MANAGEMENTOF

DIABETIC RETINOPATHY

1

FFA (fundus fluorescein angiography)

• A technique for examining the circulation of the retina and choroid using a fluorescent dye and a specialized camera.

• Fluorescein enters the ocular circulation from the internal carotid artery via the ophthalmic artery

Causes of hyperfluorescence:• leaking defects (i.e. capillary leakage, aneurysm, neovascularization)• pooling defects• staining• transmission (filling) defects• abnormal vasculatureCauses of hypofluorescence:• blocking defect (i.e. blood)• filling defect (capillary blockage)

2

3

4

Colour fundus picture and fluorescein angiography (FA) picture of an eye with more advanced proliferative diabetic retinopathy and mild absorbing vitreous haemorrhage (small arrows), neurovascularisation of the disk (large arrows) and block retinal vessels due to endothelial cell pathology (vertical arrows)

• Diabetic tractional papillopathy

5

OCT (optical coherence tomography)

• an optical signal acquisition and processing method• The use of relatively long wavelength light allows it to penetrate into the

scattering medium , near infra red light.• It captures micrometer-resolution, three-dimensional images from within

optical scattering media• OCT is highly sensitive in detecting DME.

6

•

7

• Pre and post intravitreal avastin

8

Control of diabetes and associated diseases

• Glycemic control: HbA1c : <6% excellent control 6-7% good control OHA or Insulin to control blood sugars

• Blood pressure control: tight blood pressure control <140/85mmHg

• Lipid control: Hyperlipidemia increase incidence of Macular Edema.Statins – cholestrol reducing agents.

• Correction of Anemia: Anemia causes hypoxia and contribute to already deranged metabolism of DR

• Nephropathy :Untreated retinopathy deteriorates together with renal function due to fluid retention and worsening of hypertension.

Albuminurea, decreasing GRF , increasing BP 9

DR treatment guidelines(as per AAO guidelines)

10

11

12

13

Photocoagulation• CW green argon laser (514.5nm): most commonly used, suitable for photocoagulation of RPE , choroidal and blood vessels. It is readily absorbed by melanin granules. Coagulates from choriocapillary to inner nuclear layer

• Frequency doubles Nd:YAG (neodyminum-doped Yttrium aluminium garnet) laser ( green Nd:YAG laser) (532nm). Highly absorbed by melanin and hemoglobin.

Coagulates from choriocapillary to outer nuclear layer. Uses least energy and shows least damage to macula.• Krypton red laser: (647nm). Absorbed only by melanin not by hemoglobin and xanthophyllin Coagulates deeper structures of RPE.

14

• Diode laser : (810nm)(blue laser) most important semi conductor laser. Poorly absorbed by hemoglobin, but it is a effective in reducing macular edema but causes retinal damage. It can be painful to the patient if the intensity is not reduced due to its deeper penetration.

15

Yellow laser photocoagulation• The 568-586nm (577nm) yellow wavelength has high absorption

by oxyhemoglobin so it is effective when treating vascular structures in the eye.

• It is generated by Krypton or dye lasers.• Yellow light results in less thermal spread, functional damage

and scar enlargement. • With a high oxyhaemoglobin/melanin absorption ratio,

treatment better targets deep vascular structures and not pigmented tissue in the outer retina, allowing safer treatment in the macular region.

• The yellow wavelength shows negligible absorption by macular xanthophylls, the main pigment present in the macula, increasing safety margins for macular treatment.

• Good lesion visibility

16

17

18

Mechanism

Specific λ absorbed by chromophores

(Usually melanin at RPE level)

HEAT (500-1000 C)

100 C rise Breaking of 30 & 40 bonds

Irreversible denaturation

Loss of biologic activity of

various enzymes & cell membrane moieties

19

Modes of delivery

• Slit-Lamp• Mirror arm apparatus• Use of lenses

• Indirect Ophthalmoscopy• Peripheral lesions• Hazy media

• Endoprobe• Trans-Scleral

20

LENS used in photocoagulation

21

22

Goldmann 3-mirror lens

Pan Retinal Photocoagulation(PRP)

23

Indications of PRP

• Definite :-

-PDR with high risk characteristics

-NVI, NVA• Fairly definite :-

-PDR without ischemia• Possible :-

-Very severe NPDR(4-2-1 rule)

