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1.
BMC Ophthalmol ; 24(1): 201, 2024 May 03.
Article En | MEDLINE | ID: mdl-38698363

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.


Collagen , Cross-Linking Reagents , Fluorescein Angiography , Keratoconus , Optic Disk , Retinal Vessels , Tomography, Optical Coherence , Humans , Tomography, Optical Coherence/methods , Keratoconus/physiopathology , Keratoconus/diagnosis , Male , Female , Collagen/metabolism , Young Adult , Adult , Fluorescein Angiography/methods , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Optic Disk/blood supply , Adolescent , Prospective Studies , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Macula Lutea/diagnostic imaging , Macula Lutea/blood supply
2.
Exp Eye Res ; 242: 109885, 2024 May.
Article En | MEDLINE | ID: mdl-38574944

The retinal microcirculation system constitutes a unique terminal vessel bed of the systemic circulation, and its perfusion status is directly associated with the neural function of the retina. This vascular network, essential for nourishing various layers of the retina, comprises two primary microcirculation systems: the retinal microcirculation and the choroidal microcirculation, with each system supplying blood to distinct retinal layers and maintaining the associated neural function. The blood flow of those capillaries is regulated via different mechanisms. However, a range of internal and external factors can disrupt the normal architecture and blood flow within the retinal microcirculation, leading to several retinal pathologies, including diabetic retinopathy, macular edema, and vascular occlusions. Metabolic disturbances such as hyperglycemia, hypertension, and dyslipidemia are known to modify retinal microcirculation through various pathways. These alterations are observable in chronic metabolic conditions like diabetes, coronary artery disease, and cerebral microvascular disease due to advances in non-invasive or minimally invasive retinal imaging techniques. Thus, examination of the retinal microcirculation can provide insights into the progression of numerous chronic metabolic disorders. This review discusses the anatomy, physiology and pathophysiology of the retinal microvascular system, with a particular emphasis on the connections between retinal microcirculation and systemic circulation in both healthy states and in the context of prevalent chronic metabolic diseases.


Metabolic Diseases , Microcirculation , Retinal Vessels , Humans , Microcirculation/physiology , Retinal Vessels/physiopathology , Metabolic Diseases/physiopathology , Retinal Diseases/physiopathology , Regional Blood Flow/physiology
3.
Ophthalmic Res ; 67(1): 257-265, 2024.
Article En | MEDLINE | ID: mdl-38508153

INTRODUCTION: Microcirculation of optic nerve head (ONH) in open-angle glaucoma (OAG) patients with unilateral visual field (VF) loss has yet to be fully investigated, especially the perimetrically unaffected fellow eyes. METHODS: Thirty-eight OAG patients with VF defect in one eye and normal VF in the other eye, and thirty-one healthy participants were analyzed. All participants underwent laser speckle flowgraphy (LSFG), spectral-domain optical coherence tomography (SD-OCT) imaging, and VF test for further analyses. LSFG measurements included mean blur rate in all area of ONH (MA), big vessel area of ONH (MV), and tissue area of ONH (MT). SD-OCT parameters included circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macula thicknesses. The difference of LSFG and SD-OCT indices between glaucoma patients and healthy controls were compared. The diagnostic accuracy was analyzed with the areas under the receiver operating characteristic curves (AROCs). RESULTS: Global cpRNFL thickness and macular thickness in unaffected eyes of OAG patients were higher than their fellow eyes and lower than healthy eyes. MA and MV in healthy eyes and unaffected eyes were significantly higher than in affected eyes. MT in unaffected eyes of OAG patients was higher than in their fellow affected eyes but lower than in healthy eyes. The AROCs were highest for cpRNFL (0.925), followed by macular thickness (0.838), and MT (0.834). CONCLUSIONS: ONH microcirculation in perimetrically unaffected fellow eyes was decreased in OAG patients with unilateral VF loss. LSFG can detect changes of ONH in high-risk eyes before detectable VF damage, which may reflect the vascular pathophysiology for glaucoma.


