Diabetic Retinopathy Steven Sanislo, M.D. Assistant Professor Stanford University Department of Ophthalmology

Diabetic Retinopathy Diabetic retinopathy is a leading cause of new cases of blindness in people aged 20 to 74 years in the USA Diabetic retinopathy is a leading cause of new cases of blindness in people aged 20 to 74 years in the USA Many of the complications of diabetic retinopathy can be prevented or delayed by blood glucose control and timely intervention. Many of the complications of diabetic retinopathy can be prevented or delayed by blood glucose control and timely intervention.

Ocular Anatomy

Retinal Anatomy

Retinal Histology Sclera Choroid RPE Photoreceptor outer segments Photoreceptor inner segment Outer Plexiform layer Bipolar cells Inner plexiform layer Ganglion cells Nerve fiber layer

Retinal Diagnostic Tests Fundus Photography Fundus Photography Fluorescein Angiography (FA) Fluorescein Angiography (FA) Optical Coherence Tomography (OCT) Optical Coherence Tomography (OCT) Ocular Ultrasonography Ocular Ultrasonography Electroretinography (ERG) Electroretinography (ERG)

Fundus Photos and FA

Fundus Photography

Normal FA

Optical Coherence Tomography (OCT)

Normal OCT

B-scan Ultrasound

Normal Ultrasound

Pathogenesis of DR Prolonged hyperglycemia is the major etiologic agent in all of the microvascular complications of diabetes, including diabetic retinopathy. Prolonged hyperglycemia is the major etiologic agent in all of the microvascular complications of diabetes, including diabetic retinopathy. The cellular mechanisms through which hyperglycemia acts currently remain unclear The cellular mechanisms through which hyperglycemia acts currently remain unclear

Pathogenesis of DR Mechanisms that have been proposed are: 1. hyperglycemia may alter the expression of one or more genes, leading to increased (or decreased) amounts of certain gene products that can alter cellular functions. 1. hyperglycemia may alter the expression of one or more genes, leading to increased (or decreased) amounts of certain gene products that can alter cellular functions. 2. Glycosylated proteins can undergo a series of reactions, leading to considerable alteration of proteins. 2. Glycosylated proteins can undergo a series of reactions, leading to considerable alteration of proteins. 3. Chronic hyperglycemia may produce oxidative stress in cells, leading to the formation of an excess of "toxic end products of oxidation" including peroxides, superoxides, nitric oxide, and oxygen free radicals. 3. Chronic hyperglycemia may produce oxidative stress in cells, leading to the formation of an excess of "toxic end products of oxidation" including peroxides, superoxides, nitric oxide, and oxygen free radicals.

VEGF and DR Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Promotes vascular growth and permeability Promotes vascular growth and permeability Elevated levels of circulating VEGF in conditions with retinal ischemia Elevated levels of circulating VEGF in conditions with retinal ischemia

Anatomic Changes Microanerysms Damage to endothelial cells leads to dilated capillaries and venules Damage to endothelial cells leads to dilated capillaries and venules These altered vessels allow serum and blood to leak into the retina These altered vessels allow serum and blood to leak into the retina

NPDR

NPDR FA

NPDR OCT

Retinal Ischemia

PDR

PDR

PDR FA

Vitreous Hemorrhage (VH) Vitreous Hemorrhage (VH)

VH ultrasound

TRD ultrasound

Epiretinal Membrane

PDR Retinal Detachment

Iris Neovascularization

Mechanisms of Vision Loss Retinal ischemia Retinal ischemia Macular edema Macular edema Vitreous hemorrhage Vitreous hemorrhage Epiretinal membrane formation Epiretinal membrane formation Retinal detachment Retinal detachment Neovascular glaucoma Neovascular glaucoma

Prevention Prospective controlled interventional studies have shown that strict control of blood glucose and blood pressure significantly reduces and delays the onset and severity of diabetic retinopathy. Prospective controlled interventional studies have shown that strict control of blood glucose and blood pressure significantly reduces and delays the onset and severity of diabetic retinopathy.

Screening Type 1 diabetics: First screen 5 years after onset, then annually. Type 2 diabetics: First screen upon diagnosis and then annually.

Treatment NPDR without macular edema - NPDR without macular edema - Observe Observe Macular edema - Macular edema - 1. Focal/Grid laser photocoagulation 1. Focal/Grid laser photocoagulation 2. Vitrectomy with membrane peeling 2. Vitrectomy with membrane peeling 3. Intraocular Steroid* 3. Intraocular Steroid* 4. Intraocular VEGF inhibitor* 4. Intraocular VEGF inhibitor* * Off-label use, contraversial

DME laser treatment

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Treatment Vitreous Hemorrhage - Vitreous Hemorrhage - 1. Pan-retinal photocoagulation 1. Pan-retinal photocoagulation 2. Vitrectomy with laser photocoagulation 2. Vitrectomy with laser photocoagulation 3. Intraocular VEGF inhibitor* 3. Intraocular VEGF inhibitor* Traction Retinal Detachment - Traction Retinal Detachment - 1. Observation if not involving the macula 1. Observation if not involving the macula 2. Vitrectomy with membrane dissection 2. Vitrectomy with membrane dissection * Off-label use, contraversial

Pan-retinal Photocoagulation

Vitrectomy