Lecture 4 - Diabetic Retinopathy

Question 1

If your patient’s A1c was 6, what was their average blood sugar over the last 3 months?

Answer 1

130 - you can add or subtract 30 from here (Ex: 160 is A1c 7 or 100 is 5)

Question 2

which ethnicity has the highest prevalence of DM?

Answer 2

american indians/alaska natives > non-hispanic blacks > hispanics > asian americans > whites

Question 3

for a patient with DM, what is their A1c, fasting plasma glucose and oral glucose tolerance test?

Answer 3

A1c = 6.5 or above, fasting plasma glucose = 126 or above and oral glucose tolerance test = 200 or above 
(pre-diabetes = 5.7-6.4, 100-125, 140-199 and normal = 5, 99 or below, 139 or below)

Question 4

what did the diabetes control and complications trial (DCCT) conclude?

Answer 4

demonstrated benefits of intensive blood glucose control in patients with T1DM in regards to development and progression of diabetic retinopathy

Question 5

what did the united kingdom prospective diabetes study (SUKPDS) conclude?

Answer 5

showed a 21% reduction in the risk for progression of diabetic retinopathy over a 12 year period for the intensive glycemic control group

Question 6

what did the wisconsin epidemiologic study of diabetic retinopathy (WESDR) conclude?

Answer 6

severity of diabetic retinopathy is related to duration of disease (after 20 years 99% T1DM and 60% T2DM had retinopathy)

Question 7

what did the early treatment diabetic retinopathy study (ETDRS) study conclude?

Answer 7

gave standards for grading amount or diabetic retinopathy, clinically significant macular edema, demonstrated benefit of focal or grid laser, early scattered PRP not indicated in mild/moderate DR resulted in small reduction for risk of severe vision loss and ASA therapy had no impact on DR progression, risk of vitreous hemorrhage, VA loss but did reduce risk of comorbidity and mortality

Question 8

what are some diabetic complications systemically?

Answer 8

periodontal (gum) disease, neuropathy (hands/feet, digestion, carpal tunnel, ED), foot ulcers, non-traumatic lower limb amputations, kidney failure/dialysis, heart disease/stroke, 7th cause of death

Question 9

what can prevent diabetic complications?

Answer 9

A1c point drop, BP control, control LDL, foot care programs, detecting/treating early kidney disease

Question 10

what are some ocular complications of diabetes?

Answer 10

refractive changes (increased glucose levels in lens), dry eyes (decreased corneal sensation), snowflake cataract (sorbitol), PSC, glaucoma (neo or normotensive), CN6 palsy, CN3 palsy, CN4 palsy, diabetic papillopathy (optic neuropathy)

Question 11

what causes a CN6 palsy in diabetes?

Answer 11

poor blood flow or ischemia, sudden onset, transient and resolves in 3-6 months

Question 12

what causes diabetic papillopathy (optic neuropathy)?

Answer 12

increased leakage or microaneurysms, minimal affect on VA, unilateral or bilateral, resolved in 2-10 months (different than NAION which can be caused by DM or HTN)

Question 13

what is metabolic syndrome?

Answer 13

any 3 of the following = central obesity (40 men/35”women), triglycerides > 150, HDL cholesterol 130/85, fasting BS > 100, being treated for dyslipidemia/HTN/DM

Question 14

what is classified as mild NPDR?

Answer 14

microaneurysms, dot/blot mild-moderate in less than 4 quadrants, hard exudates (lipoproteins), risk of DME

Question 15

what is the follow up recommended for mild NPDR?

Answer 15

9 months to 1 year (ODs can manage)

Question 16

what is classified as moderate NPDR?

Answer 16

microaneurysms/hemorrhages mild to moderate in more than 4 quadrants, hard exudates, CWS (cystoid bodies), venous beading in less than 2 quadrants, IRMA, risk of DME 30-35%

Question 17

what is the follow up recommended for moderate NPDR?

Answer 17

6 months

Question 18

what is classified as severe NPDR?

