Diabetes mellitus will be the seventh leading cause of death in 2030 as projected by WHO. The prevalence of diabetic retinopathy (DR) is intimately linked to the upsurge in the prevalence of diabetes mellitus.

Hyperglycemic state in diabetes mellitus results in the formation of advanced glycation end products. The formation of AGEs correlates with glycemic control. AGEs stimulate vascular endothelial growth factor (VEGF) expression. Multiple physiological and pathological effects, i.e., angiogenesis, vascular hyperpermeability, initiation of DR-like vascular changes, antithrombotic or prothrombotic responses, and neuroprotection can be attributed to VEGF. My earlier studies reported an increase in the VEGF level with an increase in the severity of DR.

Diabetic retinopathy is a microvascular complication of diabetes and is a leading cause of morbidity and disability. The prevalence of DR directly correlates with the duration of diabetes, ranging from 29% in people with diabetes for up to 5 years to 78% in people with more than 15 years of diabetes.

Diabetic retinopathy is the leading cause of vision loss in adults aged 20–74 years. Diabetic retinopathy affects ninety-three million people and among them, 21 million have a treatable form of diabetic macular edema (DME).

Diabetic macular edema is responsible for most of the visual loss experienced by patients with diabetes as it remains the major cause of vision loss in the highly prevalent type 2 diabetes mellitus (Figure). Proliferative diabetic retinopathy (PDR) is the most common vision-threatening lesion particularly among patients with type 1 diabetes mellitus.

At a global level, the outbreak of COVID-19 has generated a public health crisis. The SARS‐CoV‐2 coronavirus is an enveloped RNA virus. Infection incites a remarkable range of responses from complete lack of symptoms through to cytokine storm and life‐threatening acute respiratory distress syndrome.

COVID-19 mortality is higher amongst people who are older, male, and obese. All these factors are related to the increased prevalence of vitamin D deficiency.

Diabetes mellitus is known to be associated with an increased risk of infections. Diabetes does not seem to increase the risk of occurrence of Covid-19. However, diabetes is more frequent in patients with severe Covid-19.

Vitamin D plays a fundamental role in calcium and mineral metabolism. Vitamin D is needed for the maintenance of normal blood levels of calcium and phosphate that are required for regular functions such as mineralization of bone, muscle contraction, nerve conduction, and general cellular function.

Vitamin D is also recognized to influence a wide range of fundamental biological functions such as cell differentiation and immunomodulation associating it to a variety of clinical disorders such as diabetes, hypertension, autoimmune disorders, and malignancy. The 25-hydroxyvitamin D 25(OH)D is the major circulating metabolite. 1,25,-dihydroxy-vitamin D3 (calcitriol) is the biologically active form.

Serum 25(OH)D is the most consistent indicator of the vitamin D status of an individual. Serum 25(OH)D levels less than 20 ng/mL is considered as deficiency and levels greater than 30 ng/mL is considered normal.

Evidence supports a link between vitamin D deficiency and COVID‐19 severity. Experimentally, vitamin D causes an increase in the ratio of angiotensin‐converting enzyme (ACE) - 2 to ACE. Such an increase reduces subsequent inflammatory cytokine response to pathogens and lung injury. In European countries, a significant negative correlation has been observed between mean vitamin D levels and COVID-19 cases per one million population. However, the correlation of vitamin D with COVID-19 deaths in these countries was not significant.

Vitamin D plays an important role in normal insulin secretion in response to glucose. Vitamin D is supposed to help improve the body's sensitivity to insulin and thus reduce the risk of insulin resistance, which is often a precursor to type 2 diabetes mellitus.

Evidence suggests that vitamin D plays a role in the pathogenesis of DR, through its effects on the immune system. Inflammatory cytokines are upregulated in type 2 diabetes mellitus. Vitamin D decreases the production of several pro-inflammatory cytokines. Vitamin D also exerts an anti-inflammatory effect by reducing the proliferation of helper T-cells, cytotoxic T- cells, and natural killer cells.

Vitamin D deficiency is also associated with vascular endothelial dysfunction in middle-aged and elderly adults. This dysfunction has been found to be linked to increased vascular endothelial cell expression of pro-inflammatory factors.

Vitamin D may also contribute to DR via angiogenesis mechanisms. The active metabolite of vitamin D, calcitriol, is a potent inhibitor of retinal neovascularization in vivo. Calcitriol also inhibits retinal endothelial cell capillary morphogenesis in vitro. Also, calcitriol downregulates VEGF.

Diabetic macular edema and neovascularization are driven by VEGF production. Vitamin D could exert its positive effect via calcitriol mediated VEGF reduction. My recent study reported that deficiency of vitamin D accelerated the severity of retinopathy. Serum vitamin D levels of ≤ 18.6 ng/mL were found to serve as a sensitive and specific biomolecular biomarker for proliferative DR.

RDA of 600-800 IU is recommended to maintain adequate levels of vitamin D. People who are at higher risk of vitamin D deficiency during this global pandemic should contemplate taking vitamin D supplements to sustain the circulating 25(OH)D in the optimal levels (75–125 nmol/L). Vitamin D supplementation should be strongly advised for people likely to be deficient.

In India, Vitamin D deficiency is widespread. Clinically diagnosed cases represent only the tip of the iceberg. Indian Council of Medical Research (ICMR) recommends a daily supplement of 400 IU/day of vitamin D for Indians under situations of minimal exposure to sunlight.

In such unprecedented COVID-19 times, patients of DR should be advised vitamin D supplementation after monitoring their serum vitamin D levels. Covid-19 lockdown had added to the already existing vitamin D deficiency in the susceptible group of diabetic patients. Vitamin D deficiency needs to be taken into consideration with strong action.