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Obstructive Sleep Apnoea in patients with Primary-Open Angle Glaucoma: no role for a screening programme.Dariusz Wozniak, MD1,2, Rupert Bourne, MD2,3,4 Gil Peretz, MD4, Jane Kean, BSc4, Catherine Willshire, PhD4, Shabbir Harun, MD4, Sofia Villar, PhD5,6, Yi-Da Chiu, PhD5, Ian Smith, MD1.1Respiratory Support and Sleep Centre, Royal Papworth Hospital, Cambridge, United Kingdom; 2Vision and Eye Research Unit, School of Medicine, Anglia Ruskin University, Cambridge, 3Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, 4Department of Ophthalmology, Hinchingbrooke Hospital, North West Anglia Foundation Trust, Huntingdon, United Kingdom; 5Research and Development, Royal Papworth Hospital, Cambridge, United Kingdom; 6 Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom. Corresponding author: Dr. Dariusz Wozniak, Respiratory Support and Sleep Centre, Royal Papworth Hospital, Papworth Everard, Cambridge, CB23 3RE, UK. E-mail: dariusz.wozniak@, Tel: 00441480364165, Fax 00441480 364568Funding sourcesThe study was funded by an unrestricted research grant awarded by Breas Medical, Unit A2, The Bridge Business Centre, Timothy’s Bridge Road, Stratford-Upon-Avon, Warwickshire, CV37 9HW, UK and the Fight for Sight (Small Grant Awards Schemes), 18 Mansell Street, London E1 8AA, UK. The study was also supported by the National Institute for Health Research via the Fight for Sight grant. PrécisIn this study, we found a high prevalence of obstructive sleep apnoea (OSA) among patients with primary open-angle glaucoma but this was not different (nor was OSA more severe) to matched people without glaucoma. AbstractRationale: It has been proposed that obstructive sleep apnoea (OSA) might be a contributing factor in the development of primary open angle glaucoma (POAG) and by extension that there could be a role for screening people with POAG for OSA. Objectives: To assess whether the prevalence of OSA among patients with POAG is different from that in people without glaucoma and to examine for associations between apnoea-hypopnea index (AHI) and markers of functional and structural changes in POAG.Methods: Unselected POAG patients and control subjects were consecutively recruited in a single centre. A comprehensive ocular assessment and nocturnal multichannel cardiorespiratory monitoring were performed.Results: Data from 395 participants, 235 POAG patients, and 160 controls were analysed. The prevalence of OSA was 58% (95% CI:52-65) in POAG patients and 54% (95% CI:47-62) in controls, with 22% (95% CI:16-27) of POAG patients and 16% (95% CI:11-22) of controls diagnosed with moderate or severe OSA. 160 POAG participants were matched to the controls using propensity score matching. There was no significant difference in OSA prevalence between the matched groups (p=0.91 for AHI≥5 and p=0.66 for AHI≥15). The AHI was not associated with the severity of visual field defect or Retinal Nerve Fibre Layer thinning after adjustment for confounders. Conclusions: This study confirms a high prevalence of OSA among patients with POAG which is however not higher than in people without glaucoma matched for known OSA risk factors. Our results do not support screening for OSA in patients with POAG.Keywords: obstructive sleep apnoea, glaucoma, retinal nerve fibre layerIntroduction Primary open-angle glaucoma (POAG) is a progressive optic neuropathy defined by accelerated degeneration of retinal ganglion cells and their axons. With an estimated prevalence of 3.0%, it is one of the leading causes of blindness worldwide ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"iUHAy52s","properties":{"formattedCitation":"(1)","plainCitation":"(1)","noteIndex":0},"citationItems":[{"id":244,"uris":[""],"uri":[""],"itemData":{"id":244,"type":"article-journal","title":"Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis","container-title":"The Lancet. Global Health","page":"e1221-e1234","volume":"5","issue":"12","source":"PubMed","abstract":"BACKGROUND: Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020.\nMETHODS: In this systematic review and meta-analysis, we analysed published and unpublished population-based data for the causes of vision impairment and blindness from 1980 to 2014. We identified population-based studies published before July 8, 2014, by searching online databases with no language restrictions (MEDLINE from Jan 1, 1946, and Embase from Jan 1, 1974, and the WHO Library Database). We fitted a series of regression models to estimate the proportion of moderate or severe vision impairment (defined as presenting visual acuity of <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity of <3/60 in the better eye) by cause, age, region, and year.\nFINDINGS: We identified 288 studies of 3?983?541 participants contributing data from 98 countries. Among the global population with moderate or severe vision impairment in 2015 (216·6 million [80% uncertainty interval 98·5 million to 359·1 million]), the leading causes were uncorrected refractive error (116·3 million [49·4 million to 202·1 million]), cataract (52·6 million [18·2 million to 109·6 million]), age-related macular degeneration (8·4 million [0·9 million to 29·5 million]), glaucoma (4·0 million [0·6 million to 13·3 million]), and diabetic retinopathy (2·6 million [0·2 million to 9·9 million]). Among the global population who were blind in 2015 (36·0 million [12·9 million to 65·4 million]), the leading causes were cataract (12·6 million [3·4 million to 28·7 million]), uncorrected refractive error (7·4 million [2·4 million to 14·8 million]), and glaucoma (2·9 million [0·4 million to 9·9 million]). By 2020, among the global population with moderate or severe vision impairment (237·1 million [101·5 million to 399·0 million]), the number of people affected by uncorrected refractive error is anticipated to rise to 127·7 million (51·0 million to 225·3 million), by cataract to 57·1 million (17·9 million to 124·1 million), by age-related macular degeneration to 8·8 million (0·8 million to 32·1 million), by glaucoma to 4·5 million (0·5 million to 15·4 million), and by diabetic retinopathy to 3·2 million (0·2 million to 12·9 million). By 2020, among the global population who are blind (38·5 million [13·2 million to 70·9 million]), the number of patients blind because of cataract is anticipated to rise to 13·4 million (3·3 million to 31·6 million), because of uncorrected refractive error to 8·0 million (2·5 million to 16·3 million), and because of glaucoma to 3·2 million (0·4 million to 11·0 million). Cataract and uncorrected refractive error combined contributed to 55% of blindness and 77% of vision impairment in adults aged 50 years and older in 2015. World regions varied markedly in the causes of blindness and vision impairment in this age group, with a low prevalence of cataract (<22% for blindness and 14·1-15·9% for vision impairment) and a high prevalence of age-related macular degeneration (>14% of blindness) as causes in the high-income subregions. Blindness and vision impairment at all ages in 2015 due to diabetic retinopathy (odds ratio 2·52 [1·48-3·73]) and cataract (1·21 [1·17-1·25]) were more common among women than among men, whereas blindness and vision impairment due to glaucoma (0·71 [0·57-0·86]) and corneal opacity (0·54 [0·43-0·66]) were more common among men than among women, with no sex difference related to age-related macular degeneration (0·91 [0·70-1·14]).\nINTERPRETATION: The number of people affected by the common causes of vision loss has increased substantially as the population increases and ages. Preventable vision loss due to cataract (reversible with surgery) and refractive error (reversible with spectacle correction) continue to cause most cases of blindness and moderate or severe vision impairment in adults aged 50 years and older. A large scale-up of eye care provision to cope with the increasing numbers is needed to address avoidable vision loss.\nFUNDING: Brien Holden Vision Institute.","DOI":"10.1016/S2214-109X(17)30393-5","ISSN":"2214-109X","note":"PMID: 29032195","title-short":"Global causes of blindness and distance vision impairment 1990-2020","journalAbbreviation":"Lancet Glob Health","language":"eng","author":[{"family":"Flaxman","given":"Seth R."},{"family":"Bourne","given":"Rupert R. A."},{"family":"Resnikoff","given":"Serge"},{"family":"Ackland","given":"Peter"},{"family":"Braithwaite","given":"Tasanee"},{"family":"Cicinelli","given":"Maria V."},{"family":"Das","given":"Aditi"},{"family":"Jonas","given":"Jost B."},{"family":"Keeffe","given":"Jill"},{"family":"Kempen","given":"John H."},{"family":"Leasher","given":"Janet"},{"family":"Limburg","given":"Hans"},{"family":"Naidoo","given":"Kovin"},{"family":"Pesudovs","given":"Konrad"},{"family":"Silvester","given":"Alex"},{"family":"Stevens","given":"Gretchen A."},{"family":"Tahhan","given":"Nina"},{"family":"Wong","given":"Tien Y."},{"family":"Taylor","given":"Hugh R."},{"literal":"Vision Loss Expert Group of the Global Burden of Disease Study"}],"issued":{"date-parts":[["2017",12]]}},"label":"page"}],"schema":""} (1). Structural damage is characterized by excavation of the rim of the optic disc and thinning of the retinal nerve fibre layer (RNFL) producing reduced retinal sensitivity and visual field defects. The cause of neurodegeneration in POAG is still unclear. Intraocular pressure (IOP) plays a major role but even effective reduction of IOP does not halt the disease progression in a substantial proportion of patients ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"o6GrRcrV","properties":{"formattedCitation":"(2)","plainCitation":"(2)","noteIndex":0},"citationItems":[{"id":53,"uris":[""],"uri":[""],"itemData":{"id":53,"type":"article-journal","title":"Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial","container-title":"Archives of Ophthalmology (Chicago, Ill.: 1960)","page":"1268-1279","volume":"120","issue":"10","source":"PubMed","abstract":"OBJECTIVE: To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma.\nDESIGN: Randomized clinical trial.\nPARTICIPANTS: Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, -4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible.\nINTERVENTIONS: Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter.\nMAIN OUTCOME MEASURES: Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings.\nRESULTS: After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P =.002).\nCONCLUSIONS: The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.","ISSN":"0003-9950","note":"PMID: 12365904","title-short":"Reduction of intraocular pressure and glaucoma progression","journalAbbreviation":"Arch. Ophthalmol.","language":"eng","author":[{"family":"Heijl","given":"Anders"},{"family":"Leske","given":"M. Cristina"},{"family":"Bengtsson","given":"Bo"},{"family":"Hyman","given":"Leslie"},{"family":"Bengtsson","given":"Boel"},{"family":"Hussein","given":"Mohamed"},{"literal":"Early Manifest Glaucoma Trial Group"}],"issued":{"date-parts":[["2002",10]]}}}],"schema":""} (2). While most people present with raised IOP (high tension glaucoma-HTG), diurnal IOP is not elevated above the upper limit of the normal statistical range in 30 to 40% of patients (normal tension glaucoma-NTG) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1aK0k3ll","properties":{"formattedCitation":"(3,4)","plainCitation":"(3,4)","noteIndex":0},"citationItems":[{"id":266,"uris":[""],"uri":[""],"itemData":{"id":266,"type":"article-journal","title":"The prevalence of primary open-angle glaucoma in a population-based study in The Netherlands. The Rotterdam Study","container-title":"Ophthalmology","page":"1851-1855","volume":"101","issue":"11","source":"PubMed","abstract":"PURPOSE: The objective of this study is to assess the prevalence of primary open-angle glaucoma (POAG) in a defined population in Rotterdam, The Netherlands.\nMETHODS: The Rotterdam Study is a single-center prospective cohort study of a total population of more than 10,000 people, 55 years of age or older. For the current analysis, the first 3062 consecutive, unselected, noninstitutionalized participants were examined according to standard protocols, including perimetry. The diagnosis of POAG was based on the presence of a glaucomatous visual field defect combined with either a vertical cup: disc ratio of 0.5 or more or a cup:disc ratio asymmetry of 0.2 or more, or an intraocular pressure (IOP) more than 21 mmHg, with open and normal anterior chamber angles.\nRESULTS: The overall prevalence of POAG in the current study was 1.10% (95% confidence interval [CI]: 1.09, 1.11). Age-specific prevalence figures increased from 0.2% (95% CI: 0.16, 0.24) in the age group of 55 to 59 years to 3.3% (95% CI: 2.57, 4.04) in the age group of 85 to 89 years. Men had a more than three times higher risk of having POAG than women (odds ratio, 3.6). In 52.9% of the patients, POAG had not been diagnosed previously. Of these patients, 38.9% had IOPs of 21 mmHg or lower. In 8.8% of the eyes (2.9% of patients), visual acuity was 20/200 or less due to POAG.\nCONCLUSION: The overall prevalence of POAG in the current study was 1.1%. The prevalence of POAG was higher in men than in women. Of the untreated patients, 38.9% had IOPs of 21 mmHg or lower.","ISSN":"0161-6420","note":"PMID: 7800368","journalAbbreviation":"Ophthalmology","language":"eng","author":[{"family":"Dielemans","given":"I."},{"family":"Vingerling","given":"J. R."},{"family":"Wolfs","given":"R. C."},{"family":"Hofman","given":"A."},{"family":"Grobbee","given":"D. E."},{"family":"Jong","given":"P. T.","non-dropping-particle":"de"}],"issued":{"date-parts":[["1994",11]]}},"label":"page"},{"id":267,"uris":[""],"uri":[""],"itemData":{"id":267,"type":"article-journal","title":"Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study","container-title":"Ophthalmology","page":"1661-1669","volume":"103","issue":"10","source":"PubMed","abstract":"PURPOSE: The purpose of this study was to determine the prevalence of open-angle glaucoma and ocular hypertension in an Australian community whose residents are 49 years of age or older.\nSUBJECTS: There were 3654 persons, representing 82.4% of permanent residents from an area west of Sydney, Australia, who were examined. The population was identified by a door-to-door census of all dwellings and by closely matched findings from the national census.\nMETHODS: All participants received a detailed eye examination, including applanation tonometry, suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss stereoscopic optic disc photography. Glaucoma suspects were asked to return for full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry.\nRESULTS: A 5-point hemifield difference on the 76-point test was found in 616 persons (19% of people tested). Humphrey 30-2 tests were performed on 336 glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous field defects. Two hundred three persons had enlarged or asymmetric cup-disc ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or = 0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2 test matched the optic disc changes, without regard to the intraocular pressure level. This congruence was found in 87 participants (2.4%), whereas an additional 21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete examination findings. Open-angle glaucoma was thus found in 108 persons, a prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were diagnosed previously. An exponential rise in prevalence was observed with increasing age. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. The prevalence of glaucoma was higher in women after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex difference in the age-adjusted prevalence of ocular hypertension.