Unequal pupils: Understanding the eye's aperture.

BACKGROUND: Unequal pupils (anisocoria) may be physiological, pathological or pharmacological. Importantly, anisocoria can indicate underlying disease of the eye, orbit, brain, neck or chest. Examination of the pupils is therefore a crucial part of any eye examination. OBJECTIVE: As a clinician, it is important to determine whether a patient with anisocoria can be reassured or requires referral for further investigation. This review examines the anatomy of the pupillary pathway, and provides a structured approach to examination of the pupils. The aim is to provide clinicians with confidence when encountering patients with anisocoria. DISCUSSION: Anisocoria can imply serious underlying pathology, so accurate pupil testing and astute observation are paramount. This review discusses the differential diagnosis of a large pupil (anisocoria more obvious in the light) and a small pupil (anisocoria more obvious in the dark), and discusses the relevant afferent pupillary defect, in which there is no anisocoria but both pupils react differently depending on which eye is illuminated.

Objective Verification of Physiologic Changes during Accommodation under Binocular, Monocular, and Pinhole Conditions.

BACKGROUND: To objectively investigate accommodative response to various refractive stimuli in subjects with normal accommodation. METHODS: This prospective, non-randomized clinical trial included 64 eyes of 32 subjects with a mean spherical equivalent -1.4 diopters (D). We evaluated changes in accommodative power, pupil diameter, astigmatic value, and axis when visual stimuli were applied to binocular, monocular (dominant eye, non-dominant eye, ipsilateral, and contralateral), and pinhole conditions. Visual stimuli were given at 0.25 D (4 m), 2 D (50 cm), 3 D (33 cm), and 4 D (25 cm) and accommodative response was evaluated using open view binocular autorefractor/keratometer. RESULTS: The accommodative response to binocular stimulus was 90.9% of the actual refractive stimulus, while that of the monocular stimulus was 84.6%. The binocular stimulus induced a smaller pupil diameter than did the monocular stimulus. There was no difference in accommodative response between the dominant eye and non-dominant eye or between ipsilateral and contralateral stimuli. As the refractive stimuli became stronger, the absolute astigmatic value increased and the direction of the astigmatism axis became more horizontal. Pinhole glasses required 10%-15% less accommodative power compared with the monocular condition. CONCLUSION: Binocular stimuli enable more precise and effective accommodation than do monocular stimuli. Accommodative response is composed of 90% true accommodation and 10% pseudo-accommodation, and the refractive stimulus in one eye affects the contralateral eye to the same extent. This should be taken into account when developing guidelines for wearing smart glasses while driving, as visual stimulation is applied to only one eye, but far distance attention is constantly needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03557346.

A Rare Cause of Acute Anisocoria in a Child: The Angel's Trumpet Plant.

Anisocoria is a significant finding in several ocular and potentially life-threatening neurological disorders. The angel's trumpet (Datura suaveolens), widely used as a garden plant, is a natural alkaloid with anticholinergic effects containing high levels of scopolamine. The authors present a pediatric case of acute anisocoria secondary to contact with the angel's trumpet plant. This case report emphasizes the importance of considering herbal mydriatics in patients with acute, isolated, unilateral mydriasis. It is also important to raise public awareness about the potential risks of the angel's trumpet plant, particularly in areas close to schools and playgrounds. [J Pediatr Ophthalmol Strabismus. 2018;55:e33-e35.].

Response anisocoria in the pupillary light and darkness reflex.

The pupil constricts or dilates in response to a luminance increase or decrease, and these transient pupillary responses are controlled by the parasympathetic and sympathetic pathways. Although pupillary responses of the two eyes are highly correlated, they are not always identical (referred to as anisocoria). For example, there are unequal direct and consensual pupillary constriction responses after an increase in luminance to one eye. While contraction anisocoria (i.e. constriction) has been demonstrated in the pupillary light reflex, it is not yet known if there is also dilation anisocoria in the pupillary darkness reflex. Unlike previous studies that focused on the pupillary light reflex, we examined response anisocoria in both pupillary light and darkness reflexes. While requiring participants to maintain central fixation, we presented a light or dark stimulus to either the right or left visual field to induce transient pupillary constriction or dilation. Both the pupillary light and darkness reflexes had significantly larger ipsilateral responses compared to the contralateral responses relative to the stimulated visual field. The observed ipsilateral effects occurred significantly faster in the light than darkness reflex, suggesting that larger ipsilateral pupillary dilation after a luminance decrease cannot be only attributed to the inhibition of the parasympathetic system, but is also mediated by the excitation of the sympathetic system. Together, our results demonstrated a larger ipsilateral pupil response in both the pupillary light and darkness reflex, indicating an asymmetry in ipsilateral and contralateral neural circuitry of the pupillary darkness reflex.

