Correlation study of alterations of macular outer retinal reflectivity and the associations with macular vessel density in nonproliferative diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Feng ^1,2 , Liang Anyi ¹ , Cao Dan ¹ ,  Yu Honghua ¹ ,  Hu Yijun ¹

1. Department of Ophthalmology, Guangdong Eye Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China;
2. Department of Ophthalmology, Linyi People's Hospital, Linyi 276034, China;

Corresponding author：

Hu Yijun, Email: huyijun@gdph.org.cn

Keywords：

Diabetic retinopathy; Retinal reflectivity; Optical coherence tomography; Optical coherence tomography angiography; Retinal vessel density

DOI：

10.3760/cma.j.cn511434-20221116-00609

Video：

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Objective To observe alterations of macular outer retinal reflectivity (ORR) and the associations with macular vessel density in patients with nonproliferative diabetic retinopathy (NPDR). Methods A retrospective cross-sectional study. From August 2021 to March 2022, a total of 63 NPDR patients with 63 eyes (NPDR group) diagnosed by Department of Ophthalmology of Guangdong Provincial People's Hospital were included in the study. There were 39 males with 39 eyes and 24 females with 24 eyes. Age was 60 (52, 68) years. A total of 66 eyes of 66 healthy volunteers matching age and sex were selected as the control group. Among them, 40 men had 40 eyes and 26 women had 26 eyes. Age was 58 (52, 67) years. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed in all affected eyes. Image J software was used to calculate ORR, including the optical density of ellipsoid zone (EZ), photoreceptor outer segment (OS), photoreceptor inner segment (IS) and outer nuclear layer (ONL) by OCT examination. The sampling sites were horizontal and vertical scanning of the fovea of the macula on 500 μm (nasal₅₀₀, temporal₅₀₀, superior₅₀₀, inferior₅₀₀), 1 000 μm (nasal_{1 000}, temporal_{1 000}, superior_{1 000}, inferior_{1 000}) and 2 000 μm (nasal_{2 000}, temporal_{2 000}, superior_{2 000}, inferior_{2 000}). The software automatically divided the retina within 6 mm of the macular fovea into the fovea with a diameter of 1 mm, the parafovea with a diameter of 1-3 mm, and the perifovea with a diameter of 3-6 mm by macular OCTA examination. The blood density of superficial capillary plexus and deep capillary plexus in different zones in the macular area were measured by the built-in software of the device. Spearman correlation analysis was used to analyze the correlation between ORR and blood flow density. Results Compared with the control group, retinal reflectivity of EZ in NPDR group was significantly decreased at other sites except the fovea, retinal reflectivity of OS was significantly decreased at nasal_{2 000}, temporal_{2 000}, superior_{2 000} and superior_{1 000}; retinal reflectivity of IS was significantly decreased at superior_{1 000}, superior₅₀₀ and inferior₅₀₀. The retinal reflectivity of ONL in macular fovea was significantly decreased, and the differences were statistically significant (P＜0.05). The ORR was positively correlated with blood flow density, and the correlation coefficient in NPDR group was lower than that in control group. The results of multifactor linear regression analysis showed that the superior and temporal ORR were correlated with blood flow density (P＜0.05). Conclusions Compared with the control group, ORR is reduced and less correlated with vessel density in NPDR patients. ORR is more affected by retinal blood flow density in temporal and superior parts.

Citation： Zhang Feng, Liang Anyi, Cao Dan, Yu Honghua, Hu Yijun. Correlation study of alterations of macular outer retinal reflectivity and the associations with macular vessel density in nonproliferative diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2023, 39(11): 904-912. doi: 10.3760/cma.j.cn511434-20221116-00609 Copy

