Diabetic Retinopathy

Definition

• Progressive dysfunction of the retinal vasculature caused by chronic hyperglycemia

Epidemiology• Type I (10% of pts)

– Duration calculated from onset of puberty

upto 5 years– no retinopathy 5-10 years – 27% 10-20 years – 71%-90% 20-30 years - 95% have DR out of which 30-50% have PDR >30 years – 60% have PDR

• Type II (90% of pts)Klein et al (WESDR)

Duration of DM

Prevalence

>10yrs 67%,10%PDR

Yanko et al

Duration of DM

Prevalence

11-13yrs,>11yrs

23%, 3%PDR

>16yrs 60%

Risk Factors1. Duration of diabetes

• Obesity• Hyperlipidaemia

2. Poor metabolic control

3. Pregnancy

4. Hypertension

5. Renal disease

6. Other

• Smoking• Anaemia

PathogenesisCapillaropathy

•Loss of pericytes•Thickening of basement membrane•Damage and proliferation of endothelial cells

Haematological changes

•Deformation of erythrocytes and rouleaux formation•Activation of white blood cells•Increased platelet stickiness•Increased plasma viscosity

Microvascular leakage Microvascular occlusion

Opening of AV shunts Neovascularization

Capillary non-perfusion(retinal hypoxia)Retinal edema,

Hard exudates

Pathogenesis of diabetic retinopathy

Consequences of retinal ischaemia

Consequences of chronic leakage

Anatomical factors for the macular predisposition

Fibre layer of Henle is thickest at the macula- can absorb large amount of water

Avascularity of the central area limits absorption of fluid

Thinness of fovea with its attenuated basal lamina provides little protection against inflammatory exudates and toxic products that pass from vitreous

Location of lesions in background diabetic retinopathy

ETDRS Classification - NPDR• Mild NPDR At least one microaneurysm < Standard photograph No. 2A No other retinal lesion or abnormality associated with diabetes is present.

• Moderate NPDR Haemorrhages/microaneurysms > Standard photograph No. 2A SE (CWS), VB, or IRMAs are definitely present

• Severe NPDR (4-2-1 rule) H/Ma > standard photograph No. 2A in all four quadrants VB > standard photograph No. 6A in two or more quadrants IRMA > standard photograph No. 8A in at least one quadrant

• Very Severe NPDR Any two or more of criteria of Severe NPDR

Standard photograph No. 2A of the Modified Airlie House Classification of Diabetic Retinopathy

demonstrates a moderate degree of hemorrhage or microaneurysms

Venous Changes

• Venous caliber abnormalities are indicators of severe retinal hypoxia. These abnormalities can be venous dilatation, venous beading, or loop formation.

• There are often large areas of nonperfusion adjacent to these veins.

Standard photograph No. 6A of the Modified Airlie House Classification of Diabetic

Retinopathy demonstrates venous beading

Intraretinal microvascular abnormalities (IRMA)

IRMAs represent “shunts” through areas of nonperfusion. IRMAs – no intense leakage, do not cross major vessels,

Standard photograph No. 8A of the Modified Airlie House Classification of

Diabetic Retinopathy demonstrates IRMA

ETDRS Classification - PDR

Composed of: [1] NVD or NVE [2] preretinal or vitreous hemorrhage, [3] fibrous tissue proliferation

• Early PDR New vessels

• High-risk PDR NVD >1/3-1/2 disc area or

NVD and vitreous or preretinal hemorrhage orNVE >1/2 disc area and preretinal or vitreous hemorrhage

High risk PDR

NVD 1/4-1/3 disc in area Less extensive NVD + haemorrhage

NVE > 1/2 disc in area + haemorrhage

High Risk PDR

Standard photograph No. 10A of the Modified Airlie House Classification of Diabetic Retinopathy demonstrates NVD covering approximately

one-quarter to one-third of the disc area

Standard photograph No. 7 of the Modified Airlie House Classification of Diabetic

