Spectral dependency of the human pupillary light reflex. Influences of pre-adaptation and chronotype

Non-visual photoreceptors (ipRGCs) and rods both exert a strong influence on the human pupil, yet pupil models regularly use cone-derived sensitivity as their basis. This inconsistency is further exacerbated by the fact that circadian effects can modulate the wavelength sensitivity. We assessed the pupillary reaction to narrowband light stimuli in the mesopic range. Pupil size for eighty-three healthy participants with normal color vision was measured in nine experimental protocols with varying series of continuous or discontinuous light stimuli under Ganzfeld conditions, presented after 90 seconds of dark adaptation. One hundred and fifty series of stimulation were conducted across three experiments, and were analyzed for wavelength-dependency on the normalized pupillary constriction (nPC), conditional on experimental settings and individual traits. Traits were surveyed by questionnaire; color vision was tested by Ishihara plates or the Lanthony D15 test. Data were analyzed with generalized additive mixed models (GAMM). The normalized pupillary constriction response is consistent with L+M-cone derived sensitivity when the series of light stimuli is continuous, i.e., is not interrupted by periods of darkness, but not otherwise. The results also show that a mesopic illuminance weighing led to an overall best prediction of pupillary constriction compared to other types of illuminance measures. IpRGC influence on nPC is not readily apparent from the results. When we explored the interaction of chronotype and time of day on the wavelength dependency, differences consistent with ipRGC influence became apparent. The models indicate that subjects of differing chronotype show a heightened or lowered sensitivity to short wavelengths, depending on their time of preference. IpRGC influence is also seen in the post-illumination pupil reflex if the prior light-stimulus duration is one second. However, shorter wavelengths than expected become more important if the light-stimulus duration is fifteen or thirty seconds. The influence of sex on nPC was present, but showed no interaction with wavelength. Our results help to define the conditions, under which the different wavelength sensitivities in the literature hold up for narrowband light settings. The chronotype effect might signify a mechanism for strengthening the individual´s chronotype. It could also be the result of the participant’s prior exposure to light (light history). Our explorative findings for this effect demand replication in a controlled study.

Atypical Pupil Reactions in Brain Dead Patients

Background: During routine diagnosis of brain death, changes in pupil diameter in response to the stimulation of peripheral nerves are sometimes observed. For example, pupillary dilation after diagnosed brain death is described in the literature as the ciliospinal reflex. However, pupil constriction creates diagnostic doubts. Objective: The pupillometric analysis of pupil response to stimulation of the cervicothoracic spinal cord in patients with diagnosed brain death. Methods: Instrumental tests to confirm the arrest of cerebral circulation were performed in 30 adult subjects (mean age 53.5 years, range 26–75 years) with diagnosed brain death. In addition, a pupillometer was used to measure the change in pupil diameter in response to neck flexion. Intervention: Flexion of the neck and measuring the response in change of the pupil with the use of the pupillometer. Results: The change in the pupil was observed in the examined group of patients. Difference in pupil size ≥ 0.2 mm was observed in 14 cases (46%). In five cases (17%), pupil constriction was found (from 0.2 to 0.7 mm). Measurement error was +/− 0.1 mm. Conclusions: Both pupillary constriction and dilatation may occur due to a ciliospinal reflex in patients with brain death. This phenomenon needs further research in order to establish its pathophysiology.

Spectral dependency of the human pupillary light reflex. Influences of pre-adaptation and chronotype.

Non-visual photoreceptors (ipRGCs) and rods both exert a strong influence on the human pupil, yet pupil models regularly use cone-derived sensitivity as their basis. This inconsistency is further exacerbated by the fact that circadian effects can modulate the wavelength sensitivity. We assessed the pupillary reaction to monochromatic light stimuli in the mesopic range. Pupil size for eighty-three healthy participants with normal color vision was measured in nine experimental protocols with varying series of continuous or discontinuous light stimuli under Ganzfeld conditions, presented after 90 seconds of dark adaptation. One hundred and fifty series of stimulation were conducted across three experiments, and were analyzed for wavelength-dependency on the pupillary constriction amplitude (PCA), conditional on experimental settings and individual traits. Traits were surveyed by questionnaire; color vision was tested by Ishihara plates or the Lanthony D15 test. Data were analyzed with generalized additive mixed models (GAMM). The pupillary constriction amplitude response is consistent with L+M-cone derived sensitivity when the series of light stimuli is continuous, i.e., is not interrupted by periods of darkness, but not otherwise. The results also show that a mesopic illuminance weighing led to an overall best prediction of pupillary constriction compared to other types of illuminance measures. IpRGC influence on PCA is not readily apparent from the results. When we explored the interaction of chronotype and time of day on the wavelength dependency, differences consistent with ipRGC influence became apparent. The models indicate that subjects of differing chronotype show a heightened or lowered sensitivity to short wavelengths, depending on their time of preference. IpRGC influence is also seen in the post-illumination pupil reflex if the prior light-stimulus duration is one second. However, shorter wavelengths than expected become more important if the light-stimulus duration is fifteen or thirty seconds. The influence of sex on PCA was present, but showed no interaction with wavelength. Our results help to define the conditions, under which the different wavelength sensitivities in literature hold up for monochromatic light settings. The chronotype effect might signify a mechanism for strengthening the individual´s chronotype, but demands replication in a controlled study.

