DIABETIC RETINOPATHY 101

Tomasz Wiraszka, MD PGY-4

BACKGROUND

Prevalence

Variable between publications, probably less than 40%.

More common in type I DM
Sight-threatening diabetic retinopathy in 10% patients
Proliferative diabetic retinopathy (PDR): 5-10% of patients with diabetes.
Type 1 DM: Incidence of PDR of 60% after 30 years of diabetes.

Risk factors:

Duration of diabetes
If diagnosed before 30 yoa:
10 year incidence of retinopathy: 50%

Pregnancy
Greater risk of progression of DR if:
Poorly controlled at baseline or too aggressively controlled in
early pregnancy
Pre-eclampsia
Fluid imbalance

30 year incidence: 90%

Poor control

Early control important

Type 1 diabetics benefit more from tight control than type 2
Raised HbA1c correlates with increased risk of PDR

Hypertension
Very prevalent among DM II patients
Goal 140/80 (less if indicated by cardiovascular/stroke risk
factors)

Microangiopathy, possible direct effect on retinal cells as well.

Mechanism of toxicity: intracellular sorbitol, oxidative stress, advanced glycation end products, hyperactivity of several PK-C isoforms
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Capillary damage: pericytes and vascular smooth muscle lost, endothelial proliferation, basement membrane thickenining.

BACKGROUND

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Pathogenesis

Neovascularization: Formation of pre-retinal and intra-retinal neovascular complexes, intra-retinal shunt formation (IRMA)

Classification

Background/Non-proliferative Diabetic Retinopathy (BDR/NPDR)

Signs: Microaneurysms, dot-blot hemorrhages, exudates
Diabetic maculopathy
Changes affecting macula, with significant visual impact, e.g.
edema, ischemia
Fig. 13.1 Normal retinal capillary bed. (A) Periarteriolar capillary-free zone flat preparation of Indian ink-injected
Proliferative
diabetic retinopathy
retina; (B) endothelial cells with elongated nuclei and pericytes with rounded nuclei trypsin digest preparation
(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-Heinemann 2001)
Presence of neovascular lesions within 1 dd of disc and/or lesions
elsewhere
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Advanced diabetic disease

Tractional detachment, perisistent vitreous hemorrhage,
neovascular glaucoma

Fig. 13.2 The capillary bed in diabetic retinopathy. (A) Capillary closure with adjac
capillaries flat preparation of Indian ink-injected retina; (B) degenerate pericytes
digest preparation; (C) new capillaries (arrows) on the inner retinal surface growin
perfused areas flat preparation of Indian ink-injected retina
(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterwo

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Exudates - hard

MA/EXUDATES

Lesions in BDR

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Microaneurysms

Fig. 13.3 Location of lesions in background diabetic retinopathy

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Exudates-soft (aka cotton-wool spots)

Fig. 13.6 Exudates. (A) Histology shows irregular eosinophilic deposits mainly in the outer ple
exudates and microaneurysms; (C) incomplete ring of exudates and a few small haemorrhage
involving theFig.
fovea;
(E) plaque
of(A)
exudates
at the
macula
with(B)
cholesterol
depositio
13.12 Cotton
wool spots.
Histology shows
cytoid
bodies inassociated
the nerve fibre layer;
clinical appearance
of J Harry fig. A; K Slowinski fig. B)
(Courtesy of(Courtesy
J Harry
fig. A)

East

West

DIABETIC HEMORRHAGES -NPDR

Bloody diabetes- NPDR

North

180

160

140

120

100

80

60

40

20

0
1st Qtr

2nd Qtr

3rd Qtr

4th Qtr

DIABETIC MACULAR EDEMA

Diabetic Macular Edema (DME)

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Fig. 13.9 Diffuse diabetic maculopathy. (A) Dot and blot haemorrhages; (B) FA late phase shows extensive
hyperfluorescence at the posterior pole due to leakage

Fig. 13.8 Focal diabetic maculopathy. (A) A ring of hard exudates tempora
focal area of hyperfluorescence due to leakage corresponding to the centr

Component of diabetic maculopathy alongside ischemia and exudates

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Most common cause of visual impairment in Type II DM

Caused by generalized capillary leakage if diffuse.

Caused by leakage from microaneurysms and dilated capillaries if focal.

Fluid first accumulates in outer plexiform and inner nuclear layers,

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Fig. 13.8 Focal diabetic maculopathy. (A) A ring of hard exudates temporal to the macula; (B) FA late phase shows
focal area of hyperfluorescence due to leakage corresponding to the centre of the exudate ring

Later may also involve Inner plexiform and nerve fiber layers.

Cystoid spaces on OCT.

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Manifestations Fundus exam

Signs:
Can be relatively mild-appearing fundus exam with decreased
visual acuity or fulminant.
Cotton wool spots: Superficial, fluffy, obscure underlying vessels.
Seen only in posterior retina.
Venous changes: Diffuse dilation and turtuosity, looping, beading.
IRMA: arteriolar-venular direct communication bypassing capillary
bed. Often adjacent to area of hypo-perfusion.

