Eficacia y seguridad del uso intraocular de carbacol 0. 01 % para la inducción de miosis intraoperatoria en cirugía de catarata / Efficacy and safety of the intraocular use of 0. 01% carbacol for the induction of intraoperative miosis in cataract surgery

La catarata es definida por la Organización Mundial de la Salud (OMS) como la opacificación del lente cristalino que generalmente ocurre por el envejecimiento, trauma, o alguna enfermedad sistémica, afectando la capacidad visual de la persona. Esta disminución de la capacidad visual o incluso la ceguera, es un problema de salud pública en adultos y adultos mayores. En el Perú, aproximadamente el 0.6 % de la población tiene ceguera, cuya causa en el 47 % de los casos son por las cataratas. El tratamiento indicado para la catarata es la intervención quirúrgica, la cual consiste en reemplazar el cristalino opacificado o catarata por un lente intraocular. Hay dos formas de realizar esto, mediante la extracción extracapsular del cristalino opacificado, o mediante la facoemulsificación del cristalino, que consiste en un proceso de destrucción mediante ondas vibratorias ultrasónicas. Luego de ello, se realiza la implantación de un nuevo lente intraocular con soporte capsular, el cual reemplaza al cristalino permitiendo que el paciente vuelva tener una visión adecuada. Posterior a la implantación del lente intraocular se realiza la inducción de miosis pupilar para mantener el lente dentro de la bolsa capsular, evitar la captura del lente por el iris y el prolapso del iris por las heridas operatorias. La inducción de miosis luego de una intervención por catarata debe realizarse inmediatamente después de la implantación del lente, por lo que la vía de administración indicada es la inyección intraocular del agente miótico. De este modo, se espera que el efecto miótico se prolongue hasta por 24 horas, mientras que la aplicación tópica de un agente miótico se limita a un efecto que bordea las ocho horas, y sólo se puede realizar en el periodo postoperatorio, por lo que se genera un periodo entre la intervención quirúrgica y la aplicación del agente miótico que expone al paciente a las potenciales complicaciones anteriormente mencionadas. Aunque algunos estudios de serie de casos clínicos indican el uso de pilocarpina 2 %, el cual se encuentra disponible en el Petitorio Farmacológico de EsSalud, este medicamento no ha sido aprobado por la FDA para uso intraocular, sólo para uso tópico, dado que su uso intraocular puede ser tóxico o incrementar el riesgo de infecciones intraoculares. Así, en la actualidad EsSalud no cuenta con un medicamento miótico de uso intraocular autorizado, por lo cual, surge la necesidad de evaluar otras alternativas que pudieran ser de beneficio para dichos pacientes. OBJETIVO: objetivo del presente dictamen fue evaluar la eficacia y seguridad del uso intraocular de carbacol 0.01 % para la inducción de miosis intraoperatoria en las intervenciones quirúrgicas por catarata. Carbacol es um colinérgico o parasimpaticomimético potente, que actúa como agonista del receptor de acetilcolina, inhibiendo la acetilcolinesterasa y estimulando tanto los receptores muscarínicos como nicotínicos, produciendo miosis a través de la constricción del iris y del cuerpo ciliar, y reduciendo la presión intraocular. TECNOLOGÍA SANITARIA DE INTERÉS: CARBACOL. Carbacol, también conocido como carbamilcolina, es un colinérgico o parasimpaticomimético potente, que actúa como agonista del receptor de acetilcolina, inhibiendo la acetilcolinesterasa y estimulando tanto los receptores muscarínicos como nicotínicos, produciendo constricción del iris y del cuerpo ciliar y además reduciendo la presión intraocular. El agente colinérgico fue aprobado por la Administración de Drogas y Alimentos (FDA, por sus siglas en inglés) en el año 2002 (FDA, 2015). METODOLOGÍA: Se realizó una búsqueda sin restricción de idioma hasta mayo del 2018. La formulación de la estrategia de búsqueda incluyó los criterios de elegibilidad, los términos controlados propios de cada base y términos libres. Asimismo, se buscaron otros documentos potencialmente elegibles a través de la revisión del listado de referencias de los documentos seleccionados para lectura a texto completo. Por último, la selección de la evidencia siguió el flujograma mostrado en la subsección de resultados. RESULTADOS: Luego de la búsqueda sistemática realizada, se identificaron dos ensayos clínicos aleatorizados (ECA) Beasley, 1972 y Solomon et al., 1998; y el estudio de serie de casos de Pekel et al., 2014. Si bien estos estudios muestran algunas limitaciones que serán analizadas más adelante, es la evidencia de