Automated Pupillometry as an Adjunct to Clinical Examination in Patients With Acute Vision Loss

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Automated Pupillometry as an Adjunct to Clinical Examination in Patients With Acute Vision Loss Roshni Bhatnagar, MD, Andrea D. Birnbaum, MD, PhD, Jeanine Baqai, MD, Nicholas J. Volpe, MD Background: Despite automated pupillometry’s (AP) improved detection of relative afferent pupillary defects (RAPDs) compared with the Swinging Flashlight Test (SFT), AP remains uncommon in clinical practice. This study examined barriers to routine use of AP in evaluation of acute vision loss. Methods: (1) Ophthalmologists and optometrists’ perceptions of AP were captured via electronic survey. (2) Ophthalmologists were presented with clinical vignettes to assess their use of AP in clinical decision-making. (3) Patients presenting with decreased vision to an ophthalmology urgent care clinic underwent manual SFT and AP screening to evaluate ophthalmologists’ perceptions of the device. Results: Surveys indicated that clinicians were “neutral” to “somewhat likely” to use AP. In clinical vignettes, more physicians proceeded with workup for optic nerve pathology when presented with an RAPD by AP than SFT (77% vs 26%, P = 0.003). When SFT and AP results were discordant, more physicians proceeded with workup for optic nerve disease when AP was positive and SFT was negative than vice versa (61% vs 18%, P = 0.008). In the clinical study of 21 patients, 50% of RAPDs detected by AP were not detected by SFT, although ophthalmologists rated AP’s usefulness as only “neutral” to “somewhat useful.” Conclusion: Clinicians value pupillary examination and trust AP over SFT; however, widespread adoption and perceived value of AP may depend on its impact on clinical outcomes. Within a comprehensive diagnostic device, AP may be an important tool, but is not necessary to screen for optic nerve disease or evaluate acute vision loss. Journal of Neuro-Ophthalmology 2021;41:239–245 doi: 10.1097/WNO.0000000000000919 © 2020 by North American Neuro-Ophthalmology Society D espite its accuracy and availability, automated pupillometry (AP) to detect relative afferent pupillary defects (RAPDs) has not achieved widespread use. Previous research establishes pupillometry’s accurate and reliable detection of asymmetric macular disease, glaucoma, and optic neuropathies (1–4). AP is more accurate and sensitive than its traditional counterpart, the Swinging Flashlight Test (SFT) (5–11). Although SFT’s sensitivity is reported as 84% and inter-rater disagreement as 39% and 22% by 2 studies, AP has sensitivity of 94%, specificity of 95%, and inter-rater disagreement of 1% (1,12–14). Despite being well-studied (989 PubMed articles published since 1960 reference “pupillometer” or “pupillometry” in human subjects), AP is not used routinely (PubMed, March 22, 2020). One would predict clinician interest in an objective, reliable pupillometer given that RAPDs are a critical and early sign of optic nerve dysfunction. Nevertheless, adoption beyond clinical research is limited (15,16). Understanding barriers to use is important to the evolution of AP as an adjunct to clinical examination (2,17–19). This study offers a two-pronged approach, survey and direct comparison, to examine the barriers to use of AP for RAPD detection in outpatient evaluation of acute vision loss. METHODS Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois. Northwestern University’s Institutional Review Board approved this study before commencement. The study combined electronic surveys of providers and clinical comparison of AP and SFT to understand AP’s role in pupil examination. Early-investigator research grant from the Illinois Society for the Prevention of Blindness. Surveys The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Address correspondence to Nicholas J. Volpe, MD, Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, 645 N Michigan Avenue, Suite #440, Chicago, IL 60611; E-mail: [e-mail] Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 Using REDCap electronic data capture tools hosted at Northwestern University, electronic surveys were fielded via 2 listservs: ophthalmologists previously or currently affiliated with Northwestern Memorial Hospital (see Supplemental Digital Content, E1, http://links.lww.com/WNO/A390) and Illinois College of Optometry alumni (see Supplemental Digital