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Medical Retina > Histopathology of Diabetic retinopathy > Flashcards

Histopathology of Diabetic retinopathy Flashcards

1
Q

where in the retina are Arterioles and venules (and some capillaries) found

A

found within the nerve fibre layer/ganglion cell layer

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2
Q

where in the retina are Capillaries only found

A

at the level of the inner nuclear layer

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3
Q

what is the capillary wall made up of and how are adjacent capillaries linked

A

Capillary wall made up of a layer of endothelial cells and pericytes surrounded by a shared basement membrane
(pericytes lie outside the endothelial cells)

Capillaries are non - fenestrated and adjacent endothelial cells are linked by tight junctions

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4
Q

what do capillary pericytes:
form
provide and
inhibit

A

Pericytes form a discontinuous layer outside the endothelium

Pericytes provide mechanical support to the capillary wall and may play a role in the regulation of capillary blood flow

Pericytes have also been shown to inhibit endothelial cell division in culture

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5
Q

what to capillary pericytes and endothelial cells both share

A

the same basement membrane

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6
Q

what do capillary pericytes and endothelial cells both share

A

the same basement membrane

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7
Q

what 2 things is the capillary basement membrane composed of

A

collagen glycoproteins and proteoglycans

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8
Q

what is the capillary basement membrane a determinant of

A

vascular permeability and also plays a role in the angiogenesis process

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9
Q

what is the homeostasis of the blood-retinal barrier maintained by

A

the selective permeability of retinal vessels and tight junctions between RPE cells = outer blood retinal barrier

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10
Q

which type of examining method is the clinical integrity of the blood-retinal barrier assessed by

A

fluorescein angiography

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11
Q

what is there a causal link of with diabetic retinopathy

A

between hyperglycaemia and diabetic retinopathy

high HBA1C levels

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12
Q

list the 3 classifications of DR

A

Non-proliferative
– Background
– Pre-proliferative

Proliferative

Maculopathy

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13
Q

list 3 clinical features of background retinopathy

A

Microaneuryms • Haemorrhages • Hard exudates

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14
Q

list 3 structural microscopic changes in micro vessels

A

Basement membrane thickening
Selective pericyte loss
Endothelial damage

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15
Q

what is an early histological feature of the disease

A

Basement membrane thickening

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16
Q

how much change in thickness and what is the 2 possible causes of basement membrane thickening

A

3-5X increase in thickness

caused by increased production or reduced degradation

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17
Q

what may a thickened basement membrane impede

A

may impede endothelial:pericyte and endothelial:glial interaction

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18
Q

what is a unique feature of diabetic retinopathy that is not seen in any other retinopathy

A

Selective pericyte loss

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19
Q

what is the endothelial cell:pericyte ratio in a normal and in a diabetic person

A

normal = 1:1

diabetic = 4:1

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20
Q

what may capillary pericyte loss influence

A

local blood-flow control

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21
Q

what does the endothelial changes in diabetes result in and what does endothelial damage result in

A

Loss of ability of endothelial cells to respond to changes in perfusion pressure

Endothelial damage associated with a breakdown of the blood-retinal barrier (BRB)

22
Q

what is the first ophthalmoscopic sign of diabetic retinopathy

A

Microaneurysms

23
Q

how do Microaneurysms appear and of what size

A

Dark red dots (10-100 microns in diameter)

24
Q

name 2 possible theories of microaneurysm pathogenesis

A

abortive neovascular response or vascular occlusion/dilatation

25
Q

name 2 clinical features which shows ophthalmoscopic evidence of a compromised BRB

A

the presence of haemorrhages and hard exudates

26
Q

how in particular does hard exudates show evidence of a compromised BRB

which retinal layer are they found in

A

represent leakage of plasma lipoproteinaceous material at the level of the retinal outer plexiform layer

27
Q

how do superficial haemorrhages appear in comparison to deeper ones

A

Superficial haemorrhages are “flame” shaped e.g. in the NFL - spread laterally

Deeper haemorrhages are of the “blot” type = darker and more circular

28
Q

what sign of DR indicates chronic retinal vascular leakage

A

Macula Oedema

Diabetic maculopathy with exudates centred around the fovea which are cystoid in nature

29
Q

list 4 features of Pre-proliferative retinopathy

A

• Venous changes (beading, loops)
• Multiple cotton wool spots
• Intra-retinal microvascular abnormalities (IRMA)
• Multiple haemorrhages

