Diabetic Retinopathy

Diabetic Retinopathy Clinical Pathology & Diagnosis Optometry 8370 2008

Review of Retinal Vasculature • Important because diabetes is a disease causing occlusion and leakage of the retinal microvasculature • Level of retina effected can demonstrate degree of hypoxia and corresponding risk of neovascularization • Retinal tissue has the highest consumption of oxygen, by weight, of any tissue in the body • Density of choroid at macula creates the necessary high hemodynamic activity to metabolize the outer third of retina; creates potential for edema

Retinal Arteries • Have no elastic lamina layer (present in CRA before lamina cribrosa) • Have well-developed smooth muscle • Unless diseased, maintain strong barrier to perfusion of blood components • Intraretinal arteries not effected by parasympathetic or sympathetic innervation • Lie in the NFL and GCL, with strong connections to ILM

Retinal Arteries (cont) • Insulated from retinal tissues by glial perivascular limiting membrane of Kruckmann • Arteriosclerosis: Intimal and endothelial hyperplasia involving the CRA and its retinal branches • A/V crossing changes: Occur secondary to arteriosclerosis; due to “hard artery / soft vein”, and, the merging of artery adventitia & venous glial covering at site of crossing

Retinal Veins • Thin walled with abundant elastic tissue • Contain muscle near ONH, which are replaced by pericytes peripherally • Lack of wall structure allows for variable appearance in diseased states (e.g. DM) • Isolated attachments to retinal structure, resulting in tortuous appearance in occlusive conditions • Same glial insulating structure as arteries • CRV is drain for retinal vasculature watershed

Retinal Capillary Networks • 1. Superficial Network: • In the NFL & GCL • Post-arteriolar network • Most often affected in arterial-based diseases • Changes here (flame and preretinal hemes, CWS, capillary and arteriolar occlusion, IRMA, and venous caliber changes) indicate likely increased retinal hypoxia, and higher risk for neovascularization

Retinal Capillary Networks • 2. Deep Network: • Resides in INL, though changes involve neighboring retinal layers • Pre-venular network • Tightly packed vessels • Changes here (retinal swelling, hard exudates, microaneurysms, dod-blot hemes) indicate retinal edema, and possible need for photocoagulation if within 500 microns of fovea

Retinal Capillary Networks • Exceptions: • Circumpapillary Zone: Area of increased number of retinal capillary layers (up to 4), following the superior and inferior arcades for about 2 DD from disc; do not involve the macula; includes the radial peripapillary capillaries, which originate from pre-capillary retinal arterioles and drain into intraretinal venules on the ONH (no anastomoses with with other retinal capillary beds, so defects here can result in scotoma, e.g. glaucoma)

Retinal Capillary Networks • Exeptions: • No capillaries reside near the ora (which may contribute to peripheral neovascularization) • No capillaries around retinal vessels, especially arteries

Retinal Capillary Networks • Capillary structure: endothelial cells, intramural pericytes, basement membrane • Normal aging causes loss of endothelial cells and pericytes in peripheral retinal capillaries, leading to capillary death (Adjacent capillaries may dilate, shunts and microaneurysms may form)

Choriocapillaris • Considered capillary bed of choroid • Densest at macula • Blood supply is compartmentalized; a feeder vessel supplies a particular zone, and there is limited anastomosis of the vascular system • Infarct causes an RPE window defect and loss of photoreceptor function secondary to loss of nutrient supply (Elschnig Spots)

Choroid • Contains: Larger blood vessels than choriocapillaris, melanocytes, immune system cells, and structural extensions of Bruch’s • Sympathetic nervous supply • Also limited anastomoses • Acts to supply RPE & outer third of retina; disperses heat from light absorption and metabolic activity

Diabetes Mellitus • “A complex disorder of carbohydrate, fat and protein metabolism that is primarily a result of relative or complete lack of insulin secretion by the beta cells of the pancreas or of defects of the insulin receptors” • Mosby’s Pocket Dictionary of Medicine, Nursing, and Allied Health, 2nd ed.