Glaucoma, Open-Angle , Microcirculation , Nerve Fibers , Optic Disk , Retinal Ganglion Cells , Tomography, Optical Coherence , Visual Fields , Humans , Glaucoma, Open-Angle/physiopathology , Glaucoma, Open-Angle/diagnosis , Male , Female , Optic Disk/blood supply , Microcirculation/physiology , Visual Fields/physiology , Tomography, Optical Coherence/methods , Middle Aged , Nerve Fibers/pathology , Retinal Ganglion Cells/pathology , Aged , Intraocular Pressure/physiology , Visual Field Tests , Laser-Doppler Flowmetry , ROC Curve , Retinal Vessels/physiopathology , Retinal Vessels/diagnostic imaging
4.
Retina ; 44(5): 887-894, 2024 May 01.
Article En | MEDLINE | ID: mdl-38165995

PURPOSE: To explore the relationship between retinal hemorrhage in the green and red channels on ultra-widefield fundus images and the nonperfusion area (NPA) on ultra-widefield fundus fluorescein angiography in patients with acute branch retinal vein occlusion (BRVO). METHODS: This was a retrospective cross-sectional study with 96 patients, including 46 with ischemic BRVO and 50 with nonischemic BRVO. Correlation analysis between green channel hemorrhage (GCH), red channel hemorrhage (RCH), and NPA was performed. Panretina was divided into posterior and peripheral areas. RESULTS: Ischemic BRVO showed significantly higher GCH% and RCH% than nonischemic BRVO in the peripheral regions (both P < 0.001), whereas no significant differences were observed in the panretinal and posterior areas (all P > 0.05). Significant correlations were found between NPA% in the panretinal and peripheral areas and the corresponding GCH% and RCH% (all P < 0.01). However, no significant correlation was observed between posterior NPA% and posterior GCH% or RCH% (both P > 0.05). In addition, peripheral GCH% and RCH% were related to panretinal NPA% (r = 0.506, P < 0.001; r = 0.558, P < 0.001). CONCLUSION: Retinal hemorrhage on ultra-widefield fundus image was significantly associated with NPA, providing insights for assessing retinal perfusion status in acute BRVO patients.


Fluorescein Angiography , Fundus Oculi , Retinal Hemorrhage , Retinal Vein Occlusion , Retinal Vessels , Humans , Retinal Vein Occlusion/physiopathology , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/complications , Retrospective Studies , Fluorescein Angiography/methods , Retinal Hemorrhage/diagnosis , Retinal Hemorrhage/physiopathology , Retinal Hemorrhage/etiology , Cross-Sectional Studies , Female , Male , Aged , Middle Aged , Acute Disease , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Visual Acuity/physiology , Tomography, Optical Coherence/methods , Aged, 80 and over , Regional Blood Flow/physiology
5.
Microcirculation ; 31(4): e12844, 2024 May.
Article En | MEDLINE | ID: mdl-38241091

OBJECTIVE: We aimed to characterize several aspects of retinal vascular dynamics in a patient with arrythmia in order to elicit additional diagnostic information on microvascular dysfunction. METHODS: A 68-year-old male patient with arrythmia and an age- and gender-matched control subject underwent ocular examination including dynamic retinal vessel assessment with flicker light provocation. Retinal vessel diameters were measured continuously following a standard protocol (IMEDOS Systems, Jena, Germany). The data were evaluated using methods of signal analysis. RESULTS: Retinal vessel response following flicker provocation as well as local structural and functional behavior of retinal vessels were comparable between both individuals. The arrhythmia case demonstrated irregular arterial and venous heart rate (HR) pulsation with an average frequency of 1 Hz. Moreover, the case showed a higher magnitude and larger periods of low-frequency retinal vessel oscillations as well as lower periodicity of both HR pulsations and low-frequency vasomotions. CONCLUSIONS: Besides numerical examination of irregular HR pulsations in case of arrhythmia, from the direct noninvasive assessment of retinal vessel dynamics one can derive more detailed information on microvascular function including the whole spectrum of retinal arterial and venous pulsations and vasomotions. This may have implications for health screening not limited to atrial fibrillation.


