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Influence of transcranial magnetic stimulation on pupil size.

In 22 healthy subjects, painless repetitive transcranial magnetic stimulation (rTMS) was used to investigate the role of the cortex in the regulation of pupil size and the influence of TMS on the central autonomic nervous system. RTMS was performed over three brain regions of each hemisphere (frontal, central, parieto-occipital), over cervical nerve roots and in front of the ear (sham stimulation) while the size of the pupil was measured by infrared oculography. rTMS always elicited a dilatation of both pupils, with its maximum after approximately 1.5 s and without significant R-L difference in latency or amplitude of pupillary response. No differential effects were observed for stimulation over different cortex regions of one hemisphere, but stimulation over the right central region evoked a larger dilatation of the pupil than stimulation over the left. Pupillary dilatation was larger for cervical nerve root stimulation (+13.2+/-8.3% (S.D.) of baseline) than for suprathreshold cortex stimulation (+8.4+/-4.5%, five 10-Hz stimuli). Pupillary dilatation in response to magnetic cortex stimulation appears to reflect a mainly unspecific activation of the sympathetic system rather than an activation of a cortical pupillomotor centre. Sympathetic activation following rTMS of the cortex does not limit its experimental and therapeutic application.

Adult↗

Acute sensorimotor polyneuropathy with tonic pupils and an abduction deficit: an unusual presentation of polyarteritis nodosa.

A tonic pupil may occur in isolation or as part of a systemic disorder. We report a patient who developed tonic pupils and an abduction deficit in the setting of polyarteritis nodosa. The combination of a tonic pupil and an abduction deficit should suggest the possibility of a vasculopathic disorder, because the ciliary ganglion and lateral rectus muscle are both supplied by the lateral muscular artery. Widespread small artery and arteriolar narrowing and occlusion are the hallmarks of polyarteritis nodosa. Unusual ischemic syndromes may occur, such as this rare combination of neuro-ophthalmic signs, by involvement of both the nutrient artery and its collaterals. We are unaware of other reports of neuropathic tonic pupils in association with polyarteritis nodosa.

Acute Disease↗

Decreases in dilated pupil size in depressed patients with age may reflect adrenergic changes.

Some studies have suggested that noradrenergic activity may decrease with age in depressed patients. Pupil size is regulated by a balance between norepinephrine and acetylcholine. The present study compares pupil size in 10 unmedicated patients with unipolar depression (296. 3) and in 16 normal controls. Pupil size after dilation with tropicamide, a cholinergic antagonist, was inversely related to age in the patients (r=-0.87), but did not diminish with age in controls. The results suggest that pupil size may provide an index of diminished noradrenergic function with age in patients with major depression.

Acetylcholine↗

[A study of pupil dilation using the Mydriasert ophthalmic insert].

PURPOSE: To evaluate the tolerance and efficiency of the Mydriasert(R) ophthalmic insert on pupil dilation. METHOD: Two pharmaceutical forms of a combination of tropicamide and phenylephrine (HCl) were compared on both eyes of 80 patients. For each patient, one Mydriasert insert (Ioltech) was placed in the lower conjunctival sac of the eye. Dilation of the control eye was obtained using 0.5% tropicamide eye drops and 10% phenylephrine eye drops (Novartis Ophthalmics), which were instilled with three frequency regimens (5, 10 or 15 min). The pupil diameter was regularly measured until the maximal mydriasis had occurred. RESULTS: Both subjective and objective tolerance of the insert was excellent. The size of the maximal mydriasis obtained when using the insert was significantly greater than that obtained when using the eye drops, regardless of the frequency of the instillation (p < 0.04). The difference in maximal pupil diameter ranged from +0.16 mm to +0.38 mm. Mydriasis kinetics was slower with the insert. The time necessary to obtain a maximal mydriasis was 47.3 min when the insert was used, whereas it was in the range of 31.4 to 38.5 minutes with the eye drops (p < 0.001). As far as pupil diameter is concerned, the superiority of the insert compared to the eye drops became observable only about 45 min after the insert had been placed in the eye. The relative efficacy of the insert compared to the eye drops did not correlate with patient features (p > or = 0.06). CONCLUSION: Despite the small quantity of drug delivered by the insert, Mydriasert allows a much greater mydriasis compared to that usually obtained when the eye drops were used. However, a longer time lapse is necessary for this to occur.