mayor relevancia en torno al uso de carbacol para la inducción de miosis intraoperatoria en las intervenciones quirúrgicas por catarata. Con respecto a la eficacia de carbacol en la inducción de miosis, el estudio de Beasley, 1972 muestra que el efecto miótico a los dos minutos de la inyección intraocular es significativamente mayor en carbacol, con respecto a placebo (p<0.01) y que el efecto miótico persiste por lo menos por 15 horas. Por otro lado, a la séptima semana postoperatoria, se observó una incidencia significativamente menor de sinequias anteriores periféricas (SAP) en el grupo que recibió carbacol (11 %), en comparación al grupo que recibió a placebo (35 %). Al analizar el impacto sobre la calidad de vida por parte de carbacol mediante el cuestionario modificado de SF-36, el cual mide la percepción del paciente sobre su estado de salud, el estudio de Solomon et al., 1998 muestra que carbacol incrementa la agudeza visual durante el primer día postoperatorio, con respecto a placebo, y muestra una diferencia estadísticamente significativa en el porcentaje de sujetos que pueden descender las escaleras sin ayuda durante la primera semana posterior a la intervención quirúrgica, tanto en un ambiente con luz brillante (p=0.007) o con luz tenue (p=0.037), siendo un potencial factor protector en pacientes con riesgo de presentar caídas acci Con respecto a los eventos adversos, los estudios evaluados no encontraron casos de inflamación intraocular ni de cefalea frontal. El estudio Pekel et al., 2015 muestra que sólo en el primer día postoperatorio hubo un menor volumen macular total (VMD y del grosor macular central (GMC) con respecto al volumen preoperatorio. Mientras que, durante el seguimiento (al primer día, a la primera semana y al primer mes) no se encontraron diferencias estadísticamente significativas en la presencia de edema macular, ni en el calibre de los vasos retinianos (CVR) al comparar los pacientes que recibieron carbacol con los que no lo recibieron. dentales y fractura de caderas. CONCLUSIONES: El presente dictamen preliminar muestra la evidencia disponible hasta mayo 2018 con respecto al uso intraocular de carbacol 0.01 % en comparación con placebo para la inducción de miosis intraoperatoria en pacientes operados de cataratas. No se encontraron guías de práctica clínica, revisiones sistemáticas ni evaluaciones de tecnologías sanitarias que respondan la pregunta PICO de la presente evaluación. Finalmente, se identificaron dos ECA y un estudio de serie de casos como sustento para la elaboración del presente dictamen preliminar. Al evaluar la eficacia de carbacol en la inducción de miosis, el estudio Beasley, 1972 muestra que carbacol genera miosis dentro de los dos minutos de ser aplicado y que su efecto perdura por más de 15 horas. Esto se traduce en una menor incidencia de SAP a la sétima semana postoperatorio, con respecto a placebo. Aunque no se aprecia diferencia en la conservación de la integridad de la cámara vítrea. Con respecto a los eventos adversos, los estudios evaluados no observaron casos de inflamación intraocular ni de cefalea frontal, mientras que el estudio Pekel et al., 2015 muestra que carbacol disminuye el volumen macular total (VMT) y el grosor macular central (GMT) en el primer día postoperatorio, mas no en la primera semana, ni primer mes. Por otro lado, no se ve afectado el calibre de los vasos retinianos (CVR). Estos resultados muestran una cierta protección ante el edema macular en el postoperatorio inmediato y ausencia de secuelas en la morfología macular, sin embargo, se debe tener en cuenta el posible sesgo de medición que conlleva. En resumen, carbacol es un agente miótico que inicia su acción dentro de los dos minutos de su inyección, manteniendo su efecto por más de 15 horas, generando un beneficio en el periodo postoperatorio inmediato en la agudeza visual y en el volumen macular total. Asimismo, los estudios no reportan eventos adversos como edema macular, cefalea, y, por el contrario, refieren una reducción en la incidencia de SAP, mas no hay una diferencia en la preservación de la integridad de la cámara vítrea, al ser comparado con placebo. Con respecto a la calidad de vida en el postoperatorio, se observa un inicio más temprano de la deambulación y autonomía en el uso de las escaleras, lo que podría tener un impacto positivo en el estilo de vida de los pacientes intervenidos. Por lo expuesto, el Instituto de Evaluaciones de Tecnologías en Salud e Investigación - IETSI aprueba el uso de carbacol, según lo establecido en el Anexo N.° 1. La vigencia del presente dictamen preliminar es de dos años a partir de la fecha de publicación.

