- Email: [email protected]
Prevalence of primary open-angle glaucoma among patients with obstructive sleep apnea
Accepted Manuscript Title: Prevalence of primary open-angle glaucoma among patients with obstructive sleep apnea Author: Arthur H. Friedlander, Lindsay L. Graves, Tina I. Chang, K. Karl Kawakami, Urie K. Lee, Shannon C. Grabich, Zhuang T. Fang, Michelle R. Zeidler, JoAnn A. Giaconi PII: DOI: Reference:
S2212-4403(18)30057-9 https://doi.org/10.1016/j.oooo.2018.01.021 OOOO 1945
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received date: Revised date: Accepted date:
16-11-2017 21-12-2017 20-1-2018
Please cite this article as: Arthur H. Friedlander, Lindsay L. Graves, Tina I. Chang, K. Karl Kawakami, Urie K. Lee, Shannon C. Grabich, Zhuang T. Fang, Michelle R. Zeidler, JoAnn A. Giaconi, Prevalence of primary open-angle glaucoma among patients with obstructive sleep apnea, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2018), https://doi.org/10.1016/j.oooo.2018.01.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title Page Title: Prevalence of Primary Open-Angle Glaucoma Among Patients with Obstructive Sleep Apnea Authors: 1. Corresponding Author: Arthur H. Friedlander, DMD Associate Chief of Staff and Director of Graduate Medical Educationa Director of Quality Assurance, Hospital Dental Servicec Professor-in-Residence of Oral and Maxillofacial Surgeryb 11301 Wilshire Blvd. (14) Los Angeles, CA 90073 USA Office Phone (310) 268-3196 Fax Number (310) 268-4631 Home Phone (818) 366-5418 [email protected] 2. Lindsay L. Graves, DDS Former Oral and Maxillofacial Surgery Research Fellowa [email protected] 3. Tina I. Chang, DMD, MD Director of the Research Fellowship and Inpatient Oral and Maxillofacial Surgerya Instructor of Oral and Maxillofacial Surgeryb [email protected] 4. K. Karl Kawakami, DDS Chief of Dental Serviceb Adjunct Assistant Professor in Advanced Prosthodonticsa [email protected] 5. Urie K. Lee, DDS Oral and Maxillofacial Surgery Research Fellowa [email protected] 6. Shannon C. Grabich, PhD Epidemiologist at Gillings School of Global Public Healthd [email protected] 7. Zhuang T. Fang, MD, MSPH Clinical Professor in the Department of Anesthesiology and Perioperative Medicinec Associate Director, Stein Operating Roomc [email protected] 1
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8. Michelle R. Zeidler, MD, MS Director of the Sleep Disorders Centera Clinical Professor Medicine-Pulmonary Critical Carec Program Director – UCLA Sleep Fellowship: Division of Pulmonary, Critical Care and Sleep Medicinec [email protected] 9. JoAnn A. Giaconi, MD Chief of Ophthalmologya Associate Clinical Professor : UCLA Jules Stein Eye Institutec [email protected]
a
VA Greater Los Angeles Healthcare System 11301 Wilshire Blvd, Los Angeles, CA 90073 USA b
School of Dentistry, University of California, Los Angeles 10833 Le Conte Ave, Los Angeles, CA 90095 USA c
Ronald Reagan UCLA Medical Center 757 Westwood Plaza, Los Angeles, CA 90095 USA d
University of North Carolina at Chapel Hill
# This material is the result of work supported with resources and use of facilities at the VA Greater Los Angeles healthcare System but its contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. No conflicts of interest to disclose for any authors. ## Declarations of interest: None 891 tnuAt dA Wttc rtsbA 04 reCbCd e Wleln bdl Wttc rtsbA 6812 rtuuelAl W bsudtCuA Wttc rtsbA 99 ssunlt to Wloltlbdlu 9 ssunlt to r nelu
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Clinical Relevance: The co-occurrence of occult comorbid primary open angle glaucoma among patients with obstructive sleep apnea is substantial. Given the potential perioperative risks of heightened intraocular pressure, the status of eye health needs to be assessed before planned airway corrective surgery
Abstract Objective: Determine primary open angle glaucoma (POAG) prevalence among obstructive sleep apnea (OSA) patients because perioperative environment risks further damaging the optic nerve. Study design: Analyzed “convenience sample” referred by Sleep Medicine for oral appliances because of continuous positive pressure (CPAP) intolerance. Determined aggregate prevalence of the 3 POAG subtypes: (“classic” open angle glaucoma (COAG), normal tension glaucoma (NTG), open angle glaucoma suspect (OAGS); among the index population and compared it to that of same hospital’s general population. Similarly determined were associations between OSA severity levels (apnea-hypopnea index; AHI) and POAG subtypes. Results: Among the study sample of 225 patients with OSA (96.4% male; mean age 58.5 ± 12.3 years), 47 (20.9%) had POAG; with subtype distribution: (COAG: 12(25.5%), NTG: 8 (17.0%), OAGS: 27 (57.4%)). The POAG prevalence rate among medical center’s general population was 2.5% which was significantly less (P < .00001) than among those with
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comorbid OSA. Severity of the breathing disorder (AHI) failed to demonstrate a significant correlation to any POAG subtype (P > .05). Conclusion: The significant prevalence of POAG among OSA sufferers, suggests need for preoperative consultations from an ophthalmologist to determine eye health and possibly an anesthesiologist to avoid potential vision loss.
Introduction Oral and maxillofacial surgeons providing corrective surgery of the jaws and airway for patients with obstructive sleep apnea (OSA) are fully cognizant of the respiratory and hemodynamic derangements associated with the disorder. They may not, however, recognize that some studies have demonstrated that the associated cessation of breathing, and the resulting decrement in blood oxygen saturation levels, may trigger optic nerve damage causing comorbid primary open angle glaucoma (POAG).1-5 Specifically, this chronic ischemic environment has been linked to “classic” open angle glaucoma (COAG), in which the intraocular pressure (IOP) is > 21 mmHg, “normal tension glaucoma” (NTG), in which the IOP is ≤ 21 mm Hg, and “open-angle glaucoma suspect” (OAGS), in which IOP may be normal. COAG and NTG are both distinguished by a characteristic, progressive optic nerve atrophy (that is, loss of retinal ganglion cells and their axons) leading to visual field (VF) loss, and possibly complete blindness.6-11 Individuals with OAGS, however, do not definitively have glaucoma but have characteristics (suspicious optic nerve appearance, repeatable VF abnormalities consistent with optic nerve damage, or elevated IOP in the absence of structural or functional changes) which 4
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suggest that they are at high risk of developing the disease in the future.12,13 Recognition of all three subgroups of patients is highly desirable because intraoperative precautions may be necessary to safeguard vision. Specifically, because of the multitude of perioperative factors that can potentially further damage the optic nerve in OSA patients with occult POAG, this study was designed to answer the following clinical questions, 1) What is the aggregate prevalence of POAG among patients with OSA, 2) what is the prevalence of each of the three diagnostic subgroups, and 3) is the severity (as measured by the Apnea Hypopnea Index or AHI) of the breathing disorder related to the comorbid presence of POAG? We hypothesized that the combined (COAG, NTG, and OAGS) prevalence rate of POAG among patients with OSA would be far greater than the prevalence rate found in the general population of patients treated at the same medical center. Materials and Methods Study Design To address these research questions, the investigators designed and implemented a study based on a retrospective review of cases aggregated from selected electronic medical records (EMR).