Content, E2, http://links.lww.com/WNO/A391) (20). Informed 239 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution consent was provided at survey initiation and no identifying information was collected. Clinicians rated their confidence in SFT and the usefulness of AP on a Likert scale. To consider whether clinicians considered an RAPD an important finding, we asked whether they would feel compelled to act if a patient presented with an RAPD on exam regardless of corroboratory history or examination information. Recognizing inherent subjectivity of pupil examination, we asked respondents how often they would like access to another physician’s opinion and how often they would like access to a device when confirming a result of which they were unsure. In addition, ophthalmologists were presented with 5 vignettes for patients with similar clinical presentations presumed to be optic neuritis (Table 1). Each vignette included concordant or discordant pupillometry and SFT results to enable comparisons across vignettes. Based on the clinician’s choice to re-examine the patient, pursue workup for optic nerverelated pathology, or pursue workup for non–optic nerve-related pathology, we inferred whether the AP result was additive to SFT or affected clinical decision-making. Clinical Comparison of Swinging Flashlight Test and Automated Pupillometry We enrolled a nonconsecutive, nonrandomized group of patients, age 18 or older, presenting to the Northwestern Medicine Ophthalmology Urgent Care Clinic with complaints of acute vision loss within the previous 2 weeks in June-August 2015 and November-December 2016. Patients whose blurry vision did not improve with refraction were invited to participate. Patients with known efferent pupillary detect before examination were excluded. Participants were paid $30. Patients meeting study criteria were screened via SFT by a technician or resident physician. Neutral density filters were not used, given they are uncommon outside of neuro- TABLE 1. Five clinical scenarios presented to ophthalmologists to assess impact of pupillometry on clinical decision-making Vignette A 45-year-old man presents with pain and blurry vision in the left eye. He is being evaluated for optic neuritis and your tech determines that he has a left RAPD via SFT. His left eye visual field shows patchy defects and his optic discs appear normal. How would you proceed? Considering the patient in the prior question (45-year-old man presenting with pain and blurry vision in the left eye with patchy visual field and normal optic discs), how would you proceed if he was found to have a left RAPD by the SFT confirmed by pupillometry with a score of 0.6 log units? You are evaluating a patient who complains of a vague decrease in vision in the right eye. The technician’s exam shows a minor decrease in visual acuity and no RAPD. He is found to have a 0.6 log unit RAPD of the right eye with pupillometry. His visual field testing is unreliable and he has a normal fundus exam. Assuming the patient has already been dilated, how would you proceed? You are evaluating a patient for nonspecific visual complaints in the right eye. Your technician’s exam shows no change in visual acuity and an RAPD of the right eye. He has no other abnormalities on exam (full visual fields, normal fundus). On pupillometry, no RAPD is detected, how would you proceed? A 50-year-old man presents with pain and blurry vision in the left eye. He is being evaluated for optic neuritis and his pupillometry screen shows an RAPD of 0.6. His visual field shows patchy defects on the right and his optic discs appear normal. How would you proceed? Answer Choices a) Continue workup for optic neuritis given RAPD b) Pursue testing for non–optic nerve-related cause of decreased vision c) Re-evaluate the pupils yourself before dilation d) Follow-up in clinic next week to see whether symptoms have resolved a) Continue workup for optic neuritis given RAPD b) Pursue testing for non–optic nerve-related cause of decreased vision c) Re-evaluate the pupils yourself before dilation d) Follow-up in clinic next week to see whether symptoms have resolved a) Proceed with workup for optic nerve disease b) Proceed with workup for non–optic nerve-related cause of decreased vision c) Ask patient to return to clinic the next day to evaluate pupils without dilation d) Follow-up in clinic in a few weeks to see whether symptoms have resolved