Acetylcholine chloride 1% usage for intraoperative cataract surgery miosis / Cloridrato de Acetilcolina 1% na obtenção da miose intraoperatória na cirurgia de catarata

Abstract Objective: To test the efficacy of Acetylcholine chloride use in obtaining intraoperative miosis on phacoemulsification cataract surgery. Methods: Patients with cataract diagnosis and elected for surgical phacoemulsification procedure were selected. All patients underwent conventional phacoemulsification procedure performed by a single surgeon and all patients had 0.2 ml of Acetylcholine chloride 1% irrigated in the anterior chamber at the end of the surgery. The pupillary diameter was measured immediately before the beginning of surgery, immediately before and two minutes after the use of acetylcholine chloride 1%. Results: A total of 30 eyes from 30 patients were included in the study. 18 were female, and mean age was of 69.5 years with a 7.2y standard deviation on the population study. The mean pupillary diameter immediately before the beginning of surgery was 7.5 mm with a standard deviation of 0.56 mm; the mean pupillary diameter immediately before the acetylcholine chloride 1% use (after the intraocular lens im-plantation) was 7.1 mm with a standard deviation of 0.57 mm. The mean pupillary diameter two minutes after the use of acetylcholine chloride 1% in the anterior chamber was 3.4 mm with standard deviation of 0.66 mm. The mean maximum action time of ACH chloride 1% was 64 seconds, with a standard deviation of 8 seconds. The mean intraocular pressure on the first postoperative day was 19.1 mmHg with a standard deviation of 2.45 mmHg. Conclusion: We conclude that acetylcholine chloride 1% is an important drug to obtaining intraoperative miosis in cataract surgery.

Resumo Objetivo: Demonstrar a eficácia do cloridrato de acetilcolina 1% na obtenção da miose intraoperatória na cirurgia de catarata pela técnica de facoemulsificação. Métodos: Pacientes com diagnóstico de catarata e indicação de cirurgia foram selecionados para participar do presente estudo. Todos os pacientes foram operados pela técnica de facoemulsificação convencional pelo mesmo cirurgião, todos foram submetidos à aplicação de 0,2 ml do cloridrato de acetilcolina 1% na câmara anterior ao final do procedimento cirúrgico. A medida do diâmetro pupilar foi realizada imediatamente antes do início da cirurgia, imediatamente antes do uso do cloridrato de acetilcolina 1% e após 2 minutos. Resultados: Foram estudados 30 olhos de 30 pacientes, destes, 18 eram do sexo feminino, a média de idade do estudo foi de 69,5 anos com desvio padrão de 7,2 anos. A média do diâmetro pupilar imediatamente antes do início da cirurgia foi 7,55 mm com desvio padrão de 0,56mm, a média do diâmetro pupilar imediatamente antes do uso do cloridrato de acetilcolina 1% (após implante da lente intraocular no saco capsular) foi 7,1mm com desvio padrão de 0,57mm. A média do diâmetro pupilar após 2 minutos da aplicação da acetilcolina na câmara anterior foi de 3,4 mm com desvio padrão de 0,66mm. O tempo médio de ação máxima do medicamento foi de 64 segundos, com desvio padrão de 8 segundos. A média da pressão intraocular no primeiro dia do pós-operatório foi de 19,1 mmHg com desvio padrão de 2,45mmHg. Conclusão: O estudo acima mostrou que a acetilcolina apresenta boa eficácia na obtenção de miose intraoperatória na cirurgia de facoemulsificação, permitindo uma maior facilidade na confecções das suturas corneanas ou corneo-escleral, reduzindo a incidência de sinéquias anteriores periféricas. Concluimos que o cloridrato de acetilcolina 1% é um importante medicamento na obtenção da miose intraoperatória na cirurgia de catarata.

