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PubMed1998

Effect of intraocular acetylcholine and carbachol on the corneal endothelium. In vivo comparative study.

The purpose of this study is to evaluate differences in corneal endothelial cell loss after intraocular use of two different miotics in subjects who have undergone extracapsular cataract extraction with posterior chamber intraocular lens implantation. The patients were divided into two groups: the first received 1 ml of 1% acetylcholine chloride and the second 0.5 ml of 0.01% carbachol as intraocular miotics. The endothelial count was done preoperatively and then 1 month after cataract extraction. There were no statistically significant differences in the mean cell loss between both groups. The authors believe that both miotics could be used in cataract surgery.

Acetylcholine↗

PubMedDate not supplied

The role of drug treatment in children with strabismus and amblyopia.

Strabismus, or misalignment of the eyes, is a common ophthalmic problem in childhood, affecting 2 to 5% of the preschool population. Amblyopia is an important cause of visual morbidity frequently associated with strabismus, and both conditions should be treated simultaneously. Pharmacological means for treating strabismus and amblyopia can be divided into 3 categories: paralytic agents (botulinum toxin) used directly on the extraocular muscles to affect eye movements; autonomic agents (atropine, miotics) used topically to manipulate the refractive status of the eye and thereby affect alignment, focus and amblyopia; and centrally acting agents, including levodopa and citicoline, which affect the central visual system abnormalities in amblyopia. Botulinum toxin, the paralytic agent that causes the clinical symptoms of botulism poisoning, can be injected in minute quantities to achieve controlled paralysis of the extraocular muscles. Although the role of botulinum toxin is established in adults with paralytic strabismus, its usefulness in the treatment of comitant childhood strabismus (primary esotropia and exotropia) is not universally accepted. Botulinum injections tend to be more effective with smaller degrees of strabismus, in patients with good binocular fusion, and in managing overcorrections or undercorrections after traditional muscle surgery. Inadvertent ptosis and paralysis of adjacent muscles, unpredictable responses and technical constraints of the injections limit its use in children. Miotic therapy, by altering the refractive state of the treated eye, offers an alternative to optical correction with bifocals in treating esotropia due to excessive accommodative convergence. It is also effective in treating residual esotropia following surgery. The ease of use of glasses restricts the wide application of miotics in these common strabismus syndromes. Atropine, an anticholinergic agent, paralyses the ability of the eye to focus or accommodate. In amblyopia therapy, atropine is used to blur vision in the non-amblyopic eye and offers a useful alternative to traditional occlusion therapy with patching, especially in older children who are not compliant with patching. The neurotransmitter precursor levodopa and the related compound citicoline have been demonstrated to improve vision in amblyopic eyes. The therapeutic role of these centrally acting agents in the clinical management of amblyopia remains unproven.

Amblyopia↗

PubMed1975

Bioavailability analysis of chlorpromazine in humans from pupilometric data.

Results of studying the time variation of the miotic response intensity for periods of 6 to 8 hours after dosing in up to 16 normal human subjects who received various oral liquid and intravenous doses of chlorpromazine are reported. Relative to oral liquid doses of chlorpromazine syrup, intravenous doses of the drug slowly infused over a consistent time interval of 30 minutes are approximately 11 times as potent in eliciting miotic response activity. Miotic activity was found to be quite dose sensitive as seen from the response vs. time profiles and the dose-effect curves constructed as plots of areas under the response curves and peak response intensities. The dose-effect curves are approximately linear for both intravenous and oral dosing over the majority of the dose ranges studied. Pupilometry is demonstrated as providing a highly sensitive, reliable, rapid and convenient method for detecting differences in both rates and extents of systemic chlorpromazine bioavailability after parenteral or oral dosing with chlorpromazine. Pupilometry allows comparative bioavailability studies to be readily completed for low oral doses, e.g., 10 mg/70 kg, which are not possible to perform even under the most ideal conditions, using the best direct assay techniques presently available. It is precisely at such low oral doses that bioavailability between oral dosage forms are most pronounced and the use of pupilometry has its greatest utility.

