helmholtzeyeinstituteРоссийский офтальмологический журналRussian Ophthalmological Journal2072-00762587-5760Real time Publishers10.21516/2072-0076-2021-14-1-104-110helmholtzeyeinstitute-591Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWSОфтальмологическая диагностика в дебюте и при прогрессировании нейродегенеративных заболеванийOphthalmic examination in the debut and during progression of neurodegenerative diseasesФурсоваА. Ж.FursovaA. Zh.

Анжелла Жановна Фурсова — доктор медицинских наук, заведующая кафедрой офтальмологии, заведующая офтальмологическим отделением.

Красный проспект, д. 52, Новосибирск, 630091; ул. Немировича-Данченко, д. 130, Новосибирск, 630087

Anzhella Zh. Fursova — Dr. of Med. Sci., head of ophthalmology dept.

52, Krasny Prospect, Novosibirsk, 630091; 130, Nemirovich-Danchenko st., Novosibirsk, 630087

anzhellafursova@yandex.ruГамзаЮ. А.GamzaYu. A.

Юлия Александровна Гамза — врач-офтальмолог, ассистент кафедры офтальмологии.

Красный проспект, д. 52, Новосибирск, 630091; ул. Немировича-Данченко, д. 130, Новосибирск, 630087

Yulia A. Gamza — M.D., assistant professor of ophthalmology dept.

52, Krasny Prospect, Novosibirsk, 630091; 130, Nemirovich-Danchenko st., Novosibirsk, 630087

ЗубковаМ. Ю.ZubkovaM. Yu.

Маргарита Юрьевна Зубкова — врач-офтальмолог, ассистент кафедры офтальмологии.

Красный проспект, д. 52, Новосибирск, 630091; ул. Немировича-Данченко, д. 130, Новосибирск, 630087

Margarita Yu. Zubkova — M.D., assistant professor of ophthalmology Dept.

52, Krasny Prospect, Novosibirsk, 630091; 130, Nemirovich-Danchenko st., Novosibirsk, 630087

ДербеневаА. С.DerbenevaA. S.

Анна Сергеевна Дербенева — врач-офтальмолог, ассистент кафедры офтальмологии.

Красный проспект, д. 52, Новосибирск, 630091; ул. Немировича-Данченко, д. 130, Новосибирск, 630087

Anna S. Derbeneva — M.D., assistant professor of ophthalmology dept.

52, Krasny Prospect, Novosibirsk, 630091; 130, Nemirovich-Danchenko st., Novosibirsk, 630087

ДоронинаО. Б.DoroninaO. B.

Ольга Борисовна Доронина — кандидат медицинских наук, доцент кафедры неврологии.

Красный проспект, д. 52, Новосибирск, 630091

Olga B. Doronina — Cand. of Med. Sci., associate professor of neurology Dept.

52, Krasny Prospect, Novosibirsk, 630091

ДоронинаК. С.DoroninaK. S.

Ксения Сергеевна Доронина — преподаватель-исследователь кафедры неврологии.

Красный проспект, д. 52, Новосибирск, 630091

Ksenia S. Doronina — researcher of neurology dept.

52, Krasny Prospect, Novosibirsk, 630091

БулатоваН. В.BulatovaN. V.

Наталья Викторовна Булатова — лаборант кафедры неврологии.

Красный проспект, д. 52, Новосибирск, 630091

Natalia V. Bulatova — laboratory assistant of neurology dept.

52, Krasny Prospect, Novosibirsk, 630091

БельгибаеваА. С.BelgibaevaA. S.

Анна Сергеевна Бельгибаева — лаборант кафедры неврологии.

Красный проспект, д. 52, Новосибирск, 630091

Anna S. Belgibaeva — laboratory assistant of neurology dept.

