Factors Associated With Increased Emergency Department Utilization in Patients With Acute Optic Neuritis

Background: Symptoms of acute vision loss and eye pain may lead patients with optic neuritis to seek care in the emergency department (ED). Given the availability of lower cost alternatives for providing medical care for optic neuritis, this study aimed to identify factors associated with higher ED utilization. Methods: Subjects with acute optic neuritis were identified through a chart review of adults with International Classification of Diseases-9 (ICD-9) or ICD-10 codes for optic neuritis with corresponding gadolinium contrast enhancement of the optic nerve on MRI in the medical record research repository of a tertiary care institution. Subjects were grouped based on the number of ED visits (0-1 and 2-3) within 2 months of either ICD code or MRI. Demographics, characteristics of disease presentation, type and location of medical care, testing (chest imaging, lumbar puncture, optical coherence tomography, spine MRI, visual field, and laboratory tests), treatment, provider specialty of follow-up visits, and duration of care were extracted from the medical record. Results: Of 30 acute optic neuritis subjects (age 41 ± 16 years, range 18-76, 53% [16/30] female), 19 had 0-1 ED visit and 11 had 2-3 ED visits. Most subjects were Caucasian, non-Hispanic (47%), followed by Asian (23%), Hispanic/Latino (17%), Black (10%), and others (3%). Subjects had an initial clinical encounter primarily in the outpatient setting (63%) as compared with the ED (37%). The median time from symptom onset to initial clinical encounter was 4 days with a range of 0-13. Subjects were mostly insured through a private insurance (60%), followed by Medicare/Medicaid (23%) and uninsured (17%). Fewer ED visits were associated with an initial clinical encounter in an outpatient setting (P = 0.02, chi-square), but not residential distance from the hospital or insurance type. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). There was no significant difference in the ophthalmic, radiologic, or laboratory testing performed in both groups. Both groups presented in a similar time frame with similar symptoms and clinical signs. Treatment was similar in both groups. Conclusions: Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting and thus strategies aimed at facilitating outpatient care may help reduce unnecessary ED visits, although some, such as insurance status, may be difficult to modify. Further study in a larger sample is needed to refine these observations.

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Factors Associated With Increased Emergency Department Utilization in Patients With Acute Optic Neuritis Elena A. Muro-Fuentes, MS, Heather E. Moss, MD, PhD Background: Symptoms of acute vision loss and eye pain may lead patients with optic neuritis to seek care in the emergency department (ED). Given the availability of lower cost alternatives for providing medical care for optic neuritis, this study aimed to identify factors associated with higher ED utilization. Methods: Subjects with acute optic neuritis were identified through a chart review of adults with International Classification of Diseases-9 (ICD-9) or ICD-10 codes for optic neuritis with corresponding gadolinium contrast enhancement of the optic nerve on MRI in the medical record research repository of a tertiary care institution. Subjects were grouped based on the number of ED visits (0–1 and 2–3) within 2 months of either ICD code or MRI. Demographics, characteristics of disease presentation, type and location of medical care, testing (chest imaging, lumbar puncture, optical coherence tomography, spine MRI, visual field, and laboratory tests), treatment, provider specialty of follow-up visits, and duration of care were extracted from the medical record. Results: Of 30 acute optic neuritis subjects (age 41 ± 16 years, range 18–76, 53% [16/30] female), 19 had 0–1 ED visit and 11 had 2–3 ED visits. Most subjects were Caucasian, non-Hispanic (47%), followed by Asian (23%), Hispanic/Latino (17%), Black (10%), and others (3%). Subjects had an initial clinical encounter primarily in the outpatient setting (63%) as compared with the ED (37%). The median time from symptom onset to initial clinical encounter was 4 days with a range of 0–13. Subjects