Clinical Review & Education
Review
Nonmydriatic Ocular Fundus Photography in Neurologic Emergencies Beau B. Bruce, MD, PhD; Valérie Biousse, MD; Nancy J. Newman, MD
IMPORTANCE The ocular fundus examination is infrequently and poorly performed in clinical
settings, placing patients at risk for missed and delayed diagnosis of vision- and life-threatening neurologic disease. OBJECTIVES To review the importance of ocular fundus examination, the limitations of direct ophthalmoscopy, and the relative merits of nonmydriatic ocular fundus photography in emergency neurologic diagnosis. EVIDENCE REVIEW PubMed queries were reviewed for articles of relevance to this review. Queries included relevant combinations of the search terms ophthalmoscopy, nonmydriatic, neurology, and emergency, including variant spellings and endings. FINDINGS Nonmydriatic ocular fundus photography is more sensitive than direct ophthalmoscopy in several settings. It can be feasibly performed in emergency departments and has substantial promise in improving neurologic diagnosis, particularly headache and cerebrovascular disease. CONCLUSIONS AND RELEVANCE Nonmydriatic ocular fundus photography has notable advantages over direct ophthalmoscopy that likely outweigh its associated costs. More widespread deployment and integration into neurologic practice is expected to improve diagnosis and patient outcomes. JAMA Neurol. 2015;72(4):455-459. doi:10.1001/jamaneurol.2014.4053 Published online February 9, 2015.
T
he ocular fundus examination provides a unique opportunity to directly visualize part of the central nervous system and its accompanying microvasculature. Even with the remarkable advances achieved in the field of neuroradiology, examination of the ocular fundus may provide the only diagnostic red flag, yielding a timely and accurate diagnosis for vision- or lifethreatening neurologic disease. As one example, consider how the discovery of papilledema in a patient presenting to the neurology clinic with headache would lead to evaluation of several severe conditions, such as obstructive hydrocephalus, mass lesion, cerebral venous thrombosis, or fulminant idiopathic intracranial hypertension. This article reviews the importance of ocular fundus examination, the limitations of direct ophthalmoscopy, and the relative merits of nonmydriatic ocular fundus photography in emergency neurologic diagnosis. PubMed was searched for relevant combinations of the search terms ophthalmoscopy, nonmydriatic, neurology, and emergency, including variant spellings and endings.
Direct Ophthalmoscopy vs Nonmydriatic Ocular Fundus Photography Although ophthalmoscopy continues to be part of the armamentarium of most neurologists and emergency department (ED) phyjamaneurology.com
Author Affiliations: Department of Ophthalmology, Emory University, Atlanta, Georgia (Bruce, Biousse, Newman); Department of Neurology, Emory University, Atlanta, Georgia (Bruce, Biousse, Newman); Department of Epidemiology, Emory University, Atlanta, Georgia (Bruce); Department of Neurological Surgery, Emory University, Atlanta, Georgia (Newman). Corresponding Author: Beau B. Bruce, MD, PhD, Departments of Ophthalmology, Neurology, and Epidemiology, Emory University, 1365B Clifton Rd NE, Atlanta, GA 30322 ([email protected]). Section Editor: David E. Pleasure, MD.
sicians, ocular fundus examination is infrequently and poorly performed in clinical practice. In fact, among 350 patients presenting to a US university hospital ED with headache, focal neurologic deficits, visual loss, or diastolic blood pressure of 120 mm Hg or higher, only 48 patients (14%; 95% CI, 10%–18%) had their ocular fundus examined by the ED physicians.1,2 In 2 hospitals in Birmingham, England, only 25 of 56 inpatients (45%; 95% CI, 32%-58%) referred to the neurology department could recall being examined with an ophthalmoscope, whereas 54 (96%; 95% CI, 87%-99%) recalled being examined with a stethoscope.3 These statistics seem startling until we consider the limitations of ophthalmoscopy at the bedside used in these studies and in most neurologic practices. Although direct ophthalmoscopes are extremely portable, and even commonly mounted on the walls of clinic offices and ED examination rooms, they are difficult to use and provide a limited field of view (approximately 5°) (Figure). Indeed, even in the hands of ophthalmologists examining patients with pharmacologically dilated pupils, direct ophthalmoscopes have poor sensitivity for common conditions, such as diabetic retinopathy (52%) and hypertensive retinopathy (44%).4 The field of view and diagnostic sensitivity are further limited when direct ophthalmoscopes are used without pupillary dilation.5 Nonmydriatic ocular fundus photography holds promise as an alternative to direct ophthalmoscopy. Nonmydriatic cameras allow (Reprinted) JAMA Neurology April 2015 Volume 72, Number 4
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Figure. Nonmydriatic Ocular Fundus Photographs A
B
C
D
E
A, Normal ocular fundus, with inset showing typical field of view of a direct ophthalmoscope. B, Optic disc edema. C, Optic disc pallor. D, Isolated retinal hemorrhage (arrowhead). E, Grade III hypertensive retinopathy (black arrowhead indicates cotton wool spot; white arrowhead, hemorrhage). The black backgrounds of the original images were cropped, and the brightness and contrast were adjusted.
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Nonmydriatic Ocular Fundus Photography
wide-field (45°) photographs to be taken of the ocular fundus without pharmacologic dilation of the pupils and with relative ease, even after onlylimitedtraining.1 Inaddition,studies6,7 ofnonmydriaticfundusphotography in diabetic retinopathy screening have found nonmydriatic photography to have higher sensitivity, specificity, and interexamination agreement than ophthalmoscopy, even among ophthalmologists, and there is level I evidence that single-field fundus photography can reliably and easily identify patients with diabetic retinopathy who require referral for ophthalmic evaluation and management.
