Quantitative Assessment of Microvascular Changes in Diabetic Retinopathy and Their Association With Blood-Retinal Barrier Impairment

LEI Yingqing, LÜ Hongbin, ZHOU Qi, TIAN Min, CAO Yang

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:

PDF


References


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.