On IVFA:
Capillary non-perfusion at fovea,
Enlargement of foveal avascular zone (FAZ),
Additional areas of nonperfusion
(Posterior pole and peripheral)

IVFA

MACULAR ISCHEMIA

Macular ischemia

CSME

Criteria for Clinically significant Macular Edema

Defined in ETDRS study as:

Retinal thickening within 500 microns
of center of macula
Exudate (hard) within 500 microns of
center of macula, if associated with
adjacent thickening (thickening doesnt
have to be within 500 microns of
center, though)
Retinal thickening one disc area or
larger, any part of which is within one
disc diameter of center of macula

IVFA

Fig. 13.11 Clinically significant macular oedema

F/U in 12 mos

Microaneurysms only

Mild

F/U in 6-12 months

Any combination of: microaneurysms, retinal

hemorrhages, exudates, cotton wool spots up to level
of moderate NPDR. NO IRMA or BEADING

Moderate
Severe hemorrhages in 1-3 quadrants or mild IRMA
Significant beading in no more than 1 quadrant
Cotton wool spots commonly seen

Severe
The 4-2-1 rule
Severe hemorrhages in all 4 quadrants
Significant beading in 2+ quadrants
Moderate IRMA in 1 or more quadrants

Very Severe
Two or more criteria for severe

F/U in 6 months
PDR in up to 26%, High-risk PDR in up to
8% within 1 year
F/U in 4 months
PDR in up to 50%, High-risk PDR in up to
15% within 1 year
F/U in 2-3 months
High-risk PDR in up to 45% within 1 year

ABBREVIATED ETDRS CLASSIFICATION

Very Mild

NVD/NVE

Sequelae

PROLIFERATIVE DIABETIC RETINOPATHY

PDR

Advanced Diabetic Eye Disease

Hemorrhages (preretinal, intravitreal)
Use B-scan if necessary to rule out
underlying detachment

Tractional detachment/retinoschisis
Rubeosis iridis/NVI
With severe ischemia

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Fig. 13.26 Indications for pars plana vitrectomy. (A) Tractional detachment involving the macula; (B) large
premacular subhyaloid haemorrhage

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NVD or NVE, extent insufficient to meet high risk

criteria

High risk PDR

NVD greater than 1/3 disc area
Any NVD with vitreous or preretinal hemorrhage
NVE greater than disc area with vitreous
hemorrhage (may be obscuring NVE/NVD)

Consider treatment on individual basis. If

not treating, F/U 2 months
Treatment immediately if possible

PDR CLASSIFICATION

Mild- Moderate

Focal laser:

All eyes with CSME should be considered for laser regardless of

visual acuity

Indication:
Treat microaneurysms and IRMA in center of exudate rings
located 500-3000 microns from center of macula.
**May go up to 300 microns from center of macula in special
cases

TREATMENT reduces risk of visual loss by 50%

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Pre-treatment IVFA :
Leaking microaneurysms
Ischemia

Spot size: 50-100 microns

Time: 100 ms
Power: sufficient for GENTLE whitening or darkening of lesion

Grid laser:

For diffuse retinal thickening over 500 microns from center of

macula and 500 microns from temporal margin of disc
Spot size: 100 microns
Time: 100 ms
Power: sufficient for GENTLE whitening, lighter if treating ischemic
area

Fig. 13.8 Focal diabetic maculopathy. (A) A ring of hard exudates temporal to the macula; (B) FA late phase shows
focal area of hyperfluorescence due to leakage corresponding to the centre of the exudate ring

LASERS

CSME

Appropriate intensity burns

DRS study:
Mild NVD with hemorrhage has 26% risk of visual loss, reduced
to 4% with treatment
Severe NVD without hemorrhage has 26% risk of visual loss,
reduced to 9% with treatment
Severe NVD with hemorrhage has a 37% risk of visual loss,
reduced to 20% with treatment
Severe NVE with hemorrhage has a 30% risk of visual loss,
reduced to 7% with treatment.
Treatment aims to induce involution of abnormal new vessels and
thereby prevents vision loss.
** If CSME present, treat CSME before or at same time as doing
PRP, because PRP can exacerbate CSME. Also, do minimum
effectie amount of PRP.
Risks:
Decreased night vision, loss of peripheral vision, possibility of
accidental foveal burns, macular edema.
Parameters:
Spot size: 100-300 microns with Pan-fundus lens (e.g.Superquad)
Time:50- 100 ms
Power: Aim for light intensity burn
Dosage: 1500-2000 spots in one or more sessions

Effect of PRP on neovascular lesions

HIGH RISK PDR

High risk PDR

Anti VEGF

Vitrectomy in diabetic eyes:

Adjunctive role to PRP

-Can be used pre-op with persistent vitreous hemorrhages
-Does not obviate need for PRP

Indications:
Severe persistent vitreous hemorrhage precluding laser
- If no NVI, consider within 3 months of hemorrhage in type I
DM, or with bilateral VH.

Progressive Tractional RD
- Treat urgently if affecting macula, otherwise may observe
Combined tractional and rhegmatogenous RD
- Treat urgently even if macula spared
Premacular subhyaloid hemorrhage
- Consider vitrectomy if dense
- May stimulate fibrovascular proliferation and consequent
tractional macular epiretinal membranes and retinal
detachments

Outcomes of vitrectomy

About 70% of cases achieve visual improvement

10% get worse
Remainder unchanged
Favorable prognostic factors:

Good Preop visual acuity

Age 40 or less
Absence of pre-op NVI/NVG
Previous PRP to at least fundus

ADVANCED DIABETIC RETINOPATHY

Surgery

ETDRS Study (Key definitions and staging)

WESDR Study (epidemiology of DM)
DCCT Study (Type 1 DM)

UKPDS Study (Type 2 DM)

DRS Study (Effectiveness of photocoagulation)
DRVS study (Vitrectomy in eyes with PDR)

BCSC HIT-LIST

What Else to read in BCSC RETINA

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