Exploring the development of

neovascular age-related macular

degeneration (nAMD)

Watch an animation that explores

this mechanism of disease
nAMD Three processes 1. Age-related progressive
accumulation of lipids and proteins Explore the
are believed to leading to the formation of drusen
Mechanism contribute to nAMD 2. Initiation of local inflammation
development of nAMD
Scan the QR code to watch an animation

of Disease pathophysiology 3. Neovascularization

that explores the mechanism of disease.

The appearance of drusen is one of the earliest visible clinical signs of nAMD. Leakage of fluid
In nAMD, blood and serous exudate leak from new blood
vessels to form a domed elevation between the retinal
pigment epithelium (RPE) cells and Bruch’s membrane.
This may lead to pigment epithelial detachment.
Drusen Photoreceptors In some patients, the vasculature breaks through the
tight barrier of the RPE into the subretinal and intraretinal
spaces, leading to fluid leakage.

RPE

Choroid Bruch’s
membrane
Sub-RPE space

Production of growth factors New blood vessels Neovascularization

VEGF-A VEGFR
Inflammatory factors and oxidative stress lead
to the production of:
Hemorrhage
• Vascular endothelial growth factors (VEGF)
• VEGF-A isoforms
• VEGF-B
• Other growth factors and mediators, i.e., placental
growth factor (PLGF)
These growth factors and mediators work together
to promote neovascularization. Angiogenesis
Increased production of VEGF-A and other mediators
Angiogenesis and vasculogenesis lead to the development
leads to abnormal choroidal neovascularization, retinal
Binding of VEGF-A of new blood vessels in the choroid.
edema, and hemorrhage. These clinical hallmarks of
In the vitreous fluid of nAMD patients, VEGF levels
are increased 24-fold and 2.5-fold for PLGF, when VEGF-A binds to its receptor in the vasculature, triggering These highly permeable blood vessels may penetrate nAMD lead to distortions in vision, such as
compared to normal controls. the degradation of the cellular basement membrane with through Bruch’s membrane and reach into the sub-RPE metamorphopsia or blind spots.
increased endothelial cell migration and proliferation. space, disrupting retinal architecture.
 nAMD disease progression
may lead to central vision loss

Performing daily activities can be

a challenge with nAMD.

nAMD is the leading cause of irreversible blindness

in people 50 years of age or older. As the disease
progresses, it may result in a complete loss of central
vision, which impacts a person’s ability to read, drive,
and clearly see the faces of their family.

References
Deissler HL, Deissler H, Lang GK, Lang GE. VEGF but not PIGF disturbs the barrier of retinal endothelial cells. Exp Eye Res.
2013;115:162-171.

Gerhardt H, Golding M, Fruttiger M, et al. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol.
2003;161(6):1163-1177.

Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008;358(24):2606-2617.

Midena E, Vujosevic S. Metamorphopsia: an overlooked visual symptom. Ophthalmic Res. 2015;55(1):26-36.

Mitamura Y, Tashimo A, Ohtsuka K, Mizue Y, Nishihira J. Placenta growth factor and vascular endothelial growth factor in the
vitreous of patients with proliferative vitreoretinopathy. Clin Exper Ophthalmol. 2005;33(2):226-228.

Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy. Pharmacol Rep. 2006;58(3):353-363.

Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J Genet. 2009;88(4):495-515.

Rosenfield PJ, Martidis A, Tennant M. Age-related macular degeneration. In Ophthalmology. 3rd ed. Philadelphia, PA: Mosby; 2009.

Todorich B, Pepple K, Mruthyunjaya P. Treatment of pigment epithelial detachments in age-related macular degeneration. Retinal
Physician. https://www.retinalphysician.com/issues/2012/nov-dec/treatment-of-pigment-epithelial-detachments-in-age. November
1, 2012. Accessed September 9, 2019.

Wu L. Choroidal neovascularization. Medscape. https://emedicine.medscape.com/article/1190818-overview#a6. Updated January

7, 2019. Accessed September 9, 2019.

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