Diabetic Retinopathy Disease Background

Introduction

Diabetic retinopathy is a progressive retinal disorder that occurs in almost all patients with chronic diabetes mellitus (DM). 

Diabetic Retinopathy_Disease Background

Epidemiology

Diabetic retinopathy is one of the leading causes of preventable vision impairment and blindness worldwide. It is the principal cause of impaired vision in patients aged 25-74 years. Diabetic retinopathy is also the leading complication of DM. The estimated prevalence rate of diabetic retinopathy worldwide is around 34.6% (93 million people). The prevalence of diabetic retinopathy was noted to be highest in Africa (35.9%), North America and Caribbean (33.3%), and the Middle East and North Africa (32.9%). While the lowest was seen in South and Central America (13.4%). In the United States, the noted prevalence of diabetic retinopathy in patients with DM 40 years old and above is 28.5% (4.2 million people; those with vision-threatening diabetic retinopathy is 4.4% (0.7 million people). Worldwide, the estimated prevalence of vision-threatening diabetic retinopathy is around 10.2% (28 million people).  

In Asia, the prevalence rates of diabetic retinopathy ranges from 10% in India to as high as 43% in Indonesia. It is estimated that there are as much as 30.6 million people in South-East Asia suffering from diabetic retinopathy, with 9.6 million people with vision-threatening diabetic retinopathy. 

Pathophysiology

Diabetic retinopathy is believed to be the result of different biochemical changes (eg aldose reductase, protein glycation, protein kinase C activation, angiotensin enzyme expression, vascular endothelial growth factor expression, etc) accompanied by blood retinal barrier increased permeability and initially by increases in retinal blood flow. The resulting widened venular caliber is a marker of the severity of diabetic retinopathy. Visual loss from diabetic retinopathy is primarily caused by several complications, including macular edema, vitreous hemorrhage, neovascular glaucoma, macular capillary nonperfusion, and distortion or traction detachment of the retina.  

The basic pathological changes in the retinal vessels involve abnormal permeability and vascular occlusion with ischemia, leading to subsequent neovascularization.

Risk Factors

The major risk factors in the development of diabetic retinopathy are the duration of diabetes and the severity of hyperglycemia. Other contributing risk factors are pregnancy, puberty, cataract surgery, and other medical conditions (eg hypertension and hyperlipidemia). Diabetic retinopathy is strongly associated with poor control of blood glucose, blood lipids, and blood pressure.  

Classification

Types of Diabetic Retinopathy  

Nonproliferative diabetic retinopathy  

Nonproliferative diabetic retinopathy is the earliest clinically apparent stage of diabetic retinopathy. It is characterized by abnormalities primarily in the posterior retina and macula. These abnormalities include microvascular abnormalities (eg microaneurysms, occluded vessels, and dilated or tortuous vessels), intraretinal hemorrhages, nerve-fiber layer infarcts (cotton-wool spots), and hard exudates. Visual loss in nonproliferative diabetic retinopathy is primarily due to macular edema. As the diseases progress, gradual closure of the retinal vessels occur that eventually results to impaired perfusion and retinal ischemia. This is manifested by venous abnormalities (eg beading, dilation, loops), increasing retinal hemorrhages, intraretinal microvascular abnormalities (IRMA), and increasing exudation.  

Proliferative diabetic retinopathy  

Proliferative diabetic retinopathy is the most advanced stage of diabetic retinopathy. It is marked by the onset of neovascularization of the inner surface of the retina, that is induced by retinal ischemia. Neovascularization (new vessels at the optic disc [NVD] or new vessels elsewhere in the retina [NVE]) causes preretinal and vitreous hemorrhage, followed by fibrosis and tractional retinal detachment. Proliferative diabetic retinopathy may develop from existing severe nonproliferative diabetic retinopathy or without substantial preceding nonproliferative diabetic retinopathy.

Diabetic Retinopathy_Disease Background 2

• No abnormalities observed

Mild Nonproliferative Diabetic Retinopathy

• Have microaneurysms only

Moderate Nonproliferative Diabetic Retinopathy

• Presence of microaneurysms and other signs (eg hard exudates, cotton wool spots, dot and blot hemorrhages) but less than severe nonproliferative diabetic retinopathy

Severe Nonproliferative Diabetic Retinopathy

• ≥20 intraretinal hemorrhages in each of the 4 quadrants
• Definite venous beading in ≥2 quadrants
• Prominent IRMA in ≥1 quadrant

Non-high-risk Proliferative Diabetic Retinopathy

• Presents with neovascularization and/or vitreous or preretinal hemorrhage but does not meet the criteria for high risk proliferative diabetic retinopathy

High-risk Proliferative Diabetic Retinopathy

• Have neovascularization within 1 disc diameter of the optic nerve head that are ≥1/4 to 1/3 disc area with or without vitreous or preretinal hemorrhage or
• Vitreous and/or preretinal hemorrhage associated with less extensive NVD or  with NVE ≥1/2 disc area in size

¹International Council of Ophthalmology. Updated 2017 ICO guidelines for diabetic eye care. http://www.icoph.org/. Jan 2017.  

Diabetic Macular Edema (DME)  

Diabetic macular edema is characterized by thickening located within 2 disc diameters of the center of the macula. It can occur at any stage of diabetic retinopathy and can run an independent course. It is recommended to be evaluated through dilated examination using slit-lamp biomicroscopy, OCT and/or stereoscopic fundus photography. DME is classified as either noncenter-involved or center-involved. It must be noted that severity of DME can help determine the appropriate treatment modality to give to the patient and follow-up recommendations.  

Diabetic Macular Edema Severity Scale Based on Observation Upon Dilated Ophthalmoscopy¹  

No macular edema if there is no retinal thickening or hard exudates on the posterior pole. DME is classified as mild if the retinal thickening or hard exudates in the posterior pole is distant from the center of the macula. In moderate or noncentral-involved DME, the retinal thickening or hard exudates approaches the center of the macula but does not involve the center that is 1 mm in diameter. Lastly, in severe or central-involved DME, the retinal thickening or hard exudates involves the center of the macula that is 1 mm in diameter.  

¹Modified from: Wilkinson CP, Ferris FL III, Klen RE, et al. Proposed international clinical diabetic retinopathy & diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1679-1680. International Council of Ophthalmology. Updated 2017 ICO guidelines for diabetic eye care. http://www.icoph.org/. Jan 2017.  

Clinically Significant Macular Edema (CSME)  

CSME may occur at any stage of diabetic retinopathy and defined to include any 1 of the following features:

• Retinal thickening at or within 500 microns of the center of the macula (approximately ½ of the optic disc diameter)
• Hard exudates at or within 500 microns of the center of the macula, if associated with thickening of the adjacent retina
• Retinal thickening zone or zones of ≥1 disc area in size, any part of which is within 1 disc diameter of the center of the macula

CSME helps in differentiating the different types of diabetic retinopathy.