Influence of continuous positive airway pressure on optic nerve head vascularization in patients with severe obstructive sleep apnea syndrome: an OCT-angiography study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Influence of continuous positive airway pressure on optic nerve head vascularization in patients with severe obstructive sleep apnea syndrome: an OCT-angiography study Paul Louis MEURISSE, Fannie ONEN, Zhanlin ZHAO, Paul BASTELICA, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7906510/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Objective : To evaluate the influence of continuous positive airway pressure (CPAP) on the vascularization of the optic nerve head using optical coherence tomography angiography (OCT-A) in patients with severe obstructive sleep apnea syndrome (OSAS) naïve to any treatment. Patients and methods : Vascularization of the optic nerve head in the right eye of 22 patients with severe OSAS naïve to any treatment was assessed using OCT-A with AngioPlex® software (Carl Zeiss Meditec, Dublin, CA, USA). All patients underwent a comprehensive ophthalmological examination as well as OCT-A analysis of the radial peripapillary capillary (RPC) and macular superficial capillary plexus (SCP) vascular density (VD). Measurements were taken before and after three months of CPAP treatment. Results : After 3 months of CPAP treatment, total RPC vascular density significantly increased (44.65 ± 1.83 versus 45.70 ± 1.51, P = 0.04). Additionally, a positive correlation was found between the average nightly CPAP usage duration and the increase in RPC vascular density (P = 0.001, r = 0.65, 95% CI [0.14; 1.15]). Conclusion : CPAP may improve vascular density at the optic nerve head in patients with severe OSAS. Our study provides new insights into the potential vascular impact of OSAS on optic nerve vascularization. Glaucoma Optic nerve Obstructive Sleep Apnea Syndrome Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Obstructive sleep apnea syndrome (OSAS) is the most common sleep-related breathing disorder caused by repetitive obstruction of the upper airways during sleep [1]. It constitutes a cardiovascular risk factor associated with an increased risk of stroke, rhythm disorders, and coronary artery disease [2]. On an ocular level, OSAS is linked to various vascular pathologies, such as non-arteritic anterior ischemic optic neuropathy, central retinal vein occlusion, and exacerbation of diabetic retinopathy [3–7]. Despite a high prevalence of OSA in patients with glaucoma, reported in previous studies [8,9]. Previously considered an independent risk factor for glaucoma, recent studies suggest that OSAS may act more as an exacerbating factor. Studies have indicated that patients with OSAS may experience a faster progression of primary open-angle glaucoma (POAG). In a retrospective study involving 32 POAG patients, Fan et al. [10] reported that those with moderate or severe OSAS had an eightfold increased risk of retinal nerve fiber layer (RNFL) thinning compared to those without OSAS, after adjusting for potential confounding factors. Over a 3-year period, Wozniak et al. [11] observed that, after adjustment, the overall RNFL loss in POAG patients with OSAS was nearly double that of those without OSAS (1.1 vs. 0.6 μm/year). Furthermore, it has been demonstrated that in addition to impairing vascular endothelium [12], OSAS reduces blood flow in the posterior ciliary arteries [13], which are partially responsible for optic nerve head vascularization. OSAS also affects the retinal and optic nerve microvasculature. Tong et al., in a study employing Retinal Vessel Analysis (RVA) (Vesselmap3, Jena/Germany) and Dynamic Vessel Analysis (DVA) (Dynamic Vessel Analyzer, Imedos, Jena/Germany), showed a significant decrease in the mean diameter of retinal arterioles, a significant decrease in the arteriovenous ratio, as well as a reduction in arteriolar and venular vascular pulsation amplitude in patients with OSAS compared to controls. These reductions were inversely correlated with the Apnea-Hypopnea Index (AHI) [14]. Among 5 studies analyzing vascular density changes in OCT-Angiography (OCT-A) in OSAS patients, 4 found a decrease in vascular density, particularly in the radial peripapillary capillaries (RPC), compared to controls [15–19]. This reduction in vascular density aligns with the work of Hosking et al., who observed an abnormal response to hypercapnia in the posterior ciliary artery irrigating the RPC in OSAS patients [20]. Continuous positive airway pressure (CPAP) at night is the standard treatment of OSAS that prevents upper airway collapse. CPAP improves quality of life and cardiovascular risk and most importantly reduces mortality in OSA patients [21]. On an ocular level, it is believed to have a mitigating effect on glaucoma. A study by Chen et al. in 2014 [22] revealed that patients with OSAS had an increased risk of 1.88 for developing glaucoma compared to controls, and OSAS patients treated with CPAP showed a smaller increase of only 1.65. To our knowledge, no study has analyzed the influence of CPAP on the vascularization of the optic nerve as assessed by OCT-A in patients with severe OSAS. The objective of this study was therefore to investigate, using OCT-A, the changes in vascular density of the radial peripapillary capillaries (RPC) and the macular superficial capillary plexus (SCP) in patients with severe, untreated OSAS, both before and after CPAP treatment. Patients and methods Patients This retrospective observational study was conducted at Ambroise Paré University Hospital in Boulogne-Billancourt, Paris, France. The recruitment period began on Friday, July 2, 2021, and ended on Thursday, September 21, 2023. Data were extracted and analysed for reseearch purposes from Tuesday, November 9, 2021, to Tuesday, October 31, 2023. The study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the French Society of Ophthalmology. Participants were recruited at the sleep center of Ambroise Paré Hospital after undergoing a home respiratory polygraphy (Nox-T3, Nox Medical Inc., Reykjavik, Iceland) performed for clinically suspected sleep apnea. This device which is a type 3 portable monitor measures airflow by nasal pressure transduction, respiratory effort using inductance plethysmography, snoring, body position, activity (movement), and oxygen saturation by pulse oximetry. All studies were scored using Noxturnal software by the sleep physician (FO) according to the American Academy of Sleep Medicine 2012 scoring criteria [23,24]. An obstructive apnea was defined as a ≥ 90% reduction in airflow from baseline for at least 10 s associated with ongoing respiratory effort. A hypopnea was defined as a ≥ 30% reduction in the airflow signal for ≥ 10 s associated with a ≥ 3%. The average number of apneas and hypopneas per hour (apnea-hypopnea index, AHI) was determined based on the total analysis time of the home respiratory polygraphy recordings. Inclusion criteria were as follows: patients newly diagnosed of OSAS in whom CPAP therapy had been prescribed (AHI > 30/h or AHI > 15/h associated with excessive daytime sleepiness), patients who accepted CPAP treatment and the follow-up and age over 18 years. Objective CPAP usage, pressure setting, and mask leak and residual AHI data were collected via AirView™ (Resmed) at the 3rd month after therapy initiation. Adherence to treatment was defined as use of CPAP for a minimum of ≥ 4 h on at least ≥ 70% of nights over 30 consecutive days. Exclusion criteria were as follows: any clinical involvement of the optic nerve or alterations in the thickness of the ganglion cell complex (GCC) or the retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT), macular involvement, ocular hypertension, uveitis, or other ophthalmologic pathology. For all patients, the following data were recorded: age, gender, family history of glaucoma, best-corrected visual acuity (BCVA, logMAR), spherical equivalent (SE), intraocular pressure (IOP) using Goldmann applanation tonometry (mmHg), central corneal thickness (CCT) with an optical pachymeter (Haag-Streit International, Koeniz, Switzerland), and gonioscopy. The average retinal nerve fiber layer thickness (RNFL), the mean cup-to-disc ratio (c/d) of the optic disc, optic disc rim area, and average ganglion cell complex thickness were also assessed using optical coherence tomography (OCT) (Cirrus® spectral-domain OCT, Carl Zeiss Meditec Inc., Dublin, IE). Only the right eye of each patient was analyzed. OCT angiography Angiography images using Optical Coherence Tomography Angiography (OCT-A) were acquired using AngioPlexTM software, version 10.0, on the Zeiss Cirrus 5000 (Carl Zeiss Meditec, Dublin, CA, USA). Each patient underwent OCT-A examination at the time of obstructive sleep apnea syndrome (OSAS) diagnosis and before any treatment. A follow-up examination was conducted after 3 months of positive pressure ventilation (CPAP) treatment. The minimum required image quality was set at 8 out of 10 on the scale automatically generated by the software. In cases where the quality fell below 8 or exhibited numerous motion artifacts, the examination was repeated until a high-quality image was obtained. All tests were performed by the same professional. For acquiring angiographic images, AngioPlexTM software, version 10.0, on the Zeiss Cirrus 5000 (Carl Zeiss Meditec, Dublin, CA, USA) was utilized. This system, based on the Optical Coherence Tomography (OCT) spectral domain microangiography protocol, automatically analyzed the superficial capillary plexus (SCP). It used a central wavelength of 840 nm and a scanning speed of 68,000 A-scans per second. The A-scan images had an approximate resolution of 12.86 μm, with a total of 350 × 350 A-scans and a resolution of 245 A-scans in each B-scan. Vascular network images were obtained by analyzing signal changes (both in intensity and phase) from B-scans performed sequentially at the same position [25]. It also features an eye-tracking system to minimize the occurrence of artifacts [26,27]. For the macula, a volumetric scanner of 6x6 mm was selected. The scanning protocol involved 429 × 429 scans. For the quantitative analysis of macular vascularization in the SCP, the software subdivided the macular area according to the ETDRS (Early Treatment Of Diabetic Retinopathy Study) study map, considering a central circle with a radius of 1 mm from the fovea and including the foveal avascular zone (FAZ) (no blood flow signal) and two concentric rings, an inner ring (1 mm to 3 mm radius) and an outer ring (3 mm to 6 mm). The entire explored macular area was also taken into account (Figure 1). The parameters analyzed by AngioPlexTM included macular vascular density (VD) (the ratio between the total length of blood vessels - obtained from the skeletonized image - and the total surface area, measured in mm −1 ) [28] and macular perfusion density (total perfused area per unit surface