52, Krasny Prospect, Novosibirsk, 630091

ФГБОУ ВО Новосибирский государственный медицинский университет Минздрава России; ГБУЗ НСО Государственная Новосибирская областная клиническая больницаРоссияNovosibirsk State Medical University; Novosibirsk State Region HospitalRussian FederationФГБОУ ВО Новосибирский государственный медицинский университет Минздрава РоссииРоссияNovosibirsk State Medical UniversityRussian Federation202120032021141104110Copyright © Фурсова А.Ж., Гамза Ю.А., Зубкова М.Ю., Дербенева А.С., Доронина О.Б., Доронина К.С., Булатова Н.В., Бельгибаева А.С., 20212021Фурсова А.Ж., Гамза Ю.А., Зубкова М.Ю., Дербенева А.С., Доронина О.Б., Доронина К.С., Булатова Н.В., Бельгибаева А.С.Fursova A.Z., Gamza Y.A., Zubkova M.Y., Derbeneva A.S., Doronina O.B., Doronina K.S., Bulatova N.V., Belgibaeva A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://roj.igb.ru/jour/article/view/591

Нейродегенеративные заболевания (НДЗ) объединяют группу нозологических форм, причиной развития которых является избыточное образование белковых молекул и их агрегатов, приводящее к гибели клеток мозга. Классические патофизиологические механизмы связаны с накоплением внеклеточного амилоидного b -белка (A b) при болезни Альцгеймера (БА) и белка a -синуклеина при болезни Паркинсона (БП), которые являются маркерами нейродегенеративного процесса. Признаком функциональных нарушений при НДЗ является снижение остроты зрения, контрастной световой чувствительности с наиболее значимыми изменениями на самых высоких пространственных частотах (18 и 12 цикл/гр) и цветового зрения, коррелирующее со степенью выраженности когнитивных нарушений и длительностью заболевания. Изменения показателей психофизических тестов сопровождаются уменьшением центральной толщины сетчатки (ЦТС), что является следствием дегенерации ее внутренних слоев. Прогрессирование НДЗ характеризуется стабильностью психофизических тестов, но значительным истончением слоя нервных волокон перипапиллярной сетчатки и увеличением ЦТС, что коррелирует со снижением когнитивных функций. Отложения A b и a -синуклеина в стенках артерий вызывают сужение просвета и окклюзию сосудов, снижение плотности перфузии диска зрительного нерва, обеднение поверхностного и глубокого капиллярного сплетений, расширение аваскулярной фовеолярной зоны. Микроциркуляторные нарушения сопровождаются изменением структуры сетчатки, доказана их отрицательная связь с толщиной внутренних слоев сетчатки и длительностью заболевания. Возрастающая потребность в выявлении специфичных и чувствительных биомаркеров НДЗ на доклинической стадии для дифференциации причин, уточнения подтипа и оценки риска прогрессирования НДЗ определяет актуальность изучения и идентификации функциональных и структурных изменений нейронов и аксонов сетчатки. Неинвазивные, информативные, основанные на мультимодальной визуализации офтальмологические методы обследования представляются ценными для диагностики и мониторинга НДЗ.

Neurodegenerative diseases (NDD) are a group of nosological forms, caused by excessive formation of protein molecules and their aggregates and leading to the death of brain cells. Classical pathophysiological mechanisms are associated with the accumulation of extracellular amyloid b -protein (A b) in Alzheimer's disease (AD) and a -synuclein protein in Parkinson's disease (PD), which are markers of neurodegenerative process. Signs of functional disorders in NDD include decreasing visual acuity, lower contrast light sensitivity with the most significant changes at the highest spatial frequencies (18 and 12 cycles per degree), and reduced color vision. These disorders correlate with the severity of cognitive impairment and duration of the disease. Changes in the indicators of psychophysical tests are accompanied by lower central retinal thickness (CRT), which is a consequence of inner layers degeneration. NDD progression is characterized by the stability of psychophysical tests, significant thinning of the peripapillary retinal nerve fiber layer (RNFL) and CRT thickening, which correlates with cognitive disfunction. A b and a -synuclein deposits in artery walls cause lumen narrowing and occlusion of blood vessels, reduced optic nerve disk perfusion density, superficial and deep capillary plexus depletion, expansion of the avascular foveolar zone. Microcirculatory disorders lead to retinal changes, which were proven to correlate negatively with the thickness of inner retinal layers and duration of the disease. An ever-growing need in the identification of specific and sensitive biomarkers at the preclinical stage of NDDs, differentiation of their causes, precise subtype classification, and assessment of progression risk is an evidence of the relevance of studying and identifying functional and structural changes in retinal neurons and axons. Non-invasive and informative methods of multimodal imaging appear to be valuable for NDD diagnosis and monitoring.

