid macular edema in the intraoperative mydriasis group group, neither of them exhibiting significant differences. Conclusion: Intracameral lidocaine plus phenylephrine injection is a safe ocular and systemic option to achieve mydriasis during phacoemulsification(AU)

Tropicamide has limited clinical effect on cycloplegia and mydriasis when combined with cyclopentolate and phenylephrine.

PURPOSE: To examine the cycloplegic and mydriatic effect of tropicamide omission from a common pediatric eye drop combination. METHODS: Consecutive children examined at the Ann & Robert H. Lurie Children's Hospital of Chicago from June 8, 2017 to September 6, 2017 were enrolled prospectively. Tropicamide, cyclopentolate, and phenylephrine (TCP) was instilled in one eye; cyclopentolate and phenylephrine (CP), in the other. Spherical equivalent, maximum pupil size, and pupillary constriction in response to photostimulation were measured before and 30 minutes after instillation using an autorefractor and pupillometer. Iris pigmentation was examined as a between-subjects variable. RESULTS: A total of 75 children 4-11 years of age were included. Mean differences in spherical equivalent between TCP and CP were not statistically significant (P = 0.95). Significant interactions between eye drop regimen and iris pigmentation were observed for pupil size (P = 0.001) and constriction percentage (P = 0.02). Among only patients with dark irides, TCP yielded slightly larger pupils (7.70 vs 7.31 mm [P < 0.001]) that were less responsive to light (5.75% vs 8.07% [P = 0.002]). All pupils dilated to ≥6.0 mm, with equivalent proportions achieving ≥7.0 mm for TCP and CP (P = 0.18). CONCLUSIONS: TCP and CP elicited equivalent cycloplegic effects. Mydriatic differences between the regimens, although statistically significant in dark irides, were of limited clinical magnitude, and all pupils achieved sufficient dilation for funduscopy.

Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery.

The overall study goal was to produce a microparticle formulation containing atropine sulfate for ocular administration with improved efficacy and lower side effects, compared with that of the standard marketed atropine solution. The objective was to prepare an atropine sulfate-loaded bovine serum albumin-chitosan microparticle that would have longer contact time on the eyes as well as better mydriatic and cycloplegic effect using a rabbit model. The microparticle formulation was prepared by method of spray-drying technique. The percent drug loading and encapsulation efficiency were assessed using a USP (I) dissolution apparatus. The particle sizes and zeta potential were determined using laser scattering technique and the surface morphology of the microparticles was determined using a scanning electron microscope. The product yield was calculated from relative amount of material used. In vitro cytotoxicity and uptake by human corneal epithelial cells were examined using AlamarBlue and confocal microscopy. The effects of the microparticle formulation on mydriasis in comparison with the marketed atropine sulfate solution were evaluated in rabbit eyes. The prepared microparticle formulation had ideal physicochemical characteristics for delivery into the eyes. The in vivo studies showed that the microparticles had superior effects on mydriasis in rabbits than the marketed solutions

Determining pharmacological selectivity of the kappa opioid receptor antagonist LY2456302 using pupillometry as a translational biomarker in rat and human.

BACKGROUND: Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology. METHODS: Here, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans. RESULTS: In rats, morphine-induced mydriasis was completely blocked by the nonselective opioid receptor antagonist naloxone (3mg/kg, which produced 90% mu opioid receptor occupancy), while 100 and 300 mg/kg LY2456302 (which produced 56% and 87% mu opioid receptor occupancy, respectively) only partially blocked morphine-induced mydriasis. In humans, fentanyl-induced miosis was completely blocked by 50mg naltrexone, and LY2456302 dose-dependently blocked miosis at 25 and 60 mg (minimal-to-no blockade at 4-10mg). CONCLUSIONS: We demonstrate, for the first time, the use of translational pupillometry in the context of receptor occupancy to identify a clinical dose of LY2456302 achieving maximal kappa opioid receptor occupancy without evidence of significant mu receptor antagonism.

Bilateral acute iris transillumination.