were mostly insured through a private insurance (60%), followed by Medicare/Medicaid (23%) and uninsured (17%). Fewer ED visits were associated with an initial clinical encounter in an outpatient setting (P = 0.02, chi-square), but not resiSaint Louis University School of Medicine (EM-F), St. Louis, Missouri; Department of Ophthalmology, Department of Neurology & Neurological Sciences at Stanford University (HM), Palo Alto, California; and Department of Neurology and Neurological Sciences (HM), Palo Alto, California. Funding from the National Eye Institute (P30-026877) and unrestricted grant to Stanford Department of Ophthalmology from Research to Prevent Blindness, Inc. The authors report no conflicts of interest. Address correspondence to Heather Moss, MD, PhD, Spencer Center for Vision Research at Stanford, 2370 Watson Court, Suite 200, MC 5353, Palo Alto, CA 94303; E-mail: [e-mail] Muro-Fuentes and Moss: J Neuro-Ophthalmol 2021; 41: 335-341 dential distance from the hospital or insurance type. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). There was no significant difference in the ophthalmic, radiologic, or laboratory testing performed in both groups. Both groups presented in a similar time frame with similar symptoms and clinical signs. Treatment was similar in both groups. Conclusions: Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting and thus strategies aimed at facilitating outpatient care may help reduce unnecessary ED visits, although some, such as insurance status, may be difficult to modify. Further study in a larger sample is needed to refine these observations. Journal of Neuro-Ophthalmology 2021;41:335–341 doi: 10.1097/WNO.0000000000001294 © 2021 by North American Neuro-Ophthalmology Society I t has been estimated that 5%–6% of the national health expenditure, more than $150 billion, is spent in emergency department care (1). From 2010 to 2016, there was a reported increase in emergency department (ED) visits from 128.97 million/year to 144.82 million/year (2). Furthermore, in a study conducted from 2006 to 2011, the annual average of ED visits for ophthalmic conditions approached 2 million (3). Given the availability of lower cost alternatives for providing more efficient medical care, better understanding of factors contributing to increased ED visits is needed to facilitate more cost-effective management of patients. Although a majority of ophthalmic visits to the ED are for conjunctivitis or corneal abrasions, there remain a substantial number of visits for eye pain or visual disturbances (3). Optic neuritis (ON) is an inflammatory condition of the optic nerve that often presents with both of these. With an incidence of about 5 per 100,000 in the United States, ON may have a meaningful effect on ophthalmic ED visits (4). Unlike some conditions, typical ON 335 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution does not require ED or inpatient facilities for diagnosis nor does it require emergent treatment. It is sometimes treated with intravenous or high-dose oral corticosteroids, which studies have shown is associated with faster visual recovery (5). Although most patients recover without treatment (5), some ON subtypes may require corticosteroid and other treatments for recovery (6). These treatments also do not require ED or inpatient facilities for administration. Given this suitability of ON for outpatient diagnosis and management, this study aimed to identify factors associated with higher ED utilization in patients with optic neuritis. METHODS Subjects This is a retrospective study that was approved with waiver of informed consent by the Stanford University IRB. Inclusion criteria were adults ($18 years old) with acute ON, defined as an International Classification of Diseases (ICD) code for ON ICD-9 code 377 or ICD-10 code H46, an MRI brain and/or orbits with and without contrast (Current Procedural Terminology code 70553, or 70543) indicating gadolinium contrast enhancement of the optic nerve within 2 months (7,8) of their earliest ICD code for ON, and a clinical note written by a physician documenting a clinical diagnosis of acute ON. Exclusion criteria were exclusively ICD codes within H46 or 377 indicating a secondary cause of optic neuritis or not including the term optic neuritis (e.g., ICD-9 377.00 unspecified papilledema, 