нейродегенеративные заболеванияоптическая когерентная томографияболезнь Паркинсонаболезнь Альцгеймерацветовое зрениеконтрастная чувствительностьneurodegenerative diseasesoptical coherence tomographyParkinson's diseaseAlzheimer's diseasecolor visioncontrast sensitivityReferencesFerri C.P., Prince M., Brayne C., et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005; 366 (9503): 2112–7. doi: 10.1016/S0140-6736(05)67889-0Ferri C.P., Prince M., Brayne C., et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005; 366 (9503): 2112–7. doi: 10.1016/S0140-6736(05)67889-0Prusiner S.B. Shattuck lecture – neurodegenerative disease and prions. N. Engl. J. Med. 2001; 344 (20): 1516-26. doi: 10.1056/NEJM200105173442006Prusiner S.B. Shattuck lecture – neurodegenerative disease and prions. N. Engl. J. Med. 2001; 344 (20): 1516-26. doi: 10.1056/NEJM200105173442006Lees A.J. Unresolved issues relating to the shaking palsy on the celebration of James Parkinson's 250th birthday. Mov. Disord. 2007; 22 Suppl 17: S327–334. doi: 10.1002/mds.21684Lees A.J. Unresolved issues relating to the shaking palsy on the celebration of James Parkinson's 250th birthday. Mov. Disord. 2007; 22 Suppl 17: S327–334. doi: 10.1002/mds.21684Bodis-Wollner I., Kozlowski P.B., Glazman S., Miri S. Alpha-synuclein in the inner retina in Parkinson disease. Ann. Neurol. 2014; 75 (6): 964–66. doi: 10.1002/ana.24182Bodis-Wollner I., Kozlowski P.B., Glazman S., Miri S. Alpha-synuclein in the inner retina in Parkinson disease. Ann. Neurol. 2014; 75 (6): 964–66. doi: 10.1002/ana.24182Jack C.R. Jr., Albert M.S., Knopman D.S., et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7 (3): 257–62. doi: 10.1016/j.jalz.2011.03.004Jack C.R. Jr., Albert M.S., Knopman D.S., et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011; 7 (3): 257–62. doi: 10.1016/j.jalz.2011.03.004Avila J., Pallas N., Bolos M., Sayas C.L., Hernandez F. Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies. Expert Opin. Ther. Targets. 2016; 20 (6): 653–61. doi: 10.1517/14728222.2016.1131269Avila J., Pallas N., Bolos M., Sayas C.L., Hernandez F. Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies. Expert Opin. Ther. Targets. 2016; 20 (6): 653–61. doi: 10.1517/14728222.2016.1131269Polo V., Garcia-Martin E., Bambo M.P., et al. Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer's disease. Eye (Lond). 2014; 28 (6): 680–90. doi: 10.1038/eye.2014.51Polo V., Garcia-Martin E., Bambo M.P., et al. Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer's disease. Eye (Lond). 2014; 28 (6): 680–90. doi: 10.1038/eye.2014.51Salobrar-Garcia E., de Hoz R., Ramírez A.I., et al. Changes in visual function and retinal structure in the progression of Alzheimer's disease. PloS one. 2019; 14 (8): e0220535. doi: 10.1371/journal.pone.0220535Salobrar-Garcia E., de Hoz R., Ramírez A.I., et al. Changes in visual function and retinal structure in the progression of Alzheimer's disease. PloS one. 2019; 14 (8): e0220535. doi: 10.1371/journal.pone.0220535Leuba G., Saini K., Zimmermann V., Giannakopoulos P., Bouras C. Mild amyloid pathology in the primary visual system of nonagenarians and centenarians. Dement.Geriatr. Cogn. Disord. Karger Publishers. 2001; 12 (2): 146–52. doi: 10.1159/000051249Leuba G., Saini K., Zimmermann V., Giannakopoulos P., Bouras C. Mild amyloid pathology in the primary visual system of nonagenarians and centenarians. Dement.Geriatr. Cogn. Disord. Karger Publishers. 