Adolescent↗

Comparison of a digital and a handheld infrared pupillometer for determining scotopic pupil diameter.

To compare a digital infrared pupillometer with a handheld infrared pupillometer for determining scotopic pupil size. Department of Ophthalmology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. In 100 eyes of 50 healthy individuals (mean age 38.8 years +/- 10.7 [SD]), the scotopic pupil size was measured with a digital (Procyon) and a handheld (Colvard) infrared pupillometer. After dark adaptation of 1 minute, measurements were performed with both devices by 2 examiners (E1 and E2). Agreement and repeatability were analyzed using a comparison method described by Bland and Altman. The mean scotopic pupil diameter was 5.90 +/- 0.97 mm (range 3.24 to 7.91 mm) with the Procyon and 5.78 +/- 0.98 mm (range 3.00 to 7.30 mm) with the Colvard pupillometer. The mean difference between the 2 devices was -0.01 mm (E1) and -0.24 mm (E2). The limits of agreement ranged from 2.84 (E1) to 3.24 (E2). The coefficients of repeatability were 0.64 (Procyon) and 1.16 (Colvard). The mean difference between E1 and E2 was -0.10 for the Procyon and 0.13 for the Colvard pupillometer. The limits of agreement ranged from 1.28 (Procyon) to 2.32 (Colvard). The digital infrared pupillometer (Procyon) demonstrated better repeatability and agreement in measuring scotopic pupil size than a handheld device (Colvard).

Adult↗

Pupil size and the ablation zone in laser refractive surgery: considerations based on geometric optics.

PURPOSE: To determine whether the currently accepted method of selecting a minimum ablation zone size for refractive surgery based on dark-adapted pupil diameter is substantiated by geometric optical analysis. SETTING: Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: An optical model of the anterior segment was developed to calculate the effective corneal refractive diameter (ECRD), which is the diameter of the area of cornea that refracts all incident light rays arising from objects along the line of sight though the physical pupil (PP). The concept of the entrance pupil (EP) was reexamined and developed, and the ECRD was calculated over a range of corneal curvatures (K), anterior chamber depths (ACDs), and EP sizes. The model was generalized to include oblique light rays. Calculations were performed using MatLab Optimization Toolbox software (The MathWorks). RESULTS: For a given EP size, the ECRD was significantly influenced by K and slightly influenced by ACD. CONCLUSIONS: For objects on the line of sight, the ECRD was smaller than the EP in all cases. Regarding rays from objects in the periphery, the ECRD expanded rapidly as the angle of oblique incidence increased. For objects on the line of sight, the ECRD is always smaller than the clinically measured pupil (EP) because the EP is substantially magnified relative to the PP. Ablation zones larger than the EP should, in theory, prevent scattered or defocused light rays from contributing to the foveal image. When considering objects in the periphery, the increase in ECRD is sufficiently rapid that current refractive procedures cannot stop scattered light from these objects from contributing to the retinal image.

Cornea↗

Unobtrusively tracking eye gaze direction and pupil diameter of mammographers.

