Optic Disc Drusen Associated Anterior Ischemic Optic Neuropathy: Prevalence of Comorbidities and Vascular Risk Factors

Background: Nonarteritic anterior ischemic optic neuropathy (NA-AION) associated with optic disc drusen (ODD) is termed ODD-AION, where NA-AION with no evidence of ODD is simply termed NA-AION. Patients with ODD-AION have been found to be younger than those with NA-AION but with similar vascular risk factors. This study compares the known risk factors for NA-AION between a group with ODD-AION and a similarly aged group with NA-AION. Methods: A case-control study of 13 patients with ODD-AION and 14 patients with NA-AION diagnosed in the period 2008-2017. All patients underwent an interview designed to evaluate history of vascular risk factors and comorbidities and re-examination including enhanced depth imaging optical coherence tomography to confirm the presence or absence of ODD. Results: No significant differences were found in demographic or clinical characteristics between the ODD-AION and the NA-AION group. Significantly more ODD-AION patients than NA-AION patients had no vascular risk factors (smoking, arterial hypertension, diabetes mellitus, and dyslipidemia) present (P = 0.047). Significantly fewer patients in the ODD-AION group were diagnosed with arterial hypertension or dyslipidemia than in the NA-AION group. Conclusions: In this cross-sectional study, the ODD-AION patients more often had no vascular risk factors as compared to NA-AION patients, which supports the hypothesis that ODD are an independent risk factor for AION.

Original Contribution Optic Disc Drusen Associated Anterior Ischemic Optic Neuropathy: Prevalence of Comorbidities and Vascular Risk Factors Lea L. Rueløkke, MD, Lasse Malmqvist, MD, PhD, Marianne Wegener, MD, Steffen Hamann, MD, PhD Background: Nonarteritic anterior ischemic optic neuropathy (NA-AION) associated with optic disc drusen (ODD) is termed ODD-AION, where NA-AION with no evidence of ODD is simply termed NA-AION. Patients with ODD-AION have been found to be younger than those with NA-AION but with similar vascular risk factors. This study compares the known risk factors for NA-AION between a group with ODD-AION and a similarly aged group with NA-AION. Methods: A case-control study of 13 patients with ODD-AION and 14 patients with NA-AION diagnosed in the period 2008- 2017. All patients underwent an interview designed to evaluate history of vascular risk factors and comorbidities and reexamination including enhanced depth imaging optical coherence tomography to confirm the presence or absence of ODD. Results: No significant differences were found in demographic or clinical characteristics between the ODD-AION and the NA-AION group. Significantly more ODD-AION patients than NA-AION patients had no vascular risk factors (smoking, arterial hypertension, diabetes mellitus, and dyslipidemia) present (P = 0.047). Significantly fewer patients in the ODD-AION group were diagnosed with arterial hypertension or dyslipidemia than in the NA-AION group. Conclusions: In this cross-sectional study, the ODD-AION patients more often had no vascular risk factors as compared to NA-AION patients, which supports the hypothesis that ODD are an independent risk factor for AION. Journal of Neuro-Ophthalmology 2020;40:356-361 doi: 10.1097/WNO.0000000000000885 © 2020 by North American Neuro-Ophthalmology Society Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Glostrup, Denmark. Supported by Velux Fonden. The authors report no conflicts of interest. Address correspondence to Lea L. Rueløkke, MS, Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Valdemar Hansens Vej 13, DK-2600 Glostrup, Denmark; E-mail: Lea. [e-mail] 356 O ptic disc drusen (ODD) are calcified deposits located in the optic nerve head anterior to the lamina cribrosa (1,2). They are found in up to 2% of the population and are hypothesized to be caused by a congenital disc anomaly or by disturbance in axonal metabolism (2,3). ODD can be diagnosed by ophthalmoscopy, if they are visible as ovoid