2001; 12 (2): 146–52. doi: 10.1159/000051249Webster M.A. Evolving concepts of sensory adaptation. F1000 Biol. Rep. 2012; 4: 21. doi: 10.3410/B4-21Webster M.A. Evolving concepts of sensory adaptation. F1000 Biol. Rep. 2012; 4: 21. doi: 10.3410/B4-21Polo V., Satue M., Obis J., et al. Retinal and choroidal changes in patients with Parkinson's disease detected by Swept-Source Optical Coherence Tomography.Curr. Eye Res. 2018; 43 (1): 109–15. doi: 10.1080/02713683.2017.1370116Polo V., Satue M., Obis J., et al. Retinal and choroidal changes in patients with Parkinson's disease detected by Swept-Source Optical Coherence Tomography.Curr. Eye Res. 2018; 43 (1): 109–15. doi: 10.1080/02713683.2017.1370116Risacher S.L., Wudunn D., Pepin S.M., et al. Visual contrast sensitivity in Alzheimer’s disease, mild cognitive impairment, and older adults with cognitive complaints. Neurobiol. Aging. 2013; 34 (4): 1133–44. doi: 10.1016/j.neurobiolaging.2012.08.007Risacher S.L., Wudunn D., Pepin S.M., et al. Visual contrast sensitivity in Alzheimer’s disease, mild cognitive impairment, and older adults with cognitive complaints. Neurobiol. Aging. 2013; 34 (4): 1133–44. doi: 10.1016/j.neurobiolaging.2012.08.007Salamone G., Di Lorenzo C., Mosti S., et al. Color discrimination performance in patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. Karger Publishers. 2009; 27 (6): 501–7. doi: 10.1159/000218366.Salamone G., Di Lorenzo C., Mosti S., et al. Color discrimination performance in patients with Alzheimer’s disease. Dement. Geriatr. Cogn. Disord. Karger Publishers. 2009; 27 (6): 501–7. doi: 10.1159/000218366.Savaskan E., Wirz-Justice A., Olivieri G., et al. Distribution of melatonin MT1 receptor immunoreactivity in human retina. J. Histochem. Cytochem. 2002; 50 (4): 519–26. doi: 10.1177/002215540205000408Savaskan E., Wirz-Justice A., Olivieri G., et al. Distribution of melatonin MT1 receptor immunoreactivity in human retina. J. Histochem. Cytochem. 2002; 50 (4): 519–26. doi: 10.1177/002215540205000408Hart N.J., Koronyo Y., Black K.L., Koronyo-Hamaoui M. Ocular indicators of Alzheimer’s: exploring disease in the retina. Acta Neuropathol. Springer Berlin Heidelberg; 2016; 132 (6): 767–87. doi: 10.1007/s00401-016-1613-6Hart N.J., Koronyo Y., Black K.L., Koronyo-Hamaoui M. Ocular indicators of Alzheimer’s: exploring disease in the retina. Acta Neuropathol. Springer Berlin Heidelberg; 2016; 132 (6): 767–87. doi: 10.1007/s00401-016-1613-6Rami L., Serradell M., Bosch B., Villar A., Molinuevo J.L. Perception digital test (PDT) for the assessment of incipient visual disorder in initial Alzheimer’s0 00disease. Neurologia. 2007; 22 (6): 342–7.Rami L., Serradell M., Bosch B., Villar A., Molinuevo J.L. Perception digital test (PDT) for the assessment of incipient visual disorder in initial Alzheimer’s0 00disease. Neurologia. 2007; 22 (6): 342–7.Bodis-Wollner I., Diamond S. The measurement of spatial contrast sensitivity in cases of blurred vision associated with cerebral lesions. Brain 1976; 99 (4): 695–710. doi: 10.1093/brain/99.4.695Bodis-Wollner I., Diamond S. The measurement of spatial contrast sensitivity in cases of blurred vision associated with cerebral lesions. Brain 1976; 99 (4): 695–710. doi: 10.1093/brain/99.4.695Synder P., Johnson P., Lim Y., et al. Non-vascular retinal imaging markers of Preclinical Alzheimer’s disease. Alzheimers Dement. 