RATIONALE AND OBJECTIVES: The visual process that radiologists use for diagnosis is incompletely understood. This study developed techniques to unobtrusively track direction and pupil diameter of radiologists reading a wide variety of films. We evaluated the eye gaze patterns of mammographic experts to gain knowledge that might improve the rate of early detection of breast cancer. METHODS: A video camera with a near-infrared light filter is pointed at the mammographic expert who is reading mammograms. The video images are analyzed in real time on a personal computer to detect eye gaze direction and pupil diameter. Two separate trials were used: 1) to demonstrate the system's speed and ability to work with mammograms (a brief test with one mammographer was used) and 2) four mammographic experts evaluated 14 mammograms. RESULTS: In the first trial, the system successfully tracked the eye gaze of a mammographer who quickly recognized the patient case, with the pupil diameter briefly increasing 40%, and then the gaze direction dwelling in an area of microcalcifications. In the second trial, 66% of the false-positive results for films with masses were associated with long eye gaze dwells, whereas 33% of the prolonged dwells for films with microcalcifications were associated with true-positive diagnoses. CONCLUSIONS: This near-infrared light system successfully tracked the eye gaze direction and pupil diameter of mammographic experts evaluating films. The association of long eye gaze dwells with diagnostic accuracy varied with the type of object being viewed. In films with masses, false-positive diagnoses were associated with long dwells. In films with microcalcifications, true-positive diagnoses were associated with long dwells.

Breast Diseases↗

The effects of topical tropicamide and systemic medetomidine, followed by atipamezole reversal, on pupil size and intraocular pressure in normal dogs.

Twenty normal Golden Retrievers being screeened for eye, hip and elbow diseases were given tropicamide topically and medetomidine systemically. Medetomidine effects were later reversed with systemic atipamezole. Pupil size and intraocular pressure changes were determined. Pupil size increased significantly following tropicamide administration and continued to increase slightly but significantly after medetomidine injection. It was unclear whether the slight increase in pupil size following medetomidine administration was due to continued effect of tropicamide or due to the medetomidine itself. Atipamezole did not influence pupil size. Intraocular pressure (IOP) was not affected by these drugs. Ophthalmic screening examination for inherited disease following tropicamide administration is equally feasible prior to sedation with medetomidine and after reversal with atipamezole, but not during the period of sedation.

Administration, Oral↗

[Aberrometry due dilated pupils--Which mydriatic should be used?].

BACKGROUND: For a wavefront-based LASIK procedure aberrometric measurements are necessary via a dilated pupil. The more dilated the pupil is the more aberrations can be identified. There are different mydriatic eyedrops used to dilate the pupil. It is unclear so far which mydriatic is best for measuring aberrations before LASIK. METHODS: We performed aberrometry measurements on 50 eyes under the following different conditions: physiological mydriasis under mesopic environment, tropicamide-induced dilation, phenylephrine-induced dilation, and cyclopentolate-induced dilation. The wavefront measurements were compared with the respective subjective refraction (sr). RESULTS: The refractive myopic error measured by aberrometry was less than after subjective refraction depending on the mydriatic used. Phenylephrine-induced mydriasis resulted in 0.19 D less myopia, tropicamide induced 0.35 D less myopia, and cyclopentolate 0.42 D less on the average. The aberrometry measurements under mesopic conditions led to 0.24 D less myopia than measured subjectively. CONCLUSION: Using cyclopentolate eyedrops wavefront analysis results in a considerable difference in the preoperative refractive error compared to the standard subjective refraction. Regarding the average differences in refraction the aberrometry measurements after neosynephrine-induced dilation of the pupil usually resemble the subjective refractive error. For practical reasons we would like to recommend aberrometry measurements under mesopic conditions without applying mydriatics provided the pupillary diameter is at least 6 mm.

Adult↗

Comparison of low-level sarin and cyclosarin vapor exposure on pupil size of the Gottingen minipig: effects of exposure concentration and duration.

