Diabetic Diabetic RetinopathyRetinopathy

Steven Sanislo, M.D.Steven Sanislo, M.D.Assistant ProfessorAssistant Professor

Stanford University Department of Stanford University Department of OphthalmologyOphthalmology

Diabetic RetinopathyDiabetic Retinopathy

Diabetic retinopathy is a leading Diabetic retinopathy is a leading cause of new cases of blindness in cause of new cases of blindness in people aged 20 to 74 years in the people aged 20 to 74 years in the USAUSA

Many of the complications of diabetic Many of the complications of diabetic retinopathy can be prevented or retinopathy can be prevented or delayed by blood glucose control and delayed by blood glucose control and timely intervention.timely intervention.

Ocular AnatomyOcular Anatomy

Retinal AnatomyRetinal Anatomy

Retinal HistologyRetinal Histology

Sclera

Choroid

RPE

Photoreceptorouter segments

Photoreceptorinner segment

Outer Plexiform layer

Bipolar cells

Inner plexiform layer

Ganglion cells

Nerve fiberlayer

Retinal Diagnostic TestsRetinal Diagnostic Tests

Fundus PhotographyFundus Photography Fluorescein Angiography (FA)Fluorescein Angiography (FA) Optical Coherence Tomography Optical Coherence Tomography

(OCT)(OCT) Ocular UltrasonographyOcular Ultrasonography Electroretinography (ERG)Electroretinography (ERG)

Fundus Photos and FAFundus Photos and FA

Fundus PhotographyFundus Photography

Normal FANormal FA

Optical Coherence Optical Coherence Tomography (OCT)Tomography (OCT)

Normal OCTNormal OCT

B-scan UltrasoundB-scan Ultrasound

Normal UltrasoundNormal Ultrasound

Pathogenesis of DRPathogenesis of DR

Prolonged hyperglycemia is the Prolonged hyperglycemia is the major etiologic agent in all of the major etiologic agent in all of the microvascular complications of microvascular complications of diabetes, including diabetic diabetes, including diabetic retinopathy. retinopathy.

The cellular mechanisms through The cellular mechanisms through which hyperglycemia acts currently which hyperglycemia acts currently remain unclearremain unclear

Pathogenesis of DRPathogenesis of DR

Mechanisms that have been proposed are:Mechanisms that have been proposed are: 1. hyperglycemia may alter the expression of one 1. hyperglycemia may alter the expression of one

or more genes, leading to increased (or or more genes, leading to increased (or decreased) amounts of certain gene products that decreased) amounts of certain gene products that can alter cellular functions.can alter cellular functions.

2. Glycosylated proteins can undergo a series of 2. Glycosylated proteins can undergo a series of reactions, leading to considerable alteration of reactions, leading to considerable alteration of proteins.proteins.

3. Chronic hyperglycemia may produce oxidative 3. Chronic hyperglycemia may produce oxidative stress in cells, leading to the formation of an stress in cells, leading to the formation of an excess of "toxic end products of oxidation" excess of "toxic end products of oxidation" including peroxides, superoxides, nitric oxide, and including peroxides, superoxides, nitric oxide, and oxygen free radicals.oxygen free radicals.

VEGF and DRVEGF and DR

Vascular Endothelial Growth FactorVascular Endothelial Growth Factor Promotes vascular growth and Promotes vascular growth and

permeability permeability Elevated levels of circulating VEGF Elevated levels of circulating VEGF

in conditions with retinal ischemiain conditions with retinal ischemia

Anatomic ChangesAnatomic Changes

MicroanerysmsMicroanerysms Damage to Damage to

endothelial cells endothelial cells leads to dilated leads to dilated capillaries and capillaries and venules venules

These altered These altered vessels allow vessels allow serum and blood to serum and blood to leak into the retinaleak into the retina

NPDRNPDR

NPDR FANPDR FA

NPDR OCTNPDR OCT

Retinal IschemiaRetinal Ischemia

PDRPDR

PDRPDR

PDR FAPDR FA

Vitreous Hemorrhage Vitreous Hemorrhage (VH)(VH)

VH ultrasoundVH ultrasound

TRD ultrasoundTRD ultrasound

Epiretinal MembraneEpiretinal Membrane

PDR Retinal DetachmentPDR Retinal Detachment

Iris NeovascularizationIris Neovascularization

Mechanisms of Vision Mechanisms of Vision LossLoss

Retinal ischemiaRetinal ischemia Macular edemaMacular edema Vitreous hemorrhageVitreous hemorrhage Epiretinal membrane formationEpiretinal membrane formation Retinal detachmentRetinal detachment Neovascular glaucomaNeovascular glaucoma

PreventionPrevention

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

ScreeningScreening

Type 1 diabetics:Type 1 diabetics:First screen 5 years after onset, then First screen 5 years after onset, then annually.annually.

Type 2 diabetics:Type 2 diabetics:First screen upon diagnosis and then First screen upon diagnosis and then annually.annually.

TreatmentTreatment NPDR without macular edema -NPDR without macular edema -

ObserveObserve

Macular edema -Macular edema - 1. Focal/Grid laser photocoagulation1. Focal/Grid laser photocoagulation 2. Vitrectomy with membrane peeling2. Vitrectomy with membrane peeling 3. Intraocular Steroid*3. Intraocular Steroid* 4. Intraocular VEGF inhibitor*4. Intraocular VEGF inhibitor*

* Off-label use, contraversial

DME laser treatmentDME laser treatment

DME laser treatmentDME laser treatment

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TreatmentTreatment Vitreous Hemorrhage -Vitreous Hemorrhage -

1. Pan-retinal photocoagulation1. Pan-retinal photocoagulation 2. Vitrectomy with laser photocoagulation2. Vitrectomy with laser photocoagulation 3. Intraocular VEGF inhibitor*3. Intraocular VEGF inhibitor*

Traction Retinal Detachment - Traction Retinal Detachment - 1. Observation if not involving the macula1. Observation if not involving the macula 2. Vitrectomy with membrane dissection2. Vitrectomy with membrane dissection

* Off-label use, contraversial

Pan-retinal Pan-retinal PhotocoagulationPhotocoagulation

VitrectomyVitrectomy

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