Administration, Oral↗

PubMed2004

Effect of low-dose latrunculin B on anterior segment physiologic features in the monkey eye.

OBJECTIVES: To determine if low doses of topical latrunculin B (LAT-B) will increase outflow facility and decrease intraocular pressure without damaging the cornea and if they will inhibit miotic and accommodative responses to pilocarpine in monkeys. METHODS: We measured intraocular pressure (Goldmann tonometry) before and after 1 and 9 doses of 0.005% and 0.01% topical LAT-B and vehicle given twice daily on successive weeks; outflow facility (perfusion) following 15 doses; central corneal thickness (ultrasonic pachymetry) before and after 1 and 9 doses of 0.01% LAT-B and vehicle; pupillary diameter (calipers); and accommodation (refractometry) before and after 1 dose of 0.005% and 0.02% LAT-B. RESULTS: Latrunculin-B dose-dependently decreased intraocular pressure, multiple doses more than a single dose. Maximal mean +/- SEM hypotension after 1 dose was 2.5 +/- 0.3 mm Hg (0.005% LAT-B; n = 8; P<.001) or 2.7 +/- 0.6 mm Hg (0.01% LAT-B; n = 8; P<.005); maximal mean +/- SEM hypotension after 9 doses was 3.2 +/- 0.5 mm Hg (0.005% LAT-B; n = 8; P<.001) or 4.4 +/- 0.6 mm Hg (0.01% LAT-B; n = 8; P<.001). Outflow facility was increased by mean +/- SEM 75% +/- 13% (n = 7; P<.005). Central corneal thickness was not changed after 1 or 9 doses of 0.01% LAT-B. Miotic and accommodative responses to intramuscular pilocarpine were dose-dependently inhibited. With 0.02% LAT-B, inhibition of miosis was substantial, whereas the inhibition of accommodation was only about 25%. With 0.005% LAT-B, the effects were trivial. CONCLUSIONS: In ocular normotensive monkeys, 0.005% and 0.01% LAT-B administered topically increases outflow facility and/or decreases intraocular pressure without corneal effects. Multiple doses reduce intraocular pressure more than a single dose. Latrunculin-B dose-dependently relaxes the iris sphincter and ciliary muscle, with some separation of miotic and accommodative effects. Clinical Relevance Multiple treatments with low topical doses of LAT-B may substantially reduce outflow resistance in eyes with glaucoma without adversely affecting the cornea.

Accommodation, Ocular↗

PubMed1982

Distinguishing postganglionic from preganglionic lesions. Studies in rabbits with surgically produced Horner's syndrome.

It has been suggested that the pupillary response to hydroxyamphetamine hydrobromide eyedrops will separate distal from proximal lesions of the sympathetic pathway from the brain to the eye (the pupil fails to dilate in postganglionic lesions). We studied the pupillary response to hydroxyamphetamine in two groups of rabbits with surgically produced Horner's syndrome. Rabbits in one group had postganglionic lesions. In all animals, a miotic pupil developed ipsilateral to the surgical lesion, and oculosympathetic paresis was confirmed in each by testing pupillary response to topically applied cocaine. In rabbits with postganglionic lesions, hydroxyamphetamine failed to dilate the miotic (Horner's) pupils as well as it dilated the normal pupils, while in rabbits with preganglionic lesions both miotic and normal pupils dilated equally. Hydroxyamphetamine appears to be a diagnostically useful drug in Horner's syndrome.

Amphetamines↗

PubMed1997

Relationship between pupil size and acetylcholinesterase activity in patients exposed to sarin vapor.

