Diabetic Retinopathy Flashcards
what “regulates capillary blood flow and line the capillary endothelium”?
pericytes
what is glucose attached to amino group of proteins
glycation end products (AGEs)
what is sugar alcohol that is slowly metabolized by the body
Sorbitol
Aldose Reductase converts
glucose to sorbitol
glucotoxicity can lead to damage in every system of the body but the main ones are
nerves, retina, and kidneys
2 main things that happen in the retina secondary to diabetes:
hypoxia and edema
how to AGEs play a role in diabetic retinopathy?
- lead to disruption of the signals between proteins which leads to apoptosis of endothelial cells
- increase the amount of VegF
- cause damage to pericytes
what role does sorbitol play in diabetic retinopathy?
increase in sorbitol leads to basement membrane thickening and pericyte loss
-also plays role in cataract formation in diabetics
what has protein C been found to cause?
- pericyte apoptosis
- increase in VegF
- change blood flow
protein kinase C is activated by
blood sugar
what changes to platelet adherence and RBC change occur in diabetic ret and what does that cause?
increase in platelet adherence and RBC change shape leads to increase in thickness of blood flow as well as thickening of blood vessels and decrease in the ability of red blood cells to release/ carry oxygen
how does oxidative stress contribute to diabetic ret?
overproduction of free radicals leads to blood vessel damage and pericyte loss
retinal capillary cell death and dropout leads to what “end result”:
hypoxia and breakdown of blood-retina barrier
what does loss of pericytes (along the endothelium of the capillaries) lead to?
weakening of capillary walls and loss of capillary endothelial cells
thickening of the basement membrane occurs due to:
proliferation of endothelial cells into the lumen of the vessels which further lead to hypoxia
what type of perfusion starts the process of diabetic ret and what leads to further damage?
- hypoperfusion (hypoxia) starts the process of diabetic ret
- hyperperfusion leads to further vessel damage/progression
if diagnosed with diabetes before the age of 30, ___ % will develop retinopathy after 15 years but
if diagnosed with diabetes after the age of 30, ___ % will develop retinopathy after 15 years
97%
78%
1 risk factor to get diabetic ret is:
duration of diabetes
type 1 diabetes: __ % of patients will develop proliferative diabetic ret after 20 years
type 2 diabetes: __ % of patients will develop proliferative diabetic ret after 20 years
50%
10%
list of risk factors for diabetic retinopathy
puberty, kidney problems (check BUN, proteinuria, serum creatinine, GFR), hypertension, high cholesterol, pregnancy, genetics, ocular inflammation, sleep apnea, smoking
protective factors for diabetic ret
improving overall health issues, diet/exercise, glaucoma, myopia > -5D, carotid artery stenosis (if mild), optic atrophy, chorio-retinal scars
why can glaucoma be a protective factor for diabetic ret?
loss of ganglion cells and nerve fiber layer leads to a decrease in metabolic activity. decrease in perfusion secondary to increase in IOP
why is myopia a protective factor for diabetic ret?
longer axial length leads to retinal thinning. there is also a loss of retinal and choroidal blood flow, vessel thinning, and attenuation. PVDs are also more common and occur more quickly in myopes
which type of carotid artery stenosis is actually worst for diabetic ret?
severe: actually leads to an increase in ischemia especially if the patient already has later stages of diabetic ret
recent study: reducing blood sugar/Hba1c in Type 1 diabetics over a long period of time leads what reductions in getting diabetic ret and progression?
76% reduction in getting it
54% reduction in it progressing
does doxycycline show ant benefit to diabetic ret patients
does not appear to improve retinal function or slow progression in patients with mild to moderate NPDR
what are the benefits to put diabetic pt on a “Pril” drug such as Lisinopril?
reduced progression of diabetic ret by 50% and reduced progression of proliferative diabetic retinopathy by 80%
are NSAIDs used in diabetic ret?
may help (?) with inflammation in posterior set which may reduced chances of getting diabetic ret or progression of diabetic ret
what type of refractive error shifts can occur in diabetes
both hyperopic and myopic shifts have been associated with diabetes
(changes in thickness of lens, curvature, cortex, or milky NSC)
what Hb1ac and FBS is considered stable?
< 7.5% or FBS 180
what are you looking for on EOMs with diabetics?
CN palsies especially CN6- (esotropia seen)
4 pertinent negatives to note in diabetics chart
(-) NVI- iris
(-) NVD- disc
(-) NVE- elsewhere
(-) CSME- clinically significant macular edema
what is the size of what you see in the slit lamp in a 78D and 90D lens
78D- 1.2x
90D- 1.33x
the DCCT shows that control of blood sugar decreases development and progression by:
development by 76%
progression by 80%
tight control of BP leads to what % decrease in progression of retinopathy? what is considered tight control?