Fatores associados aos óbitos entre homens envenenados por carbamato ("chumbinho") / Factores de muertes de hombres envenenados por carbamato ("chumbinho") / Factors associated with the deaths of men poisoned by carbamato ("chumbinho")

RESUMO Objetivo Determinar os fatores associados aos óbitos em vítimas de envenenamento por carbamato (“chumbinho”). Método Estudo retrospectivo, epidemiológico tipo caso-controle, baseado nas fichas de notificação de intoxicação do centro de controle de intoxicações localizado na região metropolitana do Rio de Janeiro. Foram utilizadas 24 fichas de notificação de intoxicações de homens dos 20 aos 59 anos com história de envenenamento por carbamato entre 2005 e 2009. As fichas foram sorteadas aleatoriamente, respeitando-se a razão de 1:3 (um caso para três controles). A faixa etária variou de 23 a 58 anos; a média 43,83 anos. Resultados Os sintomas mais recorrentes foram: miose (OR = 1.0; IC 95%: 0,27 – 3,69. p= 1.0), sialorreia (OR = 0,83; IC 95%: 0,22 – 3,12. p= 0,78), dispneia (OR = 0,66; IC 95%: 0.14 – 3,03. p= 0,59). Conclusão Os óbitos apresentaram associação com sialorreia, miose e dispneia e uma forte associação com estertores pulmonares, broncoespasmos e os roncos pulmonares.

RESUMEN Objetivo Determinar los factores asociados a la muerte en las víctimas de envenenamiento por carbamato (“Chumbinho”). Método Estudio retrospectivo, epidemiológico de caso y control sobre el envenenamiento en los formularios de notificación un centro de control de envenenamiento localizado en la región metropolitana de Río de Janeiro. Utilizamos 24 formularios de notificación de envenenamiento en hombres de 20 a 59 años con intoxicación por el carbamato de 2005 a 2009. Los registros fueron seleccionados al azar, respetando la proporción de 1:3 (un caso y tres controles). El rango de edad fue de 23 a 58 años, promedio de 43,83 años. Resultados Los síntomas más frecuentes fueron miosis (OR = 1,0; IC del 95%: 0,27 a 3,69 p = 1.0.), Babeo (OR = 0,83, IC 95% 0,22-3,12 p. = 0,78), disnea (OR = 0,66; IC del 95%: 0:14 - 3.03 p = 0.59). Conclusión Las muertes se asociaron con babeo, miosis y disnea, y una fuerte asociación con estertores pulmonares, broncoespasmo y el ronquido pulmonar.

ABSTRACT Objective To determine the factors associated with death in poisoning victims by carbamate (“Chumbinho”). Method Retrospective study, epidemiological case-control based on poisoning reporting forms, a poison control center located in the metropolitan region of Rio de Janeiro. We used 24 notification forms of poisoning in men aged 20 to 59 years with poisoning by carbamate history from 2005 to 2009. The records were randomly selected, respecting the ratio 1:3 (a case to three controls). The age range was 23-58 years, average 43.83 years. Results The most frequent symptoms were myosis (OR=1.0; 95% CI: 0.27 to 3.69 p=1.0.), drooling (OR=0.83; 95% CI. 0.22 to 3.12 p=0.78), and dyspnea (OR=0.66; 95% CI: 0:14-3.03 p=0.59). Conclusion The deaths were associated with drooling, miosis and dyspnea and a strong association with pulmonary rales, bronchospasm and pulmonary snoring.

Naphazoline as a confounder in the diagnosis of carotid artery dissection.

Diagnosing Horner Syndrome can be difficult in the setting of an incomplete triad. A 27-year-old man presented with unilateral eyelid droop and intermittent ipsilateral headaches, having already seen 7 physicians. Physical examination revealed unilateral ptosis but no pupillary miosis or facial anhidrosis. Inspection of his clinical photographs revealed elevation of the ipsilateral lower eyelid, suggesting sympathetic dysfunction. On further questioning, he admitted to naphazoline dependence. Reexamination after ceasing the naphazoline unveiled the anisocoria. Vascular imaging subsequently revealed carotid dissection, and the patient was started on anticoagulant and antiplatelet therapy. The ptosis persisted after conjunctival Müllerectomy. External levator resection was recommended, but patient declined. This case underscores the importance of clinical photography, meticulous medical record review, and complete medication history including over-the-counter preparations. Clinicians should meticulously inspect the lower eyelid in cases of atypical blepharoptosis and consider the effects of eye drops when inspecting pupils for miosis.

Tonic pupil in leprosy / Pupila tônica em doença de Hansen

Pupil abnormalities in leprosy usually result from chronic iritis with loss of stroma, iris miosis, a sluggish reaction to light, and poor dilation in response to anticholinergic mydriatics. We report two patients with long-standing lepromatous leprosy who developed tonic pupils characterized by mydriasis, absence of reaction to light and hypersensitivity to weak cholinergic solution. Examination revealed iritis and iris atrophy. In both cases, instillation of dilute 0.1% pilocarpine caused miosis in the affected eyes. Tonic pupil occurs in many conditions, but its association with leprosy had not been previously reported.