The primary study population consisted of patients with OSA referred from the
Veterans Affairs Sleep Medicine section of the Greater Los Angeles Veterans Administration Hospital (VAGLA) to the hospital’s Dental Service for oral appliance fabrication prescribed to treat a) mild OSA that did not require the riskier nasal continuous positive pressure therapy (nCPAP), or b) to treat more severe OSA in patients non-compliant with n-CPAP therapy. This study conformed to precepts of the Declaration of Helsinki on medical protocol and ethics and was approved by the Ethical Review Board of the Veterans Affairs Greater Los Angeles
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Healthcare Systems (VA GLA). Informed consent exemption was granted given the retrospective nature of the project as well as the use of deidentified patient variables. Study Sample/Study Variables The study population (convenience sample), among whom the aggregate prevalence rate of POAG would be determined, consisted of patients with OSA that the Sleep Medicine Service referred to the Dental Service between January 1, 2009 to November 15, 2017. The inclusion criterion was a positive diagnosis for OSA on EMR that was determined by the VA Sleep Medicine Service using the American Academy of Sleep Medicine (AASM) standardized criteria following an overnight sleep study or by reviewing results obtained from an outside sleep laboratory study.14,15
Specifically, OSA was diagnosed when the patient had 5 or more
obstructive respiratory events (that is, apnea or hypopneas seen in association with a 3% desaturation and/or a respiratory effort-related arousal) per hour of sleep and an associated set of signs/symptoms (e.g. daytime sleepiness, snoring) or alternatively, ≥ 15/h of obstructive respiratory events in the absence of associated symptoms. Apneas were defined as cessation of air flow lasting ≥ 10 seconds and hypopnea as a ≥ 30% fall in airflow lasting ≥ 10 seconds in association with a ≥ 3% fall in oxygen saturation from baseline, or alternatively, a ≥ 30% decrease in airflow lasting ≥ 10 seconds and an associated arousal. Subjects having an AHI (total number of apneas and hypopneas per hour of sleep) of 5-14 were diagnosed as having “mild” OSA, of 15-29 as “moderate” OSA, and ≥30 events per hour, as “severe” OSA.14,15 The control group population among whom the prevalence rate of POAG would also be determined, consisted of the medical center’s approximate 300,000 unique inpatients and outpatients treated between October 1, 1999 and November 15, 2017.
To obtain this
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information, all EMRs with diagnostic codes for primary open-angle glaucoma (ICD-9 code: 365.11, and ICD-10 code: H40.11) were identified. A two-tailed z-test was run on the two populations and the alpha level was set at 0.05. The primary outcome of interest was a determination of the aggregate prevalence of POAG, among the dental patients receiving OSA appliance, as well as its subtypes, among OSA patients and an assessment of whether the severity level of OSA was a determining factor. Prediction models were run as linear or logistic regressions based on the categorization of outcomes. In prediction models, we used an alpha value of less than .01 to determine significance and a P value of < 0.05 was considered strongly significant. Patients were coded as positive for POAG if they were diagnosed by an ophthalmologist or optometrist with the disorder, had had surgical/laser treatment for it in the past or were currently under medical treatment for the disease (i.e. taking alpha adrenergic agonists, beta blockers, carbonic anhydrase inhibitors, cholinergic agonists, or prostaglandin analogs).16 [Excluded from study were patients having a history of ocular trauma, pseudo exfoliation, and pigment dispersion.] Patients were then classified into their subtypes: COAG if there was nerve damage and pre-treatment IOP was > 21, NTG if there was nerve damage and the pretreatment IOP was ≤ 21, and OAGS if the optic nerve, RNFL, or VF were suspicious for glaucomatous changes, and/or if there was evidence of consistently elevated IOP but without structural and functional changes. Lastly, aggregated and correlated was the relationship between the severity of the breathing disorder and a diagnosis of POAG. The diagnosis of open angle glaucoma involved a practitioner’s slit-lamp and dilated pupil examination of the optic nerve that recorded optic disc structural abnormalities (this is, 7
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cupping and rim thinning [cup-disk ratio ≥ 0.6 or cup-disc asymmetry ≥ 0.3] ± partial or complete notching ± nerve fiber layer defects), visual field abnormalities (that is, nasal step, arcuate, or paracentral scotoma), open and otherwise normal anterior chamber angles, and intraocular pressure (IOP) measured using the applanation tonometer.17 Results Between 2009 and 2017, the Dental Service received 225 consultation requests for fabrication of an oral appliance to manage OSA from the Sleep Medicine Service. The overwhelming majority (96.4%) of patients were male with a mean age of 58.5 ± 12.3 (Table 1). The severity of their OSA, as determined by AHI, denoted 42.7% with “mild” disease, 19.6% with “moderate” disease, and 37.8% with “severe” disease. Among these 225 individuals with OSA, 47 had POAG, yielding an aggregate prevalence rate of 20.9%. Among these 47 individuals, 12 (25.5%) had COAG, 8(17%) had NTG, and 27(57.4%) had OAGS (Table 2). From October 1, 1999 to November 12, 2017, the VA GLA treated 312,494 unique patients and of these 7,975 (2.5%) had POAG (subtype often not defined) (Table 3). The prevalence rate of POAG in the dental environment among OSA patients was significantly (P < 0.00001) greater than the hospital’s general population. The severity of the breathing disorder as classified by the AHI (mild, moderate, severe) was not found to be a predictor of POAG subtypes (COAG, NTG, OAGS) in our logistic regression models. Discussion