\nCONCLUSIONS: These data provide detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population.","ISSN":"0161-6420","note":"PMID: 8874440","journalAbbreviation":"Ophthalmology","language":"eng","author":[{"family":"Mitchell","given":"P."},{"family":"Smith","given":"W."},{"family":"Attebo","given":"K."},{"family":"Healey","given":"P. R."}],"issued":{"date-parts":[["1996",10]]}},"label":"page"}],"schema":""} (3,4). Therefore, other mechanisms that may contribute to optic nerve ischemia through vascular dysregulation or hypoxia have been investigated. Systemic endothelial and autonomic dysfunction is present in POAG across the spectrum of IOP and may be particularly relevant in NTG ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"R6DmI1jj","properties":{"formattedCitation":"(5\\uc0\\u8211{}7)","plainCitation":"(5–7)","noteIndex":0},"citationItems":[{"id":46,"uris":[""],"uri":[""],"itemData":{"id":46,"type":"article-journal","title":"Vascular and autonomic dysregulation in primary open-angle glaucoma","container-title":"Current Opinion in Ophthalmology","page":"94-101","volume":"27","issue":"2","source":"PubMed","abstract":"PURPOSE OF REVIEW: The purpose of this review is to discuss whether vascular dysfunction and autonomic dysfunction are related to primary open-angle glaucoma stratified by the intraocular pressure (IOP) level.\nRECENT FINDINGS: Patients with primary open angle glaucoma (POAG) across the spectrum of IOP exhibit a variety of ocular and nonocular vascular abnormalities. Interestingly, common genetic variation in nitric oxide synthase 3 (NOS3) and the caveolin 1/caveolin 2 (CAV1/CAV2) genomic regions, which code for proteins involved in setting vascular tone, are associated with POAG. These markers seem to stratify with POAG subtypes stratified by sex or pattern of initial visual field loss and not by IOP level. Overall, it is clear that there is also cardiovascular autonomic dysfunction in high-tension glaucoma and normal-tension glaucoma but it is unclear if this dysfunction is more common in normal-tension glaucoma compared with high-tension glaucoma.\nSUMMARY: Overall, POAG is likely a heterogeneous disease but stratifying cases by IOP level associated with initial optic nerve damage may be less useful than using other endophenotype approaches. Embracing the evidence suggesting systemic endothelial and autonomic dysfunction are operative in POAG will help us move beyond an IOP-centric view of the disease and facilitate 'tearing down the wall' that divides treating physicians and a better understanding of POAG pathogenesis.","DOI":"10.1097/ICU.0000000000000245","ISSN":"1531-7021","note":"PMID: 26720776\nPMCID: PMC4740225","journalAbbreviation":"Curr Opin Ophthalmol","language":"eng","author":[{"family":"Pasquale","given":"Louis R."}],"issued":{"date-parts":[["2016",3]]}},"label":"page"},{"id":265,"uris":[""],"uri":[""],"itemData":{"id":265,"type":"article-journal","title":"New directions in the treatment of normal tension glaucoma","container-title":"Indian Journal of Ophthalmology","page":"529-537","volume":"62","issue":"5","source":"PubMed Central","abstract":"Glaucoma is a progressive optic neuropathy that causes characteristic changes of the optic nerve and visual field in relation to intraocular pressure (IOP). It is now known that glaucoma can occur at statistically normal IOPs and prevalence studies have shown that normal tension glaucoma (NTG) is more common than previously thought. While IOP is believed to be the predominant risk factor in primary open angle glaucoma (POAG), IOP-independent risk factors, such as vascular dysregulation, are believed to play an important part in the pathogenesis of NTG. Though certain distinguishing phenotypic features of NTG have been reported, such as an increased frequency of disc hemorrhages, acquired pits of the optic nerve and characteristic patterns of disc cupping and visual field loss, there is much overlap of the clinical findings in NTG with POAG, suggesting that NTG is likely part of a continuum of open angle glaucomas. However, IOP modification is still the mainstay of treatment in NTG. As in traditional POAG, reduction of IOP can be achieved with the use of medications, laser trabeculoplasty or surgery. Studies now show that the choice of medication may also be important in determining the outcomes of these patients. Though it is likely that future treatment of NTG will involve modification of both IOP and IOP-independent risk factors, current efforts to develop IOP-independent neuroprotective treatments have not yet proven to be effective in humans.","DOI":"10.4103/0301-4738.133481","ISSN":"0301-4738","note":"PMID: 24881596\nPMCID: PMC4065500","journalAbbreviation":"Indian J Ophthalmol","author":[{"family":"Song","given":"Brian J"},{"family":"Caprioli","given":"Joseph"}],"issued":{"date-parts":[["2014",5]]}},"label":"page"},{"id":251,"uris":[""],"uri":[""],"itemData":{"id":251,"type":"article-journal","title":"Obstructive sleep apnea and optic neuropathy: is there a link?","container-title":"Current Neurology and Neuroscience Reports","page":"465","volume":"14","issue":"8","source":"PubMed","abstract":"Over the last decade, there has been an emerging interest in the link between obstructive sleep apnea (OSA) and ocular health. Though the evidence for OSA playing a role in cerebrovascular disease risk seems clear, the same cannot be said for optic neuropathies. The association between OSA and glaucoma or non-arteritic anterior ischemic optic neuropathy (NAION) has been postulated to be secondary to direct hypoxia or mechanisms of optic nerve head vascular dysregulation. Papilledema and increased intracranial pressure have also been reported in OSA and are thought to be due to increased cerebral perfusion pressure and cerebral venous dilation secondary to hypoxia and hypercapnia. This article reviews the evidence for possible pathophysiological links between OSA and optic nerve pathology. The epidemiologic and clinical evidence for an association, direct or indirect, between OSA and glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), and papilledema or idiopathic intracranial hypertension is presented.","DOI":"10.1007/s11910-014-0465-5","ISSN":"1534-6293","note":"PMID: 24942500","title-short":"Obstructive sleep apnea and optic neuropathy","journalAbbreviation":"Curr Neurol Neurosci Rep","language":"eng","author":[{"family":"Fraser","given":"Clare L."}],"issued":{"date-parts":[["2014",8]]}},"label":"page"}],"schema":""} (5–7). Obstructive sleep apnoea (OSA) has been recently shown to independently contribute to the progression of diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"a6aehrgub6","properties":{"formattedCitation":"(8,9)","plainCitation":"(8,9)","noteIndex":0},"citationItems":[{"id":268,"uris":[""],"uri":[""],"itemData":{"id":268,"type":"article-journal","title":"Obstructive Sleep Apnea and Retinopathy in Patients with Type 2 Diabetes. A Longitudinal Study","container-title":"American Journal of Respiratory and Critical Care Medicine","page":"892-900","volume":"196","issue":"7","source":"PubMed","abstract":"RATIONALE: Obstructive sleep apnea (OSA) is associated with several pathophysiological deficits found in diabetic retinopathy (DR). Hence, it's plausible that OSA could play a role in the pathogenesis of sight-threatening DR (STDR).\nOBJECTIVES: To assess the relationship between OSA and DR in patients with type 2 diabetes and to assess whether OSA is associated with its progression.\nMETHODS: A longitudinal study was conducted in diabetes clinics within two U.K. hospitals. Patients known to have any respiratory disorder (including OSA) were excluded. DR was assessed using two-field 45-degree retinal images for each eye. OSA was assessed using a home-based multichannel cardiorespiratory device.\nMEASUREMENTS AND MAIN RESULTS: A total of 230 patients were included. STDR and OSA prevalence rates were 36.1% and 63.9%, respectively. STDR prevalence was higher in patients with OSA than in those without OSA (42.9% vs. 24.1%; P?=?0.004). After adjustment for confounders, OSA remained independently associated with STDR (odds ratio, 2.3; 95% confidence interval, 1.1-4.9; P?=?0.04). After a median (interquartile range) follow-up of 43.0 (37.0-51.0) months, patients with OSA were more likely than patients without OSA to develop preproliferative/proliferative DR (18.4% vs. 6.1%; P?=?0.02). After adjustment for confounders, OSA remained an independent predictor of progression to preproliferative/proliferative DR (odds ratio, 5.2; 95% CI confidence interval, 1.2-23.0; P?=?0.03). Patients who received continuous positive airway pressure treatment were significantly less likely to develop preproliferative/proliferative DR.\nCONCLUSIONS: OSA is associated with STDR in patients with type 2 diabetes. OSA is an independent predictor for the progression to preproliferative/proliferative DR. Continuous positive airway pressure treatment was associated with reduction in preproliferative/proliferative DR. Interventional studies are needed to assess the impact of OSA treatment on STDR.","DOI":"10.1164/rccm.201701-0175OC","ISSN":"1535-4970","note":"PMID: 28594570\nPMCID: PMC5649977","journalAbbreviation":"Am. J. Respir. Crit. Care Med.","language":"eng","author":[{"family":"Altaf","given":"Quratul A."},{"family":"Dodson","given":"Paul"},{"family":"Ali","given":"Asad"},{"family":"Raymond","given":"Neil T."},{"family":"Wharton","given":"Helen"},{"family":"Fellows","given":"Hannah"},{"family":"Hampshire-Bancroft","given":"Rachel"},{"family":"Shah","given":"Mirriam"},{"family":"Shepherd","given":"Emma"},{"family":"Miah","given":"Jamili"},{"family":"Barnett","given":"Anthony H."},{"family":"Tahrani","given":"Abd A."}],"issued":{"date-parts":[["2017",10,1]]}},"label":"page"},{"id":270,"uris":[""],"uri":[""],"itemData":{"id":270,"type":"article-journal","title":"Association of Nonarteritic Ischemic Optic Neuropathy With Obstructive Sleep Apnea Syndrome: Consequences for Obstructive Sleep Apnea Screening and Treatment","container-title":"JAMA ophthalmology","page":"797-804","volume":"133","issue":"7","source":"PubMed","abstract":"IMPORTANCE: The prevalence of obstructive sleep apnea syndrome (OSAS) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and its influence on second eye involvement is not well known.\nOBJECTIVE: To evaluate the prevalence of OSAS in patients with NAION and risk factors of second eye involvement.\nDESIGN, SETTING, AND PARTICIPANTS: In this cohort study, we examined 118 patients with anterior ischemic optic neuropathy referred to a tertiary care center from January 1, 2003, through December 31, 2010.\nEXPOSURES: Patients underwent polysomnography to detect OSAS and were prospectively followed up to assess the risk of second eye involvement.\nMAIN OUTCOMES AND MEASURES: The prevalence of OSAS in patients with NAION and the risk of second eye involvement using survival analysis based on the presence of OSAS, indication for ventilation treatment with continuous positive airway pressure, and other potential ocular and systemic confounders.\nRESULTS: In 89 patients with NAION who underwent polysomnography, 67 (75%) had OSAS. Second eye involvement was found in 10 (13.7%) of 73 patients at 3 years: 8 (15.4%) of 52 patients with OSAS at 3 years and 2 (9.5%) of 21 patients without OSAS at 3 years; P?=?.04. In multivariate analysis, nonadherence to ventilation treatment with continuous positive airway pressure in patients with severe OSAS increased the risk of second eye involvement (hazard ratio, 5.54; 95% CI, 1.13-27.11; P?=?.04).\nCONCLUSIONS AND RELEVANCE: These results suggest that OSAS is common in patients with NAION and that polysomnography should be considered in these patients. These findings also suggest that patients with severe OSAS who are nonadherent to ventilation treatment with continuous positive airway pressure have an increased risk of second eye involvement.","DOI":"10.1001/jamaophthalmol.2015.0893","ISSN":"2168-6173","note":"PMID: 25928835","title-short":"Association of Nonarteritic Ischemic Optic Neuropathy With Obstructive Sleep Apnea Syndrome","journalAbbreviation":"JAMA Ophthalmol","language":"eng","author":[{"family":"Aptel","given":"Florent"},{"family":"Khayi","given":"Hafid"},{"family":"Pépin","given":"Jean-Louis"},{"family":"Tamisier","given":"Renaud"},{"family":"Levy","given":"Patrick"},{"family":"Romanet","given":"Jean-Paul"},{"family":"Chiquet","given":"Christophe"}],"issued":{"date-parts":[["2015",7]]}},"label":"page"}],"schema":""} (8,9). It is plausible that through intermittent hypoxia, hypoxic stress, endothelial dysfunction, sympathetic hyperactivity, intrathoracic pressure swings causing IOP fluctuations and transient hypercapnia altering intracranial pressure, OSA could compromise optic nerve head perfusion and oxygenation promoting glaucomatous optic neuropathy ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"a4f1d0hir6","properties":{"formattedCitation":"(10\\uc0\\u8211{}12)","plainCitation":"(10–12)","noteIndex":0},"citationItems":[{"id":337,"uris":[""],"uri":[""],"itemData":{"id":337,"type":"article-journal","title":"Normal-tension glaucoma and obstructive sleep apnea syndrome: a prospective study","container-title":"BMC ophthalmology","page":"27","volume":"14","source":"PubMed","abstract":"BACKGROUND: Today, identified risk factors for normal-tension glaucoma (NTG) include abnormal ocular blood flow, abnormal blood coagulation, systemic hypotension, ischemic vascular disorders, and autoimmune diseases. However, pathogenesis of the condition remains unclear. On the other hand, there are also a few studies suggesting that the obstructive sleep apnea syndrome (OSAS) may compromise optic nerve head perfusion and cause glaucomatous optic neuropathy by creating transient hypoxemia and increasing vascular resistance. In this study, we evaluated the possible association between OSAS and NTG.\nMETHODS: We recruited 24 patients with NTG and 24 age and sex matched controls who were also similar for systemic risk factors such as diabetes mellitus (DM), hypertension (HT) and hypercholesterolemia. All patients and controls underwent over-night polysomnography (PSG) for the diagnosis of OSAS and calculation of Apnea-Hypopnea Index (AHI).\nRESULTS: Patients and controls were statistically similar in terms of age, sex, gender, smoking, systemic risk factors, neck circumference and body mass index. The subjects with AHI?≥?20 were accepted as OSAS. Ten (41.7%) of 24 patients with NTG and 3 (12.5%) of 24 controls had OSAS (p < 0.05).\nCONCLUSIONS: The prevalence of OSAS was higher in patients with NTG and the difference between patient and control groups was statistically significant (p < 0.05).","DOI":"10.1186/1471-2415-14-27","ISSN":"1471-2415","note":"PMID: 24612638\nPMCID: PMC3975309","title-short":"Normal-tension glaucoma and obstructive sleep apnea syndrome","journalAbbreviation":"BMC Ophthalmol","language":"eng","author":[{"family":"Bilgin","given":"Gorkem"}],"issued":{"date-parts":[["2014",3,10]]}},"label":"page"},{"id":336,"uris":[""],"uri":[""],"itemData":{"id":336,"type":"article-journal","title":"Glaucoma and obstructive sleep apnoea syndrome","container-title":"Clinical & Experimental Ophthalmology","page":"408-419","volume":"40","issue":"4","source":"PubMed","abstract":"Glaucoma is increasingly recognized as a manifestation of both ocular and systemic risk factors. A number of disorders associated with reduced blood flow and ischaemia, collectively termed vascular risk factors, such as migraine, Raynaud's phenomenon, atrial fibrillation and reduced nocturnal blood pressure, lead to decreased ocular perfusion pressure. During sleep, alterations occur in cardiovascular physiology that are balanced by autoregulation to maintain homeostasis. However, in obstructive sleep apnoea (OSA), the normal physiological balance is upset. A potentially modifiable risk factor, OSA has been increasingly associated with glaucoma independent of intraocular pressure. OSA may alter blood flow to the optic nerve head and, in combination with other predisposing factors, lead to decreased ocular perfusion pressure. This in turn may directly affect the optic nerve or it may indirectly increase its susceptibility to other insults. The purpose of this review is to shed light on the association between OSA and glaucoma.","DOI":"10.1111/j.1442-9071.2012.02768.x","ISSN":"1442-9071","note":"PMID: 22339817","journalAbbreviation":"Clin. Experiment. Ophthalmol.","language":"eng","author":[{"family":"Faridi","given":"Omar"},{"family":"Park","given":"Sung Chul"},{"family":"Liebmann","given":"Jeffrey M."