The correlation of folic acid and homocysteine serum with vascular density and retinal non-perfusion area in diabetic retinopathy
Abstract
Background : Diabetic Retinopathy (DR) is the most common microvascular complication of Diabetes Mellitus (DM). Homocysteine has been studied as a biomarker in DR, while folic acid exhibits anti-proliferative effects in DR. Objective : To analyze the correlation between folic acid and homocysteine serum with vascular density and retinal non-perfusion area in healthy individuals and patients with diabetic retinopathy. Methods : This is an observational study with a cross-sectional design, conducted in Dr. Kariadi Hospital and GAKI laboratory in Semarang in January 2023. This study included 60 samples: 15 healthy individuals, 15 patients with DM but no DR, 15 patients with Non-Proliferative Diabetic Retinopathy (NPDR), and 15 patients with Proliferative Diabetic Retinopathy (PDR). Patients were examined for serum folic acid and homocysteine using blood laboratory tests, vessel density and retinal non-perfusion areas using optical coherence tomography angiography (OCTA). Results : There was a negative correlation with weak strength between folic acid levels and retinal non-perfusion area of the retina in all samples (Folic acid levels vs retinal non-perfusion area, p = 0.009, Spearman correlation = -0.335). There was a positive correlation with weak strength between folic acid levels and vascular density in all samples (Folic acid levels vs vascular density, p = 0.009, Spearman correlation = 0.337). There was a positive correlation with moderate strength between homocysteine levels and retinal non-perfusion area in all samples (Homocysteine levels vs non–perfusion area of the retina, p = 0.001, Spearman correlation = 0.426). There was a positive correlation with moderate strength between homocysteine levels and vascular density in all samples (Homocysteine levels vs vascular density, p = 0.001, Spearman correlation = -0.414). Conclusion : There was a correlation between folic acid and homocysteine serum with vascular density and retinal non-perfusion areas.Downloads
References
Wang W, Lo A. Diabetic Retinopathy: Pathophysiology and Treatments. Int J Mol Sci. 2018 Jun 20;19(6):1816.
Shukla U V, Tripathy K. Diabetic Retinopathy [Internet]. StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560805/#
Flaxman SR, Bourne RRA, Resnikoff S, Ackland P, Braithwaite T, Cicinelli M V, et al. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. Lancet Glob Health. 2017 Dec;5(12):e1221–34.
Teo ZL, Tham YC, Yu M, Chee ML, Rim TH, Cheung N, et al. Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045. Ophthalmology [Internet]. 2021 Nov;128(11):1580–91. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0161642021003213
Sasongko MB, Widyaputri F, Agni AN, Wardhana FS, Kotha S, Gupta P, et al. Prevalence of Diabetic Retinopathy and Blindness in Indonesian Adults With Type 2 Diabetes. Am J Ophthalmol [Internet]. 2017 Sep;181:79–87. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0002939417302714
Wu L. Classification of diabetic retinopathy and diabetic macular edema. World J Diabetes [Internet]. 2013;4(6):290. Available from: http://www.wjgnet.com/1948-9358/full/v4/i6/290.htm
Falcão M, Rosas V, Falcão-Reis F, Fontes ML, Hyde RA, Lim JI, et al. Diabetic Retinopathy Pathophysiology. American Academy of Ophthalmology. 2022;
Beltramo E, Porta M. Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences. Curr Med Chem [Internet]. 2013 Jul 1;20(26):3218–25. Available from: http://www.eurekaselect.com/openurl/content.php?genre=article&issn=0929-8673&volume=20&issue=26&spage=3218
Wang J, Hormel TT, You Q, Guo Y, Wang X, Chen L, et al. Robust non-perfusion area detection in three retinal plexuses using convolutional neural network in OCT angiography. Biomed Opt Express. 2020 Jan 1;11(1):330.
Rübsam A, Parikh S, Fort P. Role of Inflammation in Diabetic Retinopathy. Int J Mol Sci [Internet]. 2018 Mar 22;19(4):942. Available from: http://www.mdpi.com/1422-0067/19/4/942
Muqit M. ICO Guidelines For Diabetic Eye [Internet]. 2017 [cited 2022 Mar 10]. Available from: www.icoph.org/downloads/icoethicalcode.pdf
Simó R, Hernández C. Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives. Trends in Endocrinology & Metabolism [Internet]. 2014 Jan;25(1):23–33. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043276013001677
Chilom CG, Bacalum M, Stanescu MM, Florescu M. Insight into the interaction of human serum albumin with folic acid: A biophysical study. Spectrochim Acta A Mol Biomol Spectrosc [Internet]. 2018 Nov;204:648–56. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1386142518306358
Wang Z, Xing W, Song Y, Li H, Liu Y, Wang Y, et al. Folic Acid Has a Protective Effect on Retinal Vascular Endothelial Cells against High Glucose. Molecules. 2018 Sep 12;23(9):2326.
