Pupillometry

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Pupillometry, the measurement of pupil size and reactivity, is a key part of the clinical neurological exam for patients with a wide variety of neurological injuries. It is also used in psychology. [1] [2]

Contents

Pupillometry in critical care

For more than 100 years, clinicians have evaluated the pupils of patients with suspected or known brain injury or impaired consciousness to monitor neurological status and trends, checking for pupil size and reactivity to light. [3] In fact, before the advent of electricity, doctors checked a patient’s reaction to light using a candle.

Today, clinicians routinely evaluate pupils as a component of the neurological examination and monitoring of critically ill patients, including patients with traumatic brain injury and stroke. [4] [5] [6] In 2016, Couret et Al. showed that "Standard practice in pupillary monitoring yields inaccurate data that Automated quantitative pupillometry is a more reliable method with which to collect pupillary measurements at the bedside [7] . In 2019, the first smartphone based pupillometer was released as an accurate and economical way to determine pupil size and dynamic response objectively. [8] However, another study has shown the necessary use of an opaque eyecup as pupillary light reflex is affected by ambiant light. [7] It is important to mention that certain pupillometers and all smartphones do not have this particular feature.

NeuroLight pupillometer and its QPi score Pupillometer neurolight.jpg
NeuroLight pupillometer and its QPi score

Patient care and outcome

Numerous studies have shown the importance of pupil evaluation in the clinical setting, and pupillary information is used extensively in patient management and as an indication for possible medical intervention.

Patients who undergo prompt intervention after a new finding of pupil abnormality have a better chance of recovery. [9]

Alterations of the pupil light reflex, size of the pupil, and anisocoria (unequal pupils) are correlated with outcomes of patients with traumatic brain injury. [10] [2] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] Blood flow imaging has shown that pupil changes are highly correlated with brainstem oxygenation and perfusion, [19] [18] [21] and anisocoria can be an indicator of a pathological process or neurological dysfunction. [18] [22] [23]

Investigators have used pupil size and reactivity as fundamental parameters of outcome predictive models in conjunction with other clinical information such as age, mechanism of injury, and Glasgow Coma Scale, [21] [24] [25] and have correlated the models with the presence and location of intracranial mass lesions. [11]

The National Institutes of Health Stroke Scale (NIHSS) uses pupillary response as a systematic assessment tool to provide a quantitative measure of stroke-related neurologic deficit and to evaluate acuity of stroke patients, determine appropriate treatment, and predict patient outcome. [26]

Manual vs. automated pupil assessment

Traditionally, pupil measurements have been performed in a subjective manner by using a penlight or flashlight to manually evaluate pupil reactivity reactivity (sPLR, "s" stands for standard) and using a pupil gauge to estimate pupil size. However, manual pupillary assessment is subject to significant inaccuracies and inconsistencies. Studies have shown inter-examiner disagreement in the manual evaluation of pupillary reaction to be as high as 39 percent. [1] [2] [4] [5] [27] [28] [29] [30] Automated pupillometry involves the use of a pupillometer, a portable, handheld device that provides a reliable and objective measurement of pupillary size, symmetry, and reactivity through measurement of the pupil light reflex (qPLR). sPLR is opposed to quantitative PLR (qPLR) that is provided by an automated pupillometer. qPLR [31] corresponds to the percentage of pupillary constriction to a calibrated light stimulus. Pupillometers before 2018 predominately used infrared cameras to observe pupil diameter. Then, in 2019, advancements in machine learning have enabled visual spectrum pupillometry using a smartphone. When measuring the pupillary light reflex, it's important to use an opaque eyecup to get accurate results. [7] This is because the measurement can be affected by ambient light. It's worth noting that some devices, such as smartphones and certain pupillometers, lack this ability. Therefore, using an eyecup is even more necessary. Overall, using an eyecup helps ensure precise measurements of the pupillary light reflex. Numeric scales allow for a more rigorous interpretation and classification of the pupil response and are a primary feature of both hardware and software based pupillometers.

NPi-300 automated infrared pupillometer (NeurOptics, Inc.) NeurOptics' NPi-300 Pupillometer.png
NPi-300 automated infrared pupillometer (NeurOptics, Inc.)

Automated pupillometry removes subjectivity from the pupillary evaluation, providing more accurate and trendable pupil data, and allowing earlier detection of changes for more timely patient treatment. By using automated pupillometers and algorithms such as QPi score (Quantitative Pupillometry Index) or Reflex's "Reflex Score", doctors can easily and objectively assess pupil reactivity that could otherwise be missed by manual assessment. Automated pupillometers have been proven to be more effective than manual pupil assessment.

