[The mydriatic effect of high doses of serotonin on the rabbit pupil in vivo].
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Effects of pretreatment with mydriatics on intraocular penetration of 0.1% pranoprofen.
The mechanism by which an increase in the intraocular concentration of topically applied 0.1% pranoprofen (PPF) is induced by pretreatment with Mydrin P (0.5% tropicamide and 0.5% phenylephrine) was studied in rabbit eyes. In separate experiments, solutions of each of the various ingredients contained in Mydrin P ophthalmic solution were applied 60 minutes prior to instillation of PPF. Ninety minutes after PPF instillation, its concentration in the cornea, aqueous humor and iris-ciliary body were measured by high performance liquid chromatography. PPF concentration was not increased by pretreatment with benzalkonium chloride, chlorobutanol or tropicamide, but was increased by pretreatment with phenylephrine (PHE). After the latter, the PPF concentration was 2 to 3 times higher than that obtained without Mydrin P. It is noteworthy that the concentration of PHE in the aqueous humor also was found to be increased about 3 times in the presence of PPF. The lipophilicity of PPF, judged by the octanol/buffer partition coefficient, was increased when mixed with PHE. These findings indicate that the increase in intraocular PPF concentration after pretreatment with Mydrin P was caused by PHE. This may be attributable to the enhancement of corneal permeability to PPF resulting from formation of an ion-pair complex between the anionic PPF and the cationic PHE.
Animals↗
The influence of age, duration of diabetes, cataract, and pupil size on image quality in digital photographic retinal screening.
OBJECTIVE: To evaluate the effect of age, duration of diabetes, cataract, and pupil size on the image quality in digital photographic screening. RESEARCH DESIGN AND METHODS: Randomized groups of 3,650 patients had one-field, non-mydriatic, 45 degrees digital retinal imaging photography before mydriatic two-field photography. A total of 1,549 patients were then examined by an experienced ophthalmologist. Outcome measures were ungradable image rates, age, duration of diabetes, detection of referable diabetic retinopathy, presence of early or obvious central cataract, pupil diameter, and iris color. RESULTS: The ungradable image rate for non-mydriatic photography was 19.7% (95% CI 18.4-21.0) and for mydriatic photography was 3.7% (3.1-4.3). The odds of having one eye ungradable increased by 2.6% (1.6-3.7) for each extra year since diagnosis for nonmydriatic, by 4.1% (2.7-5.7) for mydriatic photography irrespective of age, by 5.8% (5.0-6.7) for non-mydriatic, and by 8.4% (6.5-10.4) for mydriatic photography for every extra year of age, irrespective of years since diagnosis. Obvious central cataract was present in 57% of ungradable mydriatic photographs, early cataract in 21%, no cataract in 9%, and 13% had other pathologies. The pupil diameter in the ungradable eyes showed a significant trend (P < 0.001) in the three groups (obvious cataract 4.434, early cataract 3.379, and no cataract 2.750). CONCLUSIONS: The strongest predictor of ungradable image rates, both for non-mydriatic and mydriatic digital photography, is the age of the person with diabetes. The most common cause of ungradable images was obvious central cataract.
Adult↗
The effectiveness of screening for diabetic retinopathy by digital imaging photography and technician ophthalmoscopy.
AIMS: To evaluate the introduction of a community-based non-mydriatic and mydriatic digital photographic screening programme by measuring the sensitivity and specificity compared with a reference standard and assessing the added value of technician direct ophthalmoscopy. METHODS: Study patients had one-field, non-mydriatic, 45 degrees digital imaging photography prior to mydriatic two-field digital imaging photography followed by technician ophthalmoscopy. Of these patients, 1549 were then examined by an experienced ophthalmologist using slit lamp biomicroscopy as a reference standard. The setting was general practices in Gloucestershire. Patients were selected by randomizing groups of patients (from within individual general practices) and 3611 patients were included in the study. Patients for reference standard examination were recruited from groups of patients on days when the ophthalmologist was able to attend. The main outcome measure was detection of referable diabetic retinopathy (DR) as defined by the Gloucestershire adaptation of the European Working Party guidelines. RESULTS: For mydriatic digital photography, the sensitivity was 87.8%, specificity was 86.1% and technical failure rate was 3.7%. Technician ophthalmoscopy did not alter these figures. For non-mydriatic photography, the sensitivity was 86.0%, specificity was 76.7% and technical failure rate was 19.7%. CONCLUSIONS: Two-field mydriatic digital photography is an effective method of screening for referable diabetic retinopathy. Non-mydriatic digital photography has an unacceptable technical failure rate and low specificity.