Dilute pilocarpine test for diagnosis of Adie’s tonic pupil

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.

A Systematic Literature Review on Traumatic Optic Neuropathy

Traumatic optic neuropathy (TON) is an uncommon vision-threatening disorder that can be caused by ocular or head trauma and is categorized into direct and indirect TON. The overall incidence of TON is 0.7–2.5%, and indirect TON has a higher prevalence than direct TON. Detection of an afferent pupillary defect in the presence of an intact globe in a patient with ocular or head trauma with decreased visual acuity strongly suggests TON. However, afferent pupillary defects may be difficult to detect in patients who have received narcotics that cause pupillary constriction and in those with bilateral TON. Mechanical shearing of the optic nerve axons and contusion necrosis due to immediate ischemia from damage to the optic nerve microcirculation and apoptosis of neurons is a probable mechanism. The proper management of TON is controversial. High-dose corticosteroid therapy and decompression of the optic nerve provide no additional benefit over observation alone. Intravenous erythropoietin may be a safe and efficient treatment for patients with TON.

Pupillary light reflex in ethambutol-induced optic neuropathy

We evaluated changes in the pupillary light reflex (PLR) of ethambutol (EMB)-induced optic neuropathy and analyzed the correlations between PLR parameters and other structural changes in EMB-induced optic neuropathy. This retrospective, observational, case–control study involved thirty-two eyes of 17 patients with EMB-induced optic neuropathy (EON group), sixty eyes of 60 patients without EMB-induced optic neuropathy (non-EON group) while taking ethambutol, and forty-five eyes of 45 normal controls. PLR was measured by digital pupillometry. The clinical characteristics, optical coherence tomography measurements and PLR parameters including pupil diameter, constriction latency, constriction ratio/velocity, and dilation velocity were noted. The differences in PLR measurements were compared among the three groups. Correlations between PLR parameters and other structural parameters in EMB-induced optic neuropathy were evaluated. The pupillary constriction ratio, constriction and dilation velocities were significantly reduced in the EON group compared to the non-EON group and controls (all P < 0.05). In EMB-induced optic neuropathy, average outer macular ganglion cell layer (mGCL) thickness showed a significant correlation with the pupillary constriction ratio (ß = 4.14, P = 0.003) and maximal constriction velocity (ß = 1.08, P < 0.001). This study confirmed that pupillary constriction and dilation velocities were significantly decreased in patients with EMB-induced optic neuropathy, compared to normal controls. Digital pupillometry may be a useful tool in the evaluation of EMB-induced optic neuropathy.

Connections between intrinsically photosensitive retinal ganglion cells and TBI symptoms

The majority of patients with traumatic brain injury (TBI) are classified as having a mild TBI. Despite being categorized as mild, these individuals report ongoing and complex symptoms, which negatively affect their ability to complete activities of daily living and overall quality of life. Some of the major symptoms include anxiety, depression, sleep problems, headaches, light sensitivity, and difficulty reading. The root cause for these symptoms is under investigation by many in the field. Of interest, several of these symptoms such as headaches, ocular pain, light sensitivity, and sleep disturbances may overlap and share underlying circuitry influenced by the intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells are light sensing, but non–image forming, and they influence corneal function, pupillary constriction, and circadian rhythm. In this review, we discuss these symptoms and propose a role of the ipRGCs as at least one underlying and unifying cause for such symptoms.

Objective Measurement of Sustained Pupillary Constriction: A Pilot Study Using an App-Based Pupilometer

Background: The pupillary reaction is controlled by the two main branches of the autonomic nervous system, namely the parasympathetic and sympathetic nervous systems. New discoveries in pupil research has identified that intrinsically photosensitive retinal ganglion cells have an impact on pupillary constriction, particularly sustained pupillary constriction. In the current paper, an objective measurement of sustained pupillary constriction versus the inability to maintain sustained pupillary constriction are observed. The variability in the sustained pupillary constriction, i.e. Alpha Omega pupil, can be objectively identified with the use of modern technology. Case Examples: Two female subjects were adapted to dim illumination, and then two objective pupil measurements of the right eye using Reflex – PLR Analyzer by BrightLamp© (Indianapolis, IN, USA) with sustained illumination were obtained. Subject 1, a 25 year-old-female, demonstrated normal ability of the pupil to constrict and sustain constriction for 10 seconds. She was used as a control for subject 2. Subject 2, a 27 year-old-female, demonstrated the inability to sustain pupillary constriction. She reported being under great psychological stress. Her pupil began to re-dilate between 2 and 3 seconds after the initial constriction. Conclusion: Objective pupillometry can be used to assist in many diagnoses and provides the clinician invaluable information on the state of the individual, and qualifications of sustained pupillary constriction can now be assessed in an objective manner.