Disease III Final

Dr. Yacoub (Diabetic Ret, Retinal Vascular Occlusions)

____ is the leading cause of blindness in 18-64 y/o with incidence increasing as the pt ages

diabetic retinopathy

what population of people have the highest rate of diabetes?

hispanics, african americans, native americans (15%)

• bc of genetics, socioeconomic factors, diet

____ measures the amount of blood sugar in the blood after fasting

fasting blood sugar (FBS)

• fasting = no eating/drinking for at least 8 hrs, except water

____ measures the amount of sugar attached to hemoglobin over a 3-4 month window

glycated hemoglobin (HbA1c)

• 3-4 months bc the life cycle of a RBC is 3-4 months

what lab results are considered normal for diabetes?

HbA1c: 5.6% or lower

FBS: 99 mg/dl or lower

what lab results are considered prediabetic?

HbA1c: 5.7-6.4%

FBS: 100-125 mg/dl

what lab results are considered diabetic?

HbA1c: 6.5% or above

FBS: 126 mg/dl or more

7% HbA1c = ____ mg/dl

7% = 154 mg/dl

• add or subtract 14 for every 0.5% up or down

define time in range (TIR)

the amount of time pts with diabetes spend with their blood glucose levels in a recommended target range

• a more complete picture of daily glucose fluctuations

• helps identify trends in glucose levels

• associated with better healthcare outcomes

• typically done with continuous glucose monitor

[importance of TIR]

studies have shown that large glucose fluctuations have been associated with the following:

• oxidative stress

• inflammation

• increased risk of cardiovascular disease

• decline in cognitive function

• decreased quality of life

a lower time in range (TIR) is associated with

more advanced diabetic retinopathy

according to ADA guidelines, a pt with T1DM should have a dilated eye exam ____

T2DM pts should have a dilated eye exam ____

T1DM: DFE within 5 yrs of onset and then DFE every yr

T2DM: DFE at time of diagnosis and then DFE every yr

early diagnosis and treatment of diabetes can decrease severe vision loss (5/200) by

95%

what questions do we ask a diabetic pt?

• type of dibetes?

• how long have you been diabetic?

• is the diabetes in control? seeing a PCP?

• any fluctuation of vision?

• last FBS/RBS? Hba1c? TIR?

the goal for TIR is to be _____ at least 70% of the time

70-180 mg/dl at least 70% of the time

testing done in DFE

• BCVA (may need to refract)

• pupils, EOMs, confrontations/VF screener

  • diabetic pts are prone to cranial nerve palsies, especially CN 6

• SLE

  • look for iris neo at pupillary ruff

• IOP

  • r/o POAG, neo glc

• dilated fundus exam

• OCT/OCT-A

• ERG - shows function of cells too

• Amsler grid

pertinent negatives for diabetes

• (-) NVI

• (-) NVD (neo of disc)

• (-) NVE (neo elsewhere)

• (-) CSME (clinically significant mac edema) or (-) DME (diabetic macular edema)

*always write assessment/plan regarding diabetic retinopathy even if there’s no sign of diabetic retinopathy

pathophysiology of diabetes

damaged retinal capillaries with increased permeability and occlusion with decreased perfusion → retinal capillary death

• which leads to retinal hypoxia and retinal leakage (due to breakdown of inner blood-retina barrier)

diabetes causes an increase in what role players?

• advanced glycation end products (AGEs)

• sorbital

• protein kinase C

• VEGF

diabetes leads to an increase in advanced glycation end products (AGEs). why is this bad?

increase in AGEs causes:

• apoptosis of endo cells that line retinal capillaries

• increase in oxidative stress → retinal vascular damage

• increase in inflammation

• increase in VEGF

• increase in damage to pericytes

• disruption of proteins that make up walls of retinal vasculature

diabetes leads to increase in sorbital - why is this bad?

increase in sorbital causes:

• increases basement membrane thickneing of retinal vasculature

• increases damage to pericytes

• increases cataract formation

diabetes leads to an increase in protein kinase C - why is this bad?

increase in protein kinase C causes:

