Age related macular degeneration: optometric management and medical treatment Flashcards
what leads to the increase in VEGF being produced in AMD
hypoxia increases VEGF being produced and then the vessels become more leaky
what was the first medical treatment for AMD
Macular laser photocoagulation for nAMD
for which type of AMD were all these drugs only treatable for and what type of AMD was it not treatable for and therefore what type of treatment was available for them
all medical treatments were only treatable for nAMD
not for early or dry AMD which required more lifestyle changes
what did research find that the anti-VEGF treatment Ranibizumab (Lucentis) for nAMD could do
could actually restore vision in those people with vision loss due to wet AMD
how does Macular Photocoagulation work in treating nAMD
what can this cause as a consequence
what was required
in how many and what type of AMD patients was this only suitable for
Destruction of new blood vessels with thermal laser (seals off the new blood vessels)
Slows visual loss by destroying new vessels, but does not restore vision
Causes scotoma in lasered region (retina destroyed in lasered area too due to the very high intensity)
Retreatment is often required (~60% of px in 3 years)
Only suitable for about 1/20 px with nAMD as had to be classic and extrafoveal
how does Photodynamic Therapy (PDT) work in treating nAMD
Photosensitiser (verteporfin) injected intravenously (into the blood supply)
Binds to low density lipoproteins in the blood
Low density lipoproteins taken up by active endothelial cells in growing blood vessels, such as those which occur in neovascular AMD
Therefore, verteporfin is taken up by and accumulates in the CNV membrane
A low powered laser is directed onto the area of CNV to activate the photosensitiser. This takes place 15 minutes after the start of the infusion
When the photosensitiser, verteporfin, is activated, the new blood vessels are closed off
therefore this damages the new blood vessels and stop them from growing and does not blast off the retina as the laser is just used to activate the drug thats accumulated in the new blood vessels, so is a better treatment as does not cause a scotoma
what is the difference between treating nAMD with Macular Photocoagulation and Photodynamic Therapy (PDT)
Photodynamic Therapy (PDT) = More targeted destruction of vessels – less collateral damage to retina than photocoagulation
how effective was treatment using Photodynamic Therapy (PDT) compared to someone with nAMD receiving no treatment at all
both treated and untreated groups lose vision over 2 years, but greater VA loss in untreated group
e.g. the mean visual loss was just over 20 letters with the placebo group and 10 letters with the group who received PDT treatment
what is a disadvantage of Photodynamic Therapy (PDT)
often results in the development of geographic atrophy over repeated retreatments due to reduced choroidal perfusion
what was the NICE guidelines for Photodynamic Therapy (PDT) use (give 2 conditions)
and what did this mean about the amount of nAMD px’s that were suitable for this treatment
NICE recommends PDT for people with wet AMD who have:
- a confirmed diagnosis of classic subfoveal (under fovea) choroidal neovascularisation (CNV), with no sign of occult CNV
- VA 6/60 or better
[i.e. still not suitable for all px]
Only about 1 third of wet AMD patients suitable for treatment
why is anti-VEGF drugs the new treatment of choice
as were first treatment to restore vision, suitable for most forms of nAMD
(so not restricted to classic or subfoveal like in PDT and was the first treatment that could restore vision rather than just slow down)
which anti-VEGF therapy is the treatment of choice
Ranibizumab (‘Lucentis’)
what is Ranibizumab (‘Lucentis’) and how does it work
is anti-VEGF antibody, binds to and inhibits all forms VEGF-A, thereby impeding choroidal neovascular growth beneath the retina
i.e. sticks to the VEGF molecule and inhibits them
what is the NICE guidelines and RCO guidelines for Ranibizumab as treatment of choice for nAMD when all of the 5 following criteria apply
VA 6/12-6/96 (as no evidence it improves vision in px with 6/12)
No permanent structural damage to fovea (as won’t get better)
Lesion size less than 12 disc areas
Evidence of disease progression
Blood of less than 50% in the lesion area
what is the NICE and RCO guidelines for stopping treatment/discontinuation of Ranibizumab
persistent deterioration VA; identification of anatomical changes in retina indicating inadequate response to therapy
describe the mechanism of how VEGF occurs in wet AMD
Vascular endothelial growth factor (VEGF) molecules bind to it’s receptor
This starts a cascade of chemical reactions, which leads to proliferation of vascular endothelial cells, and increased permeability and migration of vessels, all of which results in angiogenesis (the development of new vessels)
It also makes blood vessels more leaky = why we see blood build up in someone who has wet AMD
Anti VEGF therapy attempts to disrupt this cycle, thereby providing a way of treating all types of neovascular AMD
describe the mechanism of how Anti VEGF therapy attempts to disrupt this cycle of how VEGF occurs in wet AMD
Ranibizumab is an antibody which binds to all forms of the angiogenic Vascular Endothelial Growth Factor A
When the Ranibizumab molecule is bound to VEGF, VEGF is no longer able to bind to, and activate, its receptor, hence the chemical cascade initiating CNV is inhibited