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PubMed1999

The clinical efficacy of paremyd with and without dapiprazole in subjects with light and dark brown irides.

BACKGROUND: Paremyd, a mydriatic formulation of 0.25% tropicamide and 1.0% hydroxyamphetamine hydrobromide provides adequate dilation for binocular indirect ophthalmoscopy in young Caucasians. We studied the clinical effectiveness of Paremyd in dilating heavily pigmented eyes by comparing its mydriatic efficacy in Blacks, Asians and Caucasians with light and dark brown irides. We also evaluated the efficacy of one drop of dapiprazole (Rev-Eyes) in reversing Paremyd-induced mydriasis in our subject sample. METHODS: In a masked, randomized, controlled experimental design, several visual functions which included pupillary dilation, near visual acuity, amplitude of accommodation, ocular hyperemia, and discomfort glare were measured at 30-min intervals, for a total of 300 min, in subjects dilated with a single drop of Paremyd in each eye. Ease of binocular indirect ophthalmoscopy was also assessed. A 3-way analysis of variance was used to assess changes in these measures as function of irides color/pigmentation (designated as light or dark brown iris color), presence or absence of dapiprazole, and test time interval. RESULTS: We found that subjects in our light brown irides group (mainly Caucasians) dilated faster than subjects in our dark brown irides group (mainly Blacks). Dapiprazole increased the speed of recovery from pupillary dilation for all subjects, but more so for those with light rather than dark brown irides. Similarly, subjects with light rather than dark brown irides recovered accommodative function more quickly. Although neither the use of dapiprazole nor the degree of iris color/pigmentation was significantly related to visual acuity or glare discomfort, there was a clear trend that these visual measures were affected to a greater degree in subjects with dark brown (primarily Blacks) rather than light brown irides. Overall, Paremyd provided adequate dilation for binocular indirect ophthalmoscopy in all subjects irrespective of iris color/pigmentation. CONCLUSIONS: Our data indicate that a single drop of Paremyd provides adequate mydriasis, without significant side effects, for routine fundus examination of all subjects, independent of iris color/pigmentation. Furthermore, a single drop of dapiprazole was effective in speeding the return of pupillary dilation in most subjects, but had no significant effect on accommodation, near visual acuity or glare discomfort. Side effects such as stinging upon instillation, conjunctival hyperemia, and a few instances of ptosis, with possible additional cost to patients, appear to lessen its overall clinical benefit.

Accommodation, Ocular↗
PubMed1997

The influence of drop size of cyclopentolate, phenylephrine and tropicamide on pupil dilatation and systemic side effects in infants.

In this prospective study, microdrops (mean drop volume 5.6 microl) and commercially available standard drops (mean drop volume 35.4 microl) of cyclopentolate, phenylephrine and tropicamide's clinical efficacy and systemic side effects were compared. Sixty-one infants requiring diagnostic pupil dilatation were studied for pupillary diameter, systemic blood pressure, heart rate and skin flushing changes related to the instillation of mydriatic drops. Both microdrops and standard drops of the drugs produced significant increase in pupillary diameter compared with the baseline (p<0.01). In cyclopentolate and phenylephrine groups, there was no significant pupillary diameter changes between microdrops and standard drops (p>0.05). Mean blood pressure increased significantly in infants given standard drops. There was no significant change in the group that was given microdrops. In our opinion, reduced volume of mydriatics can prevent possible side effects.

Administration, Topical↗
PubMed1996

Systemic effects of screening for retinopathy of prematurity.