a) Proceed with workup for optic nerve disease b) Proceed with workup for non–optic nerve-related cause of decreased vision c) Ask patient to return to clinic the next day to evaluate pupils without dilation d) Follow-up in clinic in a few weeks to see whether symptoms have resolved a) Continue work up for optic neuritis given RAPD b) Pursue testing for non-optic nerve related cause of decreased vision c) Re-evaluate the pupils yourself before dilation d) Follow-up in clinic next week to see whether symptoms have resolved RAPD, relative afferent pupillary defect; SFT, Swinging Flashlight Test. 240 Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution ophthalmology. Before examining the patient, the attending physician completed a brief questionnaire about the utility, or clinical usefulness, of the intake SFT performed by the technician or resident and their confidence in that exam on a Likert scale from 1 to 5 where 1 was “not at all confident” and 5 was “very confident” (see Supplemental Digital Content, E3A, http://links.lww.com/WNO/A392). For example, “How confident are you in the initial clinical assessment of the pupils using the swinging flashlight test?” Patients then underwent pupillometry using the RAPDx pupillometer (Konan Medical USA, Inc, Irvine, CA). Patients underwent dark adaptation for 2 minutes after which RAPD assessment was completed by a study investigator according to the methodology established by Cohen et al (12). Constriction amplitude, the most sensitive and specific indicator of an RAPD, was the primary measure (6,9,12). Attending physicians were provided the RAPDx score, classifying RAPD as normal-to-trace (0.0–0.3 log units), mild (0.31–0.6 log units), moderate (0.61–0.9 log units), or severe (.0.91 log units). After completing their evaluation of the patient, attending physicians completed a second questionnaire indicating their confidence in and the utility of AP (see Supplemental Digital Content, E3B, http://links.lww.com/WNO/A392). These surveys were conducted separately so that the pupillometry result and the physician’s own clinical judgement would not influence their baseline opinion of the pupil screening exam conducted in clinic. ophthalmologists’ mean confidence in the SFT and pupillometry were calculated and a paired t test was performed. Clinicians’ average rating on a Likert scale of AP’s utility and its impact on clinical confidence were also calculated. RESULTS Descriptive Statistics Thirty-five ophthalmologists and 146 optometrists responded to the electronic survey, with a higher completion rate in the optometry group (P = 0.004) (Table 2). Ophthalmologists were primarily subspecialists (57%) or comprehensive ophthalmologists (30%) practicing at an academic medical center (42%) or private practice (42%). Comparatively, optometrists primarily practiced in a private practice or clinician group (83% vs 52%, P , 0.001). In the survey sample, SFT was primarily performed by a nurse or technician in ophthalmology practices and the supervising optometrist in optometry practices (P , 0.001). Twenty-six patients (65% female, ages 24 to 84) enrolled in the clinical study. Five cases were excluded due to: existing efferent pupillary defect (1), inability to complete AP exam (1), and incomplete questionnaires (3). Two comprehensive ophthalmologists alternating in the Urgent Care clinic provided survey responses in the final sample of 21 cases. Data Analysis Clinicians’ Perceptions of Pupillometry According to Survey Results Analysis was completed using Microsoft Excel 2010 (Microsoft, Redmond, WA) and SAS 10 (SAS Institute Inc, Cary, NC). To measure association between various categorical factors and variables of interest, Wilcoxon Rank Sum was performed for categorical variables, and univariate linear regression for continuous variables. To compare physician answers to multiple-choice clinical vignettes, difference in proportions tests were performed. For the clinical data set, Ninety-two percent of optometrists and 91% of ophthalmologists indicated they would pursue an RAPD on clinical exam. When asked hypothetically if they would use a pupillometer, clinicians noted they were “somewhat likely” to use AP in every day practice, verify an RAPD initially found via SFT, or follow patients with pupil abnormalities from visit to visit (Table 3). Both groups were “somewhat” to “very confident” in SFT, with no significant difference between the 2 groups (P . 