Materiały źródłowe

• #1 Wet Age-Related Macular Degeneration (AMD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572147/

  Wet (exudative or neovascular) age-related macular degeneration is the most common cause of visual impairment among older patients in developed countries. Approximately 10% of patients with age-related macular degeneration develop choroidal neovascularization, which is the hallmark of wet age-related macular degeneration. Vascular endothelial growth factor plays a critical role in the development of choroidal neovascularization, leading to complications such as bleeding under the retina, retinal pigment epithelium detachment or atrophy, hard exudate deposition, or subretinal or subretinal pigment epithelium fluid accumulation with associated vision loss. […] Vascular endothelial growth factor (VEGF) drives the development of choroidal neovascularization (CNV), where new vessels grow under or through the retinal pigment epithelium (RPE), often through breaks in the Bruch membrane. Regular administration of intravitreal anti-VEGF medications may prevent blindness in most patients with wet AMD. In the absence of such treatment, patients experience severe, irreversible vision loss.

• #2 Age-Related Macular Degeneration (AMD or ARMD) – Eye Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd

  Age-related macular degeneration (AMD) is the most common cause of irreversible central vision loss in older patients. […] Wet (exudative or neovascular): Wet AMD occurs in about 15% of people. […] Although only 15% of patients with AMD have the wet form, 80 to 90% of the severe vision loss caused by AMD results from wet AMD. […] Wet AMD occurs when new abnormal blood vessels develop under the retina in a process called choroidal neovascularization (abnormal new vessel formation). […] Intravitreal injection of antivascular endothelial growth factor (anti-VEGF) medications (usually ranibizumab, bevacizumab, or aflibercept) can substantially reduce the risk of vision loss and can preserve useful vision in 20% of patients over their lifetime and reading vision in up to one-third of patients.

• #3 Wet Macular Degeneration | Signs, Symptoms, and Treatments

  https://www.macular.org/about-macular-degeneration/wet-macular-degeneration

  Approximately 10-15% of the cases of macular degeneration are the wet (exudative) type, sometimes also referred to at neovascular macular degeneration or nAMD. […] In the wet type of macular degeneration, abnormal blood vessels (known as choroidal neovascularization or CNV) grow under the retina and macula. These new blood vessels may then bleed and leak fluid, causing the macula to bulge or lift up from its normally flat position, thus distorting or destroying central vision. Under these circumstances, vision loss may be rapid and severe. […] Once CNV has developed in one eye, whether there is a visual loss or not, the other eye is at relatively high risk for the same change. […] Early, and sustained treatment has been shown to be the best course of action to preserve as much vision as possible for as long as possible if you have developed wet macular degeneration.

• #4 Exudative (Wet) Age-Related Macular Degeneration (AMD): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1226030-overview

  In the wet, or exudative, form of age-related macular degeneration (AMD or ARMD), pathologic choroidal neovascular membranes (CNVM) develop under the retina. The CNVM can leak fluid and blood and, if left untreated, ultimately cause a centrally blinding disciform scar. […] Patients with nonexudative AMD can progress to the wet, or exudative, form of AMD, in which pathologic choroidal neovascular membranes (CNVM) develop under the retina. The CNVM can leak fluid and blood, and, ultimately, cause a centrally blinding disciform scar over a relatively short time if left untreated. […] The exact pathophysiology of AMD is relatively poorly understood; however, recent discoveries are advancing our understanding. Research has concentrated on the RPE/photoreceptor/Bruch’s membrane complex. […] Breakdown of Bruch’s membrane and a rise in vascular endothelial growth factors can lead to the growth of abnormal choroidal vessels beneath the RPE and potentially under the retina. These vessels go through a period of leakage and occasionally bleed before they eventually involute and result in scar formation. The end-stage of exudative AMD is the formation of a disciform scar in the macula that results in permanent loss of central vision.

• #5 Wet Macular Degeneration | Signs, Symptoms, and Treatments

  https://www.macular.org/about-macular-degeneration/wet-macular-degeneration

  Approximately 10-15% of the cases of macular degeneration are the wet (exudative) type, sometimes also referred to at neovascular macular degeneration or nAMD. […] In the wet type of macular degeneration, abnormal blood vessels (known as choroidal neovascularization or CNV) grow under the retina and macula. These new blood vessels may then bleed and leak fluid, causing the macula to bulge or lift up from its normally flat position, thus distorting or destroying central vision. Under these circumstances, vision loss may be rapid and severe. […] Once CNV has developed in one eye, whether there is a visual loss or not, the other eye is at relatively high risk for the same change. […] Early, and sustained treatment has been shown to be the best course of action to preserve as much vision as possible for as long as possible if you have developed wet macular degeneration.

• #6 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the developed world. While treatment is effective for the neovascular or wet form of AMD, no therapy is successful for the non-neovascular or dry form. […] The lack of preventive measures and treatment for dry AMD underscores the importance of gaining a better understanding of its pathobiology. […] Prior research has implicated strong roles for inflammation, and complement in particular, mitochondrial dysfunction, oxidative stress, lipid abnormalities, and cell death in dry AMD pathobiology, but their precise mechanisms are unclear. […] The National Advisory Eye Council established a working group to evaluate the current knowledge on dry AMD pathobiology and propose future research directions that would expedite the development of new treatments and the purpose of this perspective is to report on the findings from this working group.

• #7 Wet Age-Related Macular Degeneration (AMD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572147/

  Many findings indicate that inflammation plays a key role in the pathogenesis of wet AMD. Most notably, polymorphisms of complement factor H, which normally inhibits the alternative complement pathway, are among the best-known mutations in AMD, suggesting the important role of complement activation in its development. […] AMD is differentiated from early or dry AMD by the presence of CNV, where new blood vessels from the choroid penetrate through the Bruch membrane and proliferate either between the Bruch membrane and the RPE or in the subretinal space. Various factors contribute to the development of CNV and vision loss in patients with wet AMD. These factors include the following: VEGF accumulation, particularly the VEGF-165 isoform; growth of new blood vessels with the proliferation of fibrous tissue; leakage of fluid, proteins, and lipids from the new vessels; hemorrhage from the fragile new vessels; fibrovascular scar formation, with the death of the neurosensory retina and vision loss.

• #8 Wet Age-Related Macular Degeneration (AMD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572147/

  Wet (exudative or neovascular) age-related macular degeneration is the most common cause of visual impairment among older patients in developed countries. Approximately 10% of patients with age-related macular degeneration develop choroidal neovascularization, which is the hallmark of wet age-related macular degeneration. Vascular endothelial growth factor plays a critical role in the development of choroidal neovascularization, leading to complications such as bleeding under the retina, retinal pigment epithelium detachment or atrophy, hard exudate deposition, or subretinal or subretinal pigment epithelium fluid accumulation with associated vision loss. […] Vascular endothelial growth factor (VEGF) drives the development of choroidal neovascularization (CNV), where new vessels grow under or through the retinal pigment epithelium (RPE), often through breaks in the Bruch membrane. Regular administration of intravitreal anti-VEGF medications may prevent blindness in most patients with wet AMD. In the absence of such treatment, patients experience severe, irreversible vision loss.

• #9 Wet Age-Related Macular Degeneration (AMD) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/133116

  Various factors contribute to the development of CNV and vision loss in patients with wet AMD. These factors include the following: VEGF accumulation, particularly the VEGF-165 isoform; growth of new blood vessels with the proliferation of fibrous tissue; leakage of fluid, proteins, and lipids from the new vessels; hemorrhage from the fragile new vessels; fibrovascular scar formation, with the death of the neurosensory retina and vision loss. […] The mainstay of therapy for wet AMD is intravitreal anti-VEGF treatment. Currently used agents prevent visual loss and may also improve vision in some cases.

