Non Proliferative Diabetic Retinopathy

Brief discussion on NPDR

1. Non Proliferative Diabetic Retinopathy Dr Md Ferdous Islam Trainee Offr (FCPS Part –II) Dept of Ophthalmology CMH, Dhaka

2. RETINA RPE LRC ELM ONL OPL INL IPL GCL NFL ILM

3. RETINAL CIRCULATION CRA intima internal elastic lamina Media Tunica adventitia Retinal Arterioles Discontinuous internal elastic lamina Small venules larger then capillaries but similar structure Larger venules Veins C apillaries C apill

4. BARRIERS IN EYE

5. PREVALENCE The total number of people with diabetes is projected to rise from 285 million in 2010 to 439 million in 2030 . A round 40 % of patients with diabetes have signs of diabetic retinopathy 10% having sight threatening disease 5-10% of diabetic population develops Proliferative DR IDDM > NIDDM

6. RISK FACTORS DURATION OF DIABETES POOR GLYCAEMIC CONTROL PREGNANCY HYPERTENSION NEPHROPATHY SMOKING SEX : M > F HYPERLIPIDEMIA (TG, LDL) CATARACT SURGERY OBESITY ANEMIA (LEADING TO HYPOXIA ) ALCOHOL

7. PATHOGENESIS It is a microangiopathy caused by effect of hyperglycemia on small blood vessels leading to - Retinal capillary occlusion Retinal capillary leakage

8. CELLULAR DAMAGE Caused by- • Sorbitol accumulation (Glucose Sorbitol ) • Free radical mediated oxidative stress • Accumulation of advanced glycation end products (AGEs) • Excessive activation of protein kinase C and diacyl glycerol

9. CAPILLAROPATHY Characterized by- • Death of pericytes • Thickening of capillary basement membrane ( sorbitol pathway) • Loss of vascular smooth muscle cells (capillary acellularity ) • Endothelial proliferation • Abnormalities of RBCs (leading to defective oxygen transport) and WBCs • Increased platelet stickiness and adhesion • Increased plasma viscosity • Defective fibrinolysis and prolonged clot lysis time

10. NEOVASCULARISATION Caused by capillary non-perfusion leading to retinal hypoxia. • New vessel growth is thought to be caused by an imbalance between angiogenic and anti- angiogenic factors in an attempt to revascularise the hypoxic retina. IRMA ( Intraretinal microvascular abnormalities) are shunts that run between the retina from arterioles to venules .

11. OTHER DESCRIPTIVE CATEGORIES BACKGROUND DIABETIC RETINOPATHY (BDR) It’s the earliest phase of DR. Characterised by microaneurysms , dot and blot hemorrhages and exudates . DIABETIC MACULOPATHY Refers to presence of any retinopathy at the macula. PRE-PROLIFERATIVE DIABETIC RETINOPATHY (PPDR) Cotton wool spots, venous changes, IRMA and deep retinal hemorrhages. DIABETIC PAPILLOPATHY It is a form of optic neuropathy seen in young type I diabetics. It is unrelated to glycemic control or any other known feature of diabetes

12. VARIOUS CLASSIFICATION SYSTEM Grading of NPDR according to- International / American Academy of Ophthalmologists (AAO) classification • Mild • Moderate • Severe National Screening Committee – United Kingdom (NSC-UK) classification • Background (Level R1) • Pre-proliferative (Level R2) Scottish Diabetic Retinopathy Grading Scheme (SDRGS) • Mild background (Level R1) • Moderate background (Level R2) • Severe background (Level R3)

13. SYMPTOMS Asymptomatic in early stages of the disease. S ymptoms may include- • Blurred vision • Floaters and flashes • Distorted vision • Dark areas in the vision • Poor night vision • Impaired color vision • Partial or total loss of vision