0.05). TABLE 2. Demographics of survey respondents in ophthalmology and optometry RAPD Detection Complete responses Practicing in private practice or clinician group SFT usually completed by nurse or technician SFT usually completed by supervising clinician Clinicians who report rechecking pupils in more than 75% of cases Pupillometer in clinic “Very confident” in SFT “Somewhat confident” in SFT Ophthalmologists (n = 35) Optometrists (n = 146) P, Difference in Proportions Estimate 19, 58% 17, 52% 20, 61% 9, 27% 6, 18% 120, 82% 119, 83% 32, 22% 110, 75% 98, 71% 0.004† ,0.001* ,0.001* ,0.001* ,0.001* 2, 9% 7, 21% 8, 24% 6, 4% 46, 32% 43, 30% 0.23 0.21 0.49 *Highly statistically significant. † Statistically significant. RAPD, relative afferent pupillary defect; SFT, swinging flashlight test. Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 241 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Fewer than one third of surveyed ophthalmologists were “very confident” in the SFT performed in their practice. Most ophthalmologists indicated mild interest in pupillometry, with average frequency with which they would be interested in the device rated as 2.45 (Never = 1, Frequently = 5, Tables 2 and 3). Ophthalmologists preferred a device to a clinician’s assessment when in need of a second opinion (2.42 vs 1.82, Never = 1 and Frequently = 5, P = 0.017). When asked to rank important considerations when purchasing a new device for their office, ophthalmologists valued device accuracy and ease of use, whereas optometrists valued accuracy and billability (Tables 4 and 5). Optometrists who valued accuracy and did not value billability were significantly more likely to say they would use a pupillometer (Table 5). Understanding Physicians’ Clinical DecisionMaking: Vignette Analysis Table 6 summarizes ophthalmologists’ responses to 5 clinical vignettes including AP and SFT information. When SFT was positive, but AP negative for RAPD, 18% of physicians chose to pursue workup for optic nerve pathology. The remainder were split between pursuing a non– optic nerve-related cause of symptoms (29%) or reevaluating the patient (50%). In contrast, when AP was positive, but SFT was negative, 61% of clinicians proceeded directly with workup for optic nerve pathology (18% vs 61%, difference in proportions z estimate = 2.93, P = 0.008, Fig. 1). In 2 additional vignettes, either a positive SFT or positive pupillometry result was provided. Seventy-seven percent of ophthalmologists who presented with only a positive pupillometry result proceeded with workup for optic nerve pathology compared with 26% of ophthalmologists who presented with only positive SFT by technician exam (77% vs 26%, difference in proportions z estimate = 3.42, P = 0.003, Fig. 1). Most (70%) ophthalmologists presented with only the positive SFT result by technician exam elected to re-evaluate the pupils themselves. Utility of Pupillometry in Clinical Examination Of 21 clinical cases, 8 had clinically significant RAPDs by pupillometry, of which 4 were mild, 2 moderate, and 2 severe (Fig. 2). Of these, SFT detected only 4 RAPDs. Assuming AP as the gold standard, there is the possibility that SFT missed clinically insignificant APDs or there was a true false negative rate of 50%. In these 4 cases, RAPD measured by AP was mild (n = 3) or moderate (n = 1) in severity. One additional RAPD was detected by SFT, but scored below the 0.3 log unit threshold for clinical significance. In these cases of discrepancy, physicians did not indicate that AP changed management, nor did it affect their utility ratings. In our sample, there was no difference in ophthalmologists’ reported confidence in SFT vs pupillometry (P = 1.00). Ophthalmologists were “neutral” to “somewhat confident” in clinical decisions without pupillometry and did not report an increase in clinical confidence after receiving the RAPDx result (average agreement of 2.95, or “neutral” on 1–5 Likert scale). They rated AP utility as “neutral” to “somewhat useful” on a 1–5 Likert scale of utility where 1 was “not at all useful” and 5 was “very useful.” In one case, a patient presenting with unilateral mydriasis and RAPD by SFT rated as mild by pupillometry, the physician reported that AP changed management. CONCLUSION Pupillometry as a Screening Device Our results indicate that RAPD remains a critical finding that clinicians will act on via