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PubMed1993

Efficacy of a pediatric cycloplegic administered as a spray.

BACKGROUND: The topical administration of eyedrops is often an unpleasant procedure in the pediatric population. We sought to learn whether a combination mydriatic-cycloplegic solution would be an effective cycloplegic if delivered as a spray. METHODS: We conducted a prospective, examiner-masked, parallel-group study and randomized 38 subjects (age range 6 months to 12 years, mean = 7.3 years) into four groups such that the same combination mydriatic-cycloplegic solution was administered under the following conditions: 1) eyedrops to eyes that were open; 2) eyedrops to eyes that were closed; 3) spray to eyes that were open; 4) spray to eyes that were closed. Both eyes of each subject received the solutions administered under one of the four conditions. Residual accommodation was measured using dynamic retinoscopy and the subjective push-up method, where applicable, at times 0, 10, 20, 30, 45, and 60 mins following administration of the medications. RESULTS: Repeated measures analysis of covariance revealed no statistically significant difference (p > 0.05) in cycloplegic efficacy among the four methods of drug delivery. CONCLUSIONS: The results of this study suggest that administering cycloplegics by spray to the closed eye is as efficacious as instilling eyedrops to the open eye. Use of a cycloplegic spray can have important clinical advantages compared to conventional cycloplegic eyedrops administered to children.

Accommodation, Ocular↗
PubMed1993

Soft drugs. 12: Design, syntheses and evaluation of soft anticholinergics.

Concepts involved in the design of soft drugs (drugs which, after achieving their therapeutic role, are metabolized in a predictable manner and at a controlled rate to non-toxic moieties) have been applied to methscopolamine (1). Selected aliphatic and cycloaliphatic esters (3) of a hypothetical carboxylic acid metabolite (2) of methscopolamine were designed and found to have anticholinergic activity. Six soft drug analogs of methscopolamine were tested for mydriatic activity in rabbit eye. At equieffective doses, the AUC24 hrs and the mydriatic recovery time were found to be significantly less with some of the soft drugs compared to methscopolamine and soft drug 3a was found to be shorter acting than tropicamide. At equieffective doses the AUC24 hrs for soft drugs ranged from 23.2% to 187% of that of methscopolamine. Significant dilation of the untreated eye was observed with scopolamine but not with the soft drugs after unilateral administration. Soft drug 3a exhibited only 2.3% of the AUC6 hrs (untreated eye) of that of methscopolamine.

Animals↗
PubMed1993

Differential effects of antimuscarinic agents on intestinal motility in the conscious dog.

In this study we investigated the effects of antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with electrodes along the small bowel. Furthermore, we evaluated the chronotropic and mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.: atropine, telenzepine (M1 antagonist), AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11-dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4-diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for atropine, telenzepine, AF-DX 116 and 4-DAMP, respectively. At doses lengthening the MMC period, atropine and 4-DAMP also induced tachycardia and mydriasis. At doses shortening the MMC period, telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally, AF-DX 116, at doses inducing marked tachycardia, had a minor intestinal effect and no mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Mass screening for diabetic retinopathy--a report on diabetic retinal screening in primary care clinics in Singapore.

INTRODUCTION: Mass screening for diabetic retinopathy is expensive and inaccessible if done by institutional ophthalmalogists. Most diabetics are seen in primary care. Hence it is logical to provide mass screening in primary care clinics. In Singapore, government polyclinics are ideal centres of screening as they are well organised and accessible to the community. SCREENING METHOD: An effective mass screening strategy must provide wide coverage, be low cost and have the ability to assess diabetic eyes accurately and quickly. Non-mydriatic fundal photography was used as the screening method. Mass coverage was achieved by rotating two cameras around six government polyclinics. Cost was reduced by training existing staff and organising the programme to provide a high turnover of screenees. The photographs were read by ophthalmologists in a government-owned hospital. Patients that required referral were referred to specialist eye clinics. RESULTS: A total of 13,296 patients were screened or rescreened during a period of 2 years (25 months). 2,911 patients or 21.8% of the total screened were found to have diabetic retinopathy. About half of these (10.8%) had sight threatening retinopathy. The most common sight threatening retinopathy was maculopathy (8.0%). Twenty-two percent of cases screened were referred. These include referral for other ocular conditions detected during the screening. CONCLUSION: Non-mydriatic fundal photography has proven to be both accessible and effective in screening diabetic eyes in urban Singapore and can be recommended for mass screening of diabetic eyes in the community.