Review Clinical Review & Education
Table. Comparison of the 2 Phases of the FOTO-ED Studya
jamaneurology.com
Phase 2 (Nonmydriatic Photography) (n = 354)
Age, median (IQR), y
44.5 (31-59)
45.9 (33-57)
Women
220 (62.9)
251 (70.9)
Headache
228 (65.1)
206 (58.2)
Focal neurologic deficit
100 (28.6)
123 (34.7)
Characteristic
Chief concerns
Nonmydriatic Ocular Fundus Photography in the ED In the ED, failure to correctly evaluate the ocular fundus can have life-threatening consequences, and the Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) study1,2,8 evaluated whether nonmydriatic ocular fundus photography would be feasible and improve diagnosis in the ED compared with direct ophthalmoscopy. The study included adult patients presenting to a university ED with headaches, focal neurologic deficits, diastolic blood pressure of 120 mm Hg or higher, and/or acute visual changes. All patients had nonmydriatic ocular fundus photographs obtained by trained nurse practitioners or a medical student using a commercially available nonmydriatic ocular fundus camera (Kowa nonmyd-D series cameras; Kowa Optimed Inc). Throughout the FOTO-ED study, relevant ocular fundus abnormalities were defined as optic disc edema, isolated intraocular hemorrhage, grade III or IV hypertensive retinopathy, retinal vascular occlusion, and optic disc pallor (Figure). The first phase of the FOTO-ED study evaluated the routine clinical use of direct ophthalmoscopy by ED physicians and found that direct ophthalmoscopy was infrequently and poorly performed by ED physicians and that nonmydriatic fundus photography was a feasible alternative to direct ophthalmoscopy.1,2 In this study, 44 of the 350 enrolled patients had relevant ocular findings (13%; 95% CI, 9%– 17%) identified on nonmydriatic fundus photographs by the neuroophthalmologist reviewing the images (Table). Eleven of the findings were known before ED presentation. Of the remaining 33 findings, 6 were identified by ophthalmologic consultants, but the other 27 patients neither had a consult requested nor were identified by the ED physicians, who only examined 48 (14%) of the enrolled patients and personally identified none of the relevant findings. Thus, 82% (95% CI, 65%–93%) of the findings unknown at the time of ED presentation were missed by routine ED care. Nonmydriatic photography was well liked by patients and the nurse practitioners taking the photographs (mean ease, speed, and comfort ratings ⱖ8.7 of 10 for all). The photographs were of a quality that provided some clinical information for 97% of enrolled patients and required little time to obtain (median, 1.9 minutes; interquartile range, 1.3–2.9 minutes). In the second phase of the FOTO-ED study,8 which evaluated the routine use of nonmydriatic ocular fundus photography as interpreted by the ED physicians, of the 354 enrolled patients, 35 (10%; 95% CI, 7%–13%) had relevant findings identified by neuroophthalmologist review of the images. The ED physicians reviewed the photographs more frequently (239 patients [68%]) than they had used direct ophthalmoscopy, resulting in their improved detection of relevant abnormalities (16 [46%] of 35 patients). The
Phase 1 (Direct Ophthalmoscopy) (n = 350)
Visual changes
92 (26.3)
56 (15.8)
DBP ≥120 mm Hg
21 (6.0)
21 (5.9)
Relevant findings Optic disc edema
13 (3.7)
6 (1.7)
Grade III or IV hypertension retinopathy
10 (2.9)
6 (1.7)
Isolated intraocular hemorrhage
13 (3.7)
7 (2.0)
4 (1.1)
15 (4.2)
Optic disc pallor Retinal vascular occlusion Total Patients whose ocular fundus was viewed by ED physicians Relevant findings correctly detected by ED physician examination
4 (1.1)
1 (0.3)
44 (12.6)
35 (9.9)
48 (13.7)
239 (67.5)
0/44
16/35 (45.7)
Abbreviations: DBP, diastolic blood pressure; ED, emergency department; FOTO-ED, Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department; IQR, interquartile range. a
Data are presented as number (percentage) of patients unless otherwise indicated. Some percentages sum to more than 100% because patients were allowed to report more than 1 concern.
increased frequency of viewing the fundus and diagnosing abnormalities was particularly remarkable given that the ED physicians had not received any additional training in fundus photographic interpretation. The ED physicians also reported that the photographs were helpful in their evaluation of 125 patients (35%; 95% CI, 30%– 41%), including many cases when the photographs were normal (eg, the absence of papilledema in a patient with possible cerebrospinal fluid shunt malfunction).
Nonmydriatic Ocular Fundus Photography for Neurologic Emergencies The FOTO-ED study studied the entire population of patients in whom ocular fundus examination is considered imperative, but there are 2 specific neurologic emergencies for which routine examination of the ocular fundus is likely to bear substantial fruit: headache and cerebrovascular disease.