area, expressed as a percentage). For the optic nerve head, a 4.5 × 4.5 mm volumetric scan centered on the optic nerve was utilized. The device automatically segmented a ring bounded by inner and outer radii of 2.00 mm and 4.50 mm, respectively, which was further subdivided into four quadrants (superior, temporal, inferior, and nasal) [29] (Figure 2). Peripapillary perfusion density was measured (total surface area of perfused capillary vasculature per unit surface area in the region of interest, expressed as a percentage %). Statistical analysis Quantitative data are presented as mean with standard deviation, and qualitative data are provided as proportions in percentage. The Student's t-test was used to compare data before and after treatment. The correlation between the average time of CPAP and the difference in vascular density at the level of the radial peripapillary capillaries (RPC), as well as the correlation between RPC vascular density with SpO2 and T<90%, were analyzed using Pearson's correlation coefficient. A P-value <0.05 was considered statistically significant. Results Patients A total of 29 patients were included in the study. Seven patients discontinued CPAP treatment before a duration of 3 months or had insufficient CPAP adherence of less than 4 hours per night. Eventually, 22 patients were analyzed (Figure 3). Regarding the characteristics of the analyzed patients, the gender ratio was 14 men for 8 women, with a mean age of 61.77 years ± 11.37 (Table 1). The subjects were free of ocular pathologies, especially glaucoma, with an average intraocular pressure (IOP) of 14.36 ± 2.61 mmHg, a mean corneal thickness of 550.31 µm ± 34.39, an average retinal nerve fiber layer (RNFL) thickness of 91.82 µm ± 10.13, and a ganglion cell complex (GCC) thickness of 82.68 ± 6.56. The mean AHI before treatment was 49.55 ± 21.7, with an average SpO2 of 91.74 ± 2.90 and a time spent with oxygen saturation below 90% (T<90%) of 15.76% ± 19.23 (Table 1). The average adherence to CPAP was 6 hours and 1 minute ± 1 hour and 14 minutes, with a usage percentage over 3 months of 91.71% ± 0.76, equivalent to 82.8 days out of 90 days (Table 1). The main characteristics of the analyzed population are summarized in Table 1. Evolution of Vascular Density We observed a significant increase in the total vascular density of radial peripapillary capillaries (RPC) (45.7 ± 1.51 vs 44.65 ± 1.83, P = 0.04) (Figure 4). The vascular densities of RPC in the superior, nasal, inferior, and temporal quadrants did not change significantly after treatment, respectively: (44.64 ± 2.55 vs 46.09 ± 1.70, P = 0.06), (43.39 ± 1.83 vs 44.39 ± 2.45, P = 0.17), (45.16 ± 2.74 vs 45.23 ± 3.41, P = 0.94), and (46.62 ± 2.43 vs 47.25 ± 2.07, P = 0.35). Similarly, the vascular density of the superficial macular capillary plexus (SMCP) did not significantly increase after CPAP (18.94 ± 0.69 vs 19.11 ± 0.65, P = 0.38) (Table 2). Regarding nighttime apneas, CPAP was effective with a significant decrease in AHI (2.83 ± 3.61 vs 49.55 ± 21.70, P < 0.0001). These results are summarized in Table 2. Intraocular pressure change We did not observe any difference in IOP before and after positive pressure ventilation treatment (14.36 ± 2.61 vs 13.5 ± 2.09, P = 0.23). Similarly, no difference was found for RNFL, GCC, and CMT (Table 2). Average duration of positive pressure ventilation A positive correlation was found between the average duration of CPAP usage per night and the increase in total vascular density of RPC ( r = 0.65, 95% CI [0.14; 1.15], P = 0.01) (Figure 5). No correlation was found between the average CPAP usage duration and vascular densities of RPC in separately analyzed quadrants, nor between the average CPAP usage duration and SMCP vascular density. No relationship was observed between the average CPAP usage duration and IOP ( r = -0.04, 95% CI [-0.83; 0.74], P = 0.90), nor between the average CPAP usage duration and changes in GCC, RNFL, or CMT. Evolution of the Apnea-Hypopnea Index No correlation was found between the difference in AHI and the difference in vascular density of RPC ( r = 0.01, 95% CI [-0.03; 0.01], P = 0.37), neither in the separately analyzed quadrants nor in the difference in SMCP vascular density. Similarly, no correlation was found between the difference in AHI pre and post-treatment and changes in IOP ( r = 0.06, 95% CI [-0.02; 0.11], P = 0.07). There was also no correlation found between the average CPAP usage duration and the difference in AHI ( r = 0.02, 95% CI [-5.17; 9.62], P = 0.54). Oxygen saturation A significant positive correlation was found between RPC vascular density and SpO2 ( r = 0.25, 95% CI [0.02; 0.52], P = 0.05). A significant correlation between vascular density and T<90% was also observed (r = -0.58, 95% CI [-0.84; -0.12], P = 0.02). However, no significant correlation was found between total vascular density of RPC and min SpO2 ( r = 0.37, 95% CI [-0.08; 0.67], P = 0.12). Similarly, no correlation was observed between SpO2 and mean IOP ( r = 0.12, 95% CI [-0.78; 0.34], P = 0.32). Apnea-Hypopnea Index No correlation was found between pre-treatment AHI and RPC DV ( r = -0.20, 95% CI [-0.33; 0.63], P = 0.17), as well as between pre-treatment AHI and pre-treatment IOP ( r = -0.27, 95% CI [-0.45; 0.26], P = 0.18). Discussion Our study found a significant increase in the total vascular density of RPC after three months of treatment with CPAP in treatment-naive severe OSA patients. To our knowledge, this is the first study to investigate the evolution of papillary vascular density after treatment in patients with severe OSA. The increased density is thought to be associated with vasodilation of peripapillary capillaries and an increase in the number of peripapillary capillaries. OSA is believed to be responsible, through alternating apneas and hypopneas, for tissue hypoxia and hypercapnia alternations, leading to vascular endothelial dysfunction, narrowing of blood vessels, reduced availability of nitric oxide (a vasodilator), increased levels of endothelin-1 (a vasoconstrictor), sympathetic activation, and a pro-inflammatory environment responsible for optic nerve head ischemia and damage [ 12 , 30 – 35 ]. By correcting nocturnal hypoxemia, CPAP would halt this cascade of alterations, allowing an increase in vascular density and, consequently, reducing damage to ganglion cells, which are highly sensitive to abnormal perfusion and reduced oxygen saturation [ 31 , 36 ]. Three other studies have investigated changes in ocular vascularization after CPAP treatment. Our study is consistent with that of Wong et al. , who studied static retinal vessel caliber on fundus photography (RVA) and dynamic vascular pulsations amplitudes (DVA) in OSA patients after one year of CPAP. These authors found an increase in retinal vessel caliber in the CPAP-treated group and a narrowing of caliber in the untreated group [ 37 ]. However, our study disagrees with the other two. Tonini et al. 's study in 2010 did not find changes in choroidal vasoreactivity using laser Doppler flowmetry (LDF) after six months of CPAP [ 38 ]. Several studies, however, have directly compared the reproducibility of OCT-A with other blood flow instruments and found that its intra- and inter-visit reproducibility is generally much better than that of LDF [ 16 , 39 – 42 ]. Moreover, choroidal blood flow in Doppler ultrasound and choroidal vascular density in OCT-A are not the most relevant elements to analyze concerning the optic nerve since they are not correlated with visual field deficits [ 43 – 45 ]. On the other hand, Turnbull et al. 's study in 2020 compared retinal arteriolar diameter in DVA in two groups of OSA patients, one treated with CPAP and the other with "sham CPAP" for 14 days [ 46 ]. No changes in arteriolar diameter or alterations in vasoreactivity after a cold-water challenge were observed. The 14-day duration was probably too short to show changes in vessel caliber, especially since RVA analyzes arteriolar and venular calibers, not vascular density, including smaller vessels, as OCT-A allows. Thus, changes in blood capillaries in the optic nerve could have occurred and gone unnoticed. Finally, Turnbull et al. had composed two distinct groups, whereas in our study, we analyzed the same patients before and after, allowing for better comparability and minimizing confounding factors. Even though it was modest, the increase in vascular density in RPC in our study suggests an improvement in the microvascularization and endothelial function induced by CPAP in OSA patients. These findings are consistent with those of Ye et al. , who found an improvement in the macular density of deep and superficial plexuses as well as the foveolar avascular zone in children with OSA before and after adenoidectomy, a reference treatment for OSA in children [ 47 ]. They also found a statistically significant improvement in the diameter, density, surface, and perimeter of macular capillaries. The density of RPC was not analyzed, unlike in our study. According to Ye et al. , the decrease in vascular density is more significant in the peripapillary zone of OSA patients [ 15 , 17 , 19 ] than in the parafoveal zone. However, changes in vascular density in response to hyperoxia are more pronounced in the parafoveal region [ 48 ] than in the peripapillary region. This is why Ye et al. did not analyze vascular density in RPC. Xu et al. showed that vascular densities in RPC, but especially in the superficial macular plexus, decreased after acute hyperoxia challenge in healthy adult subjects. However, Sousa et al. observed that macular and RPC vascular densities increased similarly in response to acute hypoxia in healthy subjects [ 49 ]. Moreover, Hoskin et al. , who found an abnormal response to hypercapnia in the posterior ciliary artery supplying RPC in OSA patients, did not observe an abnormal response to hypercapnia in the central retinal artery supplying the superficial and deep macular plexuses [ 20 ]. Thus, it is not surprising that correcting OSA results in improvement in the territory of the posterior ciliary artery and therefore in RPC. Xu and Sousa suggested a decrease in vascular density during acute hyperoxia and an increase in vascular density during acute hypoxia [ 48 , 49 ]. This contradicts our results. Similarly, Cai et al. found a paradoxical significant increase in the deep macular plexus vascular density in OSA patients compared to controls [ 15 ]. This suggests a possible adaptation of vascular density to acute hypoxia episodes caused by OSA apneas. However, the studies by Xu and Sousa focused on an acute episode of oxygenation change in healthy subjects whose endothelial function had not been impaired by OSA. Similarly, the increase in deep macular plexus density in Cai's study was not found in Wang et al. 's study involving more severe OSA patients (AHI > 60) or in Turgay et al. 's study, which had an older population than Cai et al. 