Adolescent↗
Cocaine-elicited mydriasis in the rat: pharmacological comparison to clonidine, D-amphetamine and desipramine.
Agents known to influence adrenergic function were examined for their mydriatic effects in urethane-anesthetized rats. Both the direct acting adrenergic agonist, clonidine, and the "indirect" acting agonists, cocaine, desipramine and amphetamine elicited mydriatic responses. The polar alpha-2 adrenoceptor agonist, 4-hydroxyclonidine, did not elicit a mydriatic response when administered systemically; however, it did produce a pronounced mydriatic response when administered i.c.v. Inasmuch as the selective lipophilic alpha-2 adrenoceptor antagonist, yohimbine, but not the polar alpha adrenoceptor antagonist, phentolamine, reversed the mydriatic effects of clonidine and cocaine, these data suggest that centrally located alpha-2 adrenoceptors elicit the above mydriatic response. The direct acting alpha-2 adrenoceptor agonists, clonidine (i.v.) and 4-hydroxyclonidine (i.c.v.), were the most efficacious of the agents studied in eliciting the mydriatic response. The indirect acting agents, amphetamine, desipramine and cocaine, were less efficacious. The rank order potency (ED-50) of these drugs was as follows: clonidine greater than desipramine greater than cocaine = amphetamine. The mydriatic effects of cocaine were attenuated by yohimbine and reserpine pretreatments. In addition, the local anesthetic, procaine, and the polar cocaine analog, cocaine methiodide, were significantly less efficacious than cocaine. These results suggest that cocaine elicits mydriasis by indirectly acting at central and postsynaptically located alpha-2 adrenoceptors.
Animals↗
Pupil dilation with intracameral lidocaine during phacoemulsification.
PURPOSE: To evaluate pupil dilation by an intracameral injection of nonpreserved lidocaine 1% during phacoemulsification cataract extraction and compare the results with those using conventional topical mydriatics. SETTING: Department of Ophthalmology, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran. METHODS: A prospective comparative case series study was conducted. The study included 57 patients who were given topical mydriatics (30 eyes) or intracameral lidocaine (27 eyes) to dilate the pupil for phacoemulsification and intraocular lens implantation. The topical group received 3 drops of cyclopentolate 1% and phenylephrine 5% given 5 minutes apart starting 60 minutes before surgery. The intracameral group received preservative-free lidocaine 1% (0.2 to 0.3 mL) injected just before the procedure began. No epinephrine was added to the irrigating solution. In both groups, the horizontal pupil diameter was measured before and after pupil dilation using the same caliper. Total surgical time, need for a mydriatic agent during the procedure, and subjective surgical performance were recorded. RESULTS: The mean age, sex, cataract density, baseline horizontal pupil diameter, and mean duration of the surgery were the same between the topical group and intracameral group. The mean pupil dilation was 4.52 mm +/- 0.08 (SD) in the intracameral group and 4.06 +/- 0.09 mm in the topical group; the difference between groups was statistically significant (P = .001). There was no significant difference between groups in the overall subjective surgical performance (P = .74). No patient in the intracameral group and 2 patients in the topical group required an intracameral mydriatic injection. CONCLUSION: During phacoemulsification, intracameral preservative-free lidocaine 1% provided rapid, effective mydriasis comparable that of topical mydriatics.