Stereopsis Simulating Small-Aperture Corneal Inlay and Monovision Conditions.

PURPOSE: To analyze stereoscopic vision under a broad range of experimental conditions simulating small-aperture corneal inlay and monovision conditions. METHODS: A total of 10 patients participated in the study. The anisocoria generated by corneal inlays was simulated by using a small-aperture contact lens fitted on the non-dominant eye. Visual acuity, contrast sensitivity function, visual discrimination capacity (halo perception), and stereoacuity tests were performed under natural conditions or when the non-dominant eye wore the small-aperture contact lens under two conditions: induced anisocoria and induced anisocoria combined with monovision (using two add-powers: +0.75 and +1.25 diopters [D]). Stereoscopic vision and binocular summation were analyzed under those experimental conditions and for far, intermediate, and near vision. RESULTS: The results showed a deterioration in stereoacuity with respect to natural conditions, being significant mainly for near and intermediate distances. Results with other visual functions showed a deterioration of the binocular summation and therefore of visual performance, although not in a generalized way for all distances. Binocular visual acuity under the conditions that used the small-aperture contact lens was comparable to that of the natural eye. CONCLUSIONS: The deterioration of stereopsis and other binocular functions found in this study may be acceptable for patients who had this surgical technique because it is similar to the deterioration found in other surgical procedures of emmetropization. [J Refract Surg. 2018;34(7):482-488.].

Pupillometry in Chagas disease.

PURPOSE: We investigated parasympathetic innervation abnormalities of the iris sphincter and ciliary muscles in chronic Chagas disease by measuring pupillary diameter and intraocular pressure. METHODS: A group of 80 patients with Chagas disease was compared with 76 healthy individuals without chagasic infection. The following procedures were performed: pupillometry, hypersensitivity test to pilocarpine 0.125%, intraocular pressure measurement (IOP), basal pupil diameter (BPD), absolute pupillary constriction amplitude (ACA), relative pupillary constriction amplitude (RCA) and the presence of anisocoria. RESULTS: The prevalence of anisocoria was higher in chagasic patients (p<0.01). These patients had mean basal pupillary diameter, mean photopic pupillary diameter and mean value of absolute pupillary constriction amplitude significantly lower than non-chagasic ones (p<0.01, mean difference -0.50mm), (p=0.02, mean difference -0.20mm), (p<0.01, mean difference -0.29mm), respectively. The relative pupillary constriction amplitude did not differ between the two groups (p=0.39, mean difference -1.15%). There was hypersensitivity to dilute pilocarpine in 8 (10%) of the chagasic patients in the right eye and in 2 (2.5%) in the left eye and in 1 (1.25%) in both eyes. The mean value of intraocular pressure had a marginal statistical significance between the two groups (p=0.06, mean difference -0.91mmHg). CONCLUSIONS: Patients with chagasic infection may exhibit ocular parasympathetic dysfunction, demonstrable by pupillometry and the dilute pilocarpine hypersensitivity test.

Pupillometry in Chagas disease / Pupilometria na doença de Chagas

ABSTRACT Purpose: We investigated parasympathetic innervation abnormalities of the iris sphincter and ciliary muscles in chronic Chagas disease by measuring pupillary diameter and intraocular pressure. Methods: A group of 80 patients with Chagas disease was compared with 76 healthy individuals without chagasic infection. The following procedures were performed: pupillometry, hypersensitivity test to pilocarpine 0.125%, intraocular pressure measurement (IOP), basal pupil diameter (BPD), absolute pupillary constriction amplitude (ACA), relative pupillary constriction amplitude (RCA) and the presence of anisocoria. Results: The prevalence of anisocoria was higher in chagasic patients (p<0.01). These patients had mean basal pupillary diameter, mean photopic pupillary diameter and mean value of absolute pupillary constriction amplitude significantly lower than non-chagasic ones (p<0.01, mean difference -0.50mm), (p=0.02, mean difference -0.20mm), (p<0.01, mean difference -0.29mm), respectively. The relative pupillary constriction amplitude did not differ between the two groups (p=0.39, mean difference -1.15%). There was hypersensitivity to dilute pilocarpine in 8 (10%) of the chagasic patients in the right eye and in 2 (2.5%) in the left eye and in 1 (1.25%) in both eyes. The mean value of intraocular pressure had a marginal statistical significance between the two groups (p=0.06, mean difference -0.91mmHg). Conclusions: Patients with chagasic infection may exhibit ocular parasympathetic dysfunction, demonstrable by pupillometry and the dilute pilocarpine hypersensitivity test.

