A physician's perspective on the importance of diagnosing, prognosing and treating diabetic retinopathy

1. Diabetic retinopathy
A Physician’s perspective
Department of Medicine
Himalayan Institute Hospital Trust
Dehradun, India

2. What we see??

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

4. Darkening cloud of DIABETES!!
438 MILLION
Current Burden DM Patients
288 million 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.


5. Diabetes burden – Tip of the iceberg?
Diabetic  Rate of Conversion of
Population ‘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%

6. 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/dl
glucose + 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

7. 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)

8. Microvascular complications of DM
Aldose Reductase forms Sorbitol -
Non enzymatic glycosylationGrowth factors
Changes in gene expression of
Advanced
Glycosylation
Pathogenesis
End products
Sorbitol
Pathway
HMP AGEs
CHRONIC Di-
Acyl-
HYPERGLYCEMIA Glycerol
Hexoseamine
Leads to activation of Protein Kinase C
pathway

9. Ocular complications in diabetes
are frequent, distressing and
destined to become one of the
challenging problems of the
future.
- Dr. Howard Root, 1935

10. Diabetic Retinopathy
DR 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 T1DM
Prevalence of Diabetic Retinopathy
Time since onset 5yrs 15yrs 20yrs
T1Dm 25% 60-80% 100%
T2Dm 60%

11. Challenges in the management of
Diabetic retinopathy

12. Secondary
Primary
Prevention of Diabetic Retinopathy
Prevention 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 Vitrectomy
toT2DM)
NOVEL THERAPIES

 Prevention of T1DM (under active Intravitreal Anti VEGF
clinical investigation) Bevacizumab (Avastin)
Anti CD3 Monoclonal Ab Inhibitors of PKC beta
Anti B lymphocyte Mono. Ab Aldose reductase inhibitors
GAD vaccine

13. Glycemic control
ORAL AGENTS used for treatment of Diabetes Mellitus
ORAL AGENT EXAMPLES
1. Biguanides Metformin
2. Alpha Glucosidase Inhibitors Acarbose, Miglitol
3. Dipeptidyl Peptidase IV Saxagliptin, Sitagliptin, Vildagliptin
Inhibitors
4. Insulin Sulfonylureas Glimepiride, Glipizide, Glyburide
Secretagogues
Non Repaglinide, Netaglinide
Sulfonylureas
5. Thiazolidinediones Rosiglitazone, Pioglitazone
6. Bile Acid sequestrants Colesevelam

14. PARENTERAL AGENTS used for treatment of DM
PARENTERAL AGENT EXAMPLES
1. 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%regular
2. GLP1 receptor Exenatide
agonists Liraglutide
3. Amylin agonists Pramlintide

15. Newer therapies for T2DM –
Emerging Therapies 1.Sodium glucose co transporter 2
For the Treatment inhibitors
Of Diabetes dapagliflozin, canagliflozin,
ASP1941, LX4211, and B110773
2.Glucokinase activators
piragliatin, compound
14, compound 6, R1511
3.11 beta - hydroxysteroid -
dehydrogenase -1 inhibitors
INCB13739
4.Interleukin 1 Receptor antagonist
Newer therapies for T1DM –
1. Whole Pancreas transplantation
2. Pancreatic Islet transplantation
3. Closed loop pumps for continous
insulin administration

16. 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

17. 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

18. 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 progression
47% reduction in moderate visual acuity loss independent of


19. Risk factors for Diabetic Retinopathy
It 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

20. 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

21. Diabetic Nephropathy and
DR
PDR
Gross Proteinuria Presence and Severity of DR
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

22. Hyperlipidemia and DR
Increased serum lipids
Extravasted lipids in Retina
Hard exudates
Vision loss
 Statins are well recognized to be of benefit in

23. 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)

24. 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

25. 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

26. 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.

27. Surgical Management - Overview
Focal Proliferative DR
Macular Photocoagulation
Proliferative DR
Non laser Edema
Pan RetinalPhotocoagulation
ProphylacticPhotocoagulation
Diagnosed Diabetic Retinopathy

28. Surgical Management of DR
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)

29. Early detection of diabetic retinopathy through regularly
scheduled ocular examination is critical
Type of diabetes mellitus Recommended initial eye Routine follow up*
examination
Type 1 5 years after onset Yearly
or during puberty
Type 2 At time of diagnosis Yearly
Pregnancy with Prior to pregnancy •Early in first
preexisting diabetes for counseling trimester
•Each trimester or
more frequently as
indicated
•6 weeks postpartum
*Abnormal findings will dictate more frequent follow-up examinations

30. 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

31. “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