Methylene blue-related corneal edema and iris discoloration.

We report the case of a 70-year-old female patient who developed corneal edema and iris discoloration following the inadvertent use of 1% methylene blue instead of 0.025% trypan blue to stain the anterior capsule during cataract phacoemulsification surgery. Copious irrigation was performed upon realization of incorrect dye use. Corneal edema and iris discoloration developed during the early postoperative period and persisted at 24-months follow-up. However, keratoplasty was not required. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Copious irrigation for at least 30 min using an anterior chamber maintainer may improve outcomes.

Investigação oftalmológica pré-clínica do óleo essencial de Origanum vulgare L. Lamiaceae / Ophthalmological pre-clinical research about essential oil from the Origanum vulgare L. Lamiaceae

RESUMO Objetivo: Avaliar a irritação ocular aguda em coelhos, após a administração tópica de óleo essencial. Métodos: Para tanto, os animais foram divididos em três grupos, cada um com três coelhos, totalizando 6 olhos por grupo, e a diferença entre eles foi a concentração utilizada ( 1, 3 e 9%). Aplicou-se no saco conjuntival, de um dos olhos do animal, uma dose única de 0,1 ml do produto e o olho contralateral foi usado como controle. Analisou-se os efeitos causados pelo óleo essencial na conjuntiva, íris e córnea após 1, 24, 48, 72 horas e no final do sétimo dia após a aplicação tópica. As avaliações oftalmológicas foram feitas com o auxílio de um oftalmoscópio binocular indireto com e sem fluoresceína. As reações observadas foram graduadas segundo a escala de Draize. Foram realizados exames anatomopatológicos em todos os olhos estudados no final do experimento. Resultados: No grupo de animais submetidos à instilação ocular do óleo essencial a 1%, não se observou alterações. O tratamento com o óleo a 3% provocou alteração conjuntival no exame feito em 1 hora, o que foi reduzindo. A administração do óleo essencial a 9% induziu hiperemia conjuntival, não havendo qualquer alteração nos outros tempos de avaliação oftalmológica. Conclusão: A avaliação contribuiu para conhecer as alterações clínicas na superfície ocular. Desta forma, foi possível classificar o óleo a 1% como não irritante e nas concentrações de 3 e 9% como pouco irritante, tornando possível estudos clínicos, a fim de estabelecer o óleo como alternativa terapêutica em conjuntivites bacterianas.

ABSTRACT Objective: To evaluate acute eye irritation in rabbits following topical administration of essential oil. Methods: animals were divided into three groups, each containing three rabbits, with a total of 6 eyes per group. The difference between them was the concentration used (1, 3 and 9%). A single dose of 0.1 ml of the product was applied into the conjunctival sac of one eye of the animal, and the contralateral eye was used as control. The effects caused by the essential oil in the conjunctiva, iris and cornea were analyzed after 1, 24, 48 and 72 hours and at the end of the seventh day after topical application. Ophthalmologic evaluations were performed with the aid of a binocular indirect ophthalmoscope fluorescein and with and without the observed responses, before being graded according to the Draize scale. Pathological examinations were performed on all eyes studied at the end of the experiment. Results: in the group of animals subjected to the ocular instillation of 1% essential oil, there was no change. For treatment with 3% oil, conjunctival changes were found to be decreasing during the examination after 1 hour. Administration of the 9%essential oil induced conjunctival injection, without any change in the other ophthalmologic evaluation times. Conclusion: the evaluation contributed to meet the clinical changes in the ocular surface. Thus, it was possible to classify the oil at 1% as non-irritating and the concentration of 3% and 9 as mildly irritating, making it possible for clinical studies to establish the oil as an alternative therapy in bacterial conjunctivitis.

Methylene blue-related corneal edema and iris discoloration / Edema de córnea e descoloração de íris associados ao azul de metileno

ABSTRACT We report the case of a 70-year-old female patient who developed corneal edema and iris discoloration following the inadvertent use of 1% methylene blue instead of 0.025% trypan blue to stain the anterior capsule during cataract phacoemulsification surgery. Copious irrigation was performed upon realization of incorrect dye use. Corneal edema and iris discoloration developed during the early postoperative period and persisted at 24-months follow-up. However, keratoplasty was not required. The intracameral use of 1% methylene blue has a cytotoxic effect on the corneal endothelium and iris epithelium. Copious irrigation for at least 30 min using an anterior chamber maintainer may improve outcomes.

