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What they see??The vision of a patient with Diabetic retinopathy
Darkening cloud of DIABETES!! 438 MILLION Current Burden DM Patients 288 million by 2030!!6 deaths / minute attributed to Diabetic complicationsType1 Diabetics represent only 5-10% of the entire DM population India - “Diabetes capital of the world” with approx. 32 millionDiabetics13-15% urban population in India is Diabetic.
Diabetes burden – Tip of the iceberg?Diabetic Rate of Conversion ofPopulation ‘PREDIABETES’ (Impaired Plasma Glucose) to DM is 10% annually. Diagnosed Undiagnosed DM Diabetes Study Undiagnosed DM in India – 6.1% Chennai Urban Rural Undiagnosed 9.1% epidemiology study Diabetes 9% 10.5% Amrita Diabetes and endocrine survey, Kerala 1.9% Kashmir valley study 4.25%
American Diabetes Association, 2011 Diagnostic criteria for Diabetes Mellitus Normal Glucose Impaired Glucose Diabetes tolerance Tolerance „PREDIABETES‟ Mellitus Fasting plasma <100mg/dl 100-125mg/dl >/=126mg/dl glucose 2 hr plasma glucose <140mg/dl 140-199mg/dl >/=200mg/dl during an OGTT** Random Blood >/= 200mg/dlglucose + Symptoms of diabetes* A1C <5.6% 5.7-6.4% >/= 6.5%*polyuria, polydispsia, weight loss**after a glucose load of 75g anhydrous glucose dissolved in water
Implications of the new diagnostic criteria A1C 6.5% Sensitivity 99% Specificity 24%Signs of retinopathy seen in upto 10% individuals with NormalGlucose Tolerance (Aus Diab study) 8% patients with Fasting PlasmaGlucose (FPG) below the diagnostic threshold for DM (Diab. Prev. Prog)Retinopathy at baseline had 2-fold risk of developing newlydiagnosed diabetes.A1C correlates better with likelihood of Retinopathy than FPG, andbased on incidence of DR the diagnostic criteria for DM should belowered to 5.3 to 5.5%(New Hoorn Study)
Microvascular complications of DMAldose Reductase forms Sorbitol -Non enzymatic glycosylationGrowth factorsChanges in gene expression of Advanced Glycosylation Pathogenesis End products Sorbitol Pathway HMP AGEsCHRONIC Di- Acyl-HYPERGLYCEMIA Glycerol HexoseamineLeads to activation of Protein Kinase C pathway
Ocular complications in diabetes are frequent, distressing and destined to become one of the challenging problems of the future. - Dr. Howard Root, 1935
Diabetic RetinopathyDR is leading cause of legal blindness among patients aged 20- 74yrs (CDC-US,2011)20% patients of DM had retinopathy at diagnosis(US Report),35 % of female and 39 % male diabetics have some level of DR at thetime of Diabetes diagnosis (UKPDS) Early detection and timely management can prevent upto 90% ofvision loss from PDR More frequent and severe ocular complications seen in T1DM Prevalence of Diabetic RetinopathyTime since onset 5yrs 15yrs 20yrsT1Dm 25% 60-80% 100%T2Dm 60%
Challenges in the management of Diabetic retinopathy
SecondaryPrimaryPrevention of Diabetic RetinopathyPrevention of T2DM MEDICAL MANAGEMENT Lifestyle Management Glycemic Control (58% reduction in overall DM incidence) Risk Factor Control Exercise Aspirin Medical Nutrition therapy SURGICAL MANAGEMENT Metformin Photocoagulation(31% reduction in conversion of IGT VitrectomytoT2DM) NOVEL THERAPIES Prevention of T1DM (under active Intravitreal Anti VEGFclinical investigation) Bevacizumab (Avastin) Anti CD3 Monoclonal Ab Inhibitors of PKC beta Anti B lymphocyte Mono. Ab Aldose reductase inhibitors GAD vaccine
Glycemic control ORAL AGENTS used for treatment of Diabetes Mellitus ORAL AGENT EXAMPLES1. Biguanides Metformin2. Alpha Glucosidase Inhibitors Acarbose, Miglitol3. Dipeptidyl Peptidase IV Saxagliptin, Sitagliptin, Vildagliptin Inhibitors4. Insulin Sulfonylureas Glimepiride, Glipizide, Glyburide Secretagogues Non Repaglinide, Netaglinide Sulfonylureas5. Thiazolidinediones Rosiglitazone, Pioglitazone6. Bile Acid sequestrants Colesevelam
PARENTERAL AGENTS used for treatment of DMPARENTERAL AGENT EXAMPLES1. Insulin Short Acting Aspart Glulisine Lispro Regular Long Acting Detemir Glargine NPH Insulin 75%Protamine lispro + 25%lispro Combinations 70%Protamine aspart+25%aspart 50%Protamine lispro+50%lispro 70%NPH+30%regular2. GLP1 receptor Exenatideagonists Liraglutide3. Amylin agonists Pramlintide
Lack of appropriate glycemic control is a significant risk factor for the onset and progression of diabetic retinopathy. Two of the landmark trials with respect to glycemic control in DR were – DCCT and UKPDS
The Diabetes Control and Complications trial (DCCT)Intensive Glycemic control was associated with a decrease in allmicrovascular complications 76% in the risk of onset of Diabetic Retinopathy 63% in the progression of pre existing Diabetic Retinopathy 56% in the need for laser surgery predicted gain of 7.7 addditional years of vision