RESUMO Introdução: Investigaram-se anormalidades da inervação parassimpática dos músculos esfíncter da íris e ciliar na doença de Chagas crônica, através de medidas pupilares e da pressão intraocular. Métodos: Foram estudados dois grupos, um com 80 chagásicos e outro com 76 indivíduos saudáveis sem infecção chagásica. Foram realizados os seguintes procedimentos: pupilometria, teste de hipersensibilidade à pilocarpina a 0,125%, medida da pressão intraocular (PIO), diâmetro basal da pupila (DBP), amplitude de constrição pupilar absoluta (ACA), amplitude de constrição pupilar relativa (ACR), e presença de anisocoria. Resultados: A prevalência de anisocoria foi maior nos chagásicos (p<0,01). Estes pacientes apresentaram diâmetro basal pupilar médio, diâmetro fotópico médio e valor médio da amplitude de constrição pupilar absoluta, significativamente menores que os não chagásicos, (p<0,01, diferença de média -0,50mm), (p=0.02, diferença de média -0,20mm), (p<0,01, diferença de média -0,29mm), respectivamente. A amplitude de constrição pupilar relativa não diferiu entre os dois grupos (p=0,39, diferença de média -1,15%). Houve hipersensibilidade à pilocarpina diluída em 8 (10%) chagásicos no olho direito em 2 (2,5%) no olho esquerdo e em 1 (1,25%) em ambos os olhos. O valor médio da pressão intraocular teve significância marginal entre os dois grupos (p=0,06, diferença de média -0,91mmHg). Conclusões: Pacientes com infecção chagásica podem apresentar disfunção parassimpática ocular, demonstrável pela pupilometria e pelo teste de hipersensibilidade à pilocarpina diluída.

Variable phenotype in a novel mutation in PHOX2B.

We evaluated a family with three siblings, two of whom ages 2 years and 19 months, had long segment colonic agangliosis and anisocoria. The mother also had anisocoria. All three affected family members were mildly dysmorphic with a flat facial profile, square appearance to the face, depressed nasal bridge, and anteverted nares. Genetic testing identified a novel heterozygous mutation, c.234C>G, resulting in a premature stop codon in exon 1 of the PHOX2B gene. Screening for neural crest tumors was performed in the siblings and to date has been negative. This family supports a strong association between non polyalanine tract mutations, autonomic dysfunction, and Hirschsprung disease, but suggests mutation outside of the polyalanine tract may not dictate severe phenotype with significant respiratory compromise. A unique finding in this family is the association of congenital heart disease in two of the affected patients. These malformations may be a sporadic isolated finding or the result of environmental factors or a modifying allele. Given the association between congenital heart disease and aberrant neural crest cell development, however, findings are suggestive that congenital heart disease may be a rare feature of PHOX2B mutation which has not been previously reported.

Pupil-size asymmetry is a physiologic trait related to gender, attentional function, and personality.

A small difference in the size of the two pupils is common in healthy individuals, a condition termed benign or physiologic anisocoria (BA). Past research indicates that BA is probably caused by asymmetry in sympathetic nervous system (SNS) function [e.g., Rosenberg (2008). Physiologic anisocoria: A manifestation of a physiologic sympathetic asymmetry. Neuro-Ophthalmology, 32, 147-149]. This study is the first to show that BA varies with psychological factors linked to brain asymmetry and autonomic arousal, including gender, attention, and personality. Males exhibited a more directional BA than females, consistent with greater hemispheric lateralization in males. BA also varied with a self-report measure of attentional function, consistent with evidence of hemispheric asymmetry in visuospatial attention networks. Finally, BA varied with personality traits linked to autonomic arousal. Individuals exhibiting higher Meanness and Boldness, and lower Empathy scores tended to show more directional BA. This link between personality traits and BA may be related to brain asymmetries in autonomic arousal and emotion-related processing. If future studies employing direct measures of lateralized brain activity confirm the link between BA and SNS asymmetries, this new metric may prove useful in discovering new relationships between brain organization and psychological function, and how these relationships vary across individuals.

The Degree of Anisocoria in Pediatric Patients With Horner Syndrome When Compared to Children Without Disease.

