Experimental miotic cataract. I. Effects of miotics on lens structure, cation content, and hydration.
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Animals↗
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[Study of miotic cysts (cysts at edge of pupil caused by instillation of miotics)].
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Cysts↗
Untoward effects of miotic therapy in glaucoma. The mode of action of miotics.
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Glaucoma↗
[Influence of postoperative topical application of miotics after cataract extraction on intraocular pressure and the blood-aqueous barrier].
BACKGROUND: In the present study we evaluated the influence of topical miotics on intraocular pressure and the blood-aqueous barrier after uncomplicated phacoemulsification and PC-IOL implantation. PATIENTS AND METHODS: Fifty-two eyes were randomized into 2 groups: with miotics (n = 28) and without miotics (n = 24). The IOP was measured before, 6 h, 1 and 2 days after surgery. Measurement of aqueous flare was performed before and on days 1 and 2 after surgery. Patients with glaucoma, PEX or previous intraocular surgery were excluded. RESULTS: In the group without miotics the IOP was 17.9 mm Hg (+/- 3.34) 6 h postoperatively; in the second group it was 15.5 mm Hg (+/- 3.25); P = 0.04. On the first postoperative day the IOP measured in the group without miotics was 15.3 mm Hg (+/- 2.70) and with miotics 13.0 mm Hg (+/- 2. 28); P = 0.007. On the second day in the group without miotics the IOP was 13.9 mm Hg (+/- 3.05) and with miotics 12.60 mm Hg (+/- 2. 19); P = 0.53. The changes in aqueous flare on the first and second day after surgery showed no significant influence of miotics on the blood-aqueous barrier (P > 0.05). CONCLUSIONS: Immediate postoperative application of topical miotics led to a small yet significant reduction of the IOP during the first 24 h after surgery. Our data suggest that there is no need for pharmacological reduction of the IOP after uncomplicated cataract surgery.
Blood-Aqueous Barrier↗
The mechanism of peptidergic miosis. I. The structural basis of miotic potency among biologically active polypeptides.
The miotic potency of eleven naturally occurring polypeptides and poly-DL-alanine was tested on the isolated anterior segment of hooded rat and golden hamster eyes in order to gain information on the chemical nature of the peptides or classes of peptides which may be regarded as possible mediators of the miotic response of the mammalian eye to chemical irritants or mechanical or surgical trauma. Substance P, P-octapeptide, physalaemin and eledoisin, and eledoisin related peptide were found to be potent miotics on these preparations, yielding ED50 values in the range of 8 to 95 nM and complete pupillary constriction in the range of 100 to 1000 nM. This is comparable to the miotic potency of carbachol or serotonin. All of these peptides share a C-terminal sequence Phe-X-Gly-Leu-Met-NH2 (where "X" is a variable amino acid) which is characteristic of all tachykinins. Six other biologically active peptides or the synthetic poly-DL-alanine had no measureable miotic effect on these preparations up to a final concentration of 1000 to 10,000 nM. The miotic effect of SP on the rat iris was effectively, but not completely antagonized by the presence of 10(-7)M atropine sulfate in the incubation medium. Preliminary results indicate that the miotic effect of physalaemin, eledoisin and eledoisin related peptide on the anterior segment of rat eyes is similarly antagonized by atropine.
Animals↗
Miotics and retinal detachment: upgrading the community standard.
The majority of ophthalmologists who responded to a questionnaire regarding the relationship between miotics and retinal detachment felt that such a relationship does exist, and that myopia and aphakia/pseudophakia predispose to the formation of new retinal breaks or to retinal detachment from pre-existing breaks with miotics. Horseshoe breaks and dialyses are pre-existing lesions that should be treated prophylactically prior to miotic therapy. Patients with no predisposing pathology or whose eyes have lattice degeneration or operculated breaks should be warned of possible retinal detachment prior to starting miotics. Not performing a peripheral retina examination prior to prescribing a miotic is acceptable, but not optimal, medical practice. Examining the peripheral retina or obtaining a retina consultation prior to prescribing a miotic may be beneficial to the patient and could be invaluable in the defense of litigation.
