Secondary Logo

Journal Logo

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

Gruener, Anna M. BMBS, MSc, FRCOphth; Chang, Jessica R. MD; Bosley, Thomas M. MD; Al-Sadah, Zakeya M. MD; Kum, Clarissa OD; McCulley, Timothy J. MD

doi: 10.1097/WNO.0000000000000491
Original Contribution
Free

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 arteritis-related ischemia being much less frequent in Saudi Arabia.

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.

Address correspondence to Timothy J. McCulley, MD, 600 North Wolfe Street, Wilmer 110, Baltimore, MD 21287; E-mail: tmccull5@jhmi.edu

The authors report no conflict of interests.

In 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 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 clinic-based 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.

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.

Back to Top | Article Outline

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 (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.

Back to Top | Article Outline

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 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. Drafting the manuscript: A. M. Gruener, T. J. McCulley, and J. R. Chang; b. Revising it for intellectual content: A. M. Gruener, T. J. McCulley, T. M. Bosley, J. R. Chang, and C. Kum. Category 3: a. Final approval of the completed manuscript: A. M. Gruener, J. R. Chang, T. J. McCulley, T. M. Bosley, Z. M. Al-Sadah, and C. Kum.

Back to Top | Article Outline

ACKNOWLEDGMENTS

A. M. Gruener came to Johns Hopkins as a T.F.C. Frost Fellow. She would like to express her sincere gratitude to the T.F.C. Frost Charitable Trust for financially supporting her during her stay.

