1. Retinal vascular disease
dr n med. Karolina Kaźmierczak

2. Retinal vascular disease
lipid
fluid
leak
blood
vessel
neoangiogenesis
block
ischaemia
cotton wool spots

3. diabetic
retinopathy
hypertensive
Retinal vascular
disease
CRAO
arterial
BRAO
occlusive
CRVO
venous
BRVO

4. DR - risk factors 1. Duration of diabetes !!
type 1 patients experience a 25% rate of retinopathy
after 5 years of disease, and 80% at 15 years of disease
up to 21% of newly diagnosed type 2 patients have some degree of retinopathy at the time of diagnosis
Poor metabolic control (raised HbA1c is associated with an
increased risk of proliferative disease)
Pregnancy (puberty and pregnancy can trigger an increase in risk
of retinopathy in patients with previously diagnosed diabetes)
Hypertension (should be rigorously controlled (<140/80 mmHg))
Nephropathy (if severe, is associated with worsening of DR)
6. Other risk factors: obesity, hyperlipidaemia, anaemia.

5. Retinopathy screening
Type 1 diabetes - screen within 3-5 years of diagnosis after age 10
Type 2 diabetes - screen at time of diagnosis
Pregnancy - women with preexisting diabetes should be screened prior to conception and during first trimester
Follow-up annually; less frequent exams (2-3 yrs) may be considered
Examination methods - dilated indirect ophthalmoscopy coupled with biomicroscopy and fundus photography

6. Pathogenesis of DR arteriole OCCLUSION LEAKAGE venule
1. Thickening of the basement membrane
2. Degeneration of the endothelial
cells
3. Deformation of erythrocytes
4. Increased platelet stickness
and aggregation
Loss of pericytes

7. Consequences of the retinal hypoxia
arteriovenous
shunts
SIGNIFICANT CAPPILARY
OCCLUSION („DROP-OUT”)
vasoproliferative factor
retinal hypoxia
iris rubeosis
proliferative retinopathy

8. Consequences of the chronic leakage
retinal oedema
hard exudate

9. Stages of diabetic retinopathy
Background DR (non-proliferative DR)
Preproliferative DR
Proliferative DR

10. Background diabetic retinopathy (BDR)
1. Microaneurysms (localized succular outpouchings of the capillary wall that may be formed by either focal dilatation of the capillary wall or fusion of two arms of a capillary loop)
2. Retinal haemorrhages
retinal nerve fibre layer haemorrhages (flame-shaped haemorrhages)
intraretinal haemorrhages (dot haemorrhages)
Macular oedema
diffuse oedema (caused by extensive capillary leakage)
localized retinal oedema (caused by focal leakage from microaneurysm and dilated capillary segments)
4. Hard exudates (caused by chronic localized retinal oedema)

11. Management of BDR
Mild BDR – no treatment (should be reviewed annually)
More severe BDR – should be assessed if the clinically significant macular oedema is present)

12. Diabetic maculopathy
Definition: ivolvement of the fovea by oedema, hard exudates or ischaemia
It’s the most common cause of visual impairment in diabetic patients, particulary those with type 2 diabetes
Focal maculopathy – well – circumscribed retinal thickening associated with complete or incomplete rings of hard exudates
Diffuse maculopathy – diffuse retinal thickening, which may be associated with cystoid changes (because of the severe oedema, localization of the fovea may be impossible)
Ischaemic maculopathy – macula may look relatively normal (severe visual impairment)
Clinically significant macular oedema (CSMO) – is defined as specific distance (in μm) of retinal oedema and hard exudatives of the centre of the macula.

13. Preproliferative diabetic retinopathy (PPDR)
Cotton-wool spots (are composed of accumulations of neuronal debris within the nerve fibre layer – they results from disruption of nerve axons)
Intraretinal microvascular abnormalities (IRMA) (are arteriolar-venular shunts that run from retinal arterioles to venules, thus by-passing the capillary bed, and are therefore often seen adjacent to areas of capillary closure)
Other features:
- venous changes (dilatation and tortuosity, looping,
beading and „sausage-like” segmentation)
- arterial changes (peripheral narrowing, silver-wiring and
obliteration)
- dark blot haemorrhages (represent haemorrhagic retinal
infarcts and are located within the middle retinal layers)

14. Preproliferative diabetic retinopathy
Signs
cotton-wool spots – small, whitish, fluffy
superficial lesions which obscure underlying
blood vessels
venous and arterial changes
dark blot haemorrhages
dark blot changes
intraretinal microvascular
abnormalities (IRMA)
No treatment is needed, but must be
watched (risk of proliferative diabetic
retinopathy)
Proliferative diabetic retinopathy (PDR)
PDR affects 5-10% of the diabetic population
Type 1 diabetics are at particular risk with an incidence of about 60%
after 30 years
In PDR neovascularization is caused by angiogenic growth factors
elaborated by hypoxic retinal tissue in an attempt to re-vascularize
hypoxic retina (over one-quarter of the retina has to be non-perfused
before PDR develops)
Signs: - new vessels at disc (NVD)
- new vessels elsewhere (NVE)