OBJECTIVE: To elucidate the effect of sarin vapor on pupil size and erythrocyte acetylcholinesterase activity (AchE). DESIGN: Retrospective observational survey. SETTING: Emergency department of an urban teaching hospital. PATIENTS: 80 patients who were exposed to sarin in a terrorist attack in Tokyo subways. MEASUREMENTS AND RESULTS: Pupil size and AchE activity on the day of exposure were measured. Among the 80 patients, the pupils were miotic (< 3 mm) in 50 patients (62.5%), while AchE activity was below the normal range (< 1.2 U) in 34 patients (42.5%). AchE was significantly lower in the miotic group than in the group with normal pupils (1.0 +/- 0.5 U vs 1.5 +/- 0.3 U, p < 0.01). In the miotic group, AchE activity was lower than normal in 32 patients (64.0%) but was decreased in only 2 patients in the normal pupil group (6.7%) (p < 0.01). CONCLUSIONS: Miosis is a more sensitive index of exposure to sarin vapor than erythrocyte AchE. Systemic poisoning is apparently less likely to develop if the patient's pupil size is normal on arrival at the hospital.

Acetylcholinesterase↗

PubMed1993

C-terminal calcitonin gene-related peptide fragments and vasopressin but not somatostatin-28 induce miosis in monkeys.

The miotic effects of C-terminal calcitonin gene-related peptide (CGRP) fragments, somatostatin-28 and vasopressin have been evaluated with special attention being paid to possible interactions with cholecystokinin (CCK)A receptors. The peptides were injected intracamerally to anesthetized monkeys pretreated with indomethacin and atropine. CGRP-(32-37) induced a miosis with a potency 1000 times lower than that previously found with sulphated CCK-8. Two other fragments, CGRP-(30-37) and CGRP-(31-37), also had miotic properties. The CGRP-(32-37)-induced miosis was antagonized by the CCKA receptor antagonist loxiglumide. No contractile effect was elicited by 67 pmol-7.4 nmol somatostatin-28. Vasopressin (360 pmol) caused a small reduction in pupil size. Loxiglumide pretreatment did not affect the reduction in pupil size but a vasopressin receptor antagonist partly inhibited the response. The results indicate that CGRP-(32-37) is a miotic with low potency but high efficacy in the monkey eye, probably interacting with CCKA receptors, and that vasopressin is a mitotic with low potency and efficacy, probably acting via vasopressin receptors.

Analysis of Variance↗

PubMedDate not supplied

Neurotensin-induced miosis: the role of dopaminergic pathways.

In this study we investigated the role that dopaminergic pathways play in the miotic effect exerted by neurotensin after intracameral administration. Neurotensin was injected into the anterior chamber (AC) at a dose of 30 micrograms to 4 groups of albino rabbits which had previously undergone the following treatment: a) desmethylimipramine IM and, after 30 min, 6-hydroxydopamine IV 7 days prior to the neurotensin administration; b) haloperidol IM for 15 days; c) haloperidol AC 10 minutes before the neurotensin administration. Our data confirm previous observations regarding the miotic activity of neurotensin and suggest that the dopaminergic system plays an important role in the miotic effect of neurotensin.

Animals↗

PubMed2004

Effect of brimonidine tartrate 0.2% ophthalmic solution on pupil size.

PURPOSE: To evaluate the effect of brimonidine tartrate 0.2% ophthalmic solution on pupil size under scotopic and photopic luminance conditions in persons considering laser refractive surgery. SETTING: Ophthalmic Health Center, Tel Aviv, Israel. METHODS: The pupil size was measured in 36 eyes of 36 participants under scotopic and photopic conditions using the Colvard pupillometer (Oasis Medical) before and after brimonidine tartrate drops were administered. The pupil size was subsequently measured after 30 minutes and 4 and 6 hours. RESULTS: No difference was found in pupil size before brimonidine tartrate instillation in eyes with light or dark irides. Before instillation, the mean photopic pupil size was 4.81 mm +/- 0.54 (SD) (range 4.0 to 6.0 mm). At 30 minutes, all pupils became miotic, with a mean size of 3.77 +/- 0.51 mm (range 3.0 to 5.0 mm) (P<.0001). After 6 hours, 27.8% of the pupils had returned to their previous size. Before brimonidine tartrate administration, the mean scotopic pupil size was 6.22 +/- 0.73 mm (range 5.0 to 8.0 mm). There was significant miosis to 4.57 +/- 0.84 mm (range 3.0 to 6.5 mm) (P<.0001) that continued for at least 6 hours. The miotic effect of brimonidine tartrate was stronger in eyes with light irides. CONCLUSIONS: Brimonidine tartrate caused significant miosis, especially under scotopic conditions, most likely from its alpha-2 adrenergic effect. Under photopic luminance conditions, the miotic effect was pronounced.

