Quantitative Assessment of Microvascular Changes in Diabetic Retinopathy and Their Association With Blood-Retinal Barrier Impairment
Abstract
Objective
To quantitatively evaluate retinal microvascular changes in patients with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA), and to explore their association with blood-retinal barrier (BRB) disruption.
Methods
A total of 208 patients with type 2 diabetes and DR underwent OCTA to obtain microvascular parameters. Serum vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) levels were measured. Correlations were analyzed, risk factors were identified using logistic regression, and diagnostic efficacy was evaluated with ROC curves.
Results
The superficial capillary density (SCP-D) and deep capillary density (DCP-D) of the 208 DR patients were (42.67 ± 4.35)% and (47.89 ± 5.02)%, respectively. The mean values for the area, perimeter, and circularity index of the foveal avascular zone (FAZ) were (0.38 ± 0.10) mm², (2.04 ± 0.28) mm, and 0.72 ± 0.08, respectively. The mean area of the non-perfusion zone was (1.87 ± 0.45) mm². Among these patients, 121 (58.17%) cases had abnormal SCP-D (< 45%), 114 (56.25%) cases had abnormal DCP-D (< 50%), 88 (42.31%) cases had abnormal FAZ area, 77 (37.02%) cases had abnormal FAZ perimeter, 69 (33.17%) cases had abnormal FAZ circularity index, and 142 (68.27%) cases had abnormal non-perfusion zone area. The FAZ area was positively correlated with VEGF (r = 0.559, 95% CI: 0.457-0.661) and ICAM-1 (r = 0.411, 95% CI: 0.289-0.533). The FAZ circularity index, SCP-D, and DCP-D were negatively correlated with VEGF and ICAM-1 (P < 0.05). The area of the non-perfusion zone was positively correlated with both. Logistic regression showed that the duration of diabetes (odds ratio [OR] = 1.159, 95% CI: 1.060-1.267) and VEGF (OR = 1.013, 95% CI: 1.005-1.022) were independent risk factors for severe retinal microvascular changes (P < 0.05). Among the four OCTA assessment indicators, the area of the non-perfusion zone had the highest predictive value, with an area under the curve (AUC) of 0.879 (95% CI: 0.820-0.938).
Conclusion
The OCTA assessment indicators in DR patients are closely related to BRB-related markers. The area of the non-perfusion zone has the highest predictive value for severe retinal microvascular changes in DR patients.
Keywords: Diabetic retinopathy, Optical coherence tomography angiography, Retinal microvascular alterations,Blood-retinal barrier
Full Text:
PDFReferences
SUN D D, XU X. Research status and progress on the protective effects of melatonin on endothelial cells and pericytes in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(9): 745-748. doi: 10. 3760/cma.j.cn511434-20190321-00106.
LEI L Y, CAO Y, YAO J. Role of microglia-mediated intercellular communication in the retinal neurovascular unit. Chinese Journal of Experimental Ophthalmology, 2024, 42(11): 1060-1064. doi: 10.3760/cma. j.cn115989-20230627-00025.
ZHOU J, HAN M. Finerenone alleviates diabetic retinopathy in rats by inhibiting microglial inflammatory response. Chinese Journal of Pathophysiology, 2023, 39(8): 1483-1490. doi: 10.3969/j.issn.1000-4718. 2023.08.017.
ZHONG Y, JIANG P F, ZHAO P, et al. Mechanism of Yiqi Yangyin Huoxue Lishui Recipe in inhibiting microvascular pericyte apoptosis in early diabetic retinopathy rats based on PI3K/AKT signaling pathway. Journal of Hunan University of Chinese Medicine, 2023, 43(11): 2024-2033. doi: 10.3969/j.issn.1674-070X.2023.11.015.
GONG K, TANG L, SUN W T, et al. Intervention effect of human endostatin on diabetic retinopathy in rats and its influence on the expression of VCAM-1, ICAM-1, and VEGF proteins. Journal of Clinical and Experimental Medicine, 2021, 20(11): 1143-1147. doi: 10.3969/j.issn. 1671-4695.2021.11.007.
DHARMARAJAN S, CARRILLO C, QI Z, et al. Retinal inflammation in murine models of type 1 and type 2 diabetes with diabetic retinopathy. Diabetologia, 2023, 66(11): 2170-2185. doi: 10.1007/s00125-023-05995-4.
YUN J H. Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy. Microvasc Res, 2021, 133: 104103. doi: 10.1016/j.mvr.2020. 104103.
XU S, GAO F, LUAN R, et al. Normative data and correlation parameters for vessel density measured by 6×6-mm optical coherence tomography angiography in a large Chinese urban healthy elderly population: data from the Beichen eye study. BMC Ophthalmol, 2024, 24: 298. doi: 10. 1186/s12886-024-03561-z.
