RECENT ADVANCES IN

ARMDD R A M R E E N H . D E S H M U K H

M O D E R A T O R : D R A . V. A W A R G A O N K A R

OUTLINE

• Advances in ARMD

• Drugs

• Surgeries

• Bionic Eye

• Rehabilitation & low vision aids

• AMD is a complex disease with various pathologic mechanisms

• Current strategies pursued by researchers are:

• New drugs that aim to prevent damage to the retina or to slow the progression of AMD

– Inhibition of angiogenesis

– Anti-inflammatory drugs

– Complement inhibition ( inhibition of a immune system pathway)

– Alleviation of oxidative stress ( anti oxidants use)

– Neurotrophic drugs

– Reduction of accumulation of retinal toxins

– Enhancement of choroidal blood perfusion ( improving circulation of retinal circulation)

ARMD

Anti- angiogenic

drugs

Anti-inflammator

y drugs

Complement inhibitors

Anti-oxidants

Retinal toxin accumulation

inhibitors

Choroidal perfusion enhancers

Neurotrophic drugs

•ANTI-ANGIOGENIC DRUGS

ANECORTAVE ACETATE

• Anecortave acetate (Retaane®, Alcon Research), is an angiostatic steroid that does not

exhibit glucocorticoid receptor-mediated activity1

• Dosing and delivery: 15 mg delivered as a posterior juxtascleral depot every 6 months.

• Favourable dosing schedule and delivery and low risk profile

• Anecortave Acetate Risk Reduction Trial (AART) for the prevention of CNV in patients

with eyes at high risk of converting from non-neovascular to neovascular AMD.

– This study targets patients with bilateral large size drusen and pigment changes who

have a particularly high 5-year risk of progression to advanced AMD

VEGF TRAP

• Fusion protein of portions of VEGF receptor 1 and 2 and the Fc region of human IgG which

binds all VEGF isoforms tightly2

• The Clinical Evaluation of Anti-angiogenesis in the Retina (CLEAR) study was a randomized,

double-masked, ascending dose, placebo-controlled phase I trial of 18 patients with

neovascular AMD who received either placebo or 1 of 3 systemic doses of intravenous VEGF

trap (Aflibercept) (0.3, 1.0, and 3.0 mg/kg)

• The study found a dose-dependent increase in systemic blood pressure, which was clinically

significant above the 1.0 mg/kg dose and further studies of systemic VEGF trap were halted.

• CLEAR IT-1 phase I dose escalation study of a

single intravitreal injection of multiple doses

VEGF trap (0.05, 0.15, 0.5, 1, 2, and 4 mg).

• At 6 weeks, mean gain in visual acuity was 4.8

letters and mean OCT central retinal thickness

decreased from 298 to 208 m (Nguyen et al μ2006).

• The potential benefit of VEGF trap is a

sustained effect compared to single injections

of other VEGF-binding agents,

• A phase II VEGF trap study (CLEAR-AMD) is

currently in the process of enrolling patients.

SMALL INTERFERING RNA

• The 2006 Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig

Mello for their work in RNA interference, the process by which small interfering RNA (siRNA)

molecules inactivate messenger RNA, thereby suppressing RNA translation.

• For clinical use, these drugs are administered as double-stranded RNA molecules that are

imported across the cellular membrane and processed by an enzyme, Dicer, which shortens

the siRNA to 21–24 nucleotides.

• The processed siRNA is incorporated into a RNA-induced silencing complex (RISC), which,

when activated, binds complementary mRNA and digests it.

• This allows a single molecule of siRNA to degrade multiple copies of mRNA.

• Bevasiranib (formerly Cand5, Acuity Pharmaceuticals, Philadelphia, PA)-targeted against

VEGF mRNA. 3

• The Cand5 Anti-VEGF RNA Evaluation (CARE) study was a phase II study of 3 doses of

Bevasiranib (0.2, 1.5, and 3.0 mg) injected intravitreally 6 weeks apart (n = 127 eyes).