Retinal Vessels , Humans , Male , Aged , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Retinal Vessels/pathology , Heart Rate , Arrhythmias, Cardiac/physiopathology
6.
Rev Neurol (Paris) ; 179(6): 548-562, 2023 Jun.
Article En | MEDLINE | ID: mdl-36842953

Amyotrophic lateral sclerosis (ALS) is a rare fatal motor neuron disease. Although many potential mechanisms have been proposed, the pathophysiology of the disease remains unknown. Currently available treatments can only delay the progression of the disease and prolong life expectancy by a few months. There is still no definitive cure for ALS, and the development of new treatments is limited by a lack of understanding of the underlying biological processes that trigger and promote neurodegeneration. Several scientific results suggest a neurovascular impairment in ALS providing perspectives for the development of new biomarkers and treatments. In this article, we performed a systematic review using PRISMA guidelines including PubMed, EmBase, GoogleScholar, and Web of Science Core Collection to analyze the scientific literature published between 2000 and 2021 discussing the neurocardiovascular involvement and ophthalmologic abnormalities in ALS. In total, 122 articles were included to establish this systematic review. Indeed, microvascular pathology seems to be involved in ALS, affecting all the neurovascular unit components. Retinal changes have also been recently highlighted without significant alteration of the visual pathways. Despite the peripheral location of the retina, it is considered as an extension of the central nervous system (CNS) as it displays similarities to the brain, the inner blood-retinal barrier, and the blood-brain barrier. This suggests that the eye could be considered as a 'window' into the brain in many CNS disorders. Thus, studying ocular manifestations of brain pathologies seems very promising in understanding neurodegenerative disorders, mainly ALS. Optical coherence tomography angiography (OCT-A) could therefore be a powerful approach for exploration of retinal microvascularization allowing to obtain new diagnostic and prognostic biomarkers of ALS.


Amyotrophic Lateral Sclerosis , Microvessels , Retinal Vessels , Tomography, Optical Coherence , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/physiopathology , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Humans , Microvessels/diagnostic imaging , Microvessels/physiopathology , Angiography/methods , Saccades
7.
Exp Eye Res ; 237: 109703, 2023 Dec.
Article En | MEDLINE | ID: mdl-38652673

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.3 scans per eye) and UWF-FA imaging. OCTA images were registered and averaged to generate a superficial capillary plexus (SCP), deep capillary plexus (DCP), and MLC slab. We calculated geometric perfusion deficit (GPD), vessel length density, and vessel density for the SCP and DCP. MLC density was quantified by two masked graders and averaged. Ischemia on UWF-FA was measured to generate a non-perfusion area (NPA) and index (NPI). Since MLC density was non-parametrically distributed, MLC density was correlated with ischemia metrics using Spearman correlations. Forty-five treatment-naïve eyes of 45 patients (59 ± 12 years of age; 56% female) were imaged. We included 6 eyes with no DR, 7 eyes with mild non-proliferative DR (NPDR), 22 moderate NPDR, 4 severe NPDR, and 6 PDR eyes. MLC density between graders was highly correlated (r = 0.9592, p < 0.0001). MLC density was correlated with DCP GPD (r = 0.296, p = 0.049), but no other OCTA ischemia metrics. MLC density was also correlated with UWF-FA NPA (r = 0.330, p = 0.035) and NPI (r = 0.332, p = 0.034). MLC density was correlated with total ischemia on UWF-FA and local DCP GPD. Since both UWF-FA and DCP non-perfusion are associated with higher risk for DR progression, MLC density could be another potential biomarker for DR progression.


