This document provides information on diabetic retinopathy including: 1. It defines diabetic retinopathy as progressive damage to the retinal vasculature caused by chronic hyperglycemia, affecting up to 40% of diabetics. Proliferative diabetic retinopathy affects 5-10% and can lead to vision loss. 2. Risk factors include duration of diabetes, poor blood sugar control, pregnancy, hypertension, and nephropathy. The pathogenesis involves cellular damage from hyperglycemia and changes to the capillaries leading to leakage, occlusion, and neovascularization. 3. Treatment depends on the severity and includes laser photocoagulation, anti-VEGF injections, and vitrect

1. DIABETIC RETINOPATHY
PRESENTER:DR. GLORIA GEORGE
MODERATOR: DR. AJAY KAMATH

2. DEFINITION
• Progressive dysfunction of the retinal vasculature
caused by chronic hyperglycemia resulting in
structural damage to the neural retina.

3. PREVALENCE
• The reported prevalence is probably up to 40%
• It is more common in type 1 diabetes than in type 2 and sight-
threatening disease is present in up to 10%.
• Proliferative diabetic retinopathy (PDR) affects 5–10% of the
diabetic population;
• Type 1 diabetics are at particular risk with an incidence of about
60% after 30 years.

4. RISK FACTORS
• Duration of diabetes
- 50% develop DR after 10 yrs
- 70 % after 20 yrs
- 90 % after 30 yrs
• Poor control of diabetes-Type 1 diabetic patients appear to obtain greater
benefit from good control than type 2. Raised HbA1c  increased risk of
proliferative disease
• Pregnancy
• Hypertension
• Nephropathy
• Others- hyperlipidaemia, smoking, obesity and anaemia

5. PATHOGENESIS
Predominantly a microangiopathy
1. Mechanisms of cellular damage- intracellular sorbitol accumulation,
oxidative stress due to free radicals, accumulation of advanced glycation end
products,
excessive activation of several protein kinase C isoforms.
2. Capillaropathy
-death of pericytes,
-thickening of capillary basement membrane,

6. -loss of vascular smooth muscle cells,
- proliferation of endothelial cells
-Capillary dysfunction manifests with leakage and occlusion.
3. Neovascularization is caused by capillary nonperfusion-
imbalance between the
angiogenic and antiangiogenic factors- VEGF and Endostatin

7. • Abbreviated Early Treatment Diabetic Retinopathy Study
classification of diabetic retinopathy
Non-proliferative diabetic retinopathy (NPDR)
1. No DR
Management - Review in 12 months
2. Very mild NPDR
Microaneurysms only
Management - Review most patients in 12 months

8. 3. Mild NPDR
Any or all of: microaneurysms, retinal haemorrhages, exudates, cotton
wool spots, up to the level of moderate NPDR. No IRMA or significant
beading
Management- Review range 6–12 months, depending on severity of
signs, stability, systemic factors, and patient’s personal circumstances

9. 4. Moderate NPDR
• Severe retinal haemorrhages (about 20 medium-large per quadrant) in
1–3 quadrants or mild intraretinal microvascular abnormalities (IRMA)
• Significant venous beading can be present in no more than 1
quadrant
• Exudates, Cotton wool spots commonly present
Management: Review in approximately 6 months, PDR in up to 26%, high-
risk PDR in up to 8% within a year

10. 5. Severe NPDR
The 4-2-1 rule; one of:
• Severe haemorrhages in all 4 quadrants
• Significant venous beading in 2 or more quadrants
• Moderate IRMA in 1 or more quadrants
Management: Review in 4 months. PDR in up to 50%, high-risk PDR in up
to 15% within a year

11. 6. Very Severe NPDR
The 4-2-1 rule; two or more of:
• Severe haemorrhages in all 4 quadrants
• Significant venous beading in 2 or more quadrants
• Moderate IRMA in 1 or more quadrants
Management: Review in 2–3 months. High-risk PDR in up to 45% within a
year

12. Proliferative Diabetic Retinopathy
1. Mild- moderate PDR
-New vessels on the disc (NVD) or new vessels elsewhere (NVE), but
extent insufficient to meet the high-risk criteria
Management: According to severity of signs, stability, systemic factors,
and patient’s reliability of attendance for review. If not treated, review
in up to 2 months

13. 2. PDR with High Risk Characteristics
• New vessels on the disc (NVD) greater than 1/3 disc area
• Any NVD with vitreous or preretinal haemorrhage
• NVE greater than 1/2 disc area with vitreous or preretinal
haemorrhage (or haemorrhage with presumed obscured NVD/E)
Management: To be treated immediately when possible, and same day if
symptomatic presentation with good retinal view

