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PubMedDate not supplied

Pupillary stretching. A new procedure in vitreous surgery.

During vitreoretinal procedure, 26 aphakic eyes with proliferative vitreoretinopathy and diabetic traction retinal detachment were treated with a new technique for surgical dilatation of a miotic immobile pupil. Four iris loop sutures were laid in such a way that stretching of the pupil in the main directions of the four quadrants was made possible, thus forming a large, square pupil. No functional iris lesion was caused in nine eyes that developed miosis only during surgery. The other 15 eyes already had a miotic and rigid pupil preoperatively. In all but one of these cases, the stretching caused multiple small sphincter tears. The pupils remained partially dilated, but showed a reaction to miotics and mydriatics.

Adult↗
PubMed1983

[Argyll-Robertson and other pupillary abnormalities in neurosyphilis--with special reference to the detection of peripheral lesions].

The pupillary disturbances in twenty five neurosyphilitic patients were investigated. Miotic, light-rigid pupils, i.e., Argyll-Robertson pupils were found in only three of these patients. One of three patients showed unilateral Argyll-Robertson pupil. Irregular margins of the iris were associated with these miotic, light-rigid pupils. Abnormal striations of the iris were found in four of eight non-miotic (medium size), light-rigid pupils. Cocaine or ephedrine produced dilatation of two of these pupils, and, following this mydriasis, the pupils were capable of constricting to light. These abnormalities of the iris were not found in slightly light-reactive pupil. The light-rigid pupil induced by long-term administration of neuroleptics and antiparkinson drug in comparison with Argyll-Robertson pupil was also mentioned, and the findings of many authorities who have proposed a peripheral nerve pathogenesis of the Argyll-Robertson syndrome were reviewed.

Antipsychotic Agents↗
PubMed1995

Reversal of tropicamide mydriasis with single instillations of pilocarpine can induce substantial pseudo-myopia in young adults.

Pupillary dilation for diagnostic purpose has become an increasingly common procedure in UK optometry in recent years and the consensus seems currently to militate against the routine use of miotics; an eye that is judged safe to dilate is thought to be at minimal risk during the natural recovery phase to normal pupil size. Nevertheless, the optometrist does, on occasion, need to consider whether there might be some advantage in minimising the sometimes debilitating effects of cycloplegia and mydriasis produced in young adults by tropicamide. In this context we compare the effects of single instillations of two miotic agents: the alpha-adrenoceptor antagonist thymoxamine HCl (0.5%), and the parasympathomimetic pilocarpine HCl (1 and 2%). Tropicamide was used to induce mydriasis in a group of 12 volunteer student subjects aged 20-26 years (7 males, 5 female; mean 21.67 years) selected to provide low (L; n = 4), medium (M; n = 4) and high (H; n = 4) iris pigment levels. Measurements of pupil diameter (Brocca pupillometer), Snellen visual acuity and accommodative amplitude (near point rule) were made every 3 min over a 90 min recording period for 4 trials: (1) a control condition whereby a miotic was not employed; (2) thymoxamine HCl 0.5% was instilled after 30 min; (3) and (4) pilocarpine 1% and 2% was instilled after 30 min, respectively. Tropicamide induced a mean increase in pupil area from 25 to 50 mm2 after 22 min which was generally sustained over the 90 min period and was enhanced for the lower pigment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1994

Adverse effects of topical antiglaucoma medication. I. The conjunctival cell profile.

OBJECTIVE: To determine the effect of various long-term topical antiglaucoma regimens on the cell population profile of the conjunctiva. METHODS: Conjunctival biopsy specimens from 124 patients undergoing filtration surgery were assessed quantitatively by light microscopy. Preoperatively, the patients had used a drug for only a brief period (group A; n = 28), a beta-blocker alone (group B; n = 31), a beta-blocker in combination with a miotic (group C; n = 33), or a combination of beta-blocker, miotic, and sympathomimetic (group D; n = 32). RESULTS: The conjunctiva in groups A and B was similar. Group C conjunctiva differed, but the changes were most marked in biopsy specimens from patients in group D, where there was a significant decrease in goblet cells (P < .05); increase in pale cells, macrophages, and lymphocytes within the epithelium (P < .001); and increase in fibroblasts (P < .001), macrophages (P < .001), mast cells (P < .05), and lymphocytes (P = .01) in the substantia propria. In addition, the effect of duration of therapy was assessed. Administration of topical medication for more than 3 years was found to increase the numbers of pale cells within the epithelium (P < .05); fibroblasts (P < .05), macrophages (P < .001), lymphocytes (P < .01), and mast cells (P = .001) within the superficial substantia propria; and the numbers of fibroblasts (P = .01) and macrophages (P < .05) within the deep substantia propria. CONCLUSIONS: The compared treatment regimens affected the conjunctiva to different degrees, with multiple-drug topical therapy exerting the greatest effect on the degree of subclinical inflammation within the conjunctiva. The results also indicated that administration of topical medication, irrespective of type, for 3 years or more induced a significant degree of subclinical inflammation.