Headache In the ED, headache is the fourth most common chief concern overall and the most common neurologic concerns.9 Finding optic disc edema or optic disc pallor in a patient with headache is most concerning for disorders of intracranial pressure or compression of the anterior visual pathways. In a patient without a known cause, either finding should prompt an urgent evaluation for the underlying cause. (Reprinted) JAMA Neurology April 2015 Volume 72, Number 4
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Conversely, normal findings on physical examination reduce the likelihood of a secondary cause and provide reassurance that the patient is not experiencing insidious visual field loss from increased intracranial pressure or a slow-growing mass. However, studies10-12 of headache management in the ED have found ophthalmoscopy documented in only 12% to 48% of cases. In an ancillary FOTO-ED study of 497 patients presenting to the ED with headache,12 42 patients (8.5%; 95% CI, 6%–11%) had relevant abnormalities of their ocular fundus. A high proportion of the patients (41%) with abnormal fundi had normal findings on brain imaging, emphasizing the importance of ocular fundus examination even in this era of neuroimaging. Overall, a body mass index (calculated as the weight in kilograms divided by height in meters squared) of 35 or higher (odds ratio [OR], 2.3; 95% CI, 1.16-4.50; P = .02), younger age (OR, 0.7 per 10-year increase; 95% CI, 0.57-0.95; P = .02), and higher mean arterial blood pressure (OR, 1.3 per 10–mm Hg increase; 95% CI, 1.09-1.55; P = .003) were independently predictive of ocular fundus abnormalities.12 The association of fundus abnormalities with younger age suggests that examination of the ocular fundus has the potential to identify a key subset of secondary headaches because the prevalence of secondary headaches generally increases with age. Surprisingly, approximately half of the ocular fundus abnormalities detected in patients presenting to the ED with headache were attributable to systemic hypertension (isolated retinal hemorrhages [36%] and grade III or IV hypertensive retinopathy [14%]).12,13 This high proportion of findings from systemic hypertension initially appears contrary to large, well-conducted, population-based studies and the International Headache Society consensus that no association exists between mild to moderate hypertension and headache.14,15 However, headache is a common presenting symptom of hypertensive urgencies, and other studies16,17 have associated more severe hypertension with headache. These findings emphasize yet another way that consistent and thorough examination of the ocular fundus can help to detect a treatable underlying cause of neurologic disease, while also offering an early opportunity for intervention against an important cause of morbidity and mortality.
Cerebrovascular Disease Another area where nonmydriatic ocular fundus photography may be valuable for neurologic care is in the risk stratification of patients presenting with possible transient ischemic attack (TIA) or stroke. Retinal microvascular abnormalities (eg, vascular narrowing, tortuosity, and occlusion; cotton wool spots; microaneurysms; retinal hemorrhages; and hypertensive retinopathy) are known to be strongly associated with the long-term risk of stroke based on a summary18 of large epidemiologic studies, but the value of ocular fundus examination in prediction of short-term events in individual patients with acute neurologic events (eg, stroke after presentation of TIA) remains unclear. In one study,19 dilated ocular fundus photographs revealed that patients admitted to the hospital with TIA or acute stroke had an odds of focal arteriolar narrowing 7.2 to 8.9 times that of healthy controls. Ocular fundus abnormalities may represent asymptomatic underlying cerebrovascular injury in patients who present with neurologic symptoms. If so, acute microvascular fundus abnormalities would have a role analogous to the role diffusion-weighted magnetic resonance imaging abnormali458
ties have in determining the presence of acute cerebral ischemia.20 In addition, the presence of these microvascular ocular fundus abnormalities may help differentiate true TIAs (which by definition have no lesions on diffusion-weighted magnetic resonance imaging20) from noncerebrovascular causes of transient focal neurologic symptoms. In fact, we will soon begin a federally funded, multisite prospective cohort study designed to determine whether ocular fundus abnormalities are valuable in the acute risk stratification of TIA and minor stroke.
Is It Time for Nonmydriatic Photography in Routine Neurologic Practice? There is a pressing need for better and more consistent examination of the ocular fundus that nonmydriatic photography appears to fill. The price tag of a camera (approximately $25 000) vs an ophthalmoscope ($100-$500) may give one pause. However, the benefits of nonmydriatic ocular fundus photography already appear to outweigh the monetary costs when one considers (1) the high risk of poor patient outcomes and their attendant medicolegal actions,3,21 (2) the ease with which digital images can be added to electronic medical record systems for improved documentation and interpractice communication and can be shared with experts via telemedicine when diagnostic uncertainty exists,22 and (3) the challenge of improving direct ophthalmoscopy education to a level at which ophthalmoscopy would have the diagnostic sensitivity needed for clinical care.23,24 Indeed, recognizing the importance of improved ocular examination and reflecting discontent with bedside ophthalmoscopy, some have replaced direct ophthalmoscopy with ultrasonography in the ED to diagnose conditions such as papilledema and intraocular hemorrhage when photography would be more sensitive and better suited to answer the questions at hand.25 Others have attempted to augment ophthalmoscopes with smartphones to gain easier visualization of the ocular fundus and the advantages of digital photography (eg, iExaminer; Welch Allyn Inc). However, the most exciting development is commercially available, handheld nonmydriatic cameras (eg, Pictor; Volk Optical Inc; and Digital Medical Scope VersaCam; Nidek Co Ltd) that produce photographs of adequate quality for many clinical scenarios, allow examination of sicker and younger patients who cannot sit at a camera, while remaining considerably easier to use than an ophthalmoscope.
Conclusions Continued improvements will continue to lead toward the ideal digital ophthalmoscope, which will have comparable quality and ease of use to a tabletop camera, yet be as inexpensive as a direct ophthalmoscope. Yet even now, nonmydriatic photography provides a valuable evaluation method for patients at risk for acute neurologic disease, not just in the ED but also in other settings where dangerous diseases may be lurking, such as headache centers and general neurology clinics. Therefore, as we await the future, it is appropriate to integrate nonmydriatic photography into many neurologic settings to improve the care of our patients.