• #10 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Drusen play a role in inhibiting the transport of metabolites to the choroid vessels and their molecular components also initiate inflammation through the complement cascade. […] nAMD is characterized by abnormal angiogenesis within the choroid, subretinal space, and retina, driven by angiogenic signaling molecules, including vascular epithelial growth factor (VEGF). Continued damage to the RPE leads to further dysfunction of Bruch’s membrane, which in some patients, is accompanied by a rise in VEGF, resulting in the growth of new vessels under the retinal pigment epithelium and the retina.

• #11 Wet Age-related Macular Degeneration – South Pasadena, CA: Retina Eye Specialists

  https://www.retinaeye.com/contents/common-diseases/macular-conditions/wet-age-related-macular-degeneration

  Age-related Macular Degeneration (AMD) is a condition affecting people over the age of 50 and is the leading cause of blindness in people over the age of 65. Damage to the macula in AMD occurs due to oxidative stress (oxygen free-radical molecules) and inflammation. […] In around 15% of cases, Dry Age-related Macular Degeneration progresses to the more vision threatening wet form of the disease. Wet AMD is characterized by the growth of abnormal blood vessels below the retina called Choroidal Neovascularization, or CNV for short. As the RPE becomes damaged and inflamed during dry AMD, ischemia (not enough blood) occurs. When this happens, cells within the RPE release a chemical called vascular endiothelial growth factor (VEGF), which causes new blood vessels to grow. These new vessels are very fragile and tend to leak blood and fluid under the retina, causing further damage and inflammation. Damage to the macula can occur rapidly and vision loss usually progresses much more quickly than dry AMD.

• #12 Tyrosine Kinase Inhibitors for Wet AMD and Diabetic Retinopathy | Retinal Physician

  https://retinalphysician.com/issues/2024/april/tyrosine-kinase-inhibitors-for-wet-amd-and-diabetic-retinopathy/

  Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR), including diabetic macular edema (DME), are among the leading causes of vision loss. […] Anti-VEGF therapies target VEGF, the primary driver of nAMD and DR, and prevent its binding to the extracellular portion of the VEGF receptor (VEGFR). VEGFR is a receptor tyrosine kinase (RTK). Binding of VEGF to VEGFR causes RTK dimerization. […] Other RTKs involved in the pathogenesis of nAMD and DR include PDGFR, FGFR, and Tie2. […] Tyrosine kinase inhibitors (TKIs) are small molecules that diffuse into cells and act intracellularly to prevent tyrosine kinase phosphorylation and the resultant signaling cascade. […] Although both anti-VEGF and TKIs can suppress VEGFR activation, TKIs act on multiple tyrosine kinase receptors and at a different site on the receptor.

• #13 Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

  https://www.mdpi.com/1422-0067/22/3/1170

  Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. […] Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. […] Neovascular AMD, wherein abnormal vessels break through Bruch’s membrane, is one of the leading causes of blindness in the West. It is mediated through several mechanisms. […] The accumulation of photo-oxidized products in the RPE is believed to be an underlying cause of age-related macular degeneration. […] Oxidative stress triggers many other pathways, with the autocrine signaling and upregulation of VEGF being no exception. […] In nvAMD, anti-VEGF therapy is currently the only treatment available, which only slows down the progression of the disease, however more knowledge about the downstream effects of factors such as VEGF may offer another treatment modality.

• #14 Wet Age-Related Macular Degeneration (AMD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572147/

  Many findings indicate that inflammation plays a key role in the pathogenesis of wet AMD. Most notably, polymorphisms of complement factor H, which normally inhibits the alternative complement pathway, are among the best-known mutations in AMD, suggesting the important role of complement activation in its development. […] AMD is differentiated from early or dry AMD by the presence of CNV, where new blood vessels from the choroid penetrate through the Bruch membrane and proliferate either between the Bruch membrane and the RPE or in the subretinal space. Various factors contribute to the development of CNV and vision loss in patients with wet AMD. These factors include the following: VEGF accumulation, particularly the VEGF-165 isoform; growth of new blood vessels with the proliferation of fibrous tissue; leakage of fluid, proteins, and lipids from the new vessels; hemorrhage from the fragile new vessels; fibrovascular scar formation, with the death of the neurosensory retina and vision loss.

• #15 Wet Age-Related Macular Degeneration (AMD) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/133116

  Wet age-related macular degeneration (AMD), also known as exudative or neovascular AMD, primarily affects the macula and is the most common cause of central visual impairment and blindness among older individuals in developed countries. […] Many findings indicate that inflammation plays a key role in the pathogenesis of wet AMD. Most notably, polymorphisms of complement factor H, which normally inhibits the alternative complement pathway, are among the best-known mutations in AMD, suggesting the important role of complement activation in its development. […] AMD is differentiated from early or dry AMD by the presence of CNV, where new blood vessels from the choroid penetrate through the Bruch membrane and proliferate either between the Bruch membrane and the RPE or in the subretinal space.

• #16 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The degenerating retina succumbs to the final end point of geographic atrophy, choroidal neovascularization and pigment epithelial detachment. […] Treatments targeting intermediate disease mechanisms or initiating disease factors are in the minority, but may offer a more successful approach to vision preservation than those targeting relatively later steps in AMD pathophysiology (i.e., choroidal neovascularization). […] Complement factor H (CFH) is an important gene in the pathogenesis of AMD. […] Biochemical pathways and genetic association studies have shed light on the possible biochemical pathways that go awry in AMD. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD.

• #17 The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment | Eye

  https://www.nature.com/articles/eye2010196

  The complement system is a major contributor to innate immunity. […] These findings indicate that the complement components and regulators may contribute to the formation of drusen. […] This high-risk variant of CFH increases the risk of AMD by 5- to 7-fold in Caucasians. […] C3 activation is believed to contribute to AMD progression independent of CFH polymorphism. […] Given the importance of the complement system in AMD development, complement components and regulators may be targeted in novel adjunctive therapies for non-neovascular and neovascular AMD. […] The initial pathological changes in AMD appear in macular photoreceptors, RPE, Bruch’s membrane, and choriocapillaris. […] it is indisputable that inflammation, both the innate immunity and autoimmune components, has a critical role in AMD pathogenesis and progression.

• #18 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  In AMD, it is believed that an early „seeding event,” such as an area of retinal pigment epithelium atrophy with cellular debris, induces innate immune system activation at the RPE-choroid-Bruch’s membrane complex. […] Subsequently, complement attack (membrane attack complex activation) leads to collateral damage of retinal tissue.

• #19 The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment | Eye

  https://www.nature.com/articles/eye2010196

  Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. […] Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. […] Although AMD is not a classic inflammatory disease, inflammatory cells have an important role in AMD pathogenesis and progression. […] Macrophages and giant cells have been reported to localize near drusen, at the breakdown of Bruch’s membrane, and in the CNV membrane. […] In addition to macrophages, microglial cells are also involved in the pathogenesis of AMD. […] Autoimmunity has also been suggested to have a role in drusen formation and AMD pathogenesis.