14.  Diabetic maculopathy
refers to the presence of any retinopathy
at the macula, but commonly reserved for
significant changes, particularly vision
threatening oedema and ischaemia.
Advanced diabetic eye disease is characterized by
• tractional retinal detachment,
• significant persistent vitreous haemorrhage
• neovascular glaucoma

15. SIGNS
 Microaneurysms
-localized out-pouchings, mainly saccular, of the capillary wall
-focal dilatation of the capillary wall where pericytes are absent,
or by fusion of two arms of a capillary loop
-inner nuclear layer
-Loss of pericytes may also lead to endothelial cell proliferation
-May leak plasma constituents into the retina due to breakdown in
the blood–retinal barrier, or become thrombosed

16. • Tiny red dots, often initially temporal to the fovea
• The earliest signs of DR
• May be indistinguishable from dot haemorrhages
• Fluorescein angiography (FA)-
- Early frames show tiny hyperfluorescent dots
more numerous than visible clinically.
-Late frames show diffuse hyperfluorescence due to leakage

17.  Retinal Haemorrhages
1. Retinal nerve fibre layer haemorrhages
-arise from larger superficial pre-capillary arterioles
-flame-shaped
2. Intraretinal haemorrhages
-arise from the venous end of capillaries
-in the compact middle layers of the retina
-resultant red ‘dot/blot’ configuration

18. 3. Deeper dark round haemorrhages
-represent haemorrhagic retinal infarcts
-within the middle retinal layers
-marker of progression to retinal neovascularization.

19. Exudates
- caused by chronic localized retinal oedema
- composed of lipoprotein and lipid-filled macrophages
- located mainly within the outer plexiform layer
- Hyperlipidaemia may increase exudate formation
- Waxy yellow lesions with relatively distinct margins,
- often arranged in clumps and/or rings at the posterior pole
- typically surrounding leaking microaneurysms
- With time number and size tend to increase and
the fovea may be threatened or involved

20. - When leakage ceases, exudates absorb
- Chronic leakage leads to enlargement of the exudates
and the deposition of cholesterol
- FA shows hypofluorescence due to blockage of background
choroidal and retinal capillary fluorescence.

21. Cotton wool spots
-accumulations of neuronal debris within the NFL
-result from disruption of nerve axons,
-Small, whitish, fluffy superficial lesions which
obscure underlying blood vessels-
clinically evident only in the post-equatorial retina
-FA shows focal hypofluorescence due to
blockage of background choroidal fluorescence,
frequently associated with adjacent capillary non-perfusion.

22. Venous changes
- generalized dilatation and tortuosity, ‘looping’, ‘beading’ (focal narrowing and
dilatation) and ‘sausage-like’ segmentation.
- Correlates well with the likelihood of developing proliferative disease.

23. Intraretinal microvascular abnormalities (IRMA)
- arteriolar-venular shunts that run from retinal arterioles to venules, thus
bypassing the capillary bed,
seen adjacent to areas of marked capillary hypoperfusion
- Fine, irregular, red intraretinal lines that run from arterioles to venules
without crossing major blood vessels.
- FA shows focal hyperfluorescence with adjacent areas of capillary closure
(’dropout’) but without leakage.

24.  Arterial changes
- Subtle retinal arteriolar dilatation may be an early marker of ischaemic
dysfunction.
- When significant ischaemia is presentperipheral narrowing, silver-wiring
and obliteration

25. Proliferative retinopathy
-over one-quarter of the retina must be non-perfused before PDR develops
-most commonly seen at the posterior pole
1. New vessels at the disc (NVD) describes neovascularization on or within one
disc diameter of the optic nerve head
2. New vessels elsewhere (NVE) describes neovascularization further away from
the disc that may be associated with fibrosis if long-standing.