Diabetic Retinopathy , Fluorescein Angiography , Ischemia , Macrophages , Retinal Vessels , Tomography, Optical Coherence , Humans , Female , Middle Aged , Male , Tomography, Optical Coherence/methods , Fluorescein Angiography/methods , Diabetic Retinopathy/physiopathology , Diabetic Retinopathy/pathology , Retinal Vessels/pathology , Retinal Vessels/physiopathology , Retinal Vessels/diagnostic imaging , Prospective Studies , Cell Count , Ischemia/physiopathology , Ischemia/pathology , Macrophages/pathology , Aged , Fundus Oculi
9.
J Am Heart Assoc ; 11(15): e25226, 2022 08 02.
Article En | MEDLINE | ID: mdl-35876422

Background The associations of time-averaged cumulative blood pressure (BP) from midlife to late life with microvasculature expressed as retinal vessel diameters is not well studied. The aim of this study was to evaluate the association of cumulative systolic BP and diastolic BP (DBP) with retinal vessel calibers, focusing on race differences. Methods and Results The analysis included 1818 adults from the ARIC (Atherosclerosis Risk in Communities) study attending the fifth visit (2011-2013; age 77±5 years, 17.1% Black participants). Time-averaged cumulative BPs were calculated as the sum of averaged BPs from adjacent consecutive visits (visits 1-5) indexed to total observation time (24±1 years). Summarized estimates for central retinal arteriolar equivalent and central retinal venular equivalent at the fifth visit represent average retinal vessel diameters. The arteriole:venule ratio was calculated. We tested for effect modification by race. Results from multiple linear regression models suggested that higher time-averaged cumulative DBP (ß [95% CI] per 1-SD increase: -1.78 [-2.53, -1.02], P<0.001 and -0.005 [-0.009, -0.002], P=0.004, respectively) but not systolic BP (-0.52 [-1.30, 0.26], P=0.189 and 0.001 [-0.002, 0.005], P=0.485, respectively) was associated with smaller central retinal arteriolar equivalent and arteriole:venule ratio. The association between time-averaged cumulative DBP and arteriole:venule ratio was strongest in White participants (interaction P=0.007). The association of cumulative systolic BP and DBP with central retinal venular equivalent was strongest in Black participants (interaction P=0.015 and 0.011, respectively). Conclusions Exposure to higher BP levels, particularly DBP, from midlife to late life is associated with narrower retinal vessel diameters in late life. Furthermore, race moderated the association of cumulative BP exposure with retinal microvasculature.


Blood Pressure , Hypertension , Microvessels , Retinal Vessels , Age Factors , Aged , Aged, 80 and over , Arterioles/physiopathology , Black People , Blood Pressure/physiology , Diastole , Humans , Hypertension/complications , Hypertension/diagnosis , Hypertension/ethnology , Hypertension/physiopathology , Microvessels/physiopathology , Retinal Artery/physiopathology , Retinal Vein/physiopathology , Retinal Vessels/physiopathology , Systole , Time Factors , Venules/physiopathology , White People
10.
Geroscience ; 44(3): 1551-1562, 2022 06.
Article En | MEDLINE | ID: mdl-35484471

The pathognomonic hallmark of Parkinson's disease (PD), α-synuclein, has been observed in the retina of PD patients. We investigated whether biomarkers in the tears and retinal microvascular changes associate with PD risk and progression. This prospective study enrolled 49 PD patients and 45 age-matched healthy controls. The α-synuclein and neurofilament light chain (NfL) levels were measured using an electrochemiluminescence immunoassay. Retinal vessel density was assessed using optical coherence tomography angiography (OCT-A). The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Mini-Mental State Examination score were used to assess motor and cognitive progression. The α-synuclein and NfL levels in the tears were higher in PD patients than in controls (α-synuclein: 55.49 ± 8.12 pg/mL vs. 31.71 ± 3.25 pg/mL, P = 0.009; NfL: 2.89 ± 0.52 pg/mL vs. 1.47 ± 0.23 pg/mL, P = 0.02). The vessel densities in the deep plexus of central macula and the radial peripapillary capillary layer of disc region were lower in PD patients with moderate-stage compared with early-stage PD (P < 0.05). The accuracy of predicting PD occurrence using age and sex alone (area under the curve [AUC] 0.612) was significantly improved by adding α-synuclein and NfL levels and retinal vascular densities (AUC 0.752, P = 0.001). After a mean follow-up of 1.5 ± 0.3 years, the accuracy of predicting motor or cognitive progression using age, sex, and baseline motor severity as a basic model was increased by incorporating retinal microvascular and biofluid markers as a full model (P = 0.001). Our results showed that retinal microvascular densities combined with α-synuclein and NfL levels in tears are associated with risk and progression of PD.


