Oral Vitamin D Supplementation and Clinical Outcomes of Intravitreal Bevacizumab Injection for Macular Edema Secondary to Retinal Vein Occlusions
Purpose: To evaluate the therapeutic response of retinal vein occlusion (RVO) to intravitreal bevacizumab (IVB) with and without concomitant vitamin D supplementation.
Method: Seventy eyes of 68 patients with macular edema associated with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) received three monthly IVB injections. Patients with serum 25-hydroxyvitamin D (25(OH) D) higher than 30 ng/ml were considered as the sufficient group. Cases with serum 25(OH) D levels below 30 ng/ml were randomized into the treatment and control groups. The control group received 50,000 IU of oral vitamin D, weekly for two months. One month after the last IVB injection, best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured and compared with the preinjection values.
Results: While 43 eyes (61.4%) of 42 patients had BRVO, 27 eyes (38.6%) of 26 patients had CRVO. In BRVO patients, changes of CMT and BCVA were not significantly different between the sufficient, control, and treatment groups (P = 0.58 and 0.64, respectively). In the CRVO group, CMT reduction in the control group was significantly less than the sufficient and treatment groups (P = 0.048). In addition, improvement of BCVA in the control group was significantly less (P = 0.036) than the sufficient and treatment groups.
Conclusion: Oral vitamin D supplement therapy may improve anatomical and functional outcomes in patients with CRVO and vitamin D deficiency.
25-Hydroxyvitamin D, Bevacizumab, Insufficiency, Intravitreal, Macular Edema, Retinal Vein Occlusion
1. Oli A, Joshi D. Serum vitamin D levels in Indian patients with retinal venous occlusions. Saudi J Ophthalmol 2017;31:76–79.
2. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004;80:1689S– 1696S.
3. Weishaar RE, Simpson RU. Vitamin D3 and cardiovascular function in rats. J Clin Invest 1987;79:1706–1712.
4. Akin F, Ayça B, Köse N, Duran M, Sari M, Uysal OK, et al. Serum vitamin D levels are independently associated with severity of coronary artery disease. J Investig Med 2012;60:869–873.
5. Epstein D, Kvanta A, Lindqvist PG, Vitamin D. Vitamin D deficiency in patients with central retinal vein occlusion: A case control study. Curr Eye Res 2017;42:448–451.
6. Talcott KE, Eliott D. Central retinal vein occlusion associated with severe vitamin D deficiency. Ophthalmic Surg Lasers Imaging Retina 2016;47:372–375.
7. Vatandost S, Jahani M, Afshari A, Amiri MR, Heidarimoghadam R, Mohammadi Y. Prevalence of vitamin D deficiency in Iran: A systematic review and meta-analysis. Nutr Health 2018;24:269–278.
8. Zittermann A, Schleithoff SS, Götting C, Dronow O, Fuchs U, Kuhn J, et al. Poor outcome in end-stage heart failure patients with low circulating calcitriol levels. Eur J Heart Fail 2008;10:321–327.
9. Li YC. Vitamin D regulation of the renin-angiotensin system. J Cell Biochem 2003;88:327–331.
10. Snijder MB, Lips P, Seidell JC, Visser M, Deeg DJ, Dekker JM, et al. Vitamin D status and parathyroid hormone levels in relation to blood pressure: A population-based study in older men and women. J Intern Med 2007;261:558–565.
11. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25- hydroxyvitamin D and risk of myocardial infarction in men: A prospective study. Arch Intern Med 2008;168:1174–1180.
12. Targher G, Bertolini L, Padovani R, Zenari L, Scala L, Cigolini M, et al. Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients. Clin Endocrinol 2006;65:593–597.
13. Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008;25:320–325.
14. Luo BA, Gao F, Qin LL. The association between vitamin D deficiency and diabetic retinopathy in type 2 diabetes: A meta-analysis of observational studies. Nutrients 2017;9:307.
15. Yin K, Agrawal DK. Vitamin D and inflammatory diseases. J Inflamm Res 2014;7:69–87.
16. Danik JS, Manson JE. Vitamin d and cardiovascular disease. Curr Treat Options Gastroenterol 2012;14:414– 424.
17. Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: The Blue Mountains Eye Study. Arch Ophthalmol 2006;124:726–732.
18. Karia N. Retinal vein occlusion: Pathophysiology and treatment options. Clin Ophthalmol 2010;4:809–816.
19. Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, et al. Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One 2009;4:e8158.
20. Vieira MJ, Campos A, do Carmo A, Arruda H, Martins J, Sousa JP. Thrombophilic risk factors for retinal vein occlusion. Sci Rep 2019;9:18972.
21. Martins D, Meng YX, Tareen N, Artaza J, Lee JE, Farodolu C, et al. The effect of short term vitamin D supplementation on the inflammatory and oxidative mediators of arterial stiffness. Health 2014;6:1503–1511.