refractile bodies on the disc surface, or using ultrasonography, autofluorescence, fundus photography, or optical coherence tomography (OCT), if they are localized deeper in the optic nerve head (3,4). Recently, enhanced depth imaging OCT (EDI-OCT) has been found to have a higher detection rate than any other diagnostic method (5-7). Although often asymptomatic, ODD are associated with vascular anomalies in up to 20% and visual field defects in up to 87% of cases (8,9). Complications with severe visual loss are most often due to ODD-associated anterior ischemic optic neuropathy (ODD-AION) (9-11). ODD-AION or drusen-associated anterior ischemic optic neuropathy is in the literature defined as nonarteritic anterior ischemic optic neuropathy (NA-AION) occurring in eyes with ODD (12-14). NA-AION is presumed to be due to a transient hypoperfusion of the optic nerve head from the short posterior ciliary arteries leading to ischemia (15,16). NAAION is associated with a small cup disk ratio and a small scleral canal (15,17). Cardiovascular risk factors are found to be more prevalent in patients with NA-AION than in the general population (18-22). Other risk factors for developing NA-AION are sleep apnea and cataract surgery (23-25). Patients with ODD-AION are found to be younger than those with NA-AION suggesting the presence of ODD as an independent risk factor (12,14,26,27). To the best of our knowledge, no previous study has included both ODD-AION and NA-AION patients and compared prevalence of comorbidities and vascular risk factors between the 2 groups. Rueløkke et al: J Neuro-Ophthalmol 2020; 40: 356-361 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution METHODS Study Cohort We performed a hospital-based case-control study of patients with ODD-AION and a similar-sized control group of patients with NA-AION. Using diagnostic coding, we identified potential participants from the records of Rigshospitalet, Glostrup, Denmark, between 2008 and 2017. We invited all patients with coding for ischemic optic neuropathy and ODD, and we selected the 20 youngest adult patients with ischemic optic neuropathy (without ODD) in an attempt to find similarly aged patients compared with the ODD-AION group and avoid misdiagnosed giant cell arteritis. During the 2 months of data acquisition (November-December 2017), patients were also invited to participate from their follow-up clinic appointments after ODD-AION or NA-AION diagnosis, and 4 participants were recruited in this way. All participants provided written informed consent. The study was approved by the Scientific Ethics Committee of the Capital Region of Denmark (H-17021284) and performed in accordance with the Helsinki declaration. Inclusion Criteria We reviewed patient records to ensure that NA-AION was initially diagnosed when following criteria were met: 1) monocular acute visual loss 2) unilateral optic disc edema during the acute stage, 3) disc-related visual field defect (altitudinal, enlarged blind spot, and/or arcuate defects), and 4) no signs of giant cell arteritis including elevated erythrocyte sedimentation rate and C-reactive protein levels. ODD-AION patients were included if ODD were diagnosed (by either ophthalmoscopy, ultrasonography, autofluorescence, fundus photography, or OCT) and the criteria for NA-AION were met. Exclusion Criteria Exclusion criteria were as follows: 1) age ,18 years, 2) intraocular pressure (IOP) of .21 mm Hg, 3) neurologic diseases that may affect the optic nerve such as multiple sclerosis, Alzheimer disease, and Parkinson disease, and 4) no disc-related visual field loss at study examination. Data Acquisition Every included patient underwent an examination for the purpose of the study. All study examinations were performed by a single examiner (L.L.R.) from November 2017 to May 2018. Participants were all examined at least one month after the initial diagnosis to prevent masking of ODD by residual disc swelling. Participants were questioned about ophthalmic and medical history and medication use. The interview