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PubMed1980

Efferent discharge patterns in the ciliary nerve of rabbits and the pupillary light reflex.

Unitary discharges in the efferent ciliary nerves were studied in cervical sympathectomized rabbits. In all, 279 units were recorded and categorized, except 7 units, into the following 3 types from their responses to photic and other stimuli, i.e. type A (170 units), type B (42 units) and type C (60 units). Type A units were characterized by exhibiting excitatory response to ipsilateral eye illumination and the response was closely related to the luminance level. The type A was further classified into AI (excitation), AII (no change) and AIII (inhibition) on the basis of the response to contralateral illumination. It was inferred that the type A was functionally related to active pupilloconstriction. Type B units were characterized by showing an exclusively inhibitory response to ipsilateral and/or contralateral illumination and the inhibition was luminance-dependent. It was therefore assumed that the type B was concerned with active pupillodilation. Type C units were not responsive to light stimulus, though the type C displayed characteristic reflex response to mechanical or thermal stimulus within the receptive field. The reflexive response, however, was not mediated via the oculomotor nerve. In order to confirm the results of the unit analysis, pupillary light reflex was examined. In particular, the consensual reflex varied depending upon individual rabbits. Namely, one became miotic, another mydriatic and a third remained uninfluenced, which corresponded well with the response pattern of the light-sensitive units.

Accommodation, Ocular↗
PubMed1989

Chronic cocaine reduces alpha 2-adrenoceptor elicited mydriasis and inhibition of locus coeruleus neurons.

The effects of chronic cocaine (50 mg/kg per day for two weeks) administration on two alpha 2-adrenoceptor-mediated responses were studied in rats. Chronic administration of cocaine significantly (compared to sham controls) attenuated the alpha 2-adrenoceptor-mediated inhibition of noradrenergic locus coeruleus (LC) neurons as well as alpha 2-adrenoceptor elicited mydriasis. Noradrenergic LC neurons from the cocaine treated and sham sham groups differed significantly in their responsiveness to the inhibitory effects of clonidine (ED50 values micrograms/kg: sham 7.35 +/- 1.13 and cocaine-treated 17.17 +/- 4.40, P less than 0.05). The ED50 values for the mydriatic response were sham 5.71 +/- 0.49 and cocaine-treated 16.42 +/- 0.69 micrograms/kg, respectively, P less than 0.001. No differences in cardiovascular responses to systemically injected clonidine between the chronic cocaine- and sham-treated groups were observed. Chronic cocaine treatment attenuates the two alpha 2-adrenoceptor-mediated responses most likely via an interaction with central catecholaminergic neurotransmission.

Action Potentials↗
PubMed1990

Ocular effects of dipivalyl esters of epinephrine and alpha-methylepinephrine.

The intraocular pressure (IOP) and pupillary effects of dipivalyl esters of epinephrine and alpha-methylepinephrine were compared after topical application in conscious rabbits. Both dipivalyl-alpha-methylepinephrine (DP alpha meE) and dipivalylepinephrine (DPE) produced a dose-dependent pupillary dilation (PD) and decrease in IOP. The onset of PD was approximately 30 min for both agents and reached maximal plateau within 1 and 2 hr for DPE and DP alpha meE, respectively. Duration of mydriatic effect was also dose-related, although more prolonged with DP alpha meE. This probably reflects differences in rate of inactivation of these compounds. The onset of IOP lowering effect of DP alpha meE was more rapid (35-45 min) when compared with DPE (1.5-2 hr) which may be due to the initial ocular hypertensive response seen with DPE. The initial rise in IOP was prevented by transection of three rectus muscles. DP alpha meE produced initial ocular hypertension only at the highest doses. The decrease of IOP lasted more than 6 hr for both drugs, returning to normal by 24 hr. No pupillary or IOP effects were seen in the contralateral eye. Denervation supersensitivity to both the pupillary and IOP responses to DP alpha meE was seen after superior cervical ganglionectomy. These findings are consistent with the hypothesis that the pupillary and IOP responses to DP alpha meE do not require intact adrenergic innervation to the eye, and that these effects are mediated by activation of postjunctional alpha-adrenoceptors. It is concluded that DP alpha meE is a potent adrenergic ocular hypotensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The capsaicin-induced inflammatory reaction in the cat eye: antagonism by ruthenium red.

