## 2 Classifications of Microvascular and Macrovascular Complications of Diabetes Mellitus  
### Classifications of Microvascular Complications of Diabetes Mellitus  
#### 2.1.1 Diabetic Retinopathy (DR)  
Diabetic retinopathy (DR) can result in irreversible blindness, particularly in those of reproductive age, when left untreated [11]. Oxidative stress, inflammation, neurodegeneration, and microvascular are major contributors to the pathophysiology of DR [12]. However, when serum blood glucose levels are properly controlled, the onset and progression of DR can be slowed down, as well as the occurrence of oxidative stress (as a result of an imbalance between free radical oxygen species) [13] and resident inflammation. Indeed, chronic hyperglycemia causes microvascular endothelial dysfunction, which can contribute to retinal vascular ischemia and more vascular permeability [14]. Therefore, oxidative stress and other hyperglycemia-induced cellular damage underpin the fundamental mechanisms involved in the development and expression of diabetic vascular problems [15]. As a result, an effective therapeutic aimed at these pathways would be critical in fighting these disorders. Diabetic Retinopathy (DR) Classification  
Clinically, diabetic retinopathy is categorized mainly into non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), where the sequence of progression in these categories is always from NPDR into PDR, with the latter eventually progressing into macular edema (a common cause for loss of vision and blindness amongst the diabetics) [16]. Non-proliferative DR (NPDR) and proliferative DR (PDR) are the two types of DR [14]. Patients progressing from NPDR to PDR typically present with a reduction in best-corrected visual acuity and a very high risk of suffering irreversible blindness due to retinal detachment, vitreous hemorrhage, and neovascular glaucoma. The prevention of this transitory change from NPDR to PDR is critical for relieving significant financial burden on the healthcare system since treatment and administration of PDR patients is four times more expensive (USD 1.207) than those with NPDR (USD 292). Diabetic Retinopathy (DR) Prevalence  
As previously stated, diabetic mellitus (DM) long-term complications include cataracts, retinopathy, neuropathy, and nephropathy, all of which are micro-complications of DM, with diabetic retinopathy being the most common cause of blindness globally in young working-class adults [17]. End-organ damage is unavoidable with diabetes mellitus microvascular problems [18]. As a result, for people who have had diabetes for more than two decades, it is practically certain that all patients with type 1 diabetes mellitus, and only 60% of those with type 2 diabetes, will develop DR [7]. In this regard, roughly 95 million people worldwide have diabetes and 1.5 billion have blindness, with 0.4 billion instances linked to diabetes [19]. In particular, 7.7 million persons in America have DR, with an estimated 11 million by 2030 [20]. Furthermore, a decade ago, the global prevalence of DR in people with diabetes was 34.6%, with 6.96% having proliferative diabetic retinopathy (PDR), 6.81% having diabetic macular edema (DME), and 10.2% having vision-threatening diabetic retinopathy (VTDR) [12]. Diabetic Retinopathy (DR) Pathogenesis  
The loss of vascular integrity and morphological alterations is one of the symptoms of DR [18]. Furthermore, microaneurysms, hemorrhages, hard exudates, and cotton wool patches are all signs of DR [21]. Following these instances, fibrovascular growth and retinal detachment become unavoidable. Inflammation of the retina occurs in addition to the etiology of DR. This inflammatory process is seen in the retinal vasculature, which includes both choroidal and retinal vasculature. Furthermore, DR damages the blood-retinal barrier (BRB) by affecting retinal microvasculature [7].