Association between hyper-reflective dots on spectral-domain optical coherence tomography and lipid levels and systemic inflammatory factors in patients with branch or central retinal vein occlusion_Chinese Journal of Ocular Fundus Diseases

Authors：

Deng Yumeng ^1,2 , Huang Zhen ² , Ye Ya ² , Yan Ming ² ,  Song Yanping ^1,2

1. Nanchang University School of Ophthalmology & Optometry, Nanchang 330000, China;
2. Department of Ophthalmology, Central Theater Command Hospital of People’s Liberation Army, Wuhan 430070, China;

Corresponding author：

Song Yanping, Email: songyanping@medmail.com.cn

Keywords：

Retinal vein occlusion; Cholesterol; C-reactive protein; Tomography, optical coherence

DOI：

10.3760/cma.j.cn511434-20201102-00526

Video：

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Objective To investigate the correlation between hyperreflective dots (HRD) and lipid levels and systemic inflammatory factors in patients with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).Methods A cross-sectional clinical study. From December 2016 to June 2020, 118 eyes of 118 patients with retinal vein occlusion diagnosed in the Department of Ophthalmology, Central Theater Command Hospital of People's Liberation Army were included in the study. Among them, 67 cases of BRVO and 51 cases of CRVO were divided into CRVO group and BRVO group accordingly. Peripheral venous blood was drawn from the patients within 3 days after the eye examination to detect the percentage of neutrophils, monocytes, hypersensitive C-reactive protein (CRP), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a). The ratio of monocytes to high-density lipoprotein (MHR) was also calculated. The 3D OCT-2000 instrument from Topcon (Japan) was used to measure the central retinal thickness (CRT) and the numbers of HRD. According to the different distribution position, HRD is divided into inner retina HRD, outer retina HRD, and total retina HRD.The independent sample t test was used to compare the continuous variables of the two groups, and the χ² test was used to compare the rates. The correlation between HRD counts and blood lipid levels and peripheral blood inflammation indicators in patients with different types of RVO was analyzed by Spearman correlation analysis.Results The average age of patients in the BRVO group and CRVO group were 60.1±9.5 and 53.6±15.7 years, respectively; the prevalence of hypertension was 53.7% (36/67) and 24.5% (12/51), respectively. Comparison of age (t=2.634) and prevalence of hypertension (χ²=11.298) between the two groups showed statistically significant differences (P＜0.05). Gender (χ²=2.000), course of disease (t=－1.101), prevalence of diabetes (χ²=1.315), eye category (χ²=1.742), baseline visual acuity (t=1.792), intraocular pressure (t=0.708), CRT (t=1.318), and peripheral blood include the percentage of neutrophils, the absolute number of monocytes, CRP, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein(a), MHR (t=－0.559, 1.126, 0.579, 1.299, －0.134, 0.556, 1.230, －0.267, 0.483), the difference was not statistically significant. Correlation analysis showed that the HRD counts in the outer retina of BRVO patients were positively correlated with total cholesterol (r=0.289, P=0.036); the HRD in the inner retina and total HRD counts of CRVO patients were positively correlated with CRP (r=0.406, 0.343; P=0.004, 0.014). There was no correlation between HRD counts and percentage of neutrophils, absolute number of monocytes, triglycerides, high-density lipoprotein, low-density lipoprotein, lipoprotein(a), and MHR (P＞0.05).Conclusion The number of HRD is related to the blood lipid level in BRVO patients and CRP (an inflammatory index) in CRVO patients.

Citation： Deng Yumeng, Huang Zhen, Ye Ya, Yan Ming, Song Yanping. Association between hyper-reflective dots on spectral-domain optical coherence tomography and lipid levels and systemic inflammatory factors in patients with branch or central retinal vein occlusion. Chinese Journal of Ocular Fundus Diseases, 2021, 37(2): 115-121. doi: 10.3760/cma.j.cn511434-20201102-00526 Copy