The neurogenic ocular inflammatory response in the cat was investigated by means of intracameral injections of capsaicin. At a dose of 200 micrograms intracamerally the eye responded with a breakdown of the blood-aqueous barrier (BAB) and a transient ocular hypertension. A response of the same magnitude was observed when a dose of 1 microgram capsaicin was given. Most of the response to this lower dose was prevented by ruthenium red, an inorganic dye thought specifically to antagonize the effects of capsaicin on sensory nerve endings. Following injection of 200 micrograms capsaicin there was a transient increase in pupil size, but this response was not seen after 1 microgram. Repeated injections of 200 micrograms capsaicin when the effects of the first dose had vanished resulted in tachyphylaxis of the mydriatic response. A dose of 200 micrograms of capsaicin had no effect on resistance in the outflow routes for aqueous humour.

Animals↗
PubMed1986

The diagnosis of Horner's syndrome. Use and limitations of the cocaine test.

We prospectively studied the value of the cocaine test in the diagnosis of Horner's syndrome, by performing the test in 20 control subjects and in 20 patients with a provisional diagnosis of Horner's syndrome. Photographic testing of the darkness reflex of the pupil was used as an independent criterion of oculosympathetic dysfunction, and confirmed the diagnosis in 12 of the 20 patients. A mydriatic response to cocaine that was at least 1.0 mm less than in the unaffected eye occurred only with Horner's syndrome (7 patients). On the other hand, if the difference is smaller than 1.0 mm the chance that the patient does not have Horner's syndrome is only around 60%. There was no relationship between the magnitude of the response to cocaine and the site of the lesion in the sympathetic system.

Adolescent↗
PubMed1993

Antidepressant treatment and chemical sympathectomy fail to modulate alpha 1-adrenoceptor sensitivity in mouse eye.

The mydriatic response to alpha 1-adrenergic agonists was used as a functional index of postsynaptic alpha 1-adrenoceptors in mouse iris dilator muscle. Topical ocular application of methoxamine or phenylephrine caused dose-related mydriasis which was inhibited by pretreatment with prazosin or phentolamine. Chemical sympathectomy with topical 6-hydroxydopamine (6-OHDA) produced supersensitivity to phenylephrine but not methoxamine. Daily antidepressant treatment for 14 days with desipramine (10 mg/kg, i.p.), amitriptyline (10 mg/kg, i.p.), fluoxetine (2 mg/kg, i.p.), or moclobemide (40 mg/kg, i.p.) did not alter the response to methoxamine. Central alpha 1-adrenoceptors labelled with [3H]prazosin were similarly unaffected except for a modest downregulation produced by fluoxetine. These results demonstrate that postsynaptic alpha 1-adrenoceptors in mouse CNS and iris dilator muscle are refractory to manipulations known to alter their sensitivity in other tissues.

Administration, Topical↗
PubMed1984

Effect of amitraz and chlordimeform on heart rate and pupil diameter in rats: mediated by alpha 2-adrenoreceptors.

Pupillary and cardiac responses to the insecticide/acaricide amitraz (0.03 to 1.0 mg/kg, iv) and chlordimeform (0.03 to 10.0 mg/kg, iv), as well as the alpha 2-adrenergic agonists clonidine (1 to 30 micrograms/kg, iv) and xylazine (10 to 300 micrograms/kg, iv), were investigated in rats anesthetized with an ether and pentobarbital combination. Amitraz, clonidine, and xylazine caused a dose-dependent mydriasis and bradycardia. The order of potency of the mydriatic and bradycardic effects was: clonidine greater than xylazine greater than amitraz. Chlordimeform did not cause mydriasis or bradycardia at the dosages studied. Amitraz-induced mydriasis and bradycardia were blocked by antagonists with alpha 2-adrenoreceptor blocking activity: yohimbine and phentolamine (2.5 mg/kg each, iv). In contrast, these effects of amitraz were not affected by prazosin (2.5 mg/kg, iv), an alpha 1-adrenoreceptor antagonist. In rats pretreated with reserpine (7.5 mg/kg, sc, 20 hr) and alpha-methyl-p-tyrosine (250 mg/kg, ip, 5 hr) to deplete catecholamine, amitraz (0.03-1.0 mg/kg, iv) produced mydriasis of similar magnitude as in the control animals. However, amitraz did not lower the heart rate in the pretreated animals as it did in the control animals. The results demonstrated that amitraz, a formamidine, induced mydriasis and bradycardia which were not observed with administration of another formamidine, chlordimeform. The data also suggest that amitraz-induced mydriasis is mediated by postsynaptic alpha 2-adrenoreceptors while amitraz-induced bradycardia is mediated by presynaptic alpha 2-adrenoreceptors.

Amidines↗
PubMed1991

Electroretinographic changes in aged pigeons.

