Neuro-Ophthalmological Manifestations of Obstructive Sleep Apnea: Current Perspectives

Figures & data

Figure 1 Fundus photography of the (A) right and (B) left optic nerve of the patient at presentation revealing bilateral optic disc edema. The right optic nerve has resolving, pallid edema whereas the left optic disc edema appears more recent with a temporal peripapillary hemorrhage.

Table 1 Search Strategy Used for OVID MEDLINE (1946 to February 2020 Week 1) to Identify Studies That Investigated the Relationship Between OSA and NAION

#	Searches	Results
1	exp Optic Neuropath, Ischemic/	1620
2	Optic Nerve Diseases/	8819
3	Non-arteritic anterior ischemic optic neuropathy.tw.	181
4	Nonarteritic anterior ischemic optic neuropathy.tw.	435
5	NAION.tw.	487
6	Arteritic anterior ischemic optic neuropathy.tw.	235
7	exp Sleep Apnea, Obstructive/	20,406
8	Obstructive sleep apnea.tw.	22,456
9	Obstruct* Sleep Apnea*.tw.	22,522
10	Sleep apnea syndrome.tw.	6738
11	OSA.tw.	13,639
12	1 or 2 or 3 or 4 or 5 or 6 or 7	10,601
13	8 or 9 or 10 or 11 or 12	32,996
14	12 and 13	55
15	limit 14 to (English language and humans)	50

Table 2 Studies Identified Using Our Search Strategy That Investigate the Relationship Between OSA and NAION

Authors, Year	Number of Patients	Type of Study	OSA Diagnostic Test	Findings
Mojon et al^Citation16 2002	17 NAION patients and 17 age- and sex-matched controls	Prospective comparative	PSG	12/17 (71%) of NAION and 3/17 (18%) of controls had OSA
Behbehani et al^Citation17 2004	108 patients with OSA	Prospective observational	PSG	3/108 (2.78%) of the patients had NAION
Palombi et al^Citation18 2006	27 NAION patients	Prospective observational	PSG	24/27 (89%) of the patients had OSA
Li et al^Citation19 2007	73 NAION patients and 73 age- and gender-matched controls	Prospective comparative	SA-SDQ	OSA diagnosis based on a phone questionnaire 22/73 (30.1%) of NAION patients and 13/73 (17.8%) of the controls had OSA
Stein et al^Citation20 2011	2,259,061 patients, 156,336 of whom diagnosed with OSA	Retrospective comparative	Medical history	OSA patients who did not use CPAP had an NAION diagnosis rate of 0.07% as opposed to 0.05% in the controls
Arda et al^Citation21 2012	20 NAION patients and 20 age- and sex- matched controls with similar rate of hypertension and diabetes	Prospective comparative	PSG	17/20 (85%) of the NAION patients and 13/20 (65%) of the controls had OSA
Blaivas et al^Citation22 2013	1	Case report	PSG	Patient with bilateral NAION was found to be having underlying OSA due to a substernal goiter
Kolb et al^Citation23 2013	17 NAION patients	Prospective observational	PSG	11/17 (64.7%) of the NAION had OSA
Bilgin et al^Citation24 2013	27 NAION patients and 27 age- and sex-matched controls and similar systemic risk factors	Prospective comparative	PSG	15/27 (55.5%) of the NAION patients and 6/27 (22.2%) of the controls had OSA
Mohamed et al^Citation25 2014	30 OSA patients	Prospective observational	PSG	4/30 (13.33%) OSA patients had NAION
Lacharme et al^Citation26 2014	17 NAION patients	Prospective observational	PSG	12/17 (70.6%) of the patients had OSA
Aptel et al^Citation27 2015	89 NAION patients	Prospective observational	PSG	67/89 (75%) of the patients had OSA.
Ghaleh Bandi et al^Citation28 2015	19 NAION patients and 31 controls	Prospective comparative	PSG	18/19 (95%) of NAION and 13/31 (41.9%) of controls had OSA
Morsi et al^Citation29 2019	80 OSA patients and 20 controls	Retrospective	PSG	No patient had NAION
Sun et al^Citation30 2019	8488 OSA patients and 33,952 controls	Retrospective	Medical history	Rate of NAION diagnosis was 0.36% in the OSA group and 0.2% in the controls
Yang et al^Citation31 2018	919 with OSA, 9190 matched non-OSA	Retrospective	Medical history	10-year incidence probability of NAION in the OSA group (0.92%) was higher than the non-OSA group (0.42%)
Chang et al^Citation32 2019	119 patients with unilateral NAION	Retrospective	Medical history	Over a 5-year period, 24.4% of the patients developed NAION in the other eye, with CPAP non-compliance being a major risk factor
Lei et al 2019^Citation33	1	Case report	PSG	Young patient with NAION who had undiagnosed severe OSA