With an automated pupillometer and an algorithm analyzing the pupil continuously for 5 seconds, the Quantitative Pupillometry Index (QPi) can measure pupillary reactivity and provides a numerical value. It provides objective data and can detect subtle changes that might not be apparent to the naked eye.  Its quantitative nature provides objective and more reliable assessment.   Moreover, it is color-coded for a quick clinical interpretation. It displays through a qualitative scale a quantitative interval for each color associated with its number. [32]

Mobile visual spectrum automated pupillometers have been proven effective as an alternative to infrared pupillometers that typically command a higher cost. [33] [10] Controversy has risen around infrared pupillometers as some of them are routinely incapable of measuring hippus, a natural pupillary phenomenon, which has professionals concluding that NeurOptics' devices fit a curve to measured data. The NeuroLight pupillometer (IDMED), on the other hand, provides this pupillary unrest in ambient light (PUAL) function, which is described as a consistent indicator of opioid effect and is the gold standard in this field of research. [34] [35] Infrared pupillometers use an eye guard that is placed on a subject's orbit or zygomatic bone and uses a fixed distance calibration to determine pupil size which has further brought into question the validity of fixed distance measures as the human population varies widely in skull structure. The NeuroLight and NPi pupillometers are both devices for measuring pupils but differ significantly in terms of ergonomics and functionality. The main distinction lies in the NPi’s use of a transparent eye guard that contains an electronic component for patient identification and results recording, making it unique to each patient. This consumable that allows ambient light to pass through may result in data reproducibility issues and increased costs. NeuroLight, in contrast, comes with a touchscreen display and employs a reusable opaque eyecup that isolates the eye from ambient light. This design feature not only enhances the accuracy of the pupillary measurements [7] but also reduces the overall cost of usage to the initial purchase of the device.

According to the new American Heart Association guidelines, most deaths attributable to post-cardiac arrest brain injury are due to active withdrawal of life-sustaining treatment based on a predicted poor neurological outcome. The NPi and automated pupillometry have recently been included in the updated 2020 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) as an object measurement supporting brain injury prognosis in patients following cardiac arrest. [36]

A study published in the Journal of Neurosurgery found that automated pupillometers may signal an early warning of potential delayed cerebral ischemia and enable preemptive escalation of care. [37]

The American Journal of Critical Care revealed that critical care and neurosurgical nurses consistently underestimated pupil size, were unable to identify anisocoria, and incorrectly assessed pupil reactivity (sPLR). It concluded that automated pupillometry is a necessary tool for accuracy and consistency, and that it might facilitate earlier detection of subtle pupil changes, allowing more effective and timely diagnostic and treatment interventions. [1]

In addition, a study from The University of Texas Southwestern Medical Center compared 2,329 manual pupillary exams performed simultaneously by two examiners (neurology and neurosurgery attending and resident physicians, staff nurses, and mid-level practitioners) under identical conditions and showed low inter-examiner reliability. [28] [29] The American Association of Critical-Care Nurses(AACN) Procedure Manual for High Acuity, Progressive and Critical Care, 7th Edition, and the American Association of Neuroscience Nurses (AANN) Core Curriculum for Neuroscience Nursing, 6th Edition, now include sections illustrating how use of a pupillometer removes subjectivity and allows pupillary reactivity to be trended in a consistent, objective, and quantifiable way. The AACN Procedure Manual, which was extensively reviewed by more than 100 experts in critical care nursing, is the authoritative reference for procedures performed in critical care settings, and the AANN curriculum is a comprehensive resource for practicing neuroscience nurses.

Advancements in mobile-based automated pupillometry have been made in recent years to accommodate for the growing number of mobile phones being used in healthcare. Notably, brightlamp, Inc. has secured the first intellectual property relating to mobile quantitative pupillometry.

Pupillometry in psychology

Stimulants

Photographs

Hess and Polt (1960) [38] presented pictures of semi-naked adults and babies to adults (four men and two women). Pupils of both sexes dilated after seeing pictures of people of the opposite sex. In females, the difference in pupil size occurred also after seeing pictures of babies and mothers with babies. This examination showed that pupils react not only to the changes of intensity of light (pupillary light reflex) but also reflect arousal or emotions.

In 1965 Hess, Seltzer and Shlien [39] examined pupillary responses in heterosexual and homosexual males. Results showed a greater pupil dilation to pictures of the opposite sex for heterosexuals and to pictures of the same sex for homosexuals.