Anormalidades da pupila em pacientes com doença de Hansen, ocorrem mais comumente devido a irite crônica com perda do estroma iriano, miose, diminuição da reação à luz, e dificuldade de dilatação em resposta a colírios anticolinérgicos. Relatamos dois pacientes com doença de Hansen na forma lepromatosa que desenvolveram pupilas tônicas, caracterizadas por midríase, ausência de reação a luz e para perto e hipersensibilidade a fraca concentração de solução colinérgica. O exame revelou irite e atrofia iriana. Em ambos os casos a instilação de pilocarpina 0,1% causou miose nos olhos afetados. A pupila tônica tem sido relatada em muitas condições, mas sua associação com doença de Hansen ainda não havia sido descrita.

Toxic leukoencephalopathy due to transdermal fentanyl overdose.

Children with altered mental status who present to the emergency department have a broad differential diagnosis. We report a case of a 19-month-old girl who presented in coma and who was later found to have a fentanyl patch adhered to her back. She was found to have changes on brain magnetic resonance imaging consistent with a toxic spongiform leukoencephalopathy but had a good neurologic outcome. This case report illustrates the importance of a thorough physical examination in children in coma and a rarely reported magnetic resonance imaging finding that has been seen in opioid intoxication and is usually associated with severe morbidity and mortality.

Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimal and noninvasive probes for hepatic and first-pass CYP3A induction.

Systemic and oral clearances of alfentanil (ALF) are in vivo probes for hepatic and first-pass cytochrome P450 (CYP) 3A. Both ALF single-point plasma concentrations and miosis are surrogates for area under the concentration-time curve (AUC) and clearance and are minimal and noninvasive CYP3A probes. This investigation determined ALF sensitivity for detecting graded CYP3A induction and compared it with that of midazolam (MDZ). Twelve volunteers (sequential crossover) received 0, 5, 10, 25, or 75 mg oral rifampin for 5 days. MDZ and ALF were given intravenously and orally on sequential days. Dark-adapted pupil diameter was measured with blood sampling. Graded rifampin decreased plasma MDZ AUCs to 83, 76, 62, and 59% (intravenous (i.v.)) and 78, 66, 39, and 24% (oral) of control. Hepatic and first-pass CYP3A induction were detected comparably by plasma MDZ and ALF AUCs. Single ALF concentrations detected all CYP3A induction, whereas MDZ was less sensitive. ALF miosis detected induction of first-pass but not hepatic CYP3A.

[Floppy iris syndrome]. / Sindromul floppy iris.

Intraoperative floppy iris syndrome associated with the use of tamsulosin is one of the landmark discoveries of this decade in the field of cataract surgery.

The side effects of morphine and hydromorphone patient-controlled analgesia.

BACKGROUND: Despite "clinical lore" among health care providers that treatment with hydromorphone results in improved pain control and fewer adverse side effects, morphine continues to be the first-line medication for postoperative patient-controlled analgesia (PCA). In this study, we compared the efficacy and side-effect profiles of morphine and hydromorphone at concentrations producing equivalent drug effect measured by pain score and miosis. METHODS: We conducted a prospective, randomized, double-blind trial of 50 general and gynecological surgery patients. Subjects were randomly assigned to receive either morphine (1 mg/mL) or hydromorphone (0.2 mg/mL) via PCA after surgery and were followed for a period of 8 h. The primary outcome was nausea. Secondary outcome variables were pruritus, vomiting, sedation, pain report, pupillary miosis, and patient satisfaction. RESULTS: The side effect profile was not different between drugs. The incidence of nausea did not differ between morphine and hydromorphone-treated patients (1 h: 44% vs 52%, 8 h: 68% vs 64%), vomiting (1 h: 4% vs 0%, 8 h: 0% vs 4%), or pruritus (1 h: 4% vs 16%, 8 h: 40% vs 40%). There was no difference in the amount of medication required to treat side effects or patient satisfaction. The average ratio of morphine to hydromorphone use was about 7:1. The patients used 10.9+/-6.0 mg morphine versus 1.57+/-1.0 mg hydromorphone after 1 h and 29.0+/-18.0 mg morphine versus 3.9+/-2.5 mg hydromorphone after 8 h. There was no difference between the morphine and hydromorphone groups with respect to postoperative pain scores with movement at 1 h (7.9+/-2.3 vs 7.1+/-2.4) or 8 h (5.7+/-2.8 vs 5.9+/-2.7). There was also no difference in pain at rest or miosis between groups. CONCLUSIONS: We found no systematic difference between morphine and hydromorphone in opioid-related side effects. Neither was there any difference in efficacy of pain control or patient satisfaction when patients self-titrated to equal drug effect as measured by equianalgesia and pupillary miosis. The choice between morphine and hydromorphone for use in PCA should be guided by patient history, as there may be idiosyncratic reactions to either drug.

