Lecture 4 - Diabetic Retinopathy Flashcards
If your patient’s A1c was 6, what was their average blood sugar over the last 3 months?
130 - you can add or subtract 30 from here (Ex: 160 is A1c 7 or 100 is 5)
which ethnicity has the highest prevalence of DM?
american indians/alaska natives > non-hispanic blacks > hispanics > asian americans > whites
for a patient with DM, what is their A1c, fasting plasma glucose and oral glucose tolerance test?
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)
what did the diabetes control and complications trial (DCCT) conclude?
demonstrated benefits of intensive blood glucose control in patients with T1DM in regards to development and progression of diabetic retinopathy
what did the united kingdom prospective diabetes study (SUKPDS) conclude?
showed a 21% reduction in the risk for progression of diabetic retinopathy over a 12 year period for the intensive glycemic control group
what did the wisconsin epidemiologic study of diabetic retinopathy (WESDR) conclude?
severity of diabetic retinopathy is related to duration of disease (after 20 years 99% T1DM and 60% T2DM had retinopathy)
what did the early treatment diabetic retinopathy study (ETDRS) study conclude?
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
what are some diabetic complications systemically?
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
what can prevent diabetic complications?
A1c point drop, BP control, control LDL, foot care programs, detecting/treating early kidney disease
what are some ocular complications of diabetes?
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)
what causes a CN6 palsy in diabetes?
poor blood flow or ischemia, sudden onset, transient and resolves in 3-6 months
what causes diabetic papillopathy (optic neuropathy)?
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)
what is metabolic syndrome?
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
what is classified as mild NPDR?
microaneurysms, dot/blot mild-moderate in less than 4 quadrants, hard exudates (lipoproteins), risk of DME
what is the follow up recommended for mild NPDR?
9 months to 1 year (ODs can manage)
what is classified as moderate NPDR?
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%
what is the follow up recommended for moderate NPDR?
6 months
what is classified as severe NPDR?
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
what is classified as very severe NPDR?
same as severe but 2 or more of the categories
50% develop PDR in 15 months
what is the follow up recommended for severe/very severe NPDR?
3 months or a retinal consult may be needed
what is the treatment for severe/very severe NPDR?
PRP may be beneficial (ETDRS) but most surgeons hold off until PDR develops because it can cause VA loss
what is the baseline photograph testing for diabetic retinopathy?
seven standard diabetic photograph fields - then put together in a mosaic (can be done 2 times per year)
what are the 5 procedures done for document and testing in diabetes?
baseline fundus photography (2x per year), extended ophthalmoscopy (6x per year), amsler grid, OCT (4x per year) and FA
what causes retinal hypoxia in proliferative diabetic retinopathy?
capillary closure, alterations in capillary basement membrane, increased blood viscosity, altered blood oxygen transport, abnormal metabolic pathways in retinal capillaries
what is vascular endothelial growth factor (VEGF)?
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
where does neovascularization occur in PDR?
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
what was concluded from the diabetic retinopathy study (DRS)?
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
what are the low risk factors for PDR developed by the diabetic retinopathy study (DRS)?
NVD less than 1/4 to 1/3 the disc or NVE without traction = obtain a retinal consult within 1 week
what are the high risk factors for PDR developed by the diabetic retinopathy study (DRS)?
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
what is the treatment for PDR?
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)
what are some side effects/complications of PRP?
CSME (from heat/inflammation), decreased night vision, decreased VF/peripheral vision, atrophic creep (laser scars coalesce), choroidal detachment
what did the diabetic retinopathy vitrectomy study conclude?
early intervention of a vitrectomy lead to a better outcome with T1DM patients with a vitreous hemorrhage (PDR) vs. waiting 1 year
what is the difference between focal and diffuse macular edema?
focal = caused by foci of vascular abnormalities, primarily microaneurysms diffuse = caused by dilated retinal capillaries in the retina
what are the 2 types of laser used to treat macular edema?
focal laser = for focal macular edema and grid laser = for diffuse macular edema
what is clinically significant macular edema (CSME) defined by ETDRS?
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
what happens if you leave CSME untreated?
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
is a vitrectomy a good option for patients with DME?
a vitrectomy facilitates greater blood flow through retinal vessels and is useful if there is evidence of vitreomacular traction or long-standing vitreous hemorrhage
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?
- Yes
- No
- early laser reduced risk of need for vitrectomy and risk of progression to high-risk retinopathy for those with high risk characteristics
what are the causes of blindness in patients with diabetic retinopathy?
CSME, pre-retinal/vitreous hemorrhage and retinal detachment (traction from NVE)
what happens when VEGF binds to its trans-membrane VEGF receptors?
triggers angiogenesis cascade - cell proliferation, cell migration, retinal neo, choroidal neo, vascular permeability and CME
what were the 2 forms of VEGF mentioned in lecture?
VEGF A (first one discovered and key inducer of angiogenesis) and VEGF isoform 165
what are the 4 types of anti-VEGF therapies?
pegaptanib sodium (Macugen), Ranibizumab (Lucentis), Bevacizumab (Avastin) and Regeneron’s Aflibercept (Eylea)
what does pegaptanib sodium (Macugen) block?
VEGF 165 - first drug approved by FDA for neo ARMD
what does Ranibizumab (Lucentis) block?
all forms of VEGF
what did the READ 1 and READ 2 studies conclude?
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)
what did the RIDE and RISE studies conclude?
there was a 3 line improvement in vision with Lucentis vs. placebo and less progression
what are some common adverse side effects of Lucentis?
subconjunctival hemorrhages, eye pain, increased IOP and floaters
what does Bevacizumab (Avastin) block?
(mouse derived) all isoforms of VEGF - used off label in DME (more effective than focal laser)
what does Aflibercept (Eylea) block?
(human protein) all forms of VEGF-A
what did the studies VIVID and VISTA conclude?
Eylea was superior over laser to treat DME (most common side effect was cataract formation)
what did the comparison study between Eylea, Avastin and Lucentis conclude?
mild VA = outcomes were simialr
worse VA = Eylea demonstrated more effective at improving vision
what is triamcinolone acetonide?
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)
what gave a better VA outcome triamcinolone acetonide vs. focal/grid laser?
initially the steroid had better VA but after 12 months the laser had better VA
what are the 2 implants we need to know about?
ozurdex (allergan) and Iluvien (alimera sciences)
what is Ozurdex (allergan)?
biodegradable dexamethasone pellet injected into the vitreous - lasts 37 days and gave a 3 line VA improvement (can produce cataracts and increase IOP)
what is Iluvien (alimera sciences)?
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)