2016; 4: 169–17. doi: 10.1038/s41598-020-73486-2Synder P., Johnson P., Lim Y., et al. Non-vascular retinal imaging markers of Preclinical Alzheimer’s disease. Alzheimers Dement. 2016; 4: 169–17. doi: 10.1038/s41598-020-73486-2Moreno-Ramos T., Benito-León J., Villarejo A., Bermejo-Pareja F. Retinal nerve fiber layer thinning in dementia associated with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease. J. Alzheimers Dis. 2013; 34 (3): 659–64. doi: 10.3233/JAD-121975Moreno-Ramos T., Benito-León J., Villarejo A., Bermejo-Pareja F. Retinal nerve fiber layer thinning in dementia associated with Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease. J. Alzheimers Dis. 2013; 34 (3): 659–64. doi: 10.3233/JAD-121975Csincsik L., Shakespeare T., Quinn N., et al. Retinal imaging in early and late Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2016; 57: 337. doi: 10.13140/RG.2.2.35038.54080Csincsik L., Shakespeare T., Quinn N., et al. Retinal imaging in early and late Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2016; 57: 337. doi: 10.13140/RG.2.2.35038.54080Li S., Hong S., Sheparardson N., et al. Soluble oligomers of amyloid beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 2009; 62 (6): 788–801. doi: 10.1016/j.neuron.2009.05.012Li S., Hong S., Sheparardson N., et al. Soluble oligomers of amyloid beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 2009; 62 (6): 788–801. doi: 10.1016/j.neuron.2009.05.012Spund B., Ding Y., Liu T., et al. Remodeling of the fovea in Parkinson disease. J. Neural Transm. 2013; 120 (5): 745–53. doi: 10.1007/s00702-012-0909-5Spund B., Ding Y., Liu T., et al. Remodeling of the fovea in Parkinson disease. J. Neural Transm. 2013; 120 (5): 745–53. doi: 10.1007/s00702-012-0909-5Garcia-Martin E.S., Rojas B., Ramirez A.I., et al. Macular thickness as a potential biomarker of mild Alzheimer’s disease. Ophthalmology. 2014; 121 (5): 1149–51. doi: 10.1016/j.ophtha.2013.12.023Garcia-Martin E.S., Rojas B., Ramirez A.I., et al. Macular thickness as a potential biomarker of mild Alzheimer’s disease. Ophthalmology. 2014; 121 (5): 1149–51. doi: 10.1016/j.ophtha.2013.12.023Harnois C., Di Paolo T. Decreased dopamine in the retinas of patients with Parkinson’s disease. Invest Ophthalmol Vis Sci. 1990; 31 (11): 2473–5.Harnois C., Di Paolo T. Decreased dopamine in the retinas of patients with Parkinson’s disease. Invest Ophthalmol Vis Sci. 1990; 31 (11): 2473–5.Firsov M., Astakhova L. The role of dopamine in controlling retinal photoreceptor function in vertebrates. Neurosci. Behav. Physiol. 2016; 46 (2): 138–45. https://doi.org/10.1007/s11055-015-0210-9Firsov M., Astakhova L. The role of dopamine in controlling retinal photoreceptor function in vertebrates. Neurosci. Behav. Physiol. 2016; 46 (2): 138–45. https://doi.org/10.1007/s11055-015-0210-9Witkovsky P. Dopamine and retinal function. Doc Ophthal-mol. 2004; 108 (1): 17–40. doi: 10.1023/b:doop.0000019487.88486.0aWitkovsky P. Dopamine and retinal function. Doc Ophthal-mol. 2004; 108 (1): 17–40. doi: 10.1023/b:doop.0000019487.88486.0aRoth N.M., Saidha S., Zimmermann H., et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov. Disord. 2014; 29 (9): 1163–70. doi: 10.1002/mds.25896Roth N.M., Saidha S., Zimmermann H., et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov. Disord. 