Back to Top | Article Outline

REFERENCES

1. Johnson LN, Arnold AC. Incidence of nonarteritic and arteritic anterior ischemic optic neuropathy. Population-based study in the state of Missouri and Los Angeles County, California. J Neuroophthalmol. 1994;14:38–44.
2. Hayreh SS. Ischemic optic neuropathies—where are we now? Graefes Arch Clin Exp Ophthalmol. 2013;251:1873–1884.
3. Lee JL, Naguwa SM, Cheema GS, Gershwin ME. The geo-epidemiology of temporal (giant cell) arteritis. Clin Rev Allergy Immunol. 2008;35:88–95.
4. Pereira LS, Yoon MK, Hwang TN, Hong JE, Ray K, Porco T, McCulley TJ. Giant cell arteritis in Asians: a comparative study. Br J Ophthalmol. 2011;95:214–216.
5. Liu NH, LaBree LD, Feldon SE, Rao NA. The epidemiology of giant cell arteritis: a 12-year retrospective study. Ophthalmology. 2001;108:1145–1149.
6. Elling P, Olsson AT, Elling H. Synchronous variations of the incidence of temporal arteritis and polymyalgia rheumatica in different regions of Denmark; association with epidemics of Mycoplasma pneumoniae infection. J Rheumatol. 1996;23:112–119.
7. Petursdottir V, Johansson H, Nordborg E, Nordborg C. The epidemiology of biopsy-positive giant cell arteritis: special reference to cyclic fluctuations. Rheumatology (Oxford). 1999;38:1208–1212.
8. Franzen P, Sutinen S, von Knorring J. Giant cell arteritis and polymyalgia rheumatica in a region of Finland: an epidemiologic, clinical and pathologic study, 1984–1988. J Rheumatol. 1992;19:273–276.
9. Baldursson O, Steinsson K, Bjornsson J, Lie JT. Giant cell arteritis in Iceland. An epidemiologic and histopathologic analysis. Arthritis Rheum. 1994;37:1007–1012.
10. Nordborg C, Johansson H, Petursdottir V, Nordborg E. The epidemiology of biopsy-positive giant cell arteritis: special reference to changes in the age of the population. Rheumatology (Oxford). 2003;42:549–552.
11. Gran JT, Myklebust G. The incidence of polymyalgia rheumatica and temporal arteritis in the county of Aust Agder, south Norway: a prospective study 1987–94. J Rheumatol. 1997;24:1739–1743.
12. Boesen P, Sorensen SF. Giant cell arteritis, temporal arteritis, and polymyalgia rheumatica in a Danish county. A prospective investigation, 1982–1985. Arthritis Rheum. 1987;30:294–299.
13. Noltorp S, Svensson B. High incidence of polymyalgia rheumatica and giant cell arteritis in a Swedish community. Clin Exp Rheumatol. 1991;9:351–355.
14. Haugeberg G, Dovland H, Johnsen V. Increased frequency of malignancy found in patients presenting with new-onset polymyalgic symptoms suggested to have polymyalgia rheumatica. Arthritis Rheum. 2002;47:346–347.
15. Kobayashi S, Yano T, Matsumoto Y, Numano F, Nakajima N, Yasuda K, Yutani C, Nakayama T, Tamakoshi A, Kawamura T, Ohno Y, Inaba Y, Hashimoto H. Clinical and epidemiologic analysis of giant cell (temporal) arteritis from a nationwide survey in 1998 in Japan: the first government-supported nationwide survey. Arthritis Rheum. 2003;49:594–598.
16. Love DC, Rapkin J, Lesser GR, Shmookler BM, Kolsky MP, Jackson B, Barth WF. Temporal arteritis in blacks. Ann Intern Med. 1986;105:387–389.
17. Smith CA, Fidler WJ, Pinals RS. The epidemiology of giant cell arteritis. Report of a ten-year study in Shelby County, Tennessee. Arthritis Rheum. 1983;26:1214–1219.
18. Bosley TM, Riley FC. Giant cell arteritis in Saudi Arabia. Int Ophthalmol. 1998;22:59–60.
19. Chaudhry IA, Shamsi FA, Elzaridi E, Arat YO, Bosley TM, Riley FC. Epidemiology of giant-cell arteritis in an Arab population: a 22-year study. Br J Ophthalmol. 2007;91:715–718.
20. The ischemic optic neuropathy decompression trial (IONDT): design and methods. Control Clin Trials. 1998;19:276–296.
21. Weyand CM, Hunder NN, Hicok KC, Hunder GG, Goronzy JJ. HLA-DRB1 alleles in polymyalgia rheumatica, giant cell arteritis, and rheumatoid arthritis. Arthritis Rheum. 1994;37:514–520.
22. Morgan AW, Robinson JI, Barrett JH, Martin J, Walker A, Babbage SJ, Ollier WE, Gonzalez-Gay MA, Isaacs JD. Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis. Arthritis Res Ther. 2006;8:R109.
23. Torres O, Palomino-Morales R, Vazquez-Rodriguez TR, Castaneda S, Morado IC, Miranda-Filloy JA, Ortego-Centeno N, Fernandez-Gutierrez B, Martin J, Gonzalez-Gay MA. Role of the C8orf13-BLK region in biopsy-proven giant cell arteritis. Hum Immunol. 2010;71:525–529.
24. Torres O, Palomino-Morales R, Castaneda S, Vazquez-Rodriguez TR, Morado IC, Miranda-Filloy JA, Amigo-Diaz E, Vicente EF, Ortego-Centeno N, Fernandez-Gutierrez B, Martin J, Gonzalez-Gay MA. Role of BANK1 gene polymorphisms in biopsy-proven giant cell arteritis. J Rheumatol. 2010;37:1502–1504.
