{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:56:14Z","timestamp":1788184574970,"version":"build-2803163510"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007509","name":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica","doi-asserted-by":"publisher","award":["020\/2017"],"award-info":[{"award-number":["020\/2017"]}],"id":[{"id":"10.13039\/501100007509","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007509","name":"Sociedad Espa\u00f1ola de Neumolog\u00eda y Cirug\u00eda Tor\u00e1cica","doi-asserted-by":"crossref","award":["020\/2017"],"award-info":[{"award-number":["020\/2017"]}],"id":[{"id":"10.13039\/501100007509","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic retinopathy. However, the effect of apnea\u2013hypopnea suppression on retinal disease progression is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of continuous positive airway pressure (CPAP) for the reduction of retinal lesions in patients with non-proliferative diabetic retinopathy (NPDR) and OSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This open-label, parallel-group, randomized controlled trial was conducted between October 2016 and February 2020 at a university hospital in Spain. The date of final follow-up was March 2, 2021. Eighty-three patients with OSA and mild to moderate NPDR receiving stable treatment were randomized to receive CPAP and usual care (43 patients with 79 available eyes) or usual care alone (40 patients with 67 available eyes) for 52\u2009weeks. The primary outcomes were the change in the percentage of eyes with retinal exudates and the number of retinal microhemorrhages from baseline to week 52. We also assessed the effects of both interventions on retinal thickness by means of optical coherence tomography, serum concentrations of glycated hemoglobin, blood pressure, lipid concentrations, sleepiness, and quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty-two weeks of CPAP treatment was associated with reductions from baseline in the percentage of eyes with hard exudates (overall difference, \u221221.7%; P\u2009=\u20090.035) and in optical coherence tomography indices of retinal edema, including central subfield thickness and cube volume. However, in patients who met prespecified criteria for CPAP adherence, treatment was also associated with a higher number of retinal microhemorrhages at 52\u2009weeks (intergroup adjusted difference, 6.0 [95% confidence interval, 0.6\u201311.5]; P\u2009=\u20090.029), which was directly related to prescribed pressure levels. CPAP treatment also improved glycemic control, sleepiness, and general health-related quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with OSA and NPDR, long-term CPAP treatment in addition to usual care may result in slower progression of retinal disease, although it could also induce an increase in retinal microhemorrhages.<\/jats:p>\n                    <jats:p>Clinical trial registered with www.clinicaltrials.gov (NCT02874313).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.202304-296oc","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T16:05:30Z","timestamp":1696435530000},"page":"102-113","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":13,"title":["Continuous Positive Airway Pressure Effect on Progression of Retinal Disease in Patients with Sleep Apnea and Nonproliferative Diabetic Retinopathy: A Randomized Clinical Trial"],"prefix":"10.1093","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2065-9326","authenticated-orcid":false,"given":"Aldara","family":"Garc\u00eda-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Villala\u00edn-Rodes","sequence":"additional","affiliation":[{"name":"Servicio de Oftalmolog\u00eda, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Jaureguizar","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Zamarr\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Paz\u2013IdiPAZ, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Mart\u00ednez-Cer\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Paz\u2013IdiPAZ, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Casitas","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Paz\u2013IdiPAZ, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Galera","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Paz\u2013IdiPAZ, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1948-4514","authenticated-orcid":false,"given":"Carolina","family":"Cubillos-Zapata","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Paz\u2013IdiPAZ, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias, Madrid, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Servicio de Oftalmolog\u00eda, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Asencio","sequence":"additional","affiliation":[{"name":"Servicio de Oftalmolog\u00eda, Hospital Universitario La Paz, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-2238","authenticated-orcid":false,"given":"Francisco","family":"Garc\u00eda-R\u00edo","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Paz\u2013IdiPAZ, Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Respiratorias, Madrid, Spain; and"},{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,1,1]]},"reference":[{"key":"2026012203134467800_bib1","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1056\/NEJMra1909637","article-title":"Evaluation and care of patients with diabetic retinopathy","volume":"382","author":"Jampol","year":"2020","journal-title":"N Engl J Med"},{"key":"2026012203134467800_bib2","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"2026012203134467800_bib3","doi-asserted-by":"crossref","first-page":"412","DOI":"10.2337\/dc16-2641","article-title":"Diabetic retinopathy: a position statement by the American Diabetes Association","volume":"40","author":"Solomon","year":"2017","journal-title":"Diabetes Care"},{"key":"2026012203134467800_bib4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1464-5491.2010.02962.x","article-title":"The prevalence of retinopathy in men with type 2 diabetes and obstructive