OBJECTIVE: To describe a series of patients with bilateral acute iris transillumination, pigment dispersion, and sphincter paralysis. METHODS: We reviewed the medical records and clinical photographs of 26 patients seen at 5 centers in Turkey and Belgium between March 16, 2006, and July 6, 2010. Observation procedures included clinical examination, anterior segment color photography, gonioscopy, laser flare photometry, and pupillometry. RESULTS: All 26 patients (20 women and 6 men; mean [SD] age, 43.2 [10.5] years) had bilateral involvement. Twenty-three patients (88%) had acute-onset disease with severe photophobia and red eyes. Nineteen patients (73%) had a preceding flulike illness and used systemic antibiotics, including moxifloxacin. Diagnostic laboratory workup was unremarkable. There was pigment discharge into the anterior chamber, and flare was elevated in the absence of inflammatory cells. Most patients had severe diffuse transillumination of the iris and mydriatic distorted pupils. Pupillometry revealed a compromised reaction to light. The most serious complication was an intractable early rise in intraocular pressure. Gonioscopy revealed heavy pigment deposition in the trabecular meshwork. Although symptoms were relieved promptly by application of topical corticosteroid, the median duration of pigment dispersion was 5.25 months. CONCLUSIONS: Bilateral acute iris transillumination with pigment dispersion and persistent mydriasis is a new clinical entity that is not an ocular adverse effect of oral moxifloxacin treatment, as previously suggested. The etiopathogenesis of this entity remains to be elucidated.

Pupila dilatada fixa (síndrome de Urrets-Zavalia) após ceratoplastia lamelar profunda / Fixed dilated pupil (Urrets-Zavalia syndrome) after deep lamellar keratoplasty

A Síndrome de Urrets-Zavalia apresenta achados oculares bem descritos, porém sua fisiopatologia ainda é incerta. A isquemia iriana é o mecanismo proposto mais comum. Descrevemos dois casos submetidos à ceratoplastia lamelar profunda (CLP) realizadas pelo mesmo cirugião que desenvolveram a síndrome. No primeiro caso, a indicação cirúrgica foi para o tratamento de opacidade corneana e, no segundo, para o de ceratocone. No pós-operatório, ambos os pacientes evoluíram com pupila dilatada fixa que não regrediu totalmente apesar do tratamento administrado.

The Urrets-Zavalia Syndrome presents well described ocular findings, even though its physiopathology is still unsure. Iris ischemia is the most common proposing mechanism. We describe two cases that underwent deep lamellar keratoplasty (DLK) performed by the same surgeon and developed the syndrome. In the first case, the surgical indication was for corneal opacity treatment and, in the second case, for keratoconus treatment. During the post-operatory, both patients developed fixed dilated pupil, which didn't regress completely inspite of the onset treatment.

Colirio de diclofenaco sódico en cirugía de catarata por facoemulsificación / Diclofenac sodium eyedrops in cataract's surgery by phacoemulsification

OBJETIVOS: Determinar la efectividad clínica del diclofenaco sódico en colirio para mantener la midriasis pupilar durante la cirugía de catarata por facoemusificación y disminuir la inflamación en el posoperatorio, en el Instituto Cubano de Oftalmología Ramón Pando Ferrer durante el año 2010. MÉTODOS: Se estudiaron 40 ojos distribuidos al azar en dos grupos de 20 cada uno: a) se les aplicó en el preoperatorio y posoperatorio tratamiento tópico de rutina, y b) se les adicionó diclofenaco sódico en colirio durante el preoperatorio y la primera semana del posoperatorio. Se midieron los diámetros pupilares al inicio de la cirugía y al finalizar la aspiración de restos corticales. Se evaluaron los pacientes en el posoperatorio a las 24 horas, a los seis días y al mes de la intervención; se observó la presencia o no de hiperemia cilioconjuntival y celularidad en cámara anterior. RESULTADOS: Se observó que los pacientes en quienes se utilizó el diclofenaco sódico en colirio mantuvieron mayor grado de midriasis. A las 24 horas el número de pacientes del grupo 1 que presentaron hiperemia cilioconjuntival y celularidad en el humor acuoso fue superior a los del grupo 2, mientras que a los seis días y al mes estas variables se comportaron de forma similar en ambos grupos de estudio. CONCLUSIONES: Se ha comprobado que el diclofenaco sódico en colirio es efectivo en el mantenimiento de la midriasis transoperatoria y ofrece ventajas al disminuir la inflamación en la cirugía de catarata(AU)