1.	Gin TJ, Wu Z, Chew SK, et al. Quantitative analysis of the ellipsoid zone intensity in phenotypic variations of intermediate age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2017, 58(4): 2079-2086. DOI: 10.1167/iovs.16-20105.
2.	Chen H, Xia H, Qiu Z, et al. Correlation of optical intensity on optical coherence tomography and visual outcome in central retinal artery occlusion[J]. Retina, 2016, 36(10): 1964-1970. DOI: 10.1097/IAE.0000000000001017.
3.	Guyon B, Elphege E, Flores M, et al. Retinal reflectivity measurement for cone impairment estimation and visual assessment after diabetic macular edema resolution (RECOVER-DME)[J]. Invest Ophthalmol Vis Sci, 2017, 58(14): 6241-6247. DOI: 10.1167/iovs.17-22380.
4.	Borrelli E, Palmieri M, Viggiano P, et al. Photoreceptor damage in diabetic choroidopathy[J]. Retina, 2019, 40(6): 1062-1069. DOI: 10.1097/IAE.0000000000002538.
5.	Cao D, Yang D, Huang Z, et al. Optical coherence tomography angiography discerns preclinical diabetic retinopathy in eyes of patients with type 2 diabetes without clinical diabetic retinopathy[J]. Acta diabetologica, 2018, 55(5): 469-477. DOI: 10.1007/s00592-018-1115-1.
6.	中华医学会糖尿病学分会视网膜病变学组. 糖尿病视网膜病变防治专家共识[J]. 中华糖尿病杂志, 2018, 10(4): 241-247. DOI: 10.3760/cma.j.issn.1674-5809.2018.04.001.Retinopathy Group of Chinese Diabetes Society. Expert consensus in prevention of diabetic retinopathy[J]. Chin J Diabetes Mellitus, 2018, 10(4): 241-247. DOI: 10.3760/cma.j.issn.1674-5809.2018.04.001.
7.	Gong Y, Chen LJ, Pang CP, et al. Ellipsoid zone optical intensity reduction as an early biomarker for retinitis pigmentosa[J/OL]. Acta ophthalmologica, 2021, 99(2): e215-e221[2020-07-23]. http://www.ncbi.nlm.nih.gov/pubmed/32701217. DOI: 10.1111/aos.14542.
8.	Ra E, Ito Y, Kawano K, et al. Regeneration of photoreceptor outer segments after scleral buckling surgery for rhegmatogenous retinal detachment[J]. Am J Ophthalmol, 2017, 177: 17-26. DOI: 10.1016/j.ajo.2017.01.032.
9.	Xia H, Ke X, Chen LJ, et al. Reduced photoreceptor outer segment layer thickness in mild commotio retinae without ellipsoid zone disruption[J]. Graefe's Arch Clin Exp Ophthalmol, 2020, 258(7): 1437-1442. DOI: 10.1007/s00417-020-04678-9.
10.	Lin D, Luo X, Meng L, et al. Optical intensities of different compartments of subretinal fluid in acute Vogt-Koyanagi-Harada disease[J/OL]. PLoS One, 2016, 11(2): e0149376[2016-02-12]. http://www.ncbi.nlm.nih.gov/pubmed/26871896. DOI: 10.1371/journal.pone.0149376.
11.	Barber AJ, Lieth E, Khin SA, et al. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin[J]. J Clin Invest, 1998, 102(4): 783-791. DOI: 10.1172/JCI2425.
12.	Sachdeva MM. Retinal neurodegeneration in diabetes: an emerging concept in diabetic retinopathy[J]. Curr Diab Rep, 2021, 21(12): 65. DOI: 10.1007/s11892-021-01428-x.
13.	Le D, Son T, Lim JI, et al. Quantitative optical coherence tomography reveals rod photoreceptor degeneration in early diabetic retinopathy[J]. Retina, 2022, 42(8): 1442-1449. DOI: 10.1097/IAE.0000000000003473.
14.	Zhang F, Du Z, Zhang X, et al. Alterations of outer retinal reflectivity in diabetic patients without clinically detectable retinopathy[J/OL]. Graefe's Arch Clin Exp Ophthalmol, 2023, 2023: E1(2023-11-17)[2023-09-23]. http://www.ncbi.nlm.nih.gov/pubmed/37740747. DOI: 10.1007/s00417-023-06238-3. [published online ahead of print.
15.	Hoang QV, Linsenmeier RA, Chung CL, et al. Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation[J]. Vis Neurosci, 2002, 19(4): 395-407. DOI: 10.1017/s0952523802194028.