-Patients with PDR in other eye

24

ETDRS protocol for technique

• Full dilatation of pupils and anaesthetized with topical agent. • Spot size – 200 - 500 um• Duration – 0.05 – 0.10 seconds• Number – 1200 -1600 spots . 2200 spots are also reported.• Extent – 1 DD nasal to the disc, just outside the temporal

arcades and 4 DD temporal to the fovea, up to equator and beyond

• Power: around 200mW• Should be placed 1 burn apart.• In 2-3 sessions, first inferior• Need for additional t/t at 45-60days

25

26

Pre and Post PRP-patient advice

Pre PRP• More effective at preserving than

increasing the vision• Reduces the risk of vision loss by

50%• But may induce moderate vision

loss, decreased accomodation, the visual field defects, nyctalopia, color and contrast sensitivity reduction

• Re t/t may be needed• Follow up is must • Optimization of medical control of

DM, HTN and anemia are essential

• A handout may be effective in patient’s education

Post PRP• Topical cycloplegics and

steroids 3-4 times x 3 days• Tab. Acetazolamide (250mg) if

IOP spike is observed.• Post laser follow up: 3 follow

up at 3-4 week interval and subsequent after 3-4 months.

• Avoid sneezing , coughing, lifting heavy weight, sudden jerky movements.

• Propped up position.• Avoid medication containing

epinephrine and ephedrine.27

Complications

• Excessive response to treatment

-Visual field loss -CNVM/subretinal fibrosis -Chorioretinal atrophy -Hemorrhage -Exudative retinal detachment -Choroidal effusion -Increased macular edema -Raised IOP:angle closure glaucoma

• Wrong target -Burns to cornea, iris, lens -Foveal burns -Intraocular lens pits -ciliary nerve at 3 and 9 position

• Side Effects -Nyctalopia(night blindness) -Scotoma

28

Grid Photocoagulation

29

Indications of grid photocoagulation

• All areas of thickened retina showing diffuse florescence leakage or capillary non-perfusion are treated.

• Any Avascular zone other than foveal avascular zone.• Previously untreated areas of diffuse leakage , >500micron

from the macular center.• CSME / DME

30

Location of Grid photcoagulation

• Extends from arcade to arcade

• 500 to 3000 micron superior, inferior and nasal from the macular center

• 500 to 3500 micron temporal from the macular center.

31

Parameters of grid photocoagulation

• Full dilatation of pupils and anaesthetized with topical agent. • Spot size – 50-200 um• Duration – 0.10 seconds• Number – 100-200 spots • Power: 50-100mW , increase by 10-20mW to achieve light

burn intensity.• Should be placed 1 burn apart.• In 1 session• TO AVOID: -direct burns to microanurysms -overlapping burns to macullopapilla bundles -300 micron within fovea (to prevent foveal burns)

32

Focal photocoagulation

33

Indications of focal photocoagulation

in DME• Focal leakage or discrete points of retinal hyperflorescence ≥500 micron from the macular center , causing hard exudates and retinal thickening.• Treating focal Microaneurysms and IntraRetinal Microvascular Abnormalities (IRMA).• Focal lesions 300-500 micron from the macular center causing hard exudates.

34

Location of focal photocoagulation

• 500 micron away from the macular center• 500 micron temporal to the disc margin and within 3000 micron (2disc diameter) from the macular center• Focal lesions with 300-500 micron from the macular center can also be treated.

35

Parameters of focal photocoagulation

• Full dilatation of pupils and anaesthetized with topical agent. • Spot size – 50-100 um• Duration – 0.05-0.10 seconds• Number – 100-200 spots • Power: 100-400mW , sufficient for intensity grade 3• Should be placed 1 burn apart.• In 1 session• TO AVOID: -direct burns to microanurysms -overlapping burns to macullopapilla bundles -300 micron within fovea (to prevent foveal burns)

36

Focal and grid photocoagulation

• Post laser advice is similar to PRP• Post laser follow up:1. 1st follow up :4 weeks after laser.2. 2nd follow up :3-4 months after laser. FFA to be repeated.3. 3rd follow up : if retreatment is necessary.4. Regular 6 monthly follow up to track the progress.