AIMS: To detect systemic complications of screening for retinopathy of prematurity (ROP), paying particular attention to the physical examination. METHODS: Oxygen saturation, pulse rate, and blood pressure were monitored before, during, and after 110 ROP screening examinations. RESULTS: Following topical mydriatics diastolic blood pressure was elevated by a mean of 6 (SD 7.2) mm Hg. Immediately after the examination there was a further rise in both systolic and diastolic pressure of 4.3 (14.5) mm Hg and 3.3 (11.6) mm Hg, respectively. Oxygen saturation and pulse rate remained stable during the control period and administration of eyedrops. Saturation fell by a median of 3% (95% confidence interval plus or minus 1.2%) after the examination while there was rise in pulse rate of 7 (SD 23.1) beats per minute. This change in pulse rate was not observed in infants on concurrent methylxanthine therapy. No infant had clinically significant changes at the end of the study. CONCLUSION: The initial changes in blood pressure may represent side effects of topical mydriatics but the later changes following the physical examination may be an additional response to the stress of ROP screening.

Anesthetics, Local↗
PubMed2003

Effect of ibopamine on aqueous humor production in normotensive humans.

PURPOSE: Ibopamine is a prodrug of epinine (deoxyepinephrine) that exhibits activity at dopaminergic and adrenergic receptors. Topical ocular application has been shown to cause mydriasis without cycloplegia and to increase the rate of aqueous humor flow in normotensive human eyes. Mydriasis can interfere with the measurement of aqueous flow. In this study ibopamine's effect on aqueous humor production was measured while making allowance for the potential artifact caused by its mydriatic effect. METHODS: The effects of topical ibopamine on pupillary diameter, aqueous humor flow measured by fluorophotometry, and intraocular pressure were studied in 24 healthy, blue-eyed humans. Ibopamine was administered with and without the alpha-adrenergic antagonist dapiprazole, and its effects were compared with those of tropicamide, with and without dapiprazole in a double-masked, randomized, crossover design. RESULTS: Ibopamine dilated the pupil from a diameter of 3.7 +/- 0.64 (mean +/- SD, n=24) to 7.7 +/- 0.70 mm. Ibopamine, during its peak mydriasis, was associated with a very large increase in the rate of clearance of topically applied fluorescein from the cornea and anterior chamber, an effect that was not associated with tropicamide during its peak mydriasis. The mydriatic effect of ibopamine was completely blocked by dapiprazole, and the increase in fluorescein clearance was partially blocked. When mydriasis was blocked, ibopamine increased fluorescein clearance by 13% (P<0.0001), which was interpreted as an increased rate of aqueous humor production. Compared with placebo and with the tropicamide control, ibopamine decreased intraocular pressure, despite its stimulation of aqueous humor flow. CONCLUSIONS: Ibopamine is in a specific class of drug, along with pilocarpine, epinephrine, and bimatoprost that in humans increases the rate of aqueous humor flow as measured by fluorophotometry. This effect is partly responsible for its ability to increase intraocular pressure in persons suspected to have abnormally low aqueous humor outflow facility. The transient apparent doubling of aqueous humor flow, measured by fluorescein clearance after administration of ibopamine is an artifact of increased fluorescein clearance through the dilated pupil while accommodation is active.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

The effects of 2% ibopamine eye drops on the intraocular pressure and pupil motility of patients with open-angle glaucoma.

PURPOSE: Ibopamine is a prodrug of N-methyldopamine that has a non-cycloplegic mydriatic action due to its alpha-adrenergic properties and is able to induce, when topically given, a transient increase of intraocular pressure (IOP) in eyes with hydrodynamic disorders. METHODS: This is a randomized, crossover, open-labeled, two- center study. Forty patients (20 open-angle glaucoma patients and 20 healthy subjects) were treated with ibopamine 2% eye drops and phenylephrine 10% eye drops. RESULTS: Ibopamine induced a significant increase in IOP only in glaucomatous eyes (p<0.001) without a significant hypertensive effect in normal eyes. Ibopamine and phenylephrine showed a similar mydriatic activity but ibopamine was able to induce an hypertensive effect only in glaucomatous eyes. CONCLUSIONS: The results confirm the use of ibopamine as provocative test in detection of hydrodynamic disorders.

Administration, Topical↗
PubMed1998

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↗
PubMed2004

[Phacoemulsification without mydriasis before surgery: benefits to the patient].