34% decrease in progression of retinopathy and vision loss
< 130/80 or <120/75 (if pt has renal damage)
how can cholesterol and exudates affect diabetic ret?
increase in cholesterol= increase in exudates
-there is a 50% increase in progression of ret if total cholesterol > 240
what is the mechanism behind the use of lasers for diabetic ret treatment
- increase in proliferation of RPE cells
- reestablishment of blood-retina barrier
- seals off leaky vessels
- decrease in oxygen demand
- increases proliferation of end cells in retinal capillaries
focal laser is defined as
- focal treatment
- 50-100 microns in size
grid laser is defined as
- diffuse treatment
- 100-200 microns in size
- 1DD apart
pan retinal photocoagulation is defined as
- large diameter (500 microns in size)
- usually 1000-2000 spots
- placed in mid-periphery
- nasal or inf retina usually first
- always treat CSME first
pan retinal photocoagulation is specifically for
retinal neovascularization
how does PRP work?
- decreasing need for oxygen which decreases hypoxia which decreases Veg-F which makes regress
- destroys retina and prevents further release of pro-angiogenic factors
what should always been done before PRP?
focal/grid laser
where is PRP usually done first and why?
nasal or inferior retina first because it is less likely to cause macular edema
what is the typical follow up plan for PRP
f/u 4-6 weeks b/c 50% of pts will show regression at this time
if neo regressed- f/u again in 3 months
if not- continue with more laser
where should PRP not be done?
not be done within 2DD of the macula and 500 microns from the nasal aspect of the nerve
what vision changes may happen after PRP? does VA improve?
- VA does not improve
- loss of peripheral vision
- decrease in night vision
what other side effects can come from PRP?
- can make macular edema worse
- atrophic creep (if done by macula/nerve)
- vitreous heme
- Neo may not regress/may need multiple treatments
how it VegF increased?
retinal hypoxia
what does VegF lead to?
breakdown of blood-retinal barrier and neovascularization
list 4 antiVegF drugs used
- Macugen
- Lucentis
- Avastin
- Eyelea
Microaneurysms (MA) is caused by:
- weakness of capillary walls
- focal enlargement of capillary walls/outpouching
what is the earliest sign of diabetic ret
Micro-aneurysms
what is the treatment for ciliochoroidal effusion (fluid in between sclera and choroid) ?
vitrectomy or ILM strip
in what layer(s) are dot and blot hemes located?
inner nuclear layer and outer plexiform layers
what is the difference in appearance between dot and blot hemes
dot: small, distinct
blot: large, fuzzy borders
hemes resolve in about
3 months
-absorbed
list of the 5 different types of hemes
- sub-retinal
- sub-RPE
- intra-retinal
- pre-retinal
- intra-vitreal
heme that is between RPE and sensory retina
sub-retinal
heme that is below RPE (more in choroid)
sub-RPE
heme that is within retina (above photoreceptors, below ILM)
intra-retinal
where dot/blot hemes are
heme that is below post hyaloid face but above ILM
pre-retinal
heme that is in vitreous cavity
intra-vitreal
what hemes are from larger pre-capillary arterioles and thus are located in the retinal nerve fiber which is not compact. blood is able to spread horizontally
flame
what hemes are from the venous end of the capillaries and thus are located in the more compact inner nuclear/outer plexiform layer (confinement is a result of adjacent retinal cells)
dot/blot
when do flame hemes resolve vs. dot/blot hemes?
flame hemes- 6 weeks
dot/blot- 3 months
what are 2 things that may help differentiate if the flame heme is from diabetes vs. hypertension?
any vessel changes (A/V ratio that is smaller than 2/3) or more cotton wool spots than hemes are indicative of hypertension
what is the criterion for moderate non-proliferative diabetic ret
- increase in dot/blot (mod in 4 quads or severe in 1 quad)
- MAs
- cotton wool spots
- venous beading (less than 2 quads)
- IRMA (mild)
- vascular loops/omega loops
what is the risk for developing proliferative diabetic ret in 1 year if you have MODERATE non-proliferative?
12-27%
f/u for mild non-proliferative
6-12 months
f/u for moderate non-proliferative
3-6
f/u for moderate non-proliferative
3-6 months
what are cotton wool spots? what can they cause clinically?