Adrenergic alpha-Agonists↗

PubMed1991

Apraclonidine prophylaxis for postcycloplegic intraocular pressure spikes.

A randomized, prospective, double-masked study was undertaken to determine the risk of postcycloplegic intraocular pressure spikes in patients with open-angle glaucoma and to evaluate apraclonidine prophylaxis in minimizing these spikes. Patients were stratified as miotic treated or untreated and each group was randomized to receive either placebo (artificial tears) or apraclonidine in both eyes before instillation of tropicamide. In both the miotic treated and untreated groups that received placebo, there was a high incidence, (37% and 38%, respectively) of clinically significant (greater than or equal to 6 mmHg) intraocular pressure spikes after instillation of tropicamide. In both the miotic treated and untreated groups, there was a statistically significant difference in postcycloplegic intraocular pressure between the subgroup that received placebo and the group that received apraclonidine prophylaxis (P = 0.003 and P = 0.006, respectively). Additionally, four eyes that received placebo had a spike of over 10 mmHg (range, 12 to 27 mmHg), while only one eye had an increase of greater than 10 mmHg (12 mmHg) in the apraclonidine group. Thus, apraclonidine appears to be a useful agent for minimizing precipitous increases in intraocular pressure after cycloplegia in eyes of open-angle glaucoma patients prone to this complication of cycloplegia.

Adrenergic alpha-Agonists↗

PubMed1998

Evaluation of pluronic F127-based sustained-release ocular delivery systems for pilocarpine using the albino rabbit eye model.

The overall objective of this study was to develop Pluronic F127 (PF127)-containing formulations of pilocarpine hydrochloride (PHCL) which can be used for sustained-release ocular delivery of PHCL. The PF127 formulations of PHCL containing methylcellulose (MC) or hydroxypropyl methylcellulose (HPMC) as an additive had previously exhibited the slowest dissolution rates and released the drug the slowest in vitro. This study was performed to assess the in vivo performance of these two formulations using miosis in the albino rabbit eye produced by PHCL as a measure of ocular bioavailability. The PF127MC formulation (20 microL) had a significantly greater intensity of miosis compared to the same volume of an isotonic solution of PHCL. The duration and the intensity of the miotic response increased significantly as the instilled volume of the PF127MC gel formulation increased. The miotic response, expressed as % bioactivity by assigning a value of 100% to the 20 microL PF127MC treatment, was increased as the volume instilled was reduced from 60 to 20 microL. However, no difference in bioactivity between the 60 and 100 microL volumes was observed. In addition, the 100 microL volumes of both the PF127MC and PF127HPMC gel formulations exhibited bioactivity equivalent to 20 microL of an isotonic PHCL solution. Thus, for a given instilled concentration, the larger the volume instilled the greater the amount of drug present in tear fluid and thus the higher the concentration delivered to the iris sphincter muscle and hence the greater the miotic response. However, the fraction of the dose reaching the iris sphincter muscle was greater for the smaller instilled volume. On the basis of these findings and previous in vitro results, the PF127 formulations of PHCL having MC or HPMC as an additive showed considerable potential as sustained-release ocular delivery systems for PHCL. This conclusion was based upon their ability to provide a substantial prolongation of drug action and an improvement in the ocular bioavailability of pilocarpine compared to conventional eye drops and previously utilized PF127 formulations of PHCL. It appears that ocular bioavailability can be increased more readily by altering both the rheological characteristics of the delivery system and by using a smaller dose volume.