377.31 optic papillitis, 377.33 nutritional optic neuropathy, or 377.34 toxic optic neuropathy; ICD-10 H46.0 optic papillitis, H46.2 nutritional optic neuropathy, or H46.3 toxic optic neuropathy). Potential subjects with the necessary ICD and Current Procedural Terminology (CPT) codes in the appropriate time frame were identified using the Stanford Research Repository tools, a medical record repository of a tertiary care institution, and these potential subjects were screened for inclusion by manual chart review. For included subjects, the number of ED visits at Stanford Health within 2 months of the earlier of either optic neuritis ICD code or MRI with gadolinium enhancement of an optic nerve was assessed based on a chart review. Subjects were grouped by low ED utilization (0–1 visit) vs high ED utilization (2–3 visits). Data Abstraction Demographic data were extracted from the medical record, including age at time of acute optic neuritis, sex, and race or ethnicity. Presence of pre-existing MS, history of previous ON, residential distance from the clinic (calculated through Google Maps, using the fastest route from a subject’s zip code), and insurance type (private, Medicare, or Medicaid) were recorded. Two values for distance were removed because distance was .1,500 km due to out-of-state permanent address. 336 For the purposes of characterizing the initial clinical presentation, clinical documentation up to 2 weeks from initial onset of symptoms was reviewed. The subject’s initial recorded clinical encounter (outside or at Stanford) after the onset of symptoms was identified through the medical record of the initial Stanford Health visit. The specialty of the provider, type of encounter (outpatient appointment or ED visit), and days between symptom onset and encounter were recorded. In addition to worst measured visual acuity, presence of pain, decreased visual acuity, color vision impairment, relative afferent pupillary defect (rAPD), and abnormalities of the optic disc (cotton wool spot, disc elevation, edema, hemorrhage, hyperemia, pallor, or peripapillary atrophy) were recorded. For the purposes of characterizing workup, documentation up to 2 months after initial optic neuritis ICD code or MRI with gadolinium enhancement of the optic nerve was reviewed. Presence of consults to ophthalmology, neurology, or optometry was recorded. Any ophthalmic (optical coherence tomography and visual field), radiologic (chest imaging and spine MRI), laboratory (antinuclear antibody, anti-Ro, anti-La, antineutrophil cytoplasmic antibody, fluorescent treponemal antibody absorption/rapid plasma reagin/enzyme-linked immunosorbent assay, Lyme-Ab/ Western Blot, myelin oligodendrocyte glycoprotein, neuromyelitis optica [NMO], angiotensinogen-converting enzyme [ACE], B12, C-reactive protein, and erythrocyte sedimentation rate) testing, lumbar puncture, treatment, and improvement of symptoms were also recorded. Improvement of symptoms was defined as recorded improvement in documented visual acuity or physician note stating improvement in visual acuity from worst visual acuity within 2 months of the earliest ICD code. To evaluate continuity of care, completed appointments with ophthalmology and/or neurology within a year of symptom onset were tallied. The total length of care within a year from the start of symptoms to the last documented office visit was recorded. Statistical Methods Comparisons were made between the low and high ED utilization groups using t tests for independent samples continuous variables with normal distribution and Mann– Whitney test for those with high skew or kurtosis. Categorical measures were compared using the chi-squared test or Fisher exact test for any 2 · 2 tables with cell size less than 10. Statistical significance was set at P , 0.05. Statistical analysis was performed using SPSS V26 (IBM Inc). RESULTS A cohort of 1,510 potential subjects was established with ICD-9/10 codes. From the initial 1,510 subjects, 1,164 (77%) were excluded from review because of nonapplicable ICD code for optic neuritis, lack of MRI CPT code, or lack Muro-Fuentes and Moss: J Neuro-Ophthalmol 2021; 41: 335-341 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution of accessible MRI report within 2 months of earliest ICD code. Of the remaining 346 potential subjects, 271 were excluded