Relative Frequencies of Arteritic and Nonarteritic Anterior Ischemic Optic Neuropathy in an Arab Population

To evaluate the relative frequencies of arteritic and nonarteritic anterior ischemic optic neuropathy (AION) in an Arab population and to compare and contrast these findings with known epidemiological data from Caucasian populations. A retrospective review of the medical records of all patients diagnosed with AION at the King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia, between 1997 and 2012. Of 171 patients with AION, 4 had biopsy-proven giant-cell arteritis (GCA). The relative frequencies of arteritic anterior ischemic optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy (NAION) in this Arab cohort were 2.3% and 97.7%, respectively. The relative frequencies of arteritic anterior ischemic optic neuropathy and nonarteritic anterior ischemic optic neuropathy differ between Arab and North American clinic-based populations, with giant-cell arteritis-related ischemia being much less frequent in Saudi Arabia.

Original Contribution Relative Frequencies of Arteritic and Nonarteritic Anterior Ischemic Optic Neuropathy in an Arab Population Anna M. Gruener, BMBS, MSc, FRCOphth, Jessica R. Chang, MD, Thomas M. Bosley, MD, Zakeya M. Al-Sadah, MD, Clarissa Kum, OD, Timothy J. McCulley, MD Background: To evaluate the relative frequencies of arteritic and nonarteritic anterior ischemic optic neuropathy (AION) in an Arab population and to compare and contrast these findings with known epidemiological data from Caucasian populations. Methods: A retrospective review of the medical records of all patients diagnosed with AION at the King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia, between 1997 and 2012. Results: Of 171 patients with AION, 4 had biopsy-proven giant-cell arteritis (GCA). The relative frequencies of arteritic anterior ischemic optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy (NAION) in this Arab cohort were 2.3% and 97.7%, respectively. Conclusions: The relative frequencies of arteritic anterior ischemic optic neuropathy and nonarteritic anterior ischemic optic neuropathy differ between Arab and North American clinic-based populations, with giant-cell arteritisrelated ischemia being much less frequent in Saudi Arabia. Journal of Neuro-Ophthalmology 2017;37:382-385 doi: 10.1097/WNO.0000000000000491 © 2017 by North American Neuro-Ophthalmology Society I n the United States, Johnson and Arnold (1994) estimated the annual incidence of arteritic anterior ischemic optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy (NAION) in patients over 50 years of age to be 0.36 and 2.30 per 100,000, respectively (1). Hayreh reported that of 1,350 patients with anterior ischemic optic neuropathy (AION) seen in his clinic in Iowa (where The Neuro-Ophthalmology Division (AMG, JRC, TMB, CK, TJM), Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD; and Neuro-Ophthalmology Division (TMB, ZMA-S, TJM), King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. The authors report no conflict of interests. Address correspondence to Timothy J. McCulley, MD, 600 North Wolfe Street, Wilmer 110, Baltimore, MD 21287; E-mail: tmccull5@ jhmi.edu 382 there is a predominantly Caucasian population), 10% had AAION (2). Giant-cell arteritis (GCA) is thought to be most common in Caucasians (3), as compared to Asian (4) and black populations (5). According to data from several Scandinavian countries, the annual incidence of GCA in those over 50 years of age ranges from 20.4 to 32.8 per 100,000 (6-14). In contrast, the prevalence of GCA in Japanese patients over 50 years was found to be 1.47 per 100,000 (15). There are less epidemiological data available for GCA in black populations (16), but a 10-year study by Smith et al (17) found the incidence of GCA to be 7 times greater in Caucasian than in black patients. In Arabs, the true incidence of GCA is unknown, as no prospective, population-based study has yet been undertaken (18). A study from King Khaled Eye Specialist Hospital (KKESH) in Saudi Arabia reported only 7 positive results out of 106 temporal artery biopsies (TABs) performed over 22 years, compared with substantially larger numbers of positive TABs from North American referral eye centers with similar patient volumes (19). Although this suggests a low incidence, other factors likely impact this low positive biopsy rate, such as referral patterns and threshold of treating physicians to recommend biopsy. The aim of our study was to broaden our epidemiological understanding of AION by presenting the relative frequencies of AAION and NAION in a large Arab clinicbased population. This retrospective study was approved by the institutional review board of KKESH, Riyadh. KKESH is the primary referral eye center in Saudi Arabia and the largest ophthalmology facility in the Middle East, where approximately 200,000 outpatient and emergency room visits take place each year. As KKESH permits only Saudi nationals to be seen, all patients included in this study were of Saudi Arabian origin and did not include migrants. Gruener et al: J Neuro-Ophthalmol 2017; 37: 382-385 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Patients with AION were identified by reviewing the electronic database of a single neuro-ophthalmologist (TMB) between 1997 and 2012 for the diagnosis of ischemic optic neuropathy. Data, including categories of AION (i.e., AAION and NAION), TAB results, and patient demographics were tabulated. Diagnostic criteria for NAION were similar to those used in the Ischemic Optic Neuropathy Decompression Trial (IONDT) (20) and included 1) sudden onset of visual symptoms; 2) swollen optic disc at initial examination; 3) new visual field defect; and 4) absence of significant visual improvement over time. The diagnosis of AAION was based on clinical presentation and biopsy-proven GCA. One of the authors (TMB) reviewed each biopsy specimen to ensure that none had been classified incorrectly. Patients were considered to have biopsy-proven GCA if the histological examination of the temporal artery revealed arteritis, characterized by mononuclear cell infiltration of the arterial wall, as well as the presence of a granulomatous reaction and interruption of the internal elastic lamina. The relative frequencies of AAION and NAION were determined. RESULTS A total of 171 patients with AION were