• At 12 weeks after the initial injection, mean loss of vision was 4.1 letters (0.2 mg dose),

6.9 letters (1.5 mg dose), or 5.8 letters (3.0 mg dose), with 71.8–79.4% losing less than 3

lines.

• Adverse events included stroke (0.8%), arrhythmia (0.8%), and hypertension (5.5%)

(Tolentino 2006).

• By targeting a relatively upstream component of the VEGF pathway, it is currently

considered that the use of siRNA may have a delayed effect in influencing disease

processes.

• The recent FDA approval of Ranibizumab may prompt a design change in the phase III

study of Bevasiranib to include injection of a VEGF-binding agent at baseline.

• The combination of VEGF binding by Ranibizumab or Bevacizumab combined with the

mRNA interference of Bevasiranib has the theoretic advantage of preventing further vision

deterioration by immediately binding existent VEGF while interfering with the upstream

production of VEGF. (COBALT trial)

• A second siRNA drug, sirna-027 (Sirna Therapeutics, San Francisco, CA), directed against

VEGF receptor 1 (VEGFR1), has demonstrated efficacy in animal models (Shen et al 2006)

and reasonable safety in a Phase I trial and is undergoing phase II evaluation currently.

VATALANIB

• For inhibition of effect of increased VEGF within the eye with CNV we have to inhibit the

tyrosine kinase activity of VEGF receptors.

• Vatalanib (formerly PTK-787, Novartis International AG, Basel, Switzerland) is a potent

inhibitor of all known VEGF receptor tyrosine kinases, VEGFR1 (sFlt-1), VEGFR2 (KDR), and

VEGFR3 (Flt-4).

• Satisfactory oral bioavailability.

• Preclinical data have demonstrated inhibition of experimental retinal and choroidal

neovascularisation

• Clinical studies in healthy individuals have shown no serious adverse events

• Adverse events from the use of vatalanib in patients with solid and hematologic

malignancies have included nausea/vomiting, fatigue, dizziness, diarrhoea, and

hypertension

• The Study of Vatalanib and Photodynamic Therapy with Verteporfin in Patients With

Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-related Macular

degeneration (ADVANCE) is currently enrolling for a phase I/II comparison of PDT to

PDT/vatalanib.

SQUALAMINE LACTATE

• Squalamine lactate (Evizon, Genaera Corporation, Plymouth Meeting, PA) is an anti-

angiogenic amino sterol derived from cartilage of the dogfish shark, Squalus acanthus. 

• Its mechanism of action includes blockade of cell membrane ion transporters that regulate

cell function by controlling pH and metabolism.

• When bound to calmodulin, squalamine also blocks the action of VEGF and integrin

expression, thereby inhibiting angiogenesis.

• Squalamine is ineffective when administered intravitreally and therefore requires

intravenous dosing.

• However, systemic dosing has yielded promising results in rats as well as humans

• In a phase I/II clinical trial of 40 patients who had received 25 or 50 mg/m2 weekly for 4

weeks, no patients lost vision and 26% gained 3 or more lines.

• Genaera has abandoned this product and is no longer in clinical development

OTHERS

• Sphingomab (Lpath Inc., San Diego, CA) is a monoclonal antibody targeted against

sphingosine-1-phosphate, which has been implicated in angiogenesis, scar formation, and

inflammation

• Volociximab (Ophthotech, Princeton, NJ, USA) is a chimeric monoclonal antibody that

inhibits the functional activity of a5ß1 integrin, a protein found on activated endothelial

cells.

– Blocking the activity of a5ß1 integrin has been found to prevent angiogenesis.

– Volociximab is currently being investigated as an adjuvant therapy with ranibizumab

• Designed ankyrin repeat proteins (DARPins)

– Represent a novel class of drugs

– DARPins are genetically engineered antibody mimetic proteins that exhibit highly

specific, high-affinity target protein binding.

– The DARPin MP0112 is a potent VEGF inhibitor.