15. Indication to treatment of PDR
Clinical assessment:
Severity of PDR – is determined by the area covered with new vessels
Elevated new vessels – are less responsive to laser therapy than flat
Fibrosis – associated with NVD/NVE - risk of tractional RD
NVD > 1/3 disc area
Mild NVD
+ haemorrhage
NVE > 1/2 disc area
+ haemorrhage
Panretinal photocoagulation (PRP)
Laser therapy is aimed at inducing
involution of new vessels and
preventing visual loss
Final efect of PRP
Control exam after 4-8 weeks

16. Indications to pars plana vitrectomy in DR
Signs of involution
Poor involution
Good involution
persistent neovascularization
regression of neovascularization
„ghost” vessels or fibrous tissue,
decreased in venous changes,
absorption of retinal haemorrhages
disc pallor
new haemorrhage
more treatment is needed
Indications to pars plana vitrectomy in DR
Severe persistent vitreous
haemorrhage
Premacular subhyaloid
haemorrhage
Progressive proliferation
in spite of laserotherapy
Progressive tractional retinal
detachment

17. Hypertensive disease (hypertensive retinopathy)
It’s a spectrum of retinal vascular changes that are pathologically related to microvascular damage from elevated blood pressure
The primary response of the retinal arterioles to systemic hypertension is narrowing (vasoconstriction)
In sustained hypertension the inner blood-retinal barrier is disrupted in small areas, with inreased vascular permeability
Signs of hypertensive retinopathy:
Arteriolar narrowing – focal or generalized (cotton-wool spots)
Vascular leakage (flame-shaped retinal haemorrhages and retinal oedema; chronic – macular star configuration of the hard exudates)
Arterisclerosis – involves thickening of the vessel wall characterized histologically by medial hypertrophy and hyalinization. The most important sign is the presence of changes at arteriovenous crossings (AV nipping).

18. Grading of retinal arteriosclerosis
normal
Silver-wiring of arterioles
associated with grade 3
changes.
Subtle broadening of the
arteriolar light reflex , mild
generalized arteriolar attenuation, particulary of small branches , and vein concealment
Grade 4
Grade 1
copper-wiring of arterioles
banking of veins distal to
arteriovenous crossings
(Bonnet sign)
tapering of veins on both
sides of the crossings
(Gunn sign) and
right-angled deflection
of veins
Obvious broadening of the
arteriolar light reflex and
deflection of veins at
arteriovenous crossings
(Salus sign)
Grade 3
Grade 2

19. Hypertensive retinopathy classification
Keith -Wagener -Barker classification (KWB)
Grade 1
Generalised arteriolar constriction - seen as `silver wiring` and vascular tortuosities. Copper wiring.
Hard opaque vessel wall
Grade 2
Grade 1 + AV nipping
Grade 3
Grade 2 + with cotton wool spots and flame-hemorrhages
Grade 4
Grade 3 + papilledema

20. Types of embolies Cardiac embolism Carotid embolism
Vegetations (from cardiac valves
in bacterial endocarditis)
Cholesterol emboli
Fibrin-platelet
emboli
Thrombus (from the
left side of the heart)
Calcific
(from the
aortic or
mitral valves)
Myxomatous
material (from rare arterial myxoma)

21. Cholesterol emboli (Hollenhorst plaques)
intermittent showers of minute, bright, refractile, golden to yellow-orange
crystals
often located at arteriolar bifurcations
are frequently asymptomatic
Fibrin-platelet emboli
dull grey, elongated particles which are usually multiple and occasionally fill the
entire lumen
they may cause a retinal transient ischaemic attack (TIA) – amaurosis fugax
frequency of attacks may vary from several times a day to once every few months
Calcific emboli
usually single, white, non-scintillanting and often on or close to the optic disc
much more dengerous, because they may cause permanent occlusion of the central
retinal artery or one of the main branches

22. Other causes of retinal occlusion
Atherosclerosis-related thrombosis
Periarteritis
May be associated with dermatomyositis, SLE,
Polyarteritis nodosa, Wegener granulomatosis,
Behcet syndrome (BRAO)
The most common underlying cause of CRAO
(about 80% of cases)!
Uncommon causes:
- giant cell arteritis retinal migraine
cardiac embolism Susac syndrome
thrombophilic disorders sickling haemoglobinopathies

23. Branch retinal artery occlusion (BRAO)
FA in BRAO
Presentation – sudden and
profound altitudinal or
sectoral visual field loss
VA- variable
Fundus:
narrowing of arteries and
veins
claudy white retina,
resulting from oedema
emboli may be present
Delay in arterial filling and hypofluorescence of the involved segment due to blockage
of background fluorescence by retinal swelling
Prognosis – poor , unless the obstruction can be relieved within a few hours

24. Central retinal artery occlusion (CRAO)
Presentation – sudden and
profound loss of vision
VA – is severly reduced (except if
a portion of the papillomacular
bundle is supplied by
a cillioretinal artery, when
central vision may be preserved)
APD (afferent pupill defect) is
profound or total (amaurotic
pupil)
Fundus:
similar changes to BRAO (more
extensive)
„cherry-red spot” (orange reflex
from the intact choroid at
foveola)
FA in CRAO
Cilioretinal artery filling during the early phase
Delay in arterial filling and masking of background choroidal fluorescence by retinal swelling
Prognosis – poor due to retinal infarction. After a few weeks the retinal cloudiness
and the „cherry-red” spot gradually disappear and the inner retinal layers become
atrophic. Consecutive optic atrophy result in permanent visual loss.