PURPOSE: The aim of our study was to evaluate the frequency of side effects (ataxia, dizziness and dry mouth) due to systemic absorption of parasympatholytic eye-drops, before phacoemulsification. METHODS: This single surgeon, prospective, randomized and controlled study included 303 consecutive patients selected to undergo phacoemulsification with topical and intracameral anesthesia. Patients were distributed in two groups; those receiving no mydriatics before surgery (n=151) as control group and those dilated with cyclopentolate 1% and tropicamide 1% eye-drops (n=152) as the study group. Ataxia, dizziness and dry mouth were recorded in both groups by the same observer. Surgery time and changes in systolic and diastolic blood pressures were noted. Note was also taken of the cases where pupil widening maneuvers and a second intracameral instillation of lidocaine 1% plus epinephrine 1/200,000 were needed. RESULTS: Fifteen patients (9.9%) suffered ataxia in the study group vs. three patients (2%) in the control group. Twenty-three patients (15.1%) suffered dizziness in the study group vs. two patients (1.3%) in the control group. Thirty patients (19.7%) experienced dry mouth in the study group vs. ten patients (6.6%) in the control group. No significant changes in blood pressures, surgery time and pupil dilating maneuvers were noted between groups. The odds ratio for a second intracameral instillation was 2.0 in the control group vs. the study group. CONCLUSIONS: Lidocaine 1% plus epinephrine 1/200,000 as an adjunct to topical anesthesia during phacoemulsification showed to be an effective and safe alternative to abolish side effects caused by systemic absorption of mydriatics eye-drops before surgery.

Aged↗
PubMed2002

Studies on a soft glycopyrrolate analog, SG-1.

A short-acting soft drug analog (SG-1) of glycopyrrolate (G) was developed by retrometabolic design in order to minimize systemic side effects and optimize the therapeutic index. SG-1,3-(1'-hydroxycyclopentyl)phenylacetoxy-1-methyl-1- methoxycarbonylpyrrolidinium bromide, was synthesized by: (a) esterification of phenylacetic acid with N-methyl-3-pyrrolidinol by DCC to obtain N-methyl-3-pyrrolidinyl phenylacetate; (b) reaction of lithium salt of above phenylacetates with cyclopentanone to obtain N-methyl-3-pyrrolidinyl 3-(1'-hydroxycyclopentyl)phenylacetate; and (c) quarternization with methyl bromoacetate in acetonitrile to give the designed product. To evaluate the pharmacological effect of SG-1, its mydriatic activity in rabbit eyes was compared to that of glycopyrrolate. At the pharmacodynamically equivalent doses (the lowest dose that induces the maximum response) of SG-1 (1%) and glycopyrrolate (0.1%), the mydriatic activities lasted for 5 and 100 h, respectively. Compared to glycopyrrolate, the intrinsic pupil dilation potency of SG-1 was lower (approximately 1/10th) but the duration of action was much shorter (< 1/20th) as SG-1 is susceptible to facile enzymatic hydrolysis/deactivation in the rabbit eyes. In vitro metabolism and stability investigations further supported this finding. In vitro half lives of SG-1 in rat plasma, blood, and 20% liver and lung tissue homogenates were 15.62, 53.86, 263.43, and 318.35 min, respectively. In human plasma and blood, half-lives were 19.93 and 88.32 min, respectively. SG-1 was relatively stable under acidic conditions (pH 5 and lower). SG-1 is a promising, clinically useful short acting anticholinergic.

Animals↗
PubMed1988

pH dependency of effect of topically applied dipivefrine hydrochloride on intraocular pressure and pupil size in rabbits: comparative studies with epinephrine.