Aged↗
Mydriasis elicited by imidazol(in)e alpha 2-adrenomimetics in comparison with other adrenoceptor-mediated effects and hydrophobicity.
alpha 2-Adrenoceptor agonists cause both mydriasis and platelet aggregation. This work is aimed at identifying the factors accompanying and affecting mydriatic activity. For eight imidazol(in)e drugs mydriatic, hypotensive and bradycardic activities were determined in rats. The lipophilicity of the agents was determined chromatographically and calculated theoretically. A correlation was found between the hypotensive and the bradycardic potency and between the mydriatic activity and both the hypotensive and bradycardic activity. Mydriatic activity depended on the lipophilicity of the agents studied. The human platelet antiaggregatory activity of the drugs did not correlate with either the mydriatic or cardiovascular activity and it was independent of lipophilicity. The dependence of the centrally induced effects on lipophilicity and the lack of such a dependence in the case of the in vitro alpha 2-adrenoceptor-mediated platelet aggregation may be interpreted as resulting from heterogeneity of the rat cerebral and the human platelet alpha 2-adrenoceptors. The alpha 2-adrenergic activity of drugs in the model of mydriasis in rats cannot be predicted from their activity in causing human platelet aggregation in vitro.
1-Octanol↗
Pupil dilation using a pledget sponge: a randomized controlled trial.
BACKGROUND: To show that a pledget soaked in mydriatics and placed in the lower conjunctival fornix is as effective as drops in providing mydriasis for cataract surgery. METHODS: A randomized, masked, controlled trial of 56 patients assigned to either a pledget group (n=25) or a control eye drops group (n=31) was carried out. Controls had the routine practice of repeated topical mydriatic drops: tropicamide, phenylepherine and atropine. The trial group had a 3-mm pledget trimmed, soaked in mydriatics and placed in the inferior fornix for 20 min. Pupil diameter was measured using a photographic technique with a standard scale shown in each picture. Two masked observers measured the pupils using the scale of the ruler in the developed photograph. All patients completed a 0-10 stinging score prior to surgery. RESULTS: There were no complications. The mean pupil diameter in the control group was 7.23 (6.91-7.94 95% confidence intervals [CI]) and 7.44 (6.96-7.92 95% CI) in the pledget group. There was no statistically significant difference in pupil diameter between the two groups: difference between means 0.21 (-0.32 to 0.75 95% CI) and Student's t-test of the difference between means (t=0.8 and two-tailed) probability P=0.43. There was no significant difference in the stinging scores: Mann-Whitney test P=0.69. CONCLUSION: The use of a pledget cellulose sponge to deliver mydriatics prior to cataract surgery is as effective as the conventional method of repeated drop administration and was not associated with any adverse effects.
Aged↗
Renal failure caused by eyedrops containing phenylephrine in a case of retinopathy of prematurity.
The patient was a low birth weight infant with a history of renal failure. She was referred to our department 29 days after birth to undergo fundus examination. She experienced renal failure after undergoing a mydriatic test and needed medical treatment. Eyedrops containing phenylephrine were instilled several times and additional drops were also instilled during the fundal examination using an eyelid retractor, therefore the blood concentration of the drug was elevated sufficiently to contract the renal vessels, ultimately inducing renal failure. The present case suggests that since the use of mydriatic eyedrops in low birth weight infants could induce renal failure, the following points should be considered: 1) Mydriatic eyedrops should be used with caution by monitoring mydriasis and avoiding excessive instillation; 2) After instillation, the lacrimal region should be compressed to prevent the flow of mydriatic drops to the nasolacrimal canal; and 3) Vital signs should be monitored to check the onset of any adverse reactions for 12 hours after fundal examination.
Acute Kidney Injury↗
Pharmacokinetics of topical phenylephrine hydrochloride in the normal human eye.