Retinopathy demonstrates NVE greater than one-half disc diameter with a fresh hemorrhage present

International Clinical Diabetic Retinopathy (DR) Disease Severity Scale

Proposed Disease Severity Level Findings Observable With Dilated Ophthalmoscopy

No apparent DR No abnormalitiesMild nonproliferative DR Microaneurysms only

Moderate nonproliferative DR More than "mild" but less than "severe"

Severe nonproliferative DR

Any of the following:20 or more intraretinal hemorrhages in 4 quadrantsDefinite venous beading in 2 or more quadrantsProminent IRMA in 1 or more quadrantsand no neovascularization

Proliferative DR1 or more of the following:Definite neovascularizationPreretinal or vitreous hemorrhage

• Focal Maculopathy Well-circumscribed retinal

thickening associated with complete or incomplete rings of hard exudates

FFA – Focal, late hyperfluorescence due to leakage and good macular perfusion

• Diffuse maculopathy Diffuse retinal thickening ±

cystoid changes FFA - Diffuse

hyperfluorescence ± central flower petal pattern

• Ischaemic maculopathy Signs of NPDR but macula may

appear normal FFA – capillar non-perfusion at

the fovea and posterior pole and periphery

Diabetic maculopathy

Clinically significant macular edema

4 distinct patterns of DME has been described based on OCT1,2

Diffuse or spongy retinal thickening

Cystoid macular edema

Serous retinal detachment

Vitreomacular traction

II) Classification of diabetic macular edema

1. Otani et al. Patterns of diabetic macular edema with OCT. Am J Ophthalmol 1999; 127: 688-693

2. Kim et al. OCT patterns of diabetic macular edema. Am J Ophthalmol 2006: 142: 405-412

III) International Clinical Diabetic Macular Edema (DME) Disease Severity Scale

Proposed Disease Severity Level Findings on Dilated Ophthalmoscopy

DME absent No retinal thickening or hard exudates present in posterior pole

DME present Some retinal thickening or hard exudates present in posterior pole

If DME is present, it can be categorized as follows:

Proposed Disease Severity Level Findings Observable on Dilated Ophthalmoscopy

Mild DME Some retinal thickening or hard exudates in posterior polebut distant from the center of the macula

Moderate DME Retinal thickening or hard exudates approaching the centerof the macula but not involving the center

Severe DME Retinal thickening or hard exudates involving the center of the macula

Advanced diabetic eye disease• Haemorrhage – Preretinal(retrohyaloid),

intragel(vitreous)

• Tractional retinal detachment – Progressive contraction of fibrovascular membranes

• Tractional retinoschisis ± Retinal detachment

• Rubeosis iridis, May lead to Neovascular glaucoma

Management• History Duration of DM, Blood sugar control, Smoking, associated systemic

diseases – HTN, renal disease

• Unstable refraction

• Anterior segment examination – NVI– IOP is elevated, perform gonioscopy to look for angle neovascularization (NVA)– Recurrent stye, Chalazion, Xanthelasmata,– Accelerated senile cataract, snowflake cataract– Oculomotor nerve palsies– Reduced corneal sensitivity, poor tear film, dry eye

• Careful fundus examination – with 20D and 90D

Investigations

• FFA – Focal/diffuse/ischaemic diabetic

edema Early NVE/NVD Capillary non-perfusion areas,

capillary dilatation

• OCT – Diffuse macular edema

classification, response to therapy

Treatment

• Strict Glycemic control DDCT – Type 1 DM UKPDS – Type 2 DM Wisconsin Epidemiologic Study of Diabetic

Retinopathy(WESDR): population-based study showed that glycosylated haemoglobin levels and duration of diabetes are risk factors for progression of retinopathy

• Strict Blood pressure control UKPDS – Type 2 DM

DCCT – Diabetes control and complications Trial

Purpose• To compare intensive with

conventional diabetic therapy• To study their effects on the vascular

and neurological complications of DM

Inclusion CriteriaTYPE 1 DM pts

Study designIntensive control – monitoring of blood glucose 4 times a day and insulin dosage appropriatelyConventional treatment – monitoring of BG 2 times a day and insulin dosage appropriately

Conclusions• Intensive treatment (mean HbA1c 7.2%) reduced the risk of acquiring DR by 76 percent when compared to conventional treatment (mean HbA1c 9.0%).