OBJECTIVES: To determine the clinical effectiveness of diclofenac sodium eyedrops to maintain the pupillary mydriasis during cataract surgery by phacoemulsification and to decrease the postoperative inflammation in patients seen in the Ramón Pando Ferrer Cuban Institute of Ophthalmology over 2010. METHODS: Forty eyes were studied randomly distributed in two groups of 20 eyes each: a) in preoperative and postoperative periods a routine topical treatment was applied and b) eyedrops diclofenac sodium was added during the preoperative period and for the first week of postoperative period. The pupillary diameters were measured at onset of surgery and the end the aspiration or cortical remainders. The patients in the postoperative period were assessed at 24 hours, at 6 days and at month after intervention; there was or not of hyperemia cilioconjunctival and cellularity in the aqueous humor was higher than that of the group 2, whereas at 6 days and at month, these variables behaved if a similar way in both study groups. RESULTS: It was observed that the patients in whom the sodium diclofenac was used maintained a higher degree of mydriasis. After 24 hours of the surgery the number of patients of group I that showed cilioconjuntival injection and cellularity in anterior chamber was higher that the number of group 2, whereas after six days and after a month of the surgery these variables behaved in a similar form in both training groups. CONCLUSIONS: It was proved that the eyedrops diclofenac sodium is effective in maintenance of transoperative mydriasis and also decreases the inflammation in cataract's surgery(AU)

Colirio de diclofenaco sódico en cirugía de catarata por facoemulsificación / Diclofenac sodium eyedrops in cataract's surgery by phacoemulsification

OBJETIVOS: Determinar la efectividad clínica del diclofenaco sódico en colirio para mantener la midriasis pupilar durante la cirugía de catarata por facoemusificación y disminuir la inflamación en el posoperatorio, en el Instituto Cubano de Oftalmología Ramón Pando Ferrer durante el año 2010. MÉTODOS: Se estudiaron 40 ojos distribuidos al azar en dos grupos de 20 cada uno: a) se les aplicó en el preoperatorio y posoperatorio tratamiento tópico de rutina, y b) se les adicionó diclofenaco sódico en colirio durante el preoperatorio y la primera semana del posoperatorio. Se midieron los diámetros pupilares al inicio de la cirugía y al finalizar la aspiración de restos corticales. Se evaluaron los pacientes en el posoperatorio a las 24 horas, a los seis días y al mes de la intervención; se observó la presencia o no de hiperemia cilioconjuntival y celularidad en cámara anterior. RESULTADOS: Se observó que los pacientes en quienes se utilizó el diclofenaco sódico en colirio mantuvieron mayor grado de midriasis. A las 24 horas el número de pacientes del grupo 1 que presentaron hiperemia cilioconjuntival y celularidad en el humor acuoso fue superior a los del grupo 2, mientras que a los seis días y al mes estas variables se comportaron de forma similar en ambos grupos de estudio. CONCLUSIONES: Se ha comprobado que el diclofenaco sódico en colirio es efectivo en el mantenimiento de la midriasis transoperatoria y ofrece ventajas al disminuir la inflamación en la cirugía de catarata

OBJECTIVES: To determine the clinical effectiveness of diclofenac sodium eyedrops to maintain the pupillary mydriasis during cataract surgery by phacoemulsification and to decrease the postoperative inflammation in patients seen in the Ramón Pando Ferrer Cuban Institute of Ophthalmology over 2010. METHODS: Forty eyes were studied randomly distributed in two groups of 20 eyes each: a) in preoperative and postoperative periods a routine topical treatment was applied and b) eyedrops diclofenac sodium was added during the preoperative period and for the first week of postoperative period. The pupillary diameters were measured at onset of surgery and the end the aspiration or cortical remainders. The patients in the postoperative period were assessed at 24 hours, at 6 days and at month after intervention; there was or not of hyperemia cilioconjunctival and cellularity in the aqueous humor was higher than that of the group 2, whereas at 6 days and at month, these variables behaved if a similar way in both study groups. RESULTS: It was observed that the patients in whom the sodium diclofenac was used maintained a higher degree of mydriasis. After 24 hours of the surgery the number of patients of group I that showed cilioconjuntival injection and cellularity in anterior chamber was higher that the number of group 2, whereas after six days and after a month of the surgery these variables behaved in a similar form in both training groups. CONCLUSIONS: It was proved that the eyedrops diclofenac sodium is effective in maintenance of transoperative mydriasis and also decreases the inflammation in cataract's surgery

2.5% and 10% phenylephrine for mydriasis in diabetic patients with darkly pigmented irides.

