DIABETES MELLITUS AND DIABETIC EYE DISEASE

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DIABETES MELLITUS AND DIABETIC EYE DISEASE

  1. 1. DIABETES MELLITUS AND DIABETIC EYE DISEASE Dr Russell J Watkins
  2. 2. Diabetes Mellitus <ul><li>During a meal, insulin is released from the beta-cells of the pancreatic islet cells </li></ul><ul><li>Insulin is a key hormone that regulates metabolism of triglycerides & carbohydrates </li></ul><ul><li>Diabetes mellitus is a group of metabolic disorders characterised by chronic hyperglycaemia resulting from relative insulin deficiency, insulin resistance or both. </li></ul><ul><li>Usually primary but may be secondary to pancreatic disease, acromegaly, Cushing’s disease, effect of drugs. </li></ul><ul><li>Also, impaired glucose tolerance as an entity </li></ul>
  3. 3. Diabetes Mellitus <ul><li>Insulin deficiency results in impaired metabolism of carbohydrate, fat, protein, water & electrolytes </li></ul><ul><li>Death may result from </li></ul><ul><ul><li>Acute metabolic decompensation </li></ul></ul><ul><ul><li>Longstanding metabolic derangements - diabetic complications </li></ul></ul>
  4. 4. Diabetes Mellitus <ul><li>Primary DM is classified as </li></ul><ul><ul><li>Type I (insulin dependent - IDDM) </li></ul></ul><ul><ul><ul><li>Always need insulin </li></ul></ul></ul><ul><ul><ul><li>Younger </li></ul></ul></ul><ul><ul><li>Type II (non-insulin dependent NIDDM) </li></ul></ul><ul><ul><ul><li>Diet &/or oral antihyperglycaemics usual </li></ul></ul></ul><ul><ul><ul><li>May need insulin </li></ul></ul></ul><ul><ul><ul><li>Older </li></ul></ul></ul>
  5. 5. Diabetes Mellitus <ul><li>Epidemiology </li></ul><ul><ul><li>Worldwide distribution </li></ul></ul><ul><ul><li> Incidence of both type I & type II DM </li></ul></ul><ul><ul><ul><li>Prevalence of both types varies in different parts of the world </li></ul></ul></ul><ul><ul><li>UK prevalence is 1-2% of population </li></ul></ul><ul><ul><ul><li>50% of type II remain undetected </li></ul></ul></ul><ul><ul><ul><li>Ratio of type II:type I is ~7:3 </li></ul></ul></ul>
  6. 6. Diabetes Mellitus <ul><li>Uncertain aetiology </li></ul><ul><ul><li>Environmental factors interact with genetic factors </li></ul></ul><ul><ul><ul><li>Variable clinical syndrome </li></ul></ul></ul><ul><ul><ul><li>Variable timing of onset </li></ul></ul></ul><ul><ul><li>Pattern of inheritance & environmental factors differ in type I & type II </li></ul></ul>
  7. 7. Diabetes Mellitus <ul><li>Genetics of type I DM </li></ul><ul><ul><li>Polygenic </li></ul></ul><ul><ul><li>Strongest genetic association = HLA-DQ </li></ul></ul><ul><ul><li>~36% concordance with identical twin </li></ul></ul><ul><li>Genetics of type II DM </li></ul><ul><ul><li>no HLA linkage </li></ul></ul><ul><ul><li>genetic factors must be important </li></ul></ul><ul><ul><ul><li>~95% concordance in identical twins </li></ul></ul></ul><ul><ul><ul><li>genetic factors not yet identified </li></ul></ul></ul>
  8. 8. Diabetes Mellitus <ul><li>Environmental factors in DM </li></ul><ul><ul><li>Type I </li></ul></ul><ul><ul><ul><li>Viral aetiology may be important </li></ul></ul></ul><ul><ul><ul><li>Diet (?Early introduction of cow’s milk) </li></ul></ul></ul><ul><ul><ul><li>Autoimmune - association with other AI disease, HLA linkage, insulin autoantibodies detectable </li></ul></ul></ul>