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The results of our study demonstrated that nearly 21% of patients with OSA also had one of three POAG subtypes. These results are consistent with the work of other researchers who have reported that the prevalence of POAG among patients diagnosed with OSA ranges from 7.2% to 27%.18,19 Importantly, our results are dramatically different from the 2.5% diagnosed amidst the medical center’s general population as well as the 5% reported among a “general population” of mostly male (90%) older ( > 50 years) Veterans attending another VA medical center.20 Similarly our results differ from the 2% prevalence rate denoted for the “general population” in America.21,22 The difference in the 21% POAG prevalence rates found in our sample of patients with comorbid OSA and rates found in the “general population,” the majority of whom are most likely free of OSA, most plausibly arises from the effects of hypoxia upon the optic nerve head.7-12,23 Implications for the Oral and Maxillofacial Surgeon Corrective airway and jaw surgery as a therapeutic intervention for patients solely afflicted with OSA is usually only indicated when the patient evidences intolerance to n-CPAP and/or mandibular advancement appliances. However, it is now recognized that in some patients with OSA and concomitant POAG (irrespective of subtype), n-CPAP may increase central venous pressure causing an increased resistance to aqueous outflow and resulting in increased IOP.24-26 Thus, in this unique population the indications for corrective orthognathic surgery are markedly enhanced. Furthermore, given the frequent association between the two illnesses, it is suggested that all patients being evaluated for surgical correction of sleep apnea be evaluated by an eye care professional for occult POAG and/or adequate control of the eye disease, if previously 9
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diagnosed. This is necessary because of the unique vulnerability of the optic nerve to further damage during the perioperative period due to of the eye’s reduced capacity to drain aqueous humor and compensate for acute rises in IOP. The consultative discussion between clinicians should also address the risks and benefits of administering dexamethasone to persons with POAG during the perioperative phase of airway/jaw surgery in order to minimize surgical site edema that might possibly compromise the airway. Persons with POAG are at risk of elevation of IOP when exposed to dexamethasone.27 The maxillofacial surgeon should also consult with the attending anesthesiologist, drawing particular attention to the need to minimize intraoperative elevations in IOP. Suggested strategies include positioning the patient on the operating table parallel to the floor or better yet, in a reverse Trendelenburg position.28 It is also important to prevent coughing/bucking, hypoxia and hypercapnia, especially during induction of general anesthesia and endotracheal intubation. This is a critical element because coughing, and the resulting increase in intrathoracic pressure, can lead to increases of IOP.29,30 The induction phase of anesthesia may be accomplished with any of the intravenous or volatile agents with the possible exception of ketamine, given conflicting descriptions of its effects on IOP in adult patients.31 Also to be avoided is administration of the depolarizing muscle relaxant succinylcholine, which increases IOP approximately 8-10 mm Hg for about 510 minutes after administration. The etiology underlying this elevation in IOP is in dispute; some ascribing it to an increase in extraocular muscle tone and others believing that it arises from a direct effect on choroidal blood volume or on aqueous humor formation or drainage. A non-depolarizing agent is best substituted.32 The administration of IV narcotics and lidocaine 10
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prior to direct laryngoscopy for intubation is suggested given that they effectively attenuate the reactivity of the airway and coughing response.33 It should be noted that achieving adequate depth of anesthetic level prior to tracheal intubation is the most important part of anesthetic management in the prevention of coughing, and therefore the elevation of IOP.34 It is also critically important to avoid any episodes of hypoxemia and hypercarbia during the procedure since they can precipitate increased IOP.35 Furthermore, within 30 minutes of terminating the procedure, ondansetron (an antiemetic with no direct effect on IOP) should be administered to avoid post-operative straining and vomiting which is frequently associated with an increase of IOP. The antiemetic metoclopramide however probably should not be used because of conflicting reports as to its effects on IOP.36 Additional points considered The reports of the association between OSA and POAG have not gone unchallenged. Ophthalmologists in Haifa, Israel conducted a cross-sectional study evaluating almost 230 patients with OSA and noted that the prevalence of POAG was similar to that in the general population.37 Similarly, in a nested case-control study conducted at the Veterans Affairs Medical Center in Birmingham, the researchers could not demonstrate an association between POAG and OSA after adjusting for confounding factors.38 Conclusion In conclusion, finding a significant rate of POAG among OSA patients referred to the Dental Service from the Sleep Service at the VA GLA suggests the need for surgeons planning corrective airway surgery to be cognizant of this relationship and inquire about their patients’ last 11
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visit to an eye-care professional. Patients not seen in the past 1-3 years, especially those whose sleep disorder was recently diagnosed, should be expeditiously referred for examination in order to rule out or discover concomitant eye disease; and to provide early treatment if found.39 Ocular conditions need to be discussed with members of the operating room team so that the risk of intraoperative elevation in IOP and damage to the optic nerve can be minimized.
Acknowledgement: The authors gratefully acknowledge the assistance of Susan C Rosenbluth, Ph.D., Deputy Associate Chief of Staff, Graduate Medical Education, VA Los Angeles for editing the revised manuscript.
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References 1. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd Ed. Darien, IL American Academy of Sleep Medicine 2014. 2. Selim B, Won C, Yaggi HK. Cardiovascular consequence of sleep apnea. Clin Chest Med 2010;31:203. 3. Shinmei Y, Nitta T, Saito H, Ohguchi T, Kijima R, Chin S, et al. Continuous intraocular pressure monitoring during nocturnal sleep in patients with obstructive sleep apnea syndrome. Invest Ophthalmol Vis Sci 2016;57:2824. 4. Liu S, Lin Y, Liu X. Meta-analysis of association of obstructive sleep apnea with glaucoma. J Glaucoma 2016;25:1. 5. Faridi O, Park SC, Liebmann JM, Ritch R. Glaucoma and obstructive sleep apnea syndrome. Clin Experimental Ophthalmol 2012;40:408. 6. Lin PW, Friedman M, Lin HC, Chang HW, Wilson M, Lin MC. Normal tension glaucoma in patients with OSA/hypopnea syndrome. J Glaucoma 2011;20:553. 7. Thurtell MJ, Bruce BB, Newman NJ, Biousse V. An update on idiopathic intracranial hypertension. Rev Neurol Dis 2010;7:e56. 8. Nusbaum DM, Wu SM, Frankfort BJ. Elevated intracranial pressure causes optic nerve and reginal ganglion cell degeneration in mice. Exp Eye Res 2015;136:38. 9. Kario K. Obstructive sleep apnea syndrome and hypertension: ambulatory blood pressure. Hypertens Res 2009;32:428. 10. Karakucuk S, Goktas S, Aksu M, Erdogan N, Demirci S, et al. Ocular flood flow in patients with obstructive sleep apnea syndrome. (OSAS). Graefes Arch Clin Exp Ophthalmol 2008;246:129.