for lack of optic nerve enhancement on MRI, of which 143 lacked MRI orbits. Seventy-five (22%) had MRIs indicating enhancement of the optic nerve. Of those 75 subjects, 30 (45%) had acute optic neuritis as a clinical diagnosis and these were included as study subjects (Fig. 1). The other 45 potential subjects had a clinical diagnosis other than optic neuritis or insufficient data in the medical record to confirm a clinical diagnosis of optic neuritis. Alternative diagnoses included acute lymphocytic leukemia (4), ischemic optic neuropathy (2), lymphoma (2), metastases to optic nerves, mucormycosis, neuroendocrine carcinoma of sinonasal cavity with orbital extension, optic neuropathy likely related to sphenoid sinus invasive fungal sinusitis, optic neuropathy after radiation therapy, optic nerve glioma, papillophlebitis, perineuritis, sarcoidosis meningitis, and tumor vs radiation effects. Of the 30 acute optic neuritis subjects (age 41 ± 16 years, range 18%–76%, 53% [16/30] female), 19 had 0–1 ED visit and 11 had 2–3 ED visits. Subject demographic data are summarized in Table 1. Subjects with a higher number of ED visits were more likely to be of Hispanic/Latino ethnicity (P = 0.047, Fisher exact). Although the proportion of subjects who were Asian was lower in the high vs. low ED utilization group, this did not reach statistical significance (P = 0.22, Fisher exact). Subjects with fewer ED visits were more likely to have private insurance, although this did not reach statistical significance (P = 0.06, Fisher exact). Fewer ED visits were not associated with demographic variables including residential distance from the hospital or insurance type. Presenting signs and symptoms are summarized in Table 2. No significant difference was seen in worst visual acuity between the groups. Both groups presented in a similar time frame from symptoms onset with similar symptoms and clinical signs, including pain, color vision impairment, rAPD, and abnormal disc appearance. An initial clinical encounter in the outpatient setting was associated with fewer ED visits (P = 0.020, chisquare). On follow-up, most subjects saw both ophthalmology and neurology, with 99% of subjects following up with at least one of the 2 specialties. Length of care from initial encounter to last documented clinical encounter within a year ranged from 3 days to 364 days (Table 3). The number of ED visits was not associated with the duration or type of follow-up (ophthalmology, neurology, or both). Ophthalmic ancillary testing, additional radiology studies, lumbar puncture, and laboratory testing are listed in Table 4. There was an increased incidence of lumbar puncture in subjects with fewer ED visits, although this did not reach statistical significance (P = 0.063, Fisher exact). There was no significant difference in the remaining imaging and laboratory testing in both groups. Treatment and symptom improvement were similar in both groups (Table 5). CONCLUSIONS Optic neuritis is primarily a clinical diagnosis and typically can be appropriately managed in an outpatient setting (9). However, many patients may initially present to the ED or receive care through the ED at some point, and this may not be a cost-effective way to receive care with potential for a lack of transition to longitudinal follow-up. Our study sought to identify factors associated with increased ED visits in subjects with ON. Subjects with their first clinical encounter for optic neuritis in the ED had more visits to the ED overall when compared with those first seen in an outpatient setting without differences associated with age, sex, or presenting symptoms. This may indicate established outpatient care having a role in limiting ED care for acute FIG. 1. Identification of acute optic neuritis subjects. CPT, Current Procedural Terminology; ICD, International Classification of Diseases. Muro-Fuentes and Moss: J Neuro-Ophthalmol 2021; 41: 335-341 337 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Acute optic neuritis subjects Sex Female Race Caucasian, non-Hispanic Asian Hispanic/Latino Black Other Age, yrs Mean ± SD Other History of ON Pre-existing MS Insurance Private Medicare/Medicaid None Distance from clinic, km Median (range) No. of Subjects (%) (n = 30) 0–1 ED Visit (n = 19) 2–3 ED Visits (n = 11) 16 (53%) 11 (58%) 5 (45%) 14 (47%) 7 (23%) 5 (17%) 3 (10%) 1 (3%) 9 6 1 2 1 5 1 4 1 0 41 ± 16 45 ± 14 35 ± 19 3 (10%) 2 (7%) 1 (5%) 2 (11%) 2 (18%) 0 18 (60%) 7 (23%) 5 (17%) 14 (74%) 3 (16%) 2 (11%) 4 (36%) 4 (36%) 3 (27%) 32.8 (0.5–338) 24.6 (0.5–338) 56.8 (5.5–275.2) P P = 0.71* P = 0.16† (47%) (32%) (5%) (11%) (5%) (45%) (9%) (36%) (9%) P = 0.17‡ P = 0.54* P = 0.52* P = 0.13† P = 0.31§ *Fisher exact. † Chi-square. ‡ t test for independent samples. § Mann–Whitney. ED, emergency department; ON, optic neuritis; MS, multiple sclerosis. optic neuritis. These results will guide future investigations to confirm our findings and identify additional causes and consequences associated with increased ED use to inform development and implementation of novel care pathways that optimize patient care for optic neuritis. Initial subspecialty encounter may also play a role with a greater proportion of those with 2–3 ED visits (91%) not seeing either ophthalmology or neurology at their initial clinical encounter, compared with those with 0–1 ED visit (47%). This would be in-line with a study demonstrating that less ED use was associated with increased access to primary care physicians in Medicaid Health Maintenance Organization patients, specifically having longer evening hours and a lower ratio of the number of active patients per clinician hour of TABLE 2. Presenting signs and symptoms in acute optic neuritis subjects Blurry vision Color vision impairment rAPD Pain Abnormal disc appearance Edema Hyperemia Hemorrhage Pallor Peripapillary atrophy Elevation Cotton wool spot Nadir visual acuity #20/40 20/40–20/200 $20/200 Missing No. of Subjects (%) (n = 30) 0–1 ED Visit (n = 19) 2–3 ED Visits (n = 11) 30 18 24 24 20 14 5 4 3 2 1 1 19 11 17 15 15 11 3 4 3 2 1 1 11 (100%) 7 (64%) 7 (64%) 9 (82%) 5 (45%) 3 2 0 0 0 0 0 (100%) (60%) (80%) (80%) (67%) 6 (20%) 7 (23%) 15 (50%) 2 (7%) 3 6 8 2 (100%) (58%) (89%) (79%) (79%) (16%) (32%) (42%) (11%) 3 (27%) 1 (9%) 7 (64%) 0 P P P P P = = = = 1.0* 0.16* 1.0* 0.11* P = 0.83† *Fisher exact. † Linear trend. ED, emergency department; rAPD, relative afferent pupillary defect. 338 Muro-Fuentes and Moss: J Neuro-Ophthalmol 2021; 41: 335-341 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Clinical encounters for acute optic neuritis subjects No. of Subjects (%) ED Visits (0–1) ED Visits (2–3) (n = 30) (n = 19) (n = 11) Initial evaluation Emergency department 11 (37%) Outpatient 19 (63%) Ophthalmology 10 Optometry 5 Internal medicine 3 Neurology 1 Time from symptom onset to initial clinical encounter, d Median (range) 4 (0–13) Follow-up evaluation in first year Medical specialty Neurology 4 (13%) Ophthalmology 3 (10%) Both 21 (70%) Neither 2 (7%) Length of care within 1 year, d Median (range) 262 (3–364) 4 (21%) 15 (79%) 9 2 3 1 7 (64%) 4 (36%) 1 3 0 0 4 (0–13) 6 (0–11) P P = 0.047* P = 0.19† P = 0.28‡ 1 (5%) 2 (11%) 14 (74%) 2 (11%) 3 (27%) 1 (9%) 7 (64%) 0 259 (3–364) 265 (29–356) P = 0.98§ *Fisher exact. † t test for independent samples. ‡ Chi-square. § Mann–Whitney. practice time (10). Although subspecialists cannot prevent optic neuritis the same way primary care physicians may prevent medical emergencies that may contribute to lower ED use, other factors that may parallel between specialists and primary care include improved availability of the physician or physician’s office and improved patient education through a continued patient–physician relationship. Insurance is a possible factor that could affect access to outpatient care with more subjects in the low ED utilization group having private insurance, although this did not meet statistical significance. In our study, subjects of Hispanic ethnicity (only 1/5 of whom had private insurance) were more likely to have higher ED utilization. Other studies have shown a higher prevalence of Medicare/Medicaid in patients with more ED visits (11–13). A more recent study on eye-related ED visits had a similar finding, with Medicaid or uninsured patients having a higher rate of nonemergent ED visits as compared to those with private insurance (3). Relevant to neuro-ophthalmic diagnoses, ED utilization in patients with IIH was found to be higher by those on Medicare/Medicaid (14). Strategies to improve access to outpatient care include same-day access ophthalmology departments that have been shown to have lowered costs and shortened length of stay as compared