• #20 Wet Age-Related Macular Degeneration (AMD) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/133116

  Wet age-related macular degeneration (AMD), also known as exudative or neovascular AMD, primarily affects the macula and is the most common cause of central visual impairment and blindness among older individuals in developed countries. […] Many findings indicate that inflammation plays a key role in the pathogenesis of wet AMD. Most notably, polymorphisms of complement factor H, which normally inhibits the alternative complement pathway, are among the best-known mutations in AMD, suggesting the important role of complement activation in its development. […] AMD is differentiated from early or dry AMD by the presence of CNV, where new blood vessels from the choroid penetrate through the Bruch membrane and proliferate either between the Bruch membrane and the RPE or in the subretinal space.

• #21 Wet Age-Related Macular Degeneration (AMD) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/133116

  Various factors contribute to the development of CNV and vision loss in patients with wet AMD. These factors include the following: VEGF accumulation, particularly the VEGF-165 isoform; growth of new blood vessels with the proliferation of fibrous tissue; leakage of fluid, proteins, and lipids from the new vessels; hemorrhage from the fragile new vessels; fibrovascular scar formation, with the death of the neurosensory retina and vision loss. […] The mainstay of therapy for wet AMD is intravitreal anti-VEGF treatment. Currently used agents prevent visual loss and may also improve vision in some cases.

• #22 Wet Age-Related Macular Degeneration (AMD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572147/

  Many findings indicate that inflammation plays a key role in the pathogenesis of wet AMD. Most notably, polymorphisms of complement factor H, which normally inhibits the alternative complement pathway, are among the best-known mutations in AMD, suggesting the important role of complement activation in its development. […] AMD is differentiated from early or dry AMD by the presence of CNV, where new blood vessels from the choroid penetrate through the Bruch membrane and proliferate either between the Bruch membrane and the RPE or in the subretinal space. Various factors contribute to the development of CNV and vision loss in patients with wet AMD. These factors include the following: VEGF accumulation, particularly the VEGF-165 isoform; growth of new blood vessels with the proliferation of fibrous tissue; leakage of fluid, proteins, and lipids from the new vessels; hemorrhage from the fragile new vessels; fibrovascular scar formation, with the death of the neurosensory retina and vision loss.

• #23 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. The pathogenesis of nAMD involves aberrant angiogenesis and macular neovascularization (MNV, also known as choroidal neovascularization (CNV)), vascular leakage, haemorrhage and scarring, which can lead to permanent vision loss. A range of mediators have been implicated in this complex process including kinases, cytokines and growth factors; the most prominent is VEGF and its receptors (VEGFRs). Most therapeutic attention on AMD and diabetic retinopathy (DR) has focused on VEGF-A and its receptors because of its dominant capacity to promote angiogenesis and vascular permeability. The underlying nAMD lesion is the MNV (also known as CNV) complex which can be classified in terms of location type 1 is restricted to the sub-retinal pigment epithelium (RPE) space; type 2 grows through the RPE and into the sub-retinal space; and type 3 is believed to originate within the retina. A mixture of type 1 and 2 where neovascularization in both the sub-retinal and sub-RPE spaces can also occur. In addition, a particular subtype known as polypoidal choroidal vasculopathy (PCV), similar to a type 1 CNV with dilated vascular elements has also been described as part of the spectrum of nAMD and may be more prevalent among Asians. CNV is associated with other signs: retinal haemorrhage, intra- or sub-retinal fluid, pigment epithelial detachment (PED), exudate and subretinal fibrosis.

• #24 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. The pathogenesis of nAMD involves aberrant angiogenesis and macular neovascularization (MNV, also known as choroidal neovascularization (CNV)), vascular leakage, haemorrhage and scarring, which can lead to permanent vision loss. A range of mediators have been implicated in this complex process including kinases, cytokines and growth factors; the most prominent is VEGF and its receptors (VEGFRs). Most therapeutic attention on AMD and diabetic retinopathy (DR) has focused on VEGF-A and its receptors because of its dominant capacity to promote angiogenesis and vascular permeability. The underlying nAMD lesion is the MNV (also known as CNV) complex which can be classified in terms of location type 1 is restricted to the sub-retinal pigment epithelium (RPE) space; type 2 grows through the RPE and into the sub-retinal space; and type 3 is believed to originate within the retina. A mixture of type 1 and 2 where neovascularization in both the sub-retinal and sub-RPE spaces can also occur. In addition, a particular subtype known as polypoidal choroidal vasculopathy (PCV), similar to a type 1 CNV with dilated vascular elements has also been described as part of the spectrum of nAMD and may be more prevalent among Asians. CNV is associated with other signs: retinal haemorrhage, intra- or sub-retinal fluid, pigment epithelial detachment (PED), exudate and subretinal fibrosis.

• #25 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  The presence and progression of SDD can predict disease advancement to GA. […] Altered immune responses that lead to destructive neuroinflammation are thought to contribute to the dry AMD phenotype. […] This immune activation may involve close interplay between intracellular complement regulation and NLRP3 assembly in either immune cells or the RPE. […] Genetic studies have identified complement pathway gene variants with AMD risk, which strongly implicates the complement pathway in driving AMD progression. […] In dry AMD, RPE mitochondrial mass is reduced, mitochondria are morphologically abnormal, and mitochondrial DNA (mtDNA) damage increases with disease severity. […] Photoreceptor cell death is the basis for permanent visual decline in dry AMD. […] The mechanisms for RPE cell death may differ from those of photoreceptors.

• #26 Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

  https://www.mdpi.com/1422-0067/22/3/1170

  Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. […] Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. […] Neovascular AMD, wherein abnormal vessels break through Bruch’s membrane, is one of the leading causes of blindness in the West. It is mediated through several mechanisms. […] The accumulation of photo-oxidized products in the RPE is believed to be an underlying cause of age-related macular degeneration. […] Oxidative stress triggers many other pathways, with the autocrine signaling and upregulation of VEGF being no exception. […] In nvAMD, anti-VEGF therapy is currently the only treatment available, which only slows down the progression of the disease, however more knowledge about the downstream effects of factors such as VEGF may offer another treatment modality.

• #27 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  The presence and progression of SDD can predict disease advancement to GA. […] Altered immune responses that lead to destructive neuroinflammation are thought to contribute to the dry AMD phenotype. […] This immune activation may involve close interplay between intracellular complement regulation and NLRP3 assembly in either immune cells or the RPE. […] Genetic studies have identified complement pathway gene variants with AMD risk, which strongly implicates the complement pathway in driving AMD progression. […] In dry AMD, RPE mitochondrial mass is reduced, mitochondria are morphologically abnormal, and mitochondrial DNA (mtDNA) damage increases with disease severity. […] Photoreceptor cell death is the basis for permanent visual decline in dry AMD. […] The mechanisms for RPE cell death may differ from those of photoreceptors.

• #28 Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

  https://www.mdpi.com/1422-0067/22/3/1170

  Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. […] Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. […] Neovascular AMD, wherein abnormal vessels break through Bruch’s membrane, is one of the leading causes of blindness in the West. It is mediated through several mechanisms. […] The accumulation of photo-oxidized products in the RPE is believed to be an underlying cause of age-related macular degeneration. […] Oxidative stress triggers many other pathways, with the autocrine signaling and upregulation of VEGF being no exception. […] In nvAMD, anti-VEGF therapy is currently the only treatment available, which only slows down the progression of the disease, however more knowledge about the downstream effects of factors such as VEGF may offer another treatment modality.

• #29 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Drusen play a role in inhibiting the transport of metabolites to the choroid vessels and their molecular components also initiate inflammation through the complement cascade. […] nAMD is characterized by abnormal angiogenesis within the choroid, subretinal space, and retina, driven by angiogenic signaling molecules, including vascular epithelial growth factor (VEGF). Continued damage to the RPE leads to further dysfunction of Bruch’s membrane, which in some patients, is accompanied by a rise in VEGF, resulting in the growth of new vessels under the retinal pigment epithelium and the retina.

