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 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 O 2 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 aids Antioxidants

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 30 th, 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 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 Lucentis became available, ophthalmologists began using Avastin to treat AMD because 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!!