The pH and dose dependencies of topically applied dipivefrine hydrochloride (DPE) on intraocular pressure (IOP) reduction and mydriasis were compared with those of epinephrine bitartrate (EPI) in normal rabbits. Statistically significantly greater IOP lowering and mydriatic effects of DPE solutions were achieved by increasing their pH from 3 to 6 or their concentrations from 0.02% to 0.1%. The ocular hypotensive and mydriatic effects of EPI also depended on their concentrations, but not on their pH. On the other hand, blink rates of rabbits following topical application of DPE tended to be reduced by the increase of pH, while they were not influenced by the concentrations. From these results, it was indicated that the pharmacological effects of DPE were augmented about 3 times by increasing the pH of its solutions from 3 to 5, which also was associated with reduction of ocular irritation, while the effects of EPI were not altered by the changes of pH. As the result of the increase of pH from 3 to 5, DPE became about 50 times more potent than EPI as a ocular hypotensive agent.

Administration, Topical↗
PubMed1982

Prevention of physostigmine-induced lethality in rats. A pharmacological analysis.

A systematic study of a large number of compounds from various pharmacological classes was performed to better define their interaction with the cholinergic nervous system. An 'in vivo' test procedure called 'physostigmine antagonism' in rats was used; it involved the administration of the test compounds, measurement of the pupil diameter and recording of the survival time after injection of a lethal dose of physostigmine. Known peripherally acting anticholinergics, such as isopropamide and methylscopolamine did not protect from physostigmine lethality at doses up to more than 150 times the mydriatic dose. Known centrally acting anticholinergics, such as dexetimide and benztropine, protected from lethality at doses equal to or slightly higher than the mydriatic dose. Penetration into the brain of a muscarinic blocking agent thus appeared to be a sufficient condition to significantly reduce the cholinergic overstimulation of the CNS that results from inhibition of acetylcholine hydrolysis. Drugs of other pharmacological classes that are known to have anticholinergic activity in addition to their more characteristic action, were also active in the physostigmine test. They include most of the tricyclic antidepressants, some antihistamines such as diphenhydramine and cyproheptadine, some ganglion blocking agents such as mecamylamine and the neuroleptic clozapine. Drugs with hypnotic or anticonvulsant properties, sedative neuroleptics and high doses of some members of other pharmacological classes protected from physostigmine-induced lethality by a mechanism not based on anticholinergic activity. The results further show that a number of pharmacological actions: dopamine, histamine H1 and serotonin S2 antagonism, MAO-inhibition, alpha-adrenergic blockade etc. are all insufficient to produce physostigmine antagonism.

Animals↗
PubMed1982

Atropine and mepenzolate mydriasis in rabbits: a comparative pupillographic analysis of two antimuscarinic agents.

The mydriatic effects of mepenzolate, a quarternary antimuscarinic agent, has been investigated and compared with those of atropine by pupillographic analysis in rabbits. The time-response curve for the onset of action for the agents (half-time, ca.5 min) was the same for the two agents despite the difference in structures. Although the half time for the offset of action (ca.18 and 34 hrs. for atropine and mepenzolate respectively) was different, the mydriatic effects of both agents were completely eliminated in 74 hrs.

Animals↗
PubMed1982

[Pupillometry, a clinical pharmacological model / Relevance and limits (author's transl)].

A new non-invasive clinical pharmacological model, developed at the Institut für Klinische Pharmakologie, Bobenheim (FR Germany), is reported. The principle of the model is the photographic determination of the diameter of the pupilla before and after administration of drugs active at the pupillar muscle. The area of the pupilla as a parameter of drug effect can be proceeded mathematically. With the reported model the area under the time curve, the pupillary index and the mean myotic or mydriatic time is determined. The area under the curve gives information about the extent of the drug effect. The pupillary index takes the maximum diameter into account and is even more sensitive than the area under the curve, correcting steep and flat profiles of the time curve. The mean mydriatic or myotic time gives a robust measurement concerning the duration of the drug effect. To prove the relevance of our model we used N,N-diethyl-N-(2-[alpha-(tricyclo(2.2.1.02.6)hept-3-ylidene)-benzyloxy]-ethyl)- amine hydrochloride (treptilamine hydrochloride, Asta S 5521) in four different dosages orally and intravenously. The results show: 1. The model is appropriate to show the effect of drugs on the smooth pupillary muscle concerning rate and extent. 2. The drug treptilamine hydrochloride does change the diameter of the pupils. 3. The drug is active after oral application.