• #30 Age Related Macular Degeneration | Wet AMD | Non-Neovascular Macular Degeneration

  https://www.retinacenternj.com/diseases-treatment/age-related-macular-degeneration-wet-amd-or-non-ne

  ARMD is a degenerative disorder of the retina and the tissues below the retina called the retinal pigment epithelium (RPE), Buch’s membrane and choriocapillaris (small capillary like vessel in the choroid). […] ARMD begins with the accumulation of metabolic waste products from normal retinal metabolism in the space below the retina, within the cells below the retina (RPE) and/or below the RPE. The yellowish material that accumulates in these spaces is called lipofuscin. Lipofusion accumulation leads to the development of drusen. Drusen are small yellow lesions that can be seen in the macula (center of the retina) of patients with ARMD. The stage of ARMD is determined by the size of the drusen and number of drusen that are present in and around the macula. Stage 1 – Few small drusen Stage 2 – Few intermediate sized drusen or many small drusen Stage 3 – Many intermediate drusen or any large drusen Stage 4 Wet ARMD – Presence of a Choroidal Neovascular Membrane (CNVM) Stage 4 Dry ARMD – Presence of Geographic Atrophy (GA)

• #31 Age-Related Macular Degeneration: From One Medical Student to Another. EyeRounds :: The University of Iowa, Ophthalmology

  https://webeye.ophth.uiowa.edu/eyeforum/tutorials/AMD-medical-student/index.htm

  Age-Related Macular Degeneration (AMD) is the most common cause of blindness in the Western world. […] The pathogenesis of AMD is not completely clear. Scientists feel that AMD is likely a pathological extension of normal aging that occurs within the eye. […] However, it is clear that both genetics and the environment play a role in the pathogenesis. […] Bruchs membrane plays a critical role in the pathogenesis of AMD. […] As we age, Bruchs membrane tends to accumulate debris in the elastin lamina and also drusen between the collagen layer and RPE basal lamina. […] Aging is also associated with thinning and breakdown of the central elastin layer within Bruchs membrane. Thinning of this layer increases the risk of neovascularization as it reduces the number of bound anti-angiogenic proteins. […] Therefore, breakdown of elastin in Bruchs membrane not only causes a reduction in the barrier to neovascularization, but also stimulates vessel growth.

• #32 Age-Related Macular Degeneration: From One Medical Student to Another. EyeRounds :: The University of Iowa, Ophthalmology

  https://webeye.ophth.uiowa.edu/eyeforum/tutorials/AMD-medical-student/index.htm

  Age-Related Macular Degeneration (AMD) is the most common cause of blindness in the Western world. […] The pathogenesis of AMD is not completely clear. Scientists feel that AMD is likely a pathological extension of normal aging that occurs within the eye. […] However, it is clear that both genetics and the environment play a role in the pathogenesis. […] Bruchs membrane plays a critical role in the pathogenesis of AMD. […] As we age, Bruchs membrane tends to accumulate debris in the elastin lamina and also drusen between the collagen layer and RPE basal lamina. […] Aging is also associated with thinning and breakdown of the central elastin layer within Bruchs membrane. Thinning of this layer increases the risk of neovascularization as it reduces the number of bound anti-angiogenic proteins. […] Therefore, breakdown of elastin in Bruchs membrane not only causes a reduction in the barrier to neovascularization, but also stimulates vessel growth.

• #33 Pathophysiology of AMD: Vision Loss Information | Vision RELIEF

  https://provider-amd.vision-relief.com/pathophysiology-of-amd/

  Drusen play a role in inhibiting the transport of metabolites to the choroid vessels and their molecular components also initiate inflammation through the complement cascade. […] nAMD is characterized by abnormal angiogenesis within the choroid, subretinal space, and retina, driven by angiogenic signaling molecules, including vascular epithelial growth factor (VEGF). Continued damage to the RPE leads to further dysfunction of Bruch’s membrane, which in some patients, is accompanied by a rise in VEGF, resulting in the growth of new vessels under the retinal pigment epithelium and the retina.

• #34 Tyrosine Kinase Inhibitors for Wet AMD and Diabetic Retinopathy | Retinal Physician

  https://retinalphysician.com/issues/2024/april/tyrosine-kinase-inhibitors-for-wet-amd-and-diabetic-retinopathy/

  Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR), including diabetic macular edema (DME), are among the leading causes of vision loss. […] Anti-VEGF therapies target VEGF, the primary driver of nAMD and DR, and prevent its binding to the extracellular portion of the VEGF receptor (VEGFR). VEGFR is a receptor tyrosine kinase (RTK). Binding of VEGF to VEGFR causes RTK dimerization. […] Other RTKs involved in the pathogenesis of nAMD and DR include PDGFR, FGFR, and Tie2. […] Tyrosine kinase inhibitors (TKIs) are small molecules that diffuse into cells and act intracellularly to prevent tyrosine kinase phosphorylation and the resultant signaling cascade. […] Although both anti-VEGF and TKIs can suppress VEGFR activation, TKIs act on multiple tyrosine kinase receptors and at a different site on the receptor.

• #35 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Targeting the VEGF/R system has undoubtedly prevented blindness in millions of nAMD patients and improved quality of life and workforce productivity. However, given the shortcomings of current anti-VEGF therapy, there remains a need to identify other types of agents and modalities exploiting this pathway. Despite the promise of reduced treatment burden in nAMD patients brought about by brolucizumab, the future may lie with multi-target interventions. This is because considerable research suggests that factors beyond VEGF, such as other growth factors, chemokines and cytokines, also mediate the pathogenesis of nAMD. Angiogenesis and inflammation underpinning nAMD involves signalling and transcriptional regulation mediated by extracellular signal-regulated kinase-1/2, p-ERK, monocyte chemoattractant protein-1 (MCP-1/CCL2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 (IL-1) and IL-6. This may account for the inadequacy of strategies solely targeting the VEGF system and points to the therapeutic potential for strategies that also target other mediators of nAMD.

• #36 Wet Age-related Macular Degeneration – South Pasadena, CA: Retina Eye Specialists

  https://www.retinaeye.com/contents/common-diseases/macular-conditions/wet-age-related-macular-degeneration

  Age-related Macular Degeneration (AMD) is a condition affecting people over the age of 50 and is the leading cause of blindness in people over the age of 65. Damage to the macula in AMD occurs due to oxidative stress (oxygen free-radical molecules) and inflammation. […] In around 15% of cases, Dry Age-related Macular Degeneration progresses to the more vision threatening wet form of the disease. Wet AMD is characterized by the growth of abnormal blood vessels below the retina called Choroidal Neovascularization, or CNV for short. As the RPE becomes damaged and inflamed during dry AMD, ischemia (not enough blood) occurs. When this happens, cells within the RPE release a chemical called vascular endiothelial growth factor (VEGF), which causes new blood vessels to grow. These new vessels are very fragile and tend to leak blood and fluid under the retina, causing further damage and inflammation. Damage to the macula can occur rapidly and vision loss usually progresses much more quickly than dry AMD.