Type I (Usually IDDM) • Includes patients who require exogenous insulin to prevent ketoacidosis • Results from destruction of islet cells in the pancreas at any age, especially under 30 • Accounts for about 10% of all patients with DM in the U.S. • Patients tend to be acutely symptomatic at onset, with possible polydipsia, polyphagia, polyuria, unexplained weight loss, dry mouth, pruritis, leg cramps or pain, delayed healing of wounds, and recurrent infection of skin, genitals, or UT

Type II (Usually NIDDM) • Includes patients whose body tissues are resistant to the effects of insulin • Occurs more often in adults, with incidence increasing with age • Accounts for about 90% of all U.S. cases of DM • Many patients are asymptomatic, as onset may be insidious and hard to recognize • Upper body obesity is a risk factor, resulting from peripheral insulin resistance

Diabetes • Estimated to effect 7 and 14 million Americans, half of whom may be undiagnosed • Prevalence of 10% in those over 60 • 15-20% in those over 80 • 0.3% of population develops DM by age 20 • 8.6% of population may have DM by age 65

Diabetes • Patients have… • Twice the risk of stroke • 5 times the risk of MI • 8 times the risk of peripheral vasculopathy • 3 times the risk of dying from flu or pneumonia

Diabetes and the Eye • Diabetic retinopathy is leading cause of new blindness in the U.S. in those 20 to 74 • Accounts for about 12% of new cases of blindness each year • Diabetic retinopathy is more dependent on duration of disease than age • Early Tx reduces incidence of severe vision loss by 50-60%

Diabetes and the Eye • 5% of those with DM develop glaucoma (vs. 2% of the normal population) • Cataracts are 2-4% more prevalent, occur at younger ages, and progress more rapidly • Complications include: 3rd, 4th, and 6th cranial nerve neuropathy, dry eye, reduced corneal sensitivity and wound healing, rubeosis, papillopathy, and ION, among others

“I don’t dress up much anymore…I’m really more of a colorer.” Ian Crane, Age 5

Diabetic Retinopathy • Etiology of hypoxia and edema: • Poorly understood and controversial • Seems to be secondary to thickening of the capillary basement membrane, endothelial cell damage and proliferation, and loss of pericytes • Pericytes are the mesothelial cells surrounding retinal capillary endothelial cells… usually one-to-one ratio, less in the diabetic patient • Later, endothelial cells proliferate, lay down layers of basement membrane material; leakage then occurs • RBCs are deformed (decreased oxygen transport) • Platelet changes cause increased stickiness and aggregation of blood column

Diabetic Retinopathy • May be classified as: • Nonproliferative (Signs include: MA, dot-blot hemes, hard exudates, flame hemes, CW spots, IRMA, capillary and arteriolar occlusion, and venous tortuosity & beading) • Proliferative (Signs include: neo of the disc or elsewhere, fibrotic proliferation, tractional RD, and vitreous heme • Macular edema may accompany either form

Nonproliferative Retinopathy • Microaneurysms (MA): • Saccular outpouchings of the weakened retinal capillary wall • Occur in INL, first sign of retinopathy • Leak into the retina, causing edema • Difficult to see without FA, though they may be coated with blood, or may be hyalinized • May cause loss of vision if near macula

Nonproliferative Retinopathy • Dot-blot hemes: • Represent ruptures in weakened capillary walls • Indicate presence of deep retinal edema • Not treatable, but resolve on their own • Originate from venous end of capillaries • May cause loss of vision if near macula

Nonproliferative Retinopathy • Hard exudates: • Yellow, waxy spots representing areas of lipid deposits • Represent leaky capillaries of deep capillary network (INL); may extend from ILM to OPL • Arranged in clumps or rings, often with a MA or NVM at its center • Sign of chronic retinal edema • Poor prognosis for retaining good VA if found near the fovea, due to prolonged retinal compromise