The current studies estimated effective (miosis) concentrations of the nerve agents' sarin (GB) and cyclosarin (GF) as a function of exposure duration in the Gottingen minipig and determined dependency of the median effective dosage (ECT50) over time. Male and female Gottingen minipigs were exposed to various concentrations of vapor GB or GF for 10, 60, or 180 min. Infrared images of the pig's pupil before, during, and after nerve agent exposure were captured digitally and pupil area was quantified. An animal was classified "positive" for miosis if there was a 50% reduction in pupil area (as compared to baseline) at any time during or after the GB or GF exposure. Maximum likelihood estimation was used on the resulting quantal data to calculate ECT50 (miosis) values, with approximate 95% confidence intervals, for each of the six gender-exposure duration groups. As a group, male minipigs were significantly more sensitive to the pupil constricting effects of GF than were female minipigs. In male minipigs, GF is approximately equipotent to GB for 60-min exposures and more potent for 10- and 180-min exposures. In the female minipig GF is slightly more potent than GB for 10-min exposures but then progressively becomes less potent over the 60- and 180-min durations of exposure. The values of the toxic load exponents were essentially independent of the model fits used: 1.32 +/- 0.18 for GB exposures and 1.60 +/- 0.22 for GF exposures. Since neither of these intervals overlaps 1, Haber's rule is not an appropriate time-dependence model for these data sets.

Animals↗

Effect of systemic exposure to parathion on the dark adapted pupil dilation of cynomolgus monkeys.

The constriction of pupil dilation following dark adaptation was studied as a potentially useful biological monitor of systemic exposure to organophosphorus pesticides (OPs). Pupil dilation and blood cholinesterase levels were monitored in 4 cynomolgus monkeys following oral administration of 2.0 mg/kg parathion in corn oil. No consistent pattern of change in pupil/iris diameter ratios following exposure was found despite depressions in blood cholinesterase activities of 27-50% for red cells and 65-80% for plasma. A slight mydriasis was observed in one of the monkeys, who appeared the most affected behaviorally by the exposure. Results of this work suggest that the measurement of pupil dilation after dark adaptation is not a sensitive indicator for systemic exposure to OPs. However, in situations where direct exposure to the eyes may occur, such as during aerial or airblast pesticide applications, other studies indicate that constriction of pupil dilation can occur at exposure levels below those resulting in systemic effects.

Animals↗

Haploinsufficiency for Phox2b in mice causes dilated pupils and atrophy of the ciliary ganglion: mechanistic insights into human congenital central hypoventilation syndrome.

Dilp1 is a semi-dominant mouse mutation that causes dilated pupils when heterozygous and is lethal when homozygous. We report here that it is caused by a point mutation that introduces a stop codon close to the start of the coding sequence of the paired-like homeobox transcription factor Phox2b. Mice carrying a targeted allele of Phox2b also have dilated pupils and the two alleles do not complement. Phox2b is necessary for the development of the autonomic nervous system and when absent one of the consequences is that all parasympathetic ganglia fail to form. Constriction of the pupil is a parasympathetic response mediated by the ciliary ganglion and we find that in Phox2b heterozygous mutants it is highly atrophic. The development of other parasympathetic and sympathetic ganglia appears to be largely unaffected indicating that the ciliary ganglion is exquisitely sensitive to a reduction in dose of this transcription factor. PHOX2B has been implicated in human disease. Mutations, principally leading to polyalanine expansions within the protein, have been found in patients with congenital central hypoventilation syndrome (CCHS), the cardinal feature of which is an inability to breathe unassisted when asleep. Additionally, some CCHS patients have ocular abnormalities, including pupillary defects, although they principally have constricted rather than dilated pupils. The apparent phenotypic differences observed between mice carrying a loss-of-function mutation of Phox2b and CCHS patients indicate that PHOX2B mutations found in CCHS patients, all of which can produce proteins with intact DNA-binding domains, are gain-of-function mutations that alter rather than abolish protein function.

Alleles↗

Effects of low-dose naloxone on subjective alertness and pupil diameter in normal and narcoleptic subjects.