16.	Hood DC, Zhang X, Ramachandran R, et al. The inner segment/outer segment border seen on optical coherence tomography is less intense in patients with diminished cone function[J]. Invest Ophthalmol Vis Sci, 2011, 52(13): 9703-9709. DOI: 10.1167/iovs.11-8650.
17.	朱鸿静, 张薇玮, 张雅纹, 等. 重度非增生型糖尿病视网膜病变患眼黄斑区及视盘血流密度和中心凹无血管区面积观察[J]. 中华眼底病杂志, 2021, 37(2): 98-103. DOI: 10.3760/cma.j.cn511434-20200518-00220.Zhu HJ, Zhang WW, Zhang YW, et al. The flow density of macular and optic disc and area of foveal avascular zone in severe nonproliferative diabetic retinopathy[J]. Chin Ocul Fundus Dis, 2021, 37(2): 98-103. DOI: 10.3760/cma.j.cn511434-20200518-00220.
18.	Pournaras CJ, Rungger-Brändle E, Riva CE, et al. Regulation of retinal blood flow in health and disease[J]. Prog Retin Eye Res, 2008, 27(3): 284-330. DOI: 10.1016/j.preteyeres.2008.02.002.
19.	Alder VA, Su EN, Yu DY, et al. Diabetic retinopathy: early functional changes[J]. Clin Exp Pharmacol Physiol, 1997, 24(9-10): 785-788. DOI: 10.1111/j.1440-1681.1997.tb02133.x.
20.	Jung JJ, Lim SY, Chan X, et al. Correlation of diabetic disease severity to degree of quadrant asymmetry in en face OCTA metrics[J]. Invest Ophthalmol Vis Sci, 2022, 63(9): 12. DOI: 10.1167/iovs.63.9.12.
21.	Birol G, Wang S, Budzynski E, et al. Oxygen distribution and consumption in the macaque retina[J]. Am J Physiol Heart Circ Physiol, 2007, 293(3): 1696-1704. DOI: 10.1152/ajpheart.00221.2007.
22.	Scarinci F, Nesper PL, Fawzi AA. Deep retinal capillary nonperfusion is associated with photoreceptor disruption in diabetic macular ischemia[J]. Am J Ophthalmol, 2016, 168: 129-138. DOI: 10.1016/j.ajo.2016.05.002.
23.	Yi J, Liu W, Chen S, et al. Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation[J/OL]. Light Sci Appl, 2015, 4(9): e334[2015-09-25]. http://www.ncbi.nlm.nih.gov/pubmed/26658555. DOI: 10.1038/lsa.2015.107.
24.	Ryu G, Kim I, Sagong M. Topographic analysis of retinal and choroidal microvasculature according to diabetic retinopathy severity using optical coherence tomography angiography[J]. Graefe's Arch Clin Exp Ophthalmol, 2021, 259(1): 61-68. DOI: 10.1007/s00417-020-04785-7.
25.	Chen Q, Ma Q, Wu C, et al. Macular vascular fractal dimension in the deep capillary layer as an early indicator of microvascular loss for retinopathy in type 2 diabetic patients[J]. Invest Ophthalmol Vis Sci, 2017, 58(9): 3785-3794. DOI: 10.1167/iovs.17-21461.
26.	Onishi AC, Nesper PL, Roberts PK, et al. Importance of considering the middle capillary plexus on OCT angiography in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2018, 59(5): 2167-2176. DOI: 10.1167/iovs.17-23304.
27.	An D, Pulford R, Morgan WH, et al. Associations between capillary diameter, capillary density, and microaneurysms in diabetic retinopathy: a high-resolution confocal microscopy study[J]. Transl Vis Sci Technol, 2021, 10(2): 6. DOI: 10.1167/tvst.10.2.6.
28.	Hammes HP. Pericytes and the pathogenesis of diabetic retinopathy[J]. Horm Metab Res, 2005, 37(Suppl 1): S39-43. DOI: 10.1055/s-2005-861361.
29.	Raichle ME. Behind the scenes of functional brain imaging: a historical and physiological perspective[J]. Proc Natl Acad Sci USA, 1998, 95(3): 765-772. DOI: 10.1073/pnas.95.3.765.
30.	Mclenachan S, Magno AL, Ramos D, et al. Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice[J]. Exp Eye Res, 2015, 138: 6-21. DOI: 10.1016/j.exer.2015.06.023.