included specific questions about presence of sleep apnea and vascular risk factors (diabetes mellitus, arterial hypertension, dyslipidemia, and smoking) Rueløkke et al: J Neuro-Ophthalmol 2020; 40: 356-361 and other risk factors for developing NA-AION (anemia at time of diagnosis, sleep apnea, and ocular surgery at any time before the diagnosis). Obtained information was validated in patient records. All subjects underwent IOP measurement using Goldmann applanation tonometry and slit-lamp examination. Medical standard automated perimetry (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc, Dublin, CA; strategy SITA-standard, 30-2 threshold) and spectral-domain OCT was performed on every participant for identification of ODD, to substantiate the diagnosis, and to avoid misclassification of subjects. Automated perimetry was assessed by one examiner (L.L.R.) to make sure every included participant had discrelated visual field defects. OCT (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany) was performed using dense optic nerve head scan with EDI-OCT in both vertical and horizontal directions with 30 mm between each B-scan (97 scans), averaging 30 B-scans. The definition of ODD using OCT was defined as hyporeflective structures with a full or partial hyperreflective margin (Fig. 1), as previously described (28). Subjects were reclassified if the EDI-OCT findings during study examination indicated this should occur. Patients were dilated with tropicamide 0.5% during slitlamp examination before automated perimetry and OCT acquisition. Statistical Analyses To compare the demographic characteristics between ODD-AION and NA-AION patients, the Fisher exact test was used for the categoric variables and the Student's t test or Wilcoxon rank sum test (skewed distribution) was used for the continuous variables. The first eye involved was used as the study eye in patients with bilateral ODD-AION or NA-AION if both incidents were in the inclusion period. Occurrence of different well-known risk factors for developing NA-AION was given as categorical data. We used the Fisher exact test to compare occurrence of risk factors between the group of ODD-AION patients and the group of NA-AION patients. Two-tailed P values ,0.05 were considered statistically significant. Statistical analyses were performed using the R software package, V.3.3.2 (http://www.r-project.org/). RESULTS Sixteen patients with ODD-AION were identified by diagnostic coding, 1 was excluded due to low age, and 2 could not be contacted. Ten of 13 invited patients participated, 1 was identified in clinic during the data acquisition phase, and 2 more were identified as having ODD during the study examination after being coded as NA-AION (total 13 participants with ODD-AION). Of 357 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Enhanced depth imaging optical coherence tomography scans of the optic nerve head of a patient with optic disc drusen associated anterior ischaemic optic neuropathy showing superficial optic disc drusen (white arrows), deep optic disc drusen (arrow head), central retinal artery and vein (dotted arrow). A. Two weeks after debut of symptoms. B. Six weeks after debut of symptoms. The decreasing disc edema clearly reveals the deep optic disc drusen. the 391 NA-AION identified by coding, the 20 youngest, contactable, and potentially included patients were invited; 15 participated, but 4 were lost due to incomplete examination (1), normal field test (1), or detection of ODD (2). Three more participants were identified with NA-AION during the data acquisition phase (total 15 2 4+3 = 14 participants with NA-AION). All included patients were Caucasian. The 2 subjects who were reclassified as ODD-AION patients were both male, and the ODD were located deep in the optic nerve head and were not visible by ophthalmoscopy. Subject 1 was 54 years old and had ocular surgery with IOL replacement before ODD-AION. Subject 2 was 52 years and a smoker. Demographic and clinical characteristics of the included ODD-AION and NA-AION