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11. Goldblum D, Mathis J, Bohnke M, Bassetti C, Hess CW, Gugger M, et al. Nocturnal measurements of intraocular pressure in patients with normal-tension glaucoma and sleep apnea syndrome. Klin Monatsbl Augenheilkd 2000;216:246. 12. Tsang CS, Chong SL, Ho CK, Li MF. Moderate to severe obstructive sleep apnea is associated with a higher incidence of visual field defect. Eye 2006;20:38. 13. Chang RT, Singh K. Glaucoma suspect: diagnosis and management. Asia Pac J Ophthalmo (Phila) 2016;5:32-37. 14. Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Version 2.3. Am Acad Sleep Med 2007. 15. Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Quan SF, et al. AASM Scoring Manual Updates for 2017 (Version 2.4). J Clin Sleep Med 2017;13:665-666. 16. Feder RS, Olsen TW, Prum BE JR, Summers CG, Randall J, et al. Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern® Guidelines. Ophthalmology 2016;123:P209-36. 17. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma. JAMA 2014;311:1901-11. 18. Mojon DS, Hess CW, Goldblum D, Fleischhaur J, Koerner F, Bassetti C, et al. High prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology 1999;106:1009-12. 19. Bedel RE, Kaplan J, Heckman M, Friedrickson PA, Lin SC. Prevalence of glaucoma in patients with obstructive sleep apnea – a cross-sectional case series. Eye (Lond) 2008;22:1105-9. 20. Boyle-Walker M, Semes LP, Clay OJ, Liu L, Fuhr P. Sleep apnea syndrome represents a risk for glaucoma in a veterans’ affairs population. ISRN Ophthalmol 2011; Article ID: 920767
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21. Provini F, Vetrugno R, Lugaresi E, Montagna P. Sleep-related breathing disorders and headache. Neuro Sci 27 (2 suppl): 2006;S149-52. 22. Friedman DS, Wolfs RC, O’Colmain BJ, Klein BE, Taylor HR, et al. Prevalence of openangle glaucoma among adults in the United States. Arch Opthalmol 2004;122:532-8. 23. Mojon DS, Hess CW, Goldblum D, Bohnke M, Korner F, Mathis J. Primary open angle glaucoma is associated with sleep apnea syndrome. Ophthalmologica 2000;214:115-8. 24. Alvarez-Sala R, Garcia IT, Garcia F, Moriche J, Prados C, Diaz S, et al. Nasal CPAP during wakefulness increases intraocular pressure in glaucoma. Monaldi Arch Chest Dis 1994;49:394-5. 25. Kiekens S, De Veva G, Coeckelbergh T, Tassignon MJ, van de Heyning P, De Wilfried B, et al. Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea. Invest Ophthalmol Vis Sci 2008;49:934-40. 26. Cohen Y, Ben-Mair E, Rosenzweig E, Schecter-Amir D, Solomon AS. The effect of nocturnal CPAP therapy on the intraocular pressure of patients with sleep apnea syndrome. Graefes Arch CIin Exp Ophthalmol 2015;253:2263-71. 27. Chegini S, Dharinal DX. Review of evidence for the use of steroids in orthognatic surgery. Br J Oral Maxillofac Surg 2012;50:97-101. 28. Carey TW, Shaw KA, Weber ML, DeVine JG. Effect of the degree of reverse Trendelenburg position on intraocular pressure during prone spine surgery: a randomized control trial. Spine J 2014;14:2118-26. 29. Shaikh A, Ahmado A, James B. Severe cough: a cause of late bleb leak. J Glaucoma 2003;12:181-3. 30. Krist D, Cursiefen CD, Junemann A. Transitory intrathoracic and abdominal pressure elevation in the history of 64 patients with normal pressure glaucoma. Klin Monbl Augenheilkd 2001;218:209-13.
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31. Drayna PC, Estrada C, Wang W, Saville BR, Arnold DH. Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. Am J Emeg Med 2012;30:1215-8. 32. Kelly RE, Dinner M, Turner LS, Haik B, Abramson DH, Daines P. Succinylcholine increases intraocular pressure in the human eye with the extraocular muscles detached. Anesthesiology 1993;79:948-52. 33. Yukioka H, Yoshimoto N, Nishimura K, Fujimori M. Intravenous lidocaine as a suppressant of coughing during tracheal intubation. Anesth Analg 1985;64:1189-92. 34. Fang ZT: Anesthetic management of ophthalmic surgery in geriatric patients. American Academy Ophthalmology accessed at www.aao.org on May 6, 2016 35. Petounis AD, Chondreli S, Vadaluka-Sekioti A. Effect of hypercapnia and hyperventilation on human intraocular pressure during general anesthesia following acetazolamide administration. Br J Ophthalmol 1980;64:422-5. 36. Sudheera KS, Bhardwaj N, Yaddanapudi S. Effect of intravenous metoclopramide on intraocular pressure: a prospective, randomized, double-blind, placebo-controlled Study. J Postgrad Med 2008;54:195-8. 37. Geyer O, Cohen N, Segev E, Roth EZ, Melamud L, Peled R, et al. The prevalence of glaucoma in patients with sleep apnea syndrome: same as in a general population. Am J Ophthalmol 2003;136:1093-6. 38. Girkin CA, McGwin G, McNeal SF, Owsley C. Is there an association between pre-existing sleep apnea and the development of glaucoma. Br J Ophthalmol 2006;90:679-81. 39. American Academy of Ophthalmology. Policy Statement: Frequency of Ocular Examinations. Accessed May 13, 2016. http://www.aao.org/clinical-statement/frequency-ofocular-examinations--november-2009
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Table 1: Demographics & OSA Severity of Patients Referred to Dental Service Demographics and Severity of OSA Mean age ± SD Range
58.6 ± 12.3 years 24-86 years
Gender: %male
96.4%
Apnea-Hypopnea Index: % “mild” (AHI 5-14)
42.7% (CI: 36.1-49.4%)
% “moderate” (AHI 15-29)
19.6% (CI: 14.6-25.3%)
% “severe” (AHI ≥30)
37.8% (CI: 32.4-44.5%)
Table 2: Demographics and Distribution of POAG Subtypes among Dental Service OSA Patients (n = 225) “Classic” OAG NTG (n=8) OAGS (n=27) (n=12) Age ± SD Range Gender: % male
91.7% (11/12)
100.0% (8/8)
100% (27/27)
Prevalence among those 5.3% 3.6% 12.0% with OSA (n = 225) (CI: 2.8-9.1%) (CI: 1.6-6.9%) (CI: 8.1-17.0%) *Among the 47 patients with POAG; 12(25.5%) had COAG, 8(17%) had NTG, and 27(57.4%) had OAGS.