2014; 29 (9): 1163–70. doi: 10.1002/mds.25896Nir I., Harrison J.M., Haque R., et al. Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. J. Neuro-sci. 2002; 22 (6): 2063–73. doi: 10.1523/JNEUROSCI.22-06-02063.2002Nir I., Harrison J.M., Haque R., et al. Dysfunctional light-evoked regulation of cAMP in photoreceptors and abnormal retinal adaptation in mice lacking dopamine D4 receptors. J. Neuro-sci. 2002; 22 (6): 2063–73. doi: 10.1523/JNEUROSCI.22-06-02063.2002Devos D., Tir M., Maurage C.A., et al. ERG and anatomical abnormalities suggesting retinopathy in dementia with Lewy bodies. Neurology. 2005; 65 (7): 1107–10. doi: 10.1212/01.wnl.0000178896.44905.33Devos D., Tir M., Maurage C.A., et al. ERG and anatomical abnormalities suggesting retinopathy in dementia with Lewy bodies. Neurology. 2005; 65 (7): 1107–10. doi: 10.1212/01.wnl.0000178896.44905.33Gupta V., Gupta V.B., Chitranshi N., et al. One protein, multiple pathologies: multifaceted involvement of amyloid beta in neurodegenerative disorders of the brain and retina. Cell Mol. Life Sci. 2016; 73 (22): 4279–97. doi: 10.1007/s00018-016-2295-xGupta V., Gupta V.B., Chitranshi N., et al. One protein, multiple pathologies: multifaceted involvement of amyloid beta in neurodegenerative disorders of the brain and retina. Cell Mol. Life Sci. 2016; 73 (22): 4279–97. doi: 10.1007/s00018-016-2295-xMutlu U., Bonnemaijer P.W.M., Ikram M.A., et al. Retinal neurodegeneration and brain MRI markers: the Rotterdam Study. Neurobiol. Aging. 2017; 60: 183-91. doi: 10.1016/j.neurobiolaging.2017.09.003Mutlu U., Bonnemaijer P.W.M., Ikram M.A., et al. Retinal neurodegeneration and brain MRI markers: the Rotterdam Study. Neurobiol. Aging. 2017; 60: 183-91. doi: 10.1016/j.neurobiolaging.2017.09.003Mahajan D., Votruba M. Can the retina be used to diagnose and plot the progression of Alzheimer's disease? Acta Ophthalmol. 2017; 95 (8): 768–77. doi: 10.1111/aos.13472Mahajan D., Votruba M. Can the retina be used to diagnose and plot the progression of Alzheimer's disease? Acta Ophthalmol. 2017; 95 (8): 768–77. doi: 10.1111/aos.13472Lad E.M., Mukherjee D., Stinnett S.S., et al. Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer’s disease. PLoS One. 2018; 13 (2): e0192646. doi: 10.1371/journal.pone.0192646Lad E.M., Mukherjee D., Stinnett S.S., et al. Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer’s disease. PLoS One. 2018; 13 (2): e0192646. doi: 10.1371/journal.pone.0192646Armstead W.M. Cerebral blood flow autoregulation and dysautoregulation. Anesthesiol. Clin. 2016; 34 (3): 465–77. doi: 10.1016/j.anclin.2016.04.002Armstead W.M. Cerebral blood flow autoregulation and dysautoregulation. Anesthesiol. Clin. 2016; 34 (3): 465–77. doi: 10.1016/j.anclin.2016.04.002Cheung C.Y.L., Ong Y.T., Ikram M.K., et al. Microvascular network alterations in the retina of patients with Alzheimer’s disease. Alzheimer’s and Dementia. 2014; 10 (2): 135–42. doi: 10.1016/j.jalz.2013.06.009Cheung C.Y.L., Ong Y.T., Ikram M.K., et al. Microvascular network alterations in the retina of patients with Alzheimer’s disease. Alzheimer’s and Dementia. 2014; 10 (2): 135–42. doi: 10.1016/j.jalz.2013.06.009Frost S., Kanagasingam Y., Sohrabi H., et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl. Psychiatry. 2013; 3 (2): e233. doi: 10.1038/tp.2012.150Frost S., Kanagasingam Y., Sohrabi H., et al. Retinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease. Transl. Psychiatry. 