25. Marquez A, Solans R, Hernandez-Rodriguez J, Cid MC, Castaneda S, Ramentol M, Morado IC, Rodriguez-Rodriguez L, Narvaez J, Gomez-Vaquero C, Miranda-Filloy JA, Martinez-Taboada VM, Rios R, Sopena B, Monfort J, Garcia-Villanueva MJ, Martinez-Zapico A, Mari-Alfonso B, Sanchez-Martin J, Unzurrunzaga A, Raya E, de Miguel E, Hidalgo-Conde A, Blanco R, Gonzalez-Gay MA, Martin J. Analysis of two autoimmunity genes, IRAK1 and MECP2, in giant cell arteritis. Clin Exp Rheumatol. 2014;32:S30–S33.
26. Marquez A, Hernandez-Rodriguez J, Cid MC, Solans R, Castaneda S, Fernandez-Contreras ME, Ramentol M, Morado IC, Narvaez J, Gomez-Vaquero C, Martinez-Taboada VM, Ortego-Centeno N, Sopena B, Monfort J, Garcia-Villanueva MJ, Caminal-Montero L, de Miguel E, Blanco R, Palm O, Molberg O, Latus J, Braun N, Moosig F, Witte T, Beretta L, Santaniello A, Pazzola G, Boiardi L, Salvarani C, Gonzalez-Gay MA, Martin J. Influence of the IL17A locus in giant cell arteritis susceptibility. Ann Rheum Dis. 2014;73:1742–1745.
27. Elling H, Olsson AT, Elling P. Human parvovirus and giant cell arteritis: a selective arteritic impact? Clin Exp Rheumatol. 2000;18:S12–S14.
28. Gabriel SE, Espy M, Erdman DD, Bjornsson J, Smith TF, Hunder GG. The role of parvovirus B19 in the pathogenesis of giant cell arteritis: a preliminary evaluation. Arthritis Rheum. 1999;42:1255–1258.
29. Haugeberg G, Bie R, Nordbo SA. Temporal arteritis associated with Chlamydia pneumoniae DNA detected in an artery specimen. J Rheumatol. 2001;28:1738–1739.
30. Nagel MA, White T, Khmeleva N, Rempel A, Boyer PJ, Bennett JL, Haller A, Lear-Kaul K, Kandasmy B, Amato M, Wood E, Durairaj V, Fogt F, Tamhankar MA, Grossniklaus HE, Poppiti RJ, Bockelman B, Keyvani K, Pollak L, Mendlovic S, Fowkes M, Eberhart CG, Buttmann M, Toyka KV, Meyer-ter-Vehn T, Petursdottir V, Gilden D. Analysis of varicella-zoster virus in temporal arteries biopsy positive and negative for giant cell arteritis. JAMA Neurol. 2015;72:1281–1287.
31. Gilden D, White T, Khmeleva N, Heintzman A, Choe A, Boyer PJ, Grose C, Carpenter JE, Rempel A, Bos N, Kandasamy B, Lear-Kaul K, Holmes DB, Bennett JL, Cohrs RJ, Mahalingam R, Mandava N, Eberhart CG, Bockelman B, Poppiti RJ, Tamhankar MA, Fogt F, Amato M, Wood E, Durairaj V, Rasmussen S, Petursdottir V, Pollak L, Mendlovic S, Chatelain D, Keyvani K, Brueck W, Nagel MA. Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Neurology. 2015;84:1948–1955.
32. Gilden D, White T, Galetta SL, Fogt F, Nagel MA. Widespread arterial infection by varicella-zoster virus explains refractory giant cell arteritis. Neurol Neuroimmunol Neuroinflamm. 2015;2:e125.
33. Bhatt AS, Manzo VE, Pedamallu CS, Duke F, Cai D, Bienfang DC, Padera RF, Meyerson M, Docken WP. In search of a candidate pathogen for giant cell arteritis: sequencing-based characterization of the giant cell arteritis microbiome. Arthritis Rheumatol. 2014;66:1939–1944.
34. Bahijri SM, Jambi HA, Al Raddadi RM, Ferns G, Tuomilehto J. The prevalence of diabetes and prediabetes in the adult population of Jeddah, Saudi Arabia- a community-based survey. PLoS One. 2016;11:e0152559.
35. Abdelwahab SI, El-Setohy M, Alsharqi A, Elsanosy R, Mohammed UY. Patterns of use, cessation behavior and socio-demographic factors associated with smoking in Saudi Arabia: a Cross- Sectional Multi-Step study. Asian Pac J Cancer Prev. 2016;17:655–660.
36. Al-Rubeaan K, Al-Hussain F, Youssef AM, Subhani SN, Al-Sharqawi AH, Ibrahim HM. Ischemic stroke, and its risk factors in a registry-based large cross-sectional diabetic cohort in a Country facing a diabetes epidemic. J Diabetes Res. 2016;2016:4132589.
37. Wu Y, Zhou LM, Lou H, Cheng JW, Wei RL. The association between obstructive sleep apnea and nonarteritic anterior ischemic optic neuropathy: a systematic review and meta-analysis. Curr Eye Res. 2016;41:987–992.
38. Wali SO, Alsharif MA, Albanji MH, Baabbad MS, Almotary HM, Alama N, Mimish L, Alsulami A, Abdelaziz MM. Prevalence of obstructive sleep apnea among patients with coronary artery disease in Saudi Arabia. J Saudi Heart Assoc. 2015;27:227–233.
39. Jacobson DM, Vierkant RA, Belongia EA. Nonarteritic anterior ischemic optic neuropathy. A case- control study of potential risk factors. Arch Ophthalmol. 1997;115:1403–1407.
40. Lee MS, Grossman D, Arnold AC, Sloan FA. Incidence of nonarteritic anterior ischemic optic neuropathy: increased risk among diabetic patients. Ophthalmology. 2011;118:959–963.
41. Arnold AC, Costa RM, Dumitrascu OM. The spectrum of optic disc ischemia in patients younger than 50 years (an Amercian Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2013;111:93–118.
© 2017 by North American Neuro-Ophthalmology Society