• #37 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Targeting the VEGF/R system has undoubtedly prevented blindness in millions of nAMD patients and improved quality of life and workforce productivity. However, given the shortcomings of current anti-VEGF therapy, there remains a need to identify other types of agents and modalities exploiting this pathway. Despite the promise of reduced treatment burden in nAMD patients brought about by brolucizumab, the future may lie with multi-target interventions. This is because considerable research suggests that factors beyond VEGF, such as other growth factors, chemokines and cytokines, also mediate the pathogenesis of nAMD. Angiogenesis and inflammation underpinning nAMD involves signalling and transcriptional regulation mediated by extracellular signal-regulated kinase-1/2, p-ERK, monocyte chemoattractant protein-1 (MCP-1/CCL2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 (IL-1) and IL-6. This may account for the inadequacy of strategies solely targeting the VEGF system and points to the therapeutic potential for strategies that also target other mediators of nAMD.

• #38 Oculis Holding AG to Present Innovative Late-Stage Pipeline at Major Ophthalmology Conferences in 2025

  https://www.quiverquant.com/news/Oculis+Holding+AG+to+Present+Innovative+Late-Stage+Pipeline+at+Major+Ophthalmology+Conferences+in+2025

  DME occurs when blood vessels in the retina swell, and then leak, leading to a fluid build-up (edema) into the retina. […] There remains a significant need for safe, efficacious, and less burdensome treatments for DME patients. […] Licaminlimab is an anti-TNFα eye drop candidate being developed with a single chain antibody fragment (scFv) technology specifically designed to treat ocular inflammatory diseases. […] The dual anti-inflammatory and anti-necrotic mechanism of action of TNF-α inhibition has been well-established in inflammatory disorders where the systemic use of TNF-α inhibitors has led to marked improvements in the disease management and treatment outcomes.

• #39 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Targeting the VEGF/R system has undoubtedly prevented blindness in millions of nAMD patients and improved quality of life and workforce productivity. However, given the shortcomings of current anti-VEGF therapy, there remains a need to identify other types of agents and modalities exploiting this pathway. Despite the promise of reduced treatment burden in nAMD patients brought about by brolucizumab, the future may lie with multi-target interventions. This is because considerable research suggests that factors beyond VEGF, such as other growth factors, chemokines and cytokines, also mediate the pathogenesis of nAMD. Angiogenesis and inflammation underpinning nAMD involves signalling and transcriptional regulation mediated by extracellular signal-regulated kinase-1/2, p-ERK, monocyte chemoattractant protein-1 (MCP-1/CCL2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 (IL-1) and IL-6. This may account for the inadequacy of strategies solely targeting the VEGF system and points to the therapeutic potential for strategies that also target other mediators of nAMD.

• #40

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  New strategies for treating AMD are beginning to emerge, including gene therapy, WNT agonists, anti-VEGF combination drugs, TK inhibitors, senescence-targeting drugs, and advancements in VEGF inhibitors. […] Gene therapy holds promise for managing both rare genetic disorders and common conditions such as AMD. […] New upcoming gene therapies for nAMD include RGX-314, ADVM-022, and 4D-150. […] Efdamrofusp alfa (IBI302) is a novel bispecific fusion protein targeting both VEGF and complement pathways, addressing the multifactorial nature. […] The Wnt pathway, crucial for embryogenesis, tissue homeostasis, and cancer development, operates through three main pathways: the canonical Wnt/-catenin pathway, the Wnt-planar cell polarity pathway, and the Wnt-calcium pathway. […] The pathogenesis of macular degeneration involves various processes, including senescence triggered by factors such as oxidative stress.

• #41

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  New strategies for treating AMD are beginning to emerge, including gene therapy, WNT agonists, anti-VEGF combination drugs, TK inhibitors, senescence-targeting drugs, and advancements in VEGF inhibitors. […] Gene therapy holds promise for managing both rare genetic disorders and common conditions such as AMD. […] New upcoming gene therapies for nAMD include RGX-314, ADVM-022, and 4D-150. […] Efdamrofusp alfa (IBI302) is a novel bispecific fusion protein targeting both VEGF and complement pathways, addressing the multifactorial nature. […] The Wnt pathway, crucial for embryogenesis, tissue homeostasis, and cancer development, operates through three main pathways: the canonical Wnt/-catenin pathway, the Wnt-planar cell polarity pathway, and the Wnt-calcium pathway. […] The pathogenesis of macular degeneration involves various processes, including senescence triggered by factors such as oxidative stress.

• #42 Home | Unity Biotechnology

  https://unitybiotechnology.com/

  Lead senolytic candidate UBX1325 has a novel mechanism of action that potentially provides longer lasting improvements in vision compared to current standard of care for diabetic macular edema. […] Positive clinical data from the Phase 2 BEHOLD study in DME demonstrates a single injection of UBX1325 led to a sustained statistically significant and clinically meaningful improvement in vision. […] The Phase 2b ASPIRE Study is designed to evaluate UBX1325 in comparison to aflibercept in previously treated patients with active DME who are not achieving optimal benefit from standard of care.

• #43 Wet age-related macular degeneration: case study – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/wet-age-related-macular-degeneration-case-study

  Wet age-related macular degeneration (AMD) is the leading cause of blindness in adults aged over 65 years in the developed world. […] Although the dry form is the most common, the wet form of AMD causes the worst visual impairment and accounts for 90% of blindness from AMD. […] Vascular endothelial growth factor (VEGF) plays a pivotal role in physiological angiogenesis, including that of the eye. […] Over-expression of VEGF results, however, in pathological angiogenesis, which in wet AMD manifests as abnormal growth of choroidal blood vessels (choroidal neovascularisation (CNV)). […] These choroidal neovascular vessels are leaky, leading to oedema and haemorrhage beneath the macula. […] Lesions are formed which turn into scars, resulting in destruction of the macula and loss of central vision.

• #44 Wet Age-Related Macular Degeneration (AMD) | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/133116

  Various factors contribute to the development of CNV and vision loss in patients with wet AMD. These factors include the following: VEGF accumulation, particularly the VEGF-165 isoform; growth of new blood vessels with the proliferation of fibrous tissue; leakage of fluid, proteins, and lipids from the new vessels; hemorrhage from the fragile new vessels; fibrovascular scar formation, with the death of the neurosensory retina and vision loss. […] The mainstay of therapy for wet AMD is intravitreal anti-VEGF treatment. Currently used agents prevent visual loss and may also improve vision in some cases.

• #45 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  The presence and progression of SDD can predict disease advancement to GA. […] Altered immune responses that lead to destructive neuroinflammation are thought to contribute to the dry AMD phenotype. […] This immune activation may involve close interplay between intracellular complement regulation and NLRP3 assembly in either immune cells or the RPE. […] Genetic studies have identified complement pathway gene variants with AMD risk, which strongly implicates the complement pathway in driving AMD progression. […] In dry AMD, RPE mitochondrial mass is reduced, mitochondria are morphologically abnormal, and mitochondrial DNA (mtDNA) damage increases with disease severity. […] Photoreceptor cell death is the basis for permanent visual decline in dry AMD. […] The mechanisms for RPE cell death may differ from those of photoreceptors.

• #46 Macular Degeneration Treatment | BrightFocus Foundation

  https://www.brightfocus.org/macular/treatments/

  All macular degeneration starts as the dry form, where the macula increasingly thins through early, intermediate, and advanced stages. […] Dry age-related macular degeneration (AMD) can progress to the wet, more advanced, form, in which tiny, fragile blood vessels in the eye can leak and trigger inflammation. […] AREDS2 also may slow the development of wet AMD, the less common form of the disease. […] Wet AMD can be treated with injections of angiogenesis inhibitors into the eye, with photodynamic therapy, or with laser surgery. […] Anti-VEGF shots block vascular endothelial growth factor, a key molecule in the production of new blood vessels in a process called angiogenesis, and are injected into the back of the eye, which has been numbed beforehand. […] Photodynamic therapy (PDT) is most effective in a subtype of wet macular degeneration called predominantly classic subfoveal AMD, in which blood vessel growth and leakage in the fovea are well defined. […] Laser photocoagulation surgery was the first treatment used for wet macular degeneration, but it is only an option for a small number of patients.