Adolescent↗
PubMed1979

Effects of prostaglandins and norepinephrine on ocular pressure and pupil size in rabbits following bilateral cervical ganglionectomy.

We wish to report an early (10 to 30 min) 6 to 7 mm Hg increase in IOP above predrug levels following topical norepinephrine (NE) (5mumol) administration in conscious normal rabbits. This early elevation in IOP was significantly more pronounced in bilateral superior cervical ganglionectomized (BG) rabbits. The time course for peak IOP elevation slightly preceded the accompanying peak mydriatic effect in all groups. IOP returned to baseline levels in about 60 min in the BG rabbits, but the mydriasis persisted. Pretreatment with topical indomethacin significantly reversed the early hypertonic NE effect on IOP in the BG animals implying the involvement of prostaglandin synthesis. The IOP continued to fall significantly after 60 min in the BG group with indomethacin pretreatment. This latter result suggests a predominant long-lasting NE effect. The indomethacin pretreatment had no effect on pupil size of any group, but phenoxybenzamine (PBA) reduced the mydriatic effect, implying a direct or a predominant role of NE on iris muscle.

Animals↗
PubMed1996

Comparison of efficacy and tolerance between 1% hydroxyamphetamine plus 0.25% tropicamide (Paremyd) and 0.5% tropicamide combined with 2.5% phenylephrine.

BACKGROUND: Paremyd, consisting of a combination of 1.0 percent hydroxyamphetamine and 0.25 percent tropicamide, is a commercially available eyedrop used clinically for diagnostic mydriasis. This study sought to determine if one drop of Paremyd is equally effective and tolerable as the traditional combination of one drop each of 2.5 percent phenylephrine and 0.5 percent tropicamide. METHODS: A prospective, double-masked, randomized, cross-over study was conducted in 60 normal volunteers ranging from age 20 to 35 years (mean 24.3 years). Twenty-two subjects (36.7 percent) were male, and 32 subjects (53.3 percent) had brown irides. Pupil diameter, amplitude of accommodation, distance and near visual acuity, and subjective comfort of eyedrop instillation were assessed for 8 hours following drug instillation. RESULTS: Significantly more subjects (p < 0.05) experienced adverse ocular symptoms with the tropicamide plus phenylephrine (TP) combination than with Paremyd (P). There was no statistically significant (p > 0.05) difference in mydriatic response between TP and P. During the first hour, however, TP and P demonstrated significant (p = 0.001) differences in cycloplegic effect. CONCLUSIONS: Paremyd appears to be as effective a mydriatic as TP, but with greater comfort on instillation. Paremyd has less effect on accommodation.

Accommodation, Ocular↗
PubMed1980

Timolol and epinephrine: a clinical study of ocular interactions.

In a crossover design study, we assessed effects on intraocular pressure, pupillary diamter, pulse rate, and blood pressure over six hours of one drop of 0.5% timolol maleate and 2% epinephrine hydrochloride in one eye. Both eyes of each patient had been pretreated for one week with twice-daily applications pf epinephrine or timolol, respectively. In random sequence, 20 patients (40 eyes) participated in both phases of the study. Pretreatment with timolol significantly reduced the ocular hypotensive effect of epinephrine (from 15.3% to 4.6%); epinephrine pretreatment did not affect the pressure reduction of timolol. Pretreatment with timolol enhanced the mydriatic effect of epinephrine (from 35.8% to 71.9% pupillary dilation); pretreatment with epinephrine resulted in an apparent mydriatic effect for timolol.

Aged↗
PubMed1992

Screening for diabetic retinopathy: a relative cost-effectiveness analysis of alternative modalities and strategies.