Photopic electroretinograms, either to full-field light flashes (FERGs) or to contrast-reversal of square-wave gratings (PERGs) have been recorded in pigeons aged 2 years old (n = 5) and 10 years old (n = 5). Mydriatic pupil diameter, ophthalmoscopic appearance of the retinal fundus and optic media, and refractive state were comparable in the two groups. V/log I functions of individual FERG components (a-wave, b-wave and oscillatory potentials) displayed significantly lower slopes in the old birds than in the young, which suggests a reduction in retinal gain. PERG amplitude also was significantly lower in the older birds over a wide range of spatial frequencies (0.2-8.8 c/deg). Estimated visual acuity based on the extrapolated high-frequency cut off was 18 c/deg in the younger birds and 7.8 c/deg in the older birds. These results are in agreement with psychophysical data and retinal age-related losses in visual acuity, photoreceptors and retinal ganglion cells. Since these findings are comparable to those reported for humans, the results suggest that pigeons may serve as a useful model for human visual aging.

Aging↗
PubMed1982

Effects of the combination of tripelennamine and pentazocine at the behavioral and molecular levels.

The purpose of the present experiments was to determine if the antihistamine tripelennamine potentiates the morphine-like effects of the narcotic-antagonist analgesic pentazocine at the behavioral level or the molecular level or both. At the behavioral level, the effects of pentazocine were determined alone and in combination with tripelennamine in rats trained to discriminate between saline and either morphine or the psychotomimetic narcotic derivative SKF 10,047. The interaction between pentazocine and tripelennamine were also evaluated in the guinea-pig ileum preparation and in the [3H]-naloxone opiate receptor binding assay. Tripelennamine significantly enhanced the morphine-like discriminative stimulus effects of pentazocine and markedly reduced the SKF 10,047-like stimulus effects of pentazocine. Naloxone antagonized the morphine-like effects of pentazocine plus tripelennamine. Pentazocine significantly constricted pupils in the rat, an effect which was additive with the mydriatic effects of tripelennamine. Inhibition of the twitch-height of the electrically stimulated guinea-pig ileum by pentazocine was not affected by tripelennamine. Further, tripelennamine did not modify the Ke for naloxone in antagonizing pentazocine. Inhibition of specific [3H]-naloxone binding by pentazocine was also not affected by tripelennamine. These results are consistent with the hypothesis that the potentiation of the morphine-like effects of pentazocine by tripelennamine which was observed behaviorally was not due to molecular interactions at the morphine receptor. At least a part of this interaction may be attributable to tripelennamine decreasing the psychotomimetic actions of pentazocine.

Animals↗
PubMed1982

Central and peripheral components of morphine mydriasis in mice.

Mice treated with morphine (intracerebroventricularly, retrobulbarly or intraperitoneally) demonstrated dose related bilateral mydriasis. Intracerebroventricular (ICV) injection was much more potent than either retrobulbar (RB) or intraperitoneal (IP) injections. Morphine applied topically onto one eye resulted in bilateral mydriasis which was more marked in the treated eye. The mydriatic effect was antagonized by naloxone administered either IP or ICV or given on one eye. Here again, ICV naloxone was most effective. Naloxone eye drops diminished the mydriasis produced by systemic morphine bilaterally but more in the treated eye. These results suggest that in mice the mydriasis produced by morphine is mainly of central origin, but a local ocular effect also occurs.

Animals↗
PubMed1984

Heightened cholinergic responsiveness in IgE-producing rabbits.

Atopic humans express an array of autonomic nervous system abnormalities. An animal model of IgE-mediated allergy was herein employed to determine if the induction of an IgE antibody response would affect autonomic responsiveness. Rabbits were immunized so as to selectively produce IgE antibodies, and their pupillary miotic and mydriatic responses to cholinergic and alpha adrenergic stimuli, respectively, were determined. IgE-producing rabbits exhibited hyperresponsiveness to cholinergic but not alpha adrenergic stimulation, a pattern resembling that seen in nonasthmatic atopic humans. Repeated sublethal anaphylactic episodes induced in three IgE-producing rabbits did not affect the pattern of autonomic responsiveness when compared to controls challenged with saline, despite clear evidence of increased plasma histamine levels immediately after antigen challenges in the IgE group. This study indicates that elicitation of an IgE antibody response is associated with the concomitant development of cholinergic hyper-responsiveness.

Animals↗
PubMed1989

Medetomidine--a novel alpha 2-adrenoceptor agonist: a review of its pharmacodynamic effects.