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Table 3: Demographics & Clinical Characteristics of Patients Treated at a Veterans Affairs Medical Center Over a 17-year Period of Time. # Total Patients (%) # Male (%)
All Patients
312,494 (100)
273,653 (88)
POAG
7,975 (2.5)
7,777 (97)
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S2212-4403(18)30057-9 https://doi.org/10.1016/j.oooo.2018.01.021 OOOO 1945
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received date: Revised date: Accepted date:
16-11-2017 21-12-2017 20-1-2018
Please cite this article as: Arthur H. Friedlander, Lindsay L. Graves, Tina I. Chang, K. Karl Kawakami, Urie K. Lee, Shannon C. Grabich, Zhuang T. Fang, Michelle R. Zeidler, JoAnn A. Giaconi, Prevalence of primary open-angle glaucoma among patients with obstructive sleep apnea, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2018), https://doi.org/10.1016/j.oooo.2018.01.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title Page Title: Prevalence of Primary Open-Angle Glaucoma Among Patients with Obstructive Sleep Apnea Authors: 1. Corresponding Author: Arthur H. Friedlander, DMD Associate Chief of Staff and Director of Graduate Medical Educationa Director of Quality Assurance, Hospital Dental Servicec Professor-in-Residence of Oral and Maxillofacial Surgeryb 11301 Wilshire Blvd. (14) Los Angeles, CA 90073 USA Office Phone (310) 268-3196 Fax Number (310) 268-4631 Home Phone (818) 366-5418 [email protected] 2. Lindsay L. Graves, DDS Former Oral and Maxillofacial Surgery Research Fellowa [email protected] 3. Tina I. Chang, DMD, MD Director of the Research Fellowship and Inpatient Oral and Maxillofacial Surgerya Instructor of Oral and Maxillofacial Surgeryb [email protected] 4. K. Karl Kawakami, DDS Chief of Dental Serviceb Adjunct Assistant Professor in Advanced Prosthodonticsa [email protected] 5. Urie K. Lee, DDS Oral and Maxillofacial Surgery Research Fellowa [email protected] 6. Shannon C. Grabich, PhD Epidemiologist at Gillings School of Global Public Healthd [email protected] 7. Zhuang T. Fang, MD, MSPH Clinical Professor in the Department of Anesthesiology and Perioperative Medicinec Associate Director, Stein Operating Roomc [email protected] 1
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8. Michelle R. Zeidler, MD, MS Director of the Sleep Disorders Centera Clinical Professor Medicine-Pulmonary Critical Carec Program Director – UCLA Sleep Fellowship: Division of Pulmonary, Critical Care and Sleep Medicinec [email protected] 9. JoAnn A. Giaconi, MD Chief of Ophthalmologya Associate Clinical Professor : UCLA Jules Stein Eye Institutec [email protected]
a
VA Greater Los Angeles Healthcare System 11301 Wilshire Blvd, Los Angeles, CA 90073 USA b
School of Dentistry, University of California, Los Angeles 10833 Le Conte Ave, Los Angeles, CA 90095 USA c
Ronald Reagan UCLA Medical Center 757 Westwood Plaza, Los Angeles, CA 90095 USA d
University of North Carolina at Chapel Hill
# This material is the result of work supported with resources and use of facilities at the VA Greater Los Angeles healthcare System but its contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. No conflicts of interest to disclose for any authors. ## Declarations of interest: None 891 tnuAt dA Wttc rtsbA 04 reCbCd e Wleln bdl Wttc rtsbA 6812 rtuuelAl W bsudtCuA Wttc rtsbA 99 ssunlt to Wloltlbdlu 9 ssunlt to r nelu
2
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Clinical Relevance: The co-occurrence of occult comorbid primary open angle glaucoma among patients with obstructive sleep apnea is substantial. Given the potential perioperative risks of heightened intraocular pressure, the status of eye health needs to be assessed before planned airway corrective surgery
Abstract Objective: Determine primary open angle glaucoma (POAG) prevalence among obstructive sleep apnea (OSA) patients because perioperative environment risks further damaging the optic nerve. Study design: Analyzed “convenience sample” referred by Sleep Medicine for oral appliances because of continuous positive pressure (CPAP) intolerance. Determined aggregate prevalence of the 3 POAG subtypes: (“classic” open angle glaucoma (COAG), normal tension glaucoma (NTG), open angle glaucoma suspect (OAGS); among the index population and compared it to that of same hospital’s general population. Similarly determined were associations between OSA severity levels (apnea-hypopnea index; AHI) and POAG subtypes. Results: Among the study sample of 225 patients with OSA (96.4% male; mean age 58.5 ± 12.3 years), 47 (20.9%) had POAG; with subtype distribution: (COAG: 12(25.5%), NTG: 8 (17.0%), OAGS: 27 (57.4%)). The POAG prevalence rate among medical center’s general population was 2.5% which was significantly less (P < .00001) than among those with
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comorbid OSA. Severity of the breathing disorder (AHI) failed to demonstrate a significant correlation to any POAG subtype (P > .05). Conclusion: The significant prevalence of POAG among OSA sufferers, suggests need for preoperative consultations from an ophthalmologist to determine eye health and possibly an anesthesiologist to avoid potential vision loss.
Introduction Oral and maxillofacial surgeons providing corrective surgery of the jaws and airway for patients with obstructive sleep apnea (OSA) are fully cognizant of the respiratory and hemodynamic derangements associated with the disorder. They may not, however, recognize that some studies have demonstrated that the associated cessation of breathing, and the resulting decrement in blood oxygen saturation levels, may trigger optic nerve damage causing comorbid primary open angle glaucoma (POAG).1-5 Specifically, this chronic ischemic environment has been linked to “classic” open angle glaucoma (COAG), in which the intraocular pressure (IOP) is > 21 mmHg, “normal tension glaucoma” (NTG), in which the IOP is ≤ 21 mm Hg, and “open-angle glaucoma suspect” (OAGS), in which IOP may be normal. COAG and NTG are both distinguished by a characteristic, progressive optic nerve atrophy (that is, loss of retinal ganglion cells and their axons) leading to visual field (VF) loss, and possibly complete blindness.6-11 Individuals with OAGS, however, do not definitively have glaucoma but have characteristics (suspicious optic nerve appearance, repeatable VF abnormalities consistent with optic nerve damage, or elevated IOP in the absence of structural or functional changes) which 4
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suggest that they are at high risk of developing the disease in the future.12,13 Recognition of all three subgroups of patients is highly desirable because intraoperative precautions may be necessary to safeguard vision. Specifically, because of the multitude of perioperative factors that can potentially further damage the optic nerve in OSA patients with occult POAG, this study was designed to answer the following clinical questions, 1) What is the aggregate prevalence of POAG among patients with OSA, 2) what is the prevalence of each of the three diagnostic subgroups, and 3) is the severity (as measured by the Apnea Hypopnea Index or AHI) of the breathing disorder related to the comorbid presence of POAG? We hypothesized that the combined (COAG, NTG, and OAGS) prevalence rate of POAG among patients with OSA would be far greater than the prevalence rate found in the general population of patients treated at the same medical center. Materials and Methods Study Design To address these research questions, the investigators designed and implemented a study based on a retrospective review of cases aggregated from selected electronic medical records (EMR).
