AGE RELATED MACULAR DEGENERATION

AMD epidemic of aging

Prediction by United Nations 606 million over age 60 in 2000 will go to 2 billion by 2050

Population aged over 80 is expected from 69 million in 2000 to 379 million by 2050

Emergence conditions that are related to aging

AMD(Age related Macular Degeneration)

Leading cause of sever visual loss in western world in people over 50 years of age

Senile macular degeneration given by Haab as early as 1885

ARM: age related maculopathy

AMD

Second only to cataract as the cause of sever visual loss

U.N. estimates 20-25 million with AMD world wide

Prevalence of AMD 1.2% to 29.3% 1.7% in US 1.4% in Australia 4.7% in north India

Normal Macula

How does normal vision occur

Macula is an area up to 5.5mm with the fovea at its centre

Highest concentration of photoreceptors High resolution visual acuity Entire process requires O2 and nutrition from

choriocapillaries

MACULA: CROSS SECTION

AMD: Etiology

Complex and poorly understood Transport between choroid and

photoreceptors may be involved Angiogenesis is likely to be an early feature

of neovascular AMD

Types of AMD

Dry macular degeneration Wet macular degeneration

Dry AMD

About 90% of all cases Also called atrophic, nonexudative or

drusenoid macular degeneratin

AGE RELATED MACULAR DEGENERATION

Insufficient oxygen and nutrients

damages photoreceptor molecules

With ageing, the ability of RPE cells to digest these molecules decreases

Excessive accumulation of residual bodies (drusen)

RPE membrane and cells degenerate and atrophy sets in and central vision is lost

AGE RELATED MACULAR DEGENERATION

Alternatively the photoreceptors and pigment epithelium send a distress signal to choriocapillaries to make new vessels

New vessels grow behind the macula

Breakdown in the Bruch’s membrane

Blood vessels are fragile

Leak blood and fluid

Scarring of macula

Potential for rapid severe damage

DRY MACULAR DEGENERATION

Drusen Drusen is an aggregation of hyaline material located

between Bruch’s membrane and RPE Drusen are composed of waste products from

photoreceptors Drusen > 63 microns in diameter are statistically

associated with visual pathology and are termed early ARMD

Hypo/hyper pigmentation of RPE may be present

DRY MACULAR DEGENERATION: VISUAL

WET MACULAR DEGENERATION

Accounts for about 10% Also called choroidal neovascularization, subretinal

neovascularization or disciform degeneration Abnormal blood vessels grow beneath the macula These vessels leak blood and fluid into the macula

damaging photo receptors Progresses rapidly and can cause severe damage

to central vision

WET MACULAR DEGENERATION: VISUAL

AMD: COURSE AND VISUAL PROGNOSIS

Patients with only drusen (in one or both eyes) typically do not have much loss of vision, but they make require additional magnification of the text and more intense lighting to read small point

Presence of large drusen (> 63 microns in diameter) is associated with a risk of the late form of the disease

Patients with large drusen are at relatively high risk for choroidal neovascularization (CNV)

AMD: SYMPTOMS

Initial symptoms are: Blurry vision Distorted vision Straight lines appear wavy Objects may appear as the wrong shape or size A dark empty area in the centre of vision

AMD: SYMPTOMS VISUAL

AMD: SYMPTOMS

Patient’s ability to perform normal daily tasks such as reading, sewing, telling the time, driving are greatly impaired.

AMD: EFFECT ON QUALITY OF LIFE

AMD: ESTABLISHED AND POSSIBLE RISK FACTORS

Established Risk FactorsPossible Risk Factors Older age (> 60 years) Female sex

Family history Light-colored iris

Cigarette smoking Cardiovascular disease

Low dietary intake or plasma concentrations of anti-oxidant vitamins and zinc

There are currently 5 specific risk factors that are strongly associated with the development of AMD:

1. Caucasian Ancestry

2. Genetic Component

3. Hypertension

4. Aging

5. Smoking

(SO QUIT NOW!!!!)

What are the Risk Factors for AMD?

AMD: DIAGNOSIS

Visual acuity is tested using the standard eye chart. It measures vision at various distances and can detect vision loss

Amsler grid test: Assesses distorted or reduced vision and small irregularities in the central field of vision

Retinal examination: Done through slit lamp microscope examination: to detect drusen, as well as neovascularization

Fluoroscein angiography: Determines the presence and location of neovascularization

Amslir Grid

DRY AMD: MANAGEMENT

Low vision aidsAntioxidants

Preventative Approaches for AMD

The AREDS formulation should only be taken when prescribed by a physician or a P.A.

AREDS is the treatment of choice for “dry” AMD Eating fresh fruits and dark green, leafy vegetables Maintaining a low fat & low cholesterol diet Exercising regularly Wearing sunglasses with UV protection Avoiding exposure to second-hand smoke Getting an eye exam regularly

WET AMD: MANAGEMENT

Laser photocoagulation Photodynamic therapy

INVESTIGATIONAL TREATMENTS

Submacular surgery Retinal transplantation and transplantation of

RPE Retinal translocation Gene therapy Angiogenesis inhibitors: like cytochalasin E,

Anecortave acetate, Prinomastat

Current Treatments for AMD

Pegaptanib Sodium (MACUGEN®) Used to prevent further vision loss from wet AMD Was first introduced in 2004 Was the first intravitreal injectable drug developed to treat wet AMD, and requires

monthly dosing In the VISION (VEGF Inhibition Studies in Ocular Neovascularization) clinical

trials in 2003 and 2004, 70% of patients treated with a small dose of Macugen (0.3mg) injected every 6 weeks had < 15 letters of vision loss at the primary end point analysis, compared to only 55% of the control group

Macugen has less adverse effects and a better safety profile than either laser photocoagulation or PDT

Current Treatments for AMD

Ranibizumab (LUCENTIS®) Approved by the FDA on June 30th, 2006 Intravitreal injection that requires monthly dosing The only FDA-approved drug that not only drastically slows vision

loss due to AMD, but it also seems to actually restore some visual acuity that has already been lost due to wet AMD destruction

In the MARINA study in 2004-2005 researching Lucentis, out of 716 patients enrolled, at 12 months 94.5% of the group given 0.3mg of Lucentis and 94.6% of those given 0.5mg lost < 15 letters, as compared with 62.2% of patients receiving the control injections

Investigational Treatments for AMD

Bevacizumab (AVASTIN®) Avastin was approved by the FDA in February 2004 for the treatment

of metastatic colorectal cancer in combination with chemotherapy Incidentally, ranibizumab (Lucentis) is a chemically modified product

of bevacizumab (Avastin) that is affinity-matured to have a higher affinity for VEGF, and it is made by the same laboratory, Genetech, that also produces Avastin

After initial results in 2005 from clinical trials with Lucentisbecame available, ophthalmologists began using Avastin to treat AMDbecause of its similar chemical structure to Lucentis

Investigational Treatments for AMD

Avastin requires monthly intravitreal injections Outcomes in patients treated thus far with Avastin have been

virtually identical to Lucentis, with no serious ocular effects reported

It must be noted though that intravitreal treatment with Avastin has not been proven effective and safe in controlled clinical trials like Lucentis

TIPS FOR ARMD PATIENTS

Monitor your vision daily with an Amsler grid Take a multi-vitamin with zinc Incorporate dark leafy green vegetables into

your diet Always protect your eyes with sunglasses

that have UV protection Quit smoking Exercise regularly

Questions??

Thank you!!