Recent evidence suggests that endogenous opiates may be involved in the pathophysiology of narcolepsy. To test this theory, the effect of 0.8 mg naloxone hydrochloride on pupil size and subjective alertness was measured in normal and narcoleptic subjects. Naloxone resulted in significant pupillary constriction in the normal but not in the narcoleptic subjects. The extent of contraction of the pupil light reflex was reduced significantly in the narcoleptic but not in the normal subjects. There was no effect on subjective ratings of alertness on the Stanford Sleepiness Scale or the visual analogue scale in either group. The naloxone-related miosis in the normal group confirms that naloxone is not a pure opiate antagonist. The lack of naloxone-related miosis in the narcoleptics suggests that narcoleptic individuals do not respond to naloxone as do normal individuals. However, this difference can not be definitely attributed to the antagonism of endogenous opiates. The reduction of the extent of contraction of the light reflex suggests that naloxone caused an increase in supranuclear inhibition of parasympathetic pupil reflex activity. However, this finding may have resulted from mechanical limitations of a small pupil or technical limitations of the recording equipment. This study does not support previous reports that naloxone causes an increase in subjective alertness in narcoleptics.

Adult↗

Fixed dilated pupil (Urrets-Zavalia syndrome) in corneal dystrophies.

PURPOSE: To report fixed dilated pupil following penetrating keratoplasty for corneal dystrophies. METHODS: Retrospective chart analysis of subjects who underwent penetrating keratoplasty for corneal dystrophies between 1998 and 2002 at our institute. RESULTS: Three of the subjects with fixed dilated pupils after penetrating keratoplasty had Macular corneal dystrophy and one subject had Fuchs Endothelial dystrophy. Fixed dilated pupils were noticed in the immediate postoperative period. None of the subjects had evidence for glaucoma either pre- or postoperatively. The follow up period ranged from 5 to 18 months. CONCLUSIONS: Fixed dilated pupil (Urrets-Zavalia syndrome) can occur after penetrating keratoplasty for corneal dystrophies and may not be limited to eyes with keratoconus as previously reported.

Adult↗

Sector pupil dilation with phenylephrine and tropicamide.

A comparison of sector pupil dilation produced with 2.5% phenylephrine and 1.0% tropicamide was carried out on nine subjects. We found that 2.5% phenylephrine produced a significant increase in the vertical as compared to the horizontal diameter at 10, 20, 30, 40, and 50 min after instillation of the drug with the maximum vertical diameter occurring at 40 min. The pupil diameter in the vertical and horizontal meridians before drug instillation was 3.7 mm +/- 0.2 (mean +/- SE) whereas at 40 min the vertical and horizontal diameters were 6.7 mm +/- 0.4 and 5.2 mm +/- 0.3, respectively. Instillation of 1% tropicamide produced equal dilation of the vertical and horizontal diameters, which was maximum at 40 min. Before drug instillation, the pupils were 3.7 mm +/- 0.2 (mean +/- SE) in both the horizontal and vertical meridians. At 50 min the pupil diameter was 7.0 mm +/- 0.2 in both meridians in the eye that received tropicamide.

Adult↗

Effects of decreasing concentrations of tropicamide on sector pupil dilation.

We compared the effects of decreasing concentrations of tropicamide on sector pupil dilation. The concentrations of 0.25, 0.125, 0.03125, and 0.0156% tropicamide were instilled on 10 subjects and the horizontal and vertical pupil diameters measured at 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, and 90 min after drug instillation. We obtained significant pupil dilation with the 0.25% concentration but with progressively decreasing concentrations we obtained a concomitant decrease in pupil dilation, suggesting that it is the inherent action of the constrictor muscle to respond differently than the dilator muscle (no sector dilation), and this effect is not concentration dependent.

Adolescent↗

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↗

On the use of small artificial pupils to open-loop the accommodation system.

Monocular accommodation responses to stimuli at vergences from 0 to -4.5 D (i.e. effective object-eye distances from infinity to 22 cm) were measured objectively using artificial pupils of 0.5, 0.75, 1.0 and 3.0 mm diameters and a constant retinal illuminance of 7000 td. The slopes of the response/stimulus curves for the 0.75, 1.0 and 3.0 mm pupils agree with those reported previously. The 0.5 mm pupil produced open-loop accommodation, no systematic change in accommodation being observed as the stimulus vergence was varied. However, the response drifted considerably with this pupil diameter.

Accommodation, Ocular↗