Abbreviations: OSA, obstructive sleep apnea; NAION, non-arteritic anterior ischemic optic nerve; PSG, polysomnogram; SA-SDQ, Sleep Apnea scale of the Sleep Disorders Questionnaire; CPAP, continuous positive air pressure.

Table 3 Studies Identified Using Our Search Strategy That Investigate the Relationship Between OSA and IIH

Authors, Year	Number of Patients	Type of Study	OSA Diagnostic Test	Findings
Doyle et al^Citation42 1991	1	Case report	Medical history	Obese patient with OSA and IIH presenting with unilateral vision loss who improved following a lumboperitoneal shunt and tracheotomy
Purvin et al^Citation43 2000	1	Case report	Medical history	Obese patient with a 2-year history of OSA presenting with unilateral vision loss, papilledema and high ICP during sleep
Marcus et al^Citation44 2001	14 IIH patients with symptoms of sleep disturbance	Retrospective	PSG	6/14 (42.9%) of the patients had OSA
Lee et al^Citation45 2001	18 men with IIH	Retrospective	Medical history	6/18 (33.3%) of the patients had OSA
Thambisetty^Citation46 et al 2006	16 fulminant IIH female patients	Prospective observational	Medical history	None of the patients had OSA
Bruce et al^Citation47 2009	721 IIH patients	Retrospective	Medical history	25/655 (4%) of the female patients had OSA as opposed to 16/66 (24%) of the male patients
Fraser et al^Citation48 2010	24 IIH male patients and 48 sex-, age-, race-, and BMI category-matched controls	Prospective comparative	Berlin Questionnaire (BQ) for OSA	Following adjustments for BMI, IIH patients had a higher likelihood of having a positive Berlin questionnaire or history of OSA diagnosis
Thurtell et al^Citation49 2011	30 newly-diagnosed IIH patients	Prospective	PSG and BQ	PSG: 18/30 (60%) of the patients had OSA BQ: 20/30 (67.8%) of patients were at high risk of OSA
Javaheri et al^Citation50 2011	1	Case report	PSG	Female patient with IIH who was diagnosed with OSA. Her IIH improved following CPAP therapy for OSA
Stein et al^Citation20 2011	2,259,061 patients, 156,336 of whom diagnosed with OSA	Retrospective	Medical history	OSA patients who did not use CPAP had an IIH diagnosis rate of 0.04% as opposed to 0.01% in the controls
Szewka et al^Citation51 2013	414 IIH patients	Retrospective	Medical history	In patients with BMI of <40, 13/256 (5.1%) had OSA as opposed to 26/158 (16.5%) in patients with BMI >40
Abraham et al^Citation52 2013	22 IIH and 12 sex- and age-matched controls	Prospective comparative	Bedside overnight respiratory monitoring	AHI scores of IIH patients higher than the control, but both values within the normal range
Thurtell et al^Citation53 2013	24 IIH patients	Prospective observational	PSG	8/24 (33.3%) of IIH patients had OSA. The AHI scores of the IIH patients and 1741 randomly sampled individuals had no statistical difference
Wardly et al^Citation54 2017	1	Case report	PSG	Patient with OSA and IIH. Her IIH went away following a clockwise maxillomandibular advancement surgery to treat OSAS
Cappuzzo et al^Citation55 2018	18 IIH patients	Retrospective	Medical history	3/18 (16.7) of IIH patients had OSA
Ardissino et al^Citation56 2019	607 IIH patients and 230,792 controls all with BMI>30	Retrospective	Medical history	4/607 (0.7%) of IIH patients and 2204/230,792 (1%) of the controls had OSA
Radojicic et al^Citation57 2019	219 IIH patients and 67 controls	Prospective comparative	Medical history	5/219 (2.3%) of IIH patients and 7/67 (10.4%) of the controls had OSA
Onder et al^Citation58 2019a	1	Case report	Epworth Sleepiness Scale (ESS)	Patient with OSA and malignant IIH that was resolved following tonsillectomy to treat OSA
Onder et al^Citation59 2019b	1	Case report	ESS	10 year-old patient with a BMI of 20, diagnosed with IIH and suspected of OSA

