A Physician’s perspective

Department of MedicineHimalayan Institute Hospital TrustDehradun, India

Diabetic retinopathy

What we see??

What they see??The vision of a patient with Diabetic retinopathy

Darkening cloud of DIABETES!!

438 MILLION DM Patients by 2030!!

6 deaths / minute attributed to Diabetic complications

Type1 Diabetics represent only 5-10% of the entire DM population

India - “Diabetes capital of the world” with approx. 32 million Diabetics

13-15% urban population in India is Diabetic.

Current Burden 288 million

Diabetes burden – Tip of the iceberg? Rate of Conversion of

‘PREDIABETES’ (Impaired Plasma Glucose) to DM is 10% annually.

Undiagnosed Diabetes in India –

Every year 12% increase in the Diabetic population in India

Undiagnosed Diabetes

Diabetic Population

Diagnosed DM

Undiagnosed DM

Study

6.1% 9.1% Chennai Urban Rural epidemiology study

9% 10.5% Amrita Diabetes and endocrine survey,

Kerala

1.9% 4.25% Kashmir valley study

American Diabetes Association, 2011Diagnostic criteria for Diabetes Mellitus

Normal Glucose tolerance

Impaired Glucose Tolerance

‘PREDIABETES’

Diabetes Mellitus

Fasting plasma glucose

<100mg/dl 100-125mg/dl >/=126mg/dl

2 hr plasma glucose during an OGTT**

<140mg/dl 140-199mg/dl >/=200mg/dl

Random Blood glucose + Symptoms

of diabetes*

>/= 200mg/dl

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 Normal Glucose Tolerance (Aus Diab study) 8% patients with Fasting Plasma Glucose (FPG) below the diagnostic threshold for DM (Diab. Prev. Prog)

Retinopathy at baseline had 2-fold risk of developing newly diagnosed diabetes.

A1C correlates better with likelihood of Retinopathy than FPG, and based on incidence of DR the diagnostic criteria for DM should be lowered to 5.3 to 5.5%(New Hoorn Study)

Microvascular complications of DM -

Pathogenesis

AGEs

Non enzymatic glycosylation

Aldose Reductase forms Sorbitol

Leads to activation of Protein Kinase C

HMP

Changes in gene expression of Growth factors

Advanced GlycosylationEnd products

SorbitolPathway

Di-Acyl-Glycerol

Hexoseaminepathway

CHRONICHYPERGLYCEMIA

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- 74 yrs (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 the time of Diabetes diagnosis (UKPDS)

Early detection and timely management can prevent upto 90% of vision loss from PDR

More frequent and severe ocular complications seen in T1DMPrevalence of Diabetic Retinopathy

Time since onset 5yrs 15yrs 20yrsT1Dm 25% 60-80% 100%T2Dm 60%

Challenges in the management of

Diabetic retinopathy

Prevention of Diabetic Retinopathy

Primary Secondary

MEDICAL MANAGEMENT Glycemic Control

Risk Factor ControlAspirin

SURGICAL MANAGEMENTPhotocoagulationVitrectomy

NOVEL THERAPIESIntravitreal Anti VEGFBevacizumab (Avastin)Inhibitors of PKC beta Aldose reductase inhibitors

Prevention of T2DMLifestyle Management

(58% reduction in overall DM incidence)ExerciseMedical Nutrition therapyMetformin

(31% reduction in conversion of IGT toT2DM)

Prevention of T1DM (under active clinical investigation)

Anti CD3 Monoclonal AbAnti B lymphocyte Mono. AbGAD vaccine

Glycemic controlORAL AGENTS used for treatment of Diabetes Mellitus

ORAL AGENT EXAMPLES

1. Biguanides Metformin

2. Alpha Glucosidase Inhibitors Acarbose, Miglitol

3. Dipeptidyl Peptidase IVInhibitors

Saxagliptin, Sitagliptin, Vildagliptin

4. InsulinSecretagogues

Sulfonylureas Glimepiride, Glipizide, Glyburide

Non Sulfonylureas

Repaglinide, Netaglinide

5. Thiazolidinediones Rosiglitazone, Pioglitazone

6. Bile Acid sequestrants Colesevelam

PARENTERAL AGENTS used for treatment of DMPARENTERAL AGENT EXAMPLES

1. Insulin Short Acting AspartGlulisineLisproRegular

Long Acting DetemirGlargineNPH

Insulin Combinations

75%Protamine lispro + 25%lispro70%Protamine aspart+25%aspart50%Protamine lispro+50%lispro70%NPH+30%regularExenatideLiraglutidePramlintide

Emerging TherapiesFor the TreatmentOf Diabetes

Newer therapies for T2DM –1.Sodium glucose co transporter 2inhibitors

dapagliflozin, canagliflozin, ASP1941, LX4211, and B110773

2.Glucokinase activatorspiragliatin, compound 14, compound 6, R1511

3.11 beta - hydroxysteroid - dehydrogenase -1 inhibitorsINCB13739

4.Interleukin 1 Receptor antagonist

Newer therapies for T1DM –1. Whole Pancreas transplantation2. Pancreatic Islet transplantation3. Closed loop pumps for continous

insulin administration

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 all microvascular 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 of microvascular 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 blindness

With respect to control of HTN , with intensive BP control – 34% reduction in risk of DR progression47% reduction in moderate visual acuity loss independent of

glycemic control

Risk factors for Diabetic RetinopathyIt is critical for optimal ocular health of

diabetic patients that several other systemic considerations be optimized.

1. Hypertension

2. Nephropathy

3. Hyperlipidemia

4. Pregnancy

5. Puberty

6. Anemia

7. Cataract surgery

8. Smoking

9. Drugs

Hypertension and DR

Diabetes often coexists with Hypertension

Uncontrolled 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 DR

Diastolic BP Progression of NPDR

Ace inhibitors and Beta blockers are widely accepted

as first line treatment for the same

Diabetic Nephropathy and DR

Gross Proteinuria Presence and Severity of DR

PDR

PROTEINURIA

Diabetic nephropathy accelerates the progression of retinopathy, especially macular oedema.

The visual prognosis is often better if the nephropathy is treated by renal transplantation rather than by dialysis

The presence of Retinopathy itself suggests the need 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 reduction of diabetic complications.

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 severe retinoathy, in patients with preexisting

DR

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 - Overview

Diagnosed Diabetic Retinopathy

Non Proliferative DRProphylactic PhotocoagulationProliferative DRPan Retinal PhotocoagulationMacular EdemaFocal laser Photocoagulation

Dramatic 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), and

3. Diabetic Retinopathy Vitrectomy Study (DRVS)

Dedicated efforts by researchers have reduced the 5-year risk of severe visual loss from PDR to less than 2%

Surgical Management of DR

Type of diabetes mellitus Recommended initial eye examination

Routine follow up*

Type 1 5 years after onset or during puberty

      Yearly

Type 2 At time of diagnosis       Yearly

Pregnancy with preexisting diabetes

Prior to pregnancy for counseling

•Early in first trimester •Each trimester or more frequently as indicated •6 weeks postpartum

*Abnormal findings will dictate more frequent follow-up examinations

Early detection of diabetic retinopathy through regularly scheduled ocular examination is critical

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

TREAT PROMPTLY

Management of DR requires a close interaction between the patient and

a diverse healthcare team

“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 AdministrationLow altitude airshow license