Administration, Topical↗
PubMed1994

Adverse effects of topical antiglaucoma medication. II. The outcome of filtration surgery.

OBJECTIVE: To determine the effect of long-term topical antiglaucoma therapy on the results of glaucoma filtration surgery and to relate any differences to the cell population profile of the conjunctiva. METHODS: Filtration surgery was performed in 124 patients (trabeculectomy in 112 and triple procedures [trabeculectomy, cataract extraction, and intraocular lens implantation] in 12), and the outcome of these procedures was assessed after a minimum follow-up of 6 months. A conjunctival biopsy specimen was obtained at the time of surgery. The patients were divided into four groups according to the type of topical therapy administered. The duration of therapy tended to be greater for the patients treated with a greater number of medication types. The outcome of trabeculectomy was assessed in 106 of the patients. RESULTS: In comparison with the briefly treated-primary surgery group, the success rate of trabeculectomy (90% [n = 28]) was similar to that in the group treated with beta-blockers (93% [n = 29]). The trabeculectomy success rate for patients treated with beta-blockers and miotics was significantly lower (72%, P < .01 [n = 29]), and that for the group treated with beta-blockers, miotics, and sympathomimetics was even lower (45%, P < .001, [n = 20]). CONCLUSIONS: Various treatment regimens were associated with differential effects on the success rate of trabeculectomy. Long-term topical combination therapy was identified as a significant risk factor for failure of trabeculectomy. Preoperative conjunctival cell counts from patients whose trabeculectomies were successful were compared with those whose trabeculectomies failed. Failure was associated with significantly more pale cells (P < .01), macrophages (P < .05), and lymphocytes (P < .05) in the epithelium; fibroblasts (P < .05) and macrophages (P < .05) in the superficial substantia propria; and both macrophages and lymphocytes in the deep substantia propria (P < .01). Thus, preoperative subclinical conjunctival inflammation induced by previous topical medication was identified as a risk factor for failure of trabeculectomy.

Administration, Topical↗
PubMed1984

Pupillary constriction by bradykinin and capsaicin: mode of action.

The application of bradykinin or capsaicin to the rabbit eye evoked strong miosis. The effect could be prevented by pretreatment of the eye with tetrodotoxin (TTX) or a substance P (SP) antagonist. However, the miotic response could be elicited despite TTX or the SP antagonist if the dose of capsaicin or bradykinin was increased. Bradykinin and capsaicin contracted the isolated rabbit sphincter pupillae muscle. The contraction produced by bradykinin and capsaicin was unaffected by TTX but reduced by specific SP antagonists. This indicates that bradykinin and capsaicin exert their effects on the isolated sphincter muscle through the release of SP but independent of neuronal conduction. In vivo, the situation seems to be different. The finding that TTX is capable of blocking the miotic response to moderate doses of bradykinin and capsaicin suggests that the effect on the eye under these circumstances is dependent upon a normal impulse traffic.

Animals↗
PubMed1983

Efficacy of combining timolol with other antiglaucoma medications.

The ocular hypotensive effects of timolol and a carbonic anhydrase inhibitor (acetazolamide or methazolamide) are partially additive; that is, concurrent administration of these drugs produces a clinically useful reduction in intraocular pressure which is greater than the effect of either medication alone, but less than the arithmetic sum of the effects of the individual drugs. Similarly, concurrent administration of timolol and a miotic agent (pilocarpine, carbachol, or echothiophate iodide) produces a clinically useful response in most glaucoma patients. In contrast, the ocular hypotensive effects of timolol and epinephrine are poorly additive. Only a minority of patients maintain a substantial, longterm reduction in intraocular pressure when timolol is added to a regimen of epinephrine or vice versa. Ophthalmologists prescribing timolol or epinephrine for patients receiving the other drug are urged to use a therapeutic trial to one eye for several weeks to determine the efficacy of concurrent treatment. The addition of timolol to the medical regimen of patients uncontrolled on maximum tolerated antiglaucoma therapy (a miotic agent, epinephrine and a carbonic anhydrase inhibitor) reduces intraocular pressure substantially in one-third to one-half of the cases.

Acetazolamide↗
PubMed1979

Timolol therapy in secondary angle-closure glaucoma post penetrating keratoplasty.