Diabetic retinopathy is the most common cause of blindness among adults of working age in the UK. If the disease is detected early effective treatment can be provided and this has resulted in calls for a systematic national screening programme. Using data on the screening of 3423 diabetics collected as part of an experimental programme in three UK centres, the relative cost-effectiveness of various screening options is assessed. The paper utilises direct evidence on a number of single modality screening options, including ophthalmoscopy undertaken by general practitioners or ophthalmic opticians, and non-mydriatic photography. With the objective of increasing the sensitivity of screening and using data collected in the study, options based on two further potential screening strategies are modelled and evaluated: combined screening using both ophthalmoscopy and non-mydriatic photography; and selective screening where high-risk diabetics are directly referred to an ophthalmologist and low-risk cases are either left unscreened or are screened by one of the single or combined modality screening options. Given the objective of early detection, effectiveness is assessed in terms of the sensitivity and specificity of the referral decisions of screening options. Both health service and private resource costs of the various screening options are estimated, the latter in terms of travel and the opportunity cost of time. Cost effectiveness is evaluated in terms of the expected cost per true positive case of diabetic retinopathy referred by the screening options. To narrow the choice between the options, those subject to three-way domination with respect to the three choice variables of sensitivity, specificity and expected cost per true positive are excluded. Amongst the remaining options, the choice is dependent on the trade-off between the higher specifics of unselective single modality screening options and the higher sensitivities and lower expected costs per true positive case detected of combined modality and selective screening options.

Adult↗
PubMed1985

Studies on the mechanism of clonidine-induced mydriasis in the rat.

Intravenous administration of clonidine hydrochloride (3-100 micrograms/kg) produced a dose-dependent pupillary dilation in anaesthetized rats. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level. Clonidine-induced mydriasis was present only in those preparations having intact parasympathetic neural tone to the iris. Depletion of CNS monoamines by more than 95% with reserpine (5 mg/kg) and alpha-methyl-para-tyrosine (2 X 300 mg/kg) failed to alter the dose-response relation to clonidine. Pretreatment with the alpha-2-adrenoceptor antagonist, yohimbine hydrochloride (1.5 mg/kg), produced about a 10-fold shift to the right in the pupillary dose-response curve to clonidine. Yohimbine administered after the highest dose of clonidine also antagonized the mydriatic response. The above results suggest that clonidine acts on CNS post-synaptic alpha-2-adrenoceptors to produce mydriasis by withdrawal of parasympathetic neural tone to the iris. In an attempt to assess the physiological substrate(s) involved, mydriatic responses, due to parasympatho-inhibition, were evoked by electrical stimulation of ascending (sciatic nerve and medullary) and descending (hypothalamic) pathways. Yohimbine (0.3 and 1.0 mg/kg) produced a dose-dependent inhibition of the pupillary dilation evoked by stimulation of the sciatic nerve and medullary loci, whereas these doses of yohimbine failed to alter the dilation in response to hypothalamic stimulation. Similarly, monoamine depletion greatly antagonized the pupillary dilation elicited by sciatic nerve and medullary stimulation without significantly affecting mydriasis due to hypothalamic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

[Screening for diabetic retinopathy and optic disc topography with the "retinal thickness analyzer" (RTA)].

BACKGROUND: The RTA features a fundus photography mode and optic disc topography. Those two new modes were investigated regarding their clinical use. METHODS: First, the combination of wide-field photography with a retinal thickness map was assessed for tele-screening for diabetic retinopathy in 31 eyes. Second, normal values of the optic disc were collected on 30 non-glaucomatous probands in the non-mydriatic mode and compared to the results of the mydriatic mode, for which reproducibility was also investigated. RESULTS: For diabetic retinopathy, the RTA yielded mean 93% sensitivity for proliferative diabetic retinopathy and 100% sensitivity for detecting diabetic macular edema compared to clinical examination at specificities ranging from 58 to 96%. Regarding the measurements of the optic disc, the normal values in mydriasis coincided with those in miosis in all but 4 of 12 parameters. CONCLUSIONS: The RTA is suitable for application in tele-screening for diabetic retinopathy. The topography of the optic disc is highly reproducible and may be used for glaucoma diagnostics.

Diabetic Retinopathy↗