• Intensive therapy slowed the progression of retinopathy by 54 percent

•Intensive therapy reduced the risk of nephropathy (50%) and neuropathy (60%)

UKPDS – UK prospective diabetes study

Purpose• To compare intensive with

conventional diabetic therapy• To study their effects on the vascular

and neurological complications of DM

Inclusion CriteriaTYPE 2 DM pts

Study designIntensive control – FBS-110PPBS-180 and HbA1c of 6.5%Conventional control –Moderately high glucose levels were accepted

Conclusions• Reducing glucose exposure (HbA1c 7.0 % versus 7.9 % over median 10.0 years), with sulphonylurea or insulin therapy, reduced the risk of

laser treatment of the eye: by a quarter Nephropathy: by a third

• Improving blood pressure (142/82 mmHg versus 154/87 mmHg over median 8.4 years) reduced the risk of

strokes: by a third death from complication: by a third (e.g. from heart attacks or strokes) deterioration by vision: by a third

Exudative

Focal

>500μm from fovea

<500μm from fovea

Diffuse

Spongiform thickening

Cystoid macular edema

Macular edema with vitreomacular traction

Macular edema with neurosensory detachment

Ischaemic

No edema With Edema – Same as exudative

Management of diabetic macular edemaFFA

(if needed)

OCT

Laser

Anti-VEGF, IVTA

Laser

Laser

Anti-VEGF, IVTA

Anti-VEGF, IVTA

Anti-VEGF, IVTA

Evaluate for nephropathy

PPV±ILM peeling

Management of diabetic maculopathy

After prior FFA if needed – Classified as

Focal/Diffuse

Ischaemic – Poor prognosis, evaluate for nephropathy. Grid laser for thickened retina

Argon laser photocoagulation For all eyes with CSME Gold standard of treatment – 70% - maintain vision 15% - improvement 15% - worsening

DRS – Diabetic retinopathy studyPurpose• To determine whether

photocoagulation prevents severe visual loss ffrom PDR

• To determine if a difference exists in the efficacy and safety of argon versus xenon arc photocoagulation

Inclusion CriteriaVisual acuity>20/100 both eyesPDR in 1 eye OR severe NPDR in both eyes

Study design1 eye – PRP(Argon / Xenon arc)Other eye – Follow up

Conclusions• Photocoagulation decreased the risk of severe visual loss (VA<5/200) by 50% or more at 2 consecutive 4 month follow-ups• Mild risk of decrease in VA and visual field more with xenon arc photocoagulation• Treatment outweighs the risk for patients with high risk PDR

ETDRSPurpose• To evaluate the effectiveness of

argon laser photocoagulation and asprin therapy in progression of DR

• To determine the best time for PRP

• To monitor closely the effects of DM and of photocoagulation on visual function

Inclusion CriteriaVisual acuity>20/40, Visual acuity >20/200 if macular edema is presentMild NPDR to non-high risk PDR with or without macular edema.

Study design1 eye – PRP(Argon / Xenon arc) and focal laser for macular edemaOther eye – Follow up and PRP if high risk characteristics developPts randomised to asprin or placebo

Conclusions• Focal Photocoagulation reduced the risk of moderate visual loss (doubling of visual angle) by 50% or more at 2 consecutive 4 month follow-ups• Early PRP with or without Focal photocoagulation reduced the risk of severe visual loss and vitrectomy (combined end point) but the risk reduction was small and risk is very less (2.6% vs 3.7% at 5 years)• Asprin did not affect progression of DR but decreased the risk of cardiovascular disease