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ARTICLE INFORMATION Accepted for Publication: October 31, 2014. Published Online: February 9, 2015. doi:10.1001/jamaneurol.2014.4053. Author Contributions: Dr Bruce had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Bruce, Biousse, Newman. Acquisition, analysis, or interpretation of data: Bruce, Biousse, Newman. Drafting of the manuscript: Bruce. Critical revision of the manuscript for important intellectual content: Bruce, Biousse, Newman. Administrative, technical, or material support: Bruce, Newman. Study supervision: Newman. Conflict of Interest Disclosures: None reported. Funding/Support: This research was supported in part by an unrestricted departmental grant from Research to Prevent Blindness Inc (Department of Ophthalmology, Emory University) and by core grant P30-EY006360 from the National Eye Institute (Department of Ophthalmology, Emory University). Dr Newman is a recipient of the Research to Prevent Blindness Lew R. Wasserman Merit Award. Dr Bruce receives research support from grant K23-EY019341 from the National Eye Institute. Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. REFERENCES 1. Bruce BB, Lamirel C, Biousse V, et al. Feasibility of nonmydriatic ocular fundus photography in the emergency department: phase I of the FOTO-ED study. Acad Emerg Med. 2011;18(9):928-933. 2. Bruce BB, Lamirel C, Wright DW, et al. Nonmydriatic ocular fundus photography in the emergency department. N Engl J Med. 2011;364(4): 387-389. 3. Nicholl DJ, Yap CP, Cahill V, Appleton J, Willetts E, Sturman S. The TOS study: can we use our patients to help improve clinical assessment? J R Coll Physicians Edinb. 2012;42(4):306-310. 4. Benbassat J, Polak BC, Javitt JC. Objectives of teaching direct ophthalmoscopy to medical students. Acta Ophthalmol. 2012;90(6):503-507.
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5. Carlsson AM, ten Hove MW, Stockl F. Direct ophthalmoscopic examination of the eyes: does a mydriatic agent help with diagnosis? Can Fam Physician. 2006;52:958-959. 6. Ahmed J, Ward TP, Bursell SE, Aiello LM, Cavallerano JD, Vigersky RA. The sensitivity and specificity of nonmydriatic digital stereoscopic retinal imaging in detecting diabetic retinopathy. Diabetes Care. 2006;29(10):2205-2209. 7. Lin DY, Blumenkranz MS, Brothers RJ, Grosvenor DM. The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: a comparison with ophthalmoscopy and standardized mydriatic color photography. Am J Ophthalmol. 2002;134(2):204-213. 8. Bruce BB, Thulasi P, Fraser CL, et al. Diagnostic accuracy and use of nonmydriatic ocular fundus photography by emergency physicians: phase II of the FOTO-ED study. Ann Emerg Med. 2013;62(1): 28-33.e1. 9. Pitts SR, Niska RW, Xu J, Burt CW. National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. Natl Health Stat Report. 2008;(7):1-38. 10. Breen DP, Duncan CW, Pope AE, Gray AJ, Al-Shahi Salman R. Emergency department evaluation of sudden, severe headache. QJM. 2008;101(6):435-443. 11. Maizels M. Headache evaluation and treatment by primary care physicians in an emergency department in the era of triptans. Arch Intern Med. 2001;161(16):1969-1973. 12. Thulasi P, Fraser CL, Biousse V, Wright DW, Newman NJ, Bruce BB. Nonmydriatic ocular fundus photography among headache patients in an emergency department. Neurology. 2013;80(5): 432-437. 13. Henderson AD, Bruce BB, Newman NJ, Biousse V. Hypertension-related eye abnormalities and the risk of stroke. Rev Neurol Dis. 2011;8(1-2):1-9. 14. Hagen K, Stovner LJ, Vatten L, Holmen J, Zwart JA, Bovim G. Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway. J Neurol Neurosurg Psychiatry. 2002;72(4): 463-466. 15. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): 629-808.
16. Gupta VK. Systemic hypertension, headache, and ocular hemodynamics: a new hypothesis. MedGenMed. 2006;8(3):63. 17. Papadopoulos DP, Mourouzis I, Thomopoulos C, Makris T, Papademetriou V. Hypertension crisis. Blood Press. 2010;19(6):328-336. 18. Baker ML, Hand PJ, Wang JJ, Wong TY. Retinal signs and stroke: revisiting the link between the eye and brain. Stroke. 2008;39(4):1371-1379. 19. Wang JJ, Baker ML, Hand PJ, et al. Transient ischemic attack and acute ischemic stroke: associations with retinal microvascular signs. Stroke. 2011;42(2):404-408. 20. Easton JD, Saver JL, Albers GW, et al; American Heart Association; American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Interdisciplinary Council on Peripheral Vascular Disease. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke. 2009;40(6):2276-2293. 21. Schliep v Providence Yakima Medical Center (Wash App 2005). 22. Lamirel C, Bruce BB, Wright DW, Newman NJ, Biousse V. Nonmydriatic digital ocular fundus photography on the iPhone 3G: the FOTO-ED study. Arch Ophthalmol. 2012;130(7):939-940. 23. Kelly LP, Garza PS, Bruce BB, Graubart EB, Newman NJ, Biousse V. Teaching ophthalmoscopy to medical students (the TOTeMS study). Am J Ophthalmol. 2013;156(5):1056-1061.e10. 24. Mackay DD, Garza PS, Bruce BB, et al. Teaching ophthalmoscopy to medical students (TOTeMS) II: a one-year retention study. Am J Ophthalmol. 2014; 157(3):747-748. 25. Kilker BA, Holst JM, Hoffmann B. Bedside ocular ultrasound in the emergency department. Eur J Emerg Med. 2014;21(4):246-253. 26. Williams GA, Scott IU, Haller JA, Maguire AM, Marcus D, McDonald HR. Single-field fundus photography for diabetic retinopathy screening: a report by the American Academy of Ophthalmology. Ophthalmology. 2004;111(5): 1055-1062.