According to T.M. Simms (1967), [40] pupillary responses of males and females were greater when they were exposed to pictures of the opposite sex. [41] In another study, Nunnally and colleagues (1967) [42] found that seeing slides rated as 'very pleasant' was associated with greater pupil dilation as seeing slides rated as neutral or very unpleasant.

Infants showed greater pupil size when they saw pictures of faces than when they saw geometric shapes, [41] [43] [44] and greater dilation after seeing pictures of the infant's mother than pictures of a stranger. [43]

Cognitive load

Pupillary responses can reflect activation of the brain allocated to cognitive tasks. Greater pupil dilation is associated with increased processing in the brain. [45] Vacchiano and colleagues (1968) found that pupillary responses were associated with visual exposure to words with high, neutral or low value. Presented low-value words were associated with dilation, and high-value words with constriction of a pupil. [46] In decision-making tasks dilation increased before the decision as a function of cognitive load. [47] [48] In an experiment about short-term serial memory, students heard strings of words and were asked to repeat them. Greater pupil diameter was observed after the items were heard (depending on how many items were heard), and decreased after items were repeated. [49] The more difficult the task, the greater pupil diameter observed from the time preceding the solution [50] until the task was completed. [51]

Long-term memory

The pupil response reflects long-term memory processes both at encoding, predicting the success of memory formation [52] and at retrieval, reflecting different recognition outcomes. [53]

See also

Related Research Articles

<span class="mw-page-title-main">Pupil</span> Part of an eye

The pupil is a hole located in the center of the iris of the eye that allows light to strike the retina. It appears black because light rays entering the pupil are either absorbed by the tissues inside the eye directly, or absorbed after diffuse reflections within the eye that mostly miss exiting the narrow pupil. The size of the pupil is controlled by the iris, and varies depending on many factors, the most significant being the amount of light in the environment. The term "pupil" was coined by Gerard of Cremona.

<span class="mw-page-title-main">Mydriasis</span> Excessive dilation of the pupil

Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drug. It may also be of unknown cause.

<span class="mw-page-title-main">Chiari malformation</span> Medical condition

Chiari malformation (CM) is a structural defect in the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum. CMs can cause headaches, difficulty swallowing, vomiting, dizziness, neck pain, unsteady gait, poor hand coordination, numbness and tingling of the hands and feet, and speech problems. Less often, people may experience ringing or buzzing in the ears, weakness, slow heart rhythm, or fast heart rhythm, curvature of the spine (scoliosis) related to spinal cord impairment, abnormal breathing, such as central sleep apnea, characterized by periods of breathing cessation during sleep, and, in severe cases, paralysis.

<span class="mw-page-title-main">Intracranial pressure</span> Pressure exerted by fluids inside the skull and on the brain

Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF.

Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical sensitivity of the eyes, though the term is sometimes additionally applied to abnormal or irrational fear of light, such as heliophobia. The term photophobia comes from the Greek φῶς (phōs), meaning "light", and φόβος (phóbos), meaning "fear".

<span class="mw-page-title-main">Pupillary light reflex</span> Eye reflex which alters the pupils size in response to light intensity

The pupillary light reflex (PLR) or photopupillary reflex is a reflex that controls the diameter of the pupil, in response to the intensity (luminance) of light that falls on the retinal ganglion cells of the retina in the back of the eye, thereby assisting in adaptation of vision to various levels of lightness/darkness. A greater intensity of light causes the pupil to constrict, whereas a lower intensity of light causes the pupil to dilate. Thus, the pupillary light reflex regulates the intensity of light entering the eye. Light shone into one eye will cause both pupils to constrict.

<span class="mw-page-title-main">Subarachnoid hemorrhage</span> Bleeding into the subarachnoid space

Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, weakness, numbness, and sometimes seizures. Neck stiffness or neck pain are also relatively common. In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed.

<span class="mw-page-title-main">Argyll Robertson pupil</span> Medical condition

Argyll Robertson pupils are bilateral small pupils that reduce in size on a near object, but do not constrict when exposed to bright light. They are a highly specific sign of neurosyphilis; however, Argyll Robertson pupils may also be a sign of diabetic neuropathy. In general, pupils that accommodate but do not react are said to show light-near dissociation (i.e., it is the absence of a miotic reaction to light, both direct and consensual, with the preservation of a miotic reaction to near stimulus.

<span class="mw-page-title-main">Anisocoria</span> Unequal size of the eyes pupils

Anisocoria is a condition characterized by an unequal size of the eyes' pupils. Affecting up to 20% of the population, anisocoria is often entirely harmless, but can be a sign of more serious medical problems.