The United Kingdom Prospective Diabetes Study (UKPDS)In the Intensive Glycemic control group -For every 1% in A1C 35%approx. in the incidence ofmicrovascular complications 17% in the progression of DR 29% in the need for laser photocoagulation 23% in the development of Vitreous Hemorrhage. 16% in incidence of legal blindnessWith respect to control of HTN , with intensive BP control – 34% reduction in risk of DR progression47% reduction in moderate visual acuity loss independent of
Risk factors for Diabetic RetinopathyIt is critical for optimal ocular health ofdiabetic patients that several other systemic considerations be optimized.1. Hypertension2. Nephropathy3. Hyperlipidemia4. Pregnancy5. Puberty6. Anemia
Hypertension and DRDiabetes often coexists with HypertensionUncontrolled Hypertension is related to Increased development of DR Increased progression of DR Increased risk of developing Proliferative DR Increased incidence of diffuse macular edema(EUCLID, UKPDS)Acc. to Wisconsin study –Systolic BP Onset of Non Proliferative DRDiastolic BP Progression of NPDR
Diabetic Nephropathy andDR PDRGross Proteinuria Presence and Severity of DR PROTEINURIADiabetic nephropathy accelerates theprogression of retinopathy, especially macularoedema.The visual prognosis is often better if thenephropathy is treated by renal transplantationrather than by dialysisThe presence of Retinopathy itself suggests theneed for renal evaluation
Hyperlipidemia and DR Increased serum lipids Extravasted lipids in Retina Hard exudates Vision loss Statins are well recognized to be of benefit in
Pregnancy and DR Pregnancy may accelerate the progression of diabetic retinopathy by 1.63 fold (DCCT) Women who begin a pregnancy with no retinopathy, the risk of developing diabetic retinopathy is about 10%. Women who begin pregnancy with poorly controlled diabetes and who are suddenly brought under strict control frequently have severe deterioration of their retinopathy and do not always recover after delivery . (Diabetes in Early pregnancy Study)
Cataract Surgery and DR Cataract surgery may lead to progression of pre-existing macular oedema and proliferative diabetic retinopathy. Cataracts may impede fundoscopy and therefore interfere with the treatment of diabetic retinopathy. If possible, diabetic retinopathy should be treated prior to cataract surgery
Anemia and DR Low hematocrit is related to the dvelopment of high risk PDR and severe vision loss (ETDRS) In a cross sectional study of 1691 patients with, Hb <12g/dl Showed a 2-fold increase in the risk of development of retinopathy 5-fold increase in the risk of development of
Puberty and DR The onset of vision-threatening retinopathy is rare in children prior to puberty, regardless of the duration of diabetes Significant retinopathy can arise within 6 years of disease if diabetes is diagnosed between the ages of 10 and 30 years.
Surgical Management of DRDramatic strides have been made in treating diabetic retinopathy and macular edema through the effective use of scatter (panretinal) laser and other surgical techniques.The value of these techniques has received strong support from the findings of three major nationwide, randomized, and controlled clinical trials in the United States:1. Diabetic Retinopathy Study (DRS)2. Early Treatment Diabetic Retinopathy Study (ETDRS), and3. Diabetic Retinopathy Vitrectomy Study (DRVS)
Early detection of diabetic retinopathy through regularlyscheduled ocular examination is criticalType of diabetes mellitus Recommended initial eye Routine follow up* examinationType 1 5 years after onset Yearly or during pubertyType 2 At time of diagnosis YearlyPregnancy with Prior to pregnancy •Early in firstpreexisting diabetes for counseling trimester •Each trimester or more frequently as indicated •6 weeks postpartum*Abnormal findings will dictate more frequent follow-up examinations
Conclusions EXERCISE CAUTION Diabetic Retinpathy at the time of diagnosis Assymptomatic, with good visual acuity initiate Education, Medical and Ocular follow up MONITOR CAREFULLY Appropriate observation of level of ocular disease Prompt laser, other interventions (when indicated) Patients retain excellent vision
“Diabetes can be controlled and does not have to keep people from achieving their dreams” - Michael Hunter - World’s only insulin-dependent air show stunt pilot -First diabetic person to receive the Federal Aviation Administration Low altitude airshow license