  9. 9. Diabetes Mellitus <ul><li>Environmental factors in DM </li></ul><ul><ul><li>Type II </li></ul></ul><ul><ul><ul><li>“ Western diet” & obesity </li></ul></ul></ul><ul><ul><ul><li>Age </li></ul></ul></ul><ul><ul><ul><li>Pregnancy </li></ul></ul></ul>
  10. 10. Diabetes Mellitus <ul><li>Principles of treatment </li></ul><ul><ul><li>To alleviate symptoms of hyperglycaemia </li></ul></ul><ul><ul><li>To avoid hypoglycaemia </li></ul></ul><ul><ul><li>To limit complications </li></ul></ul>
  11. 11. Diabetes Mellitus <ul><li>Complications of diabetes </li></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><ul><li>Atherosclerosis (macrovascular) </li></ul></ul></ul><ul><ul><ul><li>Microvascular (retina, kidney, nerve sheath) </li></ul></ul></ul><ul><ul><li>Infections and poor wound healing </li></ul></ul><ul><ul><ul><li>Impaired PMNL function </li></ul></ul></ul>
  12. 12. Diabetes Mellitus <ul><li>The current cost of DM in the UK </li></ul><ul><ul><li>30% reduction in life expectancy </li></ul></ul><ul><ul><li>Commonest cause of blindness in 20-65 yr age group </li></ul></ul><ul><ul><li>600 patients reach ESRF per year </li></ul></ul><ul><ul><li>Lower limb amputation rate  25-fold </li></ul></ul><ul><ul><li>Use of hospital beds  6-fold </li></ul></ul><ul><ul><li>5% of total NHS budget </li></ul></ul>
  13. 13. Diabetes Mellitus <ul><li>Diabetes Control & Complications Trial (1993 onwards - NEJM 1993;329:1796  ) </li></ul><ul><ul><li>Published in NEJM, JAMA et al </li></ul></ul><ul><ul><li>Diabetic complications are preventable </li></ul></ul><ul><ul><li>The aim of treatment should be ‘near-normal’ glycaemia whilst avoiding hypoglycaemic episodes in insulin-treated patients (3-fold  in such episodes in tightly controlled patients) </li></ul></ul>
  14. 14. Diabetes Mellitus <ul><li>Early Treatment of Diabetic Retinopathy Study (ETDRS) </li></ul><ul><ul><li>Published in mid 1980’s </li></ul></ul><ul><ul><li>12 published papers </li></ul></ul><ul><ul><li>Current practice based on ETDRS guidelines </li></ul></ul><ul><ul><li>Diabetic maculopathy (Report 1) reference Arch Ophthalmol 1985;103:1796  ) </li></ul></ul>
  15. 15. Diabetes Mellitus <ul><li>The spectrum of diabetic eye disease </li></ul><ul><ul><li>Corneal hypoaesthesia & RES </li></ul></ul><ul><ul><li>Cataract </li></ul></ul><ul><ul><li>Vitreous degeneration </li></ul></ul><ul><ul><li>Cranial neuropathy </li></ul></ul><ul><ul><li>Arteriosclerotic retinopathy </li></ul></ul><ul><ul><li>Vascular retinopathy (accelerated atherosclerosis) </li></ul></ul><ul><ul><li>Diabetic papillopathy </li></ul></ul><ul><ul><li>Diabetic retinopathy </li></ul></ul><ul><ul><li>Advanced diabetic eye disease including retinal detachment and rubeosis iridis </li></ul></ul>
  16. 22. Arteriosclerotic Retinopathy <ul><li>Usually associated with hypertension; accelerated by DM </li></ul><ul><li>Signs </li></ul><ul><ul><li>AV nipping (Salus’ sign) </li></ul></ul><ul><ul><li>Dilated vein distal to AV crossing (bonnet’s sign) </li></ul></ul><ul><ul><li>Tapering of vein either side of AV crossing (gunn’s sign) </li></ul></ul><ul><ul><li>Right angle deflection of vein </li></ul></ul>