Tamsulosin and cataract surgery: hypotonic iris.

(1) Hypotonic or floppy iris syndrome has been observed during cataract surgery in patients taking tamsulosin, an alpha blocker indicated for benign prostatic hypertrophy. Hypotonic iris makes surgery more difficult and increases the risk of complications, especially those linked to the use of mechanical retractors. (2) Several studies including hundreds of patients have confirmed the role of tamsulosin in this syndrome. It is not clear how long before surgery tamsulosin should be withdrawn: cases have been reported from 2 days to 9 months after tamsulosin withdrawal. (3) It is not known whether other alpha blockers have the same effect. (4) In practice, as tamsulosin does not have a better risk-benefit balance than other alpha blockers, it should be avoided in men who have not had cataract surgery.

[Repetitive instillation of 0.1% cyclosporin A eye drops induces miosis and anterior chamber inflammation-like reactions in monkey eyes].

PURPOSE: Miosis and anterior chamber inflammation-like reactions were recognized after six instillations of 0.1% cyclosporin A eye drops every 30 minutes into rabbit conjunctival sacs. In order to consider species specificity, 0.1% cyclosporin A eye drops were applied by the same method in monkeys. METHODS: Eye drops were applied in five monkeys (monkey A, B, C, D, E); in one eye as control and in nine eyes with 0.1% cyclosporin A. We investigated the changes of pupil diameter, intraocular pressure, and anterior chamber flare before and after applying the eye drops. We also examined the effect on ocular tissue histopathologically. RESULTS: Miosis was recognized in six eyes, but no significant intraocular pressure change was observed in any eyes. In both eyes of monkey A anterior chamber flare increased significantly, and flare increased slightly in both eyes of monkeys B, C, and D. On the other hand, there was no change in either eye of monkey E, including the control eye. Localized necrosis of nonpigmented ciliary epithelium was recognized at the beginning of the ciliary process in both eyes of monkey A. Mild cystoid degeneration of nonpigmented ciliary epithelium was seen at the beginning of the ciliary process in the right eye of monkey C, and in the left eye of monkey D. CONCLUSION: No species specificity can be recognized in monkeys from the fact that there is the selective destruction of nonpigmented epithelium at the beginning of the ciliary process after repeated instillation of 0.1% cyclosporin A eye drops, although there was a difference in miosis and anterior chamber inflammation-like reaction in individual monkeys.

Influence of tamsulosin on the iris and its implications for cataract surgery.

PURPOSE: To study iris-related complications during cataract surgery in patients on tamsulosin medication. METHODS: Twenty-one consecutive cataract patients administered tamsulosin and 21 control patients were studied. Characteristics of the iris during surgery were recorded. Pupillary diameters of 16 patients were measured before and after iris dilatation. Tamsulosin concentrations in the aqueous humor and serum were analyzed. In five patients, surgery on the second eye was carried out after a 7- to 28-day pause in tamsulosin medication. RESULTS: Each patient administered tamsulosin had a sluggish hypotonic iris, along with a tendency toward miosis and a tendency for prolapse of the iris into the phaco tunnel or into the side port during cataract surgery. Sluggish irises also often adhered to the phaco tip or to the irrigation-aspiration tip. Despite a pause of 7 to 28 days in the use of tamsulosin, the adverse effects persisted. Tamsulosin concentrations varied between 0.1 and 1.0 ng/mL in the anterior chamber fluid. In three of five cases, tamsulosin remained in detectable amounts the aqueous humor after the 7- to 28-day pause. Preoperative pupillary diameter was smaller in the patients using tamsulosin than in the controls. CONCLUSIONS: Tamsulosin has selective alpha1A-adrenoreceptor antagonistic properties and obviously binds for a long period to the postsynaptic nerve endings of the iris dilator muscle, thus affecting iris dilatation and leading to complications in cataract surgery. The iris remained floppy after 7- to 28-day interruption of the tamsulosin regimen.

