Diabetic Macular Edema - Types, Causes, Complications and Treatment

Introduction:

Diabetes is a significant health issue that has become a public health problem worldwide. Increased blood sugar can damage tiny blood vessels at the back inner wall of the eye (retina) or block them completely in people with diabetes. Sometimes, protrusions can be seen on vessel walls-leaking fluid and blood into the retina. This fluid accumulation forms edema at the central part of the retina (macula), leading to thickening of the retina, vision disturbances, and loss among people with diabetes.

What Do You Mean by DME?

DME is a serious complication of diabetes due to the accumulation of fluid in the central part of the retina (macula). Increased blood sugar damages tiny blood vessels at the back inner wall of the eye (retina) or may completely block them. Fluid may ooze out of blood vessels into the retina. The global prevalence of DME is 6.8 percent among diabetics.

What Is the Difference Between Macular Edema and DME?

When fluid leaks to the central part of the retina, it is called macular edema, whereas, in DME, edema is caused specifically due to diabetes.

What Are The Other Causes of Macular Edema?

• Age-Related Macular Degeneration (AMD): Abnormal blood vessels leak fluid in the retina.

• Retinitis Pigmentosa (RP): A group of rare eye diseases affecting the retina. People are born with this disease; hence it is a genetic disease.

• Uveitis: Inflammation of the eye due to the attack on eye tissue by the immune system.

• Blocked Veins in the Retina: Due to blockage, there is a leak into the macula.

• Eye Surgery: After eye surgery, some may develop swelling in the retina.

• Medicines: Used in glaucoma can cause edema.

What Happens in DME?

The characteristic features of diabetic macular edema are as follows:

• Blurred vision.

• Vision gets worse with time.

• Objects look wavy.

• Objects look of different sizes.

• The colors look dull or faded.

What Happens if Edema Is Confined to One Eye?

If macular edema is confined to only one eye, the time taken to notice change is longer. While some may experience mild, others may experience severe changes.

What Is the Pathophysiology of DME?

Increased blood sugar levels in chronic diabetes disrupt the blood-retinal barrier (BRB). Altered BRB leads to fluid accumulation in the central part of the retina (macula) called edema. Chemokines and cytokines, inflammatory components, can be noticed in edema. They include vascular endothelial growth factor (VEGF), interleukins (ILs), matrix metalloproteinases (MMPs), and tumor necrosis factor (TNF). Due to multiple pathways, there is increased inflammation, oxidative stress, and vascular dysfunction.

When Does DME Develop?

It develops at any stage of diabetic retinopathy (DR). However, it is more frequent with the increase in the severity of DR. DR is a complication of diabetes. When there is damage to blood vessels, it leads to eye damage. Therefore, DR may not show any symptoms initially but may show mild symptoms later, which can lead to blindness. If the duration of diabetes is longer and blood sugar is not controlled, then eye complications will certainly develop.

What Are the Types of DME?

1. Based On the Amount of Swelling: A thicker retina means greater vision loss.

2. Based On the Location of Swelling: Confined to an area and widespread throughout the retina.

• Focal.

• Diffuse.

3. Based on Clinical Examination: Clinically significant macular edema, non-CSME, and CSME with central involvement (CSME-CI) involve the fovea.

• DME can be broadly characterized into two main anatomic categories:

  • Focal

  • Diffuse:

• In addition to focal and diffuse, DME is categorized based on clinical exam findings into clinically significant macular edema (CSME), non-CSME, and CSME with central involvement (CSME-CI), which involves the fovea.

What Are the Risk Factors for DME?

The risk factors of DME are-

• Diabetes.

• Poor blood sugar management.

• High cholesterol.

• High blood pressure.

• Kidney disease.

• Sleep apnea.

• Pregnancy.

What Preventive Measures Can Be Taken for DME?

The following preventive measures can be taken:

• Visit a doctor to get your eyes checked.

• Immediate care is to be taken once changes are noticed in vision.

• Take help to manage blood sugar levels.

• Take actions to keep blood pressure and cholesterol normal.

What Are the Complications of DME?

• Vision Loss: Left untreated, it may result in permanent vision loss.

• Vitreomacular Traction Syndrome: A condition in which clear gel-filled sticks to the macular change the macula's shape.

What Are the Tests Done to Know DME?

• Optical Coherence Tomography (OCT): Measure swelling in the retina.

• Fundus Imaging: Take pictures of the retina.

• Fluorescein Angiography: Dye is injected into the hand to highlight the blood flow in the retina.

How To Treat DME?

Knowing the cause of edema is very important to treat.

In DME, individuals with diabetes should take steps to control blood sugars.

One of the treatment options may be suggested by the doctor:

• Injections: VEGE inhibitors, steroids.

• Eye Drops: Nonsteroidal anti-inflammatory (NSAIDs) or steroid eye drops after surgery.

• Laser Treatment: Used in case of diabetes or retinal vein occlusion.

• Eye Surgery: Vitrectomy in which small openings are made in the eye wall to remove fluids using a suction tool.

What Are the Additional Targets and Emerging Therapies for DME?

• Mammalian Target of Rapamycin (mTOR): Tyrosinase forming two binding complexes, TORC1 and TORC2. Its activation induces the expression of HIFs, including HIF1-⍺. HIF1-⍺ controls the expression of over 60 genes, including VEGF. Rapamycin inhibits the TORC1 mTOR complex.

• Protein Kinase C (PKC): Serine threonine kinases are activated by growth hormones. The PKC-β2 isoforms play an important role in increased vascular permeability due to VEGF, and inhibitors of this isoform of PKC reduce VEGF and induce leakage.

• Intercellular Adhesion Molecule-1 (ICAM-1): Play a role in leukostasis in diabetic retinopathy and blocks increased vascular permeability. It acts by binding with lymphocyte function antigen-1 (LFA-1).

• Metalloproteinase (MMPs): These cleave structural components of extracellular matrix (ECM) and other proteins, including growth factors. Antibiotics like tetracycline inhibit MMPs.

• Receptors for Advanced Glycation End-Products (RAGE): Chronic hyperglycemia leads to the formation of advanced glycation end-products (AGEs). AGEs bind to RAGE, which can lead to the expression of VEGF, ICAM-1, inflammatory mediators, etc. RAGE inhibitors are used in DME.

• Renin-Angiotensin System (RAS): These are found in retina. In people with diabetes, RAS is increased. Angiotensin-converting enzyme (ACE)-inhibitors are used in DME.

• Combined Therapies: Combinations of therapies may be used to get the best results.

Conclusion:

DME is a serious complication of diabetes. Understanding the condition helps one manage it, and preventive measures can help avoid it. Knowing this condition may help one detect it early and seek help from their doctor at the earliest.