– Animal studies indicate that dosing frequency in patients may be reduced compared

with current therapy .

– A phase I dose escalation study demonstrated the overall safety and efficacy of MP0112

(NCT01086761)

•ANTI-INFLAMMATORY DRUGS

SIROLIMUS ( RAPAMYCIN)

• Anti fungal and immuno-supressant agent

• Inhibits the response of the immune system to IL-2 and blocks activation of T- and B-

cells

• Various phase1/2 clinical trials sponsored by National Eye Institute have been

completed

• Subconjunctival injection every 2 months for dry AMD patients with geographic

atrophy

• Another study is using an oral dose along with other agents for wet AMD

• Results will be available shortly

FLUOCINOLONE ACETONIDE

• Synthetic hydrocortisone derivative

• Intra-vitreal implant inside the eye

• Sustained release for up to 36 months

• Ongoing Phase 2 trial is enrolling patients with bilateral GA

• Will assess the rate of GA progression in a 2-year span

• This is a medicine secreting implant to protect dying retinal cells

• Infliximab (Remicade®, Centocor OrthoBiotech) is a monoclonal antibody that binds and

neutralizes tumor necrosis factor alpha.

• Methotrexate inhibits dihydrofolate reductase, inhibiting lymphocyte proliferation. It is

also being investigated as a potential therapy for wet AMD.

•COMPLEMENT INHIBITORS

POT-4

• Designed to inhibit the complement activation system

• Intra-vitreal gel sustained release system

• Neutralize early AMD inflammatory component

• A phase 1 study was completed and a phase 2 study is being pursued

• ARC1905 ( C5 inhibitor aptamer)

• Prevents C5a production

• Eyes with dry AMD stains for C5a in histopathological studies

• Possible benefit in blocking this agent

• A phase 1 study was recently completed

• Intra-vitreal injection

• Results not yet available

• Eculizumab

• An antibody against C5

• Currently FDA approved for paroxysmal nocturnal hemoglobinuria

• Phase 2 study

•  Lampalizumab

– A recombinant mAb fragment directed against factor D, has proved to be safe and to

slow lesion growth in eyes with GA in a phase 2 study (MAHALO study;

NCT01802866).

– For the first time, efficacy in terms of slowing atrophy progression has been

demonstrated when lampalizumab was administered intravitreally in monthly

intervals

•NEUROTROPHIC FACTORS

NT501

– Genetically modified RPE intra-vitreal implant

– Overexpresses ciliary neurotrophic factor, a growth factor capable of retarding cellular

and functional losses in RPE and photoreceptors in neurodegenerative diseases

– A phase 2 study reported visual stabilization in 96.3% of treated eyes vs. 75% of control

eyes

– Improvement in retinal thickness was observed as early as 4 months

– It received a FDA fast track designation for the treatment of visual loss associated with GA

ENCAPSULATED CELL TECHNOLOGY

• Developed by Neurotech, Lincoln, RI, involves implantation into the vitreous cavity of a small semi-

permeable polymer capsule.

• The capsular implant is lined with cultured cells that have been engineered to secrete certain proteins or

peptides.

• The initial studies of ECT in humans have been phase I trials of ECT containing modified human retinal

pigment epithelial cells (ARPE-19), programmed to secrete ciliary neurotrophic factor (CNTF) in the

treatment of retinitis pigmentosa and non-neovascular AMD

• Assuming that these capsules demonstrate immune privilege, ECT allows for theoretically sustained low-

dose delivery of a single or combination of proteins or other cellular products into the vitreous cavity.

PEDF

• Pigment epithelial-derived growth factor (PEDF) is a factor with neurotrophic,

neuroprotective, and anti-angiogenic properties

• Multifaceted protection of the retina and retinal pigment epithelium and inhibition of

angiogenesis.

