Oc Pharm 2 (Anti-Angiogenic Meds)

What do VEG-F inhibitor target in the eye?

choriocapillaris, choroid, and inner retinal vessels

What retinal vessels must be targeted in DM, HTN, CRVO, and BRVO patients?

inner retinal vessels

What retinal vessels must be targeted in AMD and other outer retinal conditions patients?

choroid

What are the 4 options for treating/managing diabetic macular edema/clinically significant macular edema?

observation, focal laser, steroid or anti-VEGF injections, or surgery

What is the first line of therapy in patients with center-involving diabetic macular edema?

anti-VEGF and steroid injections

Where does neovascularization secondary to diabetes grow from?

capillary layer of the inner retina

What are the intravitreal anti-VEGF injections currently available?

Eylea, Vabysmo, Lucentis, Avastin

Why is laser not the first-line of therapy for proliferative diabetic retinopathy with diabetic macular edema?

panretinal photocoagulation (laser) can worsen preexisting DME

What are the 2 forms of advanced AMD?

geographic atrophy (dry) and choroidal neovascularization (wet)

What are the treatment options for wet AMD?

laser and anti-VEGF injections

Should you ever chose to observe wet AMD with clinical evidence of active choroidal neovascularization?

No

What protein is responsible for pathological ocular neovascularization such as in wet AMD?

VEGF-A 165 and Ang-2

How does the inhibition of VEGF benefit wet AMD patients?

decreases angiogenesis and the leakage and swelling of the retina

What is the role of Ang-2 in wet AMD?

it competes with Ang-1 to bind to TIE2, inhibiting TIE2 activation leading to pericyte dropout and sensitizing vessels to VEGF

If a patient with wet AMD stops getting anti-VEGF injections what will happen?

the neovascularization and leakage will come back

Which receptor does VEGF-A bind to?

VEGFR-2

If a patient has their own lens where is the intravitreal injection done?

4mm from the limbus

If a patient has an IOL where is the intravitreal injection done?

3mm from the limbus

What will lead to choroidal neovascularization?

any type of break or crack in Bruch's membrane

Which anti-VEGF drug was systemically approved for cancer but is used off label intravitreally?

Avastin (Bevacizumab)

What is the MOA of Avastin (Bevacizumab)?

recombinant humanized IgG1 monoclonal antibody inhibitor of VEGF-A isoforms (also dries up ocular blood vessels)

What is the MOA of Lucentis (Ranibizumab)?

recombinant humanized IgG1 monoclonal antibody inhibitor of VEGF-A isoforms

What is the MOA of Susvimo (Ranibizumab)?

recombinant humanized IgG1 monoclonal antibody inhibitor of VEGF-A isoforms

What is the MOA of Eyelea (Aflibercept)?

blocks all isoforms of VEGF and placental growth factor

What is the MOA of Vabysmo (Faricimab-svoa)?

inhibits VEGF and Ang-2 (Angiopoietin-2)

What are side effects of intravitreal anti-VEGF agents?

conjunctival hemorrhage, eye pain, vitreous floater, increase in IOP

What are complications associated with intravitreal anti-VEGF agents?

retinal detachment, endophthalmitis, cataract, thromboembolic events (stroke)

What are the 3 complement pathways?

classical, alternative, lectin

Which medications are used in the treatment/management of dry AMD (geographic atrophy)?

Syfovre and Izervay

Do Syfovre and Izervay reverse damage or improve VA associated with geographic atrophy?

No, but they slow the progression

What is the MOA of Syfovre (Pegcetacoplan)?

block C3 protein

What does an C3 overactivation in the eye result in?

retinal cell death

What is the MOA of Izervay (Avacincaptad Pegol)?

blocks C5

What is the purpose of polyethylene glycol (Pegol) in Izervay (Avacincaptad Pegol)?

increase half life