1. The pharmacodynamic effects of medetomidine, a novel alpha 2-adrenoceptor agonist, are reviewed. 2. In receptor binding experiments, and in isolated organ preparations medetomidine shows high specificity and selectivity to alpha 2-adrenoceptors. Its alpha 2/alpha 1 selectivity ratio is 1620 compared to 220 of clonidine. It is a highly potent full agonist at alpha 2-adrenoceptors, a fact that also distinguishes it from clonidine. 3. Medetomidine induces a dose-dependent decrease in the central release and turnover of norepinephrine (NE) measured as changes in metabolite concentrations or using pharmacological intervention techniques. 4. The selectivity, specificity and potency of medetomidine is further supported by various in vivo experiments showing dose-dependent hypotensive, bradycardic, sedative, anxiolytic mydriatic, hypothermic and analgesic effects. 5. The pharmacological, neurochemical and behavioral effects of medetomidine can be inhibited by prior, simultaneous or subsequent administration of selective and specific alpha 2-antagonists. 6. In humans medetomidine is well-tolerated and pharmacodynamic effects including e.g. dose-dependent decrease of vigilance, blood pressure, heart rate, salivary secretion and plasma NE are compatible with an agonistic action at alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

The Santa Barbara County diabetic retinopathy screening feasibility study: significance of diabetes duration and systolic blood pressure.

The objective of this study was to examine the feasibility and utility of screening for eye disease and hypertension in a group of diabetic patients. A sample of 338 outpatients in Santa Barbara County were included and had non-mydriatic retinal photography and measurement of blood pressure and visual acuity. Each patient completed a questionnaire including age, type of diabetes (type I or type II), duration of diabetes, and smoking history. Photographs were read by an internist and ophthalmologist, and grouped into one of five categories: (1) normal, (2) background retinopathy, (3) preproliferative retinopathy, (4) proliferative retinopathy, and (5) other abnormality. Patients with abnormalities were referred for treatment. Thirty-two percent of the population had retinopathy, and 16% had disease requiring urgent referral for treatment. Mean systolic blood pressure (MSBP) was found to be higher in patients with all types of retinopathy (132 mm Hg versus 124 mm Hg, p < 0.001). The relationship remained significant when smokers and nonsmokers were considered separately. No significant difference was found in MSBP between patients with severe retinopathy (preproliferative or proliferative) and those with background changes (133 mm Hg versus 131 mm Hg, respectively, p > 0.5). The other factor found to be related to retinopathy was the duration of diabetes. Type I patients with retinopathy had diabetes for 19 years versus 12 for those without (p < 0.01). Type II patients with retinopathy had diabetes for 10 years versus 6 for those without retinopathy (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2004

Screening for sight-threatening diabetic retinopathy: comparison of fundus photography with automated color contrast threshold test.

PURPOSE: To compare tritan contrast threshold (TCT) with fundus photography in screening for sight-threatening diabetic retinopathy (STDR), before significant visual loss. DESIGN: Prospective, comparative study. METHODS: A total of 510 consenting diabetic patients attending a hospital-based photographic screening clinic were recruited over a 2-year period. Exclusion criteria included visual acuity of worse than 6/9, previous photocoagulation, and a history of previous eye disease known to affect color vision. The automated TCT test was performed using a computerized cathode ray tube-based technique. Retinal photography was performed using a Polaroid mydriatic fundus camera with a 45 degrees field. Grading of diabetic retinopathy was carried out by an ophthalmologist using slit-lamp biomicroscopy and a 78-diopters lens. Assessments of sensitivity, specificity, and predictive values for both fundus photography and the TCT test were made. RESULTS: Both the fundus photography and TCT test correlated significantly with the presence of STDR (P <.0001, chi(2) test). The TCT test yielded a sensitivity of 94% (95% confidence interval [CI], 73%- 100%) and a specificity of 95% (95% CI, 92%- 96%) for detection of STDR compared with a sensitivity of 88% (95% CI, 66%-97%) and a specificity of 95% (95% CI, 93%-97%) with fundus photography. Combined modality improved overall screening performance. CONCLUSION: The TCT assessment is an effective and clinically viable technique, in comparison with fundus photography, to screen for STDR among a diabetic population. Additionally, our results also showed that combining the TCT test with fundus photography greatly increases the performance of screening for STDR.

Adolescent↗
PubMed2005

Prospective evaluation of digital non-stereo color fundus photography as a screening tool in age-related macular degeneration.

