A Journey through the Eye Macular Degeneration Dr Dianne Sharp Ophthalmologist Retina Specialists, Auckland

A Journey through the Eye

Macular Degeneration

Dr Dianne SharpOphthalmologistRetina Specialists, Auckland

What is the Macula?

Normal Retina

macula

retinaopticnerve

• Progressive, chronic disease of central retina

• Loss of central vision

• Peripheral vision not affected

• Not black blind

What is Macular Degeneration (AMD)?

Leading cause of severe vision loss

Macular Degeneration in New Zealand

MacularDegeneration

Glaucoma

Cataract

Other

Macular DegenerationFacts and Figures

• Deloitte Access Economics 2011 and Macular Degeneration Foundation Australia

www.mdfoundation.com.au

Macular Degeneration in NZAustralian pop 22 million: NZ pop 4.4million = approx. 1/5th

Macular Degeneration (MD) is a chronic disease with no cure1

Cause of up to 50% of all blindness

Affects 1 in 7 people over 50 in some way:1

o 170,000 have early MD in NZ

o 33,400 have late MD in NZ. 7,000 are legally blind.

1 in 4 people over 80 have vision loss from MD1

The number of people with MD will increase by 70% by 20301

¹ Deloitte Access Economics

Prevalence of chronic diseasesAustralia 2010 – ref Deloitte

2x

2x

4 to 8x

3x

Risk of falls

Risk of depression

Risk of hip fracture

Rate of social dependence

3yr Nursing home admission

Employment

The Impact of Macular Degeneration*

• Access Economics & AMDAI 2010.

The impact of MD on quality of life is equivalent to cancer or coronary heart disease.

Cost of vision loss from Macular Degeneration

$AU2.55 billion in 2010 in Australia

$NZ 0.64 billion in NZ

(Adjusted for population and currency)

Deloitte Access Economics & Macular Degeneration Foundation 2011,

Optimal integrated model of care for Macular Degeneration (AMD)

1. Primary prevention2. Early detection & timely diagnosis3. Early & regular treatment with on-going

monitoring for wet AMD4. Rehabilitation & emotional support

Macular Degeneration symptoms

How does MD Develop?

MaculaRetinaRPEChoroid

Normal Retina

RETINA

CHOROID

RPE

Healthy retina

Bruch’s membrane

Early AMD -“Drusen”

Normal Retina

Drusen

Early AMD

Drusen

Early AMD

•Normally no symptoms but at risk of progression•Lipid deposits (drusen)•No treatment but progression slowed by diet and lifestyle modifications

Early Stages of MD

Dry AMDDrusen Atrophy 7rs later

http://webeye.ophth.uiowa.edu/eyeforum/images/AMD/fig-1-6.jpg

http://webeye.ophth.uiowa.edu/eyeforum/images/AMD/fig-1-6.jpg

Dry AMD

Dry AMD: • Atrophy of retinal tissue.• Gradual loss of central vision over years end stage has significant vision loss

Wet AMD: • Formation leaky blood vessels under

retina• Rapid loss central vision

Late Stages of AMD

Wet AMD

Advanced Wet AMD

Wet AMD

Dry MD: • Atrophy of retinal tissue.• Gradual loss of central vision over years end stage has significant vision loss

Wet MD: • Formation leaky blood vessels under

retina• Rapid loss central vision over weeks or

months

Late Stages of MD

Visual impairment by severity of vision loss




Risk Factors for MD

AgeAge

Prevalence AMD (%) Blue Mountains Eye Study

Age group

Early AMD

Dry Late AMD

Wet Late AMD

All Late AMD

50-59 yr 6% <0.5% <0.5% <0.5%60-69 yr 11% <0.5% 0.5% 0.5%70-79 yr 20% 1% 2% 3%80-89 yr 25% 3% 7% 10%90+ yr 35% 18% 13% 31%All 50 yr+ 13% 0.7% 1.5%

