Comparison of ultrasonographic versus infrared pupillary assessment

Pupillary assessment (i.e., bilateral evaluation of pupils size, shape, symmetry, and reactivity) is a cornerstone of the neurologic physical examination in the critically ill, particularly the neurocritically ill. Systematic pupillary assessments are routinely performed in the critically ill because they can render early signs of neurologic deterioration, which, in some cases, may be the only clinically obtainable sign. The Brain Trauma Foundation’s guidelines for the management of severe traumatic brain injury acknowledge the evaluation of pupils’ size and reactivity to light as source for early prognostic signs of neurologic pathology [1].

There are reports of pupillary assessment as far back as 1929, when Otto Lowestein first developed a technique based on the analysis of simple, direct, visual evaluations [2]. Nonetheless, despite remarkable technologic advances and substantial improvements on the understanding of the central nervous system, the pupillary examination has not much changed during the last century. Regarding the conventional, visual pupillary assessment, there is considerable intra- and inter-observer variability due to inconsistency on several factors, such as illumination of patient’s room, examiner’s visual acuity and experience, and intensity and technique of light stimuli. Therefore, alternative techniques have been proposed [3, 4].

The most accepted alternative technique is the infrared pupillary assessment (IPA), first described in 1958 by Lowestein himself, and then, as from 1993, extensively studied by Merlin Larson; by these means, both of Lowestein and Larson ended up elucidating the association between pupillary abnormalities and brainstem injuries or pharmacologic effects [5, 6]. In 2003, Taylor et al., using an infrared pupillometer, established an association between intracranial pressure and pupillary abnormalities in patients with acute brain injury [7]. In 2011, Chen et al. using the infrared pupillometer, described a significant inverse relationship between decreasing pupil reactivity and increasing intracranial pressure; the first evidence of pupil abnormalities occurred, on average, 15.9 h prior to the time of the peak of intracranial pressure [8]. Today, the IPA is being increasingly adopted as a routine part of the neurologic examination, supported by a growing body of literature demonstrating its reliability, accuracy, and ease of use. Automated pupillometry allows rapid, non-invasive, reliable, and quantifiable assessment of pupillary function which may allow rapid diagnosis of intracranial pathology that affects clinical decision-making [9, 10].

On the other hand, the first report of ocular ultrasound was made in 1956 [11]. Technologic advances in ultrasound devices have since allowed implementing ocular ultrasound in the evaluation of several ophthalmologic pathologies such as ocular trauma and intraocular foreign body identification [12‐14]. However, the ultrasonographic evaluation of the pupillary diameter and pupillary light reflex has not been well studied, let alone implemented. In cases when direct visualization of the pupil is not possible due to soft tissue injury that precludes eye opening, alternative techniques such as IPA and LED-based perimetric pupillometry have been proposed; unfortunately, most of these techniques do not overcome the physical barrier placed by the soft tissue, rely on advanced devices that are not generally available in emergency situations, and require of specialized technical support [15‐17]. In this context, UPA is particularly useful because it offers a simple yet accurate alternative that can be performed with small, portable devices at the point of care.

To the authors’ knowledge, few reports have been published regarding UPA application and clinical relevance, mostly in emergency medicine and critical care medicine. Nevertheless, none of them have evaluated and compared UPA’s accuracy to standard techniques such as IPA [18‐21].

Total of patients included were 26, most were men (60.0%), with a mean age of 45,05 (range 18–84) years, and mean glasgow coma score at the moment of the pupillary assessment of 8,69 (range 3–15). A total of 212 pupillary measures were obtained, of which 106 were on each eye (i.e., right and left eyes), and 108 were in neurocritically ill patients. Table 1 shows patients classified according to main pathology for ICU admission.

Frequencies and percentages of patients according to main pathology for intensive care unit admission.

Ultrasonographic pupillary assessment was feasible in all patients. There was a strong positive correlation between measures of reduction in pupillary diameter (pupillary light reflex) obtained by IPA and UPA (r_OD = 0.926, 95% CI 0.893–0.949, p-value < 0.001; r_OS = 0.965, 95% CI 0.949–0.976, p-value < 0.001) (Fig. 4a, b).