PURPOSE: To evaluate mydriatic, non-stereo digital color fundus photographs as a screening tool for identifying and classifying exudative age-related macular degeneration (AMD). DESIGN: Prospective case series. METHODS: Digital color fundus photographs were obtained from patients seen in the AMD screening clinic over a 9-month period at the Ivey Eye Institute in London, Ontario. Photographs for eligible patients were separated by eye, cataloged, blinded, and randomly labeled before interpretation by an experienced vitreoretinal surgeon. Exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of the fundus photographs in diagnosing, classifying, and managing cases of suspected exudative AMD were then calculated against gold standard clinical examination and fluorescein angiography. RESULTS: A total of 223 images were used from 118 eligible patients. Exact agreement between photographic evaluation and gold standard ranged from 89.2% (presence of pigment epithelial detachment (PED)) to 82.5% (evidence of retinal pigment epithelium geographic atrophy). Sensitivities ranged from 89.2% (presence of choroidal neovascular membrane (CNVM)) to 40.0% (presence of PED). Specificities ranged from 94.1% (presence of PED) to 86.8% (presence of retinal pigment epithelium geographic atrophy). Positive predictive value ranged from 86.1% (presence of CNVM) to 40.0% (presence of PED). Negative predictive value ranged from 94.1% (presence of PED) to 88.9% (presence of CNVM). As a screening tool for high-risk dry changes and active exudative changes, overall sensitivity specificity, positive predictive value, and negative predictive value were 82.1%, 79.1%, 70.4%, and 88.0%, respectively. CONCLUSIONS: Digital, non-stereo color fundus photographs are highly sensitive and have high negative predictive value as a screening tool. Very few treatable lesions are missed using telemedicine in age-related macular degeneration.

Aged↗
PubMed2005

A case of glaucomatocyclitic crisis in the emergency department.

Glaucomatocyclitic crisis is caused by an idiopathic inflammatory process of the trabecular meshwork, causing a decrease in aqueous outflow. This decrease causes the cyclitis-associated ocular hypertension. There is rarely any pain or other findings typically associated with glaucoma. Thus, the diagnosis is easily missed. Patients may present with nonspecific symptoms such as blurry vision or periorbital discomfort. Examination typically reveals a noninjected, slightly mydriatic eye. Slit-lamp examination may reveal fewer-than-expected inflammatory cells in the anterior chamber, with only occasional small nonpigmented keratic precipitates on the corneal epithelium. The intraocular pressure is typically increased (30 to 70 mm Hg), despite an open angle. Therapy is aimed at controlling the increased intraocular pressure with the use of topical imidazolines, beta-blockers, and carbonic anhydrase inhibitors. Complications related to prolonged and recurrent attacks of increased intraocular pressure may result in damage to the optic nerve head and visual field compromise.

Acute Disease↗
PubMed2005

Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide.

The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2-3.5 and 4) in buffered phosphate solutions containing 2 per thousand (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 microl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25-2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route.

Amines↗
PubMed2005

Influence of pupil and optical zone diameter on higher-order aberrations after wavefront-guided myopic LASIK.

PURPOSE: To investigate the influence of pupil and optical zone (OZ) diameter on higher-order aberrations (HOAs) after myopic wavefront-guided laser in situ keratomileusis (LASIK). METHODS: Twenty-seven myopic eyes of 19 patients were included. The mean preoperative spherical equivalent was -6.86 diopters (D) +/- 1.24 (SD) (range -4.25 to -9.5 D); the mean planned OZ diameter was 6.26 +/- 0.45 mm (range 5.7 to 7.1 mm). All patients had uneventful wavefront-guided LASIK (Zyoptix version 3.1, Bausch & Lomb) and an uncomplicated follow-up of 12 months. Wavefront measurements were performed with a Hartmann-Shack sensor in maximum mydriasis preoperatively and 12 months after LASIK. Wavefront errors were computed for pupil diameters (PDs) of 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 mm for the individual OZ diameter and for the individual mydriatic PD (7.93 +/- 0.46 mm). The impact of the relationship between pupil diameter and OZ diameter (fractional clearance [FC]) on HOA was described and quantified using curvilinear regression with a 4th-order polynomial fit. RESULTS: There was a reproducible relationship between FC and the amount of induced HOA. The change in HOA root mean square and primary spherical aberration (Z(4)0) was significantly correlated with FC. If the OZ was 16.5% larger than the pupil (FC = 1.17), only half the amount of HOA was expected to be induced than if the OZ equaled the pupil. In contrast, an OZ that was 9% smaller than the pupil (FC = 0.91) resulted in an HOA induction 50% higher than at FC = 1. CONCLUSION: The OZ zone to pupil ratio (fractional clearance) had a significant impact on HOA induction after wavefront-guided LASIK.

Adult↗