1.	Yau JW, Lee P, Wong TY, et al. Retinal vein occlusion: an approach to diagnosis, systemic risk factors and management[J]. Intern Med J, 2008, 38(12): 904-910. DOI: 10.1111/j.1445-5994.2008.01720.x.
2.	Schmidt-Erfurth U, Garcia-Arumi J, Gerendas BS, et al. Guidelines for the management of retinal vein occlusion by the European Society of Retina Specialists (EURETINA)[J]. Ophthalmologica, 2019, 242(3): 123-162. DOI: 10.1159/000502041.
3.	Cho BJ, Bae SH, Park SM, et al. Comparison of systemic conditions at diagnosis between central retinal vein occlusion and branch retinal vein occlusion[J/OL]. PLoS One, 2019, 14(8): e220880[2019-08-08]. http://europepmc.org/article/MED/31393915. DOI: 10.1371/journal.pone.0220880.
4.	Hayreh SS, Zimmerman B, McCarthy MJ, et al. Systemic diseases associated with various types of retinal vein occlusion[J]. Am J Ophthalmol, 2001, 131(1): 61-77. DOI: 10.1016/s0002-9394(00)00709-1.
5.	Turgut B, Yildirim H. The causes of hyperreflective dots in optical coherence tomography excluding diabetic macular edema and retinal venous occlusion[J]. Open Ophthalmol J, 2015, 9(1): 36-40. DOI: 10.2174/1874364101509010036.
6.	Wolf S, Wolf-Schnurrbusch U. Spectral-domain optical coherence tomography use in macular diseases: a review[J]. Ophthalmologica, 2010, 224(6): 333-340. DOI: 10.1159/000313814.
7.	Bolz M, Schmidt-Erfurth U, Deak G, et al. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema[J]. Ophthalmology, 2009, 116(5): 914-920. DOI: 10.1016/j.ophtha.2008.12.039.
8.	Lee H, Lee J, Chung H, et al. Baseline spectral domain optical coherence tomographic hyperreflective foci as a predictor of visual outcome and recurrence for central serous chorioretinopathy[J]. Retina, 2016, 36(7): 1372-1380. DOI: 10.1097/IAE.0000000000000929.
9.	Coscas G, De Benedetto U, Coscas F, et al. Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration[J]. Ophthalmologica, 2013, 229(1): 32-37. DOI: 10.1159/000342159.
10.	Do JR, Park SJ, Shin JP, et al. Assessment of hyperreflective foci after bevacizumab or dexamethasone treatment according to duration of macular edema in patients with branch retinal vein occlusion[J]. Retina, 2021, 41(2): 355-365. DOI: 10.1097/IAE.0000000000002826.
11.	Hwang HS, Chae JB, Kim J, et al. Association between hyperreflective dots on spectral-domain optical coherence tomography in macular edema and response to treatment[J]. Invest Ophthalmol Vis Sci, 2017, 58(13): 5958-5967. DOI: 10.1167/iovs.17-22725.
12.	Dursun A, Ozturk S, Yucel H, et al. Association of neutrophil/lymphocyte ratio and retinal vein occlusion[J]. Eur J Ophthalmol, 2015, 25(4): 343-346. DOI: 10.5301/ejo.5000570.
13.	Framme C, Wolf S, Wolf-Schnurrbusch U. Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2010, 51(11): 5965-5969. DOI: 10.1167/iovs.10-5779.
14.	Davoudi S, Papavasileiou E, Roohipoor R, et al. Optical coherence tomography characteristics of macular edema and hard exudates and their association with lipid serum levels in type2 diabetes[J]. Retina, 2016, 36(9): 1622-1629. DOI: 10.1097/IAE.0000000000001022.
15.	Mo B, Zhou HY, Jiao X, et al. Evaluation of hyperreflective foci as a prognostic factor of visual outcome in retinal vein occlusion[J]. Int J Ophthalmol, 2017, 10(4): 605-612. DOI: 10.18240/ijo.2017.04.17.