Microvascular Density , Neurofilament Proteins , Parkinson Disease , Retinal Vessels , alpha-Synuclein , Biomarkers , Humans , Neurofilament Proteins/metabolism , Parkinson Disease/physiopathology , Prospective Studies , Retina , Retinal Vessels/physiopathology , Tears , alpha-Synuclein/metabolism
11.
Comput Math Methods Med ; 2022: 8437066, 2022.
Article En | MEDLINE | ID: mdl-35309847

Objective: In order to analyze changes in retinal vessel flow after small incision lenticule extraction (SMILE). Methods: A total of 32 patients (62 eyes) who underwent SMILE were enrolled in this prospective study. Optical parameters, including vessel density (VD), and perfusion density (PD) of foveal, parafoveal, and perifoveal regions, respectively, were measured before surgery and at 1 day, 1 week, 1 month, and 3 months postoperation. Preoperative parameters and surgical parameters were recorded. Results: Significant decreases in VD and PD on postoperative day 1 were detected in all quadrants, both in 3 mm and in 6 mm regions (P < 0.001). One month after surgery, VD returned to preoperative levels. None of the preoperative and surgical parameters were significantly correlated with the VD and PD fluctuations (all P > 0.05). Conclusion. VD may decrease significantly with regional disparity 1 day after SMILE while recovering at 1 month. Elevation of intraocular pressure due to suction may account for such changes.


Myopia/physiopathology , Myopia/surgery , Refractive Surgical Procedures/methods , Retinal Vessels/physiopathology , Adult , Computational Biology , Female , Humans , Male , Myopia/diagnostic imaging , Postoperative Period , Prospective Studies , Refractive Surgical Procedures/adverse effects , Regional Blood Flow , Retinal Vessels/diagnostic imaging , Time Factors , Tomography, Optical Coherence/statistics & numerical data , Young Adult
12.
Biomed Environ Sci ; 35(2): 107-114, 2022 Feb 20.
Article En | MEDLINE | ID: mdl-35197175

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION: The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.


Corneal Dystrophies, Hereditary/diagnostic imaging , Corneal Dystrophies, Hereditary/physiopathology , Retinal Diseases/diagnostic imaging , Retinal Diseases/physiopathology , Adult , Aged , Angiography , Female , Humans , Male , Microvascular Density , Microvessels/diagnostic imaging , Microvessels/physiopathology , Middle Aged , Retinal Vessels/diagnostic imaging , Retinal Vessels/physiopathology , Tomography, Optical Coherence
13.
Sci Rep ; 12(1): 3089, 2022 02 23.
Article En | MEDLINE | ID: mdl-35197526

Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces, i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR.


Diabetic Retinopathy/diagnostic imaging , Diabetic Retinopathy/pathology , Fluorescein Angiography/methods , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Tomography, Optical Coherence/methods , Adult , Aged , Aged, 80 and over , Biomarkers , Female , Humans , Male , Microcirculation , Middle Aged , ROC Curve , Retinal Vessels/physiopathology , Retrospective Studies , Severity of Illness Index
14.
Retina ; 42(3): 529-539, 2022 03 01.
Article En | MEDLINE | ID: mdl-35188491

PURPOSE: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). METHODS: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. RESULTS: Macular sensitivity reduced with increasing severity of MMD (ß ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (ß = -0.08, P < 0.001), with longer axial length (ß = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (ß = -2.16, P < 0.001) or worse MMD (ß = -5.70, P < 0.001), and presence of macular posterior staphyloma (ß ≤ -2.98, P < 0.001) or Fuchs spot (ß = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (ß = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). CONCLUSION: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.