GUPTA P, THAKAR M, RAJURKAR K, et al. Analysis of foveal avascular zone by using spectral-domain optical coherence tomography angiography in healthy Indian eyes. Indian J Ophthalmol, 2024, 72(6): 838-843. doi: 10.4103/IJO.IJO_2212_23.
O'SHEA S M, O'DWYER V M, SCANLON G. Normative data on the foveal avascular zone in a young healthy Irish population using optical coherence tomography angiography. Eur J Ophthalmol, 2022, 32(5): 2824-2832. doi: 10.1177/11206721211073446.
] ALDAKHIL S, CHALLA N, ALHOSHAN S A, et al. Quantitative analysis of early retinal changes and OCT parameters in diabetic subjects with and without retinopathy. Diagnostics (Basel), 2025, 15(4): 451. doi: 10.3390/diagnostics15040451.
YUN J H. Interleukin-1β induces pericyte apoptosis via the NF-κB pathway in diabetic retinopathy. Biochem Biophys Res Commun, 2021, 546: 46-53. doi: 10.1016/j.bbrc.2021.01.108.
HUANG B B, FUKUYAMA H, BURNS S A, et al. Imaging the retinal vascular mural cells in vivo: Elucidating the timeline of their loss in diabetic retinopathy. Arterioscler Thromb Vasc Biol, 2024, 44(2): 465-476. doi: 10.1161/ATVBAHA.
HERDADE A S, SILVA I M, CALADO Â, et al. Effects of diabetes on microcirculation and leukostasis in retinal and non-ocular tissues: Implications for diabetic retinopathy. Biomolecules, 2020, 10(11): 1583. doi: 10.3390/biom10111583.
NING J, PAN M, YANG H, et al. Melatonin attenuates diabetic retinopathy by regulating EndMT of retinal vascular endothelial cells via inhibiting the HDAC7/FOXO1/ZEB1 axis. J Pineal Res, 2024, 76(6): e13008. doi: 10.1111/jpi.13008.
WANG Y, YANG X, LI Q, et al. Single-cell RNA sequencing reveals the Müller subtypes and inner blood-retinal barrier regulatory network in early diabetic retinopathy. Front Mol Neurosci, 2022, 15: 1048634. doi: 10. 3389/fnmol.2022.1048634.
RANGASAMY S, MONICKARAJ F, LEGENDRE C, et al. Transcriptomics analysis of pericytes from retinas of diabetic animals reveals novel genes and molecular pathways relevant to blood-retinal barrier alterations in diabetic retinopathy. Exp Eye Res, 2020, 195: 108043. doi: 10.1016/j.exer.2020.108043.
SIVAPRASAD Sфф, SEN S, CUNHA-VAZ J. Perspectives of diabetic retinopathy-challenges and opportunities. Eye (Lond), 2023, 37(11): 2183-2191. doi: 10.1038/s41433-022-02335-5.
HUANG Z, CHU W K, NG T K, et al. Protective effects of nattokinase against microvasculopathy and neuroinflammation in diabetic retinopathy. J Diabetes, 2023, 15(10): 866-880. doi: 10.1111/1753-0407.13439.
ELEFTHERIOU C G, IVANOVA E, SAGDULLAEV B T. Of neurons and pericytes: The neuro-vascular approach to diabetic retinopathy. Vis Neurosci, 2020, 37: E005. doi: 10.1017/S0952523820000048.
FRESTA C G, FIDILIO A, CARUSO G, et al. A new human blood-retinal barrier model based on endothelial cells, pericytes, and astrocytes. Int J Mol Sci, 2020, 21(5): 1636. doi: 10.3390/ijms21051636.
MONICKARAJ F, ACOSTA G, CABRERA A P, et al. Transcriptomic profiling reveals chemokine CXCL1 as a mediator for neutrophil recruitment associated with blood-retinal barrier alteration in diabetic retinopathy. Diabetes, 2023, 72(6): 781-794. doi: 10.2337/db22-0619.
PARK W, KIM J, CHOI S, et al. Human plasminogen-derived N-acetyl-Arg-Leu-Tyr-Glu antagonizes VEGFR-2 to prevent blood-retinal barrier breakdown in diabetic mice. Biomed Pharmacother, 2021, 134: 111110. doi: 10.1016/j.biopha.2020.111110.
SHENG X, ZHANG C, ZHAO J, et al. Microvascular destabilization and intricated network of the cytokines in diabetic retinopathy: from the perspective of cellular and molecular components. Cell Biosci, 2024, 14(1): 85. doi: 10.1186/s13578-024-01269-7.
Refbacks
- There are currently no refbacks.