RESUMO Paciente do sexo feminino com 70 anos de idade desenvolveu edema da córnea e descoloração da íris após o uso inadvertido de 1% de azul de metileno em vez de 0,025% de azul tripano para corar a cápsula anterior do cristalino durante a cirurgia de catarata por facoemulsificação. Foi realizada irrigação abundante quando detectou-se que o corante incorreto tinha sido usado. Edema da córnea e descoloração íris que ocorreu no período pós-operatório precoce persistiu durante 24 meses de seguimento; no entanto, a ceratoplastia não foi necessária. O uso intracameral de 1% de azul de metileno tem efeitos citotóxicos sobre o endotélio da córnea e epitélio da íris. A irrigação abundante durante pelo menos 30 minutos, utilizando um mantenedor de câmara anterior pode resultar em um prognóstico melhor.

Rabbit rubeosis iridis induced by intravitreal latex-derived angiogenic fraction.

PURPOSE: To describe the presence of iris neovascularization in a rabbit-model of retinal neovascularization induced by the intravitreal injection of latex-derived angiogenic fraction microspheres (LAF). MATERIALS AND METHODS: Eight New Zealand rabbits received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 50 ug of LAF in the right eye (Group A). Microspheres without the LAF (0.1 ml) were injected in controls (Group B; n = 8). Follow-up with clinical evaluation and iris fluorescein angiography was performed after 4 weeks when eyes were processed for light microscopy. RESULTS: All eyes from Group A showed significant vascular dilation, conjunctival hyperemia and neovascularization on the iris surface, after LAF injection. No vascular changes were observed in Group B. CONCLUSIONS: The intravitreal injection of microspheres containing the LAF can induce rubeosis iridis in rabbits and could be used as a simple experimental model for iris neovascularization.

Benign prostatic hyperplasia. Clinical treatment can complicate cataract surgery.

PURPOSE: To investigate the effects of alpha-1 adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia (BPH) regarding potential risks of complications in the setting of cataract surgery. AIM: To address recommendations, optimal control therapy, voiding symptoms and safety within the setting of cataract surgery. MATERIALS AND METHODS: A comprehensive literature review was performed using MEDLINE with MeSH terms and keywords "benign prostatic hyperplasia", "intraoperative floppy iris syndrome", "adrenergic alpha-antagonist" and "cataract surgery". In addition, reference lists from identified publications were reviewed to identify reports and studies of interest from 2001 to 2009. RESULTS: The first report of intraoperative floppy iris syndrome (IFIS) was observed during cataract surgery in patients taking systemic alpha-1 AR antagonists in 2005. It has been most commonly seen related to use of tamsulosin. Changes of medication and washout periods of up to 2 weeks have been attempted to reduce the risk of complications in the setting of cataract surgery. CONCLUSION: Patients under clinical treatment for BPH should be informed about potential risks of this drug class so that it can be discuss with their healthcare providers, in particular urologist and ophthalmologist, prior to cataract surgery.

Benign prostatic hyperplasia: clinical treatment can complicate cataract surgery

PURPOSE: To investigate the effects of alpha-1 adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia (BPH) regarding potential risks of complications in the setting of cataract surgery. AIM: To address recommendations, optimal control therapy, voiding symptoms and safety within the setting of cataract surgery. MATERIALS AND METHODS: A comprehensive literature review was performed using MEDLINE with MeSH terms and keywords "benign prostatic hyperplasia", "intraoperative floppy iris syndrome", "adrenergic alpha-antagonist" and "cataract surgery". In addition, reference lists from identified publications were reviewed to identify reports and studies of interest from 2001 to 2009. RESULTS: The first report of intraoperative floppy iris syndrome (IFIS) was observed during cataract surgery in patients taking systemic alpha-1 AR antagonists in 2005. It has been most commonly seen related to use of tamsulosin. Changes of medication and washout periods of up to 2 weeks have been attempted to reduce the risk of complications in the setting of cataract surgery. CONCLUSION: Patients under clinical treatment for BPH should be informed about potential risks of this drug class so that it can be discuss with their healthcare providers, in particular urologist and ophthalmologist, prior to cataract surgery.

Mechanisms underlying lipopolysaccharide-induced kinin B1 receptor up-regulation in the pig iris sphincter in vitro.