sleep apnoea","volume":"27","author":"West","year":"2010","journal-title":"Diabet Med"},{"key":"2026012203134467800_bib5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/dme.12582","article-title":"Obstructive sleep apnoea in people with type 1 diabetes: prevalence and association with micro- and macrovascular complications","volume":"32","author":"Manin","year":"2015","journal-title":"Diabet Med"},{"key":"2026012203134467800_bib6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1752-699X.2010.00216.x","article-title":"Prevalence of sleep apnoea in diabetic patients","volume":"5","author":"Schober","year":"2011","journal-title":"Clin Respir J"},{"key":"2026012203134467800_bib7","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.ajo.2008.12.027","article-title":"Relationship between diabetic retinopathy and sleep-disordered breathing","volume":"147","author":"Shiba","year":"2009","journal-title":"Am J Ophthalmol"},{"key":"2026012203134467800_bib8","doi-asserted-by":"crossref","first-page":"265","DOI":"10.5664\/jcsm.9552","article-title":"Sleep apnea and eye diseases: evidence of association and potential pathogenic mechanisms","volume":"18","author":"Garc\u00eda-S\u00e1nchez","year":"2022","journal-title":"J Clin Sleep Med"},{"key":"2026012203134467800_bib9","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1164\/rccm.201701-0175OC","article-title":"Obstructive sleep apnea and retinopathy in patients with type 2 diabetes: a longitudinal study","volume":"196","author":"Altaf","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203134467800_bib10","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1164\/rccm.201511-2260OC","article-title":"The effect of treatment of obstructive sleep apnea on glycemic control in type 2 diabetes","volume":"194","author":"Shaw","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203134467800_bib11","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1164\/rccm.201510-1942OC","article-title":"Effect of continuous positive airway pressure on glycemic control in patients with obstructive sleep apnea and type 2 diabetes: a randomized clinical trial","volume":"194","author":"Mart\u00ednez-Cer\u00f3n","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203134467800_bib12","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/dom.14247","article-title":"Benefits of continuous positive airway pressure on glycaemic control and insulin resistance in patients with type 2 diabetes and obstructive sleep apnoea: a meta-analysis","volume":"23","author":"Shang","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"2026012203134467800_bib13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3109\/10641963.2013.804546","article-title":"Obstructive sleep apnea syndrome and chronic kidney disease: a new cardiorenal risk factor","volume":"36","author":"Ozkok","year":"2014","journal-title":"Clin Exp Hypertens"},{"key":"2026012203134467800_bib14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1159\/000334090","article-title":"Visual improvement following continuous positive airway pressure therapy in diabetic subjects with clinically significant macular oedema and obstructive sleep apnoea: proof of principle study","volume":"84","author":"Mason","year":"2012","journal-title":"Respiration"},{"key":"2026012203134467800_bib15","doi-asserted-by":"crossref","first-page":"1801177","DOI":"10.1183\/13993003.01177-2018","article-title":"Continuous positive airway pressure effect on visual acuity in patients with type 2 diabetes and obstructive sleep apnoea: a multicentre randomised controlled trial","volume":"52","author":"West","year":"2018","journal-title":"Eur Respir J"},{"key":"2026012203134467800_bib16","doi-asserted-by":"crossref","first-page":"479","DOI":"10.5664\/jcsm.6506","article-title":"Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine clinical practice guideline","volume":"13","author":"Kapur","year":"2017","journal-title":"J Clin Sleep Med"},{"key":"2026012203134467800_bib17","doi-asserted-by":"crossref","first-page":"597","DOI":"10.5664\/jcsm.2172","article-title":"Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events","volume":"8","author":"Berry","year":"2012","journal-title":"J Clin Sleep Med"},{"key":"2026012203134467800_bib18","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1164\/rccm.202206-1091OC","article-title":"Continuous positive airway pressure effect on albuminuria progression in patients with obstructive sleep apnea and diabetic kidney disease: a randomized clinical trial","volume":"207","author":"Zamarr\u00f3n","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012203134467800_bib19","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1038\/s41598-021-85023-w","article-title":"Obstructive sleep apnea is associated with impaired renal function in patients with diabetic kidney disease","volume":"11","author":"Zamarr\u00f3n","year":"2021","journal-title":"Sci Rep"},{"key":"2026012203134467800_bib20","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/BF00410281","article-title":"Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study","volume":"38","author":"Aldington","year":"1995","journal-title":"Diabetologia"},{"key":"2026012203134467800_bib21","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1016\/j.ophtha.2015.08.004","article-title":"First incidence and progression study for diabetic retinopathy in Portugal, the RETINODIAB study: evaluation of the screening program for Lisbon region","volume":"122","author":"Dutra Medeiros","year":"2015","journal-title":"Ophthalmology"},{"key":"2026012203134467800_bib22","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1001\/archopht.1985.01050120030015","article-title":"Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group","volume":"103","year":"1985","journal-title":"Arch Ophthalmol"},{"key":"2026012203134467800_bib23","doi-asserted-by":"crossref","first-page":"5698","DOI":"10.1167\/iovs.15-16708","article-title":"Characterization of retinal disease progression in a 1-year longitudinal study of