Solutions of phenylephrine hydrochloride at concentrations of 1, 2 and 5% were instilled in one eye of 5 normal volunteers. Both eyes were photographed concurrently with an infrared film, and the pupil diameter was determined by an image analyzer using the developed film. The mydriatic effects were expressed by the difference in the pupil diameter of the experimental and the fellow control eyes determined concurrently. The mydriatic effects with these 3 solutions reached a peak about one hour and 15 minutes after instillation; the peak effects and the logarithm of the drug concentrations showed a linear relationship. An extrapolation of the relationship gave a least effective concentration of 0.07%. From the time course of the mydriatic effects, the pharmacokinetic coefficients were calculated using a computer. The average values were 0.24 +/- 0.08 hour for the time lag of the mydriatic response to appear, 1.31 +/- 0.19 hour-1 for the apparent elimination rate constant and 1.47 +/- 0.28 hour-1 for the apparent absorption rate constant.
Adult↗
Response of the pupil to tropicamide is not a reliable test for Alzheimer disease.
OBJECTIVE: To confirm the putative hypersensitivity of the pupil to a weak mydriatic in persons with Alzheimer dementia. DESIGN: Twenty patients with Alzheimer dementia and 20 control subjects were examined. Automated binocular infrared pupillography was performed in the dark after instillation of 0.01% tropicamide or placebo. Ocular penetration of eye drops was assessed simultaneously using 2% fluorescein sodium as a tracer. SETTING: Rochester, Minn. SUBJECTS: Twenty patients and 20 cognitively normal control subjects from the Alzheimer's Disease Patient Registry of the Mayo Clinic, Rochester, Minn. MAIN OUTCOME MEASURE: Percent change in the diameter of the pupil following topical ocular instillation of a diluted concentration of the mydriatic drug tropicamide and penetration of topically applied fluorescein into the aqueous humor. RESULTS: No statistically significant difference was found between patients with Alzheimer disease and control subjects in either the mydriatic response of the pupil or in the rate of penetration of topically applied fluorescein. CONCLUSION: No evidence of pupillary hypersensitivity to an anticholinergic mydriatic drug was found in patients with Alzheimer disease or any evidence that this putative hypersensitivity could be used as an early, simple diagnostic test for Alzheimer disease.
Aged↗
Ocular pharmacokinetics and pharmacodynamics of phenylephrine and phenylephrine oxazolidine in rabbit eyes.
The aqueous humor concentration of phenylephrine and its corresponding mydriatic response were measured over time in New Zealand albino rabbit eyes following a 10-microliters topical instillation of a phenylephrine HCl viscous solution (10%) or a phenylephrine oxazolidine (prodrug) suspension in sesame oil (1 and 10%). The bioavailability of a 1% prodrug suspension in the rabbit eye (AUC of aqueous humor concentration vs time) was 30% lower than that of a 10% phenylephrine solution (P less than 0.1) with the exception that the peak time occurred 34 min earlier with the prodrug. A 10% prodrug suspension increased the aqueous humor bioavailability approximately eightfold but improved the mydriatic activity (AUC of mydriasis vs time) only fourfold. The pharmacokinetic parameters, apparent absorption, and elimination rate constants, of phenylephrine and the prodrug were determined from aqueous humor concentration-time and mydriasis-time profiles. The study showed that the kinetic parameters of phenylephrine estimated from its mydriasis profile do not accurately reflect the kinetics of drug distribution in the iris. These parameters also varied with the instillation of phenylephrine solution or prodrug suspensions. A mydriatic tolerance of the pupil response was apparent after the topical instillation of phenylephrine solution. The mydriatic tolerance may be due to the decrease in receptor number in the iris dilator muscle.
Absorption↗
Mechanism of dexamphetamine-induced mydriasis in the anaesthetized rat.