Kinin B1 receptors are known to be highly induced after inflammatory stimuli in several biological systems. We report that incubation of pig iris sphincter with lipopolysaccharide from Escherichia coli caused a marked and time-related up-regulation of B1, accompanied by a reduction of B2 receptor-mediated contractile responses. The up-regulation of B1 receptors by lipopolysaccharide stimulation was decreased by the inhibitors of protein synthesis, cycloheximide and actinomycin D, and by dexamethasone and the nuclear factor-kappaB (NF-kappaB) inhibitor pyrrolidinedithiocarbamate (PDTC). In addition, lipopolysaccharide-induced up-regulation of B1 receptors in the pig iris sphincter was significantly reduced by the p38 inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) and to a lesser extent by the extracellular signal-regulated kinases 1 and 2 (ERK1/2) blocker 2'-amino-3'-methoxyflavone (PD98059). Molecular biology experiments demonstrated that in vitro incubation with lipopolysaccharide resulted in a time-dependent and remarkable activation of NF-kappaB and of p38 and ERK1/2 mitogen-activated protein (MAP) kinases, in pig iris sphincter preparations. While attempting to verify how MAP kinases are part of the B1 receptor-activated signaling transduction pathways, we observed that PD98059 was able to markedly reduce the contraction induced by B1 receptor activation in lipopolysaccharide-pretreated pig iris sphincter muscle but that this response was only partially decreased by SB203580. Our results extend the previous evidence on the mechanisms underlying the B1 receptor upregulation processes and demonstrate for the first time how this takes place in an ocular tissue, the pig iris sphincter. It is therefore possible to define B1 receptors as therapeutic targets for the treatment of infectious and inflammatory alterations of the eye.

New evidence on the mechanisms underlying bradykinin-mediated contraction of the pig iris sphincter in vitro.

We have reported previously that bradykinin (BK) induces potent and reproducible concentration-dependent contractions of the pig iris sphincter (PIS) muscle in vitro through the activation of BK B(2) receptors. Here we attempted to investigate additional mechanisms by which BK induces contraction of the PIS in vitro. BK-mediated contraction of the PIS relied largely on the external Ca2+ influx by a mechanism sensitive to the L-, N- and P-type of Ca2+ channel selective blockers. Likewise, BK-induced contraction of the PIS was greatly inhibited by the CGRP-(8-37), NK(2) or NK(3) receptor antagonists (SR 48968, SR 142801), and to a lesser extent by the NK(1) antagonist (FK 888). Capsaicin desensitization of PIS or capsazepine pre-incubation also significantly reduced BK-mediated contraction in the PIS. Furthermore, KT 5720 or GF 109203X (the protein kinase A and C inhibitors, respectively) also significantly inhibited BK-mediated contraction. Taken together, these results indicate that BK-mediated contraction of the PIS seems to be mediated primarily by the release of CGRP and tachykinins from sensory nerve fibers, and relies largely on extracellular Ca2+ influx via activation of L-, N- and P-type of Ca2+ channels. Finally, these responses are mediated by activation of both protein kinase A- and C-dependent mechanisms.

The role of calcium channels in substance P-induced contractile response in the rat iris.

This study was undertaken to assess the role of calcium channels in the contractile response induced by substance P in the isolated rat iris. Substance P produced graded and sustained contraction in the rat iris. Pre-incubation of preparations with thapsigargin (1 microM), verapamil (1 microM), isradipine (1 microM) or with omega-conotoxin MCIIA (0.1 microM) did not significantly inhibit substance P-mediated contraction in the isolated rat iris. However, pre-incubation of the preparations with nicardipine (1 microM) or ruthenium red (1 mM) caused parallel displacement to the right of the substance P concentration-response curve without affecting its maximal response. In contrast, amiloride (1 microM), markedly inhibited substance P-mediated contraction (73 +/- 5%), while econazole (1 mM) also significantly inhibited (44 +/- 11%) substance P-mediated contraction in the isolated rat iris. Collectively, these results suggest that substance P-mediated contractile response in the isolated rat iris depends largely on the influx of external Ca2+, by a mechanism which might involve the T-type calcium channels.

Study of the mechanisms involved in the bradykinin-induced contraction of the pig iris sphincter muscle in vitro.