26. 3. New vessels on the iris (NVI), also known as rubeosis iridis, carry a high
likelihood of progression to neovascular glaucoma.
4. FA highlights neovascularization during the early phases of the angiogram
and shows hyperfluorescence during the later stages due to intense leakage of
dye from neovascular tissue

27. Diabetic Macular Oedema
-Diabetic maculopathy (foveal oedema, exudates or ischaemia)
-Most common cause of visual impairment in diabetic patients, particularly type
2
-Diffuse retinal oedema is caused by extensive capillary leakage,
localized oedema by leakage from microaneurysms and dilated capillary
segments.
-Fluid initially between outer plexiform and inner nuclear layers;

28. -Later involves the inner plexiform and nerve fibre layers
entire thickness of the retina
-With further accumulation of fluid fovea
assumes cystoid appearance (cystoid macular oedema – CMO).
-FA shows diffuse late hyperfluorescence due to
retinal capillary leakage,nand may have a flower-petal
pattern if CMO is present
- OCT shows retinal thickening and, if present, cystoid spaces

29. Focal maculopathy
- Well-circumscribed retinal thickening with complete or incomplete rings of
exudates
- FA shows late, focal hyperfluorescence due to leakage, and good macular
perfusion

30. Diffuse maculopathy
- Diffuse retinal thickening, may be associated with cystoid changes
- Scattered microaneurysms and small haemorrhages
- Landmarks are obliterated by severe oedemalocalization of the fovea
impossible
- FA shows late diffuse hyperfluorescence, may assume a central flower-petal
pattern if CMO present.

31. Ischaemic maculopathy
-Macula may look relatively normal despite reduced visual acuity
-Pre proliferative DR may be present
-FA shows capillary non-perfusion at the fovea (an enlarged FAZ) and
other areas of capillary non-perfusion at the posterior pole and periphery

32. Clinically significant macular oedema
was defined in the ETDRS as
• Retinal thickening within 500 µm of the
centre of the macula
• Exudates within 500 µm of the centre of the macula,
if associated with retinal thickening
(which may be outside the 500 µm)
• Retinal thickening one disc area (1500 µm) or larger,
any part of which is within one disc diameter
of the centre of the macula

33. TREATMENT
General Considerations
Patient Education
Diabetic Control
Control of Hypertension, Hyperlipidemia
Fenofibrate 200mg daily reduces progression in Type 2 DM
Cessation of smoking
Anemia, renal failure to be treated

34. Treatment of clinically significant macular oedema
Specific Recommendations
CSME not involving macular centre- to be treated with photocoagulation or
micropulse laser
CSME involving macular centre with normal or minimally affected vision- can
undergo laser (>500um from macular centre) or observe if leakage is close to
fovea

35. CSME involving macular centre with reduced vision
- intravitreal anti-VEGF treatment- induction phase of monthly injections for 3-
6 months
- After induction phase, combine anti-VEGF with laser
 Pseudophakic eyes with CSME involving macular centre and poor vision
- Above mentioned regimen or intravitreal triamcinolone
Resistant cases- intravitreal triamcinolone or intravitreal steroid implant. Pars
plana vitrectomy if VM traction is present

36.  Focal treatment with Argon laser
• Burns are applied to microaneurysms and microvascular
lesions in the centre of rings of exudates located 500–3000 µm
from the centre of the macula.
• Spot size is 50–100 µm and exposure time 0.1 second
with sufficient power to obtain gentle whitening or darkening
of the microaneurysm.
• Treatment of lesions up to 300 µm from the centre of the
macula considered if CSMO persists despite
previous treatment and visual acuity is less than 6/12
, shorter exposure time of 0.05 second

37. Grid treatment
• Burns are applied to areas of diffuse retinal thickening
more than 500 µm from the centre of the macula
and 500 µm from the temporal margin of the optic disc.
• The spot size is 100 µm and exposure
time 0.1 second giving a very light intensity burn.
• Treatment should be lighter if significant
macular ischaemia is present.

38. - Approximately 70% of eyes achieve stable visual acuity,
- 15% show improvement and 15% subsequently deteriorate
- It may take up to 4 months for the oedema to resolve
- Poor prognostic factors- significant macular ischaemia, exudates involving the
fovea, diffuse macular oedema, severe retinopathy at presentation,
uncontrolled hypertension and diabetes, renal disease

39. Other lasers
• Frequency-doubled Nd:YAG laser: Less destructive, greater patient comfort
• Micropulse diode laser : very short laser pulse duration combined with a
longer cycle, burns are applied to the RPE without significantly affecting outer
retina and choriocapillaris.
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents- critical
element in the management of diabetic maculopathy- ranibizumab,
bevacizumab

40. • Ranimizumab (Lucentis) - humanized monoclonal antibody fragment
- 0.5 mg/ 0.05 ml monthly for 3 months with prompt
or deferred laser superior visual and OCT outcome
• Bevacizumab (Avastin)- complete antibody
- much cheaper
- 1.25 mg/0.05 ml, monthly or as needed
- much larger molecule, so retained in vitreous for longer
 fewer doses

41. Intravitreal triamcinolone.
- in pseudophakic eyes steroid injection followed by prompt laser- improved
vision and reduced retinal thickening.
- risk of an elevation of intraocular pressure
- Sustained release intravitreal steroid implants- promising results
Pars plana vitrectomy
- Indicated when there is associated tangential traction from a thickened and
taut posterior hyaloid.

