Several different circumstances can lead to retinopathy, but the most common among adults are chronically elevated blood sugar (diabetic retinopathy) and high blood pressure (hypertensive retinopathy).
Most vision loss associated with diabetic retinopathy is caused either by fluid buildup around the central area of the retina (macular edema) or complications from the formation of new but poorly functioning blood vessels, a process called neovascularization (Coscas 2010). Both processes are triggered by high blood glucose resulting from poorly-controlled diabetes (Crawford 2009). Chronic exposure to high blood sugar initiates biochemical and physiological changes that lead to blood vessel damage and retinal dysfunction (Cheung 2010).
One mechanism that leads to blood vessel dysfunction involves the metabolism of excess glucose in cells. As excess glucose accumulates and is processed within the cells, it causes additional water to move into cells and impairs cellular function, ultimately resulting in cellular stress and damage, leading to neovascularization (McCulloch 2013a; Lorenzi 2007).
Chronically high glucose levels lead to the formation of compounds called advanced glycation end products or AGEs. AGEs are compounds formed when sugars in the blood interact with proteins in the body and lead to damage. The resultant dysfunctional proteins (AGEs) damage blood vessels in the eyes (McCulloch 2013a; Tarr 2013). In addition to being formed inside the body as a consequence of elevated blood sugar, AGEs are also present in foods that typify the Western diet. Several protein-rich foods, especially meat, can become laden with AGEs when cooked at high temperatures via methods that utilize dry heat such as broiling or grilling. Evidence suggests these exogenous AGEs may play a significant role in several diabetic complications (Vlassara 2014).
In addition, blood vessels in the eyes of diabetics may be prone to occlusion, which contributes to further damage and may increase the risk of macular edema (McCulloch 2013a).
Decreased blood supply to the retina diminishes oxygen flow to retinal cells, a phenomenon known as hypoxia. In response, the body tries to create new blood vessels (ie, neovascularization). However, these new blood vessels are quite fragile, and as a result are prone to leakage and rupture, leading to hemorrhage and worsening of macular edema (Kollias 2010). Ultimately, this combination of macular edema and neovascularization leads to the damage of diabetic retinopathy.
Diabetic retinopathy is classified into two types – nonproliferative and proliferative (Tarr 2013).
- Nonproliferative: With nonproliferative retinopathy, the process of neovascularization has not yet begun (Cummings 2008). As a result, retinal damage is due to damage to existing blood vessels, not from the formation of malfunctioning new ones.
- One of the earliest signs of nonproliferative retinopathy is the presence of microaneurysms (ie, outward ballooning of the capillaries). Additional signs of nonproliferative retinopathy include nerve-fiber infarcts, which are areas of neuron death due to disrupted blood flow, hemorrhaging within the retina, and hard deposits (called exudates) within the retina (Kollias 2010).
- Proliferative: The proliferative phase of diabetic retinopathy is marked by the development of abnormal vessels (neovascularization) as the body seeks to restore blood flow to the retina. Proliferative retinopathy can cause additional bleeding, fibrosis (accumulation of scar tissue), and retinal detachment. Proliferative retinopathy can also cause sudden vision loss if bleeding from the blood vessels blocks light from entering the retina (Tarr 2013; Cummings 2008; Kollias 2010).
Hypertensive retinopathy occurs due to high blood pressure. Initially, mainly the small arteries (arterioles) in the retina constrict. Over time, however, these arterioles become damaged and the connective tissue that supports them breaks down. This leads to damage of the blood vessel-retina barrier, resulting in blood and blood lipids (fats in the blood) spilling from the blood vessels into the area around the retina, damaging it, and leading to swelling of a structure in the eye known as the optic disc. Also, the blood vessel damage disrupts blood flow to the retina, further injuring it (Wong 2004; McDonald 2010). In addition to damaging the retina, hypertensive retinopathy is also associated with an increased risk of stroke (Ong 2013).