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Tonic pupil: a simple screening test
Abstract
The tonic pupil has a typical appearance and characteristic reactions to both light and the near reflex. Testing with Mecholyl (methacholine) is not possible since the drug is no longer manufactured. The reactions of a group of 25 patients with tonic pupil were studied using dilute pilocarpine, and compared with the pupil responses of a separate control group. We found that concentrations of 0.2% pilocarpine produced too many false-positive reactions in the control group and that 0.05% pilocarpine produced an insufficient response. The 0.1% concentration seemed suitable for ordinary clinical examinations and is recommended for pharmacologic confirmation of the diagnosis of tonic (Adie's) pupil.
... Although the 0.125% dilute pilocarpine test is generally performed to confirm the clinical suspicion of a postganglionic parasympathetic lesion, the test's reliability to accurately distinguish Adie's tonic pupil from a preganglionic oculomotor nerve lesion has been questioned 10,17 . False positive pupillary constriction after 0.1% pilocarpine administration in dilated pupils has been reported in 15% of normal subjects and also in some preganglionic oculomotor nerve disorders 9,11,18 . While 0.125% dilute pilocarpine induces variable miosis both in the dilated pupil and the normal fellow eye, the amount of pupillary constriction is known to be more pronounced in the larger pupil 18 . ...
We have compared the diagnostic ability of different concentrations of 0.125% and 0.0625% dilute pilocarpine for detecting denervation supersensitivity in unilateral Adie’s tonic pupil. This retrospective, observational, case–control study involved 117 subjects, consisting of 56 patients with unilateral Adie’s tonic pupil and 61 controls with other causes of unilateral dilated pupils. Subjects underwent the dilute pilocarpine test with one of the two concentrations, 0.125% or 0.0625%. Pupillary light reflex was recorded with a dynamic pupillometer at baseline and at 30–40 min after instilling one of the two concentrations of dilute pilocarpine. Diagnostic accuracy of two different concentrations of the dilute pilocarpine test, 0.125% group versus 0.0625% group, were compared by area under the receiver operating characteristic curve (AUC). Diagnostic ability of the dilute pilocarpine test for detecting denervation supersensitivity in unilateral Adie’s tonic pupil was significantly better in the 0.0625% group than in the 0.125% group (AUC = 0.954 vs. 0.840, respectively, P = 0.047). In the 0.0625% group, the change in maximal pupil diameter of ≥ 0.5 mm after topical pilocarpine instillation showed 100% sensitivity and 82.8% specificity for detecting Adie’s tonic pupil. This study confirmed that pupillary constriction with 0.0625% pilocarpine is better than 0.125% pilocarpine for detecting denervation supersensitivity in Adie’s tonic pupil. Digital pupillometry is a reliable method for assessing denervation supersensitivity in Adie's tonic pupil.
... Moreover, the convergence is slow, and the accommodation re ex is attenuated (8). In addition, Adie's pupil is sensitive to diluted pilocarpine with an optimum concentration of 0.125% and constrict remarkably to its administration, but normal pupil or AR pupil will remain indifferent (9)(10)(11). It is generally believed that Adie's pupil is a characteristic pupillary change of Holmes-Adie syndrome (HAS), which is absence of deep tendon re exes and usually idiopathic and more common in young women (8). ...
Background Pupillary abnormalities play an important role in identification of neurosyphilis. Among them, Argyll Roberston pupil is most typical and has been mentioned in many reports and studies. However, papers about Adie’s pupil associated with neurosyphilis are extremely rare. In the present study, we report a case of patient with bilateral Adie’s pupils as isolated manifestation of neurosyphilis. Case presentation we describe a 58-year-old retired Chinese woman with bilateral Adie’s pupils. Further evaluation revealed serologically positive for Treponema pallidum particle agglutination (TPPA), chemiluminescence immunoassays (CLIA) and rapid plasma regain (RPR) test (1:16). The Cerebrospinal fluid (CSF) examination revealed pleocytosis, elevated protein, and positive RPR (1:2), TPPA and CLIA. Final diagnosis of Adie’s pupils associated with neurosyphilis was made and other possible causes were excluded. Cephalosporin was used for treatment due to penicillin allergy. Despite effective anti-syphilis treatment, her pupils remained unchanged. Conclusions Adie’s pupil can be caused by neurosyphilis and is one of the most important pupillary changes in early neurosyphilis. Our study further underscore the necessity of syphilis screening in patients with Adie’s pupil due to further treatment consideration.