patients are shown in Table 1. There were no significant differences between sex, age at diagnosis, years since diagnosis, laterality of disease, intraocular pressure, or visual field mean deviation between included ODD-AION and NA-AION patients. Overall, 4 of 13 participants (31%) with ODD-AION had vascular risk factors. Of these 4, they all were current/ previous smokers, 2 had hypertension, 2 had dyslipidemia, and 1 had diabetes. In the NAION group, 12 of 14 (86%) had vascular risk factors, including 8 current/previous smokers, 9 with hypertension, 8 with dyslipidemia, and 3 with diabetes. The proportion with any vascular risk factors was significantly different between groups (Fisher exact test, P = 0.047). The numbers of patients with these vascular risk factors and with sleep apnea, anemia, or previous ocular surgery are shown in Table 2. One case of hypertension in the ODD-AION group was found during study interview. This vascular risk factor was not stated anywhere in the hospital medical records. Two cases of dyslipidemia and 1 case of hypertension in the NAAION group were found during study interview. These vascular risk factors were not stated anywhere in the hospital medical records. We found 5 ODD-AION patients who had ocular surgery before the event of ODD-AION. Two had lens replacement due to presbyopia at age 44 and 45 years, respectively. Three had cataract surgery at age 65, 65, and 71 years, respectively. The time between surgery and diagnosis of ODD-AION ranged from 1 week to 4 years. DISCUSSION In this case-control study, we found that significantly more ODD-AION than NA-AION patients had none of the vascular risk factors present. Our findings suggest that TABLE 1. Demographic and clinical characteristics of the included ODD-AION and NA-AION patients Number Sex (male/female), n Age at diagnosis (range)* Years since diagnosis (range)*‡ Laterality of disease (bilateral/unilateral), n Intraocular pressure (range), mm Hg* Visual field MD* ODD-AION NA-AION P 13 10/3 45.3 (16-72) 4.1 (1-10) 4/9 13.8 (10-18) 210 (219.9 to (26)) 14 12/2 53.1 (31-76)† 3.7 (1-9) 1/13 14.7 (10-18) 212.8 (223 to (27)) 0.65§ 0.19k 0.72¶ 0.16§ 0.39k 0.22k MD, mean deviation; NA-AION, nonarteritic anterior ischemic optic neuropathy; ODD-AION, optic disc drusen associated anterior ischemic optic neuropathy. *In bilateral cases, the first eye involved is used as the study eye. † Young NA-AION patients were specifically selected. ‡ Years since diagnosis at time of participation. § Fisher exact test. k Student t-test. ¶ Wilcoxon rank-sum test. 358 Rueløkke et al: J Neuro-Ophthalmol 2020; 40: 356-361 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Presence of risk factors in patients with ODD-AION vs NA-AION Factor ODD-AION (n = 13) NA-AION (n = 14) Number (%) Number (%) Vascular risk factors Smoking† Arterial hypertension Diabetes mellitus Dyslipidemia None of the above‡ Sleep apnoea Anaemia§ Ocular surgeryk 4 2 1 2 9 1 1 5 (31) (15) (8) (15) (69) (8) (8) (38) 8 9 3 8 2 1 1 1 (57) (64) (21) (57) (14) (7) (7) (7) P* 0.047 1 1 0.08 *Fisher exact test. † Current and former smokers vs nonsmokers. ‡ None of the above risk factors vs $1 risk factors. § Anemia in relation to diagnosis of ODD-AION or NA-AION. k Ocular surgery with intraocular lens replacement before occurrence of ODD-AION or NA-AION in ipsilateral eye. NA-AION, nonarteritic anterior ischemic optic neuropathy; ODD-AION, optic disc drusen associated anterior ischemic optic neuropathy. ODD is an independent risk factor for developing anterior ischemic optic neuropathy. To the best of our knowledge, no previous study has included both groups of patients and performed individual interviews specifically about the risk factors. A retrospective study of medical records by Purvin et al (27) found 50% of ODD-AION patients to have a vascular risk factor present, but each patient only had one. In NA-AION patients, the IONDT (ischemic optic neuropathy decompression trial) (29) found 60% to have vascular risk factors. In general, we found a lower proportion of