Timolol maleate (o.25% or 0.5% twice a day) was used in 13 eyes of 13 patients with secondary angle-closure glaucoma post penetrating keratoplasty uncontrolled on miotics, carbonic anhydrase inhibitors, or both. When added to each patient's current regimen, tomolol controlled 9 of the 13 eyes that no longer required cyclocryotherapy, and it was well tolerated locally and systemically. Its ocular hypotensive effect appears to supplement miotics and carbonic anhydrase inhibitors.

Carbonic Anhydrase Inhibitors↗
PubMed1979

A pharmacologist looks at medical treatment in glaucoma--in retrospect and in prospect.

The histochemical distribution of carbonic anhydrase activity in the ciliary processes is shown. There is a multiplicity of possible points of attack of carbonic anhydrase inhibitors, We do not know which sites are critically inhibited at clinical dosage. One primary mechanism of the therapeutic action of miotics is ciliary muscle contraction, but on prolonged treatment, subsensitivity of the muscle may shift emphasis to miotic inhibition of aqueous secretion by unknown mechanisms. The trabecular meshwork is a slow tissue living off the aqueous. Aqueous composition in chronic simple glaucoma should therefore be studied with a view to possible treatment of the sick meshwork.

Animals↗
PubMed1996

Effects of acetylcholine and carbachol on bovine corneal endothelial cells in vitro.

PURPOSE: To assess the relative cytotoxicity of Miochol (1% acetylcholine and mannitol), Miostat (0.01% carbachol, sodium, potassium, magnesium, and calcium salts), and their individual components using in vitro models of bovine corneal endothelial cells (BCECs). SETTING: Laboratories of the Departments of Ophthalmology and Physiology, The University of Texas Health Science Center, Houston. METHODS: The study was divided into four experiments. Experiment 1 used a confluent model to compare the relative cytotoxicity of Miochol and Miostat on BCECs following short-term exposure. In Experiments 2, 3, and 4, the proliferation model (preconfluent BCECs) was used to detect the possible cytotoxicity of individual components in the commercial preparations of the miotics; i.e., the preconfluent BCECs were exposed to buffered salt solutions containing mannitol (1%, 3%, and 4%), acetylcholine (0.5%, 1%, and 2%), or carbachol (0.1%, 0.5%, and 1%) for 3 hours. RESULTS: Confluent BCECs exposed to Miochol for 30 minutes underwent necrosis and degeneration, while those treated with Miostat did not show any morphological changes. None of the tested solutions except 2% acetylcholine and 1% carbachol caused observable changes in the nuclear densities of BCECs at 24, 72, 120, and 168 hours. CONCLUSION: The major components of Miochol (acetylcholine and mannitol) were found to be nontoxic; the cytotoxicity of the preparation was possibly due to the lack of an appropriate balanced salt solution. These findings may influence the selection of a miotic for use during intraocular surgery.

Acetylcholine↗
PubMed2003

Effect of pupil size on multifocal pattern visual evoked potentials.

The purpose of this study was to investigate the influence of pupil diameter on the amplitude and latency of multifocal visual evoked potentials (mfVEP). The multifocal objective perimeter (Accumap; Objectivision) was used to stimulate the visual field at 56 sites extending to 32 degrees using a pseudo-random pattern stimulus. The mfVEP were recorded using bipolar occipital electrodes, 7 min/eye. Ten normal subjects were recruited from the community and one eye was randomly selected for testing. The mfVEP were recorded at four different pupil diameters (2 mm, 4 mm, 6 mm, 8 mm), obtained by applying tropicamide (0.5%) or pilocarpine (2%) in different dilutions. Appropriate refractive correction was provided to overcome cycloplegia and achieve a visual acuity of 6/7.5 or better. Analysis revealed that at most pupil diameters the normalized full field amplitude did not show significant variation, except at the most miotic pupil diameter (2 mm), where the amplitude became reduced, based on 2-way anova and Tukey's T method. There was, however, significant correlation between latency and pupil area (correlation coefficient: upper field -0.63, lower field -0.76). The results suggest that even in the presence of mydriatics or miotics, the mfVEP test can be used to assess diseases that affect amplitude, provided near correction is used. The interpretation of latency, however, must be made with caution, as a borderline conduction defect with a dilated pupil may appear normal.

Adult↗
PubMedDate not supplied

Visoltricin, a novel biologically active compound produced by Fusarium tricinctum.