's [ 16 , 17 ]. Cai's younger population with less severe OSA likely had preserved endothelial function with retained physiological response to hypoxia. These results suggest that the older and more severe the OSA, the greater the endothelial dysfunction and atherosclerosis, resulting in reduced vascular reactivity to hypoxia and decreased vascular density. It would be interesting to perform the same hypoxia or hyperoxia challenge tests in OSA patients to confirm the alteration of their vasoreactivity. In case of alteration, repeating the experiment after a few months of CPAP treatment could reveal a possible reversibility under treatment. Our study also found a positive and inverse correlation of vascular density in RPC with SpO2 and T < 90%, respectively. A positive correlation was found between the average nightly use of CPAP and the increase in total RPC vascular density. These results suggest a strong association between vascular density and the oxygenation of OSA patients. The longer the CPAP use, the greater the increase in vascular density. Previous studies had shown a similar relationship between oxygen saturation and RNFL impairment [ 50 – 52 ]. It would have been interesting to conduct a post-treatment polysomnography to obtain SpO2 and T < 90% and draw more precise conclusions about the increase in vascular density based on oxygenation parameters. Furthermore, other studies have found a beneficial effect of CPAP on the optic nerve. Liguori et al. showed that patients with good CPAP compliance over a year had improved visual evoked potentials (VEP) with an increase in P100 amplitude and a decrease in P100 latency [ 53 ]. Similarly, Himori et al. demonstrated a slowing of visual field loss after CPAP [ 54 ]. We also did not observe any difference between IOP before and after treatment (14.36 ± 2.61 vs. 13.5 ± 2.08, P = 0.23). This contradicts previous studies that found an increase of up to 3 mmHg without associated visual field alterations [ 55 , 56 ]. This increase would be related to the rise in intra-thoracic pressure caused by CPAP use. However, the only study to continuously study IOP in OSA patients treated with CPAP found an increase in nocturnal IOP without a significant difference in 24-hour IOP [ 57 ]. Muniesa et al. suggested that CPAP restores the normal IOP rhythm altered by OSA. We did not find a correlation between SpO2 and IOP. Indeed, hypoxia could play a role in IOP increase. Najmanová et al. [ 58 ] found a statistically significant increase in IOP in patients exposed to normobaric hypoxia. IOP had decreased before and after 4 and 10 minutes of hypoxia by 1.2 mmHg ± 1.9 mmHg and 0.9 mmHg ± 2.3 mmHg at minute 10, respectively. This difference was very small, and our study might not have a sufficient power to demonstrate it. To our knowledge, this is the first study analyzing the evolution of vascular density after CPAP treatment in patients with severe OSA. One of the main strengths of our study is the comparability of groups before and after treatment. Indeed, it involves the same subjects, maximizing comparability and minimizing the influence of confounding factors such as cardiovascular risk factors, BMI, smoking, among others. Finally, the average CPAP duration per night was significant (6h01), considering the usually low adherence to treatment [ 59 ]. However, our study had several limitations. Firstly, it suffered from a small sample size, leading to low statistical power. Secondly, although the reproducibility of OCT-A is known and proven [ 60 – 62 ], we did not test the inter-operator reproducibility. Moreover, the study only included 3 months of treatment; a longer-term analysis might yield more significant results. A final PSG at the end of treatment would have been desirable to refine the results related to oxygen saturation. Lastly, heavy smokers or those with respiratory failure were not excluded; there were two heavy smokers which could explain the non-concordance between AHI and SpO2. CPAP appears to be beneficial for the optic nerve by improving the vascular density of radial peripapillary capillaries (RPC). This study opens useful perspectives in evaluating the effect of CPAP in managing OSA, especially since changes in retinal vessel diameter are linked to the risk of coronary artery disease, stroke, and stroke-related mortality [ 63 , 64 ]. Finally, by better understanding the vascular changes involved at the level of the optic nerve head, this study contributes to improving the understanding of the pathophysiology of glaucoma and its relationship with OSA. Abbreviations AASM American Academy of Sleep Medicine AHI Apnea-Hypopnea Index AP-HP Assistance Publique – Hôpitaux de Paris BCVA Best-Corrected Visual Acuity BMI Body Mass Index CCT Central Corneal Thickness CESP Centre de recherche en Épidémiologie et Santé des Populations CI Confidence Interval CMT Central Macular Thickness CNRS Centre National de la Recherche Scientifique CPAP Continuous Positive Airway Pressure DVA Dynamic Vessel Analysis ETDRS Early Treatment Diabetic Retinopathy Study FAZ Foveal Avascular Zone GCC Ganglion Cell Complex IHU Institut Hospitalo-Universitaire INSERM Institut National de la Santé et de la Recherche Médicale IOP Intraocular Pressure LDF Laser Doppler Flowmetry MD Doctor of Medicine OCT Optical Coherence Tomography OCT-A Optical Coherence Tomography Angiography OSA Obstructive Sleep Apnea OSAS Obstructive Sleep Apnea Syndrome POAG Primary Open-Angle Glaucoma PhD Doctor of Philosophy Pr Professor PSG Polysomnography RGC Retinal Ganglion Cells RNFL Retinal Nerve Fiber Layer RPC Radial Peripapillary Capillaries RVA Retinal Vessel Analysis SCP Superficial Capillary Plexus SE Spherical Equivalent SMCP Superficial Macular Capillary Plexus SpO2 Peripheral capillary oxygen saturation T<90% Time spent with oxygen saturation below 90% VD Vascular Density VEP Visual Evoked Potentials Declarations Ethics approval and consent to participate The study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the French Society of Ophthalmology. Informed consent was obtained from all subjects. Consent for publication Not Applicable Acknowledgements Funding: This research received no external funding Conflicts of Interest: The author declares no conflict of interest with this work. Author Contribution PLM, FO and AL wrote the main manuscript text. ZZ and PB prepared the figured. All authors reviewed the manuscript. Data Availability The datasets generated and analyzed during the curent study are not publicly available due to patient confidentiality but are available from corresponding author on reasonable request. References Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased Prevalence of Sleep-Disordered Breathing in Adults. American Journal of Epidemiology. 2013;177:1006‑14. Thylefors B, Négrel AD, Pararajasegaram R, Dadzie KY. Global data on blindness. Bull World Health Organ. 1995;73:115‑21. Augstburger E, Ballino A, Keilani C, Robin M, Baudouin C, Labbé A. 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IOP: Intraocular Pressure, RNFL: Retinal Nerve Fiber Layer thickness, GCC: Average Macular Ganglion Cell Complex thickness, CMT: Central Macular Thickness, AHI: Apnea-Hypopnea Index, SpO2: Average Oxygen Saturation, T<90%: Time spent with saturation below 90%, Min SpO2: Minimum Oxygen Saturation. Demographic Characteristics Patients (22) % Age (years) 61.7 11.38 Gender Male 14 63.64 Female 8 36.36 Ethnicity Caucasian 16 72.72 Asian 0 0 African-American 6 27.28 General characteristics Standard deviation BMI 33.2 7.11 Ophtalmological characteristics Standard deviation IOP (mmHg) 14.36 2.61 Corneal thickness (µm) 550.31 34.39 RNFL 91.82 10.13 GCC 82.68 6.56 CMT 260.68 22.11 Pulmonary characteristics Standard deviation AHI 49.55 21.7 Average SpO2 (%) 91.74 2.9 T<90% (%) 15.76 19.23 Min SpO2 (%) 77 10.26 CPAP duration 6h01 1h14 Days of use over 3 months (%) 91.71 0.76 Table 2: Results of analyses before and after continuous positive airway pressure treatment in patients with severe obstructive sleep apnea (OSA). VD: Vascular Density, RPC: Radial Peripapillary Capillaries, SMCP: Superficial Macular Capillary Plexus, RNFL: Retinal Nerve Fiber Layer, GCC: Ganglion Cell Complex, CMT : Central Macular Thickness, IOP: Intraocular Pressure, AHI: Apnea-Hypopnea Index. Before After Average and standard deviation Average and standard deviation Significance VD RPC 44.65 ± 1.83 45.7 ± 1.51 P = 0.04 VD RPC by quadrant Supérior 44.63 ± 2.56 46.08 ± 1.70 P = 0.06 Nasal 43.39 ± 1.83 44.30 ± 2.45 P = 0.17 Inférior 45.16 ± 2.74 45.23 ± 3.41 P = 0.94 Temporal 46.62 ± 2.43 47.25 ± 2.07 P = 0.35 VD SMCP 18.94 ± 0.69 19.12 ± 0.65 P = 0.38 RNFL 96.82 ± 10.13 96.39 ± 10.04 P = 0.98 GCC 82.68 ± 6.56 82.69 ± 6.14 P = 0.99 CMT 260.68 ± 22.11 263.50 ± 24.07 P = 0.99 IOP 14.36 ± 2.61 13.5 ± 2.08 P = 0.23 AHI 49.55 ± 21.70 2.83± 3.61 P < 0,0001 Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":1062008,"visible":true,"origin":"","legend":"\u003cp\u003eSuperficial macular capillary plexus 6x6mm scan. Segmentation and analysis using AngioPlexTM. Signal strength 9/10.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-7906510/v1/2d997c7e72222e87c9fbdf74.png"},{"id":97119000,"identity":"24997678-e63c-4c6a-8fb9-1da7137fa5b5","added_by":"auto","created_at":"2025-12-01 07:42:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1557676,"visible":true,"origin":"","legend":"\u003cp\u003eRadial peripapillary capillary plexus 4.5x4.5 mm scan. Segmentation and analysis by AngioPlexTM. Signal strength: 9/10.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-7906510/v1/c1df177111dafef8518bee28.png"},{"id":97140747,"identity":"0a458383-28e4-42b6-9e73-b223f335da8d","added_by":"auto","created_at":"2025-12-01 10:05:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74988,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart. AHI: Apnea-Hypopnea Index in number of episodes per hour, CPAP: Positive Pressure Ventilation.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-7906510/v1/4fad283a99cef9811d745f91.png"},{"id":97119009,"identity":"76427d89-9e0c-4b29-8027-727b9de9c663","added_by":"auto","created_at":"2025-12-01 07:42:06","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":358976,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of vascular density before and after positive pressure ventilation treatment.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-7906510/v1/550c6f0899e933010d429738.png"},{"id":97119010,"identity":"36135f42-f641-41d5-a795-5da3a1160075","added_by":"auto","created_at":"2025-12-01 07:42:06","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":299062,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between CPAP duration and vascular density. CPAP: Continuous Positive Airway Pressure, RPC: Radial Peripapillary Capillaries.