Adult↗
PubMed1996

[Sleep modifies anticholinergic mydriasis].

In sleep, the eyelids are closed and the pupils narrow. The pupil width indicates alertness and, if it is narrow, sleepiness. The deeper the sleep, the narrower the pupil: miosis during drowsiness, sleep, sedation and general anesthesia relies on reduced inhibition of the oculomotor nucleus and, even more, on reduced sympathetic tone (it is as sympatholysis that accounts for the miosis exerted by the famous "cocktail lytique" onto an iris whose sphincter is weakened from briskly elevated IOP in angle-closure glaucoma). For whatever reason a lack of sympathetic tone occurs, a poor response to anticholinergic mydriatics will be the consequence. This communication is concerned with children who received tropicamide, cyclopentolate or atropine for diagnostic pupil dilation and cycloplegia but, during subsequent sleep, exhibited an unsatisfactory mydriatic response that could be overcome by additional administration of phenylephrine. Thus, parasympatholytic mydriasis can be proven to be a function of the sympathetic tone. The pupil shrinks during deep sleep even after atropine. If the conditions of deep sleep, sedation or general anesthesia are present and mydriasis needs to be maintained, an additional administration of a sympathomimetic compound is mandatory.

Anesthesia, General↗
PubMed1997

Ketorolac tromethamine in the maintenance of intraoperative mydriasis.

BACKGROUND AND OBJECTIVE: Mydriatics and antiprostaglandins are routinely applied preoperatively to facilitate the aspiration of cortical material during extracapsular cataract surgery and to prevent intraoperative miosis. Unfortunately, the ideal antiprostaglandin has yet to be introduced. This study represents the first prospective, case-controlled, randomized, masked, clinical trial comparing the efficacy of oral ketorolac tromethamine (KT) with the efficacy of topical flurbiprofen sodium (FS) and a placebo (normal saline) in maintaining intraoperative mydriasis without adrenaline in the irrigation solution. PATIENTS AND METHODS: Sixty-three patients, undergoing extracapsular cataract extraction with posterior chamber intraocular lens implantation, were randomly divided into three equal groups. Group 1 received 20 mg of oral KT 2 hours prior to surgery, group 2 received 0.03% FS topical solution at the recommended dosage, and group 3 received topical normal saline in a regimen identical to that of group 2. Identical mydriatics were used in both groups. The patients' pupils were measured at five stages of surgery. RESULTS: The mean pupillary diameters at each surgical stage were greater in group 1 than in group 2; however, the difference was not statistically significant. The pupils in group 3 were significantly smaller than those of group 1 or group 2 (P < .05). No systemic toxicity to KT was observed. Moreover, the need for additional postoperative analgesics was significantly greater in groups 2 and 3. CONCLUSIONS: Oral KT is safe, convenient, and as effective as topical FS, and has the added advantage of reducing postoperative pain.

Administration, Oral↗
PubMed1979

Persistent pupillary membrane: successful medical management.

Persistent pupillary membranes usually undergo considerable atrophy during the first year of life. A minimum pupillary diameter of 1.5 mm is necessary for normal retinal image formation. Mydriatics, fixation pattern determination, and occlusion therapy as indicated can obviate the need for coreoplasty in patients with an extensive persistence of the pupillary membrane. We successfully treated a patient who had an almost total persistence of the pupillary membrane.

Amblyopia↗
PubMed1986

Reduction of pupillary constriction during cataract surgery using suprofen.

The efficacy of a new nonsteroidal anti-inflammatory agent, suprofen, for reducing pupillary constriction during cataract surgery was ascertained in a double-masked, multicenter, clinical study. Prior to surgery 1.0% suprofen or a placebo was instilled; the surgeon's normal regimen of mydriatics and cycloplegics was used. Suprofen (209 patients) was far more effective than the placebo (203 patients) in maintaining a dilated pupil prior to intraocular lens (IOL) implantation (or instillation of a miotic). The mean pupillary area prior to IOL implantation was 6.3 sq mm larger (20% larger) in patients treated with suprofen than in patients receiving the placebo. The investigators' subjective evaluations of the adequacy of pupil size for IOL implantation and of the difficulty of IOL implantation favored patients treated with suprofen over those receiving the placebo.

Adult↗
PubMed1998

Screening for diabetic retinopathy: the utility of nonmydriatic retinal photography in Egyptian adults.