ODD-AION having vascular risk factors (31%) and a greater proportion of NAAION having vascular risk factors (86%). In the IONDT (29), dyslipidemia was not recorded and smoking habits were only recorded in the group of patients with visual acuity worse than or equal to 20/64. The IONDT (29) excluded patients with various medical and ophthalmic disorders (e.g., macular disease and lens opacity), where vascular risk factors are prevalent. Furthermore, the IONDT (29) registered the presence of vascular risk factors at the baseline diagnostic visit and up to 3 months after baseline, whereas our study examined patients with a mean of 3.7 years after diagnosis leaving time for the following examination of comorbidities to be conducted by the patients' general practitioners. We did identify a total of 4 cases of vascular risk factors during study interview. The vascular risk factors in these cases were not to be found in the hospital medical records. The methodological differences between the IONDT (29) and our study could explain the difference in findings regarding risk factor prevalence in NA-AION patients. The study was designed to select young NA-AION patients, but the mean age of included NA-AION patients were still higher than the ODD-AION patients although not significantly. Previous studies indicate that finding an even younger group of NA-AION patients to match our Rueløkke et al: J Neuro-Ophthalmol 2020; 40: 356-361 ODD-AION patients probably would not change the results of our study. Studies about the prevalence of vascular risk factors in NA-AION patients of different age have different findings. It has been suggested that when NAAION occurs in a young patient, it is often the result of an underlying condition predisposing the patient to vascular insufficiency (30-35). Others find that systemic risk factors and associated disorders are similar in patients younger than 50 years of age to those described in older NA-AION patients (36). We found more ODD-AION than NA-AION patients to have had ocular surgery with IOL replacement before their diagnosis. A recent study found that systemic risk factors were more common in the group of spontaneous NA-AION than NA-AION after cataract surgery (37). Further studies are needed to find out whether patients with ODD could be overrepresented in the group of postcataract surgery NA-AION. All participants underwent EDI-OCT to substantiate their diagnosis and avoid misclassification. To the best of our knowledge, no previous study has taken similar precautions. We found 2 of the 18 examined NAAION patients (11%) to have buried ODD on OCT. These 2 cases, which were reclassified, had a small or none existing load of vascular risk factors, and ODD were not visible by ophthalmoscopy. The findings imply that not every otherwise healthy NA-AION patient had been undergoing thorough ODD screening. This contradicts a potential selection bias where healthy individuals get a more thorough investigation. Our findings indicate that ODD-AION might be underdiagnosed, leaving patients misclassified in studies if OCT is not performed. As shown in Figure 1, the optic disc edema during the acute stage can mask ODD on EDI-OCT. Scanning at followup examinations and not only at the acute phase could therefore be indicated. 359 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution We found a higher incidence of bilateral eye involvement in the ODD-AION group compared with the NA-AION group. Although this finding is not statistically significant, it is consistent with the literature (38). Other studies found that bilateral eye involvement was more frequent in young NA-AION patients (35,36). Furthermore, ODD-AION patients have been found to be younger than NA-AION patients (27). Further studies are needed to investigate the impact of ODD in young patients with NA-AION. A substantial limitation of our study is the size of the study population leaving room for selection bias. Especially the group of NA-AION patients is small in comparison with the referent population. The risk of