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-7906510/v1/3c1bad2d9f665fcfd165537d.png"},{"id":97248610,"identity":"eb52f4ff-21a6-4902-a8b4-c494c2bf3d30","added_by":"auto","created_at":"2025-12-02 13:04:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4043068,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7906510/v1/858173c6-da88-4d4f-a7b1-b34c39dcdb02.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Influence of continuous positive airway pressure on optic nerve head vascularization in patients with severe obstructive sleep apnea syndrome: an OCT-angiography study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eObstructive sleep apnea syndrome (OSAS) is the most common sleep-related breathing disorder caused by repetitive obstruction of the upper airways during sleep [1]. It constitutes a cardiovascular risk factor associated with an increased risk of stroke, rhythm disorders, and coronary artery disease [2]. On an ocular level, OSAS is linked to various vascular pathologies, such as non-arteritic anterior ischemic optic neuropathy, central retinal vein occlusion, and exacerbation of diabetic retinopathy [3\u0026ndash;7]. Despite a high prevalence of OSA in patients with glaucoma, reported in previous studies [8,9]. \u003c/p\u003e\n\n\u003cp\u003ePreviously considered an independent risk factor for glaucoma, recent studies suggest that OSAS may act more as an exacerbating factor. Studies have indicated that patients with OSAS may experience a faster progression of primary open-angle glaucoma (POAG). In a retrospective study involving 32 POAG patients, Fan et al. [10] reported that those with moderate or severe OSAS had an eightfold increased risk of retinal nerve fiber layer (RNFL) thinning compared to those without OSAS, after adjusting for potential confounding factors. Over a 3-year period, Wozniak et al. [11] observed that, after adjustment, the overall RNFL loss in POAG patients with OSAS was nearly double that of those without OSAS (1.1 vs. 0.6 \u0026mu;m/year).\u003c/p\u003e\n\u003cp\u003eFurthermore, it has been demonstrated that in addition to impairing vascular endothelium [12], OSAS reduces blood flow in the posterior ciliary arteries [13], which are partially responsible for optic nerve head vascularization. OSAS also affects the retinal and optic nerve microvasculature. Tong et al., in a study employing Retinal Vessel Analysis (RVA) (Vesselmap3, Jena/Germany) and Dynamic Vessel Analysis (DVA) (Dynamic Vessel Analyzer, Imedos, Jena/Germany), showed a significant decrease in the mean diameter of retinal arterioles, a significant decrease in the arteriovenous ratio, as well as a reduction in arteriolar and venular vascular pulsation amplitude in patients with OSAS compared to controls. These reductions were inversely correlated with the Apnea-Hypopnea Index (AHI) [14]. Among 5 studies analyzing vascular density changes in OCT-Angiography (OCT-A) in OSAS patients, 4 found a decrease in vascular density, particularly in the radial peripapillary capillaries (RPC), compared to controls [15\u0026ndash;19]. This reduction in vascular density aligns with the work of Hosking et al., who observed an abnormal response to hypercapnia in the posterior ciliary artery irrigating the RPC in OSAS patients [20].\u003c/p\u003e\n\u003cp\u003eContinuous positive airway pressure (CPAP) at night is the standard treatment of OSAS that prevents upper airway collapse. CPAP improves quality of life and cardiovascular risk and most importantly reduces mortality in OSA patients [21].\u003c/p\u003e\n\n\u003cp\u003eOn an ocular level, it is believed to have a mitigating effect on glaucoma. A study by Chen et al. in 2014 [22] revealed that patients with OSAS had an increased risk of 1.88 for developing glaucoma compared to controls, and OSAS patients treated with CPAP showed a smaller increase of only 1.65.\u003c/p\u003e\n\u003cp\u003eTo our knowledge, no study has analyzed the influence of CPAP on the vascularization of the optic nerve as assessed by OCT-A in patients with severe OSAS. The objective of this study was therefore to investigate, using OCT-A, the changes in vascular density of the radial peripapillary capillaries (RPC) and the macular superficial capillary plexus (SCP) in patients with severe, untreated OSAS, both before and after CPAP treatment.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective observational study was conducted at Ambroise Par\u0026eacute; University Hospital in Boulogne-Billancourt, Paris, France. The recruitment period began on Friday, July 2, 2021, and ended on Thursday, September 21, 2023. Data were extracted and analysed for reseearch purposes from Tuesday, November 9, 2021, to Tuesday, October 31, 2023. The study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the French Society of Ophthalmology. \u003c/p\u003e\n\u003cp\u003eParticipants were recruited at the sleep center of Ambroise Par\u0026eacute; Hospital after undergoing a home respiratory polygraphy (Nox-T3, Nox Medical Inc., Reykjavik, Iceland) performed for clinically suspected sleep apnea. This device which is a type 3 portable monitor measures airflow by nasal pressure transduction, respiratory effort using inductance plethysmography, snoring, body position, activity (movement), and oxygen saturation by pulse oximetry. \u003c/p\u003e\n\u003cp\u003eAll studies were scored using Noxturnal software by the sleep physician (FO) according to the American Academy of Sleep Medicine 2012 scoring criteria [23,24]. An obstructive apnea was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;90% reduction in airflow from baseline for at least 10 s associated with ongoing respiratory effort. A hypopnea was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;30% reduction in the airflow signal for \u0026ge;\u0026thinsp;10 s associated with a\u0026thinsp;\u0026ge;\u0026thinsp;3%. The average number of apneas and hypopneas per hour (apnea-hypopnea index, AHI) was determined based on the total analysis time of the home respiratory polygraphy recordings.\u003c/p\u003e\n\n\u003cp\u003eInclusion criteria were as follows: patients newly diagnosed of OSAS in whom CPAP therapy had been prescribed (AHI \u0026gt; 30/h or AHI \u0026gt; 15/h associated with excessive daytime sleepiness), patients who accepted CPAP treatment and the follow-up and age over 18 years.\u003c/p\u003e\n\n\u003cp\u003eObjective CPAP usage, pressure setting, and mask leak and residual AHI data were collected via AirView\u0026trade; (Resmed) at the 3rd month after therapy initiation. Adherence to treatment was defined as use of CPAP for a minimum of \u0026ge;\u0026thinsp;4 h on at least\u0026thinsp;\u0026ge;\u0026thinsp;70% of nights over 30 consecutive days. \u003c/p\u003e\n\n\u003cp\u003eExclusion criteria were as follows: any clinical involvement of the optic nerve or alterations in the thickness of the ganglion cell complex (GCC) or the retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT), macular involvement, ocular hypertension, uveitis, or other ophthalmologic pathology.\u003c/p\u003e\n\u003cp\u003eFor all patients, the following data were recorded: age, gender, family history of glaucoma, best-corrected visual acuity (BCVA, logMAR), spherical equivalent (SE), intraocular pressure (IOP) using Goldmann applanation tonometry (mmHg), central corneal thickness (CCT) with an optical pachymeter (Haag-Streit International, Koeniz, Switzerland), and gonioscopy. The average retinal nerve fiber layer thickness (RNFL), the mean cup-to-disc ratio (c/d) of the optic disc, optic disc rim area, and average ganglion cell complex thickness were also assessed using optical coherence tomography (OCT) (Cirrus\u0026reg; spectral-domain OCT, Carl Zeiss Meditec Inc., Dublin, IE). Only the right eye of each patient was analyzed.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eOCT angiography\u003c/em\u003e\u003c/p\u003e\n\n\u003cp\u003eAngiography images using Optical Coherence Tomography Angiography (OCT-A) were acquired using AngioPlexTM software, version 10.0, on the Zeiss Cirrus 5000 (Carl Zeiss Meditec, Dublin, CA, USA). Each patient underwent OCT-A examination at the time of obstructive sleep apnea syndrome (OSAS) diagnosis and before any treatment. A follow-up examination was conducted after 3 months of positive pressure ventilation (CPAP) treatment. The minimum required image quality was set at 8 out of 10 on the scale automatically generated by the software. In cases where the quality fell below 8 or exhibited numerous motion artifacts, the examination was repeated until a high-quality image was obtained. All tests were performed by the same professional.\u003c/p\u003e\n\u003cp\u003eFor acquiring angiographic images, AngioPlexTM software, version 10.0, on the Zeiss Cirrus 5000 (Carl Zeiss Meditec, Dublin, CA, USA) was utilized. This system, based on the Optical Coherence Tomography (OCT) spectral domain microangiography protocol, automatically analyzed the superficial capillary plexus (SCP). It used a central wavelength of 840 nm and a scanning speed of 68,000 A-scans per second. The A-scan images had an approximate resolution of 12.86 \u0026mu;m, with a total of 350 \u0026times; 350 A-scans and a resolution of 245 A-scans in each B-scan. Vascular network images were obtained by analyzing signal changes (both in intensity and phase) from B-scans performed sequentially at the same position [25].\u003c/p\u003e\n\u003cp\u003eIt also features an eye-tracking system to minimize the occurrence of artifacts [26,27]. For the macula, a volumetric scanner of 6x6 mm was selected. The scanning protocol involved 429 \u0026times; 429 scans.\u003c/p\u003e\n\u003cp\u003eFor the quantitative analysis of macular vascularization in the SCP, the software subdivided the macular area according to the ETDRS (Early Treatment Of Diabetic Retinopathy Study) study map, considering a central circle with a radius of 1 mm from the fovea and including the foveal avascular zone (FAZ) (no blood flow signal) and two concentric rings, an inner ring (1 mm to 3 mm radius) and an outer ring (3 mm to 6 mm). The entire explored macular area was also taken into account (Figure 1).\u003c/p\u003e\n\u003cp\u003eThe parameters analyzed by AngioPlexTM included macular vascular density (VD) (the ratio between the total length of blood vessels - obtained from the skeletonized image - and the total surface area, measured in mm\u003csup\u003e\u0026minus;1\u003c/sup\u003e) [28] and macular perfusion density (total perfused area per unit surface area, expressed as a percentage).\u003c/p\u003e\n\u003cp\u003eFor the optic nerve head, a 4.5 \u0026times; 4.5 mm volumetric scan centered on the optic nerve was utilized. The device automatically segmented a ring bounded by inner and outer radii of 2.00 mm and 4.50 mm, respectively, which was further subdivided into four quadrants (superior, temporal, inferior, and nasal) [29] (Figure 2).\u003c/p\u003e\n\n\u003cp\u003ePeripapillary perfusion density was measured (total surface area of perfused capillary vasculature per unit surface area in the region of interest, expressed as a percentage %).