16.	Kolar P. Risk factors for central and branch retinal vein occlusion: a meta-analysis of published clinical data[J/OL]. J Ophthalmol, 2014, 2014: 724780[2014-06-09]. https://doi.org/10.1155/2014/724780. DOI: 10.1155/2014/724780.
17.	Ponto KA, Elbaz H, Peto T, et al. Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study[J]. J Thromb Haemost, 2015, 13(7): 1254-1263. DOI: 10.1111/jth.12982.
18.	Chatziralli IP, Sergentanis TN, Sivaprasad S. Hyperreflective foci as an independent visual outcome predictor in macular edema due to retinal vascular diseases treated with intravitreal dexamethasone or ranibizumab[J]. Retina, 2016, 36(12): 2319-2328. DOI: 10.1097/IAE.0000000000001070.
19.	Ramji DP, Davies TS. Cytokines in atherosclerosis: key players in all stages of disease and promising therapeutic targets[J]. Cytokine Growth Factor Rev, 2015, 26(6): 673-685. DOI: 10.1016/j.cytogfr.2015.04.003.
20.	Fichtlscherer S, Rosenberger G, Walter DH, et al. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease[J]. Circulation, 2000, 102(9): 1000-1006. DOI: 10.1161/01.cir.102.9.1000.
21.	刘明月, 陈佳玉, 常晨, 等. 炎症及动脉硬化相关因子与视网膜静脉阻塞的相关性[J]. 国际眼科杂志, 2020, 20(7): 1264-1268. DOI: 10.3980/j.issn.1672-5123.2020.7.33.Liu MY, Chen JY, Chang C, et al. Correlation between inflammation and arteriosclerosis related factors and retinal vein occlusion[J]. Int Eye Sci, 2020, 20(7): 1264-1268. DOI: 10.3980/j.issn.1672-5123.2020.7.33.
22.	Dodson PM, Shine B. Retinal vein occlusion: C-reactive protein and arterial hypertension[J]. Acta Ophthalmol (Copenh), 1984, 62(1): 123-130. DOI: 10.1111/j.1755-3768.1984.tb06765.x.
23.	Lee HB, Pulido JS, McCannel CA, et al. Role of inflammation in retinal vein occlusion[J]. Can J Ophthalmol, 2007, 42(1): 131-133. DOI: 10.1139/i06-101.
24.	Grigsby JG, Cardona SM, Pouw CE, et al. The role of microglia in diabetic retinopathy [J/OL]. J Ophthalmol, 2014, 2014: 705783[2014-08-31]. https://doi.org/10.1155/2014/705783. DOI: 10.1155/2014/705783.
25.	Pinna A, Porcu T, Marzano J, et al. Mean platelet volume, red cell distribution width, and complete blood cell count indices in retinal vein occlusions[J]. Ophthalmic Epidemiol, 2021, 28(1): 39-47. DOI: 10.1080/09286586.2020.1791349.
26.	Acikgoz N, Kurtoğlu E, Yagmur J, et al. Elevated monocyte to high-density lipoprotein cholesterol ratio and endothelial dysfunction in Behçet disease[J]. Angiology, 2018, 69(1): 65-70. DOI: 10.1177/0003319717704748.
27.	Sirakaya E, Duru Z, Kuçuk B, et al. Monocyte to high-density lipoprotein and neutrophil-to-lymphocyte ratios in patients with acute central serous chorioretinopathy[J]. Indian J Ophthalmol, 2020, 68(5): 854-858. DOI: 10.4103/ijo.IJO_1327_19.
28.	Şatırtav G, Mirza E, Oltulu R, et al. Assessment of monocyte/HDL ratio in branch retinal vein occlusion[J]. Ocul Immunol Inflamm, 2020, 28(3): 463-467. DOI: 10.1080/09273948.2019.1569244.
29.	Dodson PM, Galton DJ, Hamilton AM, et al. Retinal vein occlusion and the prevalence of lipoprotein abnormalities[J]. Br J Ophthalmol, 1982, 66(3): 161-164. DOI: 10.1136/bjo.66.3.161.
30.	黎晓新, 白玉婧. 关注视网膜静脉阻塞的病因病理对临床实践的指导作用[J]. 中华眼底病杂志, 2018, 34(3): 205-207. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.001.Li XX, Bai YJ. Refocusing on the etiology and pathology of retinal vein occlusion to guide clinical practice[J]. Chin J Ocul Fundus Dis, 2018, 34(3): 205-207. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.001.