% Prevalence AMD by age

Risk Factors for MD

GeneticsGenetics

• 50 -70% cases have a genetic link

• 50% risk of MD if a direct family history

AMD Principal genes CFH & ARMS2

Rotterdam Eye Study• Early AMD 75% had one

risk allele• Late AMD 93% had one

risk allele• Risk of developing AMD

by 85yrs increases with number of alleles

Genetics: Risk Alleles

CFH•Mainly dry AMD•Inhibitory effect on complement pathway•? Less effective inhibition of inflammatory pathway

ARMS2 •Mainly wet MD•Gene located in mitochondria•? Interferes with normal oxidation

Rotterdam Eye Study

Modifying Genetic Risk Factors

SmokingWith 1 CFH allele Risk of AMD:Non smokers risk 12x Smokers risk 34x

Diet1 CFH &/or ARMS2 allele

High dose Zn, omega 3, lutein rate close to no genetic risk

Risk Factors for MDSmokingSmoking

Smoking increases risk 3 to 4 times Smokers get MD 10 years earlier, on average BUT 20 years after quitting, a smoker’s risk is

the same as a non-smoker

• Eye test every 2 years or earlier if any new symptoms

• Recommend family members have eye test.

• Protect eyes from sun

• Healthy lifestyle:o Control weighto Exerciseo Eat eye health foodso Consider a supplement

Reduce Your Risk of MD

Eating for Eye HealthLutein

Dark green and naturally yellow vegetables and fruit

every day

Fish 2-3 times per week(salmon, sardines, mackerel, anchovies, tuna)

Eating for Eye HealthOmega 3

Handful of nuts per week(brazil nuts, almonds, walnuts, pine nuts)

Limit fat intake

Eating for Eye Health

Low Glycaemic Index foodsLow GI Foods

• Break down more slowly

• Prolong energy release

• Leave less waste products in the eye

3 key supplements to consider:

• AREDS formulation

• Lutein

• Omega 3 (fish oil)

What supplements?

Per day• Zinc 80mg • Vitamin C 500mg• Vitamin E 400IU• Copper 2mg• ß-carotene 15mg

AREDS Formula Age Related Eye Disease Study

Daily dose = 2 tablets

People who smoke, suffer from lung cancer or asbestosis should not take a supplement with beta-carotene. This is the reason it is removed from most

AREDS supplement products.

Macu-Vision

Diet supplements

AREDS Formulation: for intermediate or late AMD in one eye, reduces risk of progression by 20-25%

AREDS 2: trial in progress. Reducing Zn, removing beta-carotene, addition Lutein




Symptoms of Macular Degeneration

Early stageso Early MD may be asymptomatic.

Eye tests are the key.

Late stages

o Difficulty distinguishing faces

o Difficulty reading & fine vision

o Distortion (straight lines appear wavy or bent)

o Dark / blank patches in central vision

Use an Amsler grid (one eye at a time)

Normal Lines distorted Dark patches or empty spaces

Chronic disease• Dry AMD: diet and lifestyle important

• Wet AMD: treatment available•diet and lifestyle also important

Treatments for AMD

Treatment for Wet MD• Injection Lucentis or

Avastin into the eye

• Average every 4–6 weeks

• Early treatment saves sight! Aim to stabilise vision and prevent further vision loss.

***p<0.0001 vs. sham

2 4 6 8 10 12 14 16 18 20 22 24

sham -3Month

-3

-2

-1

0

1

2ANCHOR +2

MARINA +1.5

PDT -2

Lin

es o

n v

isio

n c

har

t

AMD Treatment Trials (Anchor & Marina)Lucentis treatment: Mean gain in vision over 2yr

Current drug treatments

• Lucentis or Avastino Normally given as monthly injectionso Highly effective.