OBJECTIVE: To compare the clinical efficacy and systemic side effects of2.5% and 10%phenylephrinefor mydriasis in diabetic patient with darkly pigmented irides. MATERIAL AND METHOD: A prospective randomized double-blind controlled trial was conducted. One hundred diabetic patients were randomly allocated into 2.5% and 10% phenylephrine groups by block randomization. Pupil diameter, blood pressure and heart rate were measured before and after eye drop instillations. RESULTS: The mean pupil diameters after instillation in the right eye were 7.05 +/- 0.71 mm (2.5% phenylephrine group) and 7.40 +/- 0.72 mm (10% phenylephrine group, p = 0.02) and in the left eye were 7.05 +/- 0.72 mm (2.5% phenylephrine group) and 7.39 +/- 0.72 mm (10% phenylephrine group, p = 0.02). There was no clinically significant difference in mean heart rate, mean systolic and diastolic blood pressure. CONCLUSION: In diabetic patients with darkly pigmented irides, 10% phenylephrine is more effective than 2.5% phenylephrine with statistical significance. The authors recommend a single dose of 10% phenyleprine for mydriasis in these patients. However the lower concentration is recommended for use in those who exhibit a higher prevalence ofsignificant vascular disease and autonomic dysfunction and seem to be susceptible to severe adverse reaction of phenylephrine.

Mydriasis associated with local dysfunction of parasympathetic nerves in two dogs.

In clinical practice, photophobia resulting from persistent mydriasis may be associated with dysfunction of ocular parasympathetic nerves or primary iris lesions. We encountered a 5-year-old Miniature Dachshund and a 7-year-old Shih Tzu with mydriasis, abnormal pupillary light reflexes, and photophobia. Except for sustained mydriasis and photophobia, no abnormalities were detected on general physical examination or ocular examination of either dog. We performed pharmacological examinations using 0.1% and 2% pilocarpine to evaluate and diagnose parasympathetic denervation of the affected pupillary sphincter muscles. On the basis of the results, we diagnosed a pupillary abnormality due to parasympathetic dysfunction and not to overt primary iris lesions. The test revealed that neuroanatomic localization of the lesion was postciliary ganglionic in the first dog.

Cataractous changes due to posterior chamber flattening with a posterior chamber phakic intraocular lens secondary to the administration of pilocarpine.

OBJECTIVE: To present the first reported case of cataract formation as a consequence of instillation of pilocarpine in an eye with a posterior chamber phakic intraocular lens (IOL). DESIGN: Interventional case report. INTERVENTION: A 46-year-old man received a hyperopic implantable collamer lens (ICL) bilaterally. MAIN OUTCOME MEASURES: Determination of best-corrected visual acuity (BCVA); contrast sensitivity testing with and without glare; and intraocular pressure (IOP), specular endothelial cell, and slit-lamp examinations were performed serially. In addition, the distance between the ICL and crystalline lens was measured with optical coherence tomography. RESULTS: Both eyes underwent uneventful ICL implantation for the correction of a manifest spherical equivalent of +7 diopters (D) in the right eye and +7.1 D in the left eye. The left eye was followed for 2 years without developing complications. The right eye, however, showed on the first postoperative day a fleckenlike opacification on the anterior pole of the crystalline lens after instillation on the operative day of 2% pilocarpine in an attempt to accelerate recovery from unwanted pupil dilation causing patient complaints of glare disability after surgery. Optical coherence tomography demonstrated complete contact of the ICL with the natural lens 24 hours postoperatively. Serial IOP measurements were always within the normal limits. The instillation of 1% cyclopentolate resulted in an increase in the ICL vault that measured 132 mum 24 hours later. Three days after the completion of a 3-day course of topical 1% cyclopentolate, the opacification was less dense and demarcated, and a 124-mum vault was measured. Three months postoperatively, the cataract was associated with a 3-line loss of BCVA and considerable degradation of the contrast sensitivity, especially at higher spatial frequencies and with a glare source, and corneal endothelial cell changes were within normal limits. One year after ICL implantation, the right eye had to undergo phacoemulsification and IOL implantation, which were uneventful. CONCLUSIONS: Posterior chamber flattening with resulting crystalline lens opacification can occur immediately after the instillation of pilocarpine in an eye with a hyperopic ICL. Therefore, caution should be taken with the administration of cholinergic agonists such as pilocarpine in patients with phakic IOLs, at least if they are hyperopic ICLs.