Humans↗
Retinal detachment and miotic therapy.
We studied a series of 34 eyes in 31 patients in whom retinal detachment occurred during miotic therapy. In 14 eyes, the duration of miotic use before the development of detachment was two months or less. Most detachments occurred in detachment-prone eyes either by virtue of myopia (62%), aphakia (24%), ipsilateral lattice degeneration (38%) or retinal pathology, in the fellow eye (50%). Virtually all detachments were rhegmatogenous. Distributions of retinal breaks are similar to the corresponding profiles in detached eyes not receiving miotics. The observed phenomena may be accounted for mechanistically, either with or without the role of miotics, so a specific causal role cannot be assigned to any given miotic in any given case. However, our data suggest that detachment-prone eyes may be at increased risk with miotic use, and thus demand careful retinal evaluation and prophylaxis when ominous peripheral symptoms are present.
Adult↗
Miotic tolerance to sarin vapor exposure: role of the sympathetic and parasympathetic nervous systems.
O-isopropyl methylphosphonofluoridate, also known as sarin or GB, is a highly toxic organophosphorous compound that exerts its effect by inhibiting the enzyme acetylcholinesterase. While the effects of a single exposure to GB vapor are well characterized, the effects of multiple exposures to GB vapor are less clear. Previous studies in the rat and guinea pig have demonstrated that multiple exposures result in tolerance to the miotic effect of nerve agents. The aim of the present study was to examine potential mechanisms responsible for tolerance to the miotic effect of GB vapor that has been observed in the rat after multiple exposures. Multiple whole-body inhalation exposures to GB vapor were conducted in a dynamic airflow chamber. Exposures lasted 60 min and each of the three exposures occurred at 24-h intervals. The results of the present study demonstrate that the alpha-adrenergic antagonist phentolamine and the beta-adrenergic receptor antagonist propranolol did not affect the development of tolerance to the miotic effect of GB vapor, suggesting that enhanced sympathetic tone to the eye is not responsible for the observed tolerance. Administration of atropine before the first exposure prevented the tolerance to the miotic effect of GB vapor after the third exposure, suggesting that the tolerance is the result of muscarinic receptor desensitization secondary to receptor stimulation. The present study extends the findings of previous studies to strengthen the hypothesis that the miotic tolerance observed in the rat upon repeated exposure to nerve agents is due to desensitization of muscarinic acetylcholine receptors located on the pupillary sphincter.
Adrenergic alpha-Antagonists↗
Intraoperative miotics and posterior capsular opacification following phacoemulsification with intraocular lens insertion.
BACKGROUND AND OBJECTIVES: Posterior capsular opacification (PCO) is a frequent complication following phacoemulsification with intraocular lens (IOL) implantation. A series of consecutive patients receiving capsular bag-fixated, silicone IOL implants were assessed for both incidence of PCO and the administration of intraoperative miotics. PATIENTS AND METHODS: During a 5-year period, 477 consecutive eyes were retrospectively evaluated. Surgeries were grouped according to intraoperative miotic agent: 0.01% carbachol or 1.0% acetylcholine. Patients receiving no miotic drug served as a control group. Yttrium-aluminum-garnet (YAG) laser posterior capsulotomy was performed on patients with clinically significant PCO. RESULTS: The percentage of eyes requiring YAG laser capsulotomy was similar for the three groups: 21.6% (25 of 91) for the carbachol group, 18.4% (14 of 62) for the acetylcholine group, and 18.6% (53 of 232) for the control group. A chi-squared analysis indicated that the difference among the groups was not statistically significant. The three groups also had similar average follow-up times between surgery and YAG capsulotomy (carbachol group = 52.2 weeks, acetylcholine group = 47.5 weeks, and control group = 48.3 weeks). CONCLUSION: Intraocular miotics do not increase the incidence of PCO.
Acetylcholine↗
Solutions containing miotic agents: effects on corneal transendothelial electrical potential difference.