Complications: Accidental foveal burn , increase in macular edema ,Secondary chorioretinal neovascularization( due to rupture of bruch’smembrane following small spot size and higher internsity)Paracentral scotoma , impairment of colour vision and contrast sensitivity.

37

Modified grid photocoagulation

• Direct photocoagulation of visible microaneurysm• a grid pattern to fill in the rest of the extent of the edema

38

PASCAL (pattern scan laser)ADVANTAGES• Very fast and more efficient than standard single shot• Improved comfort: Patients are likely to experience less discomfort and

therefore have more tolerance for the procedure. Full 360 degrees PRP can be done in a single sitting

• Advanced precision: Macular Grid treatment provides an improved margin of safety and dosimetry control when compared with single shot treatments. Unlike the irregular pattern placement obtained in single shot photocoagulation, PASCAL delivers even pattern burns.

• Ease of use: The PASCAL method of photocoagulation is similar to single shot photocoagulation, therefore physician training is minimal.

39

PASCAL MULTISPOTPHOTOCOAGULATOR

40

Intravitreal injectionsSTEROIDS• Triamcinolone acetonide

Sustained-release.

MOA:• Stabilize retinal vascular

endothelial tight junctions, which decreases permeability

• Ability to inhibit arachidonic acid pathway

Inhibits inflammatory mediators and VEGF

• Transient increase in IOP may favourably alter the haemodynamics within the eye

Anti-VEGF• Macugen (Pegaptanib

sodium)• Selective VEGF

blocker• Lucentis (Ranibizumab)

• More efficacious• Avastin (Bevacizumab)

• Cheaper alternative• Non - selective

• SIRNA (Bevaciranib)• VEGF-TRAP 41

Anti-VEGF

Role of VEGF:• Upregulation of VEGF • Breakdown of blood retinal

barrier • Increased vascular

permeability • Retinal oedema, • Endothelial cell growth & • Neovascularisation

Avastin (most commonly used)• Anti VEGFs block the already

released VEGF & its effects • PRP removes the incentive for

VEGF formation thus suppressing their release

• speed and degree of neovascular regression in combination treatment is much faster than PRP alone

• very rapid, dramatic effect seen with Avastin can be maintained long term with a proven effect of PRP

• minimizes the risk for exudative complications such as macular edema

42

Before intravitreal Avastin

30 days after intravitreal Avastin

43

Steroids - Intravitreal

Methodology• Dose – 4mg / 0.1 ml • Tuberculin syringe used• Pars plana entry (3.5-

4.0mm)• Directed towards mid-

vitreous• Slow injection• Transient pressure at site• Head-end elevation for 1 day• IOP monitoring

Contraindications• Local infections (dacryocystitis,

blephritis)• Glaucoma patients• Steroid responders• Systemically uncontrolled

diabetes

Complications• Increase in IOP – 19 to 50%• Dispersal leading to visual

axis blockage• Endophthalmitis• RD• Vitreous haemorrhage• Cataract

44

SteroidsIV STEROIDS• Limitations of laser Rx for

DME1. MA near foveal centre 2. Development of focal

scotomas & choroidal neovascularisation

3. Development of refractory ME

• Anti-inflamatory action• Indication of IV

triamcinolone1. Chronic ME 2. Multiple failed laser PC Rx

(Refractory) 3. Edema with very large

cystoid spaces

STEROID DEPOT PREPARATION • Retisert (Bousch & Lomb) –

Intravitreal depot Fluocinolone (0.5%).Releases for 3 yrs

In early clinical trials – 49 % had resolution of edema.

• Posurdex (Allergen) – Dexamethasone (700mcg %) .

• No FDA approval .• Side effects – rise in

IOP ,cataract, vit. hemorrhage.

45

Other pharmacological agents

Aldose reductase inhibitors

Sorbinil• Generates sorbitol during

hyperglycemia• useful in preventing DR if

administered from the onset of diabetes

• work is still needed to examine the therapeutic effect

• it has not been tested in humans

Protein kinase C inhibitorsPKC-beta has shown to increase VEGF (one of the most important signaling component for VEGF) , oxidative stress thus contributing to vascular disruption.

Ruboxistaurin(8,16,32mg/day)• In clinical trials • More effective when give at an

earlier stage of disease progression.

46

Vitreo-retinal surgeries in the management of DR

47

THANK YOU!!!

48