Abbreviations: OSA, obstructive sleep apnea; NAION, non-arteritic anterior ischemic optic nerve; PSG, polysomnogram; CPAP, continuous positive air pressure.

Mojon DS, Hedges TR, Ehrenberg B, et al. Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol. 2002;120(5):601–605. doi:10.1001/archopht.120.5.60112003609

 PubMedGoogle Scholar

Behbehani R, Mathews MK, Sergott RC, Savino PJ. Nonarteritic anterior ischemic optic neuropathy in patients with sleep apnea while being treated with continuous positive airway pressure. Am J Ophthalmol. 2005;139(3):518–521. doi:10.1016/j.ajo.2004.11.00415767063

 PubMed Web of Science ®Google Scholar

Palombi K, Renard E, Levy P, et al. Non-arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea. Br J Ophthalmol. 2006;90(7):879–882. doi:10.1136/bjo.2005.08745216556620

 PubMed Web of Science ®Google Scholar

Li J, McGwin G, Vaphiades MS, Owsley C. Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea syndrome screened by the sleep apnea scale of the sleep disorders questionnaire (SA-SDQ). Br J Ophthalmol. 2007;91(11):1524–1527. doi:10.1136/bjo.2006.11380317504857

 PubMed Web of Science ®Google Scholar

Stein JD, Kim DS, Mundy KM, et al. The association between glaucomatous and other causes of optic neuropathy and sleep apnea. Am J Ophthalmol. 2011;152(6):989–998.e3. doi:10.1016/j.ajo.2011.04.03021851924

 PubMed Web of Science ®Google Scholar

Arda H, Birer S, Aksu M, et al. Obstructive sleep apnoea prevalence in non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol. 2013;97(2):206–209. doi:10.1136/bjophthalmol-2012-30259823203698

 PubMed Web of Science ®Google Scholar

Blaivas AJ, Uddin F. Obstructive sleep apnea caused by substernal goiter presenting as nonarteritic ischemic optic neuropathy. Sleep Breath. 2013;17(2):469–471. doi:10.1007/s11325-012-0758-322899396

 PubMed Web of Science ®Google Scholar

Kolb SD, Backhouse O. Obstructive sleep apnoea prevalence in non-arteritic anterior ischaemic optic neuropathy: a response. Br J Ophthalmol. 2013;97(6):794. doi:10.1136/bjophthalmol-2013-30317923426734

 PubMed Web of Science ®Google Scholar

Bilgin G, Koban Y, Arnold AC. Nonarteritic anterior ischemic optic neuropathy and obstructive sleep apnea. J Neuroophthalmol. 2013;33(3):232–234. doi:10.1097/WNO.0b013e31828eecbd23719289

 PubMed Web of Science ®Google Scholar

Mohamed EE, Massoud TH. Effect of sleep related breathing disorders on ocular function. Egypt J Chest Dis Tuberc. 2014;63(3):663–669. doi:10.1016/j.ejcdt.2014.02.010