This study was designed to investigate the mechanisms by which bradykinin induces contraction of the pig iris sphincter muscle in vitro. Addition of bradykinin, Lys-bradykinin and Met-Lys-bradykinin to the pig iris sphincter resulted in a graded contraction with a mean EC(50s) of 21, 11 and 5 nM, respectively. The bradykinin B(1) receptor agonist des-Arg(9)-bradykinin only caused a slight contraction, measured 6 h after the tissue was set up. The B(2) receptor antagonists FR 173657 ((E)-3-(6-acetamido-3-pyridyl)-N [N-2-4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]-N-methylamino-carbonyl-ethyl] acrylamide) and Hoe 140 (D-Arg(0)-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]-bradykinin produced a graded shift to the right associated with marked inhibition of the bradykinin-induced contraction. Atropine, guanethidine or tetrodotoxin significantly reduced the bradykinin-induced contraction. Dazoxiben, an inhibitor of thromboxane A(2), and MK-571 (3-(3-(2-(7-chloro-2-quinolinyl) ethenyl) phenyl ((3-dimethyl amino-3oxo-propyl) thio) methyl) propanoic acid, a leukotriene D(4) receptor-selective antagonist, also caused inhibition of the bradykinin-mediated contraction. Cyclooxygenase-1 and -2 inhibitors, indomethacin, ibuprofen, valeryl salicylate and NS 398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]methanosulfonamide) all significantly inhibited the bradykinin-mediated contraction without affecting the carbachol-induced contraction of the pig iris sphincter. Taken together, these results indicate that the bradykinin-mediated contraction of the pig iris sphincter muscle seems to be mediated primarily by the activation of the B(2) receptor release of acetylcholine, noradrenaline and both cyclooxygenase-1 and -2 metabolites besides the release of leukotriene D(4) and tromboxane A(2) from the arachidonic acid pathway.

Mechanisms mediating substance P-induced contraction in the rat iris in vitro.

PURPOSE: To determine some of the mechanisms by which substance P (SP) induces contraction in the isolated rat iris. METHODS: Rings of rat iris were mounted in a 5-ml organ chamber containing Krebs solution at 37 degrees C under basal tension of 75 mg, and isometric tension was recorded. RESULTS: Substance P produced graded contraction in the rat iris, being approximately 40-fold more potent than carbachol. Peptidase inhibitors (captopril, phosphoramidon, thiorphan) did not affect the SP response. The SP contraction was dependent on external Ca2+ by a mechanism resistant to both nifedipine and omega-conotoxin GVIA. Atropine and tetrodotoxin significantly shifted the SP response to the right (three- and fivefold, respectively). Neither phorbol nor genistein altered the SP-induced contraction, whereas staurosporine caused a weak inhibition. Indomethacin, pyrilamine, guanethidine, 8-37 calcitonin gene-related peptide (CGRP) fragment, and NG-nitro-L-arginine methyl ester had no effect on SP response. All the natural tachykinin agonists caused concentration-dependent contraction in rat iris with similar maximal responses. The NK3 selective agonist senktide caused graded contraction, being approximately 150-fold more active than the NK2 selective agonist [beta-ala] NKA. The NK1 selective agonist SP methyl ester induced a small contraction. The NK3 and NK2 antagonists SR 142801 and SR 48968 shifted the SP response to the right. Schilds plots gave pA2 (negative logarithm of the molar concentration of antagonist causing a twofold rightward displacement of the concentration response curves) values of 9.37 and 7.97 and slopes of 0.70 and 1.02, respectively. CONCLUSIONS: Substance P produces a potent contraction in the isolated rat iris that seems to depend on the neural release of acetylcholine by tetrodotoxin-sensitive mechanisms. Its response relies largely on external Ca2+, through mechanisms independent of activation of L- or N-type Ca2+ channels, and is probably mediated via activation of NK3 and NK2 receptors.

Biochemical studies on the secretion of glycoproteins by isolated ciliary body of rabbits.

The contribution of the ciliary body to the origin of vitreous proteins was investigated in rabbits by incubating explants of this eye component under novel conditions. At the end of incubations for up to 21 h, the tissues were processed histologically and were shown to be in an excellent state of morphological preservation. When radioactive amino acids and fucose were added to the culture medium, protein and glycoprotein synthesis and secretion were detected using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) plus fluorography. The origin of these secretory products was traced by autoradiography to the ciliary epithelium. When samples of vitreous bodies - injected intravitreally with the same radioactive precursors - were run beside samples of the tissue culture media, comigration of at least 8 radioactively labelled bands including the one previously identified as transferrin was detected. This indicates that some vitreous proteins may be secreted by the ciliary body and that cultures of explants of ciliary body-iris are useful tools for studies on vitreous protein secretion.

Parasympathetic denervation of the iris in Chagas' disease.

The parasympathetic innervation of the iris along with cardiovascular reflexes involving parasympathetic and sympathetic function were studied in 45 patients with Chagas's disease and in 36 controls. The autonomic features in Chagas' disease included 15 with cardiomyopathy, three with megaoesophagus and five with megacolon. None of the patients had orthostatic hypotension. Parasympathetic cardiac reflexes (deep breathing 30:15 ratio, Valsalva) were abnormal. There were exaggerated pupillary responses to dilute pilocarpine. These studies suggest iris parasympathetic denervation and favour more widespread cholinergic involvement in patients with Chagas' disease, than previously recognized.