},{"family":"Ritch","given":"Robert"}],"issued":{"date-parts":[["2012",6]]}},"label":"page"},{"id":335,"uris":[""],"uri":[""],"itemData":{"id":335,"type":"article-journal","title":"Continuous Intraocular Pressure Monitoring During Nocturnal Sleep in Patients With Obstructive Sleep Apnea Syndrome","container-title":"Investigative Ophthalmology & Visual Science","page":"2824-2830","volume":"57","issue":"6","source":"PubMed","abstract":"PURPOSE: To evaluate intraocular pressure (IOP) changes during nocturnal sleep in patients with obstructive sleep apnea syndrome (OSAS) using a contact lens sensor (CLS).\nMETHODS: This was a prospective cohort study. Seven OSAS patients who had no ocular diseases except mild cataract were enrolled. Each subject underwent CLS-based continuous IOP monitoring on one eye simultaneously with overnight polysomnography. We classified the nocturnal IOP records into nonapnea IOP and apnea IOP, according to the duration of apnea events on polysomnography within each IOP measurement time of 30 seconds every 5 minutes.\nRESULTS: Differences between IOP levels during nonapnea and apnea phases were statistically analyzed. The mean apnea-hypopnea index, the total number of these events per hour of sleep, was 44.2 ± 21.0, indicating the participants' severity of OSAS as moderate to severe. The mean range of IOP fluctuations during nocturnal sleep was 262.3 ± 59.5 mV eq. All patients showed lower mean IOP levels during apnea events than during nonapnea phases, with statistically significant differences detected in four of the seven patients. On average, in all seven eyes, IOP values significantly decreased by 23.1 ± 16.4 mV eq in association with apnea events.\nCONCLUSIONS: Obstructive apnea led to an immediate IOP decline during nocturnal sleep in patients with OSAS. Attention should be paid to IOP-independent etiology, such as episodic hypoxia, potentially linking OSAS and glaucoma.","DOI":"10.1167/iovs.16-19220","ISSN":"1552-5783","note":"PMID: 27227351","journalAbbreviation":"Invest. Ophthalmol. Vis. Sci.","language":"eng","author":[{"family":"Shinmei","given":"Yasuhiro"},{"family":"Nitta","given":"Takuya"},{"family":"Saito","given":"Hiroshi"},{"family":"Ohguchi","given":"Takeshi"},{"family":"Kijima","given":"Riki"},{"family":"Chin","given":"Shinki"},{"family":"Ishida","given":"Susumu"}],"issued":{"date-parts":[["2016",5,1]]}},"label":"page"}],"schema":""} (10–12). Several studies have shown excessive RNFL thinning and reduced retinal sensitivity in people with OSA and otherwise healthy eyes but these associations have not been examined in people with already established glaucoma ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1fs520kv17","properties":{"formattedCitation":"(13\\uc0\\u8211{}15)","plainCitation":"(13–15)","noteIndex":0},"citationItems":[{"id":58,"uris":[""],"uri":[""],"itemData":{"id":58,"type":"article-journal","title":"Decreased retinal nerve fiber layer thickness in patients with obstructive sleep apnea syndrome: A meta-analysis","container-title":"Medicine","page":"e4499","volume":"95","issue":"32","source":"PubMed","abstract":"OBJECTIVE: To investigate the changes of retinal nerve fiber layer (RNFL) thickness in obstructive sleep apnea syndrome (OSAS) patients.\nMETHODS: Relevant studies were selected from 3 major literature databases (PubMed, Cochrane Library, and EMBASE) without language restriction. Main inclusion criteria is that a case-control study in which RNFL thickness was measured by a commercial available optical coherence tomography (OCT) in OSAS patients. Meta-analysis was performed using STATA 12.0 software. Efficacy estimates were evaluated by weighted mean difference with corresponding 95% confidence intervals (CIs). Primary outcome evaluations were: the average changes of RNFL thickness in total OSAS patients, subgroup analysis of RNFL thickness changes in patients of different OSAS stages, and subgroup analysis of 4-quadrant RNFL thickness changes in total OSAS patients.\nRESULTS: Of the initial 327 literatures, 8 case-control studies with 763 eyes of OSA patients and 474 eyes of healthy controls were included (NOS scores ≥6). For the people of total OSAS, there had an average 2.92?μm decreased RNFL thickness compared with controls (95% CI: -4.61 to -1.24, P?=?0.001). For subgroup analysis of OSAS in different stages, the average changes of RNFL thickness in mild, moderate, severe, and moderate to severe OSAS were 2.05 (95% CI: -4.40 to 0.30, P?=?0.088), 2.32 (95% CI: -5.04 to 0.40, P?=?0.094), 4.21 (95% CI: -8.36 to -0.06, P?=?0.047), and 4.02 (95% CI: -7.65 to -0.40, P?=?0.03), respectively. For subgroup analysis of 4-quadrant, the average changes of RNFL thickness in Superior, Nasal, Inferior, and Temporal quadrant were 2.43 (95% CI: -4.28 to -0.57, P?=?0.01), 1.41 (95% CI: -3.33 to 0.51, P?=?0.151), 3.75 (95% CI: -6.92 to -0.59, P?=?0.02), and 0.98 (95% CI: -2.49 to 0.53, P?=?0.203), respectively.\nCONCLUSION: Our study suggests that RNFL thickness in OSAS patients is much thinner than healthy population, especially in superior and inferior quadrant. The impact of OSAS disease on RNFL and visual function should be taken seriously in the further study.","DOI":"10.1097/MD.0000000000004499","ISSN":"1536-5964","note":"PMID: 27512867\nPMCID: PMC4985322","title-short":"Decreased retinal nerve fiber layer thickness in patients with obstructive sleep apnea syndrome","journalAbbreviation":"Medicine (Baltimore)","language":"eng","author":[{"family":"Sun","given":"Cheng-Lin"},{"family":"Zhou","given":"Li-Xiao"},{"family":"Dang","given":"Yalong"},{"family":"Huo","given":"Yin-Ping"},{"family":"Shi","given":"Lei"},{"family":"Chang","given":"Yong-Jie"}],"issued":{"date-parts":[["2016",8]]}},"label":"page"},{"id":56,"uris":[""],"uri":[""],"itemData":{"id":56,"type":"article-journal","title":"Retinal sensitivity is reduced in patients with obstructive sleep apnea","container-title":"Investigative Ophthalmology & Visual Science","page":"7119-7125","volume":"55","issue":"11","source":"PubMed","abstract":"PURPOSE: To evaluate the outcomes of standard automated perimetry (SAP) in patients with obstructive sleep apnea (OSA).\nMETHODS: Eighty OSA patients and 111 age-matched controls were consecutively and prospectively enrolled. One eye per subject was randomly selected. All participants underwent at least one reliable SAP (24-2 SITA Standard algorithm). The peripapillary retinal nerve fiber layer thickness (RNFL) was measured with spectral-domain optical coherence tomography (OCT). Patients with OSA were classified into three groups according to the apnea/hypopnea index: mild, moderate, or severe OSA. Parameters of SAP and OCT were compared between healthy controls and OSA patients. Correlation of apnea/hypopnea index with OCT and SAP measurements were calculated.\nRESULTS: Mean age, best-corrected visual acuity, and central corneal thickness were similar between groups. Intraocular pressure, however, was lower in the OSA group. Mean deviation of SAP was -0.23 ± 0.8 dB in the control group and -1.74 ± 2.8 dB in the OSA group (P < 0.001). Thickness of RNFL measured with OCT did not differ significantly between groups. Patients with OSA showed reduced sensitivity at most points tested by white-on-white perimetry compared with healthy individuals. The threshold values were more depressed in the peripheral visual field. The apnea/hypopnea index was related to the SAP indices: Pearson correlations were -0.432 with mean deviation, 0.467 with pattern standard deviation, and -0.416 with the visual field index (P < 0.001).\nCONCLUSIONS: Patients with OSA exhibited reduced retinal sensitivity measured with SAP compared with healthy controls.","DOI":"10.1167/iovs.14-14389","ISSN":"1552-5783","note":"PMID: 25301881","journalAbbreviation":"Invest. Ophthalmol. Vis. Sci.","language":"eng","author":[{"family":"Ferrandez","given":"Blanca"},{"family":"Ferreras","given":"Antonio"},{"family":"Calvo","given":"Pilar"},{"family":"Abadia","given":"Beatriz"},{"family":"Fogagnolo","given":"Paolo"},{"family":"Wang","given":"Yaowu"},{"family":"Marin","given":"Jose M."},{"family":"Iester","given":"Michele"}],"issued":{"date-parts":[["2014",10,9]]}},"label":"page"},{"id":72,"uris":[""],"uri":[""],"itemData":{"id":72,"type":"article-journal","title":"Optic Nerve Dysfunction in Obstructive Sleep Apnea: An Electrophysiological Study","container-title":"Sleep","page":"19-23","volume":"39","issue":"1","source":"PubMed Central","abstract":"Study Objectives:\nThe aim of this study was to evaluate the integrity of the visual system in patients affected by obstructive sleep apnea (OSA) by means of electroretinogram (ERG) and visual evoked potential (VEP).\n\nMethods:\nWe performed electrophysiological study of the visual system in a population of severe OSA (apnea-hypopnea events/time in bed ≥ 30/h) patients without medical comorbidities compared to a group of healthy controls similar for age, sex, and body mass index. Patients and controls did not have visual impairment or systemic disorders with known influence on the visual system. ERG and VEP were elicited by a reversal pattern generated on a television monitor at low (55') and high (15') spatial frequencies stimulation. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) in both patients and controls.\n\nResults:\nIn comparison with healthy controls (n = 27), patients with OSA (n = 27) showed a significant latency delay coupled with a significant amplitude reduction of P100 wave of VEP at all spatial frequencies in both eyes. No significant differences between groups were detected as concerning ERG components. No correlations were found between polygraphic parameters, ESS scores, or VEP and ERG components in OSA patients.\n\nConclusions:\nThis study documented that patients with OSA, without medical comorbidities, present VEP alteration as documented by lower amplitude and longer latency of the P100 component than healthy controls. These altered electrophysiological findings may be the expression of optic nerve dysfunction provoked by hypoxia, acidosis, hypercarbia and airway obstruction, frequently observed in patients with OSA. Hence, we hypothesize that OSA per se may impair optic nerve function.\n\nCitation:\nLiguori C, Palmieri MG, Pierantozzi M, Cesareo M, Romigi A, Izzi F, Marciani MG, Oliva C, Mercuri NB, Placidi F. Optic nerve dysfunction in obstructive sleep apnea: an electrophysiological study. SLEEP 2016;39(1):19–23.","DOI":"10.5665/sleep.5308","ISSN":"0161-8105","note":"PMID: 26237771\nPMCID: PMC4678339","title-short":"Optic Nerve Dysfunction in Obstructive Sleep Apnea","journalAbbreviation":"Sleep","author":[{"family":"Liguori","given":"Claudio"},{"family":"Palmieri","given":"Maria Giuseppina"},{"family":"Pierantozzi","given":"Mariangela"},{"family":"Cesareo","given":"Massimo"},{"family":"Romigi","given":"Andrea"},{"family":"Izzi","given":"Francesca"},{"family":"Marciani","given":"Maria Grazia"},{"family":"Oliva","given":"Corrado"},{"family":"Mercuri","given":"Nicola Biagio"},{"family":"Placidi","given":"Fabio"}],"issued":{"date-parts":[["2016",1,1]]}},"label":"page"}],"schema":""} (13–15). Screening for OSA has been recommended as part of the systematic work up in glaucoma ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"a1ddgksj4h6","properties":{"formattedCitation":"(16\\uc0\\u8211{}18)","plainCitation":"(16–18)","noteIndex":0},"citationItems":[{"id":263,"uris":[""],"uri":[""],"itemData":{"id":263,"type":"article-journal","title":"The association between ophthalmologic diseases and obstructive sleep apnea: a systematic review and meta-analysis","container-title":"Sleep & Breathing = Schlaf & Atmung","page":"1145-1154","volume":"20","issue":"4","source":"PubMed","abstract":"PURPOSE: The purpose of this study was to evaluate the association between obstructive sleep apnea (OSA) and ophthalmologic diseases, specifically glaucoma, nonarteritic anterior ischemic optic neuropathy (NAION), retinal vein occlusion (RVO), central serous chorioretinopathy (CSR), and floppy eyelid syndrome (FES), by performing a systematic review and meta-analysis of published studies.\nMETHODS: PubMed, Embase, and Scopus databases were searched for observational studies on OSA and its association with select ophthalmologic diseases. Data was pooled for random-effects modeling. The association between OSA and ophthalmologic diseases was summarized using an estimated pooled odds ratio with a 95?% confidence interval.\nRESULTS: Relative to non-OSA subjects, OSA subjects have increased odds of diagnosis with glaucoma (pooled odds ratio (OR)?=?1.242; P?<?0.001) and floppy eyelids syndrome (pooled OR?=?4.157; P?<?0.001). In reverse, the overall pooled OR for OSA was 1.746 (P?=?0.002) in the glaucoma group, 3.126 (P?=?0.000) in the NAION group, and 2.019 (P?=?0.028) in the CSR group. For RVO, one study with 5965 OSA patients and 29,669 controls demonstrated a 1.94-fold odds increase in OSA patients.\nCONCLUSIONS: Our results suggest significant associations between OSA and glaucoma, NAION, CSR, and FES. Screening for OSA should be considered in patients with glaucoma, NAION, CSR, or FES.","DOI":"10.1007/s11325-016-1358-4","ISSN":"1522-1709","note":"PMID: 27230013","title-short":"The association between ophthalmologic diseases and obstructive sleep apnea","journalAbbreviation":"Sleep Breath","language":"eng","author":[{"family":"Huon","given":"Leh-Kiong"},{"family":"Liu","given":"Stanley Yung-Chuan"},{"family":"Camacho","given":"Macario"},{"family":"Guilleminault","given":"Christian"}],"issued":{"date-parts":[["2016",12]]}},"label":"page"},{"id":272,"uris":[""],"uri":[""],"itemData":{"id":272,"type":"article-journal","title":"Indications for a systemic work-up in glaucoma","container-title":"Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie","page":"506-511","volume":"49","issue":"6","source":"PubMed","abstract":"Most glaucomas are primary in nature. However, many adult and childhood glaucomas are secondary, and they require systemic evaluation to pick up associated systemic disease. Conditions such as nocturnal hypotension and sleep apnea may contribute to glaucomatous progression, whereas neurologic diseases may mimic normal tension glaucoma based on disc appearance. This review highlights those conditions in which a focused systemic work-up can improve glaucoma management and potentially discover life-threatening disease.","DOI":"10.1016/j.jcjo.2014.10.001","ISSN":"1715-3360","note":"PMID: 25433739","journalAbbreviation":"Can. J. Ophthalmol.","language":"eng","author":[{"family":"Emanuel","given":"Matthew E."},{"family":"Gedde","given":"Steven J."