1. Yau JW, Lee P, Wong TY, et al. Retinal vein occlusion: an approach to diagnosis, systemic risk factors and management[J]. Intern Med J, 2008, 38(12): 904-910. DOI: 10.1111/j.1445-5994.2008.01720.x.
2. Schmidt-Erfurth U, Garcia-Arumi J, Gerendas BS, et al. Guidelines for the management of retinal vein occlusion by the European Society of Retina Specialists (EURETINA)[J]. Ophthalmologica, 2019, 242(3): 123-162. DOI: 10.1159/000502041.
3. Cho BJ, Bae SH, Park SM, et al. Comparison of systemic conditions at diagnosis between central retinal vein occlusion and branch retinal vein occlusion[J/OL]. PLoS One, 2019, 14(8): e220880[2019-08-08]. http://europepmc.org/article/MED/31393915. DOI: 10.1371/journal.pone.0220880.
4. Hayreh SS, Zimmerman B, McCarthy MJ, et al. Systemic diseases associated with various types of retinal vein occlusion[J]. Am J Ophthalmol, 2001, 131(1): 61-77. DOI: 10.1016/s0002-9394(00)00709-1.
5. Turgut B, Yildirim H. The causes of hyperreflective dots in optical coherence tomography excluding diabetic macular edema and retinal venous occlusion[J]. Open Ophthalmol J, 2015, 9(1): 36-40. DOI: 10.2174/1874364101509010036.
6. Wolf S, Wolf-Schnurrbusch U. Spectral-domain optical coherence tomography use in macular diseases: a review[J]. Ophthalmologica, 2010, 224(6): 333-340. DOI: 10.1159/000313814.
7. Bolz M, Schmidt-Erfurth U, Deak G, et al. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema[J]. Ophthalmology, 2009, 116(5): 914-920. DOI: 10.1016/j.ophtha.2008.12.039.
8. Lee H, Lee J, Chung H, et al. Baseline spectral domain optical coherence tomographic hyperreflective foci as a predictor of visual outcome and recurrence for central serous chorioretinopathy[J]. Retina, 2016, 36(7): 1372-1380. DOI: 10.1097/IAE.0000000000000929.
9. Coscas G, De Benedetto U, Coscas F, et al. Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration[J]. Ophthalmologica, 2013, 229(1): 32-37. DOI: 10.1159/000342159.
10. Do JR, Park SJ, Shin JP, et al. Assessment of hyperreflective foci after bevacizumab or dexamethasone treatment according to duration of macular edema in patients with branch retinal vein occlusion[J]. Retina, 2021, 41(2): 355-365. DOI: 10.1097/IAE.0000000000002826.
11. Hwang HS, Chae JB, Kim J, et al. Association between hyperreflective dots on spectral-domain optical coherence tomography in macular edema and response to treatment[J]. Invest Ophthalmol Vis Sci, 2017, 58(13): 5958-5967. DOI: 10.1167/iovs.17-22725.
12. Dursun A, Ozturk S, Yucel H, et al. Association of neutrophil/lymphocyte ratio and retinal vein occlusion[J]. Eur J Ophthalmol, 2015, 25(4): 343-346. DOI: 10.5301/ejo.5000570.
13. Framme C, Wolf S, Wolf-Schnurrbusch U. Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2010, 51(11): 5965-5969. DOI: 10.1167/iovs.10-5779.
14. Davoudi S, Papavasileiou E, Roohipoor R, et al. Optical coherence tomography characteristics of macular edema and hard exudates and their association with lipid serum levels in type2 diabetes[J]. Retina, 2016, 36(9): 1622-1629. DOI: 10.1097/IAE.0000000000001022.
15. Mo B, Zhou HY, Jiao X, et al. Evaluation of hyperreflective foci as a prognostic factor of visual outcome in retinal vein occlusion[J]. Int J Ophthalmol, 2017, 10(4): 605-612. DOI: 10.18240/ijo.2017.04.17.
16. Kolar P. Risk factors for central and branch retinal vein occlusion: a meta-analysis of published clinical data[J/OL]. J Ophthalmol, 2014, 2014: 724780[2014-06-09]. https://doi.org/10.1155/2014/724780. DOI: 10.1155/2014/724780.
