An Overview of Diabetic Retinopathy and its Connection to Cardiovascular Health, Along with Chronic Ocular Small Vessel Disease

Nickolas Garson^*
*Correspondence: Nickolas Garson, Department of Ophthalmology, University of Florida College of Medicine, Florida, USA, Email:

Description

In chronic hyperglycemic states, small vessel damage in the retina causes diabetic retinopathy (DR), a potentially fatal condition. Diabetic macular edema and retinal ischemia are two manifestations of the disease's complex multi-pathway pathogenesis, with the former being the most common cause of vision impairment in DR. Cytokines induced by hypoxia cause mechanical retinal damage over time by stimulating vascular endothelial growth factor (VEGF) production and angiogenesis. Center-involving diabetic macular edema can be effectively treated with anti-VEGF therapy. While laser photocoagulation continues to be the standard of care, there is growing evidence that anti-VEGF is effective in the treatment of proliferative DR as both an adjuvant and a monotherapy. In large cohort studies, it was found that DR is a separate risk factor for cardiovascular disease and death. Changes in the ratio of retinal vascular caliber to blood flow may also have an impact on women's risk of macrovascular events. Uncontrolled blood sugar leads to diabetic retinopathy (DR), a small vessel-based end organ insult that is on the rise in the United States. Researchers and clinicians continue to face difficulties in finding solutions to these issues. The pathophysiology of diabetic retinopathy, its current treatment, and the anatomy of ocular perfusion, which is crucial to understanding diabetic microvascular disease, are briefly discussed in this review [1].

The central retinal artery and the ciliary arteries, which supply the eye and its ethmoidal, palpebral, and orbital branches, are further subdivided into the ophthalmic artery. The anastomotic interlace of ciliary vessels in the circle of Zinn-Haller can be found in the posterior sclera. These vessels supply the laminar region with blood through branches that surround the optic nerve. Vascular structures make up the majority of the choroid, a significant uveal component in the eye. The choriocapillaris, along with the adjacent Sattler and Haller layers, are the primary vascular layers. Within Sattler's layer, the choriocapillaris, a single layer of vessels with fenestrated endothelium, is formed by arteriole branches. The outer third of the retina can be fed thanks to this network of capillaries. Fluid can flow through oncotic gradients thanks to its endothelial characteristics and large diameter (20–40 m). The choroid can be multifunctional and influence the structure, perfusion, and health of the retina and surrounding anatomy thanks to this ability and other structural characteristics [2].

Blood comes to the retina from two places: the choroidal vascular complex and the central retinal artery. The central retinal artery is the primary blood supply to the retina. The choroid subserves the outer one third of the retina, while the central retinal artery supplies the inner two-thirds of the retina. A cilioretinal artery—an independent branch of the ciliary circulation—may supply a full thickness portion of the retina in up to 32% of eyes. The extensive network of retinal capillaries is made up of retinal arterioles, which are produced by the central retinal artery. The foveal avascular zone (FAZ), a region of reduced light scatter, is the center of the retina (the fovea in the macula) without any capillaries. The choroidal circulation provides this region with its blood supply. The thickness of the choriocapillaris decreases by 30% in the periphery, with the highest density (10 m) in the fovea. There are four macular retinal vascular beds: the superficial plexus, intermediate plexus (above the inner nuclear retinal layer), deep plexus (below the inner nuclear retinal layer), and radial peripapillary capillary plexus (supplying the nerve fiber layer) [3].

The vasculature inside the retina ordinarily doesn't have arterio-venous anastomosis nor does it have autonomic innervation. The inward blood retinal obstruction is shaped by close intersections inside the endothelium. Tight junctions within the retinal pigment epithelial cells create the outer blood retinal barrier. Over a third of diabetics are affected by DR, with diabetes duration, glycemic control, and blood pressure control being the main risk factors. DR combines two potentially harmful elements: a condition that gets worse slowly and has no symptoms. Patients may not seek treatment until their vision becomes clearly impaired, at which point the retinopathy may have progressed. 1 percent of visual impairments worldwide are attributed to DR. In the United States, DR affects one out of every 29 people over. Uncontrolled Sort 1 diabetics, sadly, meet significant visual horribleness prior in life because of the period of determination with over 33% of those having DR with vision undermining stages. In Type 1 diabetics, DR rises significantly with age, with a prevalence of over 90% over the age of 40 [4].