14. SIGNS OF DIABETIC RETINOPATHY

15. MICROANEURYSMS •Focal saccular dilatations of the capillary wall. •Size = 20-100 μ m • Ophthalmoscopically visible (better on red free illumination) if larger than 30 μm . Smaller ones can be visualized on angiography. •Maximally seen in supero -temporal quadrant. •Caused by- -focal dilatation of the capillary wall where pericytes are absent, or -by fusion of two arms of a capillary loop • Hyperfluorescent on fluorescein angiography

16. RETINAL HAEMORRHAGES They may be small and round (dot and blot) or flame shaped depending on their depth within the retinal layers. Retinal hemorrhage spreads along the line of least resistance, constrained by the local anatomy of the particular layer from which it arises. Therefore a superficial bleed will track parallel to the nerve fiber layer resulting in a longitudinal spread becoming flame shaped . However deeper in the retina, since the layers are vertically oriented it results in circumscribed, round hemorrhages (dot and blot).

17. EXUDATES • Termed ‘hard’ exudates, are caused by chronic localised retinal oedema and develop at the junction of normal and oedematous retina. • Composed of lipoprotein and lipid-filled macrophages and are exuded from microaneurysms • Located mainly within the outer plexiform layer. • Hypofluorescent on FA

18. DIABETIC MACULAR OEDEMA Maculopathy is the most common cause of visual impairment in DM patients, particularly type II. • According to Wisconsin (WESDR ), the prevalence rate of macular oedema is 10 % in the diabetic population as a whole. • Oedema is due to capillary leakage and the fluid is initially located between the outer plexiform and inner nuclear layers. Later it may also involve the inner plexiform and nerve fibre layers. • With further accumulation of fluid the fovea assumes a cystoid appearance: Cystoid Macular Oedema (CMO). • Hyperfluorescent on FA. • Best detected by slit-lamp biomicroscopy and stereoscopic fundus photography.

19. COTTON WOOL SPOTS • Described by Mcleod D in 1975 • The term ‘soft exudates’ is a misnomer because cotton wool spots are not exudates at all, but an accumulation of intracellular fluid and organelles as a result of local ischemia • Result from interruption of axoplasmic flow in the nerve fiber layer thereby causing a gross, localized axonal distention known as ‘ cytoid bodies’. • Hypofluorescent on FA • Once the cotton wool spot resolves, the nerve fiber and ganglion cells at that spot atrophy, giving rise to ‘depression sign’. • Other causes - hypertension , retinal vein occlusion , retinal vasculitis , anemia, leukemia

20. VENOUS CHANGES • Generalised dilatation and tortuosity • ‘ Looping ’ • ‘ Beading ’ • ‘Sausage-like’ segmentation IRMA Intraretinal microvascular abnormalities are arteriolar venular shunts that run from retinal arterioles to venules , thus bypassing the capillary bed • Hyperfluorescent on FA

21. INVESTIGATIONS CFP FFA OCT

22. TREATMENT General Patient education DM control Control and treatment of other risk factors

23. TREATMENT contd.. Specific No ocular intervention is warrented , until disease reaches the proliferative stage. As proliferative stage arouses , the treatment is carried out through various measures like…. 1. Pan retinal Laser photocoagulation 2. Intra- vitreal anti VEGF injections 3 . Intra vitreal triamcinolone 4.PPV

24. Primary prevention Strict glycemic control Blood pressure control Secondary prevention Annual eye exams Tertiary prevention Retinal Laser photocoagulation Vitrectomy

25. TREATMENT contd.. Once DR threatens vision treatments can include Laser therapy to seal leaking blood vessels (focal laser) Laser therapy to reduce retinal oxygen demand (scatter laser) Surgical removal of blood from the eye ( vitrectomy )

26. TREATMENT contd.. The use of anti-vascular endothelial growth factor has been shown to be useful in the treatment of DR Anti-VEGF antibody treatment appears to be useful for both macular edema and proliferative retinopathy

27. RECOMMENDED EYE EXAM SCHEDULE

28. Thank you