(Reprinted) JAMA Neurology April 2015 Volume 72, Number 4
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459
Review
Nonmydriatic Ocular Fundus Photography in Neurologic Emergencies Beau B. Bruce, MD, PhD; Valérie Biousse, MD; Nancy J. Newman, MD
IMPORTANCE The ocular fundus examination is infrequently and poorly performed in clinical
settings, placing patients at risk for missed and delayed diagnosis of vision- and life-threatening neurologic disease. OBJECTIVES To review the importance of ocular fundus examination, the limitations of direct ophthalmoscopy, and the relative merits of nonmydriatic ocular fundus photography in emergency neurologic diagnosis. EVIDENCE REVIEW PubMed queries were reviewed for articles of relevance to this review. Queries included relevant combinations of the search terms ophthalmoscopy, nonmydriatic, neurology, and emergency, including variant spellings and endings. FINDINGS Nonmydriatic ocular fundus photography is more sensitive than direct ophthalmoscopy in several settings. It can be feasibly performed in emergency departments and has substantial promise in improving neurologic diagnosis, particularly headache and cerebrovascular disease. CONCLUSIONS AND RELEVANCE Nonmydriatic ocular fundus photography has notable advantages over direct ophthalmoscopy that likely outweigh its associated costs. More widespread deployment and integration into neurologic practice is expected to improve diagnosis and patient outcomes. JAMA Neurol. 2015;72(4):455-459. doi:10.1001/jamaneurol.2014.4053 Published online February 9, 2015.
T
he ocular fundus examination provides a unique opportunity to directly visualize part of the central nervous system and its accompanying microvasculature. Even with the remarkable advances achieved in the field of neuroradiology, examination of the ocular fundus may provide the only diagnostic red flag, yielding a timely and accurate diagnosis for vision- or lifethreatening neurologic disease. As one example, consider how the discovery of papilledema in a patient presenting to the neurology clinic with headache would lead to evaluation of several severe conditions, such as obstructive hydrocephalus, mass lesion, cerebral venous thrombosis, or fulminant idiopathic intracranial hypertension. This article reviews the importance of ocular fundus examination, the limitations of direct ophthalmoscopy, and the relative merits of nonmydriatic ocular fundus photography in emergency neurologic diagnosis. PubMed was searched for relevant combinations of the search terms ophthalmoscopy, nonmydriatic, neurology, and emergency, including variant spellings and endings.
Direct Ophthalmoscopy vs Nonmydriatic Ocular Fundus Photography Although ophthalmoscopy continues to be part of the armamentarium of most neurologists and emergency department (ED) phyjamaneurology.com
Author Affiliations: Department of Ophthalmology, Emory University, Atlanta, Georgia (Bruce, Biousse, Newman); Department of Neurology, Emory University, Atlanta, Georgia (Bruce, Biousse, Newman); Department of Epidemiology, Emory University, Atlanta, Georgia (Bruce); Department of Neurological Surgery, Emory University, Atlanta, Georgia (Newman). Corresponding Author: Beau B. Bruce, MD, PhD, Departments of Ophthalmology, Neurology, and Epidemiology, Emory University, 1365B Clifton Rd NE, Atlanta, GA 30322 ([email protected]). Section Editor: David E. Pleasure, MD.
sicians, ocular fundus examination is infrequently and poorly performed in clinical practice. In fact, among 350 patients presenting to a US university hospital ED with headache, focal neurologic deficits, visual loss, or diastolic blood pressure of 120 mm Hg or higher, only 48 patients (14%; 95% CI, 10%–18%) had their ocular fundus examined by the ED physicians.1,2 In 2 hospitals in Birmingham, England, only 25 of 56 inpatients (45%; 95% CI, 32%-58%) referred to the neurology department could recall being examined with an ophthalmoscope, whereas 54 (96%; 95% CI, 87%-99%) recalled being examined with a stethoscope.3 These statistics seem startling until we consider the limitations of ophthalmoscopy at the bedside used in these studies and in most neurologic practices. Although direct ophthalmoscopes are extremely portable, and even commonly mounted on the walls of clinic offices and ED examination rooms, they are difficult to use and provide a limited field of view (approximately 5°) (Figure). Indeed, even in the hands of ophthalmologists examining patients with pharmacologically dilated pupils, direct ophthalmoscopes have poor sensitivity for common conditions, such as diabetic retinopathy (52%) and hypertensive retinopathy (44%).4 The field of view and diagnostic sensitivity are further limited when direct ophthalmoscopes are used without pupillary dilation.5 Nonmydriatic ocular fundus photography holds promise as an alternative to direct ophthalmoscopy. Nonmydriatic cameras allow (Reprinted) JAMA Neurology April 2015 Volume 72, Number 4
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archneur.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 05/25/2015
455
Clinical Review & Education Review
Nonmydriatic Ocular Fundus Photography
Figure. Nonmydriatic Ocular Fundus Photographs A
B
C
D
E
A, Normal ocular fundus, with inset showing typical field of view of a direct ophthalmoscope. B, Optic disc edema. C, Optic disc pallor. D, Isolated retinal hemorrhage (arrowhead). E, Grade III hypertensive retinopathy (black arrowhead indicates cotton wool spot; white arrowhead, hemorrhage). The black backgrounds of the original images were cropped, and the brightness and contrast were adjusted.
456
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Nonmydriatic Ocular Fundus Photography
wide-field (45°) photographs to be taken of the ocular fundus without pharmacologic dilation of the pupils and with relative ease, even after onlylimitedtraining.1 Inaddition,studies6,7 ofnonmydriaticfundusphotography in diabetic retinopathy screening have found nonmydriatic photography to have higher sensitivity, specificity, and interexamination agreement than ophthalmoscopy, even among ophthalmologists, and there is level I evidence that single-field fundus photography can reliably and easily identify patients with diabetic retinopathy who require referral for ophthalmic evaluation and management.