• #47 Age-related macular degeneration – UpToDate

  https://www.uptodate.com/contents/age-related-macular-degeneration

  Age-related macular degeneration (AMD) is a common cause of severe central vision loss and legal blindness in adults. The etiology, diagnosis, and treatment of AMD will be reviewed here. […] AMD is a degenerative disease of the photoreceptors of the central portion of the retina (the macula) and the supporting retinal pigment epithelium. It is characterized by loss of central vision. […] For clinical purposes, AMD is classified as either „dry” or „wet”. The less common form is wet AMD (also known as exudative or neovascular AMD). […] Wet AMD is characterized by new vessel formation in and under the retina. These abnormal blood vessels have a tendency to leak, leading to collections of fluid and/or blood in and/or beneath the retina. […] Dry AMD progresses to wet AMD in a minority of patients. The risk of developing wet AMD in people with bilateral, early, dry AMD (bilateral soft drusen) was estimated at approximately 3 per 100 person-years if both eyes have early- or intermediate-stage AMD.

• #48 Wet Macular Degeneration | Signs, Symptoms, and Treatments

  https://www.macular.org/about-macular-degeneration/wet-macular-degeneration

  Approximately 10-15% of the cases of macular degeneration are the wet (exudative) type, sometimes also referred to at neovascular macular degeneration or nAMD. […] In the wet type of macular degeneration, abnormal blood vessels (known as choroidal neovascularization or CNV) grow under the retina and macula. These new blood vessels may then bleed and leak fluid, causing the macula to bulge or lift up from its normally flat position, thus distorting or destroying central vision. Under these circumstances, vision loss may be rapid and severe. […] Once CNV has developed in one eye, whether there is a visual loss or not, the other eye is at relatively high risk for the same change. […] Early, and sustained treatment has been shown to be the best course of action to preserve as much vision as possible for as long as possible if you have developed wet macular degeneration.

• #49

  https://www.aao.org/eye-health/diseases/avastin-eylea-lucentis-difference

  Anti-VEGF drugs can prevent vision loss in patients with wet age-related macular degeneration (AMD), a leading cause of blindness among older Americans. […] Wet AMD is responsible for 90 percent of all AMD-related blindness. […] Today, we have a more positive outlook about wet AMD thanks to the introduction of injectable anti-vascular endothelial growth factor (anti-VEGF) drugs. […] This growth is fueled by a signal protein called vascular endothelial growth factor, or VEGF. Anti-VEGF treatments seek out harmful VEGF molecules and block them. This reduces abnormal growth and leakage, which helps to stabilize vision loss and, in some cases, can improve sight. […] The anti-VEGF medications slow down the disease but do not cure the wet AMD. Therefore, these treatments are typically ongoing.

• #50 Wet age-related macular degeneration: case study – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/wet-age-related-macular-degeneration-case-study

  Ocular tissue hypoxia and inflammatory conditions are implicated in the upregulation of VEGF synthesis. […] Four VEGF inhibitors have received regulatory approval for clinical use: pegaptanib (Macugen), ranibizumab (Lucentis) and aflibercept (VEGF Trap-eye) have been approved for treatment of wet AMD, whereas bevacizumab (Avastin) is used off-label for wet AMD. […] All four are large molecules, which bind in different ways to certain isoforms of VEGF, thus preventing VEGF interaction with its receptors. […] They have all been shown to suppress CNV and improve visual acuity. […] The intravitreal route is the most suitable route of administration for the treatment of wet AMD with ranibizumab. […] The vitreous is close to the target site and there are fewer biological barriers for the drug to overcome to reach the site of action.

• #51 Wet age-related macular degeneration: case study – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/wet-age-related-macular-degeneration-case-study

  Ocular tissue hypoxia and inflammatory conditions are implicated in the upregulation of VEGF synthesis. […] Four VEGF inhibitors have received regulatory approval for clinical use: pegaptanib (Macugen), ranibizumab (Lucentis) and aflibercept (VEGF Trap-eye) have been approved for treatment of wet AMD, whereas bevacizumab (Avastin) is used off-label for wet AMD. […] All four are large molecules, which bind in different ways to certain isoforms of VEGF, thus preventing VEGF interaction with its receptors. […] They have all been shown to suppress CNV and improve visual acuity. […] The intravitreal route is the most suitable route of administration for the treatment of wet AMD with ranibizumab. […] The vitreous is close to the target site and there are fewer biological barriers for the drug to overcome to reach the site of action.

• #52

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  UBX1325 is a senescence-targeting drug currently being studied for the treatment of nAMD and DME. […] Aflibercept (Eylea), a well-known anti-VEGF inhibitor, binds to all VEGF-A isoforms and placental growth factor (PIGF) via a fusion of the second Ig domain of VEGFR1 and the third Ig domain of VEGFR2 fused to the Fc region of human IgG1. […] The FDA approved the first drug, SYFOVRE Pegcetacoplan, in February 2023, targeting the C3 protein. […] The second drug, Izervay (formerly known as Zimura), avacincaptad pegol, was FDA-approved in August 2023, targeting the C5 protein.

• #53 Wet AMD | Wills Eye Hospital

  https://www.willseye.org/wet-amd/

  Wet age-related macular degeneration (AMD) is a form of eye disease that affects the macula, the central part of the retina responsible for sharp, detailed vision. […] The word „wet” implies leakage and bleeding in the macula due to abnormal blood vessels (choroidal neovascularization) that may develop spontaneously in AMD. If left untreated, these abnormal blood vessels result in permanent scarring of macular tissue and severe central vision loss. […] Fortunately, there are now anti-vascular endothelial growth factor (anti-VEGF) medications available for the treatment of wet AMD. These medications, injected into the eye as an office-based procedure, are currently the preferred therapy for wet AMD due to their unprecedented efficacy. […] Lucentis is a humanized antibody fragment that works by blocking an important growth factor of choroidal neovascularization called vascular endothelial growth factor (VEGF). By blocking VEGF, both the growth and leakiness of the abnormal blood vessels is reduced.

• #54

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  New strategies for treating AMD are beginning to emerge, including gene therapy, WNT agonists, anti-VEGF combination drugs, TK inhibitors, senescence-targeting drugs, and advancements in VEGF inhibitors. […] Gene therapy holds promise for managing both rare genetic disorders and common conditions such as AMD. […] New upcoming gene therapies for nAMD include RGX-314, ADVM-022, and 4D-150. […] Efdamrofusp alfa (IBI302) is a novel bispecific fusion protein targeting both VEGF and complement pathways, addressing the multifactorial nature. […] The Wnt pathway, crucial for embryogenesis, tissue homeostasis, and cancer development, operates through three main pathways: the canonical Wnt/-catenin pathway, the Wnt-planar cell polarity pathway, and the Wnt-calcium pathway. […] The pathogenesis of macular degeneration involves various processes, including senescence triggered by factors such as oxidative stress.

