Age related macular degeneration: optometric management and medical treatment

Question 1

what leads to the increase in VEGF being produced in AMD

Answer 1

hypoxia increases VEGF being produced and then the vessels become more leaky

Question 2

what was the first medical treatment for AMD

Answer 2

Macular laser photocoagulation for nAMD

Question 3

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

Answer 3

all medical treatments were only treatable for nAMD

not for early or dry AMD which required more lifestyle changes

Question 4

what did research find that the anti-VEGF treatment Ranibizumab (Lucentis) for nAMD could do

Answer 4

could actually restore vision in those people with vision loss due to wet AMD

Question 5

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

Answer 5

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

Question 6

how does Photodynamic Therapy (PDT) work in treating nAMD

Answer 6

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

Question 7

what is the difference between treating nAMD with Macular Photocoagulation and Photodynamic Therapy (PDT)

Answer 7

Photodynamic Therapy (PDT) = More targeted destruction of vessels – less collateral damage to retina than photocoagulation

Question 8

how effective was treatment using Photodynamic Therapy (PDT) compared to someone with nAMD receiving no treatment at all

Answer 8

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

Question 9

what is a disadvantage of Photodynamic Therapy (PDT)

Answer 9

often results in the development of geographic atrophy over repeated retreatments due to reduced choroidal perfusion

Question 10

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

Answer 10

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

Question 11

why is anti-VEGF drugs the new treatment of choice

Answer 11

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)

Question 12

which anti-VEGF therapy is the treatment of choice

Answer 12

Ranibizumab (‘Lucentis’)

Question 13

what is Ranibizumab (‘Lucentis’) and how does it work

Answer 13

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

Question 14

what is the NICE guidelines and RCO guidelines for Ranibizumab as treatment of choice for nAMD when all of the 5 following criteria apply

Answer 14

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

Question 15

what is the NICE and RCO guidelines for stopping treatment/discontinuation of Ranibizumab

Answer 15

persistent deterioration VA; identification of anatomical changes in retina indicating inadequate response to therapy

Question 16

describe the mechanism of how VEGF occurs in wet AMD

Answer 16

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

Question 17

describe the mechanism of how Anti VEGF therapy attempts to disrupt this cycle of how VEGF occurs in wet AMD

Answer 17

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

Question 18

what are the 4 steps of carrying out the treatment of nAMD using

Answer 18

Topical anaesthesia
Injection into vitreous
Check retinal artery perfusion (count fingers)
Antibiotic drops (to avoid infection)

Question 19

after injecting the Ranibizumab into the patient’s eye, what must you do/check and why

Answer 19

Check retinal artery perfusion by asking px to count fingers

As it is possible that as the pressure goes up when injecting the drug that it can block the flow of blood going through the central retinal artery, so must check that px is losing vision

Question 20

what is the course of Ranibizumab treatment

what is also carried out during these treatments and why

Answer 20

three monthly loading injections on first diagnosis, followed by monthly follow up appointments pro re nata (as required)
At monthly follow ups, a combination of OCT, VA and fundus examination is used which will indicate if need to give further injections

Question 21

when will Ranibizumab injections only be given to a patient

Answer 21

First diagnosis is always based on fluorescein angiography

Injections will only be given if theres signs of progression, diagnosed by FA

Question 22

what outcome/improvement did Ranibizumab injections treatment show after 2 treatments

Answer 22

all of the fluid has now been reabsorbed
the macula is thinner (as swelling and elevation has gone down)
va has gone from 6/18 with injection 1 to 6/9 on injection 2
= immediate affect

Question 23

name 3 other anti-VEGF drugs used other than Ranibizumab (‘Lucentis’) for nAMD treatment

Answer 23

Pegaptanib (Macugen)
Bevacizumab (Avastin)
Aflibercept (Eylea; VEGF Trap Eye)

Question 24

what is the anti-VEGF drug Bevacizumab (Avastin)

Answer 24

Monoclonal anti-VEGF antibody

Developed for intravenous use in cancer treatment

Not licensed for intraocular use, but its effectiveness in the treatment of neovascular AMD has been established in randomised controlled trials, and it is used off-label as a treatment
It is not used by the NHS, but it is cheaper, so some private treatments may use it instead