 Google Scholar

Lacharme T, Almanjoumi A, Aptel F, et al. Twenty-four-hour rhythm of ocular perfusion pressure in non-arteritic anterior ischaemic optic neuropathy. Acta Ophthalmol. 2014;92(5):e346–52. doi:10.1111/aos.1235224460737

 PubMed Web of Science ®Google Scholar

Aptel F, Khayi H, Pépin JL, et al. Association of nonarteritic ischemic optic neuropathy with obstructive sleep apnea syndrome: consequences for obstructive sleep apnea screening and treatment. JAMA Ophthalmol. 2015;133(7):797–804. doi:10.1001/jamaophthalmol.2015.089325928835

 PubMed Web of Science ®Google Scholar

Ghaleh Bandi MF, Naserbakht M, Tabasi A, Marghaiezadeh A, Riazee Esfahani M, Golzarian Z. Obstructive sleep apnea syndrome and non-arteritic anterior ischemic optic neuropathy: a case control study. Med J Islam Repub Iran. 2015;29:300.26913263

 PubMedGoogle Scholar

Morsy NE, Amani BE, Magda AA, et al. Prevalence and predictors of ocular complications in obstructive sleep apnea patients: a cross-sectional case-control study. Open Respir Med J. 2019;13(1):19–30. doi:10.2174/187430640191301001931908685

 PubMedGoogle Scholar

Sun MH, Lee CY, Liao YJ, Sun CC. Nonarteritic anterior ischaemic optic neuropathy and its association with obstructive sleep apnoea: a health insurance database study. Acta Ophthalmol. 2019;97(1):e64–e70. doi:10.1111/aos.1383230171667

 PubMed Web of Science ®Google Scholar

Yang HK, Park SJ, Byun SJ, Park KH, Kim JW, Hwang JM. Obstructive sleep apnoea and increased risk of non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol. 2019;103(8):1123–1128. doi:10.1136/bjophthalmol-2018-31291030413419

 PubMed Web of Science ®Google Scholar

Chang MY, Keltner JL. Risk factors for fellow eye involvement in nonarteritic anterior ischemic optic neuropathy. J Neuro Ophthalmol. 2019;39(2):147–152. doi:10.1097/WNO.0000000000000715

 Web of Science ®Google Scholar

Lei S, Micieli JA. Severe obstructive sleep apnea diagnosed after non-arteritic anterior ischaemic optic neuropathy in a young man. BMJ Case Rep. 2019;12(11):pii: e232512. doi:10.1136/bcr-2019-232512

 Google Scholar

Doyle KJ, Tami TA. Increased intracranial pressure and blindness associated with obstructive sleep apnea. Otolaryngol Head Neck Surg. 1991;105(4):613–616. doi:10.1177/0194599891105004131762797

 PubMed Web of Science ®Google Scholar

Purvin VA, Kawasaki A, Yee RD. Papilledema and obstructive sleep apnea syndrome. Arch Ophthalmol. 2000;118(12):1626–1630. doi:10.1001/archopht.118.12.162611115256

 PubMedGoogle Scholar

Marcus DM, Lynn J, Miller JJ, Chaudhary O, Thomas D, Chaudhary B. Sleep disorders: a risk factor for pseudotumor cerebri? J Neuroophthalmol. 2001;21(2):121–123. doi:10.1097/00041327-200106000-0001411450902

 PubMed Web of Science ®Google Scholar

Lee AG, Golnik K, Kardon R, Wall M, Eggenberger E, Yedavally S. Sleep apnea and intracranial hypertension in men. Ophthalmology. 2002;109(3):482–485. doi:10.1016/S0161-6420(01)00987-311874748

 PubMed Web of Science ®Google Scholar

Thambisetty M, Lavin PJ, Newman NJ, Biousse V. Fulminant idiopathic intracranial hypertension. Neurology. 2007;68(3):229–232. doi:10.1212/01.wnl.0000251312.19452.ec17224579

 PubMed Web of Science ®Google Scholar

Bruce BB, Kedar S, Van Stavern GP, et al. Idiopathic intracranial hypertension in men. Neurology. 2009;72(4):304–309. doi:10.1212/01.wnl.0000333254.84120.f518923135