• #55 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Despite favorable outcomes in most patients, 25-35% of nAMD patients either fail to respond optimally to current anti-VEGF therapies, exhibit late failure to therapy, or require intensive, frequent IVT treatment. Of the 35% who fail to respond optimally to therapy, over 10% worsen despite treatment, while another 25% show no improvement. Despite maximal intensive anti-VEGF therapy, over 60% of eyes have persistently active disease, which can result in poor long-term outcomes. […] The present management of late AMD is focused on treating nAMD, as there are no proven treatments to date for atrophic AMD/GA. Intravitreal (IVT) anti-VEGF therapy is the standard of care for the treatment of nAMD. Therapies include aflibercept, ranibizumab, bevacizumab which is currently used as off-label therapy but due to be registered, and brolucizumab. New therapies with longer durability and better efficacy in early trials that target VEGF-A alone have not been as successful as the initial generation of anti-VEGF agents, largely due to unanticipated side effects.

• #56 Tyrosine Kinase Inhibitors for Wet AMD and Diabetic Retinopathy | Retinal Physician

  https://retinalphysician.com/issues/2024/april/tyrosine-kinase-inhibitors-for-wet-amd-and-diabetic-retinopathy/

  Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR), including diabetic macular edema (DME), are among the leading causes of vision loss. […] Anti-VEGF therapies target VEGF, the primary driver of nAMD and DR, and prevent its binding to the extracellular portion of the VEGF receptor (VEGFR). VEGFR is a receptor tyrosine kinase (RTK). Binding of VEGF to VEGFR causes RTK dimerization. […] Other RTKs involved in the pathogenesis of nAMD and DR include PDGFR, FGFR, and Tie2. […] Tyrosine kinase inhibitors (TKIs) are small molecules that diffuse into cells and act intracellularly to prevent tyrosine kinase phosphorylation and the resultant signaling cascade. […] Although both anti-VEGF and TKIs can suppress VEGFR activation, TKIs act on multiple tyrosine kinase receptors and at a different site on the receptor.

• #57 Tyrosine Kinase Inhibitors for Wet AMD and Diabetic Retinopathy | Retinal Physician

  https://retinalphysician.com/issues/2024/april/tyrosine-kinase-inhibitors-for-wet-amd-and-diabetic-retinopathy/

  TKIs inhibit the intracellular domain of VEGFR, whereas anti-VEGF molecules bind to and prevent VEGF from acting on the extracellular domain of the VEGFR. […] Encouraging initial TKI clinical trial data point toward the effectiveness of these therapies in treating nAMD and DR. The advent of sustained-delivery TKIs represents a significant advancement, potentially reducing the frequency of treatments and thereby improving patient compliance and overall treatment effectiveness in real-world scenarios.

• #58 EyePoint Pharmaceuticals, Inc. (NASDAQ:EYPT) Q1 2025 Earnings Call Transcript – Insider Monkey

  https://www.insidermonkey.com/blog/eyepoint-pharmaceuticals-inc-nasdaqeypt-q1-2025-earnings-call-transcript-1528095/

  Jay Duker: […] Notably, we continue to receive strong positive feedback from both physicians and patients for our ongoing global Phase 3 trials, LUGANO and LUCIA for DURAVYU in wet age-related macular degeneration or wet AMD, underscoring the impressive enrollment rate we are seeing. […] DURAVYU is a clinically validated, differentiated and potentially best-in-class sustained release TKI. DURAVYUs receptor level inhibition of VEGF blocking all isoforms of VEGF offers a broader and possibly more durable disease control compared to current ligand blocking therapeutics. […] By also blocking PDGF receptors, DURAVYU may help reduce fibrosis, a key driver of long-term visual loss, which could further differentiate this potential wet AMD therapy. […] Our Phase III non-inferiority program was developed in direct alignment with the FDA follows recognized industry best practices and is strategically designed to enhance the probability of both regulatory and commercial success.

• #59

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  New strategies for treating AMD are beginning to emerge, including gene therapy, WNT agonists, anti-VEGF combination drugs, TK inhibitors, senescence-targeting drugs, and advancements in VEGF inhibitors. […] Gene therapy holds promise for managing both rare genetic disorders and common conditions such as AMD. […] New upcoming gene therapies for nAMD include RGX-314, ADVM-022, and 4D-150. […] Efdamrofusp alfa (IBI302) is a novel bispecific fusion protein targeting both VEGF and complement pathways, addressing the multifactorial nature. […] The Wnt pathway, crucial for embryogenesis, tissue homeostasis, and cancer development, operates through three main pathways: the canonical Wnt/-catenin pathway, the Wnt-planar cell polarity pathway, and the Wnt-calcium pathway. […] The pathogenesis of macular degeneration involves various processes, including senescence triggered by factors such as oxidative stress.

• #60 Macular Degeneration Breakthroughs: Emerging Treatments

  https://www.verywellhealth.com/macular-degeneration-emerging-treatments-5071096

  Breakthroughs in age-related macular degeneration (AMD) treatments have revolutionized the management of this progressive and potentially devastating eye disease. […] These include treatments such as complement inhibitors and stem cell therapy for dry AMD and long-acting anti-VEGF drugs and gene therapy for more advanced wet AMD. […] With wet AMD, blood vessels start to grow abnormally in the retina, stimulated by a protein known as vascular endothelial growth factor (VEGF). […] The drugs are known as complement inhibitors because they block a part of the immune system called the complement cascade that triggers the formation of these lesions. […] The introduction of the first-generation anti-VEGF drugs Macugen (pegaptanib), Eylea (aflibercept), Lucentis (ranibizumab), and Avastin (bevacizumab) has since been followed by longer-lasting agents that require less frequent eye injection. […] One promising alternative to anti-VEGF injections is gene therapy in which the eyes are given the genetic tools to make their own anti-VEGF agents. […] If proven effective, gene therapy may displace anti-VEGF injection as the preferred form of treatment for wet AMD.

• #61

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  UBX1325 is a senescence-targeting drug currently being studied for the treatment of nAMD and DME. […] Aflibercept (Eylea), a well-known anti-VEGF inhibitor, binds to all VEGF-A isoforms and placental growth factor (PIGF) via a fusion of the second Ig domain of VEGFR1 and the third Ig domain of VEGFR2 fused to the Fc region of human IgG1. […] The FDA approved the first drug, SYFOVRE Pegcetacoplan, in February 2023, targeting the C3 protein. […] The second drug, Izervay (formerly known as Zimura), avacincaptad pegol, was FDA-approved in August 2023, targeting the C5 protein.

• #62 Complement Factor 5 Inhibition in Age-related Macular Degeneration – Retina Today

  https://retinatoday.com/articles/2010-oct/complement-factor-5-inhibition-in-age-related-macular-degeneration

  Inhibition of the alternate pathway of complement activation led to decreased proangiogenic factors and decreased CNV formation in experimental CNV. […] One promising approach to blocking the complement system in AMD is via the utilization of ARC1905 (Ophthotech, Inc., Princeton, NJ), a potent and selective inhibitor of factor C5 of the complement system. C5 inhibition prevents the formation of the key terminal fragments responsible for tissue pathology, C5a and the MAC. […] By inhibiting C5-mediated inflammatory and MAC activities, therapeutic benefit may be achieved in both dry and wet AMD while sparing the immunoprotective functions of the complement system. […] The phase 1 ARC1905 study demonstrated that the combination of PDGF and VEGF inhibition was well tolerated, with an absence of dose-limiting toxicity. ARC1905 shows great promise for enhanced efficacy in eyes with wet AMD in this large and expanding population.