30
Q

what is venous changes/loops associated with in pre proliferative DR

A

associated with partitions of the larger retinal venules, which allows blood flow around the loop

31
Q

what are Cotton wool spots associated with

A

capillary non- perfusion

32
Q

what is Capillary non-perfusion preceded by

and what has been recently implicated

A

vascular occlusion / occurs as a result of capillary plugging

Leukocyte plugging of microvessels has recently been implicated
(vessels become plugged by WBCs which become sticky and attach themselves to the capillary wall and to each other to impede blood flow)

33
Q

where in the retinal do cotton wool spots aggregate and what does electron microscopy show

A

In the nerve fibre layer

Electron microscopy shows swollen axons containing accumulated debris of degenerated axoplasm

34
Q

what are cotton wool spots thought to be caused by

A

an interruption of axoplasmic transport

35
Q

how does IRMA appear and in which areas of the retina mostly

A

Retinal vessels showing abnormal branching patterns and irregular focal dilations

Lie within the retina at margins of areas of capillary non-perfusion

36
Q

what is IRMA a significant risk factor for

A

neovascularisation

37
Q

what is Proliferative retinopathy characterised by

A

active growth of new vessels - within the retina due to ischaemia

38
Q

which 2 places can active new vessels occur and which part of the circulation do new vessels arise from

A

on the disc or elsewhere in the retina

typically arise from the venous side of the circulation - where oxygen tension is lowest

39
Q

Stages of neovascularisation

Proliferating endothelial cells breach the __________ membrane and form a capillary ______

_______ extends by further endothelial ___________

Sprout becomes ________ forming a capillary _____

Capillary tube becomes invested with __________ cells

New vessels cross the _______ _________ ________ into the retro-hyaloid space

New vessels prone to _________ and ___________

New vessel formation associated with _________ __________ (_______)

Fibrosis causes abnormal attachments to the _______

Contraction of fibrotic tissue leads to _________ traction and _______ _____ formation

__________ _________ formation carries a high risk of ________ ___________

A

Proliferating endothelial cells breach the basement membrane and form a capillary sprout

Sprout extends by further endothelial proliferation

Sprout becomes canalised forming a capillary tube

Capillary tube becomes invested with perivascular cells

New vessels cross the inner limiting membrane into the retro-hyaloid space

New vessels prone to leakage and haemhorrage

New vessel formation associated with fibroblast proliferation (fibrosis)

Fibrosis causes abnormal attachments to the vitreous

Contraction of fibrotic tissue leads to vitroretinal traction and retinal tear formation

Retinal tear formation carries a high risk of retinal detachment

40
Q

where do new vessels proliferate

A

in the retro hyaloid space

41
Q

list the 5 steps of the pathogenic mechanisms of diabetic retinopathy

A

Hyperglycaemia
leads to

Biochemical Changes - such as in Polyol pathway PKC activation AGE
leads to

Vessel Damage
leads to

Vessel occlusion - causing Vascular growth factors
leads to

New vessel formation

42
Q

what is the name of the enzyme associated with the pathogenic mechanism of diabetic retinopathy

A

PKC - protein kinase C

43
Q

what is vascularisation of the retina controlled by

A

vasoformative growth factors

44
Q

what have several angiogenic growth factors been implicated in and name 5 examples

A

implicated in retinal neovascularisation

VEGF
IGF-1
bFGF
PDGF
PIGF

45
Q

what is an early and potent angiogenic signal

A

VEGF (vascular endothelial growth factor)

46
Q

what does VEGF cause an increase in

A

vascular permeability

47
Q

list 5 cells that produce VEGF

A

RPE
ganglion cells
Muller cells
pericytes
smooth muscle cells

48
Q

what consequence does VEGF produced by the RPE lead to with diabetic retinopathy

A

VEGF acting on the other blood retinal barrier at level of RPE leads to macula oedema

49
Q

what 2 things does VEGF act synergistically with

A

other growth factors (e.g. IGF-1 and bFGF) and prostaglandins

50
Q

Both Ranibizumab (Lucentis)) and Alfibercept (Eylea) have been approved by NICE for the treatment of DMO in eyes with a central retinal thickness of?

A

400 micrometres or more at the start of treatment

Medical Retina (17 decks)

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