17. Ponto KA, Elbaz H, Peto T, et al. Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study[J]. J Thromb Haemost, 2015, 13(7): 1254-1263. DOI: 10.1111/jth.12982.
18. Chatziralli IP, Sergentanis TN, Sivaprasad S. Hyperreflective foci as an independent visual outcome predictor in macular edema due to retinal vascular diseases treated with intravitreal dexamethasone or ranibizumab[J]. Retina, 2016, 36(12): 2319-2328. DOI: 10.1097/IAE.0000000000001070.
19. Ramji DP, Davies TS. Cytokines in atherosclerosis: key players in all stages of disease and promising therapeutic targets[J]. Cytokine Growth Factor Rev, 2015, 26(6): 673-685. DOI: 10.1016/j.cytogfr.2015.04.003.
20. Fichtlscherer S, Rosenberger G, Walter DH, et al. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease[J]. Circulation, 2000, 102(9): 1000-1006. DOI: 10.1161/01.cir.102.9.1000.
21. 刘明月, 陈佳玉, 常晨, 等. 炎症及动脉硬化相关因子与视网膜静脉阻塞的相关性[J]. 国际眼科杂志, 2020, 20(7): 1264-1268. DOI: 10.3980/j.issn.1672-5123.2020.7.33.Liu MY, Chen JY, Chang C, et al. Correlation between inflammation and arteriosclerosis related factors and retinal vein occlusion[J]. Int Eye Sci, 2020, 20(7): 1264-1268. DOI: 10.3980/j.issn.1672-5123.2020.7.33.
22. Dodson PM, Shine B. Retinal vein occlusion: C-reactive protein and arterial hypertension[J]. Acta Ophthalmol (Copenh), 1984, 62(1): 123-130. DOI: 10.1111/j.1755-3768.1984.tb06765.x.
23. Lee HB, Pulido JS, McCannel CA, et al. Role of inflammation in retinal vein occlusion[J]. Can J Ophthalmol, 2007, 42(1): 131-133. DOI: 10.1139/i06-101.
24. Grigsby JG, Cardona SM, Pouw CE, et al. The role of microglia in diabetic retinopathy [J/OL]. J Ophthalmol, 2014, 2014: 705783[2014-08-31]. https://doi.org/10.1155/2014/705783. DOI: 10.1155/2014/705783.
25. Pinna A, Porcu T, Marzano J, et al. Mean platelet volume, red cell distribution width, and complete blood cell count indices in retinal vein occlusions[J]. Ophthalmic Epidemiol, 2021, 28(1): 39-47. DOI: 10.1080/09286586.2020.1791349.
26. Acikgoz N, Kurtoğlu E, Yagmur J, et al. Elevated monocyte to high-density lipoprotein cholesterol ratio and endothelial dysfunction in Behçet disease[J]. Angiology, 2018, 69(1): 65-70. DOI: 10.1177/0003319717704748.
27. Sirakaya E, Duru Z, Kuçuk B, et al. Monocyte to high-density lipoprotein and neutrophil-to-lymphocyte ratios in patients with acute central serous chorioretinopathy[J]. Indian J Ophthalmol, 2020, 68(5): 854-858. DOI: 10.4103/ijo.IJO_1327_19.
28. Şatırtav G, Mirza E, Oltulu R, et al. Assessment of monocyte/HDL ratio in branch retinal vein occlusion[J]. Ocul Immunol Inflamm, 2020, 28(3): 463-467. DOI: 10.1080/09273948.2019.1569244.
29. Dodson PM, Galton DJ, Hamilton AM, et al. Retinal vein occlusion and the prevalence of lipoprotein abnormalities[J]. Br J Ophthalmol, 1982, 66(3): 161-164. DOI: 10.1136/bjo.66.3.161.
30. 黎晓新, 白玉婧. 关注视网膜静脉阻塞的病因病理对临床实践的指导作用[J]. 中华眼底病杂志, 2018, 34(3): 205-207. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.001.Li XX, Bai YJ. Refocusing on the etiology and pathology of retinal vein occlusion to guide clinical practice[J]. Chin J Ocul Fundus Dis, 2018, 34(3): 205-207. DOI: 10.3760/cma.j.issn.1005-1015.2018.03.001.

Chinese Journal of Ocular Fundus Diseases

Association between hyper-reflective dots on spectral-domain optical coherence tomography and lipid levels and systemic inflammatory factors in patients with branch or central retinal vein occlusion

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