Impaired blood flow of optic nerve head in patients with severe obstructive sleep apnea/hypopnea syndrome
Pei-Wen Lin
Division of Glaucoma, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Sleep Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
College of Medicine, Chang Gung University, Taoyuan and Kaohsiung, Taiwan
College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
Contribution: Conceptualization, Methodology, Investigation, Validation, Formal analysis, Funding acquisition, Writing - original draft, Data curation
Search for more papers by this authorLi-Wen Chiu
Division of Glaucoma, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Contribution: Data curation, Formal analysis, Investigation, Writing - review & editing
Search for more papers by this authorChun-Tuan Chang
Institute of Healthcare Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan
Contribution: Writing - review & editing, Supervision, Formal analysis
Search for more papers by this authorCorresponding Author
Hsin-Ching Lin
Sleep Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
College of Medicine, Chang Gung University, Taoyuan and Kaohsiung, Taiwan
College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
Institute of Healthcare Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan
Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan
Department of Otolaryngology, Robotic Surgery Centre and Centre for Quality Management, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Correspondence
Hsin-Ching Lin, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833, Taiwan.
Email: [email protected]; [email protected]
Contribution: Conceptualization, Methodology, Data curation, Investigation, Supervision, Writing - review & editing
Search for more papers by this authorPei-Wen Lin
Division of Glaucoma, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Sleep Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
College of Medicine, Chang Gung University, Taoyuan and Kaohsiung, Taiwan
College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
Contribution: Conceptualization, Methodology, Investigation, Validation, Formal analysis, Funding acquisition, Writing - original draft, Data curation
Search for more papers by this authorLi-Wen Chiu
Division of Glaucoma, Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Contribution: Data curation, Formal analysis, Investigation, Writing - review & editing
Search for more papers by this authorChun-Tuan Chang
Institute of Healthcare Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan
Contribution: Writing - review & editing, Supervision, Formal analysis
Search for more papers by this authorCorresponding Author
Hsin-Ching Lin
Sleep Centre, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
College of Medicine, Chang Gung University, Taoyuan and Kaohsiung, Taiwan
College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
Institute of Healthcare Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan
Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan
Department of Otolaryngology, Robotic Surgery Centre and Centre for Quality Management, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
Correspondence
Hsin-Ching Lin, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 833, Taiwan.
Email: [email protected]; [email protected]
Contribution: Conceptualization, Methodology, Data curation, Investigation, Supervision, Writing - review & editing
Search for more papers by this authorSummary
This study prospectively analysed the difference in the blood flow of the optic nerve head (ONH) between patients with obstructive sleep apnea/hypopnea syndrome (OSA) and control subjects by laser speckle flowgraphy (LSFG), and determined the correlations between LSFG variables and the severity of OSA. A total of 100 participants consecutively underwent full-night polysomnography, ophthalmologic examinations, and LSFG measurements. The LSFG parameters were summarised as the mean blur rate in all areas of the ONH (MA), in the big vessel area of ONH (MV), and in the tissue area of ONH (MT). When the control (17 subjects) and patients with mild/moderate OSA (42 patients) were grouped together and compared with patients with severe OSA (41 patients), the MA, MV, and MT were decreased significantly in patients with severe OSA compared with control subjects and patients with mild/moderate OSA (p < 0.0001, p = 0.0001, and p = 0.0034, respectively). Negative correlations were identified between the apnea–hypopnea index and MA (ρ = −0.244, p = 0.0016), between AHI and MV (ρ = −0.263, p = 0.0006), and between AHI and MT (ρ = −0.198, p = 0.0105). Positive correlations were identified between the lowest saturation of oxygen (LSaO2) and MA (ρ = 0.332, p < 0.0001), between LSaO2 and MV (ρ = 0.354, p < 0.0001), and between LSaO2 and MT (ρ = 0.227, p = 0.0035). Our study demonstrated that OSA could have a negative impact on the microcirculation of the optic nerve head, including MA, MV, and MT measurements. Furthermore, the decreased blood flow of the optic nerve head obviously correlated with the severity of OSA.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
REFERENCES
- Atkeson, A., & Jelic, S. (2008). Mechanisms of endothelial dysfunction in obstructive sleep apnea. Vascular Health and Risk Management, 4(6), 1327–1335.
- Atkeson, A., Yeh, S. Y., Malhotra, A., & Jelic, S. (2009). Endothelial function in obstructive sleep apnea. Progress in Cardiovascular Diseases, 51(5), 351–362.
- Baillieul, S., Dekkers, M., Brill, A. K., Schmidt, M. H., Detante, O., Pépin, J. L., Tamisier, R., & Bassetti, C. L. A. (2022). Sleep apnoea and ischaemic stroke: Current knowledge and future directions. Lancet Neurology, 21(1), 78–88.