}],"issued":{"date-parts":[["2014",12]]}},"label":"page"},{"id":271,"uris":[""],"uri":[""],"itemData":{"id":271,"type":"article-journal","title":"Eye disorders associated with obstructive sleep apnoea","container-title":"Current Opinion in Pulmonary Medicine","page":"595-601","volume":"22","issue":"6","source":"PubMed","abstract":"PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. Public awareness is also growing. Although OSA is a disorder primarily of the upper airway during sleep, its physiological impact on other parts of the body is now well recognized. There is increasing interest in the association of OSA with various eye disorders. Work in this field has been directed predominantly to OSA prevalence and association studies, but some authors have tried to elucidate the effect of OSA therapies on eye diseases, including continuous positive airway pressure, upper airway surgery or bariatric surgery. This review discusses the publications in this area from the past year.\nRECENT FINDINGS: The key ocular disorders featured in the studies and meta-analayses include glaucoma, floppy eyelid syndrome, nonarteritic ischaemic optic neuropathy, keratoconus, age-related macular degeneration and diabetic retinopathy. Associations with OSA were found with all these conditions, but aspects of the studies still leave gaps in our knowledge.\nSUMMARY: This review highlights the need for ophthalmologists to consider OSA in their patients and also makes recommendations for future research studies, especially whether therapies for OSA can be effective for ocular disorders also.","DOI":"10.1097/MCP.0000000000000322","ISSN":"1531-6971","note":"PMID: 27635626","journalAbbreviation":"Curr Opin Pulm Med","language":"eng","author":[{"family":"West","given":"Sophie D."},{"family":"Turnbull","given":"Chris"}],"issued":{"date-parts":[["2016",11]]}},"label":"page"}],"schema":""} (16–18). However, before any screening programme is implemented several factors need to be considered, including: the cost of additional diagnostic tests, the risks and benefits of a new diagnosis, the strength of association between the two conditions and the causality. The starting point would be to understand the burden of OSA among patients with glaucoma. At present, it is unclear whether people with POAG are more likely to suffer from OSA, are more symptomatic or have a different profile of OSA risk factors than those without glaucoma. A few small studies have assessed the prevalence of OSA in patients with POAG but they had important methodological limitations and have provided contradictory results ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"a2ijl2rm2ml","properties":{"formattedCitation":"(19\\uc0\\u8211{}22)","plainCitation":"(19–22)","noteIndex":0},"citationItems":[{"id":277,"uris":[""],"uri":[""],"itemData":{"id":277,"type":"article-journal","title":"Primary Open-Angle Glaucoma Is Associated with Sleep Apnea Syndrome","container-title":"Ophthalmologica","page":"115-118","volume":"214","issue":"2","source":"","abstract":"<i>Introduction:</i> The etiology of primary open-angle glaucoma remains unclear. Various risk factors, including vascular abnormalities, have been associated with this disease. Sleep-asso","DOI":"10.1159/000027478","ISSN":"0030-3755, 1423-0267","note":"PMID: 10720914","journalAbbreviation":"OPH","language":"english","author":[{"family":"Mojon","given":"Daniel S."},{"family":"Hess","given":"Christian W."},{"family":"Goldblum","given":"David"},{"family":"B?hnke","given":"Matthias"},{"family":"K?rner","given":"Fritz"},{"family":"Mathis","given":"Johannes"}],"issued":{"date-parts":[["2000"]]}},"label":"page"},{"id":258,"uris":[""],"uri":[""],"itemData":{"id":258,"type":"article-journal","title":"Sleep disorders: a risk factor for normal-tension glaucoma?","container-title":"Journal of Glaucoma","page":"177-183","volume":"10","issue":"3","source":"PubMed","abstract":"PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related breathing disorders by polysomnography in patients with normal-tension glaucoma (NTG).\nPATIENTS AND METHODS: This comparative case series included 23 patients with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep history was obtained and determined to be positive or negative. Polysomnography was offered for patients with a positive sleep history. Prevalence of a positive sleep history and prevalence of sleep disorders were the main outcome measures.\nRESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23 patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG and four of six NTG suspects with a positive sleep history chose to undergo polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects undergoing polysomnography were diagnosed with a sleep disorder. Five patients with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The one comparison patient with a positive sleep history had upper airway resistance syndrome by polysomnography.\nCONCLUSIONS: Sleep-disturbed breathing may be a risk factor for NTG. Although we do not provide evidence for a cause-and-effect relationship, various physiologic factors produced by sleep-disturbed breathing may play a significant role in the pathogenesis of this optic neuropathy. We recommend obtaining a sleep history from patients with NTG and performing polysomnography in those patients with sleep disturbance symptoms.","ISSN":"1057-0829","note":"PMID: 11442179","title-short":"Sleep disorders","journalAbbreviation":"J. Glaucoma","language":"eng","author":[{"family":"Marcus","given":"D. M."},{"family":"Costarides","given":"A. P."},{"family":"Gokhale","given":"P."},{"family":"Papastergiou","given":"G."},{"family":"Miller","given":"J. J."},{"family":"Johnson","given":"M. H."},{"family":"Chaudhary","given":"B. A."}],"issued":{"date-parts":[["2001",6]]}},"label":"page"},{"id":257,"uris":[""],"uri":[""],"itemData":{"id":257,"type":"article-journal","title":"Normal-tension glaucoma and obstructive sleep apnea syndrome: a prospective study","container-title":"BMC ophthalmology","page":"27","volume":"14","source":"PubMed","abstract":"BACKGROUND: Today, identified risk factors for normal-tension glaucoma (NTG) include abnormal ocular blood flow, abnormal blood coagulation, systemic hypotension, ischemic vascular disorders, and autoimmune diseases. However, pathogenesis of the condition remains unclear. On the other hand, there are also a few studies suggesting that the obstructive sleep apnea syndrome (OSAS) may compromise optic nerve head perfusion and cause glaucomatous optic neuropathy by creating transient hypoxemia and increasing vascular resistance. In this study, we evaluated the possible association between OSAS and NTG.\nMETHODS: We recruited 24 patients with NTG and 24 age and sex matched controls who were also similar for systemic risk factors such as diabetes mellitus (DM), hypertension (HT) and hypercholesterolemia. All patients and controls underwent over-night polysomnography (PSG) for the diagnosis of OSAS and calculation of Apnea-Hypopnea Index (AHI).\nRESULTS: Patients and controls were statistically similar in terms of age, sex, gender, smoking, systemic risk factors, neck circumference and body mass index. The subjects with AHI?≥?20 were accepted as OSAS. Ten (41.7%) of 24 patients with NTG and 3 (12.5%) of 24 controls had OSAS (p < 0.05).\nCONCLUSIONS: The prevalence of OSAS was higher in patients with NTG and the difference between patient and control groups was statistically significant (p < 0.05).","DOI":"10.1186/1471-2415-14-27","ISSN":"1471-2415","note":"PMID: 24612638\nPMCID: PMC3975309","title-short":"Normal-tension glaucoma and obstructive sleep apnea syndrome","journalAbbreviation":"BMC Ophthalmol","language":"eng","author":[{"family":"Bilgin","given":"Gorkem"}],"issued":{"date-parts":[["2014",3,10]]}},"label":"page"},{"id":260,"uris":[""],"uri":[""],"itemData":{"id":260,"type":"article-journal","title":"Prevalence of nocturnal oxygen desaturation and self-reported sleep-disordered breathing in glaucoma","container-title":"Journal of Glaucoma","page":"114-118","volume":"18","issue":"2","source":"PubMed","abstract":"PURPOSE: To evaluate the prevalence of nocturnal oxygen desaturation and sleep-disordered breathing symptoms within a glaucoma population.\nPATIENTS AND METHODS: One hundred and twelve subjects (glaucoma=52, control=60) aged between 45 and 80 years were recruited for the study. Clinical assessment included overnight ambulatory pulse oximetry monitoring and administration of a self-reported sleep-disordered breathing questionnaire.\nRESULTS: There were no differences in age, sex, body mass index, or prevalence of systemic hypertension between the groups. The mean oxygen desaturation index of the glaucoma group (8.6) did not differ significantly from that of the control group (9.6) (P=0.715). The prevalence of moderate to severe respiratory dysfunction (oxygen desaturation index >20) in the glaucoma group (17%) was similar to that in the control group (12%) (P=0.463). The severity of sleep-disordered breathing symptoms was similar between the groups (P=0.157).\nCONCLUSIONS: No statistically significant association was found between glaucoma and either nocturnal oxygen desaturation or sleep-disordered breathing. Although this study cannot exclude the possibility of either impaired optic nerve head autoregulation or hypoxic damage occurring secondary to sleep apnea syndrome, the findings do not support the routine use of pulse oximetry in the workup of individuals with glaucoma.","DOI":"10.1097/IJG.0b013e318179f80c","ISSN":"1536-481X","note":"PMID: 19225346","journalAbbreviation":"J. Glaucoma","language":"eng","author":[{"family":"Roberts","given":"Timothy V."},{"family":"Hodge","given":"Chris"},{"family":"Graham","given":"Stuart L."},{"family":"Burlutsky","given":"George"},{"family":"Mitchell","given":"Paul"}],"issued":{"date-parts":[["2009",2]]}},"label":"page"}],"schema":""} (19–22). The aim of the current study was, therefore, to determine the prevalence of OSA in a larger sample of patients with POAG, assess whether this prevalence is higher than in people without glaucoma with the same risk factors for OSA and whether it differs between POAG subtypes (HTG vs NTG). We also aimed to examine potential associations between OSA severity markers and indicators of optic nerve structure and function. Methods2.1 Study design and participants The study was observational and cross-sectional including unselected patients with POAG and control subjects. The project was approved by the East of England-Cambridgeshire and Hertfordshire Research Ethics Committee (REC number 15/EE/0292) and the Anglia Ruskin University Research Ethics Panel (ref. 15/16 014). Recruitment took place in the glaucoma clinic at a single secondary care hospital in the United Kingdom (Hinchingbrooke Hospital, North West Anglia Foundation Trust). Consecutive patients with a diagnosis of POAG who attended the clinic between March 2016 and September 2017 were invited provided they were historically able to perform reliable visual field tests. Control subjects with no history of glaucoma were recruited from spouses, partners, friends, and siblings of patients with POAG. There were two routes of approaching the potential control subjects: i. relatives of glaucoma patients who accompanied them in the glaucoma clinic were directly invited by the study personnel and provided written information outlining the study, ii. unaccompanied glaucoma patients were asked to pass on the study information with an invitation letter to their partners, friends or siblings who were then advised to contact the research team should they wish to contribute to the study. Participants had to be at least 18 years old and able to give informed consent. We invited all potentially eligible subjects irrespective of sleep complaints, including known sleep-disordered breathing (SDB) to participate.2.2 Study procedures2.2.1 Ophthalmic examination All enrolled participants underwent a comprehensive ophthalmic examination which consisted of the following measurements: best-corrected visual acuity, refraction (Auto kerato-refractometer, Topcon, Tokyo, Japan), automated visual fields (Humphrey Visual Field Analyser, SITA-Fast, Carl Zeiss Meditec, Jena, Germany), slit-lamp biomicroscopy and gonioscopy (Haag-Streit International, Koeniz, Switzerland), Goldmann applanation tonometry (Haag-Streit International, Koeniz, Switzerland), central corneal thickness (Pachmate 2, DGH Technology Inc., Exton, USA) corneal hysteresis (Ocular Response Analyser, Reichert, N.Y., USA ) and fundus photography. Circumpapillary RNFL thickness was automatically measured as a global average and also in four quadrants using Spectralis Ocular Coherence Tomography (OCT) (Heidelberg Engineering Inc. MA, USA). The global RNFL measurements were used in the analysis. The Mean Deviation (MD) and the Pattern Standard Deviation from the visual field examination were used to categorize POAG patients into seven stages of glaucoma severity as per the enhanced Glaucoma Severity Staging system (eGSS) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"WQA91hNT","properties":{"formattedCitation":"(23)","plainCitation":"(23)","noteIndex":0},"citationItems":[{"id":252,"uris":[""],"uri":[""],"itemData":{"id":252,"type":"article-journal","title":"Enhanced Glaucoma Staging System (GSS 2) for classifying functional damage in glaucoma","container-title":"Journal of Glaucoma","page":"40-46","volume":"15","issue":"1","source":"PubMed","abstract":"PURPOSE: To introduce a new method, derived from the Glaucoma Staging System (GSS), for classifying glaucomatous visual field defects.\nPATIENTS AND METHODS: Four sample groups composed respectively of 471 (sample #1), 128 (sample #2), 185 (sample #3), and 131 (sample #4) patients with either ocular hypertension or chronic glaucoma were considered. The GSS 2 uses both the MD and CPSD/CLV or PSD/LV perimetric indices to classify visual field defect in 6 stages and in 3 types (generalized, localized, and mixed). The formulas were determined using sample #1. A new borderline stage was created, on the basis of sample #2. The relationship between the PSD/LV and CPSD/CLV values was studied on sample #3 to verify the possibility of using the uncorrected indices instead of the CPSD/CLV. The relationship with other classification methods was studied on sample #4.\nRESULTS: The GSS 2 showed a strong level of association with the AGIS and the Hodapp-Parrish-Anderson methods in staging defect severity. A good correlation was also found with a classification based on the Bebie curve.