Animals↗

PubMed1990

The progress of the visual field in chronic simple glaucoma and ocular hypertension treated topically with pilocarpine or with timolol.

It is theoretically possible that the vascular effects of topical sympathetic beta-blocking therapy in chronic simple glaucoma (CSG) might tend to neutralise the beneficial effect of a reduced intraocular pressure on the preservation of the visual field. We therefore followed the progress of 422 right eyes and 420 left eyes of 483 patients with CSG and 119 right eyes and 132 left eyes of 151 patients with an original diagnosis of ocular hypertension (OH). These patients were observed for a minimum of one year and up to 13 years, being followed for an average of 5.1 years in the case of CSG and of 4.5 years in OH. The majority of eyes with CSG were treated topically with a miotic and 38% of these received beta blocking therapy in the form of topical timolol. It was concluded that despite suggestions that beta blockers might reduce vascular perfusion of the optic nerve head, which might in turn cause an adverse effect on the visual field progress, the results of this analysis showed that there was less mean deterioration of visual field in eyes treated with beta blocker plus miotic treatment compared with those on miotic therapy alone.

Administration, Topical↗

PubMed1986

[Surgical pupillary dilatation within the scope of complicated retinal detachment surgery].

During vitreoretinal surgery 14 aphakic patients with complicated retinal detachment were treated with 2 new techniques for surgical dilatation of a miotic and rigid pupil. In 4 cases, iris excision was not performed in the upper part of the pars pupillaris, as usual, but in the lower part. As a result, peripheral anterior synechiae due to silicone oil injection did not occur postoperatively. In the other 10 cases the pupil was temporarily stretched during the operation with 4 iris loop sutures. These sutures were laid in such a way that a retraction of the iris in the main directions of the 4 quadrants was made possible, thereby forming a large square pupil. Postoperatively, no iris damage was found in those cases where miosis had only developed during surgery. In the case of a preoperatively miotic and rigid pupil, stretching caused multiple small sphincter tears in most cases. A few weeks after surgery these patients again showed constriction of the pupil. Their pupils reacted to light, miotics, and mydriatics, but reactions were diminished.

Diabetic Retinopathy↗

PubMed1985

Effects of somatostatin, a somatostatin analog, neurotensin and met-enkephalin in the eye with special reference to the irritative response.

The effects of somatostatin, cyclo(D-Trp-Lys-Thr-Phe-Pro-Phe) acetate, a somatostatin analog, neurotensin, and met-enkephalin were studied in the rabbit eye by measuring the intraocular pressure (IOP), aqueous humor protein concentration, ocular blood flow and the pupil diameter. Somatostatin or the analog injected intracamerally (10 micrograms/eye) and infused intra-arterially (0.6-4 micrograms/min) had no significant effect on the parameters studied in normal eyes. However, somatostatin and, particularly, the analog attenuated the miotic response to a standard nociceptive stimulus consisting of topical application of 1% neutral formaldehyde. The other component parts of the irritative response were not attenuated. Intracameral injection of 1-2 micrograms neurotensin caused vasodilation in the anterior segment of the eye, a slight increase in aqueous humor protein concentration, and some decrease in IOP. Intracameral injection of 1-50 micrograms met-enkephalin had no effect on the blood-aqueous barrier, IOP or the pupil diameter. Neither did this dose of met-enkephalin attenuate the miotic response to exogenous substance P. It seems likely that somatostatin and the somatostatin analog attenuate the miotic response to nociceptive stimuli by preventing the release of a substance, presumably substance P, from sensory nerves.

Animals↗

PubMed1999

Pharmacological profile of a new topical pilocarpine formulation.

A new formulation based on pilocarpine hyaluronate salt has been shown to improve the bioavailability of the drug and to extend the duration of activity. We evaluated the extent of intraocular pressure reduction, the duration of action and the kinetics of miotic response of this formulation in comparison with a commercial preparation with the same drug concentration. Ocular hypertension in the rabbit was induced by alpha-chymotrypsin or by water loading. The hypotensive effect of the new formulation treatment was significantly greater and longer than that observed in rabbit eyes treated with the commercial preparation both in the normotensive and in the hypertensive animals. Furthermore, we evaluated the miotic response in normotensive rabbits showing a greater miotic response and an extended duration when the eyes were treated with the new formulation. The pharmacological profile of the new formulation described in this study indicates an increase of efficacy and duration of action compared to the commercial preparation.