• cDNA encoding human PEDF has been shown to inhibit ocular neovascularization when

introduced into the vitreous and subretinal space of animal models via an adenoviral

vector

• A phase I study of AdPEDF.11 in 28 patients demonstrated no dose-limiting toxicity and

suggested that its anti-angiogenic effect lasts for months

• Furthermore, therapy does not seem to be associated with a systemic immune response,

thereby theoretically allowing for repeat injections

• The sustained effect and repeatability of therapy

BRIMONIDINE

• Highly selective α2-adrenergic agonist

• More recent experimental and animal models suggest brimonidine protects retinal ganglion cells,

bipolar cells, and photoreceptors from degeneration after a number of types of insults, including

retinal ischemia and retinal phototoxicity

• The neuroprotective effects of brimonidine are likely multifactorial. Proposed mechanisms

include upregulation of trophic factors such as brain-derived neurotrophic factor in retinal

ganglion cells and of intrinsic cell survival signaling pathways and antiapoptotic genes

• Brimonidine has been formulated as an intravitreal implant, which delivers the drug over a 3-

month period. Clinical studies are underway to assess efficacy and safety in patients with GA (e.g.,

NCT00658619)

ANTI-OXIDANTS• OT-551 (antioxidant eye drops)

– supplement the eye’s natural defense system

against disease and injury.

– Protection against both cataract and dry

AMD

– currently in a clinical study for geographic

atrophy (advanced dry AMD)

• AL-8309A

– Has shown capacity to decrease oxidative damage

in animal studies of light-induced damage

– Similar changes has been found in patients with

dry AMD

– Potential candidate

– Phase 2 study

– Topical solution for possible prevention of GA

progression as well as visual acuity changes 0ver

2-year span

REDUCTION OF RETINAL TOXINS

• Studies have shown that there is an accumulation of lipofuscin, a waste product at the leading

edge of the lesion in dry AMD

• It precedes the spreading of the lesion and death of retinal tissue

• To slow or stop progression of GA

• ACU-4429 and Fenretinide were developed to prevent the accumulation of lipofuscin by

inhibition of enzyme A2E

• Oral doses

• Phase 1 and 2 studies ongoing

• Accutane is a possible candidate

CHOROIDAL BLOOD PERFUSION ENHANCERS

• Reduction in choroidal blood flow is more pronounced in patients with AMD

• Alprostadil

– Intra-venous injection to try to improve macular blood flow

– The drug failed to reach the primary outcome

• MC-1101

– Topical drug that has been shown to increase mean choroidal blood flow

– Compelling results from a Phase 1 study have led to a fast track FDA designation for further

development of the drug

MACULOPLASTY

• Maculoplasty is an overall tissue engineering attempt to reestablish the normal subretinal

anatomy. It includes

– Removal of subretinal neovascular complex,

– Repair and refurbishment of Bruch's membrane

– Repopulation of RPE and choriocapillaris

– Restoration of healthy photoreceptor-RPE interface

– Repair of photoreceptor defect

• Excision of the subretinal neovascular complex: 

– the removal of the RPE cells surrounding the neovascular complex along with parts of the

adherent Bruch's membrane.

– Absence of RPE was followed by closure of the underlying choriocapillaris and loss of

photoreceptors

• RPE transplantation: 

– several attempts to populate the RPE defects by RPE transplants have failed

– the transplanted RPE fail to attach to the aged and partially destroyed Bruch's membrane

failure of the neighbouring native RPE to repopulate these defects. Unattached RPE cells

eventually die by apoptosis.

• Restoration of aged Bruch's membrane: 

– chemical cleaning of the debris and recoating of the Bruch's membrane with extracellular-

matrix molecules.

– Thus, a rejuvenated Bruch's membrane can support proliferation and differentiation of RPE.

• Replenishing cellular defects: 

– the recent alleviation of the restrictions on the use of stem cell research has fueled the hopes of

restoring the retinal cell mosaic by using these cells.

– Several studies have shown the differentiation of these cells into RPE5 and photoreceptors.