to the ED (15). The workup, treatment, subjective outcome, and outpatient follow-up of patients were similar regardless of ED utilization, suggesting that ED utilization did not affect care delivered in these categories. Our study demonstrates a high level of treatment for optic neuritis at the institution studied. Among both groups of subjects, all but 2 subjects received intravenous (IV) corticosteroids as treatment. IV corticosteroids have been shown to Muro-Fuentes and Moss: J Neuro-Ophthalmol 2021; 41: 335-341 accelerate visual recovery, although not associated with improvement on long-term visual outcome overall (5), they likely have an important role in treatment of NMO spectrum disease. In our study, the one subject who had detectable serum anti-aquaporin 4 IgG received IV corticosteroids, but those 2 who did not receive treatment were not tested for NMO. In an international survey, more ophthalmologists than neurologists (33% vs 4%) recommended no treatment for ON, whereas more neurologists than ophthalmologists (87% vs 48%) recommended IV corticosteroids (16). This survey also showed that more US neurologists than ophthalmologists (72% vs 35%) were prescribing steroids to improve visual function (16). A similar study conducted in Canada showed that there were significantly fewer ophthalmologists than neurologists who would treat optic neuritis with IV corticosteroids (17). This study also found that both ophthalmologists and neurologists listed additional reasons besides shortening symptoms for prescribing steroids, including affecting visual outcome and reducing future risk MS (17). Although specialty of recommending physician was not collected in our study and we were unable to reliably assess reasoning for treatment, these studies may help explain the high treatment rate in our study. Although not an objective of the study, the relatively small number of subjects confirmed to have acute optic neuritis based on chart review of potential subjects identified using ICD and CPT code searches is an important finding. Of 346 patients with an ICD code for optic neuritis and an MRI report within 2 months of the ICD code, the majority (271) did not have enhancement of the optic nerve to support a diagnosis of acute optic neuritis. Although lack of appropriate imaging may have been a factor (i.e., optic nerve enhancement would have been 339 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 4. Laboratory, ophthalmic, and radiologic testing performed in acute optic neuritis subjects Laboratory tests ESR NMO Positive Negative ANA FTA-ABS/RPR/ELISA Lyme-Ab/Western blot CRP ACE Anti-La Anti-Ro B12 ANCA MOG Positive Negative Testing Lumbar puncture Visual field Chest imaging OCT Spine MRI No. of Subjects (%) (n = 30) ED Visits (0–1) (n = 19) ED Visits (2–3) (n = 11) 20 (67%) 19 (63%) 1 18 18 (60%) 18 (60%) 14 (47%) 14 (47%) 13 (43%) 11 (37%) 11 (37%) 10 (33%) 7 (23%) 6 (20%) 3 3 12 (63%) 10 (53%) 0 10 10 (53%) 9 (47%) 7 (37%) 7 (37%) 7 (37%) 6 (32%) 6 (32%) 5 (26%) 3 (16%) 3 (16%) 1 2 8 9 1 8 8 9 7 7 6 5 5 5 4 3 2 1 18 15 13 12 12 14 (74%) 10 (53%) 8 (42%) 8 (42%) 6 (32%) 4 5 5 4 6 P P = 0.055 (60%) (50%) (43%) (40%) (40%) (73%) (82%) (73%) (82%) (64%) (64%) (55%) (45%) (45%) (45%) (36%) (27%) (36%) (45%) (45%) (36%) (55%) P P P P P = = = = = 0.063* 1.0* 1.0* 1.0* 0.27* *Fisher exact. Ab, antibody; ACE, angiotensinogen-converting enzyme; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; CRP, Creactive protein; ELISA, enzyme-linked immunosorbent assay; ESR, erythrocyte sedimentation rate; FTA-ABS, fluorescent treponemal antibody absorption; MOG, myelin oligodendrocyte glycoprotein; NMO, neuromyelitis optica; OCT, optical coherence tomography; RPR, rapid plasma reagin. detected if an appropriate scan had been performed in the appropriate window), this likely is the case for a minority of cases as 143 of the 271 had an orbit MRI with and without contrast and 232 of the 271 had scans performed within one month. Although optic neuritis is mainly a clinical diagnosis, enhancement is seen in 94% of patients with acute clinical symptoms (18). This highlights the lack of specificity in the ICD-9 and ICD-10 codes for acute vs previous optic neuritis. Our yield of ICD code plus testing suggestive of diagnostic workup was less than 10% for acute optic neuritis cases, although true optic