BACKGROUND: Anterior chamber miotic solutions are widely used during anterior chamber surgery. We examined the effects of solutions containing miotic agents such as carbachol and/or acetylcholine on corneal endothelial pumping activity. METHODS: We monitored, in vitro, the transendothelial electrical potential difference of isolated rabbit corneal endothelial preparations. As controls, we used solutions without miotics. RESULTS: We found that a solution containing 55 mM acetylcholine and minimal amounts of salts (Miochol E) maintains transendothelial electrical potential difference some 30% above control levels for up to 4 h. Two other solutions, one including balanced salts and 0.55 mM carbachol (Miostat), the other a mixture of 0.19 mM carbachol and 55 mM acetylcholine plus minimal salts, are adequate to maintain the potential difference at control levels. Lastly, a solution with acetylcholine but without any salts (Miochol) greatly decreases the potential difference, to 30% of the control level, in 100 min. CONCLUSION: Our results indicate that: (1) 55 mM (1%) acetylcholine stimulates the endothelial electrical potential difference; (2) addition of 0.19 mM (0.003%) carbachol negates the stimulatory effect of acetylcholine; and (3) absence of electrolytes severely depresses the endothelial electrical activity.
Administration, Topical↗
Enhanced miotic response to topical dilute pilocarpine in patients with Alzheimer's disease.
To determine whether miotic response to dilute (0.0625%, two drops) topical pilocarpine could be useful in detecting Alzheimer's disease (AD), we assessed the response in 14 AD patients and 10 control subjects. The miotic response to pilocarpine was significantly greater in AD patients than in control subjects (p < 0.001). In contrast, mydriatic response to the anticholinergic tropicamide (0.01%, one drop) failed to show a difference between the groups (p = 0.54). There was no significant correlation between the miotic and mydriatic responses in individuals. We conclude that dilute pilocarpine could be useful as a diagnostic tool in early AD.
Administration, Topical↗
A rapid method for measuring miotic activity of drugs in the intact mouse eye.
A rapid and precise method for evaluating the miotic activity of cholinergic drugs has been developed based on Long's method for measuring the rate of mydriasis. The rate of reversal of mydriasis developed previously in the intact mouse eye by a mild mydriatic (phenycyclidine) is used to evaluate the miotic activity. The method provides a useful tool for measuring and comparing the miotic activity of acetylcholine agonists and cholinesterase inhibitors.
Amides↗
Effects of latrunculin B on outflow facility, intraocular pressure, corneal thickness, and miotic and accommodative responses to pilocarpine in monkeys.
PURPOSE: To determine if low doses of topical latrunculin B (LAT-B) will increase outflow facility and decrease intraocular pressure (IOP) without adversely affecting the cornea, and inhibit miotic and accommodative responses to pilocarpine, in ocular normotensive monkeys. METHODS: Intraocular pressure was measured by Goldmann tonometry before and after one and nine dose(s) of 0.005% and 0.01% topical LAT-B/vehicle given twice daily on successive weeks. Outflow facility was then measured by perfusion following 15 doses. Central corneal thickness was measured by ultrasonic pachymetry before and after one and nine dose(s) of 0.01% LAT-B/vehicle. Pupillary diameter (calipers) and accommodation (refractometry) before and after one dose of 0.005% and 0.02% LAT-B were determined. RESULTS: LAT-B dose-dependently decreased IOP, multiple doses more than a single dose. Maximal hypotension after one 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 hypotension after nine 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 75 +/- 13% (n = 7; P < .005). Central corneal thickness was not changed after one or nine dose(s) of 0.01% LAT-B. The miotic and accommodative responses to intramuscular pilocarpine were dose-dependently inhibited. At 0.02% LAT-B, the inhibition of miosis was essentially complete when compared with the pre-LAT-B value, whereas the inhibition of accommodation was only about 25%. At 0.005% LAT-B, the effects were trivial. CONCLUSIONS: In ocular normotensive monkeys, 0.005/0.01% LAT-B administered topically increases outflow facility and/or decreases IOP, but does not affect the cornea. Multiple doses reduce IOP more than a single dose. LAT-B dose-dependently relaxes the iris sphincter and ciliary muscle, with some separation of the miotic and accommodative effects.
Accommodation, Ocular↗
Drugs affecting the cholinergic system in the intact mammalian eye. I. Evaluation of the miotic activity of acetylcholine-like drugs in the mouse eye.