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eQuantitative data are presented as mean with standard deviation, and qualitative data are provided as proportions in percentage. The Student\u0026apos;s t-test was used to compare data before and after treatment. The correlation between the average time of CPAP and the difference in vascular density at the level of the radial peripapillary capillaries (RPC), as well as the correlation between RPC vascular density with SpO2 and T\u0026lt;90%, were analyzed using Pearson\u0026apos;s correlation coefficient. A \u003cem\u003eP-value \u003c/em\u003e\u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA total of 29 patients were included in the study. Seven patients discontinued CPAP treatment before a duration of 3 months or had insufficient CPAP adherence of less than 4 hours per night. Eventually, 22 patients were analyzed (Figure 3). Regarding the characteristics of the analyzed patients, the gender ratio was 14 men for 8 women, with a mean age of 61.77 years \u0026plusmn; 11.37 (Table 1). The subjects were free of ocular pathologies, especially glaucoma, with an average intraocular pressure (IOP) of 14.36 \u0026plusmn; 2.61 mmHg, a mean corneal thickness of 550.31 \u0026micro;m \u0026plusmn; 34.39, an average retinal nerve fiber layer (RNFL) thickness of 91.82 \u0026micro;m \u0026plusmn; 10.13, and a ganglion cell complex (GCC) thickness of 82.68 \u0026plusmn; 6.56. The mean AHI before treatment was 49.55 \u0026plusmn; 21.7, with an average SpO2 of 91.74 \u0026plusmn; 2.90 and a time spent with oxygen saturation below 90% (T\u0026lt;90%) of 15.76% \u0026plusmn; 19.23 (Table 1). The average adherence to CPAP was 6 hours and 1 minute \u0026plusmn; 1 hour and 14 minutes, with a usage percentage over 3 months of 91.71% \u0026plusmn; 0.76, equivalent to 82.8 days out of 90 days (Table 1). The main characteristics of the analyzed population are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEvolution of Vascular Density\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe observed a significant increase in the total vascular density of radial peripapillary capillaries (RPC) (45.7 \u0026plusmn; 1.51 vs 44.65 \u0026plusmn; 1.83, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.04) (Figure 4). The vascular densities of RPC in the superior, nasal, inferior, and temporal quadrants did not change significantly after treatment, respectively: (44.64 \u0026plusmn; 2.55 vs 46.09 \u0026plusmn; 1.70, \u003cem\u003eP\u003c/em\u003e = 0.06), (43.39 \u0026plusmn; 1.83 vs 44.39 \u0026plusmn; 2.45, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.17), (45.16 \u0026plusmn; 2.74 vs 45.23 \u0026plusmn; 3.41, \u003cem\u003eP\u003c/em\u003e = 0.94), and (46.62 \u0026plusmn; 2.43 vs 47.25 \u0026plusmn; 2.07, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.35). Similarly, the vascular density of the superficial macular capillary plexus (SMCP) did not significantly increase after CPAP (18.94 \u0026plusmn; 0.69 vs 19.11 \u0026plusmn; 0.65, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.38) (Table 2). Regarding nighttime apneas, CPAP was effective with a significant decrease in AHI (2.83 \u0026plusmn; 3.61 vs 49.55 \u0026plusmn; 21.70, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.0001). These results are summarized in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIntraocular pressure change\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe did not observe any difference in IOP before and after positive pressure ventilation treatment (14.36 \u0026plusmn; 2.61 vs 13.5 \u0026plusmn; 2.09,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e = 0.23). Similarly, no difference was found for RNFL, GCC, and CMT (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAverage duration of positive pressure ventilation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA positive correlation was found between the average duration of CPAP usage per night and the increase in total vascular density of RPC (\u003cem\u003er\u003c/em\u003e = 0.65, 95% CI [0.14; 1.15], \u003cem\u003eP\u003c/em\u003e = 0.01) (Figure 5). No correlation was found between the average CPAP usage duration and vascular densities of RPC in separately analyzed quadrants, nor between the average CPAP usage duration and SMCP vascular density. No relationship was observed between the average CPAP usage duration and IOP (\u003cem\u003er\u0026nbsp;\u003c/em\u003e= -0.04, 95% CI [-0.83; 0.74], \u003cem\u003eP\u003c/em\u003e = 0.90), nor between the average CPAP usage duration and changes in GCC, RNFL, or CMT.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEvolution of the Apnea-Hypopnea Index\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo correlation was found between the difference in AHI and the difference in vascular density of RPC (\u003cem\u003er\u0026nbsp;\u003c/em\u003e= 0.01, 95% CI [-0.03; 0.01], \u003cem\u003eP\u003c/em\u003e = 0.37), neither in the separately analyzed quadrants nor in the difference in SMCP vascular density. Similarly, no correlation was found between the difference in AHI pre and post-treatment and changes in IOP (\u003cem\u003er\u003c/em\u003e = 0.06, 95% CI [-0.02; 0.11], \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.07). There was also no correlation found between the average CPAP usage duration and the difference in AHI (\u003cem\u003er\u003c/em\u003e = 0.02, 95% CI [-5.17; 9.62],\u003cem\u003e\u0026nbsp;P\u003c/em\u003e = 0.54).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOxygen saturation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA significant positive correlation was found between RPC vascular density and SpO2 (\u003cem\u003er\u003c/em\u003e = 0.25, 95% CI [0.02; 0.52], \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.05). A significant correlation between vascular density and T\u0026lt;90% was also observed (r = -0.58, 95% CI [-0.84; -0.12], P = 0.02). However, no significant correlation was found between total vascular density of RPC and min SpO2 (\u003cem\u003er\u003c/em\u003e = 0.37, 95% CI [-0.08; 0.67], \u003cem\u003eP\u003c/em\u003e = 0.12). Similarly, no correlation was observed between SpO2 and mean IOP (\u003cem\u003er\u003c/em\u003e = 0.12, 95% CI [-0.78; 0.34], \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.32).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eApnea-Hypopnea Index\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo correlation was found between pre-treatment AHI and RPC DV (\u003cem\u003er\u003c/em\u003e = -0.20, 95% CI [-0.33; 0.63], \u003cem\u003eP\u003c/em\u003e = 0.17), as well as between pre-treatment AHI and pre-treatment IOP (\u003cem\u003er\u003c/em\u003e = -0.27, 95% CI [-0.45; 0.26], \u003cem\u003eP\u003c/em\u003e = 0.18).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study found a significant increase in the total vascular density of RPC after three months of treatment with CPAP in treatment-naive severe OSA patients. To our knowledge, this is the first study to investigate the evolution of papillary vascular density after treatment in patients with severe OSA.\u003c/p\u003e\u003cp\u003eThe increased density is thought to be associated with vasodilation of peripapillary capillaries and an increase in the number of peripapillary capillaries. OSA is believed to be responsible, through alternating apneas and hypopneas, for tissue hypoxia and hypercapnia alternations, leading to vascular endothelial dysfunction, narrowing of blood vessels, reduced availability of nitric oxide (a vasodilator), increased levels of endothelin-1 (a vasoconstrictor), sympathetic activation, and a pro-inflammatory environment responsible for optic nerve head ischemia and damage [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR31 CR32 CR33 CR34\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. By correcting nocturnal hypoxemia, CPAP would halt this cascade of alterations, allowing an increase in vascular density and, consequently, reducing damage to ganglion cells, which are highly sensitive to abnormal perfusion and reduced oxygen saturation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThree other studies have investigated changes in ocular vascularization after CPAP treatment. Our study is consistent with that of Wong \u003cem\u003eet al.\u003c/em\u003e, who studied static retinal vessel caliber on fundus photography (RVA) and dynamic vascular pulsations amplitudes (DVA) in OSA patients after one year of CPAP. These authors found an increase in retinal vessel caliber in the CPAP-treated group and a narrowing of caliber in the untreated group [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. However, our study disagrees with the other two. Tonini \u003cem\u003eet al.\u003c/em\u003e's study in 2010 did not find changes in choroidal vasoreactivity using laser Doppler flowmetry (LDF) after six months of CPAP [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Several studies, however, have directly compared the reproducibility of OCT-A with other blood flow instruments and found that its intra- and inter-visit reproducibility is generally much better than that of LDF [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR40 CR41\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Moreover, choroidal blood flow in Doppler ultrasound and choroidal vascular density in OCT-A are not the most relevant elements to analyze concerning the optic nerve since they are not correlated with visual field deficits [\u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. On the other hand, Turnbull \u003cem\u003eet al.\u003c/em\u003e's study in 2020 compared retinal arteriolar diameter in DVA in two groups of OSA patients, one treated with CPAP and the other with \"sham CPAP\" for 14 days [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. No changes in arteriolar diameter or alterations in vasoreactivity after a cold-water challenge were observed. The 14-day duration was probably too short to show changes in vessel caliber, especially since RVA analyzes arteriolar and venular calibers, not vascular density, including smaller vessels, as OCT-A allows. Thus, changes in blood capillaries in the optic nerve could have occurred and gone unnoticed. Finally, Turnbull \u003cem\u003eet al.\u003c/em\u003e had composed two distinct groups, whereas in our study, we analyzed the same patients before and after, allowing for better comparability and minimizing confounding factors.\u003c/p\u003e\u003cp\u003eEven though it was modest, the increase in vascular density in RPC in our study suggests an improvement in the microvascularization and endothelial function induced by CPAP in OSA patients. These findings are consistent with those of Ye \u003cem\u003eet al.