neuritis cases were likely excluded because of our rigorous inclusion criteria. Of the 75 potential subjects with an appropriate optic neuritis ICD code and MRI supporting the diagnosis as an acute process, only 30 subjects had the corresponding clinical diagnosis, whereas 26 potential subjects had insufficient medical records and 19 potential subjects had other diagnoses. This corresponds to 61% true positive and 39% false positive for classification based on ICD and review of MRI report alone in subjects with complete data. This reinforces the finding of a high rate of misdiagnosis among patients referred to a tertiary care neuro-ophthalmology clinic for optic neuritis (almost 60%) previously reported (19). The important implication regarding the identifying cases of optic neuritis using medical claims data is that misclassification bias is high without a medical record review. One study identified ON cases by an ICD code of 377.30 or 377.32 and ACE testing within 90 days or an ICD code given at least 2 times within 90 days (20), but did not validate this algorithm. In addition, a systematic review TABLE 5. Treatment of acute optic neuritis subjects No. of Patients (%) (n = 30) ED Visits (0–1) (n = 19) 29 (97%) 1 (3%) 17 (89%) 2 (11%) 11 (100%) 0 25 (83%) 5 (17%) 16 (84%) 3 (16%) 9 (82%) 2 (18%) Treatment IV corticosteroids None VA improvement Yes No ED Visits (2–3) (n = 11) P P = 0.52* P = 1.0* *Fisher exact. IV, intravenous; VA, visual acuity. 340 Muro-Fuentes and Moss: J Neuro-Ophthalmol 2021; 41: 335-341 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution of the validity of ICD codes in various neuro-ophthalmic diseases, including ON, showed overall variable diagnostic accuracy, further emphasizing the potential lack of specificity in ICD codes (21). Further study is needed to determine whether algorithms based on coding frequency and other testing might have more sensitivity and specificity than our initial ICD and MRI CPT approach. Limitations of our study include single center and tertiary care nature as well as relatively small sample size. This was a result of use of strict inclusion criteria designed to maximize diagnostic confidence at the expense of generalizability. In other words, we minimized misclassification bias at the expense of possible selection bias because our case definition likely excluded some patients with optic neuritis because of lack of supporting information. For example, 128 of the 271 potential subjects who were excluded for lack of optic nerve gadolinium enhancement had only a brain MRI that may have been insufficient for evaluation of optic nerve enhancement. However, the perils of a less rigorous case definition are exemplified by the 19 potential subjects who met coding and MRI criteria but had alternative diagnoses. ED visits considered in this study may be an overall underestimation because they are exclusive to one health center, which may be influenced by other factors influencing locations patients receive care differing according to type of care (ED, primary, or specialty). Further studies examining larger cohorts at multiple centers are necessary to validate the generalizability of these results and identify other factors associated with ED utilization in patients with optic neuritis who were not included in this study. As the specific reason for each ED visit was not recorded, our study potentially reflects nonspecific factors associated with increased ED utilization. A strength is the rigorous inclusion criteria that increases confidence in correct classification of subjects. As our inclusion criteria greatly narrowed our eligible subjects, investigations into a more accurate system for identifying optic neuritis through administrative records or natural language processing of electronic medical records are important. Future research efforts should also be directed toward increasing patient education about and access to outpatient care for optic neuritis. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E. Muro-Fuentes and H. Moss; b. Acquisition of data: E. Muro-Fuentes; c. Analysis and interpretation of data: E. Muro-Fuentes and H. Moss. Category 2: a. Drafting the manuscript: E. Muro-Fuentes and H. Moss; b. Revising it for intellectual content: E. Muro-Fuentes and H. Moss. 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