Vascular effects of acetylcholinesterase inhibitors in the rabbit eye: a study with fasciculin and physostigmine.

The vascular effects of fasciculin and physostigmine, two acetylcholinesterase inhibitors, were studied with radioactively labelled microspheres in the rabbit eye. In addition, the effects on the intraocular pressure, pupil size and the aqueous humor protein concentration were determined. Both drugs were injected intracamerally in pentobarbital anesthetized and indomethacin pretreated animals. Fasciculin injected in a dose of 0.5 micrograms (0.7 x 10(-10)M) reduced blood flow in the anterior uvea as determined 30 and 60 min after injection. Higher doses had inconsistent effects. Physostigmine injected in a dose of 3 micrograms (1.1 x 10(-8)M) also reduced blood flow in the anterior uvea. The effect was most pronounced in the iris. Neither drug had any appreciable effect on choroidal or retinal blood flow. Both drugs caused pupillary constriction but the reduction in blood flow was not secondary to miosis. The effects on the intraocular pressure and aqueous humor protein concentration were inconsistent. The reduction in blood flow of the anterior uvea after intracameral injection of acetylcholinesterase inhibitors is consistent with a cholinergic vasoconstriction previously described in the eye during electrical stimulation of the oculomotor nerve.

Comparison of the anti-inflammatory effects of topically applied aspirin and indomethacin following photocoagulation of the rabbit iris.

1. A comparative study of the inhibitory action of topically applied indomethacin and aspirin (1% (w/v) 2 h before and immediately after trauma, totaling 4 mg each) on myosis, increase in intraocular pressure and breakdown of the blood aqueous barrier was performed. 2. Argon laser photocoagulation on the anterior surface of the left iris of pigmented rabbits, totaling 2,250 mJ, was used as traumatic stimulus. The untraumatized eye was used as a reference for measurements. 3. Four groups of 10 animals each (control, photocoagulated, photocoagulated plus indomethacin and photocoagulated plus aspirin) were studied. 4. Both drugs similarly inhibited the increase in the total protein concentration in aqueous humor and in intraocular pressure at 10, 20 and 40 min. Only aspirin showed some inhibitory action on the pupillary response 10 min after photocoagulation.

Comparison of the anti-inflammatory effects of topically applied aspirin and indomethacin following photocoagulation of the rabbit iris

A comparative study of the inhibitory action of topically applied indomethacin and aspirin (1% (w/v) 2 h before and immediately after trauma, totaling 4 mg each) on myosis, increase in intraocular pressure and breakdown of the blood aqueous barrier was performed. Argon laser photocoagulation on the anterior surface of the left iris of pigmented rabbits, totaling 2,250 mJ, was used as traumatic stimulus. The untraumatized eye was used as a reference for measurements. Four groups of 10 animals each (control, photocoagulated plus indomethacin and photocoagulated plus aspirin) were studied. Both drugs similarly inhibited the increase in the total protein concentration in aqueous humor and in intraocular pressure at 10,20 and 40 min. Only aspirin showed some inhibitory action on the pupillary response 10 min after photocoagulation

Morphine-induced pupillary fluctuation: physiological evidence against selective action on the Edinger-Westphal nucleus.

In the rat, the predominant pupillary effect of morphine sulfate (30 mg/kg, i.p.) is mydriasis, interrupted periodically by miotic excursions. Using infrared video pupillometry, respirometry and EEG recording, we had previously reported that miotic excursions are always correlated with the onset of EEG bursting, while mydriatic excursions are preceded by respiratory slowing and correlated with EEG burst cessation. In the current study, we found that during morphine-induced EEG bursting and related miosis, delivery of an alerting stimulus to the rat caused an immediate conversion sequence composed of respiratory slowing, burst cessation and mydriatic excursion. We also simulated morphine-induced EEG bursting through non-opioid means by delivering kindling electrical stimuli to the amygdala. When the stimulus was given during morphine-induced mydriasis, the stimulus-induced bursting resulted in a miotic excursion identical to spontaneous morphine-induced miotic excursions. These results indicate 1) that the reticular activating system is involved in morphine-induced mydriatic excursions and 2) that EEG bursting is not simply correlated with morphine-induced miotic excursions, but causes them. Collectively, these results strengthen our hypothesis that the Edinger-Westphal nucleus is not the site in which the selective, receptor-mediated pupillary effects of morphine are initiated.