Systemic Disease and the Eye: Risks and Recommendations

Metabolic syndrome (MetS) is defined as having at least three of the following conditions: high blood pressure, high blood sugar (hyperglycemia), obesity, and alterations in cholesterol.¹ MetS can lead to arterial plaque buildup (ie, atherosclerosis) and other organ damage. One third of the US adult population has been diagnosed with MetS, and its prevalence is increasing.¹ The clinical presentation of MetS is variable and depends on the underlying atherosclerotic cardiovascular disease. Although the prevalence of MetS is on the rise, medications along with conscientious lifestyle changes can slow or even prevent MetS from causing serious health conditions, such as coronary heart disease, type 2 diabetes, and stroke.^1-4

Associations between systemic disease and ocular conditions, including the development of diabetic retinopathy (DR), cataract, and glaucoma, have been established in the last several decades.⁵ However, few studies directly correlate MetS as a constellation of risk factors for these ocular findings. This article reviews the evidence supporting associations between MetS and ocular disease. It also discusses the risk factors and conditions for acquiring MetS and helps practitioners guide their patients in taking appropriate actions.

CENTRAL OBESITY

Central obesity is a primary component of MetS, leading to insulin resistance, hypertension, and dyslipidemia.⁴ Obesity is a multisystem disease, and its treatment may include lifestyle modifications, medication, and surgical management. It is imperative to ensure the patient has committed to implementing a healthier lifestyle before considering pharmacological or surgical options for managing MetS. Premature cataract, glaucoma, and age-related macular degeneration (AMD) have been shown to have a strong association with obesity (Figure 1).⁶ Therefore, clinicians should look for lens opacities, glaucomatous cupping, macular drusen, and macular neovascularization when examining these patients.

INSULIN RESISTANCE

In MetS, there is typically a buildup of fatty tissue, especially in the abdomen, leading to insulin resistance.⁷ Proinflammatory cytokines such as tumor necrosis factor, leptin, adiponectin, plasminogen activator inhibitor, and resistin are released from the enlarged adipose tissue, which adversely alters insulin.⁸

Insulin resistance can be acquired or occur due to genetic predisposition. Impairment of the signaling pathway, insulin receptor defects, and defective insulin secretion can all contribute. Visceral (ie, abdominal) obesity has been identified as the main trigger of all pathways involved in the pathogenesis of MetS, and high-calorie intake is the primary cause of visceral fat accumulation.⁴ Over time, these factors can cause the development of MetS, presenting as vascular and autonomic damage.⁹

Modest weight reduction via caloric restriction to about 1,200 calories a day can lead to a reduction of liver fat and a reversal of liver insulin resistance and type 2 diabetes. Even a 10% weight reduction can make a difference, which is likely part of how glucagon-like peptide-1 receptor agonists work to reverse type 2 diabetes.¹⁰

Insulin resistance is caused by the desensitization of muscle to the insulin released by the pancreas to elicit glucose uptake, leading to elevated blood glucose levels. Skeletal muscle insulin resistance can appear decades before the onset of β-cell failure and symptomatic type 2 diabetes.¹¹

Physical activity opens the door for glucose transport into the muscle cell, bypassing the block in insulin action. Patients with muscle insulin resistance can normalize the storage of ingested carbohydrate into the muscle as glycogen, decreasing the conversion of carbohydrate to fat in the liver. This helps prevent the development of fatty liver disease and improves the plasma lipid profile, which can protect against the development of atherosclerosis.¹² Accumulated evidence has demonstrated a strong relationship between insulin resistance and a higher incidence of DR, AMD, and glaucoma (Figure 2).¹³

HYPERTENSION

This condition is defined as a blood pressure of 130/85 mm Hg or higher, while normal blood pressure is defined as less than 120/80 mm Hg. High blood pressure is strongly correlated to obesity and is often found in patients with insulin resistance. Insulin resistance is responsible for eventual microvascular damage that predisposes blood vessels to endothelial dysfunction, atherosclerotic formation, vessel wall inflammation, and vascular resistance—leading to hypertension. Peripheral vascular disease, left ventricular hypertrophy, and cardiomyopathy are all sequalae of hypertension. An increase in blood pressure may lead to hypertensive retinopathy, choroidopathy, and optic neuropathy. It can eventually cause retinal arteriolar sclerosis and possibly lead to retinal artery and vein occlusion. If dyslipidemia occurs with MetS, it can drive the atherosclerotic process, often leading to symptomatic ischemic heart disease.³

HYPERLIPIDEMIA

The liver and the intestines are responsible for approximately 80% of cholesterol production needed to maintain healthy bodily functions, while the remaining 20% of cholesterol should come from the ingestion of food. Cholesterol cannot travel alone in the bloodstream; therefore, the body packages cholesterol and other lipids into protein-covered particles, known as lipoproteins, that can travel easily within the blood.¹⁴

Lipoproteins vary in shape and size, and each type has its own role in promoting health or disease:

• High-density lipoprotein (HDL) carries cholesterol through the blood to the liver for excretion. HDL is also used to build cell membranes and make essential hormones. If HDL is low, cholesterol may begin to accumulate in the blood and blood vessel wall, instead of being appropriately processed by the liver.^14,15
• Low-density lipoprotein (LDL) is responsible for plaque formation in arteries and an excess can lead to heart disease and is associated with retinal vein occlusion.^14,15
• Very LDL (VLDL) is made by the liver and carries triglycerides to tissues. It can increase the risk of heart disease.¹⁴
• Intermediate-density lipoprotein (IDL) particles form as the VLDLs give up their fatty acids. Some IDLs are removed rapidly by the liver, while others are eventually changed into LDLs.¹⁴
• Triglycerides are the most common type of fat in the body. They are primarily carried by chylomicrons and are acquired mainly from the intake of foods that are high in fat.^14,15

Hyperlipidemia is defined as having high blood lipid levels that include both triglycerides and LDLs, while hypercholesterolemia is defined as having only high LDL. Hyperlipidemia may increase the risk of retinal exudation along with retinal artery and vein occlusion (Figure 3).¹⁶

IT’S A WIN-WIN TO DISCUSS SYSTEMIC HEALTH

Educating patients on making appropriate lifestyle choices, taking their prescribed medications, and following up with their primary care physician will empower them to reduce their risk of systemic disease and vision-threatening ocular sequelae.