Morphine-induced reduction of intraocular pressure and pupil diameter: role of nitric oxide.

The present study was performed to evaluate the role of nitric oxide in the intraocular pressure (IOP) lowering effect and in the miotic action of morphine. The IOP was measured in conscious, normal, dark-adapted New Zealand white rabbits using a calibrated pneumatonometer. Experiments were conducted, in which rabbits' eyes were treated with morphine topically and unilaterally, while the fellow eyes received vehicle. IOP and pupil diameter (PD) measurements were taken 0.5 and 0 h before morphine administration and 0.5, 1, 2, 3, 4, and 5 h thereafter. The effects of a nonselective opioid receptor antagonist (naloxone), a nitric oxide synthase inhibitor (Nomega-nitro-L-arginine methyl ester; L-NAME), and a sulfhydryl reagent (reduced L-glutathione; GSH) on morphine-mediated changes in IOP and PD were also determined. Morphine (10, 33, and 100 microg) produced concentration-dependent decreases in IOP and reduced PD in both treated and untreated eyes of New Zealand white rabbits. IOP-lowering effect of morphine (100 microg) and reduction in PD were both significantly inhibited by pretreatment with naloxone (100 microg), L-NAME (0.5%), or GSH (100 microg). The results from this study indicate that morphine-induced ocular hypotension and reduction in PD are opioid-receptor-mediated responses that are associated with the release of nitric oxide. Because the mu3 opioid receptor subtype has a nitric-oxide-releasing activity and is sensitive to inactivation by GSH, it is concluded that morphine-induced ocular hypotension and miosis are mediated, in part, by activation of mu3 opioid receptors.

Possible involvement of nitric oxide in morphine-induced miosis and reduction of intraocular pressure in rabbits.

The role of mu3 opioid receptors in morphine-induced intraocular pressure (IOP) lowering effect and miosis was evaluated in conscious, dark-adapted New Zealand white (NZW) rabbits using a masked-design study. IOP and pupil diameter (PD) measurements were taken at just before and 0.5, 1, 2, 4, 6 h after monolateral instillation of morphine (10, 50 and 100 microg/30 microl) as compared to vehicle administered in the contralateral eye. Morphine-induced ocular effects were challenged by a pre-treatment with the non-selective opioid receptor antagonist, naloxone (100 microg/30 microl), the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 1%, 30 microl), or the non-selective mu3 opioid receptor inhibitor, reduced L-glutathione (GSH, 1%, 30 microl). Morphine induced a dose-dependent decrease in IOP and PD. Pre-treatment with naloxone totally prevented morphine-induced decrease in IOP and miosis. Ocular administration of L-NAME or GSH alone failed to affect IOP or PD of NZW rabbits. However, pre-treatment with either drugs significantly reduced, but not totally prevented ocular effects of morphine. These results suggest that biochemical mechanisms related to nitric oxide release are involved, at least in part, in morphine effects on the eye. Since the mu3 opioid receptor subtype is able to release nitric oxide and is sensitive to inactivation by GSH, it may be possible that mu3 opioid receptors are involved in morphine-induced miosis and reduction in IOP.

New fluoroprostaglandin F(2alpha) derivatives with prostanoid FP-receptor agonistic activity as potent ocular-hypotensive agents.

To find new prostanoid FP-receptor agonists possessing potent ocular-hypotensive effects with minimal side effects, we evaluated the agonistic activities of newly synthesized prostaglandin F(2alpha) derivatives for the prostanoid FP-receptor both in vitro and in vivo. The iris constrictions induced by the derivatives and their effects on melanin content were examined using cat isolated iris sphincters and cultured B16 melanoma cells, respectively. The effects of derivative ester forms on miosis and intraocular pressure (IOP) were evaluated in cats and cynomolgus monkeys, respectively. Of these derivatives, 6 out of 12 compounds were more potent iris constrictors, with EC(50) values of 0.6 to 9.4 nM, than a carboxylic acid of latanoprost (EC(50)=13.6 nM). A carboxylic acid of latanoprost (100 microM) significantly increased the melanin content of cultured B16 melanoma cells, but some 15,15-difluoro derivatives, such as AFP-157 and AFP-172, did not. Topically applied AFP-168, AFP-169 and AFP-175 (isopropyl ester, methyl ester and ethyl ester forms, respectively, of AFP-172) induced miosis in cats more potently than latanoprost. AFP-168 (0.0005%) reduced IOP to the same extent as 0.005% latanoprost (for at least 8 h). These findings indicate that 15,15-difluoroprostaglandin F(2alpha) derivatives, especially AFP-168, have more potent prostanoid FP-receptor agonistic activities than latanoprost. Hence, AFP-168 may be worthy of further evaluation as an ocular-hypotensive agent.