The effect of concentration and pH on the miotic activity of five acetylcholine-like drugs were studied in the intact mouse eye. The data suggests that it is mainly the nonionized form of the drug which contributes to its miotic activity. Acetylcholine-like drugs, degradable by cholinesterases, exert their miotic activity at higher concentrations than do those which are resistant to enzymatic hydrolysis. More active acetylcholine-like drugs appear to be less sensitive to concentration changes.
Acetylcholine↗
Effects of flurbiprofen and suprofen on the miotic activity of 1% acetylcholine and 0.01% carbachol.
The nonsteroidal antiinflammatory agents (NSAIAs) flurbiprofen and suprofen applied topically to reduce miosis may counteract the desired effects of miotics used during ocular surgery. In a pigmented rabbit model, 1% acetylcholine was shown to cause a greater, significant initial (for the first 30 minutes) constriction (P less than .05) than 0.01% carbachol in eyes pretreated with flurbiprofen and suprofen. From 2 to 8 hours, NSAIA pretreatment had a greater miotic effect with carbachol than with acetylcholine. There were no significant differences between flurbiprofen and suprofen on the miotic effect of carbachol or acetylcholine.
Acetylcholine↗
Drug-biomolecule interactions: bioelectrometric study of the mechanism of carbachol interactions with the cornea and its relation to miotic activity.
The augmentation of carbachol miotic activity attributable to enhanced transcorneal absorption, which results from the action of cationic adjuvants included in ophthalmic vehicles, suggested a study of carbachol-corneal tissue interaction as a further step toward understanding the phenomenon. The present study was performed in vivo using an innocuous electrometric technique. A fixed charge density of the corneal epithelial surface versus carbachol concentration profile was obtained from the electrometric results; it revealed three distinct concentration regions defined by precipitous decreases of fixed charge over extremely small concentration ranges. This anomalous behavior is attributed to cooperative alterations in the binding affinities of fixed anionic sites on the tissue surface, which result in an all-or-none release of protons and/or other nicrocations. The unmasked anionic sites become reoccupied with carbachol except in the last region where the reoccupation by carbachol is competitive with other cations in the solution in contact with the surface. This behavior, postulated on the basis of the construction of a carbachol-tissue binding isotherm from which thermodynamic interaction affinities were computed, was corroborated by the observed dependency of the duration of miotic activity on carbachol concentration. Allosteric interactions between anionic binding sites, which are mediated through electron inductive and electrostatic field effects and likely involve a cooperative alteration in tissue water structure, are implicated as underlying the observed phenomena.
Animals↗
[Modification of the visual field during temporary interruption of miotic treatment].
The visual field of 27 eyes with chronic open angle glaucoma was examined with the "Octopus 1-2-3" automatic perimeter. The visual fields with and without miotics were compared using the "mean defect" (MD) as parameter. The MD decreases significatively (p = 0.003) after interruption of the miotic treatment. As presumed, the IOP and the pupillary diameter increased significantly (p less than 0.001). The CLV insignificatively decreased. The short term modifications of the pupillary diameter seem to be a more important factor than this of IOP.
Aged↗
Factors determining the potency of cholinomimetic miotic drugs and their effect upon the light reflex in man.
1. Television pupillometry was used to measure the effect of six topically applied cholinomimetic drugs on the resting diameter and light reflex amplitude of the human pupil. Drug potency was obtained from dose response curves. 2. The tertiary amines arecoline, aceclidine and pilocarpine were considerably more effective miotics than the choline esters carbachol, methacholine and acetylcholine. 3. All the drugs which caused miosis also reduced light reflex amplitude proportionally. 4. The in vitro potency of these drugs was also measured on preparations of rabbit iris sphincter and guinea pig ileum. 5. Dose response relationships for pilocarpine in man and in vitro showed evidence of partial agonist activity on the rabbit iris only. 6. A comparison of the in vivo and in vitro results showed that three factors influenced the potency of topically applied miotics: accessibility to the iris; sensitivity to cholinesterase; and cholinoceptor agonist potency.
Adult↗