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AGE RELATED MACULAR DEGENERATION
An epidemic of “ageing” is impending in the Western world. According to the latest predictions released by the United Nations, the number of people aged over 60 will triple from 606 million worldwide in 2000 to nearly 2 billion by 2050. The increase in population aged over 80 is expected to be more than five fold, from 69 million in 2000 to 379 million by 2050.
Ref: BMJ 2003; 326: 485-8
One major implication of this demographic change is the emergence of conditions that are directly related to ageing.
Ref: BMJ 2003; 326: 485-8
AGE RELATED MACULAR DEGENERATION
Age related macular degeneration (AMD) is the leading cause of severe visual loss in the western world in people over 50 years of age.
Ref: Surveys of ophthalmology 32 (6) 1988: 375-413
AMD: TERMINOLOGY
Degeneration is the change of a tissue to a less functionally active form.
Referred as senile macular degeneration, a name given by Haab as early as 1885,
Age Related macular degeneration has recently been named by Professor A C Bird and coworkers who performed the International ARM Epidemiological study group.
The disorder is either referred to age related maculopathy (ARM) or age related macular degeneration (AMD)
AGE RELATED MACULAR DEGENERATION
The UN estimates the number of people with age related macular degeneration at 20-25 million worldwide
WHO’s estimate is 8 million people with severe visual impairment
AMD was found to be second only to cataract as the cause of severe visual loss
Ref: BMJ 2003; 326: 485-8
AMD: PREVALENCE
Prevalence of AMD varies from 1.2% to 29.3%3 population based studies; the Beaver Dam Eye Study, Blue Mountain Eye Study and the Rotterdam study report the prevalence rates to be 1.7% in US, 1.4% in Australia and 1.2% in Netherlands respectively
1. Invest Ophthalmology vis. Sci 2001; 42: 2237-412. Am J. Epidemiology 1977; 106: 133
3. Ophthalmology 1992; 99; 933-434. Ophthalmology 1995; 102: 1450-60
5. Ophthalmology 1995; 102: 205-10
AMD: PREVALENCE IN INDIA
In South India, the prevalence is 1.1% whereas, another study from North India reports the prevalence rate to be 4.7%
1. Invest Ophthalmol Vis Sci (abstract) 2000; 41; 5119
2. Ind. J Ophthalmol 1984; 32: 343-6
HOW DOES NORMALVISION OCCURS
NORMAL MACULA
Ref: http://www/ahaf.org
The macula is the posterior aspect of the retinaHas highest concentration of photoreceptors which facilitate central vision and permit high resolution visual acuityThe macula is an area up to 5.5 mm in diameter with the fovea at its centre
NEJM; 342(7): 2000; 483-492
MACULA: CROSS SECTION
Ref: http://www.eyesight.org
The retinal pigment epithelium (RPE) is a single layer of hexagonally shaped cells. They reach out to the photoreceptor layer of the retinaFunctions of RPE includes maintainance of the photoreceptors, absorption of stray light, formation of the outer blood retinal barrier, phagocytosis and regeneration of visual pigmentBruch’s membrane separates the RPE from vascular choroid,
Function of Bruch’s membrane is to provide support to the retinaChoroid capillaries are a layer of fine blood vessels that nourishes the retina and provides O2
Ref: http://www.ahaf.orghttp://www.eyesight.org
Vision in the retina depends on photoreceptor cells (rods and cones)
Photoreceptor sit on a layer of RPE
Contain pigment called RhodopsinOpsin->glycoprotein
Rhodopsin Cis-retinal -> derivative of vit A
Cis-retinal in presence of light
Trans-retinal
Electric impulse destined for the brain is generated
Also, trans-retinal -> recycled to cis-retinal in RPE.
This entire process requires oxygen and nutrition supplied by the fine blood vessels of the choriocapillaries
WHAT GOES WRONG IN AMD?
AMD : Etiology
Etiology is complex and poorly understoodFlawed transport between choroid vessels and photoreceptors may be involved Angiogenesis is likely to be an early feature of neovascular ARMD
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
BMJ 326, 2003; 485-488
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
BMJ 326; 2003: 485-488
AGE RELATED MACULAR DEGENERATION TYPES
Dry macular degeneration
Wet macular degeneration
Ref: NEJM, Vol. 342 (7): 483-492
DRY MACULAR DEGENERATION
1. Accounts for about 90% of all cases2. Also called atrophic, non exudative or
drusenoid macular degeneration
DRY MACULAR DEGENERATION
DrusenDrusen is an aggregation of hyaline material located between Bruch’s membrane and RPEDrusen are composed of waste products from photoreceptorsDrusen > 63 microns in diameter are statistically associated with visual pathology and are termed early ARMDHypo/hyper pigmentation of RPE may be present
NEJM, Vol 342 (7): 483-492
DRY MACULAR DEGENERATION: VISUAL
WET MACULAR DEGENERATION
Accounts for about 10%Also called choroidal neovascularization, subretinal neovascularization or disciform degenerationAbnormal blood vessels grow beneath the maculaThese vessels leak blood and fluid into the macula damaging photo receptorsProgresses rapidly and can cause severe damage to central vision
http://www.blindness.org
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: COURSE AND VISUAL PROGNOSIS
Geographic atrophy is the severest form of the dry macular degeneration representing a zone of RPE atrophy 175 microns or greater in diameter with exposure of the underlying choroidal vesselsLeakage of blood or serum as a result of choroidal neovascularization may occur precipitously and is often associated with the abrupt loss of visionPatients with CNV have a rapid decline in vision (20/200) within weeksMore frequently, visual acuity deteriorates more slowly and stabilises within 3 yearsOnce CNV has developed in one eye, the other eye is at relatively high risk for the same change
NEJM; Vol. 342(7); 483-492
AMD: SYMPTOMS
Initial symptomsBlurry visionDistorted visionStraight lines appear wavyObjects may appear as the wrong shape or sizeA dark empty area in the centre of vision
http://www.kellogg.umich.edu/
AMD: SYMPTOMS VISUAL
Macular_Update[1].swf
AMD: SYMPTOMS
Patient’s ability to perform normal daily tasks such as reading, sewing, telling the time, driving are greatly impaired.