2013; 3 (2): e233. doi: 10.1038/tp.2012.150Lahme L., Esser E.L., Mihailovic N., et al. Evaluation of ocular perfusion in Alzheimer’s disease using Optical Coherence Tomography Angiography. J. Alzheimer’s Dis. 2018; 66 (4): 1745–52. doi: 10.3233/JAD-180738Lahme L., Esser E.L., Mihailovic N., et al. Evaluation of ocular perfusion in Alzheimer’s disease using Optical Coherence Tomography Angiography. J. Alzheimer’s Dis. 2018; 66 (4): 1745–52. doi: 10.3233/JAD-180738Bambo M.P., Garcia-Martin E., Otin S., et al. Visual function and retinal nerve fibre layer degeneration in patients with Alzheimer disease: correlations with severity of dementia. Acta Ophthalmol. 2015; 93 (6): e507– e508. doi: 10.1111/aos.12635Bambo M.P., Garcia-Martin E., Otin S., et al. Visual function and retinal nerve fibre layer degeneration in patients with Alzheimer disease: correlations with severity of dementia. Acta Ophthalmol. 2015; 93 (6): e507– e508. doi: 10.1111/aos.12635Zabel P., Kaluzny J.J., Wilkosc-Debczynska M., et al. Comparison of retinal microvasculature in patients with Alzheimer’s disease and primary open-angle glaucoma by optical coherence tomography angiography. Invest. Ophthalmol. Vis. Sci. 2019; 60 (10): 3447–55. doi: 10.1167/iovs.19-27028Zabel P., Kaluzny J.J., Wilkosc-Debczynska M., et al. Comparison of retinal microvasculature in patients with Alzheimer’s disease and primary open-angle glaucoma by optical coherence tomography angiography. Invest. Ophthalmol. Vis. Sci. 2019; 60 (10): 3447–55. doi: 10.1167/iovs.19-27028Zhang Y.S., Zhou N., Knoll B.M., et al. Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer’s Disease on optical coherence tomography angiography. PLoS ONE. 2019; 14 (4): e0214685. doi: 10.1371/journal.pone.0214685Zhang Y.S., Zhou N., Knoll B.M., et al. Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer’s Disease on optical coherence tomography angiography. PLoS ONE. 2019; 14 (4): e0214685. doi: 10.1371/journal.pone.0214685Jiang H., Wei Y., Shi Y., et al. Altered macular microvasculature in mild cognitive impairment and Alzheimer disease. J. Neuro Ophthalmol. 2018; 38 (3): 292–8. doi: 10.1097/WNO.0000000000000580Jiang H., Wei Y., Shi Y., et al. Altered macular microvasculature in mild cognitive impairment and Alzheimer disease. J. Neuro Ophthalmol. 2018; 38 (3): 292–8. doi: 10.1097/WNO.0000000000000580O’Bryhim B.E., Apte R.S., Kung N., Coble D., Van Stavern G.P. Association of preclinical Alzheimer disease with Optical Coherence Tomographic Angiography findings. JAMA Ophthalmol. 2018; 136 (11): 1242–8. doi: 10.1001/jamaophthalmol.2018.3556O’Bryhim B.E., Apte R.S., Kung N., Coble D., Van Stavern G.P. Association of preclinical Alzheimer disease with Optical Coherence Tomographic Angiography findings. JAMA Ophthalmol. 2018; 136 (11): 1242–8. doi: 10.1001/jamaophthalmol.2018.3556Shi C., Chen Y., Kwapong W.R., et al. Characterization by fractal dimension analysis of the retinal capillary network in Parkinson disease. Retina. 2019; 40 (8): 1483–91. doi: 10.1097/IAE.0000000000002641Shi C., Chen Y., Kwapong W.R., et al. Characterization by fractal dimension analysis of the retinal capillary network in Parkinson disease. Retina. 2019; 40 (8): 1483–91. doi: 10.1097/IAE.0000000000002641

The authors declare that there are no conflicts of interest present.