The major compound responsible for toxicity to Artemia salina of some Fusarium tricinctum strains has been isolated, and its structure has been elucidated by spectroscopical methods, i.e. UV, IR, MS, 1H-NMR and 13C-NMR. The novel compound, trivially named visoltricin, is the first imidazole derivative produced by Fusarium spp., and its structure has been established as the methyl ester of 3-[1-methyl-4-(3-methyl-2-butenyl)-imidazol-5yl]-2-propenoic acid (molecular formula C13H18N2O2; MW = 234.297). Visoltricin was toxic to A. salina larvae (LD50 = 8.5 x 10(-7) M), and inhibited the growth of six human tumour cell lines (out of 60 lines tested) at concentrations lower than 10(-5) M. Tested on rabbit eye it showed an interesting miotic activity similar to that of pilocarpine, a miotic agent largely used in the therapy of glaucoma. This biological activity could be explained in part by the anticholinesterase properties shown by visoltricin towards both human serum and pure enzymes (EC 3.1.1.7 and EC 3.1.1.8). Kinetics studies showed for visoltricin a mixed-type and reversible inhibition of the EC 3.1.1.7 enzyme with the competitive inhibition constant (Ki) = 1.9 x 10(-4) M.

Animals↗
PubMedDate not supplied

In vivo evaluation of submicron emulsions with pilocarpine: the effect of pH and chemical form of the drug.

Submicron emulsions containing 2.0% w/v pilocarpine as pilocarpine HCl, soybean oil (10% w/v) and egg lecithin (1.2% w/v) were formulated. Emulsions at pH 5.0, 6.5 and 8.5 were applied to the rabbit's eye, and the reduction in pupil diameter was measured for 6 h. The miotic effect was compared with that obtained with aqueous solutions at the same pH. A prolonged miotic effect was observed when the submicron emulsion was used as a vehicle. After application of emulsions at pH 5.0, 6.5 or 8.5, the time when 20% reduction of pupil diameter was still observed was 3.9 +/- 1.1 h, 4.3 +/- 1.3 h and 5.3 +/- 0.8 h, respectively, while, after application of a solution, this parameter was shorter by 30-40%. AUC(0-6h) values were larger after application of the submicron emulsions in comparison to aqueous solutions; however, statistically significant differences were only observed for emulsions at pH 6.5. Although the bioavailability of the drug is pH dependent, emulsions at higher pH cannot be considered for clinical use because of pilocarpine degradation which occurs with a similar rate as in aqueous solutions. Introduction of pilocarpine into the oily phase in the form of pilocarpine base or its oleate did not improve either the physicochemical or the pharmacological properties of the formulations. Irrespective of the pH and chemical form of pilocarpine used for emulsion preparation, practically all drug was found in the aqueous phase of the emulsion; thus, partitioning to the oily phase was negligible.

Animals↗
PubMed1981

Ocular responses to antidromic trigeminal stimulation, intracameral prostaglandin E1 and E2, capsaicin and substance P.

The role of nerve conduction was studied in acute experimental uveitis caused by antidromic trigeminal nerve stimulation, prostaglandin E1 and E2 (PGE1 and PGE2), capsaicin and substance P (SP). Systemic indomethacin was used to prevent formation of endogenous prostaglandins, and intracameral injection of tetrodotoxin (TTX) was used to block nerve conduction. 10 micrograms TTX prevented the miosis and reduced the rise in intraocular pressure (IOP) usually caused by antidromic trigeminal nerve stimulation. At a low dose of PGE1 the IOP rise was blocked by TTX. At higher doses of PGE1 and PGE2 the pressure effect was not blocked by TTX; the miotic effect was markedly diminished. Capsaicin caused a rise in IOP that was almost totally blocked by TTX, while the miosis at high doses seemed unaffected. At low doses, capsaicin-induced miosis could be abolished by TTX. SP caused miosis in TTX treated eyes similar to that in untreated eyes; the IOP rise was delayed by TTX. The results indicate that nerve conduction plays a role in the IOP reaction caused by low doses of PGE1 and by capsaicin and SP. The mechanism suggested is an axon reflex, elicited in the anterior uvea and resulting in transmitter release in the ciliary processes. Nerve conduction with release of SP or a similar substance in the iris seems to be required for the miotic effects of PGE1 and PGE2. SP and capsaicin are similar in not requiring nerve conduction to cause miosis, but the capsaicin effect probably requires presence of nerves, since denervated eyes--which respond to SP--have been reported no to respond to capsaicin does similar to those used here.

Animals↗
PubMed1978

Effect of vehicle on pilocarpine-induced miosis.