Macular Degeneration/physiopathology , Myopia, Degenerative/physiopathology , Retina/physiology , Retinal Vessels/physiopathology , Adult , Aged , Axial Length, Eye , Capillaries/physiopathology , Computed Tomography Angiography , Female , Humans , Macular Degeneration/diagnosis , Male , Middle Aged , Myopia, Degenerative/diagnosis , Refraction, Ocular , Sensitivity and Specificity , Tomography, Optical Coherence , Visual Acuity/physiology , Visual Field Tests , Visual Fields/physiology
15.
Sci Rep ; 12(1): 329, 2022 01 10.
Article En | MEDLINE | ID: mdl-35013324

Vessel and perfusion densities may decrease before diabetic retinopathy appears; it is unknown whether these changes affect the contribution of vessel density to perfusion density. This was a non-experimental, comparative, prospective, cross-sectional study in non-diabetic subjects (group 1) and diabetics without retinopathy (group 2). Vessel and perfusion densities in the superficial capillary plexus were compared between groups at the center, inner, and full regions and by field (superior, temporal, inferior, nasal) using optical coherence tomography angiography. Coefficients of determination (R2) between vessel and perfusion densities were calculated to find the contribution of larger retinal vessels to perfusion density. Percent differences were used to evaluate the contribution of these vessels to perfusion density in a regression model. There were 62 participants, 31 eyes by group; vessel and perfusion densities as well as the coefficients of determination between them were lower in group 2, especially in the nasal field (R2 0.85 vs. 0.71), which showed a higher contribution of larger retinal vessels to perfusion density. The regression model adjusted to a quadratic equation. In diabetics without retinopathy the contribution of vessel density to perfusion density may decrease; a low vessel density may increase the contribution of larger retinal vessels to perfusion density.


Angiography , Diabetes Mellitus/diagnostic imaging , Perfusion Imaging , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence , Adult , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus/physiopathology , Female , Humans , Male , Microvascular Density , Middle Aged , Predictive Value of Tests , Prospective Studies , Regional Blood Flow , Retinal Vessels/physiopathology
16.
PLoS Comput Biol ; 18(1): e1009728, 2022 01.
Article En | MEDLINE | ID: mdl-34986147

Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). MA leakage or rupture may precipitate local pathology in the surrounding neural retina that impacts visual function. Thrombosis in MAs may affect their turnover time, an indicator associated with visual and anatomic outcomes in the diabetic eyes. In this work, we perform computational modeling of blood flow in microchannels containing various MAs to investigate the pathologies of MAs in DR. The particle-based model employed in this study can explicitly represent red blood cells (RBCs) and platelets as well as their interaction in the blood flow, a process that is very difficult to observe in vivo. Our simulations illustrate that while the main blood flow from the parent vessels can perfuse the entire lumen of MAs with small body-to-neck ratio (BNR), it can only perfuse part of the lumen in MAs with large BNR, particularly at a low hematocrit level, leading to possible hypoxic conditions inside MAs. We also quantify the impacts of the size of MAs, blood flow velocity, hematocrit and RBC stiffness and adhesion on the likelihood of platelets entering MAs as well as their residence time inside, two factors that are thought to be associated with thrombus formation in MAs. Our results show that enlarged MA size, increased blood velocity and hematocrit in the parent vessel of MAs as well as the RBC-RBC adhesion promote the migration of platelets into MAs and also prolong their residence time, thereby increasing the propensity of thrombosis within MAs. Overall, our work suggests that computational simulations using particle-based models can help to understand the microvascular pathology pertaining to MAs in DR and provide insights to stimulate and steer new experimental and computational studies in this area.


Computer Simulation , Diabetic Retinopathy/physiopathology , Microaneurysm/physiopathology , Retinal Vessels/physiopathology , Blood Flow Velocity/physiology , Diabetic Retinopathy/diagnostic imaging , Erythrocytes/physiology , Hematocrit , Humans , Microaneurysm/diagnostic imaging , Retinal Vessels/diagnostic imaging , Thrombosis/diagnostic imaging , Thrombosis/physiopathology
17.
Med Sci Monit ; 28: e932996, 2022 Jan 10.
Article En | MEDLINE | ID: mdl-35001073