Answer 18

4-2-1 rule (at least one needed) = microaneurysms/hemorrhages in all 4 quadrants, venous beading in 2 or more quadrants, moderately severe IRMA in one quadrant
50% develop PDR in 15 months

Question 19

what is classified as very severe NPDR?

Answer 19

same as severe but 2 or more of the categories

50% develop PDR in 15 months

Question 20

what is the follow up recommended for severe/very severe NPDR?

Answer 20

3 months or a retinal consult may be needed

Question 21

what is the treatment for severe/very severe NPDR?

Answer 21

PRP may be beneficial (ETDRS) but most surgeons hold off until PDR develops because it can cause VA loss

Question 22

what is the baseline photograph testing for diabetic retinopathy?

Answer 22

seven standard diabetic photograph fields - then put together in a mosaic (can be done 2 times per year)

Question 23

what are the 5 procedures done for document and testing in diabetes?

Answer 23

baseline fundus photography (2x per year), extended ophthalmoscopy (6x per year), amsler grid, OCT (4x per year) and FA

Question 24

what causes retinal hypoxia in proliferative diabetic retinopathy?

Answer 24

capillary closure, alterations in capillary basement membrane, increased blood viscosity, altered blood oxygen transport, abnormal metabolic pathways in retinal capillaries

Question 25

what is vascular endothelial growth factor (VEGF)?

Answer 25

a chemical signal (signaling protein) produced by cells that stimulate the growth of new blood vessels - it assists in restoring oxygen by creating new blood vessels

Question 26

where does neovascularization occur in PDR?

Answer 26

initially intraretinal - breaks through the ILM and lies between it and the vitreous, has a fibrous ground substance that contracts with the vessel growth = NVD/NVE/NVI

Question 27

what was concluded from the diabetic retinopathy study (DRS)?

Answer 27

provided low risk and high risk factors for PDR and found that laser photocoagulation reduced the risk of severe vision loss by more than 50% in eyes with high risk PDR

Question 28

what are the low risk factors for PDR developed by the diabetic retinopathy study (DRS)?

Answer 28

NVD less than 1/4 to 1/3 the disc or NVE without traction = obtain a retinal consult within 1 week

Question 29

what are the high risk factors for PDR developed by the diabetic retinopathy study (DRS)?

Answer 29

NVD greater than 1/4 to 1/3 the disc, NVD less than 1/4 to 1/3 the disc with vitreous/pre-retinal hemorrhage, NVE with vitreous/pre-retinal hemorrhage = obtain retinal consult within 24-48 hours

Question 30

what is the treatment for PDR?

Answer 30

pan-retinal photocoagulation (PRP) = argon laser applied throughout the mid-periphery and peripheral retina (does not go closer than 2DD from macula (S/I/T) and 1/2DD nasal to the disc)

Question 31

what are some side effects/complications of PRP?

Answer 31

CSME (from heat/inflammation), decreased night vision, decreased VF/peripheral vision, atrophic creep (laser scars coalesce), choroidal detachment

Question 32

what did the diabetic retinopathy vitrectomy study conclude?

Answer 32

early intervention of a vitrectomy lead to a better outcome with T1DM patients with a vitreous hemorrhage (PDR) vs. waiting 1 year

Question 33

what is the difference between focal and diffuse macular edema?