To determine the effect of 1.4% polyvinyl alcohol (PVA) and castor oil vehicles on the pilocarpine-induced miosis, we studied the miotic effect of 2% pilocarpine-PVA and oily drops on 4 young and 10 elderly people and the miotic effect of 4% pilocarpine-PVA and oily drops on 13 elderly people. The miosis developed fast within 15 min, and maximum miosis was rached within 1 h. Oily drops of pilocarpine induced stronger maximum miosis than corresponding PVA-drops. The pupil remained contracted to less than 50% of its starting diameter after pilocarpine-PVA drops for 3-4 h and after oily drops for 9 h and returned to its starting diameter after pilocarpine-PVA drops 9-10 h and after oily drops 20-24 h following administration. The difference in the effect between pilocarpine-PVA and oily drops was independent of the subjects' age.

Adult↗
PubMed1978

Implantation of a scleral strip into the supraciliary space and cyclodialysis in glaucoma.

Since 1975 the operation of implantation of a scleral strip (10 mm long and 2 mm wide) has been performed on 75 glaucomatous patients. The following variants of surgical technique were used: (1) implantation of an autoscleral strip into the supraciliary space, (2) implantation of an autoscleral strip combined with cyclodialysis and (3) implantation of a homoscleral (cadaver) strip combined with cyclodialysis. The first technique was employed in 12 cases. The intraocular pressure was controlled by surgery alone in only four eyes, though a decrease in the level of the intraocular pressure and an increase in the C-value occurred in each case. No significant difference between the results obtained with the second and the third techniques was found. Of 63 eyes operated on, the intraocular pressure was controlled in 41 eyes (65%) by surgery alone and in 11 other eyes with the help of miotics 3 to 4 weeks after surgery. Follow-up was for a period of from 12 to 23 months in 51 cases. The pressure was under control in 36 eyes (71%) without medication and in 10 more eyes with miotics. The rate of complications was low. Hyphaema appeared in 10 cases and mild iridocyclitis occurred in 11 cases. There was no case of choroidal detachment, persistent hypotony or flat anterior chamber after surgery.

Anterior Chamber↗
PubMed2004

Persistency and treatment failure in newly diagnosed open angle glaucoma patients in the United Kingdom.

AIM: To determine utilisation patterns and calculate treatment failure and discontinuation rates in patients with open angle glaucoma treated in the United Kingdom with any of six groups of intraocular pressure (IOP) lowering agents. METHODS: The UK General Practice Research Database was used to identify newly diagnosed (after 1 January 1997) open angle glaucoma patients who were naive to therapy with any of six index drug groups: carbonic anhydrase inhibitors, latanoprost, miotics, sympathomimetics, timolol, and other (non-timolol) beta blockers. Analyses included drug treatment data for 1 year following diagnosis. Outcomes were (1) time to therapy failure, defined as either change in index drug (replacement or addition of therapy) or patient referral for surgery, and (2) time to therapy discontinuation, defined as either therapy failure or no refill of the index drug in a period twice that covered by the first prescription fill. Cox proportional hazard regression and Kaplan-Meier and life table methods were used to compare groups. RESULTS: Among the 2001 eligible patients, a beta blocker other than timolol was the most widely prescribed (42%), followed by timolol (32%), carbonic anhydrase inhibitors (10%), and latanoprost (7%). Compared to latanoprost, those treated with any alternative agent were significantly more likely to fail (p < or = 0.005 for each comparison) and to discontinue (p < or = 0.05 for each comparison) therapy. Failure rates ranged from 13% (latanoprost) to 45% (sympathomimetics), and discontinuation rates ranged from 30% (latanoprost) to 63% (miotics). CONCLUSION: Latanoprost treated patients demonstrated lower rates of therapy failure and therapy discontinuation compared with patients treated with other widely used IOP lowering medications, including beta blockers.

Adrenergic beta-Antagonists↗
PubMed2006

Characterization of pilocarpine-loaded chitosan/Carbopol nanoparticles.

Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The physicochemical properties of the prepared nanoparticles were investigated using dynamic light scattering, zeta-potential, transmission electron microscopy, Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The sustained-release effects of pilocarpine-loaded nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and compared with pilocarpine in solution, gel and liposomes. We found that the prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested that an electrostatic interaction between CS and Carbopol contributes at least in part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared with pilocarpine in solution, gel or liposomes, the best slow-release profile of pilocarpine from the prepared nanoparticles occurred in a dissolution test. In the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the most significant long-lasting decrease in the pupil diameter of rabbits. The advantages of CS and Carbopol are good biocompatibility, biodegradability and low toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol nanoparticles may provide an excellent potential alternative ophthalmic sustained-release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles may also be useful for a variety of other therapeutic delivery systems.

Acrylic Resins↗