 PubMed Web of Science ®Google Scholar

Fraser JA, Bruce BB, Rucker J, et al. Risk factors for idiopathic intracranial hypertension in men: a case-control study. J Neurol Sci. 2010;290(1–2):86–89. doi:10.1016/j.jns.2009.11.00119945715

 PubMed Web of Science ®Google Scholar

Thurtell MJ, Bruce BB, Rye DB, Newman NJ, Biousse V. The Berlin questionnaire screens for obstructive sleep apnea in idiopathic intracranial hypertension. J Neuroophthalmol. 2011;31(4):316–319. doi:10.1097/WNO.0b013e31821a4d5421537196

 PubMed Web of Science ®Google Scholar

Javaheri S, Qureshi Z, Golnik K. Resolution of papilledema associated with OSA treatment. J Clin Sleep Med. 2011;7(4):399–400. doi:10.5664/JCSM.120221897778

 PubMed Web of Science ®Google Scholar

Szewka AJ, Bruce BB, Newman NJ, Biousse V. Idiopathic intracranial hypertension: relation between obesity and visual outcomes. J Neuroophthalmol. 2013;33(1):4–8. doi:10.1097/WNO.0b013e31823f852d22217456

 PubMed Web of Science ®Google Scholar

Abraham A, Peled N, Khlebtovsky A, et al. Nocturnal carbon dioxide monitoring in patients with idiopathic intracranial hypertension. Clin Neurol Neurosurg. 2013;115(8):1379–1381. doi:10.1016/j.clineuro.2012.12.03723369399

 PubMed Web of Science ®Google Scholar

Thurtell MJ, Trotti LM, Bixler EO, et al. Obstructive sleep apnea in idiopathic intracranial hypertension: comparison with matched population data. J Neurol. 2013;260(7):1748–1751. doi:10.1007/s00415-013-6858-623412355

 PubMed Web of Science ®Google Scholar

Wardly D, Wolford LM, Veerappan V. Idiopathic intracranial hypertension eliminated by counterclockwise maxillomandibular advancement: a case report. Cranio. 2017;35(4):259–267. doi:10.1080/08869634.2016.120163427370206

 PubMed Web of Science ®Google Scholar

Cappuzzo JM, Hess RM, Morrison JF, et al. Transverse venous stenting for the treatment of idiopathic intracranial hypertension, or pseudotumor cerebri. Neurosurg Focus. 2018;45(1):E11. doi:10.3171/2018.5.FOCUS18102

 PubMed Web of Science ®Google Scholar

Ardissino M, Moussa O, Tang A, Muttoni E, Ziprin P, Purkayastha S. Idiopathic intracranial hypertension in the British population with obesity. Acta Neurochir. 2019;161(2):239–246. doi:10.1007/s00701-018-3772-930564882

 PubMed Web of Science ®Google Scholar

Radojicic A, Vukovic-Cvetkovic V, Pekmezovic T, Trajkovic G, Zidverc-Trajkovic J, Jensen RH. Predictive role of presenting symptoms and clinical findings in idiopathic intracranial hypertension. J Neurol Sci. 2019;399:89–93. doi:10.1016/j.jns.2019.02.00630782528

 PubMed Web of Science ®Google Scholar

Onder H, Ergun O, Kaygisiz M, Daltaban IS. Total improvement after surgery for obstructive sleep apnea syndrome in a patient with concurrent malignant idiopathic intracranial hypertension. J Neurosurg. 2018;131(2):582–586. doi:10.3171/2018.3.JNS17166330117763

 PubMed Web of Science ®Google Scholar

Onder H, Aksoy M. Resolution of idiopathic intracranial hypertension symptoms by surgery for obstructive sleep apnea in a pediatric patient. J Pediatr Neurosci. 2019;14(2):110–112. doi:10.4103/jpn.JPN_30_1931516635

 PubMed Web of Science ®Google Scholar