\nCONCLUSIONS: The GSS 2 was able to correctly classify both damage severity and perimetric defect type in the sample studied, using either the corrected or uncorrected visual field indices. It is a quick and easy method, and its formulas can be introduced in any software.","ISSN":"1057-0829","note":"PMID: 16378017","journalAbbreviation":"J. Glaucoma","language":"eng","author":[{"family":"Brusini","given":"Paolo"},{"family":"Filacorda","given":"Stefano"}],"issued":{"date-parts":[["2006",2]]}}}],"schema":""} (23). Patients who had IOP≤21 mmHg prior to starting glaucoma treatment and during follow up constituted the NTG group. The diagnosis of POAG was confirmed by a consultant ophthalmologist specializing in glaucoma based on a typical optic disc appearance, reproducible visual field defect, and OCT results. Recruited POAG patients who did not meet the diagnostic criteria were excluded. Similarly, any control subjects found to have definite or suspected glaucoma were excluded.2.2.1 Sleep studies Participants who met the eligibility criteria following the ocular assessment underwent nocturnal multichannel cardiorespiratory monitoring at home (type 3 sleep study) using a portable device (Embletta MPR and GOLD; Natus Medical Inc., Pleasanton, USA). Sleep studies of suboptimal quality or duration were repeated once; if the second attempt was unsuccessful or declined the participant was excluded. People using treatment for OSA were asked to withdraw it a week prior to the sleep test. All sleep studies were scored manually in an accredited tertiary sleep centre (Respiratory Support and Sleep Centre, Royal Papworth Hospital, Cambridge) by one polysomnographer and in accordance with current American Academy of Sleep Medicine guidelines ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9zyBO8Wj","properties":{"formattedCitation":"(24)","plainCitation":"(24)","noteIndex":0},"citationItems":[{"id":262,"uris":[""],"uri":[""],"itemData":{"id":262,"type":"article-journal","title":"Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine","container-title":"Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine","page":"597-619","volume":"8","issue":"5","source":"PubMed","abstract":"The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions.The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO(2) signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults.The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for ≥ 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ 10 seconds in association with either ≥ 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is ≥ 20 seconds in duration, (2) the event is associated with an arousal or ≥ 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ the duration of 2 breaths in association with either ≥ 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO(2) are the end-tidal PCO(2) or transcutaneous PCO(2) (diagnostic study) or transcutaneous PCO(2) (titration study). For adults, sleep hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 55 mm Hg for ≥ 10 minutes or there is an increase in the arterial PCO(2) (or surrogate) ≥ 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of ≥ 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring.","DOI":"10.5664/jcsm.2172","ISSN":"1550-9397","note":"PMID: 23066376\nPMCID: PMC3459210","title-short":"Rules for scoring respiratory events in sleep","journalAbbreviation":"J Clin Sleep Med","language":"eng","author":[{"family":"Berry","given":"Richard B."},{"family":"Budhiraja","given":"Rohit"},{"family":"Gottlieb","given":"Daniel J."},{"family":"Gozal","given":"David"},{"family":"Iber","given":"Conrad"},{"family":"Kapur","given":"Vishesh K."},{"family":"Marcus","given":"Carole L."},{"family":"Mehra","given":"Reena"},{"family":"Parthasarathy","given":"Sairam"},{"family":"Quan","given":"Stuart F."},{"family":"Redline","given":"Susan"},{"family":"Strohl","given":"Kingman P."},{"family":"Davidson Ward","given":"Sally L."},{"family":"Tangredi","given":"Michelle M."},{"literal":"American Academy of Sleep Medicine"}],"issued":{"date-parts":[["2012",10,15]]}}}],"schema":""} (24). The polysomnographer was blinded to the glaucoma status. Participants with predominantly central sleep apnoea were excluded. Obstructive sleep apnoea was diagnosed based on an apnoea-hypopnoea index (AHI) of greater than or equal to 5. The usual clinical thresholds were used to categorize OSA severity: mild (AHI≥5 to <15), moderate (AHI≥15 to <30), severe (AHI≥30).For the analysis of associations between ocular and OSA parameters, the eye with the lower MD (greater visual field loss) was selected for each participant, unless it was affected by a comorbid condition which could have impacted visual field results or RNFL thickness. These comorbidities included: retinal vascular disease, diabetic retinopathy, age-related macular degeneration, prior retinal detachment, advanced cataract or neurological scotomas. Subjects with ocular comorbidity in both eyes or in the glaucomatous eye in case of unilateral POAG, and also those who were using treatment for OSA, were excluded from the association analysis (Figure 1).2.3 Statistical analysisContinuous data are presented as mean (SD) or median (IQR) depending on the distribution. For all data, the assumption of normality was assessed using the Shapiro-Wilk test and by visual inspection of histograms. Independent continuous variables were compared using Student's t-test or, in case of non-parametric data, the Mann-Whitney U test. The chi-square test was used to compare proportions. In order to reduce confounding from imbalances between the groups in known OSA predictors, we performed propensity score matching using one-to-one nearest neighbour algorithm. The prevalence of OSA between POAG and control groups was then compared in the matched groups. We used an ordinal logistic regression model to assess for an association between POAG severity stages as the outcome measure and AHI as an independent variable. Univariate linear regression models were developed to examine the relationship between AHI and the global RNFL thickness. To assess whether OSA is a predictor of RNFL thickness after adjusting for previously reported predictors of glaucoma progression and/or RNFL thinning we built a multivariable linear model with AHI and other predictors as co-variates (forced entry method). All statistical test assumptions were adhered to throughout the analysis and only models meeting these assumptions are reported. The propensity score matching was implemented in R (version 3.4.1) using the Matchit package. All other analyses were conducted using SPSS software version 22.0 (IBM SPSS, IL, USA).Results3.1 OSA prevalence We included 395 participants in the OSA prevalence analysis comprising 235 with POAG and 160 control subjects (see Figure 1 for the study flow chart and Supplement 1 for demographic data on invited POAG patients who consented vs those who declined participation in the study). Spouses, partners, and friends of recruited POAG patients constituted 99% of the control group. OSA was diagnosed in 58% (95% CI:52-65) of POAG patients and in 54% (95% CI:47-62) of control participants (p=0.44, for between groups comparison). Moderate to severe OSA was found in 22% (95% CI:16-27) of POAG patients and in 16% (95% CI:11-22) controls (p=0.15, for between groups comparison). In the POAG group, five patients had been previously diagnosed with OSA. Two of them were using Continuous Positive Airway Pressure treatment. One participant in the control group had a prior diagnosis of OSA and was not on treatment. In the entire cohort age, male sex, BMI, neck size and diabetes were significant predictors of OSA in unadjusted analyses (see Supplement 2). There were statistically significant (or close to being statistically significant) imbalances between the groups for sex and age, however, each of the participants in the control group was successfully matched with one of 160 POAG patients (Table 1). There was no significant difference in OSA prevalence between the matched groups (53.8% [POAG] vs. 54.4% [Control], p=0.91). Similarly, the prevalence of moderate to severe OSA was not significantly different (18.1% [POAG] vs 16.3% [Control], p=0.66), Figure 2. The level of sleepiness and the prevalence of OSA syndrome defined by a diagnosis of OSA and the presence of self-reported sleepiness (Epworth Sleepiness Scale score above 10) did not differ between the participants with and without POAG (see Table 1). Data on baseline IOP prior to starting IOP lowering treatment were available in 92% of POAG patients. Of those, 35.6% were diagnosed with NTG and the remainder with HTG. The prevalence of OSA was not significantly different between these two subgroups (55.8% [NTG] versus 57.6% [HTG], p=0.89). Moderate to severe OSA was diagnosed in 16.9 % of NTG patients and 24.5% of HTG cases (p=0.23).3.2 Associations between OSA and ocular parameters After exclusion of participants with treated OSA and ocular co-morbidities, data from 216 POAG patients and 153 control subjects were available for the association analysis.The POAG group consisted of patients with all stages of functional visual field impairment (Figure 3). According to the chosen classification, Stage 0 represents no detectable visual field defect and the higher the stage the more severe the visual field loss. All visual field tests were reliable (false negative errors <20%, false positive errors <20%, fixation loses<33%) and there were no missing data. In an ordinal logistic regression analysis, AHI was not a significant predictor of the disease severity stages (p=0.40), Figure 4. To assess whether there was a relationship between AHI and the structural damage we used linear regression models. Subjects with missing data or inadequate quality images were not included in the models (for further details see Supplement 3). The AHI did not predict RNFL thinning in an unadjusted model and remained non-significant in a multivariable model. Highest ever recorded IOP, IOP measured at the study visit, and corneal hysteresis were independently associated with RNFL thickness. We constructed similar linear regression models in the control group and found no significant associations between AHI and RNFL thickness. In a multivariable model, older age, female sex and higher degree of myopia were the only independent predictors of RNFL thinning (Table 2). Furthermore, there was no difference in the global RNFL thickness between people with and without OSA in both groups. The global RNFL thickness did not differ even when participants without OSA were compared with those with moderate to severe OSA (Table 3).DiscussionBased on plausible pathophysiological mechanisms and some epidemiological data it has been hypothesized that OSA may play a role in the development and progression of glaucomatous optic nerve neuropathy ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"fgW2ya3F","properties":{"formattedCitation":"(7,18,25,26)","plainCitation":"(7,18,25,26)","noteIndex":0},"citationItems":[{"id":250,"uris":[""],"uri":[""],"itemData":{"id":250,"type":"article-journal","title":"Obstructive sleep apnea-hypopnea syndrome (OSAHS) and glaucomatous optic neuropathy","container-title":"Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie","page":"1345-1357","volume":"252","issue":"9","source":"PubMed","abstract":"Obstructive sleep apnea-hypopnea syndrome (OSAHS) is becoming widely accepted as a risk factor for glaucoma. We discuss the proposed mechanism involved in the pathogenesis of glaucoma in OSAHS, and review the published data on the association between these two conditions, as well as papers regarding functional and structural tests related with glaucomatous damage. There is increasing evidence that the prevalence of glaucoma is higher in OSAHS patients, especially in those with severe disease with apnea-hypopnea index (AHI) >30, and also that sleep disorders may be more frequent in patients with glaucoma, especially in those with normal tension glaucoma (NTG). Several ophthalmic signs and symptoms have been associated with this condition. Raised intraocular pressure (IOP), possibly related to increased body mass index, thinning of retinal nerve fiber layer (RNFL), and alteration of visual field (VF) indices has been demonstrated in many studies, in patients with no history of glaucoma or evidence of glaucomatous changes in the ophthalmic examination. A correlation of AHI with RNFL and VF indices has been described in some studies. Finally, corneal thinning, suspicious glaucomatous disc changes and anomalies in electrophysiological tests such as multifocal visual evoked potential have been described in patients with OSAHS, even in patients with normal findings in the optic nerve and VF, suggesting subclinical optic nerve involvement not detectable in conventional ophthalmic examinations. The pathogenesis of optic nerve involvement has been related to vascular and mechanical factors. Vascular factors include recurrent hypoxia with increased vascular resistance, autonomic deregulation, oxidative stress and inflammation linked to hypoxia and subsequent reperfusion, decreased cerebral perfusion pressure and direct hypoxic damage to the optic nerve. Proposed mechanical factors include increased IOP at night related to supine position and obesity, raised intracranial pressure and elastic fiber depletion in the lamina cribosa and/or trabeculum. In conclusion, ophthalmic evaluation should be recommended in patients with severe OSAHS, and the presence of sleep disorders should be investigated in patients with glaucoma, especially in NTG patients and in those with progressive damage despite controlled IOP, as treatment with continuous positive airway pressure may contribute to stabilizing the progression of glaucomatous damage.","DOI":"10.1007/s00417-014-2669-4","ISSN":"1435-702X","note":"PMID: 24859387","journalAbbreviation":"Graefes Arch. Clin. Exp. Ophthalmol.","language":"eng","author":[{"family":"Pérez-Rico","given":"Consuelo"},{"family":"Gutiérrez-Díaz","given":"Esperanza"},{"family":"Mencía-Gutiérrez","given":"Enrique"},{"family":"Díaz-de-Atauri","given":"María Josefa"},{"family":"Blanco","given":"Román"}],"issued":{"date-parts":[["2014",9]]}},"label":"page"},{"id":251,"uris":[""],"uri":[""],"itemData":{"id":251,"type":"article-journal","title":"Obstructive sleep apnea and optic neuropathy: is there a link?","container-title":"Current Neurology and Neuroscience Reports","page":"465","volume":"14","issue":"8","source":"PubMed","abstract":"Over the last decade, there has been an emerging interest in the link between obstructive sleep apnea (OSA) and ocular health. Though the evidence for OSA playing a role in cerebrovascular disease risk seems clear, the same cannot be said for optic neuropathies. The association between OSA and glaucoma or non-arteritic anterior ischemic optic neuropathy (NAION) has been postulated to be secondary to direct hypoxia or mechanisms of optic nerve head vascular dysregulation. Papilledema and increased intracranial pressure have also been reported in OSA and are thought to be due to increased cerebral perfusion pressure and cerebral venous dilation secondary to hypoxia and hypercapnia. This article reviews the evidence for possible pathophysiological links between OSA and optic nerve pathology. The epidemiologic and clinical evidence for an association, direct or indirect, between OSA and glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), and papilledema or idiopathic intracranial hypertension is presented.","DOI":"10.1007/s11910-014-0465-5","ISSN":"1534-6293","note":"PMID: 24942500","title-short":"Obstructive sleep apnea and optic neuropathy","journalAbbreviation":"Curr Neurol Neurosci Rep","language":"eng","author":[{"family":"Fraser","given":"Clare L."}],"issued":{"date-parts":[["2014",8]]}},"label":"page"},{"id":271,"uris":[""],"uri":[""],"itemData":{"id":271,"type":"article-journal","title":"Eye disorders associated with obstructive sleep apnoea","container-title":"Current Opinion in Pulmonary Medicine","page":"595-601","volume":"22","issue":"6","source":"PubMed","abstract":"PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. Public awareness is also growing. Although OSA is a disorder primarily of the upper airway during sleep, its physiological impact on other parts of the body is now well recognized. There is increasing interest in the association of OSA with various eye disorders. Work in this field has been directed predominantly to OSA prevalence and association studies, but some authors have tried to elucidate the effect of OSA therapies on eye diseases, including continuous positive airway pressure, upper airway surgery or bariatric surgery. This review discusses the publications in this area from the past year.\nRECENT FINDINGS: The key ocular disorders featured in the studies and meta-analayses include glaucoma, floppy eyelid syndrome, nonarteritic ischaemic optic neuropathy, keratoconus, age-related macular degeneration and diabetic retinopathy. Associations with OSA were found with all these conditions, but aspects of the studies still leave gaps in our knowledge.\nSUMMARY: This review highlights the need for ophthalmologists to consider OSA in their patients and also makes recommendations for future research studies, especially whether therapies for OSA can be effective for ocular disorders also.","DOI":"10.1097/MCP.0000000000000322","ISSN":"1531-6971","note":"PMID: 27635626","journalAbbreviation":"Curr Opin Pulm Med","language":"eng","author":[{"family":"West","given":"Sophie D."