PDR is the most advanced type of DR. End organ ocular damage caused by diabetes is at its highest level, and it can take the form of neovascular glaucoma, mechanical destruction of the retina with fibrotic transformation, or localized growth of abnormal vasculature. Through the action of the VEGF receptor 2, the VEGF-A isoform promotes microvasculature permeability, endothelial proliferation, and migration. New vessels emerge from the border of perfused and non-perfused retina under hypoxic conditions as well as from the optical disc. A fibrovascular membrane complex (FVM) is created when these vessels penetrate the internal limiting membrane and grow into the posterior vitreous cortex. Due to their compromised integrity, these vessels frequently bleed into and under the vitreous gel, obscuring vision and the surface of the retina. Antero-posterior and tangential traction with contraction of the vitreous cortex-fibrovascular membrane complex are the results of continued growth [5].

Epiretinal trauma and tractional retinal detachments are brought on by the tethering of vessels from the retina into the vitreous cortex. Full-thickness retinal ischemia and mechanical damage result from the eventual ischemia of the outer retina, which is now mechanically separated from the choriocapillaris perfusion, and inner retinal ischemia from inherent retinal capillary loss. A favorable to fibrotic reaction from development factors, for example, changing development factor beta (TGFβ) and connective tissue development factor (CTGF) cause inevitable fibrotic change. Chronic diabetic tractional retinal detachments frequently exhibit fibrotic bands. A negative feedback loop of ischemic drive and the fibrotic response eventually resulted in a vicious cycle of catastrophic damage. The gap between microvascular and macrovascular disease is narrowing, in contrast to the traditional view that they were distinct entities due to vascular caliber. Since the end of the 1990s and the beginning of the new millennium, there have been more studies looking into this connection [2].

Type 2 diabetics, even those with a mild stage of retinopathy, had a higher 5-year risk of first-time myocardial infarction (MI) and congestive heart failure (CHF) than those without retinopathy, according to a much more recent study that took place in 2021. A group of Type 1 diabetics was examined for a median of 9.5 years in large cohort studies like the Finish Diabetic Nephropathy Study (FinnDiane) of 2018. A history of photocoagulation, which is considered severe diabetic disease, was found to be an independent predictor of cardiovascular events, peripheral vascular disease, and coronary artery disease in univariate analysis. Although the reasons for this have not yet been established, it is possible that overlapping factors contribute to the development of both microvascular and macrovascular diseases. For instance, HIF-1 plays a significant role in the stimulation of VEGF in the retinal microvasculature. Large vessel plaque advancement has also been linked to HIF. These findings shed light on the possible explanations for why a variety of vascular damage may be more common than previously thought [3].

Arteriolar to venular diameters and DR were evaluated for cardiovascular disease and mortality risk in the landmark Wisconsin study (2004), which had a retention rate of over 60% after a 20-year follow-up period. MI was statistically associated with DR severity and lower arterio-venous ratio (AVR). In multivariate analysis, a trend of increasing heart-related mortality with increasing severity of DR was also found to be associated with severity of DR. Diabetes duration, blood pressure, and diabetic kidney disease were all correlated with both measured variables. However, the data from larger studies contain significant inconsistencies and gaps. The discoveries referenced in the FinnDiane were rather than concentrates, for example, the Wisconsin concentrate on which showed an absence of free gamble increment of cardiovascular occasions from diabetic retinopathy alone in Type 1 diabetics. Glycemic levels and coronary disease were also not found to be significantly related in the Wisconsin Study [4].

A wealth of information regarding the significance of small vessel disease in cardiovascular disease risk has been provided by longitudinal studies in the literature. Confounding conclusions may have been influenced by data and analysis variations. However, the pattern of the information that has been gathered suggests that microvascular disease may indicate a risk for the onset of microvascular and macrovascular cardiovascular disease, as well as their association. Even if there are no signs of end organ damage like diabetic retinopathy, vessel capacity may still be an important indicator of mortality risk. Similar conditions may cause microvascular damage in different ways in men and women. To better understand these nuances, additional research is required, which may pave the way for a more targeted approach to disease risk stratification and prevention [5].

Acknowledgement

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Conflict of Interest

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