Name: 4D-150 in Neovascular age-related macular degeneration: Pathophysiology
Published: 2026-09-17T18:33:01-04:00

Product information and disease description Place of product in therapy Disease description

Pathophysiology

6 evidence topics · 4 sources

Macular neovascularization types 1, 2, and 3

“Type 3 neovascularization is to be used when the vascular complex originates in the retina. Type 1 neovascularization is applied when the vessels originate from the choroid and remain under the RPE. Type 2 neovascularization is denoted if neovascularization that originates in the choroid breaks through the RPE to reach the subretinal space.” (opens the source at this quote in a new tab)
“The main causes of vision loss in neovascular AMD include those directly related to the new vessels such as leakage, hemorrhage, and fibrosis. Another important cause of vision loss, particularly in treated cases, is atrophy.” (opens the source at this quote in a new tab)

“Type 1 MNV: a neovascular complex located in the sub-RPE space originating from the choroid through a defect in Bruch’s membrane” (opens the source at this quote in a new tab)
“Type 3 MNV: pathologic angiogenesis originating from the deep retinal capillary plexus and extending to the outer retina (historically referred to as retinal angiomatous proliferation)” (opens the source at this quote in a new tab)

VEGF-A and VEGF-C in choroidal neovascularization

“With nAMD, immune cells are recruited to the macula, where they secrete proangiogenic cytokines (e.g., VEGF-A and VEGF-C) and proinflammatory cytokines (e.g., IL-31, LIF, and SDF1α)” (opens the source at this quote in a new tab)
“These VEGF ligand molecules stimulate endothelial cell proliferation and migration, angiogenesis, and increased vascular permeability, ultimately resulting in leakage of blood vessel fluid that damages the photoreceptor layer and impairs vision” (opens the source at this quote in a new tab)
“Interestingly, hypoxia-induced retinal expression of VEGF-C can induce pathological retinal neovascularization to an extent similar to that of VEGF-A” (opens the source at this quote in a new tab)

Compensatory VEGF-C and VEGF-D upregulation after VEGF-A inhibition

“Other ligand angiogenic mediators, VEGF-C and VEGF-D, are important in the pathogenesis of cancer and retinal vascular diseases; and evidence shows they are upregulated after VEGF-A suppression.” (opens the source at this quote in a new tab)
“In a laser-induced mouse model of CNV (a major cause of visual loss in patients with nAMD), the ability of anti-VEGF-C/-D monotherapy to reduce vascular leakage and CNV area was similar to that of aflibercept (which targets VEGF-A/-B and PIGF); and when used in combination, the efficacy was superior to that of either therapeutic approach alone” (opens the source at this quote in a new tab)

Complement dysregulation linked to CFH

“The CFH gene product is involved in regulation of the complement system through binding to factor C3b.” (opens the source at this quote in a new tab)

Pathogenic processes implicated in drusen formation and photoreceptor degeneration

“Chronic inflammation, lipid deposition, oxidative stress and impaired extracellular matrix maintenance are strongly implicated in AMD pathogenesis.” (opens the source at this quote in a new tab)
“However, the exact interactions of pathophysiological events that culminate in drusen formation and the associated degeneration processes remain to be elucidated.” (opens the source at this quote in a new tab)

Disease spectrum of distinct phenotypes with different pathogenic mechanisms

“Compelling progress in high-resolution retinal imaging has enabled refined phenotyping of AMD in vivo.” (opens the source at this quote in a new tab)
“Hence, our current understanding promotes the view that AMD represents a disease spectrum comprising distinct phenotypes with different mechanisms of pathogenesis.” (opens the source at this quote in a new tab)