1. Gin TJ, Wu Z, Chew SK, et al. Quantitative analysis of the ellipsoid zone intensity in phenotypic variations of intermediate age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2017, 58(4): 2079-2086. DOI: 10.1167/iovs.16-20105.
2. Chen H, Xia H, Qiu Z, et al. Correlation of optical intensity on optical coherence tomography and visual outcome in central retinal artery occlusion[J]. Retina, 2016, 36(10): 1964-1970. DOI: 10.1097/IAE.0000000000001017.
3. Guyon B, Elphege E, Flores M, et al. Retinal reflectivity measurement for cone impairment estimation and visual assessment after diabetic macular edema resolution (RECOVER-DME)[J]. Invest Ophthalmol Vis Sci, 2017, 58(14): 6241-6247. DOI: 10.1167/iovs.17-22380.
4. Borrelli E, Palmieri M, Viggiano P, et al. Photoreceptor damage in diabetic choroidopathy[J]. Retina, 2019, 40(6): 1062-1069. DOI: 10.1097/IAE.0000000000002538.
5. Cao D, Yang D, Huang Z, et al. Optical coherence tomography angiography discerns preclinical diabetic retinopathy in eyes of patients with type 2 diabetes without clinical diabetic retinopathy[J]. Acta diabetologica, 2018, 55(5): 469-477. DOI: 10.1007/s00592-018-1115-1.
6. 中华医学会糖尿病学分会视网膜病变学组. 糖尿病视网膜病变防治专家共识[J]. 中华糖尿病杂志, 2018, 10(4): 241-247. DOI: 10.3760/cma.j.issn.1674-5809.2018.04.001.Retinopathy Group of Chinese Diabetes Society. Expert consensus in prevention of diabetic retinopathy[J]. Chin J Diabetes Mellitus, 2018, 10(4): 241-247. DOI: 10.3760/cma.j.issn.1674-5809.2018.04.001.
7. Gong Y, Chen LJ, Pang CP, et al. Ellipsoid zone optical intensity reduction as an early biomarker for retinitis pigmentosa[J/OL]. Acta ophthalmologica, 2021, 99(2): e215-e221[2020-07-23]. http://www.ncbi.nlm.nih.gov/pubmed/32701217. DOI: 10.1111/aos.14542.
8. Ra E, Ito Y, Kawano K, et al. Regeneration of photoreceptor outer segments after scleral buckling surgery for rhegmatogenous retinal detachment[J]. Am J Ophthalmol, 2017, 177: 17-26. DOI: 10.1016/j.ajo.2017.01.032.
9. Xia H, Ke X, Chen LJ, et al. Reduced photoreceptor outer segment layer thickness in mild commotio retinae without ellipsoid zone disruption[J]. Graefe's Arch Clin Exp Ophthalmol, 2020, 258(7): 1437-1442. DOI: 10.1007/s00417-020-04678-9.
10. Lin D, Luo X, Meng L, et al. Optical intensities of different compartments of subretinal fluid in acute Vogt-Koyanagi-Harada disease[J/OL]. PLoS One, 2016, 11(2): e0149376[2016-02-12]. http://www.ncbi.nlm.nih.gov/pubmed/26871896. DOI: 10.1371/journal.pone.0149376.
11. Barber AJ, Lieth E, Khin SA, et al. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin[J]. J Clin Invest, 1998, 102(4): 783-791. DOI: 10.1172/JCI2425.
12. Sachdeva MM. Retinal neurodegeneration in diabetes: an emerging concept in diabetic retinopathy[J]. Curr Diab Rep, 2021, 21(12): 65. DOI: 10.1007/s11892-021-01428-x.
13. Le D, Son T, Lim JI, et al. Quantitative optical coherence tomography reveals rod photoreceptor degeneration in early diabetic retinopathy[J]. Retina, 2022, 42(8): 1442-1449. DOI: 10.1097/IAE.0000000000003473.
14. Zhang F, Du Z, Zhang X, et al. Alterations of outer retinal reflectivity in diabetic patients without clinically detectable retinopathy[J/OL]. Graefe's Arch Clin Exp Ophthalmol, 2023, 2023: E1(2023-11-17)[2023-09-23]. http://www.ncbi.nlm.nih.gov/pubmed/37740747. DOI: 10.1007/s00417-023-06238-3. [published online ahead of print.
15. Hoang QV, Linsenmeier RA, Chung CL, et al. Photoreceptor inner segments in monkey and human retina: mitochondrial density, optics, and regional variation[J]. Vis Neurosci, 2002, 19(4): 395-407. DOI: 10.1017/s0952523802194028.