ODD investigation occurring less frequently in NA-AION patients with several vascular risk factors is possible. In the clinical setting, the presence of vascular risk factors would be enough to satisfy the doctors need to explain the underlying cause. This would potentially lead to a selection bias where patients with vascular risk factors less often get ODD diagnosed. The small sample size also means that adjustments for confounders in the statistical analyses were not possible to perform. Further studies are needed to support our findings and the significance of our results. To the best of our knowledge, this is the first prospective study to include both patients with ODD-AION or NAAION to compare prevalence of risk factors. In the agedmatched group of NA-AION patients, we found a greater proportion having vascular risk factors than in the ODDAION group. The findings suggest ODD as a risk factor in the development of anterior ischemic optic neuropathy and not just a coincidental coexistence. Using EDI-OCT, we found undiagnosed ODD in some NA-AION patients. The findings implicate the importance of EDI-OCT in the diagnosis of NA-AION patients with no or few vascular risk factors. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: L. L. Rueløkke, S. Hamann, L. Malmqvist, and M. Wegener; b. Acquisition of data: L. L. Rueløkke, S. Hamann, and M. Wegener; c. Analysis and interpretation of data: L. L. Rueløkke, S. Hamann, and L. Malmqvist. Category 2: a. Drafting the manuscript: L. L. Rueløkke, S. Hamann, and L. Malmqvist; b. Revising it for intellectual content: L. L. Rueløkke, S. Hamann, and L. Malmqvist. Category 3: a. Final approval of the completed manuscript: L. L. Rueløkke, S. Hamann, L. Malmqvist, and M. Wegener. REFERENCES 1. Friedman AH, Henkind P, Gartner S. Drusen of the optic disc. A histopathological study. Trans Ophthalmol Soc U K. 1975;95:4-9. 2. Friedman AH, Gartner S, Modi SS. Drusen of the optic disc. A retrospective study in cadaver eyes. Br J Ophthalmol. 1975;59:413-421. 3. Hamann S, Malmqvist L, Costello F. Optic disc drusen: understanding an old problem from a new perspective. Acta Ophthalmol. 2018;96:673-684. 360 4. Shah A, Szirth B, Sheng I, Xia T, Khouri AS. Optic disc drusen in a child: diagnosis using noninvasive imaging tools. Optom Vis Sci. 2013;90:E269-E273. 5. Sato T, Mrejen S, Spaide RF. Multimodal imaging of optic disc drusen. Am J Ophthalmol. 2013;156:275-282.e1. 6. Silverman A, Tatham A, Medeiros F, Weinreb R. Assessment of optic nerve head drusen using enhanced depth imaging and swept source optical coherence tomography. Arch Ophthalmol. 1999;117:1045-1049. 7. Merchant KY, Su D, Park SC, Qayum S, Banik R, Liebmann JM, Ritch R Enhanced depth imaging optical coherence tomography of optic nerve head drusen. Ophthalmology. 2013;120:1409- 1414. 8. Borruat FX, Sanders MD. Vascular anomalies and complications of optic nerve drusen. Klin Monbl Augenheilkd. 1996;208:294-296. 9. Lorentzen SE. Drusen of the optic disk. A clinical and genetic study. Acta Ophthalmol (Copenh). 1966;90:1-180. 10. Ayhan Z, Yaman A, Soylev Bajin M, Saatci AO. Unilateral acute anterior ischemic optic neuropathy in a patient with an already established diagnosis of bilateral optic disc drusen. Case Rep Ophthalmol Med. 2015;2015:730606. 11. Kamath GG, Prasad S, Phillips RP. Bilateral anterior ischaemic optic neuropathy due to optic disc drusen. Eur J Ophthalmol. 2000;10:341-343. 12. Nanji AA, Klein KS, Pelak VS, Repka MX. Nonarteritic anterior ischemic optic neuropathy in a child with optic disk drusen. J AAPOS. 2012;16:207-209. 13. Liew SCK, Mitchell P. Anterior ischaemic optic neuropathy in a patient with optic disc drusen. Aust N Z J Ophthalmol. 1999;27:157-160. 14. Newman WD, Dorell DE. Anterior ischemic optic neuropathy associated with disc Drusen.pdf. J Neuroophthalmol. 1996;16:7-8. 15. Storoni M, Chan CKM, Cheng ACO, Chan NCY, Leung CKS. The pathogenesis of nonarteritic anterior ischemic optic neuropathy. Asia Pac J Ophthalmol (Phila). 2013;2:132-135. 16. Berry S, Lin W, Sadaka A, Lee A. Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management. Eye Brain. 2017;9:23-28. 17. Miller NR, Arnold AC. Current concepts in the diagnosis, pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy. Eye Nat Publishing Group. 2014;29:1-20. 18. Hayreh SS, Zimmerman MB. Nonarteritic anterior ischemic optic neuropathy: clinical characteristics in diabetic patients versus nondiabetic patients. Ophthalmology. 2008;115:1818-1825. 19. 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. 20. 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. 21. Salomon O, Huna-Baron R, Kurtz S, Steinberg DM, Moisseiev J, Rosenberg N, Yassur I, Vidne O, Zivelin A, Gitel S, Davidson J, Ravid B, Seligsohn U Analysis of prothrombotic and vascular risk factors in patients with nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 1999;106:739-742. 22. Talks S, Chong NHV, Gibson M, Dodson PM. Fibrinogen, cholesterol and smoking as risk factors for non-arteritic anterior ischaemic optic neuropathy. Eye. 1995;9:85-88. 23. Mojon DS, Hedges TR III, Ehrenberg B, Karam EZ, Goldblum D, Abou-Chebl A, Gugger M, Mathis J. Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2002;120:601-605. 24. Palombi K, Renard E, Levy P, Chiquet C, Deschaux Ch, Romanet JP, Pépin JL Non-arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea. Br J Ophthalmol. 2006;90:879-882. 25. McCulley TJ, Lam BL, Feuer WJ. Incidence of nonarteritic anterior ischemic optic neuropathy associated with cataract extraction. Ophthalmology. 2001;108:1275-1278. Rueløkke et al: J Neuro-Ophthalmol 2020; 40: 356-361 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution 26. Gittinger JW, Lessell S, Bondar RL. Ischemic optic neuropathy associated with optic disc drusen. J Clin Neuroophthalmol. 1984;4:79-84. 27. Purvin V, King R, Kawasaki A, Yee R. Anterior ischemic optic neuropathy in eyes with optic disc drusen. Arch Ophthalmol. 2004;122:48-53. 28. Malmqvist L, Bursztyn L, Costello F, Digre K, Fraser A, Fraser C, Katz B, Lawlor M, Petzold A, Sibony P, Warner J, Wegener M, Wong S, Hamann S. The optic disc drusen studies consortium recommendations for diagnosis of optic disc drusen using optical coherence tomography. J Neuroophthalmol. 2018;38:299-307. 29. Ischemic Optic Neuropathy Decompression Trial Research Group. Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the ischemic optic neuropathy decompression trial. Arch Ophthalmol. 1996;114:1366-1374. 30. Janáky M, Fülöp Z, Pálffy A, Benedek K, Benedek G. Nonarteritic ischaemic optic neuropathy (NAION) in patients under 50 years of age. Acta Ophthalmol Scand. 2005;83:499-503. 31. Dufek S, Feldkoetter M, Vidal E, Litwin M, Munk M, Reitner A, Mueller-Sacherer T, Aufricht C, Arbeiter K, Boehm M Anterior ischemic optic neuropathy in pediatric peritoneal dialysis: risk factors and therapy. Pediatr Nephrol. 2014;29:1249-1257. Rueløkke et al: J Neuro-Ophthalmol 2020; 40: 356-361 32. Chutorian AM, Winterkorn JMS, Geffner M. Anterior ischemic optic neuropathy in children: case reports and review of the literature. Pediatr Neurol. 2002;26:358-364. 33. Taylor D, Ramsay J, Day S, Dillon M. Infarction of the optic nerve head in children with accelerated hypertension. Br J Ophthalmol. 1981;65:153-160. 34. Deramo VA, Sergott RC, Augsburger JJ, Foroozan R, Savino PJ, Leone A. Ischemic optic neuropathy as the first manifestation of elevated cholesterol levels in young patients. Ophthalmology. 2003;110:1041-1046. 35. 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. 36. Preechawat P, Bruce BB, Newman NJ, Biousse V. Anterior ischemic optic neuropathy in patients younger than 50 years. Am J Ophthalmol. 2007;144:953-960. 37. Moradi A, Kanagalingam S, Diener-West M, Miller NR. Post- cataract surgery optic neuropathy: prevalence, incidence, temporal relationship, and fellow eye involvement. Am J Ophthalmol. 2017;175:183-193. 38. Chang MY, Keltner JL. Risk factors for fellow eye involvement in nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol 2018;39:147-152. 361 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.