The primary study population consisted of patients with OSA referred from the
Veterans Affairs Sleep Medicine section of the Greater Los Angeles Veterans Administration Hospital (VAGLA) to the hospital’s Dental Service for oral appliance fabrication prescribed to treat a) mild OSA that did not require the riskier nasal continuous positive pressure therapy (nCPAP), or b) to treat more severe OSA in patients non-compliant with n-CPAP therapy. This study conformed to precepts of the Declaration of Helsinki on medical protocol and ethics and was approved by the Ethical Review Board of the Veterans Affairs Greater Los Angeles
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Healthcare Systems (VA GLA). Informed consent exemption was granted given the retrospective nature of the project as well as the use of deidentified patient variables. Study Sample/Study Variables The study population (convenience sample), among whom the aggregate prevalence rate of POAG would be determined, consisted of patients with OSA that the Sleep Medicine Service referred to the Dental Service between January 1, 2009 to November 15, 2017. The inclusion criterion was a positive diagnosis for OSA on EMR that was determined by the VA Sleep Medicine Service using the American Academy of Sleep Medicine (AASM) standardized criteria following an overnight sleep study or by reviewing results obtained from an outside sleep laboratory study.14,15
Specifically, OSA was diagnosed when the patient had 5 or more
obstructive respiratory events (that is, apnea or hypopneas seen in association with a 3% desaturation and/or a respiratory effort-related arousal) per hour of sleep and an associated set of signs/symptoms (e.g. daytime sleepiness, snoring) or alternatively, ≥ 15/h of obstructive respiratory events in the absence of associated symptoms. Apneas were defined as cessation of air flow lasting ≥ 10 seconds and hypopnea as a ≥ 30% fall in airflow lasting ≥ 10 seconds in association with a ≥ 3% fall in oxygen saturation from baseline, or alternatively, a ≥ 30% decrease in airflow lasting ≥ 10 seconds and an associated arousal. Subjects having an AHI (total number of apneas and hypopneas per hour of sleep) of 5-14 were diagnosed as having “mild” OSA, of 15-29 as “moderate” OSA, and ≥30 events per hour, as “severe” OSA.14,15 The control group population among whom the prevalence rate of POAG would also be determined, consisted of the medical center’s approximate 300,000 unique inpatients and outpatients treated between October 1, 1999 and November 15, 2017.
To obtain this
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information, all EMRs with diagnostic codes for primary open-angle glaucoma (ICD-9 code: 365.11, and ICD-10 code: H40.11) were identified. A two-tailed z-test was run on the two populations and the alpha level was set at 0.05. The primary outcome of interest was a determination of the aggregate prevalence of POAG, among the dental patients receiving OSA appliance, as well as its subtypes, among OSA patients and an assessment of whether the severity level of OSA was a determining factor. Prediction models were run as linear or logistic regressions based on the categorization of outcomes. In prediction models, we used an alpha value of less than .01 to determine significance and a P value of < 0.05 was considered strongly significant. Patients were coded as positive for POAG if they were diagnosed by an ophthalmologist or optometrist with the disorder, had had surgical/laser treatment for it in the past or were currently under medical treatment for the disease (i.e. taking alpha adrenergic agonists, beta blockers, carbonic anhydrase inhibitors, cholinergic agonists, or prostaglandin analogs).16 [Excluded from study were patients having a history of ocular trauma, pseudo exfoliation, and pigment dispersion.] Patients were then classified into their subtypes: COAG if there was nerve damage and pre-treatment IOP was > 21, NTG if there was nerve damage and the pretreatment IOP was ≤ 21, and OAGS if the optic nerve, RNFL, or VF were suspicious for glaucomatous changes, and/or if there was evidence of consistently elevated IOP but without structural and functional changes. Lastly, aggregated and correlated was the relationship between the severity of the breathing disorder and a diagnosis of POAG. The diagnosis of open angle glaucoma involved a practitioner’s slit-lamp and dilated pupil examination of the optic nerve that recorded optic disc structural abnormalities (this is, 7
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cupping and rim thinning [cup-disk ratio ≥ 0.6 or cup-disc asymmetry ≥ 0.3] ± partial or complete notching ± nerve fiber layer defects), visual field abnormalities (that is, nasal step, arcuate, or paracentral scotoma), open and otherwise normal anterior chamber angles, and intraocular pressure (IOP) measured using the applanation tonometer.17 Results Between 2009 and 2017, the Dental Service received 225 consultation requests for fabrication of an oral appliance to manage OSA from the Sleep Medicine Service. The overwhelming majority (96.4%) of patients were male with a mean age of 58.5 ± 12.3 (Table 1). The severity of their OSA, as determined by AHI, denoted 42.7% with “mild” disease, 19.6% with “moderate” disease, and 37.8% with “severe” disease. Among these 225 individuals with OSA, 47 had POAG, yielding an aggregate prevalence rate of 20.9%. Among these 47 individuals, 12 (25.5%) had COAG, 8(17%) had NTG, and 27(57.4%) had OAGS (Table 2). From October 1, 1999 to November 12, 2017, the VA GLA treated 312,494 unique patients and of these 7,975 (2.5%) had POAG (subtype often not defined) (Table 3). The prevalence rate of POAG in the dental environment among OSA patients was significantly (P < 0.00001) greater than the hospital’s general population. The severity of the breathing disorder as classified by the AHI (mild, moderate, severe) was not found to be a predictor of POAG subtypes (COAG, NTG, OAGS) in our logistic regression models. Discussion