Although regular screening for diabetic retinopathy with ophthalmoscopy or retinal photography is widely recommended in the United States and Europe, few reports of its use in developing countries are available. We compared the performance of screening by retinal photography with that of indirect ophthalmoscopy by using data from a population-based survey of diabetes and its complications in Egypt. During that project, 427 persons with diabetes underwent an eye examination and fundus photography with a non-mydriatic camera through a dilated pupil. Data from the examinations of the right eye of each patient are presented. Ninety-two (22%) of the 427 retinal photographs were ungradable; in 58 eyes (63%), this was due to media opacity (42 eyes with cataract, 3 with corneal opacity, and 13 with both). Agreement between retinal photography and indirect ophthalmoscopy was poor (kappa = 0.33; 95% CI = 0.27-0.39) and primarily due to the large number of eyes (n = 79) with ungradable photographs that could be graded by ophthalmoscopy. None of these eyes was judged by ophthalmoscopy to have sight-threatening retinopathy. Fifty-four photographs were diagnosed with greater retinopathy than found on ophthalmoscopy. Retinal photography with the nonmydriatic camera through a dilated pupil is a useful method to screen for diabetic retinopathy in most adults in Egypt. However, such screening strategies have limited use in older persons and in persons with corneal disease or cataract.

Adult↗
PubMed1976

Synthesis and activity of (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride: a prodrug form of (R)-(-)-phenylephrine.

Optically pure (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride was synthesized by the following sequence: (R)-(-)-phenylephrine was condensed with acetone in the presence of calcium carbide to give an oxazolidine derivative and then treated with thallous ethoxide in ether followed by trimethylacetyl chloride to yield the phenolic ester. Finally, the oxazolidine ring was cleaved by one equivalent of hydrogen chloride in ethanol. Condensation of phenylephrine with benzaldehyde, with or without solvents, gave either 1,1,2-trimethyl-4,6-dihydroxy-1,2,3,4-tetrahydroisoquinoline or a mixture of side-chain oxazolidine and the tetrahydroisoquinoline. Condensation of epinephrine with opianic acid in pyridine also gave a tetrahydroisoquinoline only. When applied on rabbit eyes, the prodrug (R)-(-)-m-trimethylacetoxy-alpha[(methylamino)methyl]benzyl alcohol hydrochloride exhibited an unexpected, three times higher mydriatic activity than the corresponding racemic prodrug and was 15 times more active than the parent, (R)-(-)-phenylephrine.

Animals↗
PubMed1983

Penalization in strabismus.

Penalization includes all those methods apart from total occlusion which disturb the central vision of one eye by favouring the other eye. Penalization has a sensory action on functional amblyopia; moreover it also has a motor action, influencing the non-accommodative element of spasm in esotropia. Optical penalization is the most classical method. However, one should also be aware of penalization with partial occlusion or fogging, penalization with mydriatics, and penalization with sectors, which are very often used in association with the classical technique.

Amblyopia↗
PubMed1981

Guanethidine - adrenaline eye drops in glaucoma simplex. Pupil behaviour and response of intraocular pressure.

In the study reported here, the relation between the dilatation of the pupil and the course of intraocular pressure (IOP) is examined in open angle glaucoma patients and in glaucoma suspects after topical administration of the combination of guanethidine 3% and adrenaline 0.5% in one eye drop (GA). By treating one eye with GA and leaving the fellow eye untreated on the same day, there was a symmetrical response of IOP, independent of the mydriasis in the treated eyes. It leads to the conclusion that the mydriatic response has no influence on the course of IOP. The physiological explantation for the symmetrical course of IOP in both treated and untreated fellow eyes seems to be a mediation by the bloodstream of GA to the eye which was left untreated.

Drug Combinations↗
PubMedDate not supplied

Pupil size and the steady-state pattern reversal visual evoked cortical potential.

30 eye-healthy subjects were being examined, with their pupils reacting, mydriatic or miotic. Their pattern reversal visual evoked cortical potentials (PRVECP's) were recorded under steady-state conditions. Test conditions allowed establishing a statistically significant influence of pupil size on the PRVECP.

Cerebral Cortex↗
PubMed1982

Studies on the mechanism of methyl-dopa-induced mydriasis in the cat.