identified, 14 (8.2%) of whom underwent TAB. Four (28.6%) out of these 14 TABs yielded positive results, which means that 2.3% of patients with AION had biopsy-proven GCA. The median age of patients with AAION was 71.5 years (range, 62-79 years), and 3 (75%) were men. Two (50%) had bilateral AAION. Three (75%) patients with AAION (including those men with bilateral involvement) also were known diabetics. NAION was diagnosed in 167 (97.7%) patients. The mean and median age of patients with NAION was 56 years (range, 21-93 years), and 117 (70%) were men (among a clinic population that was 53% male). Two (1.2%) out of 167 patients with NAION were in their twenties, 11 (6.6%) were in their thirties, and 37 (22.2%) were in their forties. Thus, 50 (30%) patients with NAION were below 50 years of age. Our youngest patient was a 21-year-old man with congenital kidney disease and small, anomalous-looking optic discs, who was diagnosed with unilateral NAION following dialysis. Our second youngest patient was a 29-year-old man with a 13-year history of type 1 diabetes mellitus. Thirty-three (66%) out of 50 patients under the age of 50 had at least one known atherosclerotic cardiovascular disease (ASCVD) risk factor, including diabetes, hypertension, and hyperlipidemia. Ninety-one (78%) out of 117 patients aged 50 years or older had at least one ASCVD risk factor. The most common ASCVD risk factor encountered in our cohort was diabetes, being present in 26 (52%) out of 50 patients under the age of 50, and 76 (65%) out of 117 patients aged 50 years or older. None of our patients with NAION had systemic or retinal vasculitis Gruener et al: J Neuro-Ophthalmol 2017; 37: 382-385 (including Behcet disease). All had a negative antinuclear antibody (ANA) test that was performed as part of their routine diagnostic work-up, and none developed a clinical course suspicious of GCA or any other vasculitis. The relative frequencies of AAION and NAION in our cohort were 2.3% and 97.7%, respectively. DISCUSSION Epidemiology is an important tool for the assessment of risk, weighing the likelihood of a range of differential diagnoses. Large health data sets are more readily available for Western populations, but may not be applicable to populations of different ethnicities. Hayreh's large data set from a predominantly Caucasian clinic-based cohort showed relative frequencies of AAION and NAION of 10% and 90%, respectively (2). The aim of our study was to estimate the relative frequencies of AAION and NAION in a clinic-based Arab population. Our findings demonstrate a much lower relative frequency of AAION (2.3%) and correspondingly higher frequency of NAION (97.7%). This supports the notion that GCA-related ischemic optic neuropathy is relatively infrequent in the Arab population. However, the true incidence or prevalence of NAION or AAION in Arabs cannot be extrapolated from our data. The predilection of GCA for Caucasians, and relative sparing of non-Caucasian patients, implies genetic influences. Data suggest that GCA is a complex polygenic disease in which various genetic loci and polymorphisms contribute to disease susceptibility and clinical expression (21-26). Other potential explanations include geography and environmental factors. For example, various bacteria and viruses have been suggested as potential pathogens in GCA (6,27- 29). Recently, varicella zoster virus in temporal artery biopsies has been strongly implied in the immunopathology of GCA (30-32), although an earlier study of 17 TAB biopsy specimens demonstrated no significant differences in the microbiomes of temporal arteries from patients with GCA compared to controls (33). A nationwide survey showed a relatively low prevalence of GCA in Japan (15). Another study assessing the occurrence rate of GCA in Asians, compared to Caucasians, was conducted entirely within the United States; in this study, with presumably similar environmental factors between Asians and Caucasians, the low incidence in Asians persisted (4). This suggests that in these populations, differences are more apt to be genetic in nature. More research is needed to determine how much the observed low percentage of patients with GCA in Arab populations relates to genetic and possibly other factors. Limitations of our study include potential biases inherent in all retrospective analyses. Another difficulty is that the term "Arab" does not refer to a particular race, but rather a pan-ethnic group with ancestral origins in the Middle 383 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution East, North Africa and to a lesser degree, Europe. Moreover, although the most likely interpretation of our findings is that AAION is less frequent in the Arab population, an alternative explanation is that NAION is more prevalent. A recent population survey from Saudi Arabia found almost half of people aged 50 years or older to be diabetic (34), which exceeds the prevalence of diabetes in the United States and Europe. In our cohort, diabetes was a known comorbidity in 52% of patients under the age of 50 and 65% in those aged 50 years or older. In addition, smoking is very common in Saudi Arabia and has been reported in 49.2% of men aged 15 years and over (35). It therefore comes as little surprise that cardiovascular and cerebrovascular diseases are major health problems in that region (36). Furthermore, the prevalence of obstructive sleep apnea (OSA), another independent risk factor for the development of NAION (37), is particularly high (56.4%) in Saudi patients (38). Since ASCVD risk factors, and in particular diabetes (39,40), have been strongly associated with the development of NAION, a high incidence of NAION in Arabs (both relative and absolute) seems logical. Patients under age 50 years accounted for 30% of our NAION cohort, and this is more than double the percentage reported in a North American study that reviewed 848 NAION cases (41). In conclusion, when managing Arab patients with AION, our data suggest that there is less than 3% chance that it is due to GCA. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: T. J. McCulley; b. Acquisition of data: T. M. Bosley, Z. M. Al-Sadah, A. M. Gruener, and T. J. McCulley; c. Analysis and interpretation of data: A. M. Gruener, J. R. Chang, T. M. Bosley, T. J. McCulley, and Z. M. Al-Sadah. Category 2: a. 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