- Bulloch, G., Seth, I., Alphonse, S., Sathe, A., Jennings, M., Sultan, D., Rahmeh, R., & McNab, A. A. (2023). Prevalence of obstructive sleep apnea with floppy eyelid syndrome: A systemic review and meta-analysis. Ophthalmic Plastic & Reconstructive Surgery, 39(3), 243–253.
- Chopra, S., Rathore, A., Younas, H., Pham, L. V., Gu, C., Beselman, A., Kim, I. Y., Wolfe, R. R., Perin, J., Polotsky, V. Y., & Jun, J. C. (2017). Obstructive sleep apnea dynamically increases nocturnal plasma free fatty acids, glucose, and cortisol during sleep. The Journal of Clinical Endocrinology and Metabolism, 102(9), 3172–3181.
- Christou, E. E., Kostikas, K., Asproudis, C., Zafeiropoulos, P., Stefaniotou, M., & Asproudis, I. (2022). Retinal microcirculation characteristics in obstructive sleep apnea/hypopnea syndrome evaluated by OCT-angiography: A literature review. International Ophthalmology, 42(12), 3977–3991.
- Cowie, M. R., Linz, D., Redline, S., Somers, V. K., & Simonds, A. K. (2021). Sleep disordered breathing and cardiovascular disease: JACC state-of-the-art review. Journal of the American College of Cardiology, 78(6), 608–624.
- Delaey, C., & Van De Voorde, J. (2000). Regulatory mechanisms in the retinal and choroidal circulation. Ophthalmic Research, 32(6), 249–256.
- Enomoto, N., Anraku, A., Tomita, G., Iwase, A., Sato, T., Shoji, N., Shiba, T., Nakazawa, T., Sugiyama, K., Nitta, K., & Araie, M. (2021). Characterization of laser speckle flowgraphy pulse waveform parameters for the evaluation of the optic nerve head and retinal circulation. Scientific Reports, 11(1), 6847.
- Faridi, O., Park, S. C., Liebmann, J. M., & Ritch, R. (2012). Glaucoma and obstructive sleep apnoea syndrome. Clinical & Experimental Ophthalmology, 40(4), 408–419.
- Hashim, S. P., Al Mansouri, F. A., Farouk, M., Al Hashemi, A. A., & Singh, R. (2014). Prevalence of glaucoma in patients with moderate to severe obstructive sleep apnea: Ocular morbidity and outcomes in a 3 year follow-up study. Eye, 28(11), 1304–1309.
- Jelic, S., Padeletti, M., Kawut, S. M., Higgins, C., Canfield, S. M., Onat, D., Colombo, P. C., Basner, R. C., Factor, P., & LeJemtel, T. H. (2008). Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea. Circulation, 117(17), 2270–2278.
- Kobayashi, T., Shiba, T., Nishiwaki, Y., Kinoshita, A., Matsumoto, T., & Hori, Y. (2019). Influence of age and gender on the pulse waveform in optic nerve head circulation in healthy men and women. Scientific Reports, 9(1), 17895.
- Lévy, P., Kohler, M., McNicholas, W. T., Barbé, F., McEvoy, R. D., Somers, V. K., Lavie, L., & Pépin, J. L. (2015). Obstructive sleep apnoea syndrome. Nature Reviews. Disease Primers, 1, 15015.
- Lin, P. W., Friedman, M., Lin, H. C., Chang, H. W., Pulver, T. M., & Chin, C. H. (2011). Decreased retinal nerve fiber layer thickness in patients with obstructive sleep apnea/hypopnea syndrome. Graefe's Archive for Clinical and Experimental Ophthalmology, 249(4), 585–593.
- Lin, P. W., Friedman, M., Lin, H. C., Chang, H. W., Wilson, M., & Lin, M. C. (2011). Normal tension glaucoma in patients with obstructive sleep apnea/hypopnea syndrome. Journal of Glaucoma, 20(9), 553–558.
- Lin, P. W., Lin, H. C., Chang, C. T., Lin, M. C., Friedman, M., & Salapatas, A. M. (2023). Decreased peripapillary and macular vascular densities in patients with moderate/severe obstructive sleep apnea/hypopnea syndrome. Nature and Science of Sleep, 15, 1–12.
- Mentek, M., Aptel, F., Godin-Ribuot, D., Tamisier, R., Pepin, J. L., & Chiquet, C. (2018). Diseases of the retina and the optic nerve associated with obstructive sleep apnea. Sleep Medicine Reviews, 38, 113–130.