http://www.medscape.com
AMD: EFFECT ON QUALITY OF LIFE
AMD: ESTABLISHED AND POSSIBLE RISK FACTORS
Established Risk Factors Possible 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
NEJM; Vol. 342 (7): 2000: 483-492
AMD: DIAGNOSIS
Visual acuity is tested using the standard eye chart. It measures vision at various distances and can detect vision lossAmsler grid test: Assesses distorted or reduced vision and small irregularities in the central field of visionRetinal examination: Done through slit lamp microscope examination: to detect drusen, as well as neovascularizationFluoroscein angiography: Determines the presence and location of neovascularization
Ref: http://www.visionchannel.net
AMD: MANAGEMENT
DRY AMD: MANAGEMENT
Low vision aids
Antioxidants
AREDS STUDY
Aim To evaluate the effect of anti-oxidant vitamins and zinc on
the progression of dry AMD. The study was initiated by National Institutes of Health.
No. of centres11
No. of people4767 participants aged 55-80 years
AREDS STUDY (contd.)
Patients divided into 4 categories:Category 1: little or no AMD -> randomized to antioxidants or placebo to determine any effect on lens
changes
Category 2: early AMDCategory 3: intermediate AMDCategory 4: advanced AMD in one eye
Category 2, 3 and 4 randomized to receive: 1. Placebo2. Antioxidants alone3. Zinc alone4. Antioxidants plus zinc (Vit. C: 500 mg, Vit. E: 400 IU, Betacarotene: 15 mg, Zn oxide: 80 mg, Copper:
2mg)
Category 2, 3, 4 were followed for visual loss for the development of advanced AMD
Patients followed up: 6.3 years
AREDS STUDY (contd.)
Results
For category 2, only 13% of patients progressed to advanced AMD.
For categories 3 and 4 (who are at greater risk for developing advanced AMD), it was found that the combination of zinc and antioxidants were most effective in reducing the progression to advanced AMD.
Conclusion
It was recommended that patients with intermediate or advanced AMD should consider taking antioxidant vitamins and zinc
WET AMD: MANAGEMENT
Laser photocoagulation
Photodynamic therapy
LASER PHOTOCOAGULATION
Intravenous fluoroscein angiography is performedWell-circumscribed new blood vessels identified on the fluoroscein angiogramTreated with laser photo coagulation after topical or local anaesthesia
The Principle of Photodynamic therapy
In contrast with the conventional hot laserPDT helps to selectively close off subretinal new
vesselstwo stage treatment
• Injecting the photosensitiser drug• Applying cold laser to activate the drug
– Releases the singlet oxygen molecule that damages the endothelium
– Thrombosis of the capillaries
PHOTODYNAMIC THERAPY
PDT for AMD is a two stage process comprising a 10 minute intravenous infusion of 6 mg/kg verteporfin followed by activation 5 minutes later by 689 nm diode laser for 83 seconds at 503/cm2
The photosensitive verteporfin is selectively taken up by rapidly proliferating endothelial cells within the target CNV reaching its peak concentration at 15 minutesCytotoxic reactive oxygen intermediates damage cellular proteins and cause microvascular thrombosis
PHOTODYNAMIC THERAPY (contd.)
The recent publication of the Treatment of Age-related Macular Degeneration (TAP) report and Verteporfin in Photodynamic Therapy (VIP) trialsFor predominantly classic lesions the frequency of stable/improved vision was: 12 months-67% treated, 39% placebo
Copy of PhotodynamicTherapyFinal[1].swf
INVESTIGATIONAL TREATMENTS
Submacular surgeryRetinal transplantation and transplantation of RPERetinal translocationGene therapyAngiogenesis inhibitors: like cytochalasin E, Anecortave acetate, Prinomastat
TIPS FOR ARMD PATIENTS
Monitor your vision daily with an Amsler gridTake a multi-vitamin with zincIncorporate dark leafy green vegetables into your dietAlways protect your eyes with sunglasses that have UV protectionQuit smokingExercise regularly
Thank you