25. Treatment of acute retinal artery occlusion
The treatment may be tried in patients with occlusions of less than 48 hours duration at presentation!!
Management:
Ocular massage (using a three-mirror contact lens for approximately 10 seconds, followed by 5 seconds of relase (causing changes in arterial flow)
Anterior chamber paracentesis (may be carried out)
Intravenous and topical acetazolamide (to obtain prolonged lowering of intraocular pressure)

26. Retinal venous occlusive disease – predisposing factors
General
advancing age
hypertension
hyperlipidaemia
diabetes mellitus
Ocular
raised intraocular pressure
vasculitis
Both arterial and venous disease
contribute to retinal vein occlusion.
Arteriolosclerosis is an important
causative factor for BRVO.

27. Pathophysiology of vein occlusion
Stagnation
of blood flow
Increase of tissue
pressure
hypoxia
edema,
haemorrhage

28. Branch retinal vein occlusion (BRVO)
FA in BRVO
Presentation – depends on the amount
of the macular drainage compromised
by the occlusion.
VA – variable (if macula involved – sudden
onset of blurred vision, RAPD,
metamorphopsia
Fundus:
dilatation and tortuosity of the veins
distal to the occlusion
flame-shaped and dot-blot haemorrhages,
retinal oedema
cotton-wool spots (sometimes)
Prognosis: reasonably good
(within 6 months 50% of eyes develop
efficient collaterals, with return of VA
to at least 6/12)
FA early phases shows hypofluorescence due to blockage
by blood and slight staining of vessel walls
Late phase – hyperfluorescence
due to diffuse oedema
Signs of old BRVO
hard exudates, venous sheating, collaterals and residual haemorrhages
vision- threatening complications: chronic macular oedema, neovascularization

29. Management in chronic macular oedema in BRVO
the most common cause of visual impairment
wait 6-12 weeks, than follow with control FA
Macular non-perfusion and poor VA – laser
treatment will not improve vision
Good macular perfusion and
VA=6/12 or worse after 3-6 months
- consider laser photocoagulation
Management in neovascularization
- neovascularization usually appears within months – it can lead to reccurent vitreous
haemorrhage and occasionally tractional retinal detachment - NVD develops in about 10% and NVE in 25%
scatter laser photocoagulation should be performed follow-up after 4-6 weeks (if neovascularization persist, re-treatment is frequently effective)

30. Non-ischaemic central retinal vein occlusion (non-ischaemic CRVO)
FA in non-ischaemic CRVO
Non –ischaemic CRVO is the most common
type (about 75% of all cases)
Presentation – sudden unilateral blurred
vision
VA – is impaired to a moderate-severe
degree ( > CF)
APD – absent or mild
Fundus:
tortuosity and dilatation of all branches
dot-blot and flame-shaped haemorrhages
(mainly peripheral retina)
cotton-woll spots
optic disc and macular oedema (common)
Prognosis: is reasonably good (if not become
ischaemic) with return of vision to normal or
near normal in 50% (if macular oedema is
absent)
Delayed arteriovenous transit time, blockage by haemorrhages, good retinal
capillary perfusion and late leakage
Treatment: - intravitreal triamcinolone acetonide or anty-VEGF (for chronic
macular oedema (laserotherapy – is not beneficial)

31. Ischaemic central retinal vein occlusion (ischaemic CRVO )
Ischaemic CRVO is characterized by
rapid onset venous obstruction
resulting in decreased retinal
perfusion, capillary closure , retinal
hypoxia.
Presentation: sudden and severe visual
imairment
VA: usually CF or worse
APD is marked
Fundus:
severe tortuosity and engorgement of all
branches of the central retinal vein
extesnive dot-blot and flame-shaped
haemorrhages (peripheral retina and
postrior pole)
- severe disc oedema and hyperaemia
cotton-woll spots may be present
Prognosis – extremely poor!! (due to macular
ischaemia)
FA in ischaemic CRVO
Marked delay in arteriovenous transit time, central masking by retinal haemorrhages,
Extensive areas of capillary non-perfusion and vessel wall staining
- hypoxia may lead to profound vascular leakage, rubeosis iridis and neovascular
glaucoma.
most acute signs resolve over 9-12 months.
rubeosis iridis develops in about 50% of eyes (usually between 2-4 months ) - high risk
of neovascular glaucoma (100-day glaucoma)

32. Management in ischaemic CRVO
Control exams monthly for 6
months to detect anterior segment neovascularization (gonioscopy
- angle neovascularization)!!
Laser PRP (panretinal
photocoagulation) should be
performed without delay in eyes
with angle neovascularization
or rubeosis iridis!!