Diabetic Retinopathy Flashcards
Pathophysiology of Diabetic retinopathy
- Prog. damage to retina due to complications of diabetes mellitus
- can cause blindness
The retina is composed of the ____ and the _____.
- Macula
- Fovea
What is the macula?
- Retinal area about 5 mm diameter; directly behind pupil
- high conc. of cones for crisp central vision
What is the fovea?
- Found at center of macula
- highest density of cones in retina
- important for central vision (color res., driving, reading)
What are the 3 classifications of diabetic retinopathy?
- Nonproliferative DR (inital stage of disease)
- Proliferative DR (advanced stage)
- Diabetic macular edema (can occur at any stage of disease)
What initiates the cascade of biochemical processes that drive DR disease progression?
Chronic intracellular hyperglycemia
Which processes are compromised in the cascade?
- Aldose reductase(Sorbitol) and protein kinase pathways(PKC)
- Renin-angiotensin system (RAS)
- Oxidative stress
- Accumulation of advanced glycation end products (AGE)
- Release of inflamm. mediators and VEGF which damage ophthalmic vascular endothelial cells
non-proliferative DR can be classified as mild, ____, and ______.
moderate and severe
Mild NPDR
-tiny swellings (microaneurysms) in retinal capillary walls
Moderate NPDR
- has exudates (lipid-rich deposits from leaky damaged capillaries)
- edema and retinal hemorrhages
- capillary occlusions (body trying to repair vessel damage—>ischemic retina)
- cotton wool spots (formed by oxygen-deficit distal to capillary occlusion)
Severe NPDR
-severe hemorrhages, microaneurysms, and exudate formation
Describe the clinical findings of diabetic macular edema (DME)
- retinopathy (thickening and edema) within macula area
- most common cause of vision loss in DR
- peripheral vision is sustained
- can occur at any stage of DR
Clinical findings: Pathophysiology of Proliferative DR
- Occlusion of blood vessels with ischemia –>upregulation of growth factors
- ->stimulate formation of new blood vessels
What are the complications of proliferative DR?
- New blood vessels are abnormal and thin
- easily ruptured; bleed into retina and vitreous
- scar tissue may form on blood vessels
- damaged tissue may pull on retina (retinal detachment)–>spotty vision, light flashes, vision loss
How does proliferative DR’s vision loss differ from nonproliferative DR?
Proliferative DR causes more severe vision loss, and it can affect both central and peripheral vision.
Why is VEGF important in Proliferative DR?
- major factor in new blood vessel formation
- increased levels reported in patients with disorder
- activates two kinase receptors (VEGFR-1 and VEGFR-2)–>regulate pathophysiological angiogenesis
- proliferation, migration, survival, and angiogenesis of endothelial cells
VEGF also increases retinal vascular permeability and causes breakdown of ____ leading to ______.
- blood-retinal barrier
- retinal edema
What is the strategy of pharmacological intervention in DR?
prevent, slow, or reverse vision loss in order to maintain or improve vision-related quality of life
Which drug classes are used in the treatment of DR?
- Corticosteroids
- VEGF inhibitors
Which corticosteroids are used?
- Dexamethasone
- Fluocinolone
Corticosteroid MOA
produce anti inflamm actions by:
- decrease release of vasoactive/chemo-active factors at sites
- decreased secretion of lipolytic and proteolytic enzymes
- decrease leukocyte migration
- increase tight junctions b/t capillary endothelial cells
What is Dexamethasone used to treat? How is it administered?
-intravitreally active
-Treats macular edema following branch or central retinal vein occlusion
-Treats diabetic macular edema
-Treats non-infectious uveitis affecting
posterior segment of eye
What is Fluocinolone used to treat? How is it administered?
- Active intravitreally (as an implant)
- Treats diabetic macular edema in pats previously treated with corticosteroids without significant rise in IOP
What is the MOA of VEGF inhibitors?
inhibit VEGF production and preventing retinal neovascularization
How is Ranibizumab used for DR?
- recombinant humanized antibody fragment; active against all VEGF-A isoforms
- active intravitreally
- Treats DR, diabetic macular edema, neovascular (wet) age-related macular degeneration*
- macular edema following retinal occlusion
- myopic choroidal neovascularization*
How is Aflibercept used?
- recombinant fusion protein
- binds VEGF-A w/ higher aff than ranibizumab
- binds VEGF-B and placental growth factor
- active intravitreally
- Treats DR, diabetic macular edema, neovascular (wet) age-related macular degeneration*
- macular edema following retinal vein occlusion