},{"family":"Turnbull","given":"Chris"}],"issued":{"date-parts":[["2016",11]]}},"label":"page"},{"id":161,"uris":[""],"uri":[""],"itemData":{"id":161,"type":"article-journal","title":"Glaucoma and obstructive sleep apnoea syndrome","container-title":"Clinical & Experimental Ophthalmology","page":"408-419","volume":"40","issue":"4","source":"PubMed","abstract":"Glaucoma is increasingly recognized as a manifestation of both ocular and systemic risk factors. A number of disorders associated with reduced blood flow and ischaemia, collectively termed vascular risk factors, such as migraine, Raynaud's phenomenon, atrial fibrillation and reduced nocturnal blood pressure, lead to decreased ocular perfusion pressure. During sleep, alterations occur in cardiovascular physiology that are balanced by autoregulation to maintain homeostasis. However, in obstructive sleep apnoea (OSA), the normal physiological balance is upset. A potentially modifiable risk factor, OSA has been increasingly associated with glaucoma independent of intraocular pressure. OSA may alter blood flow to the optic nerve head and, in combination with other predisposing factors, lead to decreased ocular perfusion pressure. This in turn may directly affect the optic nerve or it may indirectly increase its susceptibility to other insults. The purpose of this review is to shed light on the association between OSA and glaucoma.","DOI":"10.1111/j.1442-9071.2012.02768.x","ISSN":"1442-9071","note":"PMID: 22339817","journalAbbreviation":"Clin. Experiment. Ophthalmol.","language":"eng","author":[{"family":"Faridi","given":"Omar"},{"family":"Park","given":"Sung Chul"},{"family":"Liebmann","given":"Jeffrey M."},{"family":"Ritch","given":"Robert"}],"issued":{"date-parts":[["2012",6]]}},"label":"page"}],"schema":""} (7,18,25,26). According to this hypothesis, a high OSA burden could be expected among glaucoma patients and there would be a rational to evaluate screening for OSA. In our study of unselected POAG patients prospectively examined with a diagnostic test for sleep-disordered breathing (SDB) in a real-world clinic scenario, we found no evidence that patients with POAG are more likely to suffer from OSA or have more severe OSA than control subjects. After statistical matching of participants with and without glaucoma, the prevalence of OSA was remarkably close between the groups. In addition, we have found no difference between the groups in several markers of nocturnal hypoxia associated with OSA and the levels of subjective sleepiness (when considered on its own or in a combination with OSA diagnosis as OSA syndrome) were similar. This indicates that if routine OSA screening was to be implemented in glaucoma clinics the yield of patients who would then be considered for OSA treatment, according to the current clinical practice, would be the same as in the general population of middle to elderly aged people. The reported prevalence of OSA (defined as ≥5 AHI) in the general adult population varies widely from 9 % to 38% ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"njsEo5JM","properties":{"formattedCitation":"(27)","plainCitation":"(27)","noteIndex":0},"citationItems":[{"id":1182,"uris":[""],"uri":[""],"itemData":{"id":1182,"type":"article-journal","title":"Prevalence of obstructive sleep apnea in the general population: A systematic review","container-title":"Sleep Medicine Reviews","page":"70-81","volume":"34","source":"PubMed","abstract":"With this systematic review we aimed to determine the prevalence of obstructive sleep apnea (OSA) in adults in the general population and how it varied between population sub-groups. Twenty-four studies out of 3807 found by systematically searching PubMed and Embase databases were included in this review. Substantial methodological heterogeneity in population prevalence studies has caused a wide variation in the reported prevalence, which, in general, is high. At ≥5 events/h apnea-hypopnea index (AHI), the overall population prevalence ranged from 9% to 38% and was higher in men. It increased with increasing age and, in some elderly groups, was as high as 90% in men and 78% in women. At ≥15 events/h?AHI, the prevalence in the general adult population ranged from 6% to 17%, being as high as 49% in the advanced ages. OSA prevalence was also greater in obese men and women. This systematic review of the overall body of evidence confirms that advancing age, male sex, and higher body-mass index increase OSA prevalence. The need to a) consider OSA as having a continuum in the general population and b) generate consensus on methodology and diagnostic threshold to define OSA so that the prevalence of OSA can be validly compared across regions and countries, and within age-/sex-specific subgroups, is highlighted.","DOI":"10.1016/j.smrv.2016.07.002","ISSN":"1532-2955","note":"PMID: 27568340","title-short":"Prevalence of obstructive sleep apnea in the general population","journalAbbreviation":"Sleep Med Rev","language":"eng","author":[{"family":"Senaratna","given":"Chamara V."},{"family":"Perret","given":"Jennifer L."},{"family":"Lodge","given":"Caroline J."},{"family":"Lowe","given":"Adrian J."},{"family":"Campbell","given":"Brittany E."},{"family":"Matheson","given":"Melanie C."},{"family":"Hamilton","given":"Garun S."},{"family":"Dharmage","given":"Shyamali C."}],"issued":{"date-parts":[["2017"]]}}}],"schema":""} (27). There are multiple reasons for these differences across the studies. Of particular importance are population specific factors, such as: age, ethnicity and the prevalence of obesity. There are also factors related to OSA measurement techniques including the type of sleep study used and the scoring criteria for respiratory events which have changed several times in the last two decades. This highlights the importance of having a well matched concurrent control group and using the same diagnostic tools whenever OSA prevalence is studied in disease-specific cohorts of patients.Although the OSA prevalence figures found in the current study in both groups seem high they are in keeping with relatively high rates of OSA reported in older people. For instance, in a study from Iceland OSA (AHI ≥5) was found in 43.1% of participants aged 40-65 years who were also examined with type 3 sleep study ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"qFXo6Nv0","properties":{"formattedCitation":"(28)","plainCitation":"(28)","noteIndex":0},"citationItems":[{"id":1187,"uris":[""],"uri":[""],"itemData":{"id":1187,"type":"article-journal","title":"Obstructive sleep apnoea in the general population: highly prevalent but minimal symptoms","container-title":"The European Respiratory Journal","page":"194-202","volume":"47","issue":"1","source":"PubMed","abstract":"The aim was to assess the prevalence of obstructive sleep apnoea (OSA) as defined by an apnoea-hypopnea index (AHI) ≥15 in the middle-aged general population, and the interrelationship between OSA, sleep-related symptoms, sleepiness and vigilance.A general population sample of 40-65-year-old Icelanders was invited to participate in a study protocol that included a type 3 sleep study, questionnaire and a psychomotor vigilance test (PVT).Among the 415 subjects included in the study, 56.9% had no OSA (AHI <5), 24.1% had mild OSA (AHI 5-14.9), 12.5% had moderate OSA (AHI 15-29.9), 2.9% had severe OSA (AHI ≥30) and 3.6% were already diagnosed and receiving OSA treatment. However, no significant relationship was found between AHI and subjective sleepiness or clinical symptoms. A relationship with objective vigilance assessed by PVT was only found for those with AHI ≥30. Subjects already on OSA treatment and those accepting OSA treatment after participating in the study were more symptomatic and sleepier than others with similar OSA severity, as assessed by the AHI.In a middle-aged general population, approximately one in five subjects had moderate-to-severe OSA, but the majority of them were neither symptomatic nor sleepy and did not have impaired vigilance.","DOI":"10.1183/13993003.01148-2015","ISSN":"1399-3003","note":"PMID: 26541533","title-short":"Obstructive sleep apnoea in the general population","journalAbbreviation":"Eur. Respir. J.","language":"eng","author":[{"family":"Arnardottir","given":"Erna S."},{"family":"Bjornsdottir","given":"Erla"},{"family":"Olafsdottir","given":"Kristin A."},{"family":"Benediktsdottir","given":"Bryndis"},{"family":"Gislason","given":"Thorarinn"}],"issued":{"date-parts":[["2016",1]]}}}],"schema":""} (28). In a slightly older (mean age of 68 years) French cohort, 57% of participants were diagnosed with OSA (AHI ≥15) based on the same type of sleep study ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"sDLp3cEk","properties":{"formattedCitation":"(29)","plainCitation":"(29)","noteIndex":0},"citationItems":[{"id":1184,"uris":[""],"uri":[""],"itemData":{"id":1184,"type":"article-journal","title":"Sex differences in obstructive sleep apnoea in an elderly French population","container-title":"The European Respiratory Journal","page":"1137-1143","volume":"37","issue":"5","source":"PubMed","abstract":"Obstructive sleep apnoea (OSA) affects females and males differently, and increases in prevalence with age. The aim of the present study was to characterise clinical, anthropometric and polygraphic sex differences in a large elderly OSA population. A total of 641 subjects aged 68 yrs were examined. Measurements of fat mass, using dual-energy X-ray absorptiometry (DEXA) and polygraphy, were obtained in all subjects. An apnoea/hypopnoea index (AHI) of >15 events·h?? identified the presence of OSA. OSA was diagnosed in 57% of the sample, 34% having a mild form and 23% having an AHI of >30 events·h??. Females with OSA exhibited a lower AHI, less severe hypoxaemia and greater peripheral fat mass, and frequently reported anxiety and depression. Comparison of females with and without OSA did not reveal significant differences in clinical, anthropometric and DEXA data. After adjustment for body mass index, hypertension, diabetes, smoking, anxiety and depression, logistic regression analysis revealed that the presence of hypertension was significantly associated with OSA risk in females (OR 1.52, p = 0.04). In a general community healthy population, the prevalence of undiagnosed OSA in females increases with age, with a risk similar to that in males. In females, the clinical spectrum, anthropometric data and fat distribution appear to be more sex-related than OSA-dependent. The occurrence of OSA contributes to hypertensive risk in elderly females.","DOI":"10.1183/09031936.00043210","ISSN":"1399-3003","note":"PMID: 20817711","journalAbbreviation":"Eur. Respir. J.","language":"eng","author":[{"family":"Sforza","given":"E."},{"family":"Chouchou","given":"F."},{"family":"Collet","given":"P."},{"family":"Pichot","given":"V."},{"family":"Barthélémy","given":"J. C."},{"family":"Roche","given":"F."}],"issued":{"date-parts":[["2011",5]]}}}],"schema":""} (29). The largest to date population based study conducted in Switzerland which used a more sensitive type 2 sleep study (unsupervised full polysomnography) found OSA (AHI ≥5) in 84% of people aged 60-85 years ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"zf92U5If","properties":{"formattedCitation":"(30)","plainCitation":"(30)","noteIndex":0},"citationItems":[{"id":1190,"uris":[""],"uri":[""],"itemData":{"id":1190,"type":"article-journal","title":"Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study","container-title":"The Lancet. Respiratory Medicine","page":"310-318","volume":"3","issue":"4","source":"PubMed","abstract":"BACKGROUND: Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample.\nMETHODS: Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index.\nFINDINGS: The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292).\nINTERPRETATION: The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised.\nFUNDING: Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.","DOI":"10.1016/S2213-2600(15)00043-0","ISSN":"2213-2619","note":"PMID: 25682233\nPMCID: PMC4404207","title-short":"Prevalence of sleep-disordered breathing in the general population","journalAbbreviation":"Lancet Respir Med","language":"eng","author":[{"family":"Heinzer","given":"R."},{"family":"Vat","given":"S."},{"family":"Marques-Vidal","given":"P."},{"family":"Marti-Soler","given":"H."},{"family":"Andries","given":"D."},{"family":"Tobback","given":"N."},{"family":"Mooser","given":"V."},{"family":"Preisig","given":"M."},{"family":"Malhotra","given":"A."},{"family":"Waeber","given":"G."},{"family":"Vollenweider","given":"P."},{"family":"Tafti","given":"M."},{"family":"Haba-Rubio","given":"J."}],"issued":{"date-parts":[["2015",4]]}}}],"schema":""} (30). Previous prospective studies assessed the prevalence of OSA among POAG patients but had important methodological limitations related to small sample sizes, pre-selecting patients based on symptoms, including historic control groups, using only low-grade sleep tests or indeed just questionnaires to assess for possible OSA ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ag6f95njb2","properties":{"formattedCitation":"(19\\uc0\\u8211{}22,31)","plainCitation":"(19–22,31)","noteIndex":0},"citationItems":[{"id":256,"uris":[""],"uri":[""],"itemData":{"id":256,"type":"article-journal","title":"High prevalence of sleep-disordered breathing in patients with primary open-angle glaucoma","container-title":"Acta Ophthalmologica Scandinavica","page":"638-641","volume":"78","issue":"6","source":"PubMed","abstract":"PURPOSE: Elevated intraocular pressure and systemic hemodynamic changes are main risk factors in primary open-angle glaucoma (POAG). Sleep-disordered breathing (SDB) characterized by snoring, excessive daytime sleepiness and insomnia is accompanied by large swings in blood pressure and repetitive hypoxic periods during sleep. The aim of this study was to evaluate whether there is any relationship between SDB and POAG.\nMETHODS: Consecutively, 212 outpatients with POAG and 218 outpatients without POAG were recruited. Both eyes were examined. An interviewer-administered semi-structured questionnaire was used to collect SDB-related symptoms.\nRESULTS: After controlling for age, relative to control group, POAG patients showed a high prevalence of snoring (47.6%, p=0.04), snoring plus, excessive daytime sleepiness (27.3%, p=0.01) and snoring plus, excessive daytime sleepiness, plus insomnia (14.6%, p=0.01).\nCONCLUSION: We found a high prevalence of SDB in patients with POAG. Chronic hemodynamic changes and recurrent severe hypoxia resulting from SDB may contribute to anoxic optic nerve damage, implicated in glaucoma.","ISSN":"1395-3907","note":"PMID: 11167222","journalAbbreviation":"Acta Ophthalmol Scand","language":"eng","author":[{"family":"Onen","given":"S. H."},{"family":"Mouriaux","given":"F."},{"family":"Berramdane","given":"L."},{"family":"Dascotte","given":"J. C."},{"family":"Kulik","given":"J. F."},{"family":"Rouland","given":"J. F."}],"issued":{"date-parts":[["2000",12]]}},"label":"page"},{"id":277,"uris":[""],"uri":[""],"itemData":{"id":277,"type":"article-journal","title":"Primary Open-Angle Glaucoma Is Associated with Sleep Apnea Syndrome","container-title":"Ophthalmologica","page":"115-118","volume":"214","issue":"2","source":"","abstract":"<i>Introduction:</i> The etiology of primary open-angle glaucoma remains unclear. Various risk factors, including vascular abnormalities, have been associated with this disease. Sleep-asso","DOI":"10.1159/000027478","ISSN":"0030-3755, 1423-0267","note":"PMID: 10720914","journalAbbreviation":"OPH","language":"english","author":[{"family":"Mojon","given":"Daniel S."},{"family":"Hess","given":"Christian W."