Answer 33

``` focal = caused by foci of vascular abnormalities, primarily microaneurysms diffuse = caused by dilated retinal capillaries in the retina ```

Question 34

what are the 2 types of laser used to treat macular edema?

Answer 34

focal laser = for focal macular edema and grid laser = for diffuse macular edema

Question 35

what is clinically significant macular edema (CSME) defined by ETDRS?

Answer 35

retinal thickening at/within 500 microns of center of macula, retinal thickening greater than 1DD within 1DD from center of macula, hard exudates at/within 500 microns of center of macula with adjacent retinal thickening

Question 36

what happens if you leave CSME untreated?

Answer 36

25-30% of patients exhibit a doubling of the visual angle within 3 years (if the patient has CSME but 20/20 you still treat because in 3 years they will be 20/40) = focal or grid laser

Question 37

is a vitrectomy a good option for patients with DME?

Answer 37

a vitrectomy facilitates greater blood flow through retinal vessels and is useful if there is evidence of vitreomacular traction or long-standing vitreous hemorrhage

Question 38

EDTRS asked 3 questions = is PRP effective in DME treatment? Is aspirin effective in diabetic retinopathy? and When should PRP be initiated to be most effective?

Answer 38

1. Yes 2. No 3. early laser reduced risk of need for vitrectomy and risk of progression to high-risk retinopathy for those with high risk characteristics

Question 39

what are the causes of blindness in patients with diabetic retinopathy?

Answer 39

CSME, pre-retinal/vitreous hemorrhage and retinal detachment (traction from NVE)

Question 40

what happens when VEGF binds to its trans-membrane VEGF receptors?

Answer 40

triggers angiogenesis cascade - cell proliferation, cell migration, retinal neo, choroidal neo, vascular permeability and CME

Question 41

what were the 2 forms of VEGF mentioned in lecture?

Answer 41

VEGF A (first one discovered and key inducer of angiogenesis) and VEGF isoform 165

Question 42

what are the 4 types of anti-VEGF therapies?

Answer 42

pegaptanib sodium (Macugen), Ranibizumab (Lucentis), Bevacizumab (Avastin) and Regeneron's Aflibercept (Eylea)

Question 43

what does pegaptanib sodium (Macugen) block?

Answer 43

VEGF 165 - first drug approved by FDA for neo ARMD

Question 44

what does Ranibizumab (Lucentis) block?

Answer 44

all forms of VEGF

Question 45

what did the READ 1 and READ 2 studies conclude?

Answer 45

READ 1 = Lucentis reduced the mean retinal thickness | READ 2 = Lucentis have the greatest vision gain, reduction in retinal thickness (vs. PRP or combo therapy)

Question 46

what did the RIDE and RISE studies conclude?

Answer 46

there was a 3 line improvement in vision with Lucentis vs. placebo and less progression

Question 47

what are some common adverse side effects of Lucentis?

Answer 47

subconjunctival hemorrhages, eye pain, increased IOP and floaters

Question 48

what does Bevacizumab (Avastin) block?

Answer 48

(mouse derived) all isoforms of VEGF - used off label in DME (more effective than focal laser)

Question 49

what does Aflibercept (Eylea) block?

Answer 49

(human protein) all forms of VEGF-A

Question 50

what did the studies VIVID and VISTA conclude?

Answer 50

Eylea was superior over laser to treat DME (most common side effect was cataract formation)

Question 51

what did the comparison study between Eylea, Avastin and Lucentis conclude?

Answer 51

mild VA = outcomes were simialr | worse VA = Eylea demonstrated more effective at improving vision

Question 52

what is triamcinolone acetonide?

Answer 52

a steroid injection = suppresses inflammation, reduces fluid from leaking blood vessels, inhibits fibrovascular proliferation and down regulates VEGF production (elevated IOP, cataracts and endopthalmitis can occur)

Question 53

what gave a better VA outcome triamcinolone acetonide vs. focal/grid laser?

Answer 53

initially the steroid had better VA but after 12 months the laser had better VA

Question 54

what are the 2 implants we need to know about?

Answer 54

ozurdex (allergan) and Iluvien (alimera sciences)

Question 55

what is Ozurdex (allergan)?

Answer 55

biodegradable dexamethasone pellet injected into the vitreous - lasts 37 days and gave a 3 line VA improvement (can produce cataracts and increase IOP)

Question 56

what is Iluvien (alimera sciences)?

Answer 56

cylindrical fluocinolone acetonide implant that stays in the vitreous base - lasts up to 36 months and gave a VA improvement of 15 letters (elevated IOP and cataracts)