42. Laser photocoagulation for proliferative retinopathy
The Diabetic Retinopathy Study (DRS) investigated the effect of panretinal
photocoagulation (PRP). The benefits demonstrated included:
• Mild NVD with haemorrhage carries a 26% risk of visual loss reduced to 4%
with treatment.
• Severe NVD without haemorrhage carries a 26% risk of visual loss reduced
to 9% with treatment.
• Severe NVD with haemorrhage carries a 37% risk of visual loss reduced to
20% with treatment.
• Severe NVE with haemorrhage carries a 30% risk of visual loss reduced to
7% with treatment.

43. Informed consent
- visual field defects, risk to central vision
- night and colour vision may be affected.
If CSMO is also present, laser for this should preferably
be carried out prior to PRP or at the same session
Laser settings
a. Spot size - depends on the contact lens used-
Goldmann lens spot size is set at 200–500 µm,
panfundoscopic-type lens it is set at 100–300 µm
b. Duration of the burn is 0.05–0.1 second.
c. Power should be sufficient to produce only a
light intensity burn

44. Initial treatment involves 1500–2000 burns in a scatter pattern from posterior
fundus to peripheral retina in one or more sessions
The amount of treatment is governed by the patient’s pain threshold;
discomfort least at the posterior pole and greatest in the periphery
A suggested treatment sequence is as follows:
a. Step 1. Close to the disc, below the inferior temporal arcades

45. • b. Step 2. Protective barrier around the macula to prevent inadvertent
treatment of the fovea; above the superotemporal arcade

46. • c. Step 3. Nasal to the disc ,completion of posterior pole treatment .

47. d. Step 4. Peripheral treatment until completion
In very severe PDR it is advisable to treat the inferior fundus
first, since any vitreous haemorrhage will gravitate inferiorly
and obscure this area, precluding further treatment.

48. Follow-up is after 4–6 weeks. In severe NVD,
3000 or more burns may be required.
Signs of involution - regression of
neovascularization leaving ‘ghost’ vessels or fibrous tissue,
decrease in venous changes, absorption of retinal haemorrhages
and disc pallor. Patients should remain under observation.
Treatment of recurrences -laser photocoagulation
to fill in any gaps
Fibrosis associated with neovascularization carries
increased risk of tractional retinal detachment if it bleeds

49. VEGF inhibition for proliferative retinopathy
- For resolution of persistent vitreous haemorrhage, avoiding vitrectomy
- As initial treatment of rubeosis iridis
- Rapid control of very severe PDR to minimize risk of haemorrhage

50. ADVANCED DIABETIC EYE DISEASE
Serious vision threatening complication of DR where treatment has been
inadequate or unsuccessful.
1. Haemorrhage may be preretinal (retrohyaloid), intragel or both.
- Intragel haemorrhages usually take longer to clear than preretinal .
- Bleeding may be precipitated by severe physical exertion or straining,
hypoglycaemia and direct ocular trauma.

51. 2. Tractional retinal detachment
-caused by progressive contraction of fibrovascular
membranes over areas of vitreoretinal attachment.
3. Rubeosis iridis (iris neovascularization)
-if severe may lead to neovascular glaucoma
-particularly common in eyes with severe retinal
ischaemia or persistent retinal detachment following
unsuccessful pars plana vitrectomy.

52. • Indications for pars plana vitrectomy
1. Severe persistent vitreous haemorrhage
2. Progressive tractional RD
3. Combined tractional and rhegmatogenous RD
4. Large premacular subhyaloid haemorrhage

53.  Visual results of pars plana vitrectomy
• About 70% of cases achieve visual improvement, about 10% are made worse
and the rest are unchanged
• Favourable prognostic factors
-Good preoperative visual function
-Age 40 years or less
-Absence of preoperative rubeosis and glaucoma.
-Previous PRP to at least one-quarter of the fundus.

54. REFERENCES
• Kanski’s Clinical Ophthalmology 8th Edition
• Yanoff and Duker Textbook of Ophthalmology 4th Edition
• Ryan, Retina 5th Edition

55. Thank You!