MACULAR TRANSLOCATION

• The rationale of macular translocation is that moving the neurosensory retina of the fovea

in one eye with recent-onset subfoveal CNV to a new location before the occurrence of

permanent retinal damage, may allow it to recover or to maintain its visual function over a

healthier bed of RPE-Bruch’s membrane-choriocapillaris complex.

• Allows the ablation of the CNV, by laser photocoagulation without destroying the fovea, in

an attempt to preserve central vision.

• Combined macular translocation with CNV removal, allowing the fovea to be relocated to

an area outside the RPE defect created during submacular surgery

• Two types

– Full macular translocation

– Limited macular translocation.

• Full Macular Translocaton

– Machemer and Steinhorst 1993

– Procedure- lensectomy, complete vitrectomy, planned total retinal detachment by transretinal

infusion of fluid under the retina, 360º peripheral circumferential retinotomy, rotation of the

retina around the optic disc, and reattachment of the retina with silicone oil tamponade.

• Limited Macular Translocation

– de juan 1998

– Procedure- transretinal hydrodissection using small posterior retinotomies to induce a subtotal

retinal detachment, a complete vitrectomy, anterior-posterior shortening near the equator and

retinal reattachment.

– As no large retinal break was created, the likelihood of developing PVR was thought to be lower.

SUBFOVEAL NVM REMOVAL

•  In summary, these techniques include standard pars plana vitrectomy, with or without

posterior hyaloid membrane removal; posterior retinotomy followed by infusion of

subretinal saline solution or r-TPA into lesions with a large haemorrhagic component,

membrane mobilization and its removal with surgical forceps, followed by eventual

aspiration of blood or clot aspiration, depending on the situation.

• Possible intraocular haemorrhages may be controlled by increasing the intraocular

pressure, either by raising the irrigation bottle or using heavy perfluorocarbon liquids.

• The procedure is finished with a fluid-air exchange, followed by gas buffering, maintaining

the patient in the prone position until gas reabsorption

• First described by Oosterhuis et al. in 1998 for treatment of choroidal melanoma.

• The goal of TTT is to create and maintain tissue hyperthermia.

• The diode laser (810 nm, near infrared):

– low absorption in xanthophyll, minimising nerve fibre layer damage

– poorly absorbed by haemoglobin, allowing treatment through preretinal and subretinal blood

– mainly absorbed in the choroid, enabling effective treatment of choroidal lesions.

• In ongoing trials: 3 mm spot, 800 mW, 60 sec.

TRANSPUPILLARY THERMOTHERAPY (TTT)

• TELETHERAPY (EBRT):

– Studies have shown equivocal results.

– Adverse effects: Cataract, keratoconjunctivitis siccs, epiphora

• BRACHYTHERAPY (Plaque Radiotherapy):

– Published reports include use of Palladium-103 (103 Pd)1, Strontium-90 (90

Sr)2 and Ruthenium-106 (106 Ru)3

– These studies have shown less vision loss in study group than controls.

– Adverse effects: Radiation induced vasculitis, retinal edema, necrosis of

adjacent tissue

RADIATION THERAPY

• The CNV Secondary to AMD Treated with Beta Radiation Epiretinal Therapy (CABERNET,

CLH002) study is a phase 3 multicenter, randomized, controlled trial of epimacular

brachytherapy using a prototype device.

• The trial recently completed its recruitment target of 450 patients at 45 clinical centers

worldwide with phase 3 results from CABERNET on the immediate horizon, epimacular

brachytherapy may become a viable therapeutic option capable of reducing the treatment

burden to health care systems globally. 