- Mojon, D. S., Hedges, T. R., 3rd, Ehrenberg, B., Karam, E. Z., Goldblum, D., Abou-Chebl, A., Gugger, M., & Mathis, J. (2002). Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Archives of Ophthalmology, 120(5), 601–605.
- Mursch-Edlmayr, A. S., Luft, N., Podkowinski, D., Ring, M., Schmetterer, L., & Bolz, M. (2018). Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in normal tension glaucoma and healthy individuals: A pilot study. Scientific Reports, 8(1), 5343.
- Pengo, M. F., Soranna, D., Giontella, A., Perger, E., Mattaliano, P., Schwarz, E. I., Lombardi, C., Bilo, G., Zambon, S., Steier, J., Parati, G., Minuz, P., & Fava, C. (2020). Obstructive sleep apnoea treatment and blood pressure: Which phenotypes predict a response? A systematic review and meta-analysis. The European Respiratory Journal, 55(5), 1901945.
- Purvin, V. A., Kawasaki, A., & Yee, R. D. (2000). Papilledema and obstructive sleep apnea syndrome. Archives of Ophthalmology, 118(12), 1626–1630.
- Rina, M., Shiba, T., Takahashi, M., Hori, Y., & Maeno, T. (2015). Pulse waveform analysis of optic nerve head circulation for predicting carotid atherosclerotic changes. Graefe's Archive for Clinical and Experimental Ophthalmology, 253(12), 2285–2291.
- Riva, C. E., Hero, M., Titze, P., & Petrig, B. (1997). Autoregulation of human optic nerve head blood flow in response to acute changes in ocular perfusion pressure. Graefe's Archive for Clinical and Experimental Ophthalmology, 235, 618–626.
- Shiba, T., Takahashi, M., Hashimoto, R., Matsumoto, T., & Hori, Y. (2016). Pulse waveform analysis in the optic nerve head circulation reflects systemic vascular resistance obtained via a swan-Ganz catheter. Graefe's Archive for Clinical and Experimental Ophthalmology, 254(6), 1195–1200.
- Shiga, Y., Omodaka, K., Kunikata, H., Ryu, M., Yokoyama, Y., Tsuda, S., Asano, T., Maekawa, S., Maruyama, K., & Nakazawa, T. (2013). Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma. Investigative Ophthalmology & Visual Science, 54(12), 7699–7706.
- Sugiyama, T., Araie, M., Riva, C. E., Schmetterer, L., & Orgul, S. (2010). Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmologica, 88(7), 723–729.
- The Report of an American Academy of Sleep Medicine Task Force. (1999). Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Sleep, 22(5), 667–689.
- Ucak, T., & Unver, E. (2020). Alterations in parafoveal and optic disc vessel densities in patients with obstructive sleep apnea syndrome. Journal of Ophthalmology, 2020, 4034382.
- von Känel, R., & Dimsdale, J. E. (2003). Hemostatic alterations in patients with obstructive sleep apnea and the implications for cardiovascular disease. Chest, 124(5), 1956–1967.
- Wang, L., Cull, G. A., & Fortune, B. (2015). Optic nerve head blood flow response to reduced ocular perfusion pressure by alteration of either the blood pressure or intraocular pressure. Current Eye Research, 40(4), 359–367.
- Yanagida, K., Iwase, T., Yamamoto, K., Ra, E., Kaneko, H., Murotani, K., Matsui, S., & Terasaki, H. (2015). Sex-related differences in ocular blood flow of healthy subjects using laser speckle flowgraphy. Investigative Ophthalmology & Visual Science, 56(8), 4880–4890.
- Yazgan, S., Erboy, F., Celik, H. U., Ornek, T., Ugurbas, S. H., Kokturk, F., Ayar, O., Akdemir, M. O., & Celik, E. (2017). Peripapillary choroidal thickness and retinal nerve fiber layer in untreated patients with obstructive sleep apnea-hypopnea syndrome: A case-control study. Current Eye Research, 42(11), 1552–1560.
- Yu, J., Xiao, K., Huang, J., Sun, X., & Jiang, C. (2017). Reduced retinal vessel density in obstructive sleep apnea syndrome patients: An optical coherence tomography angiography study. Investigative Ophthalmology & Visual Science, 58(9), 3506–3512.
- Yu, J. G., Mei, Z. M., Ye, T., Feng, Y. F., Zhao, F., Jia, J., Fu, X. A., & Xiang, Y. (2016). Changes in retinal nerve fiber layer thickness in obstructive sleep apnea/hypopnea syndrome: A meta-analysis. Ophthalmic Research, 56(2), 57–67.
Citing Literature