In the subgroup of patients with critical neurological pathology, a total of 108 measures were obtained with UPA and IPA (54 for OD, 54 for OS) in 8 patients. There was found a strong positive association between UPA and IPA (rOD = 0.935, p value < 0.001; rOS = 0.965, p value < 0.001) (Fig. 4c, d).

Adjusted analysis through simple linear regression models showed good concordance between IPA and UPA (regression line for OD, y = 1, 013x + 0, 0192; regression line for OS, y = 0.8915x + 0.0806). Upon evaluation of normal distribution of the data, 11 measures for OD (differences between-technique measures greater than 0, 3 mm) and 7 for OS (differences between-technique measures less than − 0, 3 mm) were discarded. Taking IPA as reference measure, the percent error for all subjects was 2.77% and 2.15% for OD and OS, respectively (Fig. 5a, b). Regarding concordance between IPA and UPA for measures of reduction in pupillary diameter that were less than 10% (i.e., abnormal), techniques differed in 1 observation for OD and 3 observations for OS, over a total of 106 observations for each eye.

In the subgroup of patients with critical neurological pathology, adjusted analysis through simple linear regression models showed good concordance between IPA and UPA (regression line for OD, y = 0, 986x + 0.0134; regression line for OS, y = 0, 9089x + 0, 0483). Taking IPA as reference measure, the percent error for all subjects was 3.21% and 2.44% for OD and OS, respectively (Fig. 5c, d). Regarding concordance between IPA and UPA for measures of reduction in pupillary diameter that were less than 10% (i.e., abnormal), techniques differed in 1 observation for OD and none for OS, over a total of 54 observations for each eye.

In cases of patients with anisocoria (11 observations), defined as a difference of at least 1 mm between resting pupillary diameter, there was also a strong positive association between UPA and IPA (r = 0.91, 95% CI 0.68–0.98, p-value < 0.001 OD; r = 0.954, 95% CI 0.828–0.988, p-value < 0.001 OS).

This study found a strong correlation between ultrasonographic and infrared pupillary assessments in critically ill patients, including those with neurologic pathology. UPA could, therefore, be utilized for the evaluation of pupillary diameter and pupillary light reflex in critically ill patients in whom eye opening is not possible. To the authors’ knowledge, this is the first study comparing UPA with IPA.

Unfortunately, the fact that there were very few cases of patients with anisocoria precludes the authors from drawing further conclusions about the role of UPA in this specific patient population. Further studies with a larger patient population are needed.

Regarding the small differences between UPA and IPA, the authors hypothesize that they could be related to the less-intense light stimuli in the case of UPA, because the light stimuli is shown over the closed eye, as opposed to the light stimuli shown directly over the open eye for IPA.

This study shows that UPA is a quick, non-invasive, point-of-care, practical method that provides reliable information, when compared to IPA, regarding pupillary size and pupillary light reflex, which permits assessment of brain herniation. In patients at high risk of brain herniation, UPA becomes particularly useful because it removes the intra- and inter-observer variability inherent to direct visualization of the pupil (i.e., conventional pupillary physical exam). The most important application of UPA would be to provide accurate pupillary assessment in patients in whom eye opening is not possible (e.g., periorbital soft tissue edema) as well as in patients with significant eyelid edema as usually occurs in those with extensive burn injuries. It is not uncommon that patients at risk of or under suspicion of critical neurologic pathology such as brain herniation have concurrent periorbital edema (e.g., traumatic brain injury). UPA could be performed while waiting for computer tomography in the emergency department, ICU, operating room, as well as in emergency pre-hospital settings or underserved areas wherein computed tomography or resonance magnetic imaging is not available.

The small patient population of this study is its major limitation. The greater limitation for UPA is the experience of the operator, for the reliability and accuracy of UPA are directly related to operator skills. Finally, we used different iPhone models that have different technologies generating the flash light used as light stimulus; however, it is unclear whether minor variations in intensity and type of light can significantly affect the assessment of the pupillary light reflex.

Ultrasonographic pupillary assessment is strongly correlated with infrared pupillary assessment in critically ill patients, including neurocritically ill patients. Ultrasonographic pupillary assessment is a quick, feasible, non-invasive method that allows accurate evaluation of pupillary size and pupillary light reflex in patients in whom a more precise measurement of the pupil is required or eye opening is not possible (e.g., periorbital edema due to traumatic brain injury).