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Etiology, Pathogenesis, ClassificationTop
Diabetic retinopathy develops in the majority of patients with diabetes mellitus (within ≥15 years of the diagnosis it affects almost all patients with type 1 diabetes and around 25%-50% of patients with type 2 diabetes). The key factors in its pathogenesis are hyperglycemia and hypertension.
The American Academy of Ophthalmology established the International Classification of Diabetic Retinopathy and Diabetic Macular Edema, which describes 5 clinical levels of diabetic retinopathy:
1) No apparent retinopathy and no abnormalities.
2) Mild nonproliferative diabetes retinopathy (NPDR) with microaneurysms only.
3) Moderate NPDR with microaneurysms and other abnormalities but less than severe NPDR.
4) Severe NPDR with any of the following: ≥20 intraretinal hemorrhages in each of the 4 retinal quadrants, definite venous beading in ≥2 retinal quadrants, prominent intraretinal microvascular abnormalities in ≥1 retinal quadrants, and no proliferative diabetic retinopathy (PDR).
5) PDR with at least one of the following: Retinal neovascularization, vitreous hemorrhage, or preretinal hemorrhage.
Diabetic macular edema (DME) can be present with any level of diabetic retinopathy. The DME classification is based on the ophthalmic findings (retinal thickening or hard exudates in the posterior pole):
1) Mild DME: Some findings present but distant from the center of the macula.
2) Moderate DME: Findings approaching but not involving the center of the macula.
3) Severe DME: Findings involving the center of the macula.
Glaucoma, cataracts, and other disorders of the eye occur earlier and more frequently in people with diabetes.
Diagnosis and Follow-UpTop
The first ophthalmologic examination should be performed within 5 years of establishing the diagnosis of type 1 diabetes and at the moment of diagnosis of type 2 diabetes. In patients with no retinopathy, perform follow-up examinations once a year; in patients with the early stages of NPDR, every 6 months; in patients with more advanced retinopathy, every 3 months; and in pregnancy and the postpartum period, every month (regardless of the severity of retinopathy). Examination of visual acuity and color vision through ophthalmoscopy (always after pupil dilation) and color photography of the fundus are usually sufficient; rarely, specialized studies are indicated, such as fluorescein angiography of the fundus (usually done by an ophthalmologist), which is useful in patients with very early retinopathy (undetectable by ophthalmoscopy), macular edema, and NPDR, as well as for the assessment of the effects of laser therapy.
Prevention and TreatmentTop
1. Early detection and control of diabetes to reduce the risk or slow the progression of diabetic retinopathy. Target levels of preprandial glucose are 4.4 to 7.2 mmol/L (80-130 mg/dL) and postprandial glucose, ≤10.0 mmol/L (180 mg/dL), with glycated hemoglobin ≤7.0% in the general population. Effective treatment of hypertension and hyperlipidemia is of key importance.
2. The goal of treatment of no apparent retinopathy and mild and moderate NPDR is to optimize medical therapy. The mainstay of treatment aimed at inhibiting the progression of vascular lesions is laser retinal photocoagulation, which is used in patients with macular edema, advanced NPDR, and early proliferative retinopathy. Advanced proliferative retinopathy (vitreous hemorrhages, connective tissue proliferation) is an indication for vitrectomy.
In patients with severe macular edema, injections of anti-vascular endothelial growth factor (anti-VEGF) preparations (bevacizumab, ranibizumab, and aflibercept) into the vitreous can be used as an alternative or an adjunct to laser photocoagulation,Evidence 1Weak recommendation (benefits likely outweigh downsides; but the balance is close or uncertain; an alternative course of action may be better for some patients). Note that a weak rather than strong recommendation is related to the moderate quality of evidence and high cost of intervention. Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to indirectness and no long-term follow-up. Virgili G, Parravano M, Menchini F, Evans JR. Anti-vascular endothelial growth factor for diabetic macular oedema. Cochrane Database Syst Rev. 2014 Oct 24;(10):CD007419. doi: 10.1002/14651858.CD007419.pub4. Review. Update in: Cochrane Database Syst Rev. 2017 Jun 22;6:CD007419. PubMed PMID: 25342124. although the cost of some may be a limiting factor in their use. Ranibizumab, a selective monoclonal antibody to VEGF, is the first-line agent in all patients with DME with central foveal involvement. Aflibercept is another agent also indicated for the treatment of visual impairment due to DME.