BACKGROUND The aim of this study was to assess use of lncRNAs as biomarkers in serum and aqueous humor of patients with diabetic macular edema (DME). MATERIAL AND METHODS Optical coherence tomography and fundus photography were used to analyze the retinal features of the patients. RT-qPCR was used to analyze the differential expression of lncRNA snhg5 in patients who have idiopathic macular hole (MH), DME, or refractory DME. The relationship between SNHG5 and the clinical characteristics of the patients was analyzed. The effect of SNHG5 on the hyperplasia and apoptosis of human retino-microvascular endothelial cells (HRMECs) and its mechanism were analyzed in vitro. RESULTS Patients with idiopathic MH developed retinal nerve epithelium rupture and retinal fundus thickening, and patients with DME or refractory DME showed significant macular edema with hemorrhaging. The refractory DME patients improved after treatment but still showed significant macular edema and multiple laser scarring. SNHG5 expression was not only low in the atrial fluid and plasma in DME patients, but also lower in the refractory DME group compared to the idiopathic MH patients. SNHG5 expression in the aqueous humor and plasma was negatively correlated with disease duration, body mass index, and levels of fasting blood glucose, glycated hemoglobin, proteinuria, and glycosuria. In the in vitro experiments, SNHG5 expression was significantly downregulated in high glucose-induced HMECs. After SNHG5 overexpression, cell proliferation, angiogenesis, and VEGF-A protein levels were distinctly downregulated. CONCLUSIONS SNHG5 correlates with the development of DME and is a potential target for therapy.


Aqueous Humor/metabolism , Diabetic Retinopathy , Endothelial Cells/metabolism , Macular Edema/metabolism , RNA, Long Noncoding , Vascular Endothelial Growth Factor A/metabolism , Biomarkers/blood , Biomarkers/metabolism , Diabetic Retinopathy/blood , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/physiopathology , Female , Fluorescein Angiography/methods , Gene Expression Profiling/methods , Humans , Macular Edema/diagnosis , Macular Edema/etiology , Male , Middle Aged , RNA, Long Noncoding/blood , RNA, Long Noncoding/metabolism , Retina/diagnostic imaging , Retina/pathology , Retinal Neovascularization/diagnostic imaging , Retinal Neovascularization/etiology , Retinal Vessels/pathology , Retinal Vessels/physiopathology , Tomography, Optical Coherence/methods , Visual Acuity
18.
Retina ; 42(2): 357-368, 2022 02 01.
Article En | MEDLINE | ID: mdl-34510129

PURPOSE: To assess global, zonal, and local correlations between vessel density changes measured by optical coherence tomography angiography and retinal sensitivity measured by microperimetry across diabetic retinopathy severity. METHODS: Diabetic patients and nondiabetic controls underwent optical coherence tomography angiography imaging and microperimetry testing. Pearson's correlation was used to assess associations between average sensitivity and skeletonized vessel density (SVD) or foveal avascular zone area centrally. Linear mixed effects modeling was used to assess relationships between local SVD measurements and their spatially corresponding retinal sensitivity measurements. RESULTS: Thirty-nine eyes from 39 participants were imaged. In all slabs, there was a statistically significant positive correlation between retinal sensitivities and SVDs on both global and zonal scales. No statistically significant correlation was found between central retinal sensitivities and the foveal avascular zone areas. Assessment of 1,136 spatially paired retinal sensitivity and SVD measurements revealed a statistically significant local relationship; this seemed to be driven by eyes with proliferative diabetic retinopathy that had reduced retinal sensitivities. CONCLUSION: This study supports positive correlations between SVD and retinal sensitivity at global and zonal spatial scales in diabetic eyes. However, our analysis did not find evidence of statistically significant correlations between retinal sensitivity and SVD on a local scale until advanced diabetic retinopathy.