Review Clinical Review & Education
Table. Comparison of the 2 Phases of the FOTO-ED Studya
jamaneurology.com
Phase 2 (Nonmydriatic Photography) (n = 354)
Age, median (IQR), y
44.5 (31-59)
45.9 (33-57)
Women
220 (62.9)
251 (70.9)
Headache
228 (65.1)
206 (58.2)
Focal neurologic deficit
100 (28.6)
123 (34.7)
Characteristic
Chief concerns
Nonmydriatic Ocular Fundus Photography in the ED In the ED, failure to correctly evaluate the ocular fundus can have life-threatening consequences, and the Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department (FOTO-ED) study1,2,8 evaluated whether nonmydriatic ocular fundus photography would be feasible and improve diagnosis in the ED compared with direct ophthalmoscopy. The study included adult patients presenting to a university ED with headaches, focal neurologic deficits, diastolic blood pressure of 120 mm Hg or higher, and/or acute visual changes. All patients had nonmydriatic ocular fundus photographs obtained by trained nurse practitioners or a medical student using a commercially available nonmydriatic ocular fundus camera (Kowa nonmyd-D series cameras; Kowa Optimed Inc). Throughout the FOTO-ED study, relevant ocular fundus abnormalities were defined as optic disc edema, isolated intraocular hemorrhage, grade III or IV hypertensive retinopathy, retinal vascular occlusion, and optic disc pallor (Figure). The first phase of the FOTO-ED study evaluated the routine clinical use of direct ophthalmoscopy by ED physicians and found that direct ophthalmoscopy was infrequently and poorly performed by ED physicians and that nonmydriatic fundus photography was a feasible alternative to direct ophthalmoscopy.1,2 In this study, 44 of the 350 enrolled patients had relevant ocular findings (13%; 95% CI, 9%– 17%) identified on nonmydriatic fundus photographs by the neuroophthalmologist reviewing the images (Table). Eleven of the findings were known before ED presentation. Of the remaining 33 findings, 6 were identified by ophthalmologic consultants, but the other 27 patients neither had a consult requested nor were identified by the ED physicians, who only examined 48 (14%) of the enrolled patients and personally identified none of the relevant findings. Thus, 82% (95% CI, 65%–93%) of the findings unknown at the time of ED presentation were missed by routine ED care. Nonmydriatic photography was well liked by patients and the nurse practitioners taking the photographs (mean ease, speed, and comfort ratings ⱖ8.7 of 10 for all). The photographs were of a quality that provided some clinical information for 97% of enrolled patients and required little time to obtain (median, 1.9 minutes; interquartile range, 1.3–2.9 minutes). In the second phase of the FOTO-ED study,8 which evaluated the routine use of nonmydriatic ocular fundus photography as interpreted by the ED physicians, of the 354 enrolled patients, 35 (10%; 95% CI, 7%–13%) had relevant findings identified by neuroophthalmologist review of the images. The ED physicians reviewed the photographs more frequently (239 patients [68%]) than they had used direct ophthalmoscopy, resulting in their improved detection of relevant abnormalities (16 [46%] of 35 patients). The
Phase 1 (Direct Ophthalmoscopy) (n = 350)
Visual changes
92 (26.3)
56 (15.8)
DBP ≥120 mm Hg
21 (6.0)
21 (5.9)
Relevant findings Optic disc edema
13 (3.7)
6 (1.7)
Grade III or IV hypertension retinopathy
10 (2.9)
6 (1.7)
Isolated intraocular hemorrhage
13 (3.7)
7 (2.0)
4 (1.1)
15 (4.2)
Optic disc pallor Retinal vascular occlusion Total Patients whose ocular fundus was viewed by ED physicians Relevant findings correctly detected by ED physician examination
4 (1.1)
1 (0.3)
44 (12.6)
35 (9.9)
48 (13.7)
239 (67.5)
0/44
16/35 (45.7)
Abbreviations: DBP, diastolic blood pressure; ED, emergency department; FOTO-ED, Fundus Photography vs Ophthalmoscopy Trial Outcomes in the Emergency Department; IQR, interquartile range. a
Data are presented as number (percentage) of patients unless otherwise indicated. Some percentages sum to more than 100% because patients were allowed to report more than 1 concern.
increased frequency of viewing the fundus and diagnosing abnormalities was particularly remarkable given that the ED physicians had not received any additional training in fundus photographic interpretation. The ED physicians also reported that the photographs were helpful in their evaluation of 125 patients (35%; 95% CI, 30%– 41%), including many cases when the photographs were normal (eg, the absence of papilledema in a patient with possible cerebrospinal fluid shunt malfunction).
Nonmydriatic Ocular Fundus Photography for Neurologic Emergencies The FOTO-ED study studied the entire population of patients in whom ocular fundus examination is considered imperative, but there are 2 specific neurologic emergencies for which routine examination of the ocular fundus is likely to bear substantial fruit: headache and cerebrovascular disease.