GENE THERAPY

• The idea is to replace or remove a defective gene to stimulate the cell not to die and

function properly again

• Different abnormal genes related to AMD have been identified

• The new gene is introduced into the retina via a virus (vector) , which deliver the genetic

information for the rest of the patient’s life

• Gene replacement therapy

• Studies using animal models are now underway

MACULAR DEGENERATION AND STEM CELLS

• On January 3, 2011, Advanced Cell Technology received a FDA approval to treat advanced

dry AMD using retinal pigment cells (RPE) from human embryonic stem cells

• Uses a proprietary technique to extract a single cell from a young embryo allowing the

rest to remain intact and develop normally

• Phase1/2 study to determine the safety of RPE sub retinal implantation

• July 9, 2012, FDA approved an increase of stem cell dosage to 100,000 RPE cells derived

from human embryonic stem cells

• June, 2012, a total of 16 patients started transplantation with Human Central nervous system stem

cells ( non embryonic)

• Study criteria:

– 50 years old or older

– Have no prior or current choroidal neovascularization

– Specific degree and extend of geographic atrophy

– No Diabetic retinopathy, cancer, glaucoma or autoimmune disease

• Allogenic cells ( another source other than the patient) and will receive immunosuppressive drugs X

3 months

• 4 patients have been transplanted with a single dose of 200,000 HuCNS-SC

BIONIC EYE

• Designed for patients who are blind due to diseases like retinitis pigmentosa or AMD

• Can also be tried for those with severe vision loss

• Relies on patient having a healthy optic nerve and a developed visual cortex

• Cannot be used for people who were born blind

• The prosthesis consists of :

– A digital camera built into a pair of glasses

– A video processing microchip built into a hand held unit

– A radio transmitter on the glasses

– A receiver implanted above the ear

– A retinal implant with electrodes on a chip behind the retina

Camera captures an image

Send image to microchip

Convert image to electrical impulse of light and dark pixels

Send image to radiotansmitter

Transmits pulses wirelessly to the receiver

Sends impulses to the retinal implant by a hair thin implanted wire

The stimultaed electrodes generate electrical signals that travel to the visual cortex

• Requires training by the subject to actually see an object

• Subjects have to learn to interpret the array of white and dark dots as object

• It is still in clinical trial stage

REHABILITATION &

LOW VISION AIDS

LOW VISIONDEFINITION (INDIA)• According to the Person with Disabilities Act 1995, “A person with low vision means a

person with impairment of visual functioning even after treatment of standard

refractive correction but who uses or is potentially capable of using vision for the planning

or execution of a task with appropriate assistive device.”

DEFINITION(WHO)

• WHO (ICD-10) definition

– “A person with low vision is one who suffers visual acuity between 6/18 to 3/60 in the better eye after

the best possible correction or a field of vision between 20 to 30 degrees.”

– Used for reporting and comparison of data

• The WHO working definition of Low Vision (Bangkok definition, 1992)

– “A person with low vision is one who has impairment of visual functioning even after treatment, and/ or

standard refractive correction, and has a visual acuity of less than 6/18 to light perception or a visual field of

less than 10 degrees from the point of fixation, but who uses, or is potentially able to use, vision for the

planning and/or execution of a task .”

– Defines population in need of low vision services

VISUAL DISABILITY CHART

Category no. Good eye Worse eye Percent blindness

0 6/9-6/18 6/24-6/36 20%

1 6/18-6/36 6/60-nil 40%

2 6/60-4/60 3/60-nil 75%

3 3/60-1/60 CF 1 ft- nil 100%

4 CF 1 ft – nil CF 1 ft - nil 100%

5 6/6 nil 30%

WHAT IS LOW VISION AID??

• Low vision aid refers to an optical device that improves or enhances residual vision by

magnifying the image of the object at the retinal level

• Non-optical aids also work as LVAs as they may help in enhancing the visual performance

GOALS OF LOW VISION MANAGEMENT

• Increase functionality

– Make the most of the remaining vision

• Provide link to community resources and support services

• Education

STRATEGIES

• Be oriented towards activities of daily living

• Use appropriate technology

• Be cost effective

• Utilize appropriate educational and vocational adaption

• Focus on target groups

• Make things brighter

– Improve lighting. Use a gooseneck lamp directed onto your task. Carry a penlight.

– Reduce glare. Indoors, cover wood tables and shiny counters; wear yellow clip-on or fitover

glasses. Outdoors, try dark yellow or amber glasses. Visors can be useful indoors or out.