eyes with mild nonproliferative retinopathy in diabetes type 2","volume":"56","author":"Ribeiro","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026012203134467800_bib24","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0300-2896(15)30037-5","article-title":"Validation of the Spanish version of the Epworth Sleepiness Scale in patients with a sleep apnea syndrome [in Spanish]","volume":"35","author":"Chiner","year":"1999","journal-title":"Arch Bronconeumol"},{"key":"2026012203134467800_bib25","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.ophtha.2008.12.039","article-title":"Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema","volume":"116","author":"Bolz","year":"2009","journal-title":"Ophthalmology"},{"key":"2026012203134467800_bib26","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1097\/IAE.0000000000001022","article-title":"Optical coherence tomography characteristics of macular edema and hard exudates and their association with lipid serum levels in type 2 diabetes","volume":"36","author":"Davoudi","year":"2016","journal-title":"Retina"},{"key":"2026012203134467800_bib27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ajo.2019.11.014","article-title":"Effect of intravitreal ranibizumab on intraretinal hard exudates in eyes with diabetic macular edema","volume":"211","author":"Srinivas","year":"2020","journal-title":"Am J Ophthalmol"},{"key":"2026012203134467800_bib28","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1016\/j.ophtha.2010.06.019","article-title":"Optical coherence tomographic evaluation of foveal hard exudates in patients with diabetic maculopathy accompanying macular detachment","volume":"117","author":"Ota","year":"2010","journal-title":"Ophthalmology"},{"key":"2026012203134467800_bib29","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/S0161-6420(95)30989-X","article-title":"Retinal distortion and cotton-wool spots associated with epiretinal membrane contraction","volume":"102","author":"Arroyo","year":"1995","journal-title":"Ophthalmology"},{"key":"2026012203134467800_bib30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.5935\/0004-2749.20160070","article-title":"Evaluation of posterior ocular changes using enhanced depth imaging-optical coherence tomography in patients with obstructive sleep apnea syndrome","volume":"79","author":"Yuvac\u0131","year":"2016","journal-title":"Arq Bras Oftalmol"},{"key":"2026012203134467800_bib31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.smrv.2014.06.003","article-title":"Does obstructive sleep apnea cause endothelial dysfunction? A critical review of the literature","volume":"20","author":"Hoyos","year":"2015","journal-title":"Sleep Med Rev"},{"key":"2026012203134467800_bib32","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s11325-011-0519-8","article-title":"Endothelial mechanisms of endothelial dysfunction in patients with obstructive sleep apnea","volume":"16","author":"Feng","year":"2012","journal-title":"Sleep Breath"},{"key":"2026012203134467800_bib33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.4187\/respcare.03739","article-title":"Effect of CPAP on endothelial function in subjects with obstructive sleep apnea: a meta-analysis","volume":"60","author":"Xu","year":"2015","journal-title":"Respir Care"},{"key":"2026012203134467800_bib34","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s11325-018-1660-4","article-title":"Impact of continuous positive airway pressure on vascular endothelial growth factor in patients with obstructive sleep apnea: a meta-analysis","volume":"23","author":"Qi","year":"2019","journal-title":"Sleep Breath"},{"key":"2026012203134467800_bib35","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/resp.12573","article-title":"Effect of CPAP therapy on endothelial function in obstructive sleep apnoea: a systematic review and meta-analysis","volume":"20","author":"Schwarz","year":"2015","journal-title":"Respirology"},{"key":"2026012203134467800_bib36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/tvst.5.2.9","article-title":"VEGF: from discovery to therapy: the Champalimaud Award lecture","volume":"5","author":"Miller","year":"2016","journal-title":"Transl Vis Sci Technol"},{"key":"2026012203134467800_bib37","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1001\/archophthalmol.2010.220","article-title":"Frequent loss of nyctohemeral rhythm of intraocular pressure restored by nCPAP treatment in patients with severe apnea","volume":"128","author":"P\u00e9pin","year":"2010","journal-title":"Arch Ophthalmol"},{"key":"2026012203134467800_bib38","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1167\/iovs.06-1418","article-title":"Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea","volume":"49","author":"Kiekens","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026012203134467800_bib39","doi-asserted-by":"crossref","first-page":"15937","DOI":"10.1038\/s41598-020-72813-x","article-title":"Density-based classification in diabetic retinopathy through thickness of retinal layers from optical coherence tomography","volume":"10","author":"Mohammed","year":"2020","journal-title":"Sci Rep"}],"container-title":["Annals of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/21\/1\/102\/66009905\/annalsats_21_1_102.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/article-pdf\/21\/1\/102\/66009905\/annalsats_21_1_102.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:14:44Z","timestamp":1769069684000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/article\/21\/1\/102\/8382102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,1]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1,1]]},"published-print":{"date-parts":[[2024,1,1]]}},"URL":"https:\/\/doi.org\/10.1513\/annalsats.202304-296oc","relation":{},"ISSN":["2329-6933","2325-6621"],"issn-type":[{"value":"2329-6933","type":"print"},{"value":"2325-6621","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2024,1,1]]},"assertion":[{"value":"2023-04-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}