Question 25

how does the anti-VEGF drug Aflibercept (Eylea; VEGF Trap Eye) work
what is the course of treatment

Answer 25

Not an antibody, but a fusion protein made of two parts of VEGF-receptor molecule

In this way it binds to and inhibits/blocks VEGF-A and B and Placental Growth Factor

3x 4-weekly loading dose
8-weekly maintenance dosing (potential advantage over monthly follow-ups required for Ranibizumab)

Question 26

what advantage does anti-VEGF drug Aflibercept (Eylea; VEGF Trap Eye) have over Ranibizumab and what do some hospitals do

Answer 26

after the first 3 month dose, they only need a follow up every 2 months instead of every 1 months with Ranibizumab = cheaper for hospitals

Used by some hospitals on patients unresponsive to Ranibizumab

Question 27

what is the speed of referral for nAMD i.e. with suspect newly developed neovascular AMD

Answer 27

Urgent referral

Question 28

what 8 following signs need to be true of a suspect newly developed neovascular AMD in order to warrant rapid access pathways for a urgent referral

Answer 28

• Recent onset markedly distorted, blurred, or absent lines on Amsler grid
• Recent onset marked reduction in VA
• Hyperopic shift in Rx (retina smaller, eyes swollen)

And/ or retinal signs include any one of the following:

• Haemorrhage (sub-RPE, sub-retinal, intra-retinal)
• Exudates (requires urgent referral as it is a sign of leakage from new vessels)
• Visible retinal elevation
• Sub-retinal, intra-retinal or sub-RPE fluid
• Sub-retinal neovascular membrane (which may be seen as a green/grey lesion)

if there is a recent onset reduction in VA (whilst treatment will only be given to those in the range 6/12-6/96, newly developed CNV should still be referred urgently if the VA is outside of this range), or if a hyperopic shift in Rx has occurred

Question 29

what 3 things should you do for when referring and managing a px with nAMD

Answer 29

Find out your LOCAL REFERRAL PATHWAY for wet AMD – many areas have special referral paths to rapid access clinics straight to the local macular specialist - so don’t always have to go via GP

EDUCATE patients with unilateral nAMD of symptoms of wet AMD (check for distortions and sudden onset visual loss), and encourage them to monitor fellow eye daily using Amsler chart, window frame, or similar.

Advise on LIFESTYLE CHANGES, e.g. stopping smoking, changing diet to green leafy vegetables and potential vitamin supplementation (AREDS formula) may also be appropriate

Question 30

which 2 types of patients with end stage AMD is not suitable for treatment and what should you still do

Answer 30

Not treatable:
Longstanding wet AMD with scar tissue formation, and nAMD with VA worse than 6/96

Geographic atrophy

However best to refer all newly diagnosed wet AMD for ophthalmological opinion and let them diagnose px as not treatable

Question 31

list 8 things as optometrists we should do to help patients with of untreatable end stage nAMD and GA

Answer 31

Check fellow eye
Education
Lifestyle Advice
Nutritional Supplements
Refraction
Low vision assessment
Referral to Social Services, ROVIs etc
Referral to Voluntary Sector

Question 32

why would you want to check the fellow eye of a px with untreatable end stage nAMD and GA and how

Answer 32

For signs of incipient neovascular AMD, which may be amenable to treatment
To make sure of no new met AMD in other eye
Or for people with GA, check their GA just to double make sure theres no new wet AMD

Thorough fundus check, Amsler chart

Question 33

list 7 ways of how you will educate a px with untreatable end stage nAMD and GA

Answer 33

• Disease awareness
• Future prognosis
• Risk of development of AMD in second eye (12% chance every year)
• Need for check ups with Optom / Ophthalmologist for any other pathology
• Symptoms of neovascular AMD (monitoring of fellow eye)
• Risk factors (see Lifestyle Advice)
• Provide written information - for px to remember all this

Question 34

what 3 pieces of lifestyle Advice will you give to a px with untreatable end stage nAMD and GA

Answer 34

Stop smoking (biggest modifiable risk factor)

Wear sunglasses

Diet: College of Optometrists recommend…

• Eat balanced diet containing lots of coloured fruit and vegetables.
• Increased dark leafy veg intake likely to be protective.
• Increased oily fish intake likely to be beneficial in AMD.

