What is diabetic retinopathy (Diabetic Retinopathy)?

From the Guidelines

Diabetic retinopathy is a serious eye condition that affects people with diabetes and is the leading cause of blindness in working-age adults, and the most effective way to manage it is through prevention by maintaining tight blood sugar control, blood pressure control, and regular eye examinations.

Key Points

• Diabetic retinopathy occurs when high blood sugar levels damage the blood vessels in the retina, causing them to leak fluid or bleed, which distorts vision 1.
• There are two main stages: non-proliferative diabetic retinopathy (early stage) where blood vessels weaken and may leak, and proliferative diabetic retinopathy (advanced stage) where new, abnormal blood vessels grow on the retina, potentially causing severe vision loss 1.
• Symptoms often don't appear until the condition is advanced and may include blurry vision, floaters, dark areas in vision, and eventually blindness if left untreated 1.
• Risk factors include poor blood sugar control, high blood pressure, high cholesterol, longer diabetes duration, and smoking 1.
• Management focuses on prevention through tight blood sugar control (maintaining HbA1c below 7%), blood pressure control (below 130/80 mmHg), and regular eye examinations (annually for most diabetics) 1.
• Treatment options include laser photocoagulation to seal leaking vessels, anti-VEGF injections like bevacizumab (Avastin), ranibizumab (Lucentis), or aflibercept (Eylea) to reduce abnormal vessel growth, steroid injections to reduce inflammation, and vitrectomy surgery for advanced cases 1.

Prevention and Screening

• Early detection through regular screening is crucial as treatment is most effective before symptoms develop, which is why all diabetic patients should have comprehensive dilated eye exams at least once yearly 1.
• Patients with type 1 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist within 3–5 years after the onset of diabetes, and patients with type 2 diabetes should have an initial dilated and comprehensive eye examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes 1.

Treatment

• Laser photocoagulation surgery is an effective treatment for preventing visual loss in patients with diabetic retinopathy, particularly those with high-risk characteristics 1.
• Anti-VEGF injections and steroid injections can also be effective in reducing abnormal vessel growth and inflammation, respectively 1.
• Vitrectomy surgery may be necessary for advanced cases of diabetic retinopathy 1.

From the FDA Drug Label

In Studies D-1 and D-2, patients received monthly ranibizumab 0.3 mg or 0.5 mg intravitreal injections or monthly sham injections during the 24-month controlled treatment period. All enrolled patients in Studies D-1 and D-2 had DR and DME at baseline. Study D-3 enrolled DR patients with and without DME; 88 (22%) eyes with baseline DME and 306 (78%) eyes without baseline DME and balanced across treatment groups At baseline, 62% of patients had non-proliferative diabetic retinopathy (NPDR) (ETDRS-DRSS less than 60) and 31% had proliferative diabetic retinopathy (PDR) (ETDRS-DRSS greater than or equal to 60) After monthly treatment with ranibizumab 0. 3 mg, the following clinical results were observed: Table 7 ≥3-Step and ≥2-Step Improvement at Month 24 in Study D-1 and Study D-2 Outcome Measure | Study* | Sham | Ranibizumab 0.3 mg | Estimated Difference (95% CI)† ≥3-step improvement from baseline | D-1: Sham, n=124; | 2% | 17% | 15% (7%, 22%) in ETDRS-DRSS | ranibizumab 0.3 mg, n=117 | | | | D-2: Sham, n=115; | 0% | 9% | 9% (4%, 14%) | ranibizumab 0.3 mg, n=117 | | | ≥2-step improvement from baseline | D-1: Sham, n=124; | 4% | 39% | 35% (26%, 44%) in ETDRS-DRSS | ranibizumab 0.3 mg, n=117 | | | | D-2: Sham, n=115; | 7% | 37% | 31% (21%, 40%) | ranibizumab 0.3 mg, n=117 | | |

Diabetic Retinopathy (DR) is a condition where patients have damage to the blood vessels in the retina due to diabetes.

• Non-proliferative diabetic retinopathy (NPDR) is an early stage of DR where the blood vessels in the retina become weakened and start to leak.
• Proliferative diabetic retinopathy (PDR) is a more advanced stage of DR where new, fragile blood vessels grow in the retina and can cause vision loss. The ETDRS-DRSS is a scale used to measure the severity of DR, ranging from 10 to 75. In Studies D-1 and D-2, patients with DR and DME were treated with monthly ranibizumab 0.3 mg or 0.5 mg intravitreal injections or monthly sham injections. The results showed that after monthly treatment with ranibizumab 0.3 mg, there was a significant improvement in DR severity, with 17% of patients achieving a ≥3-step improvement and 39% achieving a ≥2-step improvement in ETDRS-DRSS at Month 24. These results suggest that ranibizumab 0.3 mg can be effective in improving DR severity in patients with DR and DME 2.

From the Research

Definition and Prevalence of Diabetic Retinopathy

• Diabetic retinopathy (DR) is a complication of diabetes that affects the eyes and can lead to severe vision loss or blindness if left untreated 3.
• It is estimated that about 90 million diabetics suffer from DR, and it remains the leading cause of vision loss in working-age adults (20-65 years) in developed countries 3.
• The number of patients suffering from diabetes mellitus is expected to increase significantly, with an estimated 440 million people suffering from diabetes mellitus worldwide by 2030 4.

Classification and Symptoms of Diabetic Retinopathy

• DR can be classified into nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) 3.
• NPDR is featured with intraretinal microvasculature changes and can be further divided into mild, moderate, and severe stages that may associate with diabetic macular oedema (DME) 3.
• PDR involves the formation and growth of new blood vessels (retinal neovascularisation) under low oxygen conditions 3.
• In its early stages, DR is asymptomatic, but over time, chronic hyperglycemia can lead to sensitive retinal damage, leading to fluid accumulation and retinal haemorrhage (HM), resulting in cloudy or blurred vision 3.

Risk Factors and Treatment Options for Diabetic Retinopathy

• The main risk factors for DR are chronic hyperglycemia, high blood pressure, and plasma lipids 3.
• Early identification and treatment are key priorities for reducing the morbidity of diabetic eye disease 3.
• Treatment options for DR include tight control of glycemia, blood pressure, and plasma lipids, as well as regular monitoring 3.
• In advanced stages, the main treatments of DR include intraocular injections of anti-vascular endothelial growth factor (VEGF) antibodies, laser treatments, and vitrectomy 3, 5, 6.
• Anti-VEGF drugs have been shown to be slightly better than panretinal photocoagulation at preventing vision loss, and may have greater benefits for preventing complications such as macular oedema 5.

Pathophysiological Mechanisms and Treatment Perspectives

• Vascular endothelial growth factor (VEGF) plays a pivotal role in the retinal microvascular complications of diabetes, and represents an exciting target for therapeutic intervention in diabetic retinopathy 7.
• The cellular and molecular alterations that characterize experimental models of diabetes are considered in relation to the influence of high glucose-mediated oxidative stress on VEGF expression and on the mechanisms of VEGF's actions under hyperglycemic induction 7.
• Potential therapeutic strategies for preventing VEGF overexpression or blocking its pathological effects in the diabetic retina are being considered 7.