Animals↗

PubMed1980

The effects of sensory denervation on the responses of the rabbit eye to prostaglandin E1, bradykinin and substance P.

1 Six to eight days after diathermic destruction of the fifth cranial nerve in the rabbit, the ocular hypertensive and miotic responses to intracameral administration of capsaicin, bradykinin, and prostaglandin E1 were greatly reduced or completely abolished. The response to substance P was not abolished. 2 A response could still be obtained to chemical irritants 36 h after coagulation of the nerve and it is deduced that manifestation of the response is dependent upon functional sensory nerve terminals, and is independent of central connections. 3 It is suggested that prostaglandin E1 and bradykinin act directly upon the sensory nerve endings and that propagation of the response is augmented by axon reflex. 4 In view of the ability of substance P to induce miosis in the denervated eyes, it is presumed that its actions are not mediated via sensory nerves. 5 It is considered possible that the mediator(s) released from sensory nerve endings after chemical irritation or antidromic stimulation may act in the same way as substance P with regard to the miotic effect. 6 Synthetic substance P will only produce ocular hypertension in doses which induce a maximal miotic response. This may either be a question of access or a partial resemblance to the endogenous mediator.

Animals↗

PubMed1978

Experience with trepanotrabeculectomy.

The authors analysed the effect of 100 trepanotrabeculectomy operations performed in primary (79 cases), in congenital (16 cases) and in secondary (5 cases) types of glaucoma. The operation itself could normalize the intraocular pressure in 87% of the cases, in 8% the intraocular pressure was normalized by miotics after the operation. In 3% of the cases the pressure could not be controlled even by the additional application of miotics and in 2% of the cases the operation produced a hypotony. The intraoperative and postoperative complications were temporary and without definitive sequels. As the blebs were present in 76% of cases, the authors concluded that the drainage took place under the scleral and conjunctival flap. In the smaller group, the blebs were absent but the intraocular tension was normalized. In these cases it is supposed that Schlemm's canal represents the main route of drainage. According to the authors' experience, trapanotrabeculectomy represents an operation which is easy to perform, which can not cause severe operative or postoperative complications and which can achieve normalization of the intraocular pressure, either by itself or with miotics, in a high percentage of cases.

Adolescent↗

PubMed1999

Comparison of the effects of diazepam on the fear-potentiated startle reflex and the fear-inhibited light reflex in man.

It has been shown previously that the amplitude of the acoustic startle reflex is enhanced, and the amplitude of the light reflex reduced, when subjects anticipate an aversive event, compared to periods when subjects are resting ('fear-potentiated startle reflex' and 'fear-inhibited light reflex'). We examined whether the anxiolytic diazepam would reverse the effects of threat on the startle and pupillary reflexes. Twelve male volunteers participated in three weekly sessions in which they received oral treatment with placebo, diazepam 5 mg and diazepam 10 mg, according to a balanced crossover double-blind design. One hour after ingestion of the treatments, miotic responses to light pulses and electromyographic responses of the orbicularis oculi muscle to sound pulses were elicited during alternating periods in which the threat of an electric shock (electrodes attached to the subject's wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with a significant increase in the amplitude of the electromyographic (EMG) response, a significant reduction of the miotic response amplitude, and an increase in self-rated anxiety. Diazepam attenuated all these effects of THREAT. Diazepam did not affect the amplitude of the miotic response under the SAFE condition, but did suppress the EMG response under this condition. These results confirm the validity of the fear-potentiated startle reflex and fear-inhibited light reflex as laboratory models of human anxiety, and reveal some differences between the effects of diazepam on the two reflexes.

Acoustic Stimulation↗