Diabetic Retinopathy/physiopathology , Retina/physiology , Retinal Vessels/physiopathology , Visual Fields/physiology , Adult , Aged , Aged, 80 and over , Computed Tomography Angiography , Cross-Sectional Studies , Diabetic Retinopathy/diagnostic imaging , Female , Humans , Male , Middle Aged , Prospective Studies , Regional Blood Flow/physiology , Retinal Vessels/diagnostic imaging , Tomography, Optical Coherence , Visual Acuity/physiology , Visual Field Tests
19.
Microvasc Res ; 139: 104238, 2022 01.
Article En | MEDLINE | ID: mdl-34492257

BACKGROUND: Regular exercise positively affects cardiovascular physiology, translating into the adequate capacity of microvascular blood vessels to dilate in response to acute bouts of exercise. However, this remains unstudied in patients with chronic obstructive pulmonary disease (COPD), who often suffer from cardiovascular comorbidity. Therefore, we studied acute changes in retinal blood vessel diameters in response to high-intensity exercise in patients with COPD. The effect of an exercise-based 8-week pulmonary rehabilitation (PR) program was evaluated. We consider changes in these retinal metrics as an indicator of microvascular reactivity. METHODS: Demographics and clinical characteristics of 41 patients were collected at the start and end of the PR program. Patients performed a high-intensity exercise test on a cycle ergometer at the start and end of the PR program, during which we collected retinal images. Fundus images were taken immediately before and 0, 5, 10, 15, and 30 min after the ergometer test. Widths of retinal blood vessels, represented as Central Retinal Arteriolar and Venular Equivalents (CRAE and CRVE), were calculated. RESULTS: Thirty patients with COPD completed the study protocol (57% males; mean age: 64 ± 7 years; mean FEV1: 45 ± 17%pred). We did not observe a change in retinal vessel widths following the ergometer test at the start of the PR program. This null result remained at the end of the 8-week PR program. Our observations did not alter when considering responders and non-responders to PR. CONCLUSION: Retinal blood vessel diameters of patients with COPD did not change following an exercise test on an ergometer. The exercise-based PR program of eight weeks did not counteract the blunted retinal microvascular response.


Exercise Therapy , Lung/physiopathology , Microcirculation , Microvessels/physiopathology , Pulmonary Disease, Chronic Obstructive/rehabilitation , Retinal Vessels/physiopathology , Vasodilation , Aged , Bicycling , Exercise Test , Female , Humans , Male , Microvessels/diagnostic imaging , Middle Aged , Photography , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Retinal Vessels/diagnostic imaging , Time Factors , Treatment Outcome
20.
Retina ; 42(1): 152-158, 2022 01 01.
Article En | MEDLINE | ID: mdl-34369439

PURPOSE: To define the effect of age-related macular degeneration (AMD) and diabetic retinopathy (DR) on the ocular thermographic profile. METHODS: This retrospective cross-sectional study included subjects diagnosed with DR or AMD between January and April 2019. Individuals without ocular disease served as controls. A thermal imaging camera was used for ocular surface temperature (OST) acquisition. The mean temperatures of the medial cantus, lateral cantus, and cornea were calculated. RESULTS: Thermographic images were obtained from 133 subjects (260 eyes, 97 DR and 163 AMD) and 48 controls (55 eyes). Ocular surface temperature was higher among patients with AMD and lowest among patients with DR (P < 0.001). A subgroup analysis revealed that eyes with diabetic macular edema had significantly higher OSTs than DR eyes without diabetic macular edema. Moreover, the OST in eyes with diabetic macular edema was similar to the measurements of the AMD group. There were no differences in OSTs between neovascular and nonneovascular AMD eyes. CONCLUSION: Although AMD and DR are considered posterior segment conditions, their effect on OST implies that the entire globe is involved. Although both conditions result from similar multifactorial pathophysiologic changes, the differences in OST between DR and AMD might be due to dissimilarity in the balance of pathologic processes involved in each condition. Further research is required to better understand the pathophysiology of these diseases and their effect on OST as well as to determine the effect of vasculature, circulation, and tissue metabolism on ocular temperature.


Body Temperature/physiology , Eye/physiopathology , Retinal Diseases/physiopathology , Retinal Vessels/diagnostic imaging , Thermography/methods , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Retina/diagnostic imaging , Retina/physiopathology , Retinal Diseases/diagnosis , Retinal Vessels/physiopathology , Retrospective Studies , Tomography, Optical Coherence/methods
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