The pupil size at any moment is determined by the relative actions of the dilator and sphincter muscles of the iris, which act independently but simultaneously. Pupillary reactivity, whether dilation or constriction, is determined by the pattern and amount of autonomic innervation to the muscles of the iris. The dilator muscle of the iris is innervated by neurons from the sympathetic (adrenergic) autonomic nervous system, while the sphincter muscle is innervated by neurons of the parasympathetic (cholinergic) autonomic nervous system.
Cholinergic drugs can exert biological activity by modifying the normal mechanism of ACh-mediated autonomic neurotransmission in several ways (Fig. 1; Koelle 1975 a): interference with transmitter synthesis (hemicholinium); prevention of transmitter release (botulinum toxin); displacement of transmitter from ax-onal terminal (carbachol); mimicry of transmitter at postsynaptic receptor (methacholine, carbachol, nicotine); blockade of transmiter at postsynaptic receptor (atropine, D-tubocurarine, hexamethonium); inhibition of enzymatic breakdown of transmitter (anticholinesterases).
Background: This study determines how pupil size, anisocoria, and ambient light influence miotic responses to dilute pilocarpine. The aim is to establish whether mechanical properties of the iris affect miotic behavior using a cholinergic agonist and, if so, to define a more specific clinical definition of supersensitivity testing for suspected tonic pupil disorders. Methods: The right pupil of 42 normal subjects was first dilated with phenylephrine to create an experimental anisocoria. Then, pilocarpine 0.1 % was placed in both eyes. Net constriction of the larger right pupil was determined by subtracting the amount of pilocarpine-induced constriction of the control left pupil from the amount of pilocarpineinduced constriction of the experimental right pupil. Pupil diameters were measured in room light and darkness. Results: In only a few subjects, the larger right pupil became smaller than the left pupil after pilocarpine administration. Net constriction of the right pupil was greater when determined in room light than in darkness. The amount of net constriction of the right pupil showed good correlation with the degree of baseline anisocoria when evaluated in room light, but not so in darkness. Conclusion: Pupil size, degree of anisocoria, and light conditions influence the amount of pilocarpine-induced change in anisocoria. If a patient's larger pupil becomes the smaller pupil in darkness after dilute pilocarpine is applied to both eyes, then it is likely that such a response occurred independent of mechanical properties of the iris, and likely represents a supersensitive response.
This paper is not a detailed didactic review of Adie's syndrome. The history of the discovery and naming of the condition will not be dwelt upon since this material was carefully reviewed by Lowenstein and Loewenfeld in 1965. Only those aspects of the syndrome will be discussed to which some new information can be added. This new information is based on a series of patients with Adie's syndrome examined during the last ten years. The collection of cases began in 1966 and does not include cases previously reported by the author. The patients were encouraged to return for annual review and as many of the examinations listed in a table were done as time and patience permitted.
In patients with unilateral Adie's syndrome, we compared the relative supersensitivity of the tonic pupil to methacholine hydrochloride (Mecholyl 2.5%) and pilocarpine 0.125%. We tested a large series of patients and photographed the pupils before and 30 minutes after the eyedrops. In a group of 36 patients, Mecholyl was positive in 64% of the tests; and in a group of 20 patients, pilocarpine 0.125% was positive in 80% of the tests. Eight patients who failed to show supersensitivity with Mecholyl were tested with pilocarpine and five of the eight were shown to be supersensitive. We concluded that pilocarpine, in this concentration is not only an adequate substitute for Mecholyl 2.5%, but is a more sensitive testing substance in unilateral cases, simply because it has a slightly stronger miotic action.