reexamination, pupillometry, or further diagnostic workup. Ophthalmologists preferred AP to a second physician opinion, likely because they recognize the subjective nature of SFT or prefer not to disturb a colleague in clinic. In clinical vignettes, when provided the AP result in addition to or in place of the SFT result, physicians proceeded with the clinical workup indicated by AP. SFT result without AP result prompted variability in clinicians’ choice in next step, whereas AP result without SFT result elicited greater consensus regarding next step, perhaps indicating that AP is sufficiently compelling for physician decision-making. These patterns endured whether AP was positive or negative. Surprisingly, clinicians indicated only mild interest in and presumably less perceived value toward AP despite fewer than one third of respondents feeling “very confident” in SFT performed at their clinic. Challenges to widespread use of pupillometry may include lack of proven critical value to clinical decisionmaking, added inefficiency, and inability to bill for use. TABLE 3. Average likelihood that ophthalmologists and optometrists would use a pupillometer in every day practice, to verify swinging flashlight test findings, or to follow-up with patients known to have pupil abnormalities (1 = unlikely; 5 = likely) Potential Use of Pupillometry Use in every day practice Verify findings of SFT Follow patients from visit to visit Ophthalmologists (n = 21) Optometrists (n = 122) P for t-statistic Difference in Means 3.79 3.58 3.66 3.93 3.38 — 0.652646 0.512035 SFT, swinging flashlight test. 242 Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 4. Ophthalmologist rankings of 5 factors related to choosing a new device for their office (1 = Top Factor, 5 = last factor); association with likelihood to use a pupillometer (n = 19) Device Factor Accuracy of result Ease of use Speed of use Billable use/return on investment Size of device/space constraints Average Rank (1–5) Linear Regression Estimate of Association With Likelihood to Use a Pupillometer P 1.47 2.89 3.42 3.68 0.11 20.29 0.11 20.12 0.62 0.27 0.60 0.54 4.16 20.21 0.39 In our clinical sample, SFT had a false negative rate of 50%. Given that most physicians do not recheck the pupil exam when SFT is negative and SFT has low established inter-rater reliability, SFT alone may have insufficient sensitivity to screen for RAPDs in patients at risk for optic nerve disease (13,14). This study is limited by low sample size and variable examiner expertise, but further evaluation of SFT’s false negative rate compared with AP is warranted. Factors Influencing Routine Use of Pupillometry Clinicians’ Awareness of and Appreciation for Automated Pupillometry’s Superior Accuracy Despite AP’s superior accuracy compared with SFT, results suggest that AP may have unclear value to clinicians. AP changed management in only one of 21 clinical cases and minimally increased clinical confidence. Clinicians may remain unaware of existing research or feel they can adequately assess a patient with physical exam and other diagnostic testing despite SFT’s poor inter-rater reliability (3,4,17,21). They may believe that the incidence of optic nerve pathology detected primarily based on RAPD is insufficient to warrant time and monetary investment. Moreover, it is difficult to determine a device’s value based on a single experience, as clinicians did in this study. The relative advantage of AP may be obscured by a lack of experiences in which clinicians recognize that an RAPD was missed or would have altered management, especially because it is difficult to identify inconsistencies in SFT or isolate their impact. Perhaps clinical vignettes isolated the impact of pupillometry in a way that the clinical setting did not. Previous reports suggest that dissemination of innovation depends on perception and observability of its benefits (22– 25). A study on the adoption of endoscopic procedures among surgeons determined that perception of a new technique’s additional benefit is prerequisite to other factors influencing the decision (23). Previous studies demonstrating AP’s accuracy have been limited in demonstration of improved patient outcomes or reduced unnecessary workup. Our results suggest a preference rather than a compelling need for pupillometry, thus direct comparison of the impact of AP and SFT on avoided workup and clinical outcomes is needed. Logistical Barriers May