• increases damage to pericytes

• increases VEGF

• increase in platelet adherence/clotting → decrease in retinal blood flow

the ____ of retinal capillaries is typically a thin, fine structure that gives support to the capillary endo cells and pericytes

basement membrane of retinal capillaries

____ surround the retina capillary lumen, controls blood flow, synthesizes basement membrane

pericytes

what causes damaged retinal capillaries with increased permeability and decrease in perfusion in diabetes ?

increase in retinal vascular inflammation

+

damage to pericytes

+

apoptosis of endo cells that line retinal capillaries

+

basement membrane thickening

damaged retinal capillaries with increased permeability and decrease in perfusion will result in

proliferation of endo cells into lumen of capillaries (to fix capillary damage) → further thickening of basement membrane of capillaries

• due to being overworked → burnout of endo and vascular repair

• body tries to fix it

hypoperfusion vs. hyperperfusion

hypoperfusion: starts the process of diabetic retinopathy

hyperperfusion: leads to further vessel damage and progression

50% of pts with ____ will likely develop proliferative diabetic retinopathy after 20 yrs

type 1 DM

#1 risk factor for development of diabetic retinopathy

age of onset and duration = significant risk factor

• the earlier pt is diagnosed, the more likely they will have diabetic retinopathy

____ is thought to increase risk of diabetic retinopathy due to changes in hormones and poor control that tends to occur during this age

puberty

diabetes leads to progressive scarring and strain on the ____, which is found in the nephron, filters blood, and is highly vascular

glomerulus

diabetes leads to progressive scarring and strain on glomerulus → damaged glomerulus →

increase in proteinuria (albumin), blood urea nitrogen (BUN), serum creatine (waste build up in blood due to muscle activity) and decrease in GFR

• kidney damage → increase in BP → hyperperfusion in retina

*proteinuria = protein in urine

T/F: HTN increases risk of diabetic retinopathy due to further damage of retinal vasculature and hyperperfusion

true

sleep apnea leads to ____ which in turn causes damage to nerves involved with baroreceptor activity

systemic hypoxia

sleep apnea → damage baroreceptor activity →

nocturnal HTN → further damage retinal vascular and increase in hyperperfusion

____ increases activation of platelets and leukocytes, leading to retinal vascular damage and decrease in perfusion

smoking

how does smoking increase BP?

nicotine causes severe vasoconstriction → increases BP

• also increases risk of other CVD

high cholesterol is associated with increased accumulation of ____

retinal exudates (esp when looking at total cholesterol and LDLs)

T/F: high hematocrit was found to be significant risk factor for developing diabetic retinopathy due to increased hypoxia

false - low hematocrit (<40% in men, <34% in women)

• hematocrit measures volume % of RBC in blood

T/F: metformin can exacerbate anemia in pts bc it’s been associated with decrease in vit B12 and folic acid (needed for health and development of RBC)

true

hematocrit measures the

volume % of RBC in blood

____ increases systemic glucocorticoids leads to increase in free fatty acids and further insulin resistance

stress

_____ increases risk of insulin resistance, increase in hunger, and increase in calorie intake

sleep deprivation

_____ increases the presence of cytokines, glycerol, and fatty acids, which leads to insulin resistance and a decrease in insulin production

obesity

• also associated with CVD

• fam hx plays a role too

____ increases risk of retinal vascular permeability, development of retinal neo, and increase in platelet adherence

ocular inflammation

goal for HbA1c in diabetes

7%

BP goal for diabetics

<130/80

or <120/75 if pt has renal damage

why does lisinopril reduce progression of diabetic retinopathy and progression of proliferative diabetic retinopathy ?

lisinopril lowers BP and protects kidney function

____ and ____ decreases overall metabolic demand of the retina

thinning of ganglion cell layer and NFL

T/F: chronic elevated IOP leads to vasoconstriction of retinal vasculature, which decreases risk of hyperperfusion

true

____ and ____ associated with myopia lead to a decreased risk of hyperperfusion

retinal vascular thinning and attenuation

T/F: PVDs tend to happen earlier in myopes, which is a good thing

true - it’s good bc the vitreous tends to have high conc. of VEGF

what are some things that decrease overall metabolic demand of the retina?