  17. 23. Arteriosclerotic Retinopathy <ul><li>Signs (cont.) </li></ul><ul><ul><li>Arteriolar “silver wiring” </li></ul></ul><ul><ul><li>Ischaemic choroidal infarcts (elschnig bodies) </li></ul></ul><ul><ul><li>Retinal arterial macroaneurysm </li></ul></ul><ul><ul><li>Ischaemic optic neuropathy </li></ul></ul>
  18. 26. Diabetic Retinopathy <ul><li>Prevalence of retinopathy at time of diagnosis: </li></ul><ul><ul><li>1.5% age 20-40yrs </li></ul></ul><ul><ul><li>7% age 50-60yrs </li></ul></ul><ul><ul><li>10% age 60+ </li></ul></ul><ul><li>Diabetic retinopathy develops after >~8yrs duration of DM </li></ul><ul><ul><li>79% of diabetics have retinopathy after 20yrs </li></ul></ul>
  19. 27. Diabetic Retinopathy <ul><li>DR is the most common cause of blind & partial sight registration in 30-60yr age group </li></ul><ul><li>Blind diabetics </li></ul><ul><ul><li>50% are dead within 3-4 yrs of registration </li></ul></ul><ul><ul><li>Only 20% survive for 10 yrs </li></ul></ul>
  20. 28. Diabetic Retinopathy <ul><li>Possible pathogenic mechanisms </li></ul><ul><ul><li>Thickening of capillary basement membrane </li></ul></ul><ul><ul><li>Capillary endothelial cell damage (aldose reductase) </li></ul></ul><ul><ul><li>Impaired RBC function   O 2 transport </li></ul></ul><ul><ul><li> Stickiness & aggregation of platelets </li></ul></ul><ul><ul><li>Loss of vascular pericytes (aldose reductase) </li></ul></ul>
  21. 29. Diabetic Retinopathy <ul><li>Classification </li></ul><ul><ul><li>Background </li></ul></ul><ul><ul><li>Pre-proliferative </li></ul></ul><ul><ul><li>Proliferative </li></ul></ul><ul><ul><li>Maculopathy (can occur at any stage) </li></ul></ul><ul><ul><li>Advanced </li></ul></ul>
  22. 30. Background Retinopathy <ul><li>Signs of background diabetic retinopathy </li></ul><ul><ul><li>Microaneurysms </li></ul></ul><ul><ul><ul><li>First clinically detectable sign </li></ul></ul></ul><ul><ul><ul><li>INL </li></ul></ul></ul><ul><ul><li>Hard exudates </li></ul></ul><ul><ul><ul><li>OPL & INL </li></ul></ul></ul><ul><ul><li>Haemorrhages </li></ul></ul><ul><ul><ul><li>Flame shaped </li></ul></ul></ul><ul><ul><ul><li>Dot & blot </li></ul></ul></ul>
  23. 34. Pre-proliferative Retinopathy <ul><li>Pre-proliferative retinopathy </li></ul><ul><ul><li>Cotton wool spots </li></ul></ul><ul><ul><li>Venous dilatation & beading </li></ul></ul><ul><ul><li>Arteriolar narrowing </li></ul></ul><ul><ul><li>Large blot haemorrhages </li></ul></ul><ul><ul><li>IRMA </li></ul></ul><ul><ul><li>Capillary closure on FFA </li></ul></ul>
  24. 35. Pre-proliferative Retinopathy <ul><ul><li>Risk of progression to proliferative retinopathy as predicted by ETDRS </li></ul></ul><ul><ul><ul><li>Venous beading - >4x </li></ul></ul></ul><ul><ul><ul><li>Haemorrhages/microaneurysms - 4x </li></ul></ul></ul><ul><ul><ul><li>IRMA - 4x </li></ul></ul></ul><ul><ul><ul><li>CWS - 2x </li></ul></ul></ul><ul><ul><li>Management is controversial - some would photocoagulate; others would monitor closely & treat NV </li></ul></ul>
  25. 39. Proliferative Retinopathy <ul><li>Proliferative retinopathy </li></ul><ul><ul><li>Overall Incidence of Proliferative Change Is 10-20% of Diabetics </li></ul></ul><ul><ul><li>Type I>type II </li></ul></ul><ul><ul><li>Neovascularisation Is Pathognomonic of Proliferative DR </li></ul></ul><ul><ul><li>NVD & NVE </li></ul></ul><ul><ul><li>Fibrovascular Epiretinal Membrane; Initially Transparent, Becomes Opaque </li></ul></ul><ul><ul><li>Vitreous traction with RD </li></ul></ul>