\u003c/em\u003e, who found an improvement in the macular density of deep and superficial plexuses as well as the foveolar avascular zone in children with OSA before and after adenoidectomy, a reference treatment for OSA in children [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. They also found a statistically significant improvement in the diameter, density, surface, and perimeter of macular capillaries. The density of RPC was not analyzed, unlike in our study. According to Ye \u003cem\u003eet al.\u003c/em\u003e, the decrease in vascular density is more significant in the peripapillary zone of OSA patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] than in the parafoveal zone. However, changes in vascular density in response to hyperoxia are more pronounced in the parafoveal region [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] than in the peripapillary region. This is why Ye \u003cem\u003eet al.\u003c/em\u003e did not analyze vascular density in RPC. Xu \u003cem\u003eet al.\u003c/em\u003e showed that vascular densities in RPC, but especially in the superficial macular plexus, decreased after acute hyperoxia challenge in healthy adult subjects. However, Sousa \u003cem\u003eet al.\u003c/em\u003e observed that macular and RPC vascular densities increased similarly in response to acute hypoxia in healthy subjects [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Moreover, Hoskin \u003cem\u003eet al.\u003c/em\u003e, who found an abnormal response to hypercapnia in the posterior ciliary artery supplying RPC in OSA patients, did not observe an abnormal response to hypercapnia in the central retinal artery supplying the superficial and deep macular plexuses [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Thus, it is not surprising that correcting OSA results in improvement in the territory of the posterior ciliary artery and therefore in RPC.\u003c/p\u003e\u003cp\u003eXu and Sousa suggested a decrease in vascular density during acute hyperoxia and an increase in vascular density during acute hypoxia [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. This contradicts our results. Similarly, Cai \u003cem\u003eet al.\u003c/em\u003e found a paradoxical significant increase in the deep macular plexus vascular density in OSA patients compared to controls [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This suggests a possible adaptation of vascular density to acute hypoxia episodes caused by OSA apneas. However, the studies by Xu and Sousa focused on an acute episode of oxygenation change in healthy subjects whose endothelial function had not been impaired by OSA. Similarly, the increase in deep macular plexus density in Cai's study was not found in Wang \u003cem\u003eet al.\u003c/em\u003e's study involving more severe OSA patients (AHI\u0026thinsp;\u0026gt;\u0026thinsp;60) or in Turgay \u003cem\u003eet al.\u003c/em\u003e's study, which had an older population than Cai \u003cem\u003eet al.\u003c/em\u003e's [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Cai's younger population with less severe OSA likely had preserved endothelial function with retained physiological response to hypoxia. These results suggest that the older and more severe the OSA, the greater the endothelial dysfunction and atherosclerosis, resulting in reduced vascular reactivity to hypoxia and decreased vascular density. It would be interesting to perform the same hypoxia or hyperoxia challenge tests in OSA patients to confirm the alteration of their vasoreactivity. In case of alteration, repeating the experiment after a few months of CPAP treatment could reveal a possible reversibility under treatment.\u003c/p\u003e\u003cp\u003eOur study also found a positive and inverse correlation of vascular density in RPC with SpO2 and T\u0026thinsp;\u0026lt;\u0026thinsp;90%, respectively. A positive correlation was found between the average nightly use of CPAP and the increase in total RPC vascular density. These results suggest a strong association between vascular density and the oxygenation of OSA patients. The longer the CPAP use, the greater the increase in vascular density. Previous studies had shown a similar relationship between oxygen saturation and RNFL impairment [\u003cspan additionalcitationids=\"CR51\" citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. It would have been interesting to conduct a post-treatment polysomnography to obtain SpO2 and T\u0026thinsp;\u0026lt;\u0026thinsp;90% and draw more precise conclusions about the increase in vascular density based on oxygenation parameters. Furthermore, other studies have found a beneficial effect of CPAP on the optic nerve. Liguori \u003cem\u003eet al.\u003c/em\u003e showed that patients with good CPAP compliance over a year had improved visual evoked potentials (VEP) with an increase in P100 amplitude and a decrease in P100 latency [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Similarly, Himori \u003cem\u003eet al.\u003c/em\u003e demonstrated a slowing of visual field loss after CPAP [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWe also did not observe any difference between IOP before and after treatment (14.36\u0026thinsp;\u0026plusmn;\u0026thinsp;2.61 vs. 13.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.23). This contradicts previous studies that found an increase of up to 3 mmHg without associated visual field alterations [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. This increase would be related to the rise in intra-thoracic pressure caused by CPAP use. However, the only study to continuously study IOP in OSA patients treated with CPAP found an increase in nocturnal IOP without a significant difference in 24-hour IOP [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Muniesa \u003cem\u003eet al.\u003c/em\u003e suggested that CPAP restores the normal IOP rhythm altered by OSA. We did not find a correlation between SpO2 and IOP. Indeed, hypoxia could play a role in IOP increase. Najmanov\u0026aacute; \u003cem\u003eet al.\u003c/em\u003e [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e] found a statistically significant increase in IOP in patients exposed to normobaric hypoxia. IOP had decreased before and after 4 and 10 minutes of hypoxia by 1.2 mmHg\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 mmHg and 0.9 mmHg\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 mmHg at minute 10, respectively. This difference was very small, and our study might not have a sufficient power to demonstrate it.\u003c/p\u003e\u003cp\u003eTo our knowledge, this is the first study analyzing the evolution of vascular density after CPAP treatment in patients with severe OSA. One of the main strengths of our study is the comparability of groups before and after treatment. Indeed, it involves the same subjects, maximizing comparability and minimizing the influence of confounding factors such as cardiovascular risk factors, BMI, smoking, among others. Finally, the average CPAP duration per night was significant (6h01), considering the usually low adherence to treatment [\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e]. However, our study had several limitations. Firstly, it suffered from a small sample size, leading to low statistical power. Secondly, although the reproducibility of OCT-A is known and proven [\u003cspan additionalcitationids=\"CR61\" citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e], we did not test the inter-operator reproducibility. Moreover, the study only included 3 months of treatment; a longer-term analysis might yield more significant results. A final PSG at the end of treatment would have been desirable to refine the results related to oxygen saturation. Lastly, heavy smokers or those with respiratory failure were not excluded; there were two heavy smokers which could explain the non-concordance between AHI and SpO2.\u003c/p\u003e\u003cp\u003eCPAP appears to be beneficial for the optic nerve by improving the vascular density of radial peripapillary capillaries (RPC). This study opens useful perspectives in evaluating the effect of CPAP in managing OSA, especially since changes in retinal vessel diameter are linked to the risk of coronary artery disease, stroke, and stroke-related mortality [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. Finally, by better understanding the vascular changes involved at the level of the optic nerve head, this study contributes to improving the understanding of the pathophysiology of glaucoma and its relationship with OSA.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAASM\u0026nbsp;American Academy of Sleep Medicine\u003c/p\u003e\n\u003cp\u003eAHI\u0026nbsp; \u0026nbsp; \u0026nbsp;Apnea-Hypopnea Index\u003c/p\u003e\n\u003cp\u003eAP-HP\u0026nbsp;Assistance Publique \u0026ndash; H\u0026ocirc;pitaux de Paris\u003c/p\u003e\n\u003cp\u003eBCVA\u0026nbsp;Best-Corrected Visual Acuity\u003c/p\u003e\n\u003cp\u003eBMI\u0026nbsp; \u0026nbsp; \u0026nbsp;Body Mass Index\u003c/p\u003e\n\u003cp\u003eCCT\u0026nbsp; \u0026nbsp;\u0026nbsp;Central Corneal Thickness\u003c/p\u003e\n\u003cp\u003eCESP\u0026nbsp; \u0026nbsp;Centre de recherche en \u0026Eacute;pid\u0026eacute;miologie et Sant\u0026eacute; des Populations\u003c/p\u003e\n\u003cp\u003eCI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Confidence Interval\u003c/p\u003e\n\u003cp\u003eCMT\u0026nbsp; \u0026nbsp;Central Macular Thickness\u003c/p\u003e\n\u003cp\u003eCNRS\u0026nbsp;\u0026nbsp;Centre National de la Recherche Scientifique\u003c/p\u003e\n\u003cp\u003eCPAP\u0026nbsp;\u0026nbsp;Continuous Positive Airway Pressure\u003c/p\u003e\n\u003cp\u003eDVA\u0026nbsp; \u0026nbsp;\u0026nbsp;Dynamic Vessel Analysis\u003c/p\u003e\n\u003cp\u003eETDRS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Early Treatment Diabetic Retinopathy Study\u003c/p\u003e\n\u003cp\u003eFAZ\u0026nbsp; \u0026nbsp; \u0026nbsp;Foveal Avascular Zone\u003c/p\u003e\n\u003cp\u003eGCC\u0026nbsp; \u0026nbsp;\u0026nbsp;Ganglion Cell Complex\u003c/p\u003e\n\u003cp\u003eIHU\u0026nbsp; \u0026nbsp; \u0026nbsp;Institut Hospitalo-Universitaire\u003c/p\u003e\n\u003cp\u003eINSERM\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Institut National de la Sant\u0026eacute; et de la Recherche M\u0026eacute;dicale\u003c/p\u003e\n\u003cp\u003eIOP\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Intraocular Pressure\u003c/p\u003e\n\u003cp\u003eLDF\u0026nbsp; \u0026nbsp; \u0026nbsp;Laser Doppler Flowmetry\u003c/p\u003e\n\u003cp\u003eMD\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Doctor of Medicine\u003c/p\u003e\n\u003cp\u003eOCT\u0026nbsp; \u0026nbsp;\u0026nbsp;Optical Coherence Tomography\u003c/p\u003e\n\u003cp\u003eOCT-A\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Optical Coherence Tomography Angiography\u003c/p\u003e\n\u003cp\u003eOSA\u0026nbsp; \u0026nbsp;\u0026nbsp;Obstructive Sleep Apnea\u003c/p\u003e\n\u003cp\u003eOSAS\u0026nbsp;\u0026nbsp;Obstructive Sleep Apnea Syndrome\u003c/p\u003e\n\u003cp\u003ePOAG\u0026nbsp;Primary Open-Angle Glaucoma\u003c/p\u003e\n\u003cp\u003ePhD\u0026nbsp; \u0026nbsp; \u0026nbsp;Doctor of Philosophy\u003c/p\u003e\n\u003cp\u003ePr\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Professor\u003c/p\u003e\n\u003cp\u003ePSG\u0026nbsp; \u0026nbsp; \u0026nbsp;Polysomnography\u003c/p\u003e\n\u003cp\u003eRGC\u0026nbsp; \u0026nbsp;\u0026nbsp;Retinal Ganglion Cells\u003c/p\u003e\n\u003cp\u003eRNFL\u0026nbsp;\u0026nbsp;Retinal Nerve Fiber Layer\u003c/p\u003e\n\u003cp\u003eRPC\u0026nbsp; \u0026nbsp; \u0026nbsp;Radial Peripapillary Capillaries\u003c/p\u003e\n\u003cp\u003eRVA\u0026nbsp; \u0026nbsp;\u0026nbsp;Retinal Vessel Analysis\u003c/p\u003e\n\u003cp\u003eSCP\u0026nbsp; \u0026nbsp; \u0026nbsp;Superficial Capillary Plexus\u003c/p\u003e\n\u003cp\u003eSE\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Spherical Equivalent\u003c/p\u003e\n\u003cp\u003eSMCP\u0026nbsp;\u0026nbsp;Superficial Macular Capillary Plexus\u003c/p\u003e\n\u003cp\u003eSpO2\u0026nbsp; \u0026nbsp;Peripheral capillary oxygen saturation\u003c/p\u003e\n\u003cp\u003eT\u0026lt;90%\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Time spent with oxygen saturation below 90%\u003c/p\u003e\n\u003cp\u003eVD\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Vascular Density\u003c/p\u003e\n\u003cp\u003eVEP \u0026nbsp; \u0026nbsp; Visual Evoked Potentials\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the French Society of Ophthalmology. Informed consent was obtained from all subjects.