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The results of our study demonstrated that nearly 21% of patients with OSA also had one of three POAG subtypes. These results are consistent with the work of other researchers who have reported that the prevalence of POAG among patients diagnosed with OSA ranges from 7.2% to 27%.18,19 Importantly, our results are dramatically different from the 2.5% diagnosed amidst the medical center’s general population as well as the 5% reported among a “general population” of mostly male (90%) older ( > 50 years) Veterans attending another VA medical center.20 Similarly our results differ from the 2% prevalence rate denoted for the “general population” in America.21,22 The difference in the 21% POAG prevalence rates found in our sample of patients with comorbid OSA and rates found in the “general population,” the majority of whom are most likely free of OSA, most plausibly arises from the effects of hypoxia upon the optic nerve head.7-12,23 Implications for the Oral and Maxillofacial Surgeon Corrective airway and jaw surgery as a therapeutic intervention for patients solely afflicted with OSA is usually only indicated when the patient evidences intolerance to n-CPAP and/or mandibular advancement appliances. However, it is now recognized that in some patients with OSA and concomitant POAG (irrespective of subtype), n-CPAP may increase central venous pressure causing an increased resistance to aqueous outflow and resulting in increased IOP.24-26 Thus, in this unique population the indications for corrective orthognathic surgery are markedly enhanced. Furthermore, given the frequent association between the two illnesses, it is suggested that all patients being evaluated for surgical correction of sleep apnea be evaluated by an eye care professional for occult POAG and/or adequate control of the eye disease, if previously 9
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diagnosed. This is necessary because of the unique vulnerability of the optic nerve to further damage during the perioperative period due to of the eye’s reduced capacity to drain aqueous humor and compensate for acute rises in IOP. The consultative discussion between clinicians should also address the risks and benefits of administering dexamethasone to persons with POAG during the perioperative phase of airway/jaw surgery in order to minimize surgical site edema that might possibly compromise the airway. Persons with POAG are at risk of elevation of IOP when exposed to dexamethasone.27 The maxillofacial surgeon should also consult with the attending anesthesiologist, drawing particular attention to the need to minimize intraoperative elevations in IOP. Suggested strategies include positioning the patient on the operating table parallel to the floor or better yet, in a reverse Trendelenburg position.28 It is also important to prevent coughing/bucking, hypoxia and hypercapnia, especially during induction of general anesthesia and endotracheal intubation. This is a critical element because coughing, and the resulting increase in intrathoracic pressure, can lead to increases of IOP.29,30 The induction phase of anesthesia may be accomplished with any of the intravenous or volatile agents with the possible exception of ketamine, given conflicting descriptions of its effects on IOP in adult patients.31 Also to be avoided is administration of the depolarizing muscle relaxant succinylcholine, which increases IOP approximately 8-10 mm Hg for about 510 minutes after administration. The etiology underlying this elevation in IOP is in dispute; some ascribing it to an increase in extraocular muscle tone and others believing that it arises from a direct effect on choroidal blood volume or on aqueous humor formation or drainage. A non-depolarizing agent is best substituted.32 The administration of IV narcotics and lidocaine 10
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prior to direct laryngoscopy for intubation is suggested given that they effectively attenuate the reactivity of the airway and coughing response.33 It should be noted that achieving adequate depth of anesthetic level prior to tracheal intubation is the most important part of anesthetic management in the prevention of coughing, and therefore the elevation of IOP.34 It is also critically important to avoid any episodes of hypoxemia and hypercarbia during the procedure since they can precipitate increased IOP.35 Furthermore, within 30 minutes of terminating the procedure, ondansetron (an antiemetic with no direct effect on IOP) should be administered to avoid post-operative straining and vomiting which is frequently associated with an increase of IOP. The antiemetic metoclopramide however probably should not be used because of conflicting reports as to its effects on IOP.36 Additional points considered The reports of the association between OSA and POAG have not gone unchallenged. Ophthalmologists in Haifa, Israel conducted a cross-sectional study evaluating almost 230 patients with OSA and noted that the prevalence of POAG was similar to that in the general population.37 Similarly, in a nested case-control study conducted at the Veterans Affairs Medical Center in Birmingham, the researchers could not demonstrate an association between POAG and OSA after adjusting for confounding factors.38 Conclusion In conclusion, finding a significant rate of POAG among OSA patients referred to the Dental Service from the Sleep Service at the VA GLA suggests the need for surgeons planning corrective airway surgery to be cognizant of this relationship and inquire about their patients’ last 11
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visit to an eye-care professional. Patients not seen in the past 1-3 years, especially those whose sleep disorder was recently diagnosed, should be expeditiously referred for examination in order to rule out or discover concomitant eye disease; and to provide early treatment if found.39 Ocular conditions need to be discussed with members of the operating room team so that the risk of intraoperative elevation in IOP and damage to the optic nerve can be minimized.
Acknowledgement: The authors gratefully acknowledge the assistance of Susan C Rosenbluth, Ph.D., Deputy Associate Chief of Staff, Graduate Medical Education, VA Los Angeles for editing the revised manuscript.
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References 1. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd Ed. Darien, IL American Academy of Sleep Medicine 2014. 2. Selim B, Won C, Yaggi HK. Cardiovascular consequence of sleep apnea. Clin Chest Med 2010;31:203. 3. Shinmei Y, Nitta T, Saito H, Ohguchi T, Kijima R, Chin S, et al. Continuous intraocular pressure monitoring during nocturnal sleep in patients with obstructive sleep apnea syndrome. Invest Ophthalmol Vis Sci 2016;57:2824. 4. Liu S, Lin Y, Liu X. Meta-analysis of association of obstructive sleep apnea with glaucoma. J Glaucoma 2016;25:1. 5. Faridi O, Park SC, Liebmann JM, Ritch R. Glaucoma and obstructive sleep apnea syndrome. Clin Experimental Ophthalmol 2012;40:408. 6. Lin PW, Friedman M, Lin HC, Chang HW, Wilson M, Lin MC. Normal tension glaucoma in patients with OSA/hypopnea syndrome. J Glaucoma 2011;20:553. 7. Thurtell MJ, Bruce BB, Newman NJ, Biousse V. An update on idiopathic intracranial hypertension. Rev Neurol Dis 2010;7:e56. 8. Nusbaum DM, Wu SM, Frankfort BJ. Elevated intracranial pressure causes optic nerve and reginal ganglion cell degeneration in mice. Exp Eye Res 2015;136:38. 9. Kario K. Obstructive sleep apnea syndrome and hypertension: ambulatory blood pressure. Hypertens Res 2009;32:428. 10. Karakucuk S, Goktas S, Aksu M, Erdogan N, Demirci S, et al. Ocular flood flow in patients with obstructive sleep apnea syndrome. (OSAS). Graefes Arch Clin Exp Ophthalmol 2008;246:129.