Alpha-methyl-Dopa (10-100 mg/kg, i.v.) produced a dose-dependent mydriasis in cats anaesthetized with pentobarbital (30 mg/kg, i.p.). The onset was gradual, reaching a maximum plateau in 2-2.5 h. Intracerebroventricular administration of 1 or 3 mg of alpha-methyl Dopa (MD) also produced pupillary dilation with a similar time course. These dosages were without effect when given intravenously. Pretreatment with the alpha 2-adrenoceptor antagonist, yohimbine (0.5 mg/kg i.v.), blocked the pupillary response to MD. The alpha 1-adrenoceptor antagonist, prazosin (1.0 mg/kg. i.p.), was ineffective. Selective enzymatic blockade with 3-hydroxy-benzyl-hydrazine (NSD-1015; 25 mg/kg, i.p.), a Dopa-decarboxylase enzyme inhibitor, as well as with bis (4-methyl-homopiperazinyl-thiocarbonyl) disulfide (FLA-63; 2.5 mg/kg, i.p.), a dopamine-beta-hydroxylase blocker, prevented the mydriatic effect of MD. These results support the hypothesis that MD produces a clonidine-like, CNS mediated mydriasis in the cat, primarily by action of its metabolite alpha-methyl-noradrenaline acting on alpha 2-adrenoceptors.

Animals↗
PubMed1975

Pupillometric studies in the beagle dog.

A method of measuring pupillary diameter in the dog using a Kowa RC-2 fundus camera, to which an eyepiece graticule had been fitted, is described. Pupil diameter was measured either directly by reading off from the calibrated graticule or from photographs. The pupillary diameters of 105 (53 male, 52 female) untreated English beagles aged between 8 and 32 months were measured under light intensities of 150-200 lux and 1000-1400 lux. Mydriatic and miotic pupillary diameters were measured in 62 male and 80 female dogs. Time-effect curves were plotted for two groups of 5 beagles receiving 75 mug/kg or 175 mug/kg atropine and 100 mug/kg or 300 mug/kg propantheline intravenously. The dose-effect curve for propantheline was found to be linear. A dose of 109 (97-121) mug/kg propantheline increased pupillary diameter by 3 mm, 20 min after administration. The time- and dose-effect curves, the significant sex differences and age dependency seen in this study indicate both a high degree of accuracy and the suitability of both of these methods for use in pharmacological and toxicological studies.

Age Factors↗
PubMed1980

Methyldopa produces central inhibition of parasympathetic activity in the cat.

alpha-Methyldopa (10-100 mg/kg i.v.) produced a dose-dependent pupillary dilation in anaesthetized cats which was antagonized by subsequent administration of yohimbine hydrochloride (0.5 mg/kg i.v.). The peak effects were observed approximately 2-3 h after injection. This alpha-methyldopa-induced mydriasis was present only when the parasympathetic innervation to the iris was intact. Prior treatment with yohimbine (0.5 mg/kg i.v.) 30 min before alpha-methyldopa also antagonized the mydriatic effect, whereas pretreatment with phenoxybenzamine (2.5 mg/kg i.v.) did not. In contrast, phenoxybenzamine, but not yohimbine, effectively antagonized the pupillary dilation produced by adrenaline (0.3-10.0 microgram/kg i.v.). These results suggest that alpha-methyldopa produces mydriasis in the cat by means of CNS inhibition of tonic outflow from the oculomotor nucleus and that an alpha-adrenergic inhibitory mechanism may be involved. This conclusion is supported further by experiments in which direct measurements of ciliary nerve activity were made.

Animals↗
PubMed1979

Evidence for a central postsynaptic action of clonidine.

Intravenous administration of clonidine (1--100 micrograms/kg) produces a dose-dependent mydriasis in cats by inhibition of parasympathetic tone to the iris. The magnitude of CNS-induced pupillary dilation was similar in both normal anaesthetized cats and in anaesthetized preparations pretreated with reserpine (5 mg/kg i.p.) and alpha-methyl-p-tyrosine (2 x 300 mg/kg i.p.). Pretreatment reduced the concentrations of noradrenaline, dopamine and serotonin to less than 3% of that control levels in most parts of the CNS in which these amines were measured. Clonidine produced bradycardia in control animals but not in pretreated cats. In amine depleted animals in which only one eye was innervated by the ciliary nerves (parasympathetic), clonidine produced mydriasis only on the innervated side. These experiments confirm our previous observations that clonidine produces mydriasis in the cat by means of inhibition of parasympathetic tone to the iris. It is concluded that if clonidine produces this effect by stimulating noradrenergic, dopaminergic or serotonergic receptors, then clonidine exerts its centrally-induced mydriatic effect by acting on post-synaptic mechanisms.

Animals↗
PubMed1998

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.

Antidotes↗