PURPOSE: To study the magnitude of anisocoria in pediatric patients using the plusoptiX A08 (plusoptiX GmbH, Nuremberg, Germany) photoscreener as compared to a literature review of pediatric patients with known Horner syndrome to determine if anisocoria alone should raise suspicion for the diagnosis. METHODS: The medical records of 592 consecutive patients, neonates to 9 years old, were collected and analyzed. All patients had complete ophthalmic examinations that included photoscreening with the plusoptiX A08. Data included age, pupil sizes, and anisocoria. A complete literature search of documented pupillary size in pediatric patients with the diagnosis of Horner syndrome was performed. This was then compared to the normative pediatric pupil data from the study. RESULTS: Of the 592 children without Horner syndrome, 372 had an anisocoria of 0.1 to 0.5 mm (62.84%), 167 had an anisocoria of 0.6 to 1.2 mm (28.16%), and 21 had an anisocoria of 1.3 mm or greater (3.70%). There was no correlation between increasing age and severity of anisocoria (P = .55). For pediatric patients with a diagnosis of Horner syndrome, the average level of anisocoria was 1.37 mm in room light and 2 mm in darkness. In room light, three children had anisocoria of 0.1 to 0.5 mm (9.4%), 14 had anisocoria of 0.6 to 1.2 mm (43.8%), and 15 had anisocoria of 1.3 mm or greater (46.9%). In darkness, the level of anisocoria increased in 19 patients, causing the first category, 0.1 to 0.5 mm, to include 1 patient (3.1%), the second group to include 5 patients (15.6%), and the last group to include 26 patients (81.3%). Other associated signs/symptoms included ptosis (100%), heterochromia (28.1%), anhidrosis (9.4%), straight hair on affected/curly on unaffected side (9.4%), and neck mass (6.3%). In 37.5% of cases, imaging results were negative and no specific etiology was determined. CONCLUSIONS: In a study of 592 children without Horner syndrome, the average pupillary size increased with age, but the degree of anisocoria remained stable with increasing age. Over half of the children studied had anisocoria up to 0.5 mm (62.84%), but rarely had anisocoria greater than 1.3 mm (3.70%). In children with a diagnosis of Horner syndrome, the majority had anisocoria greater than 1.3 mm, with the discrepancy in pupil size becoming more apparent in low levels of light intensity. Anisocoria greater than 1.3 mm is unlikely to be physiologic in a child; therefore, he or she should be carefully evaluated for other localizing signs, such as ptosis, anhidrosis, and neck mass. [J Pediatr Ophthalmol Strabismus. 2016;53(3):186-189.].

Oral Implant-Prostheses: New Teeth for a Brighter Brain.

Several studies have demonstrated that chewing can be regarded as a preventive measure for cognitive impairment, whereas masticatory deficiency, associated with soft-diet feeding, is a risk factor for the development of dementia. At present the link between orofacial sensorimotor activity and cognitive functions is unknown. In subjects with unilateral molar loss we have shown asymmetries in both pupil size and masticatory muscles electromyographic (EMG) activity during clenching: the molar less side was characterized by a lower EMG activity and a smaller pupil. Since implant-prostheses, greatly reduced both the asymmetry in EMG activity and in pupil's size, trigeminal unbalance, leading to unbalance in the activity of the Locus Coeruleus (LC), may be responsible for the pupil's asymmetry. According to the findings obtained in animal models, we propose that the different activity of the right and left LC may induce an asymmetry in brain activity, thus leading to cognitive impairment. According to this hypothesis, prostheses improved the performance in a complex sensorimotor task and increased the mydriasis associated with haptic tasks. In conclusion, the present study indicates that the implant-prosthesis therapy, which reduces the unbalance of trigeminal proprioceptive afferents and the asymmetry in pupil's size, may improve arousal, boosting performance in a complex sensorimotor task.

Sensorimotor trigeminal unbalance modulates pupil size.

We studied whether patients affected by Temporo-Mandibular Disorder (TMD), showing asymmetric electromyographic (EMG) activity of masticatory muscles also display asymmetries in pupil size. In 30 pain free TMD patients a highly significant, positive correlation was found between left-right differences in EMG and pupil size. The asymmetry in pupil size was induced by the asymmetric sensorimotor signals arising from the orofacial region, since pupils became of about the same size following orthotic correction, which greatly reduced the EMG asymmetry. Moreover, bite wearing bilaterally increased the mydriasis induced by performing haptic tasks. Finally, unbalancing the occlusion by a precontact increased the diameter of the ipsilateral pupil and abolished the mydriasis induced by haptic tasks. In conclusion, trigeminal sensorimotor signals may exert a tonic control on autonomic structures regulating pupil size at rest and during sensorimotor tasks. Since task-associated mydriasis is correlated with task performance and is strictly proportional to the phasic release of noradrenaline at cerebral cortical level, the present findings may suggest an impact of unbalanced trigeminal activity on brain processing not directly related to the orofacial region.