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot Applicable\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eThis research received no external funding\u003c/p\u003e\n\u003ch2\u003eConflicts of Interest:\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe author declares no conflict of interest with this work.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003ePLM, FO and AL wrote the main manuscript text. ZZ and PB prepared the figured. All authors reviewed the manuscript.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets generated and analyzed during the curent study are not publicly available due to patient confidentiality but are available from corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePeppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased Prevalence of Sleep-Disordered Breathing in Adults. American Journal of Epidemiology. 2013;177:1006‑14.\u003c/li\u003e\n\u003cli\u003eThylefors B, N\u0026eacute;grel AD, Pararajasegaram R, Dadzie KY. Global data on blindness. Bull World Health Organ. 1995;73:115‑21.\u003c/li\u003e\n\u003cli\u003eAugstburger E, Ballino A, Keilani C, Robin M, Baudouin C, Labb\u0026eacute; A. Follow-Up of nonarteritic Anterior Ischemic Optic Neuropathy With Optical Coherence Tomography Angiography. 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Obstructive Sleep Apnea Patients Having Surgery Are Less Associated with Glaucoma. Journal of Ophthalmology. 2014;2014:1‑6.\u003c/li\u003e\n\u003cli\u003eBerry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. 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. J Clin Sleep Med. 2012;8:597‑619.\u003c/li\u003e\n\u003cli\u003eLiguori C, Palmieri MG, Pierantozzi M, Cesareo M, Romigi A, Izzi F, et al. Optic Nerve Dysfunction in Obstructive Sleep Apnea: An Electrophysiological Study. Sleep. 2016;39:19‑23.\u003c/li\u003e\n\u003cli\u003eLim HB, Lee MW, Park JH, Kim K, Jo YJ, Kim JY. Changes in Ganglion Cell-Inner Plexiform Layer Thickness and Retinal Microvasculature in Hypertension: An Optical Coherence Tomography Angiography Study. 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J Glaucoma. 2019;28:465‑72.\u003c/li\u003e\n\u003cli\u003eTsang CSL, Chong SL, Ho CK, Li MF. Moderate to severe obstructive sleep apnoea patients is associated with a higher incidence of visual field defect. Eye (Lond). 2006;20:38‑42.\u003c/li\u003e\n\u003cli\u003eKergoat H, H\u0026eacute;rard M-E, Lemay M. RGC sensitivity to mild systemic hypoxia. Invest Ophthalmol Vis Sci. 2006;47:5423‑7.\u003c/li\u003e\n\u003cli\u003eFlammer J, Org\u0026uuml;l S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res. 2002;21:359‑93.\u003c/li\u003e\n\u003cli\u003eFoster GE, Poulin MJ, Hanly PJ. Intermittent hypoxia and vascular function: implications for obstructive sleep apnoea. Exp Physiol. 2007;92:51‑65.\u003c/li\u003e\n\u003cli\u003eKario K. Obstructive sleep apnea syndrome and hypertension: mechanism of the linkage and 24-h blood pressure control. Hypertens Res. 2009;32:537‑41.\u003c/li\u003e\n\u003cli\u003eNadeem R, Singh M, Nida M, Kwon S, Sajid H, Witkowski J, et al. Effect of CPAP treatment for obstructive sleep apnea hypopnea syndrome on lipid profile: a meta-regression analysis. J Clin Sleep Med. 2014;10:1295‑302.\u003c/li\u003e\n\u003cli\u003eFaridi O, Park SC, Liebmann JM, Ritch R. Glaucoma and obstructive sleep apnoea syndrome. Clin Exp Ophthalmol. 2012;40:408‑19.\u003c/li\u003e\n\u003cli\u003eWong B, Tong JY, Schulz AM, Graham SL, Farah CS, Fraser CL. The impact of continuous positive airway pressure treatment on retinal vascular changes in obstructive sleep apnea. J Clin Sleep Med. 2021;17:983‑91.\u003c/li\u003e\n\u003cli\u003eTonini M, Khayi H, Pepin J-L, Renard E, Baguet J-P, L\u0026eacute;vy P, et al. Choroidal blood-flow responses to hyperoxia and hypercapnia in men with obstructive sleep apnea. Sleep. 2010;33:811‑8.\u003c/li\u003e\n\u003cli\u003eJia Y, Bailey ST, Hwang TS, McClintic SM, Gao SS, Pennesi ME, et al. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. Proc Natl Acad Sci U S A. 2015;112:E2395-2402.\u003c/li\u003e\n\u003cli\u003eJoos KM, Pillunat LE, Knighton RW, Anderson DR, Feuer WJ. Reproducibility of laser Doppler flowmetry in the human optic nerve head. J Glaucoma. 1997;6:212‑6.\u003c/li\u003e\n\u003cli\u003eJonescu-Cuypers CP, Harris A, Bartz-Schmidt KU, Kagemann L, Boros AS, Heimann UE, et al. Reproducibility of circadian retinal and optic nerve head blood flow measurements by Heidelberg retina flowmetry. Br J Ophthalmol. 2004;88:348‑53.\u003c/li\u003e\n\u003cli\u003eYaoeda K, Shirakashi M, Funaki S, Funaki H, Nakatsue T, Fukushima A, et al. Measurement of microcirculation in optic nerve head by laser speckle flowgraphy in normal volunteers. Am J Ophthalmol. 2000;130:606‑10.\u003c/li\u003e\n\u003cli\u003eL\u0026eacute;v\u0026ecirc;que P-M, Z\u0026eacute;boulon P, Brasnu E, Baudouin C, Labb\u0026eacute; A. Optic Disc Vascularization in Glaucoma: Value of Spectral-Domain Optical Coherence Tomography Angiography. Journal of Ophthalmology. 2016;2016:1‑9.\u003c/li\u003e\n\u003cli\u003eWuDunn D, Takusagawa HL, Sit AJ, Rosdahl JA, Radhakrishnan S, Hoguet A, et al. OCT Angiography for the Diagnosis of Glaucoma. Ophthalmology. 2021;128:1222‑35.\u003c/li\u003e\n\u003cli\u003eMarangoni D, Falsini B, Colotto A, Salgarello T, Anselmi G, Fadda A, et al. Subfoveal choroidal blood flow and central retinal function in early glaucoma. Acta Ophthalmol. 2012;90:e288-294.\u003c/li\u003e\n\u003cli\u003eTurnbull CD, Stockley JA, Madathil S, Huq SSA, Cooper BG, Ali A, et al. Effect of obstructive sleep apnoea on retinal microvascular function: a randomised controlled trial. Graefes Arch Clin Exp Ophthalmol [Internet]. 2022 [cit\u0026eacute; 20 avr 2022]; Disponible sur: https://link.springer.com/10.1007/s00417-022-05596-8\u003c/li\u003e\n\u003cli\u003eYe H, Zheng C, Lan X, Zhao L, Qiao T, Li X, et al. Evaluation of retinal vasculature before and after treatment of children with obstructive sleep apnea-hypopnea syndrome by optical coherence tomography angiography. Graefes Arch Clin Exp Ophthalmol. 2019;257:543‑8.\u003c/li\u003e\n\u003cli\u003eXu H, Deng G, Jiang C, Kong X, Yu J, Sun X. Microcirculatory Responses to Hyperoxia in Macular and Peripapillary Regions. Invest Ophthalmol Vis Sci. 2016;57:4464‑8.\u003c/li\u003e\n\u003cli\u003eSousa DC, Leal I, Moreira S, Dion\u0026iacute;sio P, Abeg\u0026atilde;o Pinto L, Marques-Neves C. Hypoxia challenge test and retinal circulation changes - a study using ocular coherence tomography angiography. Acta Ophthalmol. 2018;96:e315‑9.\u003c/li\u003e\n\u003cli\u003eKarakucuk S, Goktas S, Aksu M, Erdogan N, Demirci S, Oner A, et al. Ocular blood flow in patients with obstructive sleep apnea syndrome (OSAS). Graefes Arch Clin Exp Ophthalmol. 2008;246:129‑34.\u003c/li\u003e\n\u003cli\u003eLin P-W, Friedman M, Lin H-C, Chang H-W, Pulver TM, Chin C-H. Decreased retinal nerve fiber layer thickness in patients with obstructive sleep apnea/hypopnea syndrome. Graefes Arch Clin Exp Ophthalmol. 2011;249:585‑93.\u003c/li\u003e\n\u003cli\u003eHuseyinoglu N, Ekinci M, Ozben S, Buyukuysal C, Kale MY, Sanivar HS. Optic disc and retinal nerve fiber layer parameters as indicators of neurodegenerative brain changes in patients with obstructive sleep apnea syndrome. Sleep Breath. 2014;18:95‑102.\u003c/li\u003e\n\u003cli\u003eLiguori C, Placidi F, Palmieri MG, Izzi F, Ludovisi R, Mercuri NB, et al. Continuous Positive Airway Pressure Treatment May Improve Optic Nerve Function in Obstructive Sleep Apnea: An Electrophysiological Study. Journal of Clinical Sleep Medicine. 2018;14:953‑8.\u003c/li\u003e\n\u003cli\u003eHimori N, Ogawa H, Ichinose M, Nakazawa T. CPAP therapy reduces oxidative stress in patients with glaucoma and OSAS and improves the visual field. Graefes Arch Clin Exp Ophthalmol. 2020;258:939‑41.\u003c/li\u003e\n\u003cli\u003eKiekens S, Veva De Groot, Coeckelbergh T, Tassignon M-J, van de Heyning P, Wilfried De Backer, 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.\u003c/li\u003e\n\u003cli\u003eCohen Y, Ben-Mair E, Rosenzweig E, Shechter-Amir D, Solomon AS. The effect of nocturnal CPAP therapy on the intraocular pressure of patients with sleep apnea syndrome. Graefes Arch Clin Exp Ophthalmol. 2015;253:2263‑71.\u003c/li\u003e\n\u003cli\u003eMuniesa MJ, Ben\u0026iacute;tez I, Ezpeleta J, S\u0026aacute;nchez de la Torre M, Pazos M, Mill\u0026agrave; E, et al. Effect of CPAP Therapy on 24-Hour Intraocular Pressure-Related Pattern From Contact Lens Sensors in Obstructive Sleep Apnea Syndrome. Trans Vis Sci Tech. 2021;10:10.\u003c/li\u003e\n\u003cli\u003eNajmanov\u0026aacute; E, Pluh\u0026aacute;ček F, Botek M, Krejč\u0026iacute; J, Jaro\u0026scaron;ov\u0026aacute; J. Intraocular Pressure Response to Short-Term Extreme Normobaric Hypoxia Exposure. Front Endocrinol (Lausanne). 2018;9:785.\u003c/li\u003e\n\u003cli\u003eRotenberg BW, Murariu D, Pang KP. Trends in CPAP adherence over twenty years of data collection: a flattened curve. J Otolaryngol Head Neck Surg. 2016;45:43.\u003c/li\u003e\n\u003cli\u003eManalastas PIC, Zangwill LM, Saunders LJ, Mansouri K, Belghith A, Suh MH, et al. Reproducibility of Optical Coherence Tomography Angiography Macular and Optic Nerve Head Vascular Density in Glaucoma and Healthy Eyes. J Glaucoma. 2017;26:851‑9.\u003c/li\u003e\n\u003cli\u003eLiu L, Jia Y, Takusagawa HL, Pechauer AD, Edmunds B, Lombardi L, et al. Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma. JAMA Ophthalmol. 2015;133:1045‑52.\u003c/li\u003e\n\u003cli\u003eP\u0026eacute;rez-Garc\u0026iacute;a P, Morales-Fern\u0026aacute;ndez L, Fern\u0026aacute;ndez-Vigo JI, S\u0026aacute;enz-Franc\u0026eacute;s F, Burgos-Blasco B, G\u0026uuml;emes-Villahoz N, et al. Repeatability of Macular and Optic Nerve Head Measurements by Optical Coherence Tomography Angiography in Healthy Children. Curr Eye Res. 2021;46:1574‑80.