RNFL infarct which leads to blockage of axoplasmic flow. after resolution of CWS, there is atrophy of ganglion cell and nerve fibers which leads to a “depression” sign VF defect
what does venous beading look like and what causes it?
looks like sausaging
-due to weakening of blood vessel walls and sludging of blood
what is IRMA (intra-retinal microvascular abnormalities)? what layer is it located in?
new blood vessel growth from existing blood vessels vs. remodeling of pre-existing vessels which shunt blood over non perfused areas (at level of sensory retina)
how do you differentiate IRMA and neovascularization?
- IRMA is intra-retinal and it doesn’t really leak on the FA
- Neo forms more of a reticular network than IRMA
- Neo goes across both arteries and veins
- Neo usually has fibrovascular proliferation associated with it
what is the 4:2:1 rule for severe non-proliferative?
-4 quadrants of hemes
-2 or more quadrants of venous beading
-1 moderate-severe IRMA
(1 item severe, 2 items very severe)
f/u for severe non-proliferative?
1 month
what is the risk for developing proliferative diabetic ret in 1 year if you have SEVERE non-proliferative?
52%
what is the BEST indicator for potential proliferation?
venous beading
proliferative diabetic ret means you have one of what things?
NVD, NVE, NVI, NVA, pre-retinal hemorrhage, vitreal hemorrhage
what areas does neo grow towards?
towards the posterior hyaloid surface of the vitreous and towards areas of capillary non-perfusion
_____ is the process of growing new blood vessels
angiogenesis
what are neo vessels like and what can they lead to?
- they are weak and leak
- they carry fibrotic tissue (increases risk of fibrovascular proliferation)
- leaky vessels along the posterior hyaloid face leads to early liquefaction of the vitreous (PVD)
4 step process of neo
- stimulus: hypoxia, cyokines (increase with inflammation)
- Veg-F released (vascular endothelial cell growth)
- Veg-F binds to receptors on blood vessels that are nearby the initial stimulus
- new blood vessels develop towards the source of the signal
what is the specifications for NVD?
within 1DD of the optic nerve
-usually arises from large veins
where does NVI usually start on the iris?
pupillary ruff
specifications for classification Proliferative Diabetic Ret (LOW RISK)
- NVD less than 1/3 the size of the disc
- NVE less than 1/2 the size of the disc
follow up and treatment for Proliferative Diabetic Ret (LOW RISK)
-consult in 1-2 weeks
-treatment anti-VegF and PRP
(vitrectomy also considered)
specifications for classification Proliferative Diabetic Ret (HIGH RISK)
- NVD more than 1/3 the size of the disc
- NVE more than 1/2 the size of the disc
- any amount of NVD or NVE with a vitreal hemorrhage or a pre-retinal heme
follow up and treatment for Proliferative Diabetic Ret (HIGH RISK)
-consult in 24-48 hours
-treatment anti-VegF / PRP
(vitrectomy also considered)
what are collateral vessels?
- vessels develop within the retina vascular framework to join obstructed to non-obstructed vessels (pre-formed capillaries)
- not new vessels
- thin vessels but not as tortuous as neo
- no leakage on FA
what affect do collateral vessels have on neo?
they actually help reduce the amount of neo
what are the 3 types of collateral vessels
- A to A
- V to V
- A to V
optociliary shunt vessels are connections between:
central retinal vein and the peri-papillary choroidal veins
when do optociliary shunt vessels show up? what do they look like?
- occurs when retinal venous circulation is compromised
- does not leak
- thick
what other conditions can optociliary shunt vessels show up in?
- chronic glaucoma
- CRVO
- optic nerve sheath menangioma
- papilledema
- optic nerve gliomas
- disc drusen
what is the most common cause of decrease in vision in patients with diabetic retinopathy?
clinically significant macular edema
why does CSME occur?
breakdown of blood-retina barrier leads to leakage of plasma and exudates (lipoproteins) from small retinal vessels in the macula (especially the capillaries)
what is the appearance of CSME
circinate ring with exudates on the outside and leakage in the middle
3 criteria for CSME
- retinal thickening at or within 500microns (1/3DD) of the center of the macula
- exudates at or within 500microns (1/3DD) of the center of the macula with retinal thickening (b/c exudates can be present without any active edema)
- retinal thickening greater than 1DD in size within 1DD of the center of the macula
treatment options for CSME
- retina consult within 2 weeks
- controlling blood sugar (decreases risk of edema by 46%)
- focal/grid laser
- anti-VegF
does treatment for CSME improve VA?
stabilizes VA but doesn’t really improve it
for treatment of CSME, what did the READ-2 Study, RESTORE study, and BOLT study conclude?
antiVegF gold standard w/best outcomes or can be combined with laser- only downside is antivegF may need to be repeated more
what is an alternative treatment for CSME and what are the potential risks?
steroids for edema (for inflammatory component) such as Iluvien intravitreal implant, has risk for increased IOP and secondary glaucoma
what do you see on an OCT of CSME
- cystic spaced
- sub-retinal fluid
- decrease in reflectivity of RPE
- hyperreflective exudates
what is the difference in appearance between micro and macro aneurysms
macro are much larger, thicker, and irregular, has non-homogenous contents and typically surrounding edema and exudates will be present
what is the appearance of focal laser scars?