Lei XW, Li Q, Zhang JZ, Zhang YM, Liu Y, Yang KH. The Protective Roles of Folic Acid in Preventing Diabetic Retinopathy Are Potentially Associated with Suppressions on Angiogenesis, Inflammation, and Oxidative Stress. Ophthalmic Res [Internet]. 2019;62(2):80–92. Available from: https://www.karger.com/Article/FullText/499020
Sharma GS, Bhattacharya R, Singh LR. Functional inhibition of redox regulated heme proteins: A novel mechanism towards oxidative stress induced by homocysteine. Redox Biol [Internet]. 2021 Oct;46:102080. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2213231721002391
Lei X, Zeng G, Zhang Y, Li Q, Zhang J, Bai Z, et al. Association between homocysteine level and the risk of diabetic retinopathy: a systematic review and meta-analysis. Diabetol Metab Syndr [Internet]. 2018 Dec 2;10(1):61. Available from: https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-018-0362-1
Rocholz R, Corvi F, Weichsel J, Schmidt S, Staurenghi G. High Resolution Imaging in Microscopy and Ophthalmology: New Frontiers in Biomedical Optics. OCT Angiog. Bille JF, editor. Springer New York; 2019.
Liu L, Xia F, Hua R. Retinal nonperfusion in optical coherence tomography angiography. Photodiagnosis Photodyn Ther [Internet]. 2021 Mar;33:102129. Available from: https://linkinghub.elsevier.com/retrieve/pii/S157210002030483X
Wang J, Hormel TT, You Q, Guo Y, Wang X, Chen L, et al. Robust non-perfusion area detection in three retinal plexuses using convolutional neural network in OCT angiography. Biomed Opt Express [Internet]. 2020 Jan 1;11(1):330. Available from: https://opg.optica.org/abstract.cfm?URI=boe-11-1-330
Liu X, Cui H. The palliative effects of folic acid on retinal microvessels in diabetic retinopathy via regulating the metabolism of DNA methylation and hydroxymethylation. Bioengineered [Internet]. 2021 Dec 20;12(2):10766–74. Available from: https://www.tandfonline.com/doi/full/10.1080/21655979.2021.2003924
Malaguarnera G, Gagliano C, Salomone S, Giordano M, Bucolo C, Pappalardo A, et al. Folate status in type 2 diabetic patients with and without retinopathy. Clinical Ophthalmology. 2015 Aug;1437.
Lei XW, Li Q, Zhang JZ, Zhang YM, Liu Y, Yang KH. The Protective Roles of Folic Acid in Preventing Diabetic Retinopathy Are Potentially Associated with Suppressions on Angiogenesis, Inflammation, and Oxidative Stress. Ophthalmic Res. 2019;62(2):80–92.
Kowluru RA. Diabetic Retinopathy: Mitochondria Caught in a Muddle of Homocysteine. J Clin Med [Internet]. 2020 Sep 19;9(9):3019. Available from: https://www.mdpi.com/2077-0383/9/9/3019
Tawfik A, Mohamed R, Elsherbiny N, DeAngelis M, Bartoli M, Al-Shabrawey M. Homocysteine: A Potential Biomarker for Diabetic Retinopathy. J Clin Med. 2019 Jan 19;8(1):121.
Luo WM, Zhang ZP, Zhang W, Su JY, Gao XQ, Liu X, et al. The Association of Homocysteine and Diabetic Retinopathy in Homocysteine Cycle in Chinese Patients With Type 2 Diabetes. Front Endocrinol (Lausanne). 2022 Jun 29;13.
Tawfik A, Mohamed R, Elsherbiny N, DeAngelis M, Bartoli M, Al-Shabrawey M. Homocysteine: A Potential Biomarker for Diabetic Retinopathy. J Clin Med [Internet]. 2019 Jan 19;8(1):121. Available from: http://www.mdpi.com/2077-0383/8/1/121
Chua J, Sim R, Tan B, Wong D, Yao X, Liu X, et al. Optical Coherence Tomography Angiography in Diabetes and Diabetic Retinopathy. J Clin Med. 2020 Jun 3;9(6):1723.
Hirano T, Kitahara J, Toriyama Y, Kasamatsu H, Murata T, Sadda S. Quantifying vascular density and morphology using different swept-source optical coherence tomography angiographic scan patterns in diabetic retinopathy. British Journal of Ophthalmology. 2019 Feb;103(2):216–21.
Liu T, Lin W, Shi G, Wang W, Feng M, Xie X, et al. Retinal and Choroidal Vascular Perfusion and Thickness Measurement in Diabetic Retinopathy Patients by the Swept-Source Optical Coherence Tomography Angiography. Front Med (Lausanne). 2022 Mar 18;9.
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Copyright (c) 2024 Andhika Guna Dharma, Arief Wildan, Maharani Maharani, Riski Prihatningtias, Fifin Luthfia Rahmi, Trilaksana Nugroho, Arnila Novitasari Saubig, Zahira Rikiandraswida
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