Focal treatment

Burns – Centre of Ma/H in the centre of rings of Hard exudates 500-

3000μm from fovea Treatment may be done within 300μm of fovea

– if other leaks have been treated, – VA<6/12 and– treatment is not likely to destroy the existing perifoveal capillary

network

Spot size- 50-100μm Exposure time- 0.05-0.1sec Gentle whitening or darkening of lesions

Grid treatment

Burns – Areas of diffuse retinal thickening more than 500μm from

the fovea and 500μm from the temporal margin of the optic disc

Spot size- 50-100μm Exposure time- 0.05-0.1sec Very light intensity burn

• IVTA - Intravitreal triamcinolone acetonide 4mg – esp for diffuse diabetic macular edema

• Long term steroid implants - Fluocinolone acetonide implant

• PST - (Posterior sub-tenon triamcinolone acetonide 40mg injection)

• Anti-VEGF agents – bevacizumab, ranibizumab

• Pars plana vitrectomy – esp. when associated with tangential traction and taut posterior hyaloid (TPHM)

• Oral atorvastatin

ScreeningMild NPDR Moderate

NPDRSevere NPDR

Very Severe NPDR

Early PDR

Risk of PDR within 1 year

5% 12-27% 52% 75%

Risk of High-risk PDR within 5 years

15% 33% 60% - 75%

Appropriate follow-up period

6-12 months 6-12 months 2-4 months 2-3 months

In pregnancy – At conception, every trimester and after delivery

At conception No retinopathy

NPDR Treated PDR Untreated PDR

Chance of NPDR 10% PDR 4% No worsening Worsening

Pan-retinal photocoagulation

Burns – 1000-2000 burns in a scatter pattern extending from the

arcades outward till the vortex ampullae(equator) in 2-3 sessions

Placed with one burn width apart Laser not applied over traction, vessels, elevated retina.

Spot size- 200-500μm – goldmann lens 100-300μm – panfunduscopic type of lens Exposure time- 0.1-0.2sec Light intensity burn – blanching of adjacent RPE

• Step 1 Close to disc and inferior arcades

• Step 2 Protective barrier around macula &

superior arcades

• Step 3 nasal to disc and temporal to macula

• Step 4 Peripheral treatment

• Persistent neovascularization

• Haemorrhage

Poor involution

• Re-treatment required

• Regression of neovascularization• Residual ‘ghost’ vessels or fibrous tissue

Good involution

• Disc pallor

Assessment after photocoagulation

Treatment of recurrences in neovascularization Fill-in PRP Add-on PRP Cryotherapy

Complications Constriction of field, Para central scotomas Decreased vision due to Lateral creeping of juxtafoveal laser scars into the

fovea Macula subretinal fibrosis Cystoid macular edema Accidental foveal photocoagulation CNVM, choriodal detachments

Vitrectomy surgery

Indications – • Severe persistent vitreous haemorrhage• Progressive tractional Retinal detachment• Combined tractional and rhegmatogenous retinal

detachment• Premacular subhyaloid haemorrhage

DVS – Diabetes vitrectomy study

Purpose• To compare early

vitrectomy versus conventional management for recent severe vitreous hemorrhage secondary to diabetic retinopathy.

Inclusion CriteriaRecent severe VH (within 5 months) or PDR with extensive active FVP and useful vision in patients with Type 1 and Type 2 diabetes mellitus

Study designEarly vitrectomy - 1-6 monthsConventional management includes vitrectomy if hemorrhage fails to clear during a waiting period of 12 months or if retinal detachment involving the center of the macula develops at any time

Conclusions• Good vision was obtained in 35.6% of patients in early treatment group vs 11.6% pts in the conventionally treated group in Type 1 pts

RecommendationsVitrectomy within 3 months in Type 1 ptsVitrectomy within 6 months in Type 2 pts

THANK YOU

Microaneursyms

• Cellular

• Types of lasers for prp

Hard and soft exudates