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11. Goldblum D, Mathis J, Bohnke M, Bassetti C, Hess CW, Gugger M, et al. Nocturnal measurements of intraocular pressure in patients with normal-tension glaucoma and sleep apnea syndrome. Klin Monatsbl Augenheilkd 2000;216:246. 12. Tsang CS, Chong SL, Ho CK, Li MF. Moderate to severe obstructive sleep apnea is associated with a higher incidence of visual field defect. Eye 2006;20:38. 13. Chang RT, Singh K. Glaucoma suspect: diagnosis and management. Asia Pac J Ophthalmo (Phila) 2016;5:32-37. 14. Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Version 2.3. Am Acad Sleep Med 2007. 15. Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Quan SF, et al. AASM Scoring Manual Updates for 2017 (Version 2.4). J Clin Sleep Med 2017;13:665-666. 16. Feder RS, Olsen TW, Prum BE JR, Summers CG, Randall J, et al. Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern® Guidelines. Ophthalmology 2016;123:P209-36. 17. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma. JAMA 2014;311:1901-11. 18. Mojon DS, Hess CW, Goldblum D, Fleischhaur J, Koerner F, Bassetti C, et al. High prevalence of glaucoma in patients with sleep apnea syndrome. Ophthalmology 1999;106:1009-12. 19. Bedel RE, Kaplan J, Heckman M, Friedrickson PA, Lin SC. Prevalence of glaucoma in patients with obstructive sleep apnea – a cross-sectional case series. Eye (Lond) 2008;22:1105-9. 20. Boyle-Walker M, Semes LP, Clay OJ, Liu L, Fuhr P. Sleep apnea syndrome represents a risk for glaucoma in a veterans’ affairs population. ISRN Ophthalmol 2011; Article ID: 920767
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21. Provini F, Vetrugno R, Lugaresi E, Montagna P. Sleep-related breathing disorders and headache. Neuro Sci 27 (2 suppl): 2006;S149-52. 22. Friedman DS, Wolfs RC, O’Colmain BJ, Klein BE, Taylor HR, et al. Prevalence of openangle glaucoma among adults in the United States. Arch Opthalmol 2004;122:532-8. 23. Mojon DS, Hess CW, Goldblum D, Bohnke M, Korner F, Mathis J. Primary open angle glaucoma is associated with sleep apnea syndrome. Ophthalmologica 2000;214:115-8. 24. Alvarez-Sala R, Garcia IT, Garcia F, Moriche J, Prados C, Diaz S, et al. Nasal CPAP during wakefulness increases intraocular pressure in glaucoma. Monaldi Arch Chest Dis 1994;49:394-5. 25. Kiekens S, De Veva G, Coeckelbergh T, Tassignon MJ, van de Heyning P, De Wilfried B, et al. Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea. Invest Ophthalmol Vis Sci 2008;49:934-40. 26. Cohen Y, Ben-Mair E, Rosenzweig E, Schecter-Amir D, Solomon AS. The effect of nocturnal CPAP therapy on the intraocular pressure of patients with sleep apnea syndrome. Graefes Arch CIin Exp Ophthalmol 2015;253:2263-71. 27. Chegini S, Dharinal DX. Review of evidence for the use of steroids in orthognatic surgery. Br J Oral Maxillofac Surg 2012;50:97-101. 28. Carey TW, Shaw KA, Weber ML, DeVine JG. Effect of the degree of reverse Trendelenburg position on intraocular pressure during prone spine surgery: a randomized control trial. Spine J 2014;14:2118-26. 29. Shaikh A, Ahmado A, James B. Severe cough: a cause of late bleb leak. J Glaucoma 2003;12:181-3. 30. Krist D, Cursiefen CD, Junemann A. Transitory intrathoracic and abdominal pressure elevation in the history of 64 patients with normal pressure glaucoma. Klin Monbl Augenheilkd 2001;218:209-13.
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31. Drayna PC, Estrada C, Wang W, Saville BR, Arnold DH. Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. Am J Emeg Med 2012;30:1215-8. 32. Kelly RE, Dinner M, Turner LS, Haik B, Abramson DH, Daines P. Succinylcholine increases intraocular pressure in the human eye with the extraocular muscles detached. Anesthesiology 1993;79:948-52. 33. Yukioka H, Yoshimoto N, Nishimura K, Fujimori M. Intravenous lidocaine as a suppressant of coughing during tracheal intubation. Anesth Analg 1985;64:1189-92. 34. Fang ZT: Anesthetic management of ophthalmic surgery in geriatric patients. American Academy Ophthalmology accessed at www.aao.org on May 6, 2016 35. Petounis AD, Chondreli S, Vadaluka-Sekioti A. Effect of hypercapnia and hyperventilation on human intraocular pressure during general anesthesia following acetazolamide administration. Br J Ophthalmol 1980;64:422-5. 36. Sudheera KS, Bhardwaj N, Yaddanapudi S. Effect of intravenous metoclopramide on intraocular pressure: a prospective, randomized, double-blind, placebo-controlled Study. J Postgrad Med 2008;54:195-8. 37. Geyer O, Cohen N, Segev E, Roth EZ, Melamud L, Peled R, et al. The prevalence of glaucoma in patients with sleep apnea syndrome: same as in a general population. Am J Ophthalmol 2003;136:1093-6. 38. Girkin CA, McGwin G, McNeal SF, Owsley C. Is there an association between pre-existing sleep apnea and the development of glaucoma. Br J Ophthalmol 2006;90:679-81. 39. American Academy of Ophthalmology. Policy Statement: Frequency of Ocular Examinations. Accessed May 13, 2016. http://www.aao.org/clinical-statement/frequency-ofocular-examinations--november-2009
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Table 1: Demographics & OSA Severity of Patients Referred to Dental Service Demographics and Severity of OSA Mean age ± SD Range
58.6 ± 12.3 years 24-86 years
Gender: %male
96.4%
Apnea-Hypopnea Index: % “mild” (AHI 5-14)
42.7% (CI: 36.1-49.4%)
% “moderate” (AHI 15-29)
19.6% (CI: 14.6-25.3%)
% “severe” (AHI ≥30)
37.8% (CI: 32.4-44.5%)
Table 2: Demographics and Distribution of POAG Subtypes among Dental Service OSA Patients (n = 225) “Classic” OAG NTG (n=8) OAGS (n=27) (n=12) Age ± SD Range Gender: % male
91.7% (11/12)
100.0% (8/8)
100% (27/27)
Prevalence among those 5.3% 3.6% 12.0% with OSA (n = 225) (CI: 2.8-9.1%) (CI: 1.6-6.9%) (CI: 8.1-17.0%) *Among the 47 patients with POAG; 12(25.5%) had COAG, 8(17%) had NTG, and 27(57.4%) had OAGS.
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Table 3: Demographics & Clinical Characteristics of Patients Treated at a Veterans Affairs Medical Center Over a 17-year Period of Time. # Total Patients (%) # Male (%)
All Patients
312,494 (100)
273,653 (88)
POAG
7,975 (2.5)
7,777 (97)
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