Pupillometer, also spelled pupilometer, is a medical device intended to measure by reflected light the size of the pupil of the eye. In addition to measuring pupil size, current automated pupillometers may also be able to characterize pupillary light reflex. Some instruments for measuring pupillary distance (PD) are often, but incorrectly, referred to as pupilometers.

<span class="mw-page-title-main">Relative afferent pupillary defect</span> Medical condition

A relative afferent pupillary defect (RAPD), also known as a Marcus Gunn pupil, is a medical sign observed during the swinging-flashlight test whereupon the patient's pupils dilate when a bright light is swung from the unaffected eye to the affected eye. The affected eye still senses the light and produces pupillary sphincter constriction to some degree, albeit reduced.

<span class="mw-page-title-main">Decompressive craniectomy</span> Neurosurgical procedure to treat swelling

Decompressive craniectomy is a neurosurgical procedure in which part of the skull is removed to allow a swelling or herniating brain room to expand without being squeezed. It is performed on victims of traumatic brain injury, stroke, Chiari malformation, and other conditions associated with raised intracranial pressure. Use of the surgery is controversial.

<span class="mw-page-title-main">Dilated fundus examination</span>

Dilated fundus examination (DFE) is a diagnostic procedure that uses mydriatic eye drops to dilate or enlarge the pupil in order to obtain a better view of the fundus of the eye. Once the pupil is dilated, examiners use ophthalmoscopy to view the eye's interior, which makes it easier to assess the retina, optic nerve head, blood vessels, and other important features. DFE has been found to be a more effective method for evaluating eye health when compared to non-dilated examination, and is the best method of evaluating structures behind the iris. It is frequently performed by ophthalmologists and optometrists as part of an eye examination.

<span class="mw-page-title-main">Pupillary response</span> Physiological response that varies the size of the pupil

Pupillary response is a physiological response that varies the size of the pupil, via the optic and oculomotor cranial nerve.

<span class="mw-page-title-main">Task-invoked pupillary response</span>

Task-invoked pupillary response is a pupillary response caused by a cognitive load imposed on a human and as a result of the decrease in parasympathetic activity in the peripheral nervous system. It is found to result in a linear increase in pupil dilation as the demand a task places on the working memory increases. Beatty evaluated task-invoked pupillary response in different tasks for short-term memory, language processing, reasoning, perception, sustained attention and selective attention and found that it fulfills Kahneman's three criteria for indicating processing load. That is, it can reflect differences in processing load within a task, between different tasks and between individuals. It is used as an indicator of cognitive load levels in psychophysiology research.

<span class="mw-page-title-main">Nicholas Theodore</span> American neurosurgeon

Nicholas Theodore is an American neurosurgeon and researcher at Johns Hopkins University School of Medicine. He is known for his work in spinal trauma, minimally invasive surgery, robotics, and personalized medicine. He is Director of the Neurosurgical Spine Program at Johns Hopkins and Co-Director of the Carnegie Center for Surgical Innovation at Johns Hopkins.

<span class="mw-page-title-main">Pressure reactivity index</span>

Pressure reactivity index or PRx is tool for monitoring cerebral autoregulation in the intensive care setting for patients with severe traumatic brain injury or subarachnoid haemorrhage, in order to guide therapy to protect the brain from dangerously high or low cerebral blood flow.

Clinicians routinely check the pupils of critically injured and ill patients to monitor neurological status. However, manual pupil measurements have been shown to be subjective, inaccurate, and not repeatable or consistent. Automated assessment of the pupillary light reflex has emerged as an objective means of measuring pupillary reactivity across a range of neurological diseases, including stroke, traumatic brain injury and edema, tumoral herniation syndromes, and sports or war injuries. Automated pupillometers are used to assess an array of objective pupillary variables including size, constriction velocity, latency, and dilation velocity, which are normalized and standardized to compute an indexed score such as the Neurological Pupil index (NPi).

<span class="mw-page-title-main">Sandi Lam</span> Canadian pediatric neurosurgeon

Sandi Lam is a Canadian pediatric neurosurgeon and is known for her research in minimally invasive endoscopic hemispherectomy for patients with epilepsy. Lam is the Vice Chair for Pediatric Neurological Surgery at Northwestern University and the Division Chief of Pediatric Neurosurgery at Lurie Children's Hospital. She has spent her career advancing pediatric brain surgery capabilities globally through her work in Kenya performing surgeries as well as training and mentoring local residents and fellows.

Marjorie Wang is an American neurosurgeon, researcher, and academic. She is a professor of Neurosurgery and Director of the Complex Spine Fellowship Program at the Medical College of Wisconsin.

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