\u003c/li\u003e\n\u003cli\u003eWong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, et al. Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The Atherosclerosis Risk in Communities Study. JAMA. 2002;287:1153‑9.\u003c/li\u003e\n\u003cli\u003eWong TY, Klein R, Nieto FJ, Klein BEK, Sharrett AR, Meuer SM, et al. Retinal microvascular abnormalities and 10-year cardiovascular mortality: a population-based case-control study. Ophthalmology. 2003;110:933‑40.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Demographic, clinical, and paraclinical characteristics of patients. IOP: Intraocular Pressure, RNFL: Retinal Nerve Fiber Layer thickness, GCC: Average Macular Ganglion Cell Complex thickness, CMT: Central Macular Thickness, AHI: Apnea-Hypopnea Index, SpO2: Average Oxygen Saturation, T\u0026lt;90%: Time spent with saturation below 90%, Min SpO2: Minimum Oxygen Saturation.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"481\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eDemographic Characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003ePatients (22) \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e61.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e11.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e63.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e36.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 141px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e72.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eAfrican-American\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e27.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eGeneral \u0026nbsp; \u0026nbsp; characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e33.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e7.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eOphtalmological characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eIOP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e14.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eCorneal thickness (\u0026micro;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e550.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e34.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eRNFL\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e91.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e10.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eGCC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e82.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e6.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eCMT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e260.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e22.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003ePulmonary characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eAHI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e49.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e21.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eAverage SpO2 (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e91.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eT\u0026lt;90% (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e15.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e19.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eMin SpO2 (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e10.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eCPAP duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e6h01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e1h14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 231px;\"\u003e\n \u003cp\u003eDays of use over 3 months (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e91.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2: Results of analyses before and after continuous positive airway pressure treatment in patients with severe obstructive sleep apnea (OSA). VD: Vascular Density, RPC: Radial Peripapillary Capillaries, SMCP: Superficial Macular Capillary Plexus, RNFL: Retinal Nerve Fiber Layer, GCC: Ganglion Cell Complex, CMT : Central Macular Thickness, IOP: Intraocular Pressure, AHI: Apnea-Hypopnea Index.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"607\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003eBefore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eAfter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003eAverage and standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eAverage and standard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003eSignificance\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eVD RPC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e44.65 \u0026plusmn; 1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e45.7 \u0026plusmn; 1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eVD RPC \u0026nbsp;by quadrant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eSup\u0026eacute;rior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e44.63 \u0026plusmn; 2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e46.08 \u0026plusmn; 1.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eNasal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e43.39 \u0026plusmn; 1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e44.30 \u0026plusmn; 2.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eInf\u0026eacute;rior\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e45.16 \u0026plusmn; 2.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e45.23 \u0026plusmn; 3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eTemporal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e46.62 \u0026plusmn; 2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e47.25 \u0026plusmn; 2.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eVD SMCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e18.94 \u0026plusmn; 0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e19.12 \u0026plusmn; 0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eRNFL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e96.82 \u0026plusmn; 10.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e96.39 \u0026plusmn; 10.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eGCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e82.68 \u0026plusmn; 6.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e82.69 \u0026plusmn; 6.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eCMT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e260.68 \u0026plusmn; 22.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e263.50 \u0026plusmn; 24.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eIOP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e14.36 \u0026plusmn; 2.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e13.5 \u0026plusmn; 2.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e = 0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eAHI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 172px;\"\u003e\n \u003cp\u003e49.55 \u0026plusmn; 21.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e2.83\u0026plusmn; 3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0,0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Glaucoma, Optic nerve, Obstructive Sleep Apnea Syndrome","lastPublishedDoi":"10.21203/rs.3.rs-7906510/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7906510/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective :\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo evaluate the influence of continuous positive airway pressure (CPAP) on the vascularization of the optic nerve head using optical coherence tomography angiography (OCT-A) in patients with severe obstructive sleep apnea syndrome (OSAS) na\u0026iuml;ve to any treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePatients and methods :\u003c/b\u003e\u003c/p\u003e\u003cp\u003eVascularization of the optic nerve head in the right eye of 22 patients with severe OSAS na\u0026iuml;ve to any treatment was assessed using OCT-A with AngioPlex\u0026reg; software (Carl Zeiss Meditec, Dublin, CA, USA). All patients underwent a comprehensive ophthalmological examination as well as OCT-A analysis of the radial peripapillary capillary (RPC) and macular superficial capillary plexus (SCP) vascular density (VD). Measurements were taken before and after three months of CPAP treatment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults :\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAfter 3 months of CPAP treatment, total RPC vascular density significantly increased (44.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83 versus 45.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51, P\u0026thinsp;=\u0026thinsp;0.04). Additionally, a positive correlation was found between the average nightly CPAP usage duration and the increase in RPC vascular density (P\u0026thinsp;=\u0026thinsp;0.001, r\u0026thinsp;=\u0026thinsp;0.65, 95% CI [0.14; 1.15]).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion :\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCPAP may improve vascular density at the optic nerve head in patients with severe OSAS. Our study provides new insights into the potential vascular impact of OSAS on optic nerve vascularization.\u003c/p\u003e","manuscriptTitle":"Influence of continuous positive airway pressure on optic nerve head vascularization in patients with severe obstructive sleep apnea syndrome: an OCT-angiography study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 07:42:01","doi":"10.21203/rs.3.rs-7906510/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-15T09:12:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-02T14:59:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-24T14:52:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"260731098879892524256197671143230776784","date":"2025-11-24T11:51:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150835885835666234795828459374846496748","date":"2025-11-24T11:25:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"259557788534189432718066008401232194385","date":"2025-11-23T04:10:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-22T09:15:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-22T09:11:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-21T09:53:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-21T09:13:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-11-21T09:09:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2775a9aa-1898-4dcc-9290-a902532aa7e1","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T09:24:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 07:42:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7906510","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7906510","identity":"rs-7906510","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
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