16. Hood DC, Zhang X, Ramachandran R, et al. The inner segment/outer segment border seen on optical coherence tomography is less intense in patients with diminished cone function[J]. Invest Ophthalmol Vis Sci, 2011, 52(13): 9703-9709. DOI: 10.1167/iovs.11-8650.
17. 朱鸿静, 张薇玮, 张雅纹, 等. 重度非增生型糖尿病视网膜病变患眼黄斑区及视盘血流密度和中心凹无血管区面积观察[J]. 中华眼底病杂志, 2021, 37(2): 98-103. DOI: 10.3760/cma.j.cn511434-20200518-00220.Zhu HJ, Zhang WW, Zhang YW, et al. The flow density of macular and optic disc and area of foveal avascular zone in severe nonproliferative diabetic retinopathy[J]. Chin Ocul Fundus Dis, 2021, 37(2): 98-103. DOI: 10.3760/cma.j.cn511434-20200518-00220.
18. Pournaras CJ, Rungger-Brändle E, Riva CE, et al. Regulation of retinal blood flow in health and disease[J]. Prog Retin Eye Res, 2008, 27(3): 284-330. DOI: 10.1016/j.preteyeres.2008.02.002.
19. Alder VA, Su EN, Yu DY, et al. Diabetic retinopathy: early functional changes[J]. Clin Exp Pharmacol Physiol, 1997, 24(9-10): 785-788. DOI: 10.1111/j.1440-1681.1997.tb02133.x.
20. Jung JJ, Lim SY, Chan X, et al. Correlation of diabetic disease severity to degree of quadrant asymmetry in en face OCTA metrics[J]. Invest Ophthalmol Vis Sci, 2022, 63(9): 12. DOI: 10.1167/iovs.63.9.12.
21. Birol G, Wang S, Budzynski E, et al. Oxygen distribution and consumption in the macaque retina[J]. Am J Physiol Heart Circ Physiol, 2007, 293(3): 1696-1704. DOI: 10.1152/ajpheart.00221.2007.
22. Scarinci F, Nesper PL, Fawzi AA. Deep retinal capillary nonperfusion is associated with photoreceptor disruption in diabetic macular ischemia[J]. Am J Ophthalmol, 2016, 168: 129-138. DOI: 10.1016/j.ajo.2016.05.002.
23. Yi J, Liu W, Chen S, et al. Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation[J/OL]. Light Sci Appl, 2015, 4(9): e334[2015-09-25]. http://www.ncbi.nlm.nih.gov/pubmed/26658555. DOI: 10.1038/lsa.2015.107.
24. Ryu G, Kim I, Sagong M. Topographic analysis of retinal and choroidal microvasculature according to diabetic retinopathy severity using optical coherence tomography angiography[J]. Graefe's Arch Clin Exp Ophthalmol, 2021, 259(1): 61-68. DOI: 10.1007/s00417-020-04785-7.
25. Chen Q, Ma Q, Wu C, et al. Macular vascular fractal dimension in the deep capillary layer as an early indicator of microvascular loss for retinopathy in type 2 diabetic patients[J]. Invest Ophthalmol Vis Sci, 2017, 58(9): 3785-3794. DOI: 10.1167/iovs.17-21461.
26. Onishi AC, Nesper PL, Roberts PK, et al. Importance of considering the middle capillary plexus on OCT angiography in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2018, 59(5): 2167-2176. DOI: 10.1167/iovs.17-23304.
27. An D, Pulford R, Morgan WH, et al. Associations between capillary diameter, capillary density, and microaneurysms in diabetic retinopathy: a high-resolution confocal microscopy study[J]. Transl Vis Sci Technol, 2021, 10(2): 6. DOI: 10.1167/tvst.10.2.6.
28. Hammes HP. Pericytes and the pathogenesis of diabetic retinopathy[J]. Horm Metab Res, 2005, 37(Suppl 1): S39-43. DOI: 10.1055/s-2005-861361.
29. Raichle ME. Behind the scenes of functional brain imaging: a historical and physiological perspective[J]. Proc Natl Acad Sci USA, 1998, 95(3): 765-772. DOI: 10.1073/pnas.95.3.765.
30. Mclenachan S, Magno AL, Ramos D, et al. Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice[J]. Exp Eye Res, 2015, 138: 6-21. DOI: 10.1016/j.exer.2015.06.023.

Chinese Journal of Ocular Fundus Diseases

Correlation study of alterations of macular outer retinal reflectivity and the associations with macular vessel density in nonproliferative diabetic retinopathy

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