Headache In the ED, headache is the fourth most common chief concern overall and the most common neurologic concerns.9 Finding optic disc edema or optic disc pallor in a patient with headache is most concerning for disorders of intracranial pressure or compression of the anterior visual pathways. In a patient without a known cause, either finding should prompt an urgent evaluation for the underlying cause. (Reprinted) JAMA Neurology April 2015 Volume 72, Number 4
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Nonmydriatic Ocular Fundus Photography
Conversely, normal findings on physical examination reduce the likelihood of a secondary cause and provide reassurance that the patient is not experiencing insidious visual field loss from increased intracranial pressure or a slow-growing mass. However, studies10-12 of headache management in the ED have found ophthalmoscopy documented in only 12% to 48% of cases. In an ancillary FOTO-ED study of 497 patients presenting to the ED with headache,12 42 patients (8.5%; 95% CI, 6%–11%) had relevant abnormalities of their ocular fundus. A high proportion of the patients (41%) with abnormal fundi had normal findings on brain imaging, emphasizing the importance of ocular fundus examination even in this era of neuroimaging. Overall, a body mass index (calculated as the weight in kilograms divided by height in meters squared) of 35 or higher (odds ratio [OR], 2.3; 95% CI, 1.16-4.50; P = .02), younger age (OR, 0.7 per 10-year increase; 95% CI, 0.57-0.95; P = .02), and higher mean arterial blood pressure (OR, 1.3 per 10–mm Hg increase; 95% CI, 1.09-1.55; P = .003) were independently predictive of ocular fundus abnormalities.12 The association of fundus abnormalities with younger age suggests that examination of the ocular fundus has the potential to identify a key subset of secondary headaches because the prevalence of secondary headaches generally increases with age. Surprisingly, approximately half of the ocular fundus abnormalities detected in patients presenting to the ED with headache were attributable to systemic hypertension (isolated retinal hemorrhages [36%] and grade III or IV hypertensive retinopathy [14%]).12,13 This high proportion of findings from systemic hypertension initially appears contrary to large, well-conducted, population-based studies and the International Headache Society consensus that no association exists between mild to moderate hypertension and headache.14,15 However, headache is a common presenting symptom of hypertensive urgencies, and other studies16,17 have associated more severe hypertension with headache. These findings emphasize yet another way that consistent and thorough examination of the ocular fundus can help to detect a treatable underlying cause of neurologic disease, while also offering an early opportunity for intervention against an important cause of morbidity and mortality.
Cerebrovascular Disease Another area where nonmydriatic ocular fundus photography may be valuable for neurologic care is in the risk stratification of patients presenting with possible transient ischemic attack (TIA) or stroke. Retinal microvascular abnormalities (eg, vascular narrowing, tortuosity, and occlusion; cotton wool spots; microaneurysms; retinal hemorrhages; and hypertensive retinopathy) are known to be strongly associated with the long-term risk of stroke based on a summary18 of large epidemiologic studies, but the value of ocular fundus examination in prediction of short-term events in individual patients with acute neurologic events (eg, stroke after presentation of TIA) remains unclear. In one study,19 dilated ocular fundus photographs revealed that patients admitted to the hospital with TIA or acute stroke had an odds of focal arteriolar narrowing 7.2 to 8.9 times that of healthy controls. Ocular fundus abnormalities may represent asymptomatic underlying cerebrovascular injury in patients who present with neurologic symptoms. If so, acute microvascular fundus abnormalities would have a role analogous to the role diffusion-weighted magnetic resonance imaging abnormali458
ties have in determining the presence of acute cerebral ischemia.20 In addition, the presence of these microvascular ocular fundus abnormalities may help differentiate true TIAs (which by definition have no lesions on diffusion-weighted magnetic resonance imaging20) from noncerebrovascular causes of transient focal neurologic symptoms. In fact, we will soon begin a federally funded, multisite prospective cohort study designed to determine whether ocular fundus abnormalities are valuable in the acute risk stratification of TIA and minor stroke.
Is It Time for Nonmydriatic Photography in Routine Neurologic Practice? There is a pressing need for better and more consistent examination of the ocular fundus that nonmydriatic photography appears to fill. The price tag of a camera (approximately $25 000) vs an ophthalmoscope ($100-$500) may give one pause. However, the benefits of nonmydriatic ocular fundus photography already appear to outweigh the monetary costs when one considers (1) the high risk of poor patient outcomes and their attendant medicolegal actions,3,21 (2) the ease with which digital images can be added to electronic medical record systems for improved documentation and interpractice communication and can be shared with experts via telemedicine when diagnostic uncertainty exists,22 and (3) the challenge of improving direct ophthalmoscopy education to a level at which ophthalmoscopy would have the diagnostic sensitivity needed for clinical care.23,24 Indeed, recognizing the importance of improved ocular examination and reflecting discontent with bedside ophthalmoscopy, some have replaced direct ophthalmoscopy with ultrasonography in the ED to diagnose conditions such as papilledema and intraocular hemorrhage when photography would be more sensitive and better suited to answer the questions at hand.25 Others have attempted to augment ophthalmoscopes with smartphones to gain easier visualization of the ocular fundus and the advantages of digital photography (eg, iExaminer; Welch Allyn Inc). However, the most exciting development is commercially available, handheld nonmydriatic cameras (eg, Pictor; Volk Optical Inc; and Digital Medical Scope VersaCam; Nidek Co Ltd) that produce photographs of adequate quality for many clinical scenarios, allow examination of sicker and younger patients who cannot sit at a camera, while remaining considerably easier to use than an ophthalmoscope.
Conclusions Continued improvements will continue to lead toward the ideal digital ophthalmoscope, which will have comparable quality and ease of use to a tabletop camera, yet be as inexpensive as a direct ophthalmoscope. Yet even now, nonmydriatic photography provides a valuable evaluation method for patients at risk for acute neurologic disease, not just in the ED but also in other settings where dangerous diseases may be lurking, such as headache centers and general neurology clinics. Therefore, as we await the future, it is appropriate to integrate nonmydriatic photography into many neurologic settings to improve the care of our patients.