  26. 40. Proliferative Retinopathy <ul><li>Results from </li></ul><ul><ul><ul><li>Extensive capillary closure </li></ul></ul></ul><ul><ul><ul><li>Angiogenic factor causes friable NV at watersheds </li></ul></ul></ul><ul><ul><ul><li>Endothelial buds from the venous end of capillaries </li></ul></ul></ul><ul><ul><ul><li>Fibrovascular network adherent to vitreous face </li></ul></ul></ul><ul><ul><ul><li>PVD may elevate vessels </li></ul></ul></ul>
  27. 41. Proliferative Retinopathy <ul><li>Management </li></ul><ul><ul><ul><li>Photocoagulation </li></ul></ul></ul><ul><ul><ul><li>Good glycaemic control (DCCT) </li></ul></ul></ul><ul><ul><ul><li>Stop smoking &  heavy alcohol intake </li></ul></ul></ul><ul><ul><ul><li>Treat systemic hypertension </li></ul></ul></ul><ul><ul><ul><li>Avoid physical exertion </li></ul></ul></ul><ul><ul><ul><li>Avoid direct trauma </li></ul></ul></ul>
  28. 42. Proliferative Retinopathy
  29. 52. Diabetic Maculopathy <ul><li>Diabetic maculopathy </li></ul><ul><ul><li>Retinopathy in the macula area </li></ul></ul><ul><ul><li>Most common cause of visual loss in DM </li></ul></ul><ul><ul><li>Type ii>type I </li></ul></ul><ul><ul><li>Treatment based on ETDRS guidelines </li></ul></ul><ul><ul><li>Classified as </li></ul></ul><ul><ul><ul><li>Exudative/focal </li></ul></ul></ul><ul><ul><ul><li>Oedematous/diffuse </li></ul></ul></ul><ul><ul><ul><li>Ischaemic </li></ul></ul></ul><ul><ul><ul><li>Mixed </li></ul></ul></ul>
  30. 53. Diabetic Maculopathy <ul><li>Exudative </li></ul><ul><ul><li>Exudates in the macula area  circinate </li></ul></ul><ul><ul><li>Photocoagulation may be beneficial when VA>6/60 </li></ul></ul><ul><ul><li>Rx to centre of circinate ring or site of leakage </li></ul></ul><ul><li>Oedematous </li></ul><ul><ul><li>Macular oedema (ECF in Henle’s layer) </li></ul></ul><ul><ul><li>Rx with grid laser when VA>6/18 </li></ul></ul>
  31. 54. Diabetic Maculopathy <ul><li>Ischaemic </li></ul><ul><ul><li>FFA reveals capillary non-perfusion </li></ul></ul><ul><ul><li>No proven Rx </li></ul></ul><ul><ul><li>30% proceed to proliferative DR within 2yrs so eventually require PRP </li></ul></ul><ul><li>Mixed </li></ul><ul><ul><li>Exudates, oedema, ischaemia </li></ul></ul><ul><ul><li>Laser may be of benefit </li></ul></ul>
  32. 55. Diabetic Maculopathy <ul><li>ETDRS guidelines (CSME) </li></ul><ul><ul><li>Thickening of retina at or within 500  m of the fovea </li></ul></ul><ul><ul><li>Exudates at or within 500  m of the fovea, if thickening of adjacent retina </li></ul></ul><ul><ul><li>A zone or zones of retinal thickening 1 disc area or larger, any part of which is within 1 disc diameter of the fovea </li></ul></ul>
  33. 59. Advanced Diabetic Eye Disease <ul><li>Persistent vitreous haemorrhage </li></ul><ul><li>Tractional retinal detachment </li></ul><ul><li>Posterior hyaloid membrane </li></ul><ul><li>Neovascular glaucoma with rubeosis iridis </li></ul><ul><li>Patients will usually require vitrectomy, cutting of traction membranes, epiretinal membrane peeling </li></ul>

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