• loss of retinal tissue

• retinal thinning

  • thinning of GCL and NFL

_____ decreases risk of hyperperfusion and is considered protective of diabetes progression but can lead to asymmetric diabetic retinopathy

mild carotid artery stenosis (15-49% of carotid artery occluded)

• the side without the occlusion is going to be worse

• moderate-severe carotid artery stenosis also leads to asymmetric diabetic retinopathy, but too much hypoxia

____ (too much hypoxia) increases progression of diabetes and is considered a risk factor and leads to asymmetric diabetic retinopathy

mod-severe carotid artery stenosis (50-100% of carotid artery occluded)

a pt presents with asymmetric dbe and 25% occlusion of right internal carotid artery. which eye will have the more severe diabetic retinopathy?

OS

a pt presents with asymmetric diabetic retinopathy and 75% occlusion of right internal carotid artery. which eye will have the more severe diabetic retinopathy ?

diabetic retinopathy more severe on same side - right eye

what’s the key sign that differentiates non-proliferative vs. proliferative diabetic retinopathy?

neovascularization

signs of non-proliferative diabetic retinopathy (NPDR)

• microaneurysms (MA)

• dot/blot hemorrhages

• flame hemorrahges

• roth spots

• cotton wool spots (CWS)

• venou beading

• vascular loops/omega loops

• intraretinal microvascular abnormalities (IRMA)

• capillary non-perfusion/dropout

define microaneurysms (MA)

earliest sign of diabetic retinopathy

• focal enlargement of capillary walls/outpouching due to weakening of capillary walls

• INL (hyper-reflective ring, non-homo inner content on OCT)

• temporal to fovea typically

• potential to be a permanent finding in retina

• best seen with FA, OCT-A

what does a MA look like on OCT?

• located in INL

• hyper-reflective ring with non-homogenous inner content

• small

• posterior shadowing

what does a MA look like on OCT-A?

disorganization of capillaries with focal areas of bulging seen in deep vascular complex slab

what does a MA look like on FA?

early bright hyperfluorescence, minimal leakage

• walls of MA are weak and leak slightly around the outpouching

• “christmas tree lights”

• best way to view MA

____ are small hemorrhages with distinct borders and form when MA or capillaries burst/leak

dot hemorrhages

dot hemorrhages are located in ____ and resolve in _____

INL, OPL (intraretinal)

resolves in 3 months

____ are large hemorrhages with indistinct/fuzzy borders and occur when MA or capillaries burst/leak

blot hemorrhages

_____ appear as linear, horizontal hemorrahges and occurs when larger pre-capillary arterioles burst/leak

flame hemorrhages

flame hemorrhages are located in ____ and resolve in ____

located in NFL (where axons of ganglion cells run horizontal/parallel to retina) - intraretinal

• resolves in 6 weeks

_____ are intraretinal hemorrhages with a white center and represents an acute systemic change (ex: rapidly increasing blood sugar)

roth spots

what do dot/blot/flame hemorrhages and roth spots look like on OCT?

uniform hyper-reflectivity

• might not show up if small

what do dot/blot/flame hemorrhages and roth spots look look like on FA?

hypofluorescence (blockage)

roth spots are intraretinal hemorrhages, typically a ___ or ____ hemorrhage

blot or flame hemorrhage

what do dot/blot/flame hemorrhages, roth spots, and CWS look like on FAF?

decrease in AF

cotton wool spots (CWS) are a build up of ____ which occur due to blockage of axoplasmic flow associated with a RNFL infarct

buildup of axoplasmic debris

CWS appear as a superficial white fluffy deposit in the ____ layer

retinal nerve fiber layer (NFL)

resolution of CWS

resolves in 3-4 months

• CWS will get smaller, waxy, more gray color

• after resolution → localized atrophy of ganglion cells and nerve fibers → leads to “depression” sign

• if a CWS or depression sign is large enough → lead to VF defect

what do CWS look like on OCT?