JAMA Neurology April 2015 Volume 72, Number 4 (Reprinted)
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Nonmydriatic Ocular Fundus Photography
ARTICLE INFORMATION Accepted for Publication: October 31, 2014. Published Online: February 9, 2015. doi:10.1001/jamaneurol.2014.4053. Author Contributions: Dr Bruce had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Bruce, Biousse, Newman. Acquisition, analysis, or interpretation of data: Bruce, Biousse, Newman. Drafting of the manuscript: Bruce. Critical revision of the manuscript for important intellectual content: Bruce, Biousse, Newman. Administrative, technical, or material support: Bruce, Newman. Study supervision: Newman. Conflict of Interest Disclosures: None reported. Funding/Support: This research was supported in part by an unrestricted departmental grant from Research to Prevent Blindness Inc (Department of Ophthalmology, Emory University) and by core grant P30-EY006360 from the National Eye Institute (Department of Ophthalmology, Emory University). Dr Newman is a recipient of the Research to Prevent Blindness Lew R. Wasserman Merit Award. Dr Bruce receives research support from grant K23-EY019341 from the National Eye Institute. Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. REFERENCES 1. Bruce BB, Lamirel C, Biousse V, et al. Feasibility of nonmydriatic ocular fundus photography in the emergency department: phase I of the FOTO-ED study. Acad Emerg Med. 2011;18(9):928-933. 2. Bruce BB, Lamirel C, Wright DW, et al. Nonmydriatic ocular fundus photography in the emergency department. N Engl J Med. 2011;364(4): 387-389. 3. Nicholl DJ, Yap CP, Cahill V, Appleton J, Willetts E, Sturman S. The TOS study: can we use our patients to help improve clinical assessment? J R Coll Physicians Edinb. 2012;42(4):306-310. 4. Benbassat J, Polak BC, Javitt JC. Objectives of teaching direct ophthalmoscopy to medical students. Acta Ophthalmol. 2012;90(6):503-507.
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5. Carlsson AM, ten Hove MW, Stockl F. Direct ophthalmoscopic examination of the eyes: does a mydriatic agent help with diagnosis? Can Fam Physician. 2006;52:958-959. 6. Ahmed J, Ward TP, Bursell SE, Aiello LM, Cavallerano JD, Vigersky RA. The sensitivity and specificity of nonmydriatic digital stereoscopic retinal imaging in detecting diabetic retinopathy. Diabetes Care. 2006;29(10):2205-2209. 7. Lin DY, Blumenkranz MS, Brothers RJ, Grosvenor DM. The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: a comparison with ophthalmoscopy and standardized mydriatic color photography. Am J Ophthalmol. 2002;134(2):204-213. 8. Bruce BB, Thulasi P, Fraser CL, et al. Diagnostic accuracy and use of nonmydriatic ocular fundus photography by emergency physicians: phase II of the FOTO-ED study. Ann Emerg Med. 2013;62(1): 28-33.e1. 9. Pitts SR, Niska RW, Xu J, Burt CW. National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. Natl Health Stat Report. 2008;(7):1-38. 10. Breen DP, Duncan CW, Pope AE, Gray AJ, Al-Shahi Salman R. Emergency department evaluation of sudden, severe headache. QJM. 2008;101(6):435-443. 11. Maizels M. Headache evaluation and treatment by primary care physicians in an emergency department in the era of triptans. Arch Intern Med. 2001;161(16):1969-1973. 12. Thulasi P, Fraser CL, Biousse V, Wright DW, Newman NJ, Bruce BB. Nonmydriatic ocular fundus photography among headache patients in an emergency department. Neurology. 2013;80(5): 432-437. 13. Henderson AD, Bruce BB, Newman NJ, Biousse V. Hypertension-related eye abnormalities and the risk of stroke. Rev Neurol Dis. 2011;8(1-2):1-9. 14. Hagen K, Stovner LJ, Vatten L, Holmen J, Zwart JA, Bovim G. Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway. J Neurol Neurosurg Psychiatry. 2002;72(4): 463-466. 15. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9): 629-808.
16. Gupta VK. Systemic hypertension, headache, and ocular hemodynamics: a new hypothesis. MedGenMed. 2006;8(3):63. 17. Papadopoulos DP, Mourouzis I, Thomopoulos C, Makris T, Papademetriou V. Hypertension crisis. Blood Press. 2010;19(6):328-336. 18. Baker ML, Hand PJ, Wang JJ, Wong TY. Retinal signs and stroke: revisiting the link between the eye and brain. Stroke. 2008;39(4):1371-1379. 19. Wang JJ, Baker ML, Hand PJ, et al. Transient ischemic attack and acute ischemic stroke: associations with retinal microvascular signs. Stroke. 2011;42(2):404-408. 20. Easton JD, Saver JL, Albers GW, et al; American Heart Association; American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Interdisciplinary Council on Peripheral Vascular Disease. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. Stroke. 2009;40(6):2276-2293. 21. Schliep v Providence Yakima Medical Center (Wash App 2005). 22. Lamirel C, Bruce BB, Wright DW, Newman NJ, Biousse V. Nonmydriatic digital ocular fundus photography on the iPhone 3G: the FOTO-ED study. Arch Ophthalmol. 2012;130(7):939-940. 23. Kelly LP, Garza PS, Bruce BB, Graubart EB, Newman NJ, Biousse V. Teaching ophthalmoscopy to medical students (the TOTeMS study). Am J Ophthalmol. 2013;156(5):1056-1061.e10. 24. Mackay DD, Garza PS, Bruce BB, et al. Teaching ophthalmoscopy to medical students (TOTeMS) II: a one-year retention study. Am J Ophthalmol. 2014; 157(3):747-748. 25. Kilker BA, Holst JM, Hoffmann B. Bedside ocular ultrasound in the emergency department. Eur J Emerg Med. 2014;21(4):246-253. 26. Williams GA, Scott IU, Haller JA, Maguire AM, Marcus D, McDonald HR. Single-field fundus photography for diabetic retinopathy screening: a report by the American Academy of Ophthalmology. Ophthalmology. 2004;111(5): 1055-1062.
(Reprinted) JAMA Neurology April 2015 Volume 72, Number 4
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