– Increase contrast. Use a black ink gel or felt pen, not a ballpoint. Draw a dark line where you

need to sign. Use a white cup for coffee, for example.

• Make things bigger

– Move closer. Sit close to the TV, and up front at performances.

– Enlarge. Get large checks, large-print playing cards, bingo cards, crosswords, phone dials, TV

remotes, calendars, keyboards, and books.

– Magnify. Low vision magnifiers come in many powers and types, suited to different people and

different tasks: hand-held for price tags and menus, stands and video magnifiers (CCTVs or

closed circuit TVs) for sentences, magnifying computer mouse.

LOW VISION AIDS

OPTICAL

DISTANCE

• Hand held telescopes

• Mounted telescopes

• Intra-ocular LVA (IO-LVA)

NEAR • Spectacles

– Prismatic ½ eyes– Bifocals

• Magnifiers– Hand held vs. stand– Illuminated vs. non-illuminated

• Electronic Devices

• Others

– Absorptive lenses

• Tinted lenses

• Photochromatic lenses

• Polarization

• Filters- Corning CPF, Younger PLS

– Visual field enhancement devices

• Fresnel prisms

• Gottlieb field expanders

• Reverse telescopes

• Hemianopic mirrors

NON-OPTICAL

• Approach magnification

• Lighting

• Contrast enhancement

• Increasing size of object

• Personal items

• Auditory aids

• Electronic magnifiers

– CCTV

– Large print computers

– Low vision imging system

– V- max (enhanced vision system)

• Writing & communication devices

• Medical assisted devices

• Sensory substitute assistive & adaptive devices

• Orientation & mobility LVA

– Primary- canes, guide dog

– Secondary- electronic orientatation devices, GPS

• Newer technology LVA- E-readers, smart phones , tablets

CONCLUSION

• The real goal of exudative AMD treatment lies in preventing subretinal choroidal neovascularization

• Apart from AREDS formula change of life style, such as diet and cessation of smoking, has been shown to affect the development of AMD

• Targeting upstream molecules will undoubtedly result in more rational and effective treatment strategies in the future.

• Timely diagnosis, treatment, counselling and visual rehabilitation form the major cornerstones in ARMD

REFERENCES

1. Augustin AJ, D’Amico DJ, Mieler WF, et al. Safety of posterior juxtascleral depot administration of

the angiostatic cortisene anecortave acetate for treatment of subfoveal choroidal

neovascularization in patients with age-related macular degeneration. Graefes Arch Clin Exp

Ophthalmol. 2005;243:9–12.

2. Michael W Stewart et al, Aflibercept (VEGF Trap-eye): the newest anti-VEGF drug Br J Ophthalmol.

2012 Sep; 96(9): 1157–1158. doi:  10.1136/bjophthalmol-2011-300654 PMCID: PMC3432488

3. Reich SJ, Fosnot J, Kuroki A, Tang W, Yang X, Maguire AM, Bennett J, Tolentino MJ. Small interfering

RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model.Mol

Vis. 2003;9:210-216.

4. Chappelow AV, Kaiser PK, Neovascular age-related macular degeneration: potential therapies.

5. M Vaughn Emerson and Andreas K Lauer , Current and emerging therapies for the treatment of

age-related macular degeneration Clin Ophthalmol. 2008 Jun; 2(2): 377–388.

PMCID: PMC2693977

6. Yoreh Barak, Wesley J. Heroman, and Tongalp H. Tezel, The Past, Present, and Future of

Exudative Age-Related Macular Degeneration Treatment, Middle East Afr J Ophthalmol. 2012

Jan-Mar; 19(1): 43–51.

7. Surgery in AMD, Angelina Meireles, MD, Rui Martinho, MD

8. Frank G. Holz, Steffen Schmitz-Valckenberg, and Monika Fleckenstein; Recent

developments in the treatment of age-related macular degeneration, The journal of

clinical Investigation

THANK YOU