},{"family":"Goldblum","given":"David"},{"family":"B?hnke","given":"Matthias"},{"family":"K?rner","given":"Fritz"},{"family":"Mathis","given":"Johannes"}],"issued":{"date-parts":[["2000"]]}},"label":"page"},{"id":258,"uris":[""],"uri":[""],"itemData":{"id":258,"type":"article-journal","title":"Sleep disorders: a risk factor for normal-tension glaucoma?","container-title":"Journal of Glaucoma","page":"177-183","volume":"10","issue":"3","source":"PubMed","abstract":"PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related breathing disorders by polysomnography in patients with normal-tension glaucoma (NTG).\nPATIENTS AND METHODS: This comparative case series included 23 patients with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep history was obtained and determined to be positive or negative. Polysomnography was offered for patients with a positive sleep history. Prevalence of a positive sleep history and prevalence of sleep disorders were the main outcome measures.\nRESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23 patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG and four of six NTG suspects with a positive sleep history chose to undergo polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects undergoing polysomnography were diagnosed with a sleep disorder. Five patients with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The one comparison patient with a positive sleep history had upper airway resistance syndrome by polysomnography.\nCONCLUSIONS: Sleep-disturbed breathing may be a risk factor for NTG. Although we do not provide evidence for a cause-and-effect relationship, various physiologic factors produced by sleep-disturbed breathing may play a significant role in the pathogenesis of this optic neuropathy. We recommend obtaining a sleep history from patients with NTG and performing polysomnography in those patients with sleep disturbance symptoms.","ISSN":"1057-0829","note":"PMID: 11442179","title-short":"Sleep disorders","journalAbbreviation":"J. Glaucoma","language":"eng","author":[{"family":"Marcus","given":"D. M."},{"family":"Costarides","given":"A. P."},{"family":"Gokhale","given":"P."},{"family":"Papastergiou","given":"G."},{"family":"Miller","given":"J. J."},{"family":"Johnson","given":"M. H."},{"family":"Chaudhary","given":"B. A."}],"issued":{"date-parts":[["2001",6]]}},"label":"page"},{"id":257,"uris":[""],"uri":[""],"itemData":{"id":257,"type":"article-journal","title":"Normal-tension glaucoma and obstructive sleep apnea syndrome: a prospective study","container-title":"BMC ophthalmology","page":"27","volume":"14","source":"PubMed","abstract":"BACKGROUND: Today, identified risk factors for normal-tension glaucoma (NTG) include abnormal ocular blood flow, abnormal blood coagulation, systemic hypotension, ischemic vascular disorders, and autoimmune diseases. However, pathogenesis of the condition remains unclear. On the other hand, there are also a few studies suggesting that the obstructive sleep apnea syndrome (OSAS) may compromise optic nerve head perfusion and cause glaucomatous optic neuropathy by creating transient hypoxemia and increasing vascular resistance. In this study, we evaluated the possible association between OSAS and NTG.\nMETHODS: We recruited 24 patients with NTG and 24 age and sex matched controls who were also similar for systemic risk factors such as diabetes mellitus (DM), hypertension (HT) and hypercholesterolemia. All patients and controls underwent over-night polysomnography (PSG) for the diagnosis of OSAS and calculation of Apnea-Hypopnea Index (AHI).\nRESULTS: Patients and controls were statistically similar in terms of age, sex, gender, smoking, systemic risk factors, neck circumference and body mass index. The subjects with AHI?≥?20 were accepted as OSAS. Ten (41.7%) of 24 patients with NTG and 3 (12.5%) of 24 controls had OSAS (p < 0.05).\nCONCLUSIONS: The prevalence of OSAS was higher in patients with NTG and the difference between patient and control groups was statistically significant (p < 0.05).","DOI":"10.1186/1471-2415-14-27","ISSN":"1471-2415","note":"PMID: 24612638\nPMCID: PMC3975309","title-short":"Normal-tension glaucoma and obstructive sleep apnea syndrome","journalAbbreviation":"BMC Ophthalmol","language":"eng","author":[{"family":"Bilgin","given":"Gorkem"}],"issued":{"date-parts":[["2014",3,10]]}},"label":"page"},{"id":260,"uris":[""],"uri":[""],"itemData":{"id":260,"type":"article-journal","title":"Prevalence of nocturnal oxygen desaturation and self-reported sleep-disordered breathing in glaucoma","container-title":"Journal of Glaucoma","page":"114-118","volume":"18","issue":"2","source":"PubMed","abstract":"PURPOSE: To evaluate the prevalence of nocturnal oxygen desaturation and sleep-disordered breathing symptoms within a glaucoma population.\nPATIENTS AND METHODS: One hundred and twelve subjects (glaucoma=52, control=60) aged between 45 and 80 years were recruited for the study. Clinical assessment included overnight ambulatory pulse oximetry monitoring and administration of a self-reported sleep-disordered breathing questionnaire.\nRESULTS: There were no differences in age, sex, body mass index, or prevalence of systemic hypertension between the groups. The mean oxygen desaturation index of the glaucoma group (8.6) did not differ significantly from that of the control group (9.6) (P=0.715). The prevalence of moderate to severe respiratory dysfunction (oxygen desaturation index >20) in the glaucoma group (17%) was similar to that in the control group (12%) (P=0.463). The severity of sleep-disordered breathing symptoms was similar between the groups (P=0.157).\nCONCLUSIONS: No statistically significant association was found between glaucoma and either nocturnal oxygen desaturation or sleep-disordered breathing. Although this study cannot exclude the possibility of either impaired optic nerve head autoregulation or hypoxic damage occurring secondary to sleep apnea syndrome, the findings do not support the routine use of pulse oximetry in the workup of individuals with glaucoma.","DOI":"10.1097/IJG.0b013e318179f80c","ISSN":"1536-481X","note":"PMID: 19225346","journalAbbreviation":"J. Glaucoma","language":"eng","author":[{"family":"Roberts","given":"Timothy V."},{"family":"Hodge","given":"Chris"},{"family":"Graham","given":"Stuart L."},{"family":"Burlutsky","given":"George"},{"family":"Mitchell","given":"Paul"}],"issued":{"date-parts":[["2009",2]]}},"label":"page"}],"schema":""} (19–22,31). Most of these studies suggested that OSA may be more common in patients with POAG but Roberts et al. who performed nocturnal oximetry on the largest previously published sample (52 POAG patients and 60 control subjects) found no significant differences in SDB prevalence. In their study, 17% of POAG subjects and 12% of controls were diagnosed with SDB based on a 4% oxygen desaturation index (ODI) above 20. Our study has the added value of a larger sample size, multichannel sleep tests which allowed us to assess SDB more accurately and a concurrent control group who had glaucoma excluded based on a detailed ocular examination. Although, it has been suspected that OSA may be particularly relevant in NTG where retinal ganglion cell apoptosis seems less IOP dependent, in our study the prevalence rates of OSA were not different when patients with NTG and HTG were compared. We have found no previous studies which directly compared OSA burden between patients with NTG and HTG. To further explore the relationship between OSA and POAG we examined potential associations between AHI and RNFL thickness. Despite adjusting for factors which were likely to have a dominant effect on RNFL thickness, including IOP, we have not found AHI to be a predictor of RNFL thinning in POAG patients or in the control group. Furthermore, the RNFL thickness was similar when people with moderate to severe OSA were compared with participants without OSA separately in both groups. Previous studies have assessed RNFL thickness in relation to OSA in people with otherwise healthy eyes. Most reported thinner RNFL in people with OSA as summarized in three recent meta-analyses ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"a2ems3gqo8f","properties":{"formattedCitation":"(32\\uc0\\u8211{}34)","plainCitation":"(32–34)","noteIndex":0},"citationItems":[{"id":68,"uris":[""],"uri":[""],"itemData":{"id":68,"type":"article-journal","title":"Retinal nerve fiber layer thickness changes in obstructive sleep apnea syndrome: a systematic review and Meta-analysis","container-title":"International Journal of Ophthalmology","page":"1651-1656","volume":"9","issue":"11","source":"PubMed Central","abstract":"AIM\nTo evaluate the retinal nerve fiber layer (RNFL) thickness changes in patients with obstructive sleep apnoea syndrome (OSAS), and detect possible prevalence of glaucoma in this population.\n\nMETHODS\nComprehensive studies were conducted on the Cochrane Library, PubMed and Embase through March, 2015. Only studies that fit the selection criteria about RNFL and OSAS would be included. For the measures, we calculated the 95% confidence interval (CI) and weighted mean differences (WMD). The systematic review and Meta-analysis was performed by RevMan 5.2 software.\n\nRESULTS\nNine case-control studies were analyzed containing a total of 1086 cases and 580 controls. Average RNFL thickness in OSAS was reduced significantly compared with healthy controls in random effects model (WMD=-2.56, 95% CI: -4.82 to -0.31, P =0.003, I2=57%). A significant RNFL thickness reduction were found between the two groups in inferior quadrant (WMD=-3.11, 95% CI: -5.53 to -0.69, P=0.01), superior quadrant (WMD=-2.37, 95%CI: -4.7 to 0.04, P=0.05). In nasal quadrant (WMD=-2.54, 95% CI: -6.53 to 1.45, P=0.21) and temporal quadrant (WMD=-1.26, 95% CI: -2.19 to 0.47, P=0.15) there was no difference of RNFL thickness between the two groups.\n\nCONCLUSION\nThe results show that RNFL thickness is lower in patients with moderate or severe OSAS than in normal subjects or patients with mild OSAS according to the nine homogeneity studies.","DOI":"10.18240/ijo.2016.11.19","ISSN":"2222-3959","note":"PMID: 27990371\nPMCID: PMC5145096","title-short":"Retinal nerve fiber layer thickness changes in obstructive sleep apnea syndrome","journalAbbreviation":"Int J Ophthalmol","author":[{"family":"Wang","given":"Jia-Song"},{"family":"Xie","given":"Hua-Tao"},{"family":"Jia","given":"Ye"},{"family":"Zhang","given":"Ming-Chang"}],"issued":{"date-parts":[["2016",11,18]]}},"label":"page"},{"id":247,"uris":[""],"uri":[""],"itemData":{"id":247,"type":"article-journal","title":"Obstructive Sleep Apnea and Retinal Nerve Fiber Layer Thickness: A Meta-analysis","container-title":"Journal of Glaucoma","page":"e413-418","volume":"25","issue":"4","source":"PubMed","abstract":"STUDY OBJECTIVES: The association between obstructive sleep apnea syndrome (OSAS) and retinal nerve fiber layer (RNFL) thickness has been examined in many studies. However, the findings are inconsistent. Our goal is to evaluate the association between OSAS and RNFL thickness by performing a meta-analysis.\nMETHODS: We conducted a PubMed database search in November 2014 to identify studies on OSAS and RNFL. Reference lists of retrieved articles were also reviewed. A fixed-effects model was used to compute the summary mean difference (MD).\nRESULTS: Six studies involving 1034 eyes were included in the meta-analysis. The overall combined MD of RNFL in OSAS patients compared with control participants was -2.03 ?m [95% confidence interval (CI), -3.67 to -0.4; P=0.01]. The overall combined MDs of RNFL thickness in relation to moderate OSAS and severe OSAS were -2.49 ?m (95% CI: -4.54 to -0.44; P=0.02) and -6.36 ?m (95% CI: -8.4 to -4.32; P<0.001). But no significant difference was observed in mild OSAS; the combined MD was -2.05 ?m (95% CI: -4.23 to 0.13; P=0.07). Association was also observed in OSAS and RNFL thickness of the inferior quadrant, with a combined MD of -3.31 ?m (95% CI: -6.19 to -0.42; P=0.02).\nCONCLUSIONS: This meta-analysis provides evidence that OSAS is associated with RNFL thickness. Furthermore, it was observed that the greater the severity of OSAS, the greater the loss of RNFL. Among the 4 quadrants observed, the most affected quadrant was the inferior quadrant, and the least affected was the temporal quadrant. OSAS may have an impact on changes in RNFL and therefore more attention should be paid to patients with this condition.","DOI":"10.1097/IJG.0000000000000349","ISSN":"1536-481X","note":"PMID: 26550970","title-short":"Obstructive Sleep Apnea and Retinal Nerve Fiber Layer Thickness","journalAbbreviation":"J. Glaucoma","language":"eng","author":[{"family":"Zhao","given":"Xiao-Jing"},{"family":"Yang","given":"Cheng-Cheng"},{"family":"Zhang","given":"Jie-Chang"},{"family":"Zheng","given":"Hui"},{"family":"Liu","given":"Ping-Ping"},{"family":"Li","given":"Qin"}],"issued":{"date-parts":[["2016",4]]}},"label":"page"},{"id":248,"uris":[""],"uri":[""],"itemData":{"id":248,"type":"article-journal","title":"Changes in Retinal Nerve Fiber Layer Thickness in Obstructive Sleep Apnea/Hypopnea Syndrome: A Meta-Analysis","container-title":"Ophthalmic Research","page":"57-67","volume":"56","issue":"2","source":"PubMed","abstract":"PURPOSE: To evaluate and compare changes in retinal nerve fiber layer (RNFL) thickness in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS).\nMETHODS: The Cochrane Library, Medline, and Embase were screened using our key words. Results were carefully reviewed to ensure that the included studies met the inclusion/exclusion criteria, and the quality of the studies was assessed using the Newcastle-Ottawa Scale. All included studies categorized patients with OSAHS into 3 groups (mild, moderate, and severe), and measured average and 4-quadrant (temporal, superior, nasal, and inferior) RNFL thickness. All studies included a healthy control group. The weighted mean differences and 95% confidence intervals were calculated for the continuous outcomes.\nRESULTS: Ten case-control studies were included in the meta-analysis, consisting of a total of 811 OSAHS group and 868 healthy eyes. A meta-analysis of the data showed that the average RNFL thicknesses in the mild, moderate, and severe OSAHS groups were significantly decreased compared to healthy controls. Additionally, RNFL thickness was significantly reduced in all but the temporal quadrant in the moderate and severe OSAHS groups when compared to healthy controls.