Studying the effect of iris mechanics on the pupillary light reflex using brimonidine-induced anisocoria.

PURPOSE: To study and correct for the limiting effect of iris mechanics on the amplitude of light-evoked pupil contractions in order to derive a more clinically accurate assessment of afferent input to the visual system. METHODS: Transient pupil responses were recorded to a series of 1-second red Ganzfeld light stimuli with a stepwise increase in stimulus intensity using a binocular infrared computerized pupillometer. One eye of eight healthy subjects was treated with 0.2% brimonidine tartrate ophthalmic solution to induce pupil size reduction. The amount of pupil contraction as a function of stimulus intensity was compared between the brimonidine-treated, miotic eye and the untreated eye. RESULTS: BRIMONIDINE TREATMENT PRODUCED SIGNIFICANT REDUCTION IN PUPIL SIZE IN HEALTHY SUBJECTS (MEAN REDUCTION IN PUPIL SIZE: 1.78 ± 0.35 mm, P < 0.05). For increasing light intensity, the treated pupil started to show reduced pupil contractions compared with the contralateral untreated pupil when the peak of pupil contraction reached an average pupil size of 3.25 ± 0.61 mm (range, 2.38-4.44 mm). When measured by percent pupil contraction (contraction amplitude/baseline pupil diameter), the pupil response as a function of stimulus intensity in the treated, miotic eye did not differ from that in the untreated eye. CONCLUSIONS: Iris mechanics limits the amount of pupil contraction and can act to reduce the assessed neuronal integration of the pupil light reflex. Pupil response assessed by using percent contraction amplitude is least affected by mechanical effects and provides a more accurate approximation of afferent input.

[Characteristics of pupil function in patients with dissociated vertical divergence]. / Bestehen Besonderheiten der Pupillomotorik bei dissoziiertem Höhenschielen?

Dissociated vertical divergence (DVD) is frequently associated with the infantile strabismus syndrome. There are different theories on the pathomechanism of this disorder, but none of them is generally accepted. Some authors believe that the slow upward movement of the covered eye is due to a different illumination of both retinae and consequently an unequal activity of the oculomotor nerve's nuclei. In one hypothesis a predominance of crossing pupillary tract fibres from the pretectal area to motor and parasympathetic nuclei of the oculomotor nerve was supposed. The consequence of this abnormal pathway in the midbrain would be a pronounced contraction anisocoria in patients with DVD. In contraction anisocoria the directly illuminated pupil contracts more strongly than the contralateral pupil without any efferent defect. In a small study we compared direct and indirect pupillary light reflexes in 11 DVD patients and 10 normal subjects. We found no significant differences of contraction anisocoria between the two groups. The results do not support the hypothesis of a different pupillary tract pathway in the midbrain of patients with DVD.

Síndrome disautonómico de Ross: variaciones de un tema / Disautonomic Ross syndrome: variations about one theme

El síndrome de Ross fue descrito en 1958 como una afección degenerativa del sistema nervioso autónomo definido por la tríada de anhidrosis generalizada, disminución de los reflejos tendinosos y pupila tónica. Desde su descripción inicial se han descrito cerca de cuarenta casos. Comunicamos tres pacientes con variantes de interés que incluyen la presencia de espasmos cíclicos espontáneos del esfínter de iris, el desarrollo conjunto de síndrome de Holmes-Adie en un lado y síndrome Horner posganglionar en el otro, trastornos del desarrollo piloso en el lado de la anhidrosis, alteraciones de la motilidad intestinal, lengua sin papilas gustativas y disfunción sexual.

Ross Syndrome was described in 1958 as a degenerative condition of the autonomic nervous system defined by a triad of generalized anhidrosis, reduction of tendon reflexes and tonic pupil. Since its initial description about 40 cases have been described. We communicate three cases with variants of interest involving the presence of the simultaneous development of syndrome of Holmes-Adie on one side and Horner syndrome in the other, disorders of pilous follicle development on the side of anhidrosis, spontaneous disturbances of intestinal motility, tonque without papillae and sexual dysfunction.

Early diagnosis of Horner syndrome using topical apraclonidine.

The diagnosis of Horner syndrome (HS) using apraclonidine eye drops is an alternative to the use of topical cocaine drops. A number of reports have described the efficacy of apraclonidine testing, but there is some debate over its sensitivity in the acute setting. We describe a patient with HS secondary to carotid dissection who had a positive response to apraclonidine 3 hours after the onset of symptoms. The case is made for a larger study of apraclonidine use to determine its true sensitivity and specificity, identify confounding factors, and redefine the criteria for positive testing.