Question 35

which Nutritional Supplements is advised to be taken by a px with untreatable end stage nAMD and GA

Answer 35

AREDS and AREDS 2 formulae only ones with proven effect at preventing AMD progression

Question 36

give 3 reasons why it is useful to carry out a thorough refraction when managing a px with untreatable end stage nAMD and GA

Answer 36

Improves VA in 11% of low vision patients

Amblyopic eye may become better eye - this px who used to have a balance lens will now need full rx

Refraction may change as eccentric viewing develops

Question 37

list all the reasons why you will want to manage a px with untreatable end stage nAMD and GA with a low vision assessment (by referring or manage ourselves)

Answer 37

Help for reading

Patients with bilateral central scotoma, may benefit from eccentric viewing and steady eye strategy training

Help for distance vision includes:

• Prescription of telescopes
• Practical advice may also be given, such as getting a larger TV
• When going to the cinema, theatre, sports events, try to get a seat nearer to the front
• Use audio description facilities on TV

Lighting advice
- Light falls in an inverse square fashion
“Halve the distance, quadruple the light”
- Over the shoulder minimises glare
- Type of bulb unimportant

Question 38

when a px with untreatable end stage nAMD and GA is referred to Social Services, ROVIs etc, list all the 8 types of help they should get from them

Answer 38

• Home visit
• Advice on performing daily living skills
• Discussion (provision?) of lighting
• Demonstration (supply?) of non-optical aids
• Mobility training if required
  including symbol cane, long cane, training
• Advice on benefits/welfare rights
• Advice on computer training
• Emotional support (remember prevalence of depressive symptoms in people with advanced AMD ~30-40%)

Anyone can refer px to social services, so doesnt have to be via the GP, px can refer themselves or we can write a letter

Question 39

when a px with untreatable end stage nAMD and GA is referred to the Voluntary Sector, which 2 main voluntary sectors are there and list all types of help they should/can get from them

Answer 39

The macular society:

• Information distribution
• “Sideview”
• Information leaflets
• Conferences
• Counselling/emotional support
• Active web forum
• Local groups
• Research support
• Eccentric viewing training

RNIB:

• support
• information
• courses
• resource centres
• books
• campaigning

and local societies

Question 40

when managing a px with untreatable end stage nAMD and GA, for what 3 reasons will you still want to refer them to the ophthalmologist

Answer 40

• Assessment of fellow eye - if px wants second opinion
• Registration as sight impaired / severely sight impaired
• Other diseases e.g. cataract

Question 41

what is the 5 main things you will do to manage are those with bilateral early AMD – that is, just drusen and or pigmentary changes
and what 2 things do you want to look out for

Answer 41

As theres no medical treatment for early AMD: 
Education
Self monitoring
Lifestyle changes
Nutritional supplements
Patient support groups

Look out for:

• Risk factors for progression present? e.g. lots of large soft and confluent drusen, focal pigmentary changes
• Monitor these patients carefully - review this px yearly if theres no other concerns

Question 42

what did the AREDS 1 trial results reveal

Answer 42

Significant reduction in OR (~20% risk reduction) for development of advanced AMD in 5 years with zinc + antioxidants.

Effect increased if people with early AMD excluded - i.e. showed no sign of benefitting

And no evidence for those who don’t have AMD as they weren’t included in the trial

Therefore those who should be treated with AREDS 1 are - those with middle/intermediate stage AMD and ones who got advanced AMD in one eye and not the other

Question 43

what are the 4 risks/disadvantages to the AREDS 1 supplement

Answer 43

Increased risk lung cancer in smokers taking beta-carotene/vit A

Increased risk heart failure in people with vascular disease taking vit E

Increased genitourinary complications in people taking zinc?

No evidence that it prevents AMD in people who don’t have it to start with

So recommend px to discuss with GP before starting the supplements