\nCONCLUSIONS: On the basis of these results, we suggest that peripapillary RNFL thickness as measured by optical coherence tomography could be a useful tool to monitor and assess the severity of OSAHS in patients. Further studies are required in order to differentiate these RNFL changes from glaucomatous changes. This has not been properly examined in any of the studies we were able to identify.","DOI":"10.1159/000444301","ISSN":"1423-0259","note":"PMID: 27198559","title-short":"Changes in Retinal Nerve Fiber Layer Thickness in Obstructive Sleep Apnea/Hypopnea Syndrome","journalAbbreviation":"Ophthalmic Res.","language":"eng","author":[{"family":"Yu","given":"Ji-Guo"},{"family":"Mei","given":"Zhong-Ming"},{"family":"Ye","given":"Ting"},{"family":"Feng","given":"Yi-Fan"},{"family":"Zhao","given":"Fang"},{"family":"Jia","given":"Jun"},{"family":"Fu","given":"Xun-An"},{"family":"Xiang","given":"Yi"}],"issued":{"date-parts":[["2016",7]]}},"label":"page"}],"schema":""} (32–34). The relationship between AHI, or other markers of OSA, and RNFL was rarely examined in the source papers for these meta-analyses, and when it was the models were not adjusted for other important RNFL predictors ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"TYqKeBzO","properties":{"formattedCitation":"(35,36)","plainCitation":"(35,36)","noteIndex":0},"citationItems":[{"id":282,"uris":[""],"uri":[""],"itemData":{"id":282,"type":"article-journal","title":"Optic disc and retinal nerve fiber layer parameters as indicators of neurodegenerative brain changes in patients with obstructive sleep apnea syndrome","container-title":"Sleep and Breathing","page":"95-102","volume":"18","issue":"1","source":"link.","abstract":"PurposeRetina is a unique part of the central nervous system (CNS) for visualizing the processes of axonal and neuronal degeneration. Optical coherence tomography (OCT) allows direct visualization and measurement of retinal nerve fiber layer (RNFL) thickness, macular volume, and optic disc (OD) parameters. One of the disorders associated with atrophy in different brain regions is obstructive sleep apnea syndrome (OSAS). In the present study, we aimed to determine OD and RNFL changes measured by OCT for investigating the progress of neurodegeneration development in OSAS, excluding all the other conditions that can directly affect RNFL thickness and optic nerve parameters.MethodsBoth eyes of 101 patients with OSAS and 20 controls were investigated by OCT. Full-night polysomnography (PSG) and ophthalmologic examination including automated visual field (VF) examination and OCT were performed in all of the patients.ResultsAccording to the OSAS grading, patients were grouped as mild (n = 15), moderate (n = 27), and severe (n = 59). We found significant decrease in RNFL thickness only in the patients with severe OSAS compared with the other groups and decreased macular ganglion cell thickness in the severe OSAS group compared with the control group. VF parameters were significantly worsened in all the OSAS subgroups compared to the control group. We found different data such as normal or increased optic nerve parameters as result of subtle OD edema, which may mask possible peripapillar axonal loss.ConclusionsWe think that evaluation of neurodegeneration in OSAS is not always possible by examining OD and RNFL because there are difficulties due to the confounding issues of cerebral atrophy and OD edema.","DOI":"10.1007/s11325-013-0854-z","ISSN":"1520-9512, 1522-1709","journalAbbreviation":"Sleep Breath","language":"en","author":[{"family":"Huseyinoglu","given":"Nergiz"},{"family":"Ekinci","given":"Metin"},{"family":"Ozben","given":"Serkan"},{"family":"Buyukuysal","given":"Cagatay"},{"family":"Kale","given":"Murat Yildirim"},{"family":"Sanivar","given":"Hilal Safak"}],"issued":{"date-parts":[["2014",3,1]]}},"label":"page"},{"id":246,"uris":[""],"uri":[""],"itemData":{"id":246,"type":"article-journal","title":"Retinal nerve fibre layer measurements are reduced in patients with obstructive sleep apnoea syndrome","container-title":"Eye (London, England)","page":"575-579","volume":"19","issue":"5","source":"PubMed","abstract":"PURPOSE: To determine the retinal nerve fibre layer (RNFL) thickness in patients with obstructive sleep apnoea syndrome (OSAS) in order to investigate the possibility of detecting early signs of glaucoma in this population.\nMETHODS: A total of 66 consecutive patients admitted for polysomnographic evaluation of suspected OSAS. Patients underwent an overnight sleep study in an effort to diagnose and determine the severity of OSAS. Patients who had the disease were classified as having mild and severe OSAS, while patients who did not have the disease were classified as controls. All patients received physical, neurological, and ophthalmological evaluation including visual acuity, slit-lamp examination, Goldmann applanation tonometry, gonioscopy with a three mirror contact lens, and fundus examination. After these examinations, patients with glaucoma and patients who had ophthalmological and/or systemic disease known to affect RNFL thickness were excluded from the study. The RNFL thickness was assessed with a scanning laser polarimeter (Nerve Fiber Analyzer GDx, Laser Diagnostic Technologies Inc., San Diego, CA, USA).\nRESULTS: A total of 34 patients with obstructive sleep apnoea (19 mild, 15 severe) and 20 age-matched controls were included in the study. The thickness of RNFL was reduced in patients with OSAS compared to controls. The decrease in RNFL was found to be correlated with the severity of sleep apnoea (r=0.78, P=0.01).\nCONCLUSIONS: The sleep apnoea syndrome is correlated with a proportional decrease in the RNFL. Decreased ocular perfusion related to hypoxia and vasospasm associated with OSAS may cause RNFL thinning, which may precede clinically detectable glaucoma.","DOI":"10.1038/sj.eye.6701582","ISSN":"0950-222X","note":"PMID: 15332101","journalAbbreviation":"Eye (Lond)","language":"eng","author":[{"family":"Kargi","given":"S. H."},{"family":"Altin","given":"R."},{"family":"Koksal","given":"M."},{"family":"Kart","given":"L."},{"family":"Cinar","given":"F."},{"family":"Ugurbas","given":"S. H."},{"family":"Ayoglu","given":"F."}],"issued":{"date-parts":[["2005",5]]}},"label":"page"}],"schema":""} (35,36). Nevertheless, our findings cannot be simply compared with the previous studies due to a different cohort of subjects in our control group. In contrast with the previous studies which exclusively recruited people who presented to sleep centres with OSA symptoms (and therefore may have represented enriched samples of patients also at higher risk of systemic effects of OSA), our control group consisted of a population-based sample of largely asymptomatic participants screened for OSA. Thus, it is possible that patients with only certain OSA phenotypes are at risk of aggravated RNFL loss. The main limitation of our study is its cross-sectional design. Although we have recruited a representative sample of patients with all stages of glaucoma severity we cannot rule out the possibility that OSA contributes to POAG progression. This can be determined only in a longitudinal study. We invited all consecutive glaucoma patients without prior knowledge of their sleep history but, since 58% of those invited declined study participation, we cannot exclude selection bias. Further, because of the nature of our recruitment pathways in the control group we could not ascertain the proportion of potentially eligible subjects who were invited via the glaucoma patients but declined to take part in the study. Therefore, we cannot compare the actual recruitment rates between the groups. It could be argued that glaucoma patients were more likely to take part in the study even though they had no sleep related symptoms because of the long-term relationship with the health care provider and perceived benefits of contributing to a research into the disease which affected them. On the contrary, the control subjects may have been incentivised to enrol only if they had relevant sleep complaints. This could lead to underestimation of OSA prevalence in the POAG group and its overestimation in the control group. However, against this hypothesis are no differences detected between the groups in the ESS which assesses subjective sleepiness, a cardinal symptom of OSA, and the STOP-BANG questionnaire which estimates the likelihood of OSA and incorporates questions about snoring, tiredness and witnessed apnoeas. It is also worth noting that spouses of glaucoma patients who took part in this study constituted 85% (spouses and friends-99%) of the control group and there were no recruits among relatives of those glaucoma patients who decline study participation. This indicates that glaucoma patients and their spouses were willing to contribute to this research as couples and this may have helped to reduce the risk of selection bias at least for the between group comparisons. If the selection bias did occur, most likely it would have affected the OSA prevalence rates in both groups in the same direction, although we cannot exclude other possible scenarios. Finally, as over 90% of our patients were of white European origin our findings are not generalizable to other ethnic backgrounds. In conclusion, based on the prevalence analysis and assessment of associations between OSA and POAG markers we have found no evidence to support the suspected relationship between these two conditions. Therefore, we do not recommend the systematic screening of POAG patients for OSA. Future longitudinal studies should address the question of whether untreated OSA is associated with faster rates of glaucoma progression. AcknowledgmentsThe authors acknowledge Paula Turnbull and Aaron Woods from the Research and Development Department at the North West Anglia Foundation Trust for their help with recruitment and Samantha Moir from the Royal Papworth Hospital for scoring the sleep studies. The authors also acknowledge Professor Russell Foster of the Nuffield Department of Clinical Neurosciences, University of Oxford and Mrs. Susan Downes, Consultant? Ophthalmic Surgeon at the Oxford Eye Hospital for?their involvement with the study's grant application and constructive critique of the study's design.References: ADDIN ZOTERO_BIBL {"custom":[]} CSL_BIBLIOGRAPHY 1. Flaxman SR, Bourne RRA, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, et al. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob Health. 2017 Dec;5(12):e1221–34. 2. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, et al. 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Eye Lond Engl. 2005 May;19(5):575–9. Figures Legend Figure 1. Flow diagram of the study.Abbreviations: POAG=primary open-angle glaucoma, OHT=ocular hypertension, OSA=obstructive sleep apnoea, CSA=central sleep apnoea, CPAP=continuous positive airway pressure.Figure 2. Distribution of participants in the matched POAG and the control group according to OSA severity.Definition of abbreviations: POAG=primary open-angle glaucoma, OSA=obstructive sleep apnoea.Figure 3. Severity of functional damage among recruited POAG patients based on the Enhanced Glaucoma Staging System (eGSS).Figure 4. Distribution of AHI across POAG severity stages (Error bars represent 95% CI). Definition of abbreviations: AHI=apnoea-hypopnea index, POAG=primary-open-angle glaucoma.Figure 1. Flow diagram of the study. Abbreviations: POAG=primary open angle glaucoma, OHT=ocular hypertension, OSA=obstructive sleep apnoea, CSA=central sleep apnoea, CPAP=continuous positive airway pressure. Figure 2. Distribution of participants in the matched POAG and the control group according to OSA severity. Definition of abbreviations: POAG=primary open-angle glaucoma, OSA=obstructive sleep apnoea.Figure 3. Severity of functional damage among recruited POAG patients (unmatched group) based on the Enhanced Glaucoma Staging System (eGSS). Figure 4. Distribution of AHI across POAG severity stages (Error bars represent 95% CI). Data analysed in an unmatched POAG group. Definition of abbreviations: AHI=apnoea-hypopnea index, POAG=primary-open angle glaucoma.Supplement 1. Predictors of OSA (AHI≥5) in the entire cohort based on univariate logistic regression analyses. Predictor Nagelkerke R2OR95% CIP value Age 0.0551.051.023-1.0710.000Male sex0.0210.60.4-0.90.013BMI0.121.161.1-1.230.000Neck size0.091.161.09-1.20.000Diabetes0.0180.450.22-0.920.028Definition of abbreviations: OSA=obstructive sleep apnoea, AHI-apnoea-hypopnoea index, BMI=body mass indexSupplement 2. Missing data and exclusions for the analysis of associations between AHI and ocular parameters. Reason for exclusion POAG group N=235Control group N=160Treated OSA, n (%)2 (0.85)0 (0)Ocular comorbidities, n (%)17 (7)7 (4.4)Inadequate quality OCT images, n (%)(relevant to all RNFL regression models) 14 (6)7 (4.4)Missing at least one covariate, n (%)(relevant to fully adjusted RNFL regression models) 13 (5.5)15 (9.4)Definition of abbreviations: AHI=apnoea hypopnea index, POAG=primary open-angle glaucoma, OCT=ocular coherence tomography, OSA=obstructive sleep apnoea, RNFL= Retinal Nerve Fibre Layer.Table 1. Baseline Characteristics of Participants in Relation to OSA.All POAG patients (n=235)Control Group(n=160)P value* Matched POAG patients (n=160)P value?Male sex, n (%)Age, yr, (sd)White European ethnicity, n (%)BMI, kg/m2, (IQR)Neck size, cm, (IQR)135 (57)70 (13)227 (97)27.3 (5.2)40 (6.0)69 (43)68.5 (11.8)156 (98)27.3 (6.4)39 (5.9)0.0050.0560.60.390.1173 (46)69 (11)154 (96)27.1 (5.6)39 (6.3)0.650.920.520.520.91Diabetes type 2, n (%)Hypertension, n (%)Ischemic heart disease, n (%)CVA, n (%)Atrial Fibrillation, n (%)28 (12)106 (45)25 (11)12 (5)14 (6)13 (8)74 (46)15 (9)7 (4)14 (9)0.230.820.680.740.2913 (8)74 (46)16 (10)5 (3)11 (7)1.01.00.850.560.53AHI, per h, (IQR)ODI, per h, (IQR)T90, %, (IQR)MeanSpO2, %, (IQR)MinSpO2, %, (IQR)Sleep Time (self-reported), h, (IQR)Time in Bed (device recorded), h, (IQR)ESS score, (IQR)ESS score>10, n (%)OSAS, n (%)STOP-Bang score 6 (10.8)4.1 (7.5)17 (82)93 (1.9)85 (6)7.3 (1.5)7.6 (1.2)6 (6)31 (13)19 (8)4 (3)5.7 (9.7)3.3 (7.1)15 (76)92.8 (2.0)86 (6.0)7.3 (1.3)7.6 (1.4)5 (6.0)26 (16)14 (9)3 (3)0.260.290.480.980.50.550.420.920.40.840.195.2 (8.5)3.7 (6.4)15 (80)93 (2.0)86 (6.0)7.3 (1.5)7.6 (1.2)5 (5)16 (10)10 (6)3 (3)0.960.790.760.720.730.920.280.350.10.40.8 *For the difference between All POAG patients and Control Group ?For the difference between Matched POAG patients and Control Group Definition of abbreviations: BMI=body mass index, CVA=cerebrovascular accident, AHI=apnoea-hypopnoea index (the measurement of reduction and cessation of airflow per hour), ODI=oxygen desaturation index ( the number of 4% oxygen dip per hour), T90=time spent with oxygen saturation less than 90%, MeanSpO2=mean oxygen saturation, MinSpO2=minimum oxygen saturation, ESS=Epworth Sleepiness Scale, OSAS=obstructive sleep apnoea syndrome (AHI≥5 and ESS>10), STOP-Bang is a questionnaire used to evaluate the likelihood of OSA. It consists of questions about: snoring, tiredness/sleepiness/fatigue, witnessed apnoeas, hypertension, BMI, age, neck circumference and gender. The minimum score is 0 and the maximum 8. Table 2. Summary of the linear regression models for the associations between AHI and global RNFL thickness. All models were constructed in unmatched groups following exclusions described in Supplement 3. ModelNAdjusted R2Betat value P value 95% CIPOAGUnadjusted: AHI2020.0040.0951.40.18-1.6 to 8.5Fully adjusted:1890.160.000 AHI0.0030.410.97-0.18 to 0.19 IOPpeak-0.23-3.20.002-0.77 to -0.18 IOPcurrent0.293.90.000 0.48 to 1.5 Hysteresis 0.243.00.003 0.55 to 2.6 CVS-0.13-1.90.061-8.10 to 0.19 Male sex0.121.80.074-3.50 to 7.6 Age 0.0110.1440.9 -0.23 to 0.26 CCT0.0480.650.52-0.04 to 0.08 SER0.0580.770.44-0.46 to 1.1Controls Unadjusted: AHI146.008-0.12-1.40.15-7.4 to 1.1Fully adjusted: 1310.20.000 AHI0.010.130.9-0.14 to 0.16 SER0.344.40.0000.9 to 2.4 Male sex0.273.40.0012.4 to 9.2 Age-0.16-2.10.041 -3.8 to -0.01Definition of abbreviations: RNFL=retinal nerve fibre layer, AHI=apnoea-hypopnea index, N=number of subjects in the model (subjects without missing data), CI=confidence interval, AHI=apnoea-hypopnea index, IOPpeak=highest ever recorded intraocular pressure, IOPcurrent=intraocular pressure recorded at the study visit, SER= Spherical Equivalent Refraction , CCT=central corneal thickness, CVS=cardiovascular co-morbidities (at least one of the following: diabetes, hypertension, ischemic heart disease, atrial fibrillation, cerebro-vascular accident, heart failure, over 20 pack year smoking historyTable 3. Retinal Nerve Fibre Layer thickness according to OSA status.No OSAOSAP value*Moderate to Severe OSAP value?POAG group Global RNFL (μm)62.6 (14.7)63.9 (14.3)0.5465.2 (15.2)0.37Control groupGlobal RNFL (μm)94.8 (11.1)92.5 (10.5)0.294.8 (9.9)0.99 *For the difference between No OSA (AHI<5) and OSA (AHI≥5).? For the difference between No OSA (AHI<5) and moderate to severe OSA (AHI≥15).Definition of abbreviations: OSA=obstructive sleep apnoea, RNFL= Retinal Nerve Fibre Layer. ................
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