Nonproliferative Retinopathy • Flame hemes, CW spots, IRMA, capillary nonperfusion, venous tortuosity & beading: • All are signs of retinal hypoxia • Represent immediate precursors to vasoproliferative stimuli • Involve superficial capillary network

Nonproliferative Retinopathy • Flame hemes: • Result from compromised arterioles in the NFL, usually in the radial peripapillary distribution • Follow-up should occur in 3-6 months

Nonproliferative Retinopathy • CW spots: • Result from microinfarcts of NFL • Cotton-like appearance results from axoplasmic stasis and resulting debris deposition • Usually occur within 3 DD of ONH • Follow-up in 3-6 months

Nonproliferative Retinopathy • IRMA: • Intraretinal Microvascular Abnormalities • Represent intraretinal shunting system and dilated capillaries in an area of capillary nonperfusion • Usually formed of venous endothelium, with few intramural pericytes • Form to attempt to drain an area of stasis • Considered to be germination bed for neovascularization • May leak early in development, and may appear similar to neovascularization (need FA to distinguish) • Indicates direct immediate potential for neo • Follow up in 3-4 months

Nonproliferative Retinopathy • Venous tortuosity & beading • Results from sludging and slowing of venous blood, causing local venule dilation • Represents stasis to the point of hypoxia • Appearance related to thin-walled, elastic structure of veins, and occasional vein-to-retina attachments • Follow up in 3-4 months

Nonproliferative Retinopathy • Capillary nonperfusion: • Only visible with high resolution FA • Appears as dark spots in the normally lightly fluorescein colored capillary bed • Represents area of localized infarcts of the capillary bed, with relative hypoxia • Follow up in 3-4 months

Macular Edema • Macular edema the leading cause of legal blindness in diabetic patients • Pockets of fluid in the OPL (CME variant) • Prompt referral necessary for CSME (Clinically Significant Macular Edema): • Retinal thickening within 500 microns (1/3 DD) of the fovea • Hard exudates within 500 microns of the fovea, if adjacent retinal thickening • An area or areas of retinal thickening at least disc area in size, at least part of which is within 1 DD of the fovea

Proliferative Retinopathy • Represents new retinal vessel formation at the disc or elsewhere, or, fibrous tissue formation • Occurs in response to lack of oxygenated blood • New vessels very fragile and subject to leakage, fibrosis, and hemorrhage (unlike IRMA, usually leak profusely) • Thought to be a proliferation of the endothelium of capillaries and veins, though pathogenesis is controversial • Almost always requires referral to retinal specialist

Proliferative Retinopathy • The Diabetic Retinopathy Study (DRS) conclusively demonstrated that laser PRP significantly reduces risk for severe vision loss from PDR (by at least 50%) • High-risk patients require immediate referral for PRP, within 24-48 hours • Timely and appropriate laser surgery can reduce the 5-year risk for severe vision loss from PDR to 5% or less

Proliferative Retinopathy • High-risk PDR: • NVD approx. one-fourth to one-third disc area or more in size • NVD less than one-fourth disc area in size if fresh vitreous or preretinal heme present • NVE greater than or equal to one-half disc area in size if fresh vitreous or preretinal heme

Diabetes and the Optometrist • Optometrists have huge responsibility: • Diagnose patients who previously did not know they were diabetic • Carefully monitor and appropriately refer IDDM and NIDDM patients • Must hone ophthalmoscopy skills to the point of confidence in skills (diabetic signs can be quite subtle) • Must help coordinate care of patients with a chronic, potentially devastating disease • Incidence of diabetic retinopathy is increasing, and will continue to do so for quite some time

Diabetes and the Optometrist • Key Examination Considerations: • Must take careful history, carefully assess systemic disease and care regimen • Must assess visual symptoms • What nonproliferative signs are present? Where are they? At what level of the retina are the signs? • What do the signs reveal about the patient’s imminent risk of hypoxia? • Is there any suspected neovascularization, at the disc or elsewhere?

Diabetic Retinopathy