Impressed by the benefit two patients with Adie's Syndrome derived from topical 0.1% pilocarpine therapy, we performed the present study to examine the measurable effects of 0.1% pilocarpine in several patients with this syndrome. Our study suggests those patients with Adie's Syndrome who lack stereoacuity may benefit from long term therapy with dilute pilocarpine if their stereoacuity may benefit from long term therapy with dilute pilocarpine if their stereoacuity improves following a single drop of 0.1% pilocarpine. Therefore, we recommend measuring stereoacuity during pupil diagnostic testing with 0.1% pilocarpine hydrochloride. Potential problems concerning medical therapy of Adie's Syndrome with parasympathomimetics are discussed.
To evaluate the association between the degree of diabetic retinopathy and autonomic neuropathy, and to test whether ocular parasympathetic denervation is correlated to the degree of diabetic retinopathy.
Cross-sectional pilot study.
The tertiary ophthalmic centre for the Atlantic provinces in Halifax.
Twelve randomly selected patients (six women and six men with a mean age of 36.6 years) with insulin-dependent diabetes mellitus who had diabetic retinopathy.
Degree of diabetic retinopathy, hemoglobin Alc level, orthostatic change in systolic and diastolic blood pressure and in serum catecholamine levels, degree of pupillary supersensitivity to 0.125% pilocarpine (pilo-pupil ratio average [PPRA]).
The degree of diabetic retinopathy was significantly correlated with the duration of diabetes (p = 0.035), the hemoglobin Alc level (p = 0.004), the orthostatic change in diastolic blood pressure (p = 0.022) and the PPRA (p = 0.0007).
The degree of diabetic retinopathy was significantly correlated with autonomic neuropathy and with the PPRA. Given these results, further study is indicated to determine whether autonomic neuropathy is a predictor of the severity of diabetic retinopathy.
The poorly reactive and dilated pupil observed in a comatose patient is often thought to represent an acute third nerve palsy owing to brain herniation or aneurysm. In the well patient, however, the isolated dilated pupil is unlikely to be owing to a third nerve palsy. It is more commonly owing to other benign causes such as local iris sphincter abnormalities, pharmacologic dilation, tonic pupil syndrome, or sympathetic irritation. This article presents a diagnostic flowchart to help the primary care physician analyze this problem and prevent costly and unnecessary imaging of these patients.
To determine the amount of pupillary constriction to four different concentrations of pilocarpine in normal human subjects and to determine if pupillary constriction correlates with bioavailability of the instilled concentrations. The amount of pupillary constriction to dilute pilocarpine is utilized as a diagnostic test for Adie tonic pupil as distinguished from a normal pupil response.
Twenty healthy volunteers had automated binocular infrared pupillography in the dark after instillation of four different concentrations of dilute pilocarpine. Ocular penetration of eye drops was also assessed using 2% fluorescein sodium as a tracer.
Prospective institutional double-masked study of both eyes of twenty healthy volunteers, ten with brown irides, ten with blue irides, between the ages of 20-40 years.
A pilocarpine dose-dependent curve showed decreased pupil size within 15 minutes, peaking at 30-60 minutes. No difference was noted between right and left eyes, iris color, or corneal permeability.
Normal pupils constrict to dilute concentrations of pilocarpine (0.25% or 0.125%), but constrict insignificantly to concentrations of 0.0313% or 0.0625%. Pupil constriction with 0.0625% pilocarpine should distinguish an Adie pupil from normal. This confirms the utility of this simple office diagnostic procedure.
Anisocoria, or a difference in pupil size, is a common condition. Its aetiology ranges from benign to life-threatening conditions. The clinical evaluation of anisocoria is discussed, emphasising the pharmacological aids (e.g., cocaine 10% eye drops, hydroxyamphetamine eye drops, pilocarpine 0.1% eye drops, pilocarpine 1% eye drops, apraclonidine) used in differentiating the different causes of anisocoria (e.g., physiological anisocoria, Horner syndrome, Adie pupil, pharmacological anisocoria, third nerve palsy).
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