superficial hyper-reflective nodule at RNFL

• posterior shadowing

• inner retinal thinning (“depression sign”) may be noted following resolution of CWS

what do CWS look like on FA?

hypofluorescence (blockage) due to CWS itself with adjacent hypofluorescence (filling defect) due to non-perfusion

____ are composed of lipoproteins and appear as small, shiny yellow flecks typically associated with retinal fluid or edema

exudates

in diabetic retinopathy, exudates appear as

circinate rings with edema/fluid found in middle of the ring

exudates are found at ____ and resolve in ____

found in OPL, ONL (can infiltrate other layers too)

• take months-yrs to resolve

it’s visuallly devastating to have exudates in foveal region because

exudates can lead to fibrotic scarring and loss of retinal structures

• photoreceptor damage

what do exudates look like on OCT?

hyper-reflective spot at ONL/OPL

• can be associated with clear/hypo-reflective cystic spaces (fluid/edema)

• posterior shadowing

• lead to fibrotic scarring and loss of retinal structures

what do exudates look like on FA/FAF?

FA: hypofluorescence (blockage) due to exudates themselves with areas of adjacent hyper fluorescence (leakage)

• aka exudates are dark, leakage is bright

FAF: decrease in AF

venous beading occurs due to

weakening of venous walls and sludging/thickening of blood

• affects retinal veins/venules

• appears as sausaing

vascular loops and venous beading should show _____ on FA, OCT, OCT-A

no evidence of leakage, fibrotic tissue, or growth of vessels toward vessels

vascular loops/omega loops occur due to

extensive manipulation of vein/venule

• formed to bypass an occlusive area in vein/venule

• appears as loop

define intraretinal microvascular abnormalities (IRMA)

remodeling and dilation of pre-existing capillaries that occur to supply areas of capillary non-perfusion

• these capillaries are “backup”

• borders areas of capillary non-perfusion, in between arteries/arterioles and veins/venules

• brings blood supply to areas of non-perfusion

• looks almost identical to neo

IRMAs are found

at the level of superficial or inner retina (stays w/in the retina)

• unlike neo, which grows into vitreous

what does IRMA look like on OCT-A?

irregular vascular network in superficial vascular complex slab

• shouldn’t see these vessels in vitreoretinal interface (IRMA doesn’t grow into vitreous)

on FA and OCT, IRMA should look like

no evidence of leakage, fibrotic tissue, or growth toward vitreous

• some argue there’s slight leakage but much less than retinal neo

____ occurs due to capillary dropout/loss or lack of capillary blood flow, associated with retinal ischemia

capillary non-perfusion

on fundus, capillary non-perfusion looks like

an area in retina that’s mottled/irregular

• difficult to see

what does capillary non-perfusion look like on OCT?

disorganization and thinning of inner retina

what does capillary non-perfusion look like on OCT-A?

best seen on OCT-A

• areas of flow void in deep vascular complex slab

what does capillary non-perfusion look like on FA?

hypofluorescence (filling defect) due to loss of retinal capillaries

mild non-proliferative diabetic retinopathy is defined as ____

and should be treated as ____

microaneurysms only

treatment

• monitor, give amsler grid

• control BP, blood sugar, cholesterol + other potential risk factors

• see pt back in 1 yr

• 5% risk of progression to proliferative diabetic retinopathy within 1 yr

____ risk of mild non-proliferative diabetic retinopathy progression to proliferative diabetic retinopathy within 1 yr

5% risk of progression

define moderate non-proliferative diabetic retinopathy

• microaneurysms

• dot/blot/flame hemes

  • dot/blot > flame and CWS

• roth spots

• capillary non-perfusion/dropout

• cotton wool spots

• exudates

• venous beading

• omega/vascular loops

• IRMA

treatment of moderate non-proliferative diabetic retinopathy

• monitor, give amsler grid

• control BP, blood sugar, cholesterol + other potential risk factors

• see pt back in 6-12 months depending on level of blood sugar control and other systemic conditions/risk factors

• 12% risk of progression to proliferative diabetic retinopathy diabetic retinopathy within 1 yr