1. The effect of intravenous administration of dexamphetamine [+)-Amp) on rat pupil diameter was investigated. In all experiments, the vagosympathetic trunks were sectioned bilaterally at the cervical level. 2. In rats anaesthetized with urethane, (+)-Amp (0.1-0.3 mg kg-1, i.v.) produced a dose-related increase in pupil size. The mydriatic effects of (+)-Amp were evident immediately after administration. 3. Pretreatment with the alpha 2-adrenoceptor antagonists yohimbine (1.5 mg kg-1 i.v.) or idazoxan (0.5 mg kg-1, i.v.) blocked the pupillary response to (+)-Amp. Yohimbine caused about a 30 fold shift to the right in the dose-response curve whereas idazoxan almost completely abolished the mydriatic response to (+)-Amp. 4. In contrast, pretreatment with the alpha 1-adrenoceptor antagonist phenoxybenzamine (2 mg kg-1, i.v.), failed to alter significantly the pupillary response to (+)-Amp. 5. Depletion of central nervous system (CNS) monoamines with reserpine (5 mg kg-1, i.p.) and alpha-methyl-p-tyrosine (2 x 300 mg kg-1, i.p.) prevented the pupillary response to (+)-Amp. 6. The mydriatic effect of (+)-Amp was present only in preparations that had intact parasympathetic neural tone to the iris. Central preganglionic denervation of the oculomotor nerve abolished the mydriatic response of (+)-Amp. 7. These results indicate the (+)-Amp acts in the CNS to produce mydriasis in the anaesthetized rat by stimulating CNS postsynaptic alpha 2-adrenoceptors, findings that are consistent with the hypothesis that (+)-Amp acts predominantly as an indirect sympathomimetic agent to release endogenous stores of a monoaminergic neurotransmitter (perhaps noradrenaline).
Adrenergic alpha-Antagonists↗
[Near triad measurement--accommodative pupillometry with horizontal eye tracking and its qualitative analysis].
PURPOSE: Recording of "near triad responses" was done by static accommodative stimulation to reveal the qualitative analysis of asthenopia. METHOD: Twelve healthy subjects in agegroups of 20, 30, and 40 years were examined before and after several hours of visual display terminal (VDT) work after informed consent. Three trials of forward <-> backward movement of focusing on a target were carried out. Response curves of horizontal eye tracking and pupillary diameter, that is, convergence with miosis and divergence with mydriasis, were recorded continuously, bilaterally and simultaneously by TriIRIS. RESULTS: 1) Normal patterns of vergence and pupillary responses with constant amplitudes were recorded in five subjects and were stable. 2 ) Gradual decline of the mydriatic peak was observed in two subjects, suggesting spastic accommodation. Increasing mydriatic peak or notching of mydriatic phase was seen in one eye each, suggesting tonic disaccommodation. These abnormal patterns were reversed by adequate refractive correction, and classified as an eye-fatigue group. 3) Abruption of miotic phase was observed in two cases of exophoria. 4) Low and declining amplitudes despite normal light response were observed in two subjects, suggesting debilitated accommodation, and they were classified as an eye-strain group. 5) Post-traumatic mydriatic anisocoria responded in parallel, suggesting paretic accommodation. CONCLUSIONS: Coordinated dynamics of near triad responses revealed remarkable characteristics of accommodative iris movements with vergence. These objective findings revealed the different patterns of functional disorder of accommodation.
Accommodation, Ocular↗
The effects on pupil size and accommodation of sympathetic and parasympatholytic agents.
The time-response effect of two currently used mydriatics, phenylephrine and tropicamide, were evaluated in 524 eyes. Four different types of dilating regimens were used: 2.5% phenylephrine, 10% phenylephrine, 0.5% tropicamide, and the combination of 2.5% phenylephrine and 0.5% tropicamide. The analysis indicated that the recovery from mydriasis occurs between 5.5 and 7.0 hours with 2.5% phenylephrine and at more than 7 hours with 10% phenylephrine. The 0.5% tropicamide induced rapid dilation, whereas the combined treatment, 2.5% phenylephrine plus 0.5% tropicamide, produced the largest maximum pupillary diameter. Tropicamide, alone or in combination, also produced a longer mydriatic effect, lasting more than 7.0 hours. The recovery from the cycloplegic effect of the mydriatics occurred between five and seven hours in the majority of patients, with tropicamide alone or in combination with phenylephrine requiring the most time to revert to normal ranges of accommodation. The findings in this study indicate that, in normal subjects, the recovery from the effect of mydriatic agents is longer than what is generally reported in the literature.