Effect of brimonidine tartrate ophthalmic solution 0.2% on pupil size in normal eyes under different luminance conditions.

PURPOSE: To evaluate the effect of brimonidine tartrate ophthalmic solution 0.2% (Alphagan) on pupil size in normal eyes. Three luminance conditions were used to assess the potential use of brimonidine in postoperative refractive patients who experience nighttime vision problems related to large pupil size. SETTING: McDonald Eye Associates, Fayetteville, Arkansas, USA. METHODS: Pupil size was measured in 16 eyes of 16 participants with the Colvard pupillometer under 3 luminance conditions. One drop of brimonidine 0.2% was administered to each patient. Pupil size was then measured using the same technique 30 minutes and 4 and 6 hours after drop administration. RESULTS: Under scotopic conditions, 100% of the pupils showed significant miosis at 30 minutes (P <.05). The effect continued in all eyes for 4 hours. At 6 hours, a miotic effect was still present in 81.3%. However, under photopic luminance, there was no significant effect on pupil size in all 16 eyes (P >.05). The pupil size in 5 eyes (31.2%) was not affected at 30 minutes or 4 or 6 hours. At 6 hours, 15 eyes (93.8%) had returned to their preinstillation size. CONCLUSION: Brimonidine tartrate 0.2% had a significant effect in decreasing pupil size under scotopic conditions. The results indicate that the drug can decrease night-vision difficulties such as halos, star bursts, glare, and monocular diplopia in postoperative refractive patients.

Ocular signs and symptoms caused by exposure to sarin gas.

PURPOSE: Ocular signs and symptoms that occurred in people exposed to sarin gas in a subway sarin gas attack were studied. METHODS: Among victims of sarin gas exposure, 96 were treated by us. RESULTS: Ocular signs and symptoms caused by sarin gas exposure included miosis, conjunctival injection, and ocular pain. CONCLUSIONS: Ocular signs and symptoms spontaneously resolved between three and 21 days after exposure in most cases. Treatment with 0.5% tropicamide ophthalmic solution was effective in decreasing ocular pain.

Neuroleptic malignant-like syndrome: a complication of acute organophosphate poisoning.

We report a 60-yr-old woman with schizophrenia, who manifested a neuroleptic malignant (NM)-like syndrome after acute organophosphate poisoning (OPP). She attempted suicide by ingesting 40% emulsions of DMTP (S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadizol-3-yl-methyl O,O-dimethyl phosphorodithioate) 100 ml. On admission, she was unconscious and demonstrated convulsions, depressed respiratory movements, miosis and profuse salivation. Plasma cholinesterase concentration (842 IU.L-1) was very low and OPP was diagnosed. She was treated with gastric lavage, atropine and pralidoxime (PAM). By the seventh day after admission, symptoms of OPP disappeared and serum ChE had recovered to a sub-normal level. On the 13th day, she demonstrated coma, high fever (41.0 degrees C) and lead-pipe rigidity. Serum CPK was increased (1631 IU.L-1). Dantrolene sodium iv was administered for three days. Body temperature began to decrease in 24 hr, and her consciousness, muscle rigidity and other neurological symptoms returned to normal by the 16th day after admission. She was discharged from the hospital without sequelae 55 days after admission. We conclude that OPP can predispose to an NM-like syndrome and that dantrolene may be effective in the management.

Intraocular miotics and postoperative inflammation.

Sixty patients scheduled for planned extracapsular cataract extraction with intraocular lens (IOL) implantation were randomly assigned to receive acetylcholine chloride, carbachol, or balanced salt solution (BSS) immediately after IOL placement and at the end of the surgical case. As part of the postoperative evaluation, patients were examined at the first and eighth postoperative day with a Kowa FC-1000 laser flare and cell meter to assess objectively the amount of postoperative inflammation. At day one and day eight, the amount of cell and flare in the carbachol group was significantly greater than in the acetylcholine group or in the BSS control group. The acetylcholine group had significantly less flare than the BSS group at day one; yet there was no difference between the two groups at day eight, nor was there a significant difference in the amount of cells between day one and day eight. It is presumed that the prolonged miosis seen in the carbachol group delays the re-establishment of the blood-aqueous barrier after surgery, causing the inflammatory response.