- absence/thinning of the retina
- photoreceptor/RPE loss
- increased reflectivity of the choroid and sclera
OCT appearance of exudates and
what can exudates lead to?
- hyper-reflective areas at the level of the OPL/ONL
- isolated and clustered
- posterior shadowing
- can eventually lead to fibrotic scarring and loss of retinal structures
OCT appearance of neovascularization and where does it start going/ eventually grow to?
hyper-reflective, fibrovascular formation along the ILM
-starts developing in the inner retina and will eventually grow into the vitreous (will become elevated)
OCT appearance of cotton wool spots
- superficial hyper-reflective nodule at the level of the RNFL
- can be fusiform
- posterior shadowing “screen effect”
what can cotton wool stops look similar to (but can be differentiated with an OCT)
myelnated RNFL
OCT appearance of intra-retinal hemorrhages
rarely visible on scan due to low reflectivity
OCT appearance of pre-retinal hemorrhage
- hyper-reflective
- posterior shadowing
FA appearance of dot/blot hemes
dark (hypo)
FA appearance of micro aneurysms
lighted dot with adjacent mild hyper fluorescence (leaky slightly around adjacent tissue)
FA appearance of leakage/ neo
hyper fluorescence increases (both in size and frequency) as the phases get later
FA appearance of cotton wool spots
dark areas (hypo) due to non-perfusion
FA appearance of capillary non-perfusion/ ischemia
dark areas
FA appearance of IRMA
no leakage or little leakage (not as much as neo)
is tractional RD non-rhegmatogenous or rhegmatogenous
non
list some things fibrovascular tissue can lead to
- dragging.distortion of the macula and optic nerve
- tractional retinal detachment
- vitreal hemorrhages
- macular hole
- retinal tears
pre-retinal hemorrhage (sub-hyaloid):
- what layer
- what appearance
- what type of patient
- in b/w ILM and posterior hyaloid face
- boat shaped appearance inferiorly or linear streak superiorly
- usually in younger patients
vitreal hemorrhage (intra-vitreal):
- what causes it
- what do they look like if old
- outcomes/ treamtment
- caused by neo growing into vitreous and hemorrhaging
- old ones turn brown or white and sink to bottom
- poor vision
- tx: anti-veg-F, vitrectomy (next option)
what are some indications for a vitrectomy?
- non-clearning vitreous heme with anti-VegF treatment
- tractional RD
- dense pre-retinal heme
- severe PDR
- tractional macular edema
- progressive neo despite full PRP
- pre-retinal heme over macula
complications and f/u for vitrectomy:
- complications: endophthalmitis, cataract, RD, corneal decompensation
- f/u: 1 day, 1 week, 1 month, 3 month, and frequent DFEs
treatment for angle closure
- cycloplegia 1% BID
- topical steroids
- dilate: decrease IOP by increasing outflow through uveo-scleral pathway
- glaucoma drops (except pilocarpine and prostaglandins)
- PRP/ anti-Veg-F
- bleb/shunt
what can make macular ischemia worse
lots of laser in that area
what does capillary non-perfusion look like on OCT
-disorganization and thinning of the inner retina
-outer retina typically intact
(dark- areas without capillaries)
what is a form of non-AION that is has mild optic nerve head edema, prominent surface vessels with fine hemorrhages on the disc, and with a small APD present
diabetic papillopathy
what were roth spots believe to be from and what is it believed to be currently
- initially thought to be bacterial emboli or leukocytes
- white center represents coagulated fibrin thrombus from a ruptured vessel
- represents more of an acute systemic change
what are some systemic causes of roth spots
- bacterial endocarditis
- leukemia
- anemia (pernicious usually)
- HIV (rarely)
- carbon monoxide poisoning
- hypertensive retinopathy
- shaken baby syndrome
- sickle cell
- lupus (or other connective tissue disorders)
when is diabetic ret involutional
“they have it but not active”
- decrease in the caliber of vessels
- fibrovascular proliferation
- ghost vessels