Accommodation, Ocular↗
Retinopathy screening in type 2 diabetes: reliability of wide angle fundus photography.
The purpose of the study was to assess the reliability of mydriatic 60 degrees fundus photography in a retinopathy screening programme for Type 2 diabetic patients in a primary health care setting. In 323 eligible consecutive Type 2 diabetic patients above 40 years of age, attending a regional shared care diabetes project, mydriatic wide angle fundus photography was compared with standardized fundoscopy in dilated pupils as the recommended test for the detection of diabetic retinopathy. Fundus photography included two black and white transparencies per eye visualizing the central and nasal retinal field. Fundoscopy findings and pictures were scored according to modified Wisconsin criteria. Fundoscopy revealed in 95/646 eyes (14.7%) some degree of diabetic retinopathy. Sensitivity and specificity of fundus photography (omitting ungradable transparencies) were 97% for the diagnosis of any diabetic retinopathy (DRP). All patients with moderate and severe DRP (Wisconsin grade 3 and worse) according to fundoscopy were detected by fundus photography. In conclusion, mydriatic wide angle 60 degrees fundus photography, making two pictures per eye, can be applied effectively and reliably in the detection of diabetic retinopathy in patients with Type 2 diabetes.
Adult↗
Improving the ocular absorption of phenylephrine.
An oxazolidine prodrug of phenylephrine and the base form of phenylephrine were synthesized, suspended in sesame oil, and tested for mydriatic activity against phenylephrine HCl. The HCl salt was formulated as a viscous aqueous solution and as a sesame oil suspension. A dosing volume of 10 microliter was instilled into rabbit eyes and the pupillary diameter was measured over time. A 0.045 M prodrug suspension was judged equal in mydriatic activity to a 0.45 M viscous solution of phenylephrine HCl with the exception that the time of maximum response occurred 60 min earlier with the prodrug. When phenylephrine base was suspended in sesame oil at 0.045, 0.12, and 0.45 M, the mydriatic activity was also greater than equimolar suspensions of phenylephrine HCl. The pH of tear fluids was also measured over time and found to rise 1.1, 0.70, and 0.30 pH units for 0.45, 0.12, and 0.045 M suspensions of the base form but remain unchanged when phenylephrine HCl was instilled in the rabbit eye. The greater activity associated with the base form of phenylephrine was judged a result of the change in pH to favour the absorption of phenylephrine. This latter approach should be applicable to either weak acids or weak bases with pKa values outside of the normal pH range (7-8) of the tears and in concentrations greater than 0.045 M suspended in a non-aqueous vehicle.
Absorption↗
Solubilization of tropicamide by hydroxypropyl-beta-cyclodextrin and water-soluble polymers: in vitro/in vivo studies.
1% (w/v) aqueous solutions of tropicamide (TR), a poorly water-soluble mydriatic-cycloplegic drug, are usually obtained by adjusting the pH to approximately 5.0, at the expense, however, of ocular tolerance and bioavailability. The capacity of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to solubilize TR in pH 7.4 0.02 M phosphate buffer was investigated in the absence and presence of hydrophilic polymers (PVP, CMC and HPMC). Approximately 3.5% (w/v) HP-beta-CD was required to solubilize 1% (w/v) TR in pH 7.4 buffer at room temperature. The required amount was reduced to 0.9% (w/v) by heating at 120 degrees C in the presence of 0.1% (w/v) HPMC. Mydriatic activity tests in rabbits showed an improved bioavailability and maximal mydriatic response for two CD formulations, with and without HPMC, when compared to standard 1% (w/v) TR eyedrops, buffered at pH 5.0. The improved in vivo behaviour of the CD formulations are likely due to their physiological pH, resulting in a reduced irritant effect, although an effect of HP-beta-CD on corneal permeability cannot be dismissed a priori.
2-Hydroxypropyl-beta-cyclodextrin↗