• CATT study: Comparing Lucentis and Avastino Similar effect at 24 monthso Still some unanswered questions re adverse

events with Avastin




AMD treatment trials (PIER) Subset analysis highlights need for individualised

dosing

No initial gain (no gain at month 3) (n=21, 34% total)

Initial gain not maintained(n=24, 40% total & 60% initial gainers)

Maintained initial gain (>0 at month 3)(n=16, 26% total & 40% initial gainers)

Mean (SE) change in BCVA from baseline (letters)

Month0 1 2 3 4 5 6 7 8 9 10 11 12

-15

-10

-5

0

5

10

15

BCVA, best corrected visual acuity

New Therapies on horizon

• Treatments that allow decreased Rx frequency• Improved drug delivery methods (drops, oral)• Therapies allowing self monitoring rather than

doctor visits• Combined drug therapies →improve efficacy

& decreasing Rx burden• Drugs that reverse disease process

Wet AMD: New treatments• VEGF Trap-Eye

o Similar effect to Lucentis / Avastino lasts two monthso Available later this year in NZ

• Pazopanib (Eye drop)o Used with anti-VEGF injections to help spread

number of injectionso In phase 3 trials

Dry AMD: New treatments

• FenretinideA tablet, derived from Vitamin A

• Slows development of drusen• Reduces risk of wet AMD by 2 fold• In phase 3 trials

• BrimonidineAn implant inside eye

• May protect against late dry AMD• In phase 2 trials

Laser for early (dry) AMD

• Ellex 2RT (Laser)oUltra-short duration, non-thermal laser o Appears to reduce formation of drusenoMay improve waste transport in retina

o Trials ongoing

Gene therapy for wet AMD

• Gene therapy inserts a ‘normal’ gene into cells to replace disease-causing genes.

• RetinoStat – gene-therapy to stop new blood vessel formation.

Early clinical trials.

When retinal cells die

• Treatments that could directly replace lost retinal cells• RPE cell transplantation from donor• Stem Cell treatment

• Artificial (‘bionic’) vision– Only useful if total vision loss

Retinal cell transplantation

• Many animal studies, some human studies

• Only limited efficacy reported

• Very difficult surgery

Stem cells

• Stem cells have the ability to develop into different types of adult cells such as photoreceptor cells or RPE cells

• Possible sources: Embryonic stem cells (Most adaptable), Adult stem cells (more restricted)

Please note: MDNZ recognises and respects different points of view concerning stem cell research. Our role is to simply report on all research occurring for your information.

Stem cell treatment

Artificial vision “Bionic eyes”

An electronic prosthesis to replace the function of dead retinal cells.

NOTE:

Current ‘bionic eyes’ provide MUCH LESS vision than most people with end stage AMD already possess.

Pathogenesis of AMD for future treatments

Early AMD: Drusen OCT

Infra redAuto fluorescence

Anti-inflammatory

Pro-inflammatory

Normal

AMD

Drusen

Complement inflammation pathways

Membrane Attack Complex

Rattner and Nathans 7, 860–872 (November 2006) | doi:10.1038/ nrn2007

Complement mediated inflammation in AMD

Anti-C5b-9 Membrane Attack Complex

C5 cleavage products beneath RPE.

Drusen contain almost all alternative complement pathway proteins


CFH

CFB

Exercise


CFH

Tobacco CFB

Exercise

CFH


CFH

Tobacco CFB

Exercise

CFH

High fat intake


CFH

Tobacco

HDL

CFB

Exercise

CFH

High fat intake


INTERACTION OF ENVIRONMENTAL AND GENETIC RISK FACTORS IN AMD

Risk of AMD•Genetic and environmental risk factors are not merely additive•Resultant risk in some cases is greater than that conferred by each risk factor individually.

Potential Targets for AMD Therapy


AMD is a complex disease

• Medical research takes time and vast amounts of money.oNew drug: 12 years and $500m - $1.2 billion oOther research:

New mechanisms Identify risk and protective factors

• More research is needed!







Our Vision:

To reduce the incidence and impact

of

Macular Degeneration in New Zealand

Our Objectives

• Education

• Awareness

• Representation

• Research

• Support Services

For more information

0800 MACULAFree call, NZ-wide

Web: www.mdnz.co.nz

http://www.mdnz.com.au/

The Ageing Eye: Integrated Care

GP

Optometrist Ophthalmologist

The Ageing Eye: Integrated Care

GP

Optometrist Ophthalmologist

Documents

A Journey through the Eye Macular Degeneration Dr Dianne Sharp Ophthalmologist Retina Specialists, Auckland