Inhibit Pupillometer Use Few, if any, studies have addressed additional requirements for provider time, clinic space, or financial resources to perform pupillometry, but these logistical demands may drive clinicians’ relative neutrality toward AP. Disruption of clinic flow, lengthening of overall visit time, or increased complexity of new technology can hinder its uptake (22,25). Although AP may not be widely adopted as a standalone device, inclusion into a combination device with an TABLE 5. Optometrist rankings of 5 factors related to choosing a new device for their office (1 = Top Factor, 5 = last factor); association with likelihood to use a pupillometer (n = 120) Device Factor Accuracy of result Ease of use Speed of use Billable use/return on investment Size of device/space constraints Average Rank (1–5) Linear Regression Estimate of Association With Likelihood to Use a Pupillometer P 1.47 2.85 3.31 2.81 20.16 20.003 20.19 0.14 0.008* 0.91 0.06 0.03* 4.56 0.01 0.22 *Statistically significant. Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 243 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 6. Physicians’ evaluation of potential neurogenic vision loss based on pupillometry and swinging flashlight test findings in clinical scenarios (n = 23–25) Scenario Scenario Number 1 2 3 4 5 Information Provided Answers Selected by Clinicians (%) Potential for Neurogenic Vision Loss Based Pupillometry on Patient History SFT Result Result Neurogenic Neurogenic Neurogenic Non-neurogenic Neurogenic + Not provided + + 2 + + 2 Not + provided Proceed With Workup for Optic Neuropathy Proceed With Workup for Non–Optic NerveRelated Disease Re-examine Pupils 26 87 61 18 77 4 4 9 32 5 70 9 30 50 18 SFT, swinging flashlight test. automated refractor or screening visual field test may offer long-term cost savings and reduce the time and space required. For example, automated refraction may have initially seemed redundant with manual refraction, but as part of a suite of tools for visual acuity assessment it can save time or clarify complex cases. In addition, incorporation of AP with telediagnostics may improve remote ophthalmic screening for neurogenic vision loss. While sensitivity optimization in academic ophthalmology practices with access to neuro-ophthalmologists and advanced diagnostic testing may be only marginally valuable, AP’s accuracy may be better leveraged for remote diagnosis. Limitations and Future Directions The present study has limitations. Low sample size, single institution inclusion, and a predominance of participants from the Midwest reduce study power and skew our sample. A tertiary ophthalmology urgent care clinic may treat more complex patients than other ophthalmology or general urgent care centers. Surveys were not validated before this study, reducing generalizability of conclusions. The voluntary nature of surveys and reliance on self-report introduce selection bias and response bias respectively. Two attending ophthalmologists staffed the Urgent Care clinic during the study period, resulting in repeated sampling of these 2 clinicians. Despite enhanced RAPD detection, AP’s role in clinical practice remains limited, likely because of low perceived value and ability to localize vision loss with clinical examination and advanced imaging, particularly optical coherence tomography. We believe that for patients to benefit from AP’s improved accuracy, it must be combined with other screening technologies or assist with remote consultation and telediagnostics. Given the importance of RAPD detection in the evaluation of neurogenic vision loss, further research must identify the clinical impact of AP’s improved diagnostic accuracy before it will achieve widespread use. FIG. 1. In hypothetical clinical scenarios, physicians’ predominantly chose their next diagnostic step based on pupillometry results. RAPD, relative afferent pupillary defect; SFT, Swinging Flashlight Test. 244 Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. RAPD detection by pupillometry and SFT in 21 urgent care cases. RAPD, relative afferent pupillary defect; SFT, Swinging Flashlight Test. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: R. Bhatnagar and N. J. Volpe; b. Acquisition of data: R. Bhatnagar, N. J. Volpe, J. Baqai, and A. D. Birnbaum; c. Analysis and interpretation of data: R. Bhatnagar, N. J. Volpe, J. Baqai, and A. D. Birnbaum. Category 2: a. Drafting the manuscript: R. Bhatnagar and N. J. Volpe; b. Revising it for intellectual content: R. Bhatnagar, N. J. Volpe, J. Baqai, and A. D. Birnbaum. Category 3: a. Final approval of the completed manuscript: R. Bhatnagar, N. J. Volpe, J. Baqai, and A. D. Birnbaum. REFERENCES 1. Meeker M, Du R, Bacchetti P, Privitera CM, Larson MD, Holland MC, Manley G. Pupil examination: validity and clinical utility of an automated pupillometer. J Neurosci Nurs. 2005;37:34–40. 2. Park JG, Moon CT, Park DS, Song SW. Clinical utility of an automated pupillometer in patients with acute brain lesion. J Korean Neurosurg Soc. 2015;58:363–367. 3. Waisbourd M, Lee B, Ali MH, Lu L, Martinez P, Faria B, Williams A, Moster MR, Katz LJ, Spaeth GL. Detection of asymmetric glaucomatous damage using automated pupillography, the swinging flashlight method and the magnified-assisted swinging flashlight method. Eye (Lond). 2015;29:1321–1328. 4. Takayama K, Ito Y, Kaneko H, Nagasaka Y, Tsunekawa T, Sugita T, Terasaki H. Cross-sectional pupillographic evaluation of relative afferent pupillary defect in age-related macular degeneration. Medicine (Baltimore). 2016;95:e4978. 5. Fison P, Garlick D, Smith S. Assessment of unilateral afferent pupillary defects by pupillography. Br J Ophthalmol. 1979;63:195–199. 6. Cox T. Pupillographic characteristics of simulated relative afferent pupillary defects. Invest Ophthalmol Vis Sci. 1989;30:1127–1131. 7. Kawasaki A, Moore P, Kardon RH. Variability of the relative afferent pupillary defect. Am J Ophthalmol. 1995;120:622–633. 8. Volpe NJ, Plotkin ES, Maguire MG, Hariprasad R, Galetta SL. Portable pupillography of the swinging flashlight test to detect afferent pupillary defects. Ophthalmology. 2000;107:1913–1921. 9. Bergamin O, Zimmerman MB, Kardon RH. Pupil light reflex in normal and diseased eyes: diagnosis of visual dysfunction using waveform partitioning. Ophthalmology. 2003;110:106–114. 10. Wilhelm H. Neuro-ophthalmology of pupillary function–practical guidelines. J Neurol. 1998;245:573–583. Bhatnagar et al: J Neuro-Ophthalmol 2021; 41: 239-245 11. Levatin P. Pupillary escape in disease of the retina or optic nerve. AMA Arch Ophthalmol. 1959;62:768–779. 12. Cohen LM, Rosenberg MA, Tanna AP, Volpe NJ. A novel computerized portable pupillometer detects and quantifies relative afferent pupillary defects. Curr Eye Res. 2015;40:1120–1127. 13. Bell RA, Waggoner PM, Boyd WM, Akers RE, Yee CE. Clinical grading of relative afferent pupillary defects. Arch Ophthalmol. 1993;111:938–942. 14. Ichhpujani P, Rome JE, Jindal A, Khator P, Leiby BE, Gordon H, Chen B, Spaeth GL. Comparative study of 3 techniques to detect a relative afferent pupillary defect. J Glaucoma. 2011;20:535–539. 15. Riordan-Eva P. Clinical assessment of optic nerve disorders. Eye. 2004;18:1161. 16. Fotiou F, Fountoulakis K, Goulas A, Alexopoulos L, Palikaras A. Automated standardized pupillometry with optical method for purposes of clinical practice and research. Clin Physiol. 2000;20:336–347. 17. Lee MH, Mitra B, Pui JK, Fitzgerald M. The use and uptake of pupillometers in the Intensive Care Unit. Aust Crit Care. 2018;31:199–203. 18. Chen JW, Gombart ZJ, Rogers S, Gardiner SK, Cecil S, Bullock RM. Pupillary reactivity as an early indicator of increased intracranial pressure: the introduction of the Neurological Pupil index. Surg Neurol Int. 2011;2:82. 19. Anderson M, Elmer J, Shutter L, Puccio A, Alexander S. Integrating quantitative pupillometry into regular care in a neurotrauma intensive care unit. J Neurosci Nurs. 2018;50:30–36. 20. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadatadriven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–381. 21. Hults KN, Knowlton SL, Oliver JW, Wolfson T, Gamst A. A study of pupillary assessment in outpatient neurosurgical clinics. J Neurosci Nurs. 2006;38:447–452. 22. Rogers EM. Diffusion of Innovations. New York, NY: Simon and Schuster, 2010. 23. Dirksen CD, Ament AJ, Go PM. Diffusion of six surgical endoscopic procedures in The Netherlands. Stimulating and restraining factors. Health Policy. 1996;37:91–104. 24. Meyer M, Johnson JD, Ethington C. Contrasting attributes of preventive health innovations. J Commun. 1997;47:112–131. 25. Greenhalgh T, Robert G, Macfarlane F, Bate P, Kyriakidou O. Diffusion of innovations in service organizations: systematic review and recommendations. Milbank Q. 2004;82:581– 629. 245 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.