• #63

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  UBX1325 is a senescence-targeting drug currently being studied for the treatment of nAMD and DME. […] Aflibercept (Eylea), a well-known anti-VEGF inhibitor, binds to all VEGF-A isoforms and placental growth factor (PIGF) via a fusion of the second Ig domain of VEGFR1 and the third Ig domain of VEGFR2 fused to the Fc region of human IgG1. […] The FDA approved the first drug, SYFOVRE Pegcetacoplan, in February 2023, targeting the C3 protein. […] The second drug, Izervay (formerly known as Zimura), avacincaptad pegol, was FDA-approved in August 2023, targeting the C5 protein.

• #64 Home | Unity Biotechnology

  https://unitybiotechnology.com/

  Lead senolytic candidate UBX1325 has a novel mechanism of action that potentially provides longer lasting improvements in vision compared to current standard of care for diabetic macular edema. […] Positive clinical data from the Phase 2 BEHOLD study in DME demonstrates a single injection of UBX1325 led to a sustained statistically significant and clinically meaningful improvement in vision. […] The Phase 2b ASPIRE Study is designed to evaluate UBX1325 in comparison to aflibercept in previously treated patients with active DME who are not achieving optimal benefit from standard of care.

• #65

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  New strategies for treating AMD are beginning to emerge, including gene therapy, WNT agonists, anti-VEGF combination drugs, TK inhibitors, senescence-targeting drugs, and advancements in VEGF inhibitors. […] Gene therapy holds promise for managing both rare genetic disorders and common conditions such as AMD. […] New upcoming gene therapies for nAMD include RGX-314, ADVM-022, and 4D-150. […] Efdamrofusp alfa (IBI302) is a novel bispecific fusion protein targeting both VEGF and complement pathways, addressing the multifactorial nature. […] The Wnt pathway, crucial for embryogenesis, tissue homeostasis, and cancer development, operates through three main pathways: the canonical Wnt/-catenin pathway, the Wnt-planar cell polarity pathway, and the Wnt-calcium pathway. […] The pathogenesis of macular degeneration involves various processes, including senescence triggered by factors such as oxidative stress.

• #66 EyePoint Pharmaceuticals, Inc. (NASDAQ:EYPT) Q1 2025 Earnings Call Transcript – Insider Monkey

  https://www.insidermonkey.com/blog/eyepoint-pharmaceuticals-inc-nasdaqeypt-q1-2025-earnings-call-transcript-1528095/

  Jay Duker: […] Notably, we continue to receive strong positive feedback from both physicians and patients for our ongoing global Phase 3 trials, LUGANO and LUCIA for DURAVYU in wet age-related macular degeneration or wet AMD, underscoring the impressive enrollment rate we are seeing. […] DURAVYU is a clinically validated, differentiated and potentially best-in-class sustained release TKI. DURAVYUs receptor level inhibition of VEGF blocking all isoforms of VEGF offers a broader and possibly more durable disease control compared to current ligand blocking therapeutics. […] By also blocking PDGF receptors, DURAVYU may help reduce fibrosis, a key driver of long-term visual loss, which could further differentiate this potential wet AMD therapy. […] Our Phase III non-inferiority program was developed in direct alignment with the FDA follows recognized industry best practices and is strategically designed to enhance the probability of both regulatory and commercial success.

• #67

  https://www.marketbeat.com/earnings/reports/2025-5-7-eyepoint-pharmaceuticals-inc-stock/

  Notably, we continue to receive strong positive feedback from both physicians and patients for our ongoing global Phase III trials, Lugano and LUTIA for DuraVu in wet age related macular degeneration or wet AMD, underscoring the impressive enrollment rate we are seeing. […] DuraVu is clinically validated differentiated and potentially best in class sustained release TKI. DuraVu’s receptor level inhibition of VEGF blocking all isoforms of VEGF offers a broader and possibly more durable disease control compared to current ligand blocking therapeutics. […] DuraVu has established a very favorable safety profile with no DuraVu related ocular or systemic SAEs observed in over one hundred and ninety patients evaluated across clinical trials for multiple indications. […] Our Phase III non inferiority program was developed in direct alignment with the FDA, follows recognized industry best practices and is strategically designed to enhance the probability of both regulatory and commercial success.

• #68 Wet Age-Related Macular Degeneration (AMD) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK572147/

  Wet (exudative or neovascular) age-related macular degeneration is the most common cause of visual impairment among older patients in developed countries. Approximately 10% of patients with age-related macular degeneration develop choroidal neovascularization, which is the hallmark of wet age-related macular degeneration. Vascular endothelial growth factor plays a critical role in the development of choroidal neovascularization, leading to complications such as bleeding under the retina, retinal pigment epithelium detachment or atrophy, hard exudate deposition, or subretinal or subretinal pigment epithelium fluid accumulation with associated vision loss. […] Vascular endothelial growth factor (VEGF) drives the development of choroidal neovascularization (CNV), where new vessels grow under or through the retinal pigment epithelium (RPE), often through breaks in the Bruch membrane. Regular administration of intravitreal anti-VEGF medications may prevent blindness in most patients with wet AMD. In the absence of such treatment, patients experience severe, irreversible vision loss.

• #69

  https://journals.lww.com/ijo/fulltext/2025/01001/dry_and_neovascular__wet__age_related_macular.8.aspx

  The age-related macular degeneration (AMD) field is witnessing promising advancements in therapeutic options. […] While several antivascular endothelial growth factor (VEGF) inhibitors have been approved for wet AMD, challenges persist with the need for frequent dosing. […] In Wet AMD, increased inflammation and complement activity lead to abnormal blood vessel growth with blood and fluid leakage and eventually scar tissue formation beneath the neuro-epithelium and in the retinal stroma. […] Vascular endothelial growth factor (VEGF), a signaling protein that stimulates new blood vessel creation, is critical in ocular neovascularization. […] Despite successes, challenges remain, including the burden of frequent clinical visits leading to undertreatment with lower visual acuity improvement in practice compared to clinical studies.

• #70 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Despite favorable outcomes in most patients, 25-35% of nAMD patients either fail to respond optimally to current anti-VEGF therapies, exhibit late failure to therapy, or require intensive, frequent IVT treatment. Of the 35% who fail to respond optimally to therapy, over 10% worsen despite treatment, while another 25% show no improvement. Despite maximal intensive anti-VEGF therapy, over 60% of eyes have persistently active disease, which can result in poor long-term outcomes. […] The present management of late AMD is focused on treating nAMD, as there are no proven treatments to date for atrophic AMD/GA. Intravitreal (IVT) anti-VEGF therapy is the standard of care for the treatment of nAMD. Therapies include aflibercept, ranibizumab, bevacizumab which is currently used as off-label therapy but due to be registered, and brolucizumab. New therapies with longer durability and better efficacy in early trials that target VEGF-A alone have not been as successful as the initial generation of anti-VEGF agents, largely due to unanticipated side effects.

• #71 Wet Macular Degeneration | Signs, Symptoms, and Treatments

  https://www.macular.org/about-macular-degeneration/wet-macular-degeneration

  Approximately 10-15% of the cases of macular degeneration are the wet (exudative) type, sometimes also referred to at neovascular macular degeneration or nAMD. […] In the wet type of macular degeneration, abnormal blood vessels (known as choroidal neovascularization or CNV) grow under the retina and macula. These new blood vessels may then bleed and leak fluid, causing the macula to bulge or lift up from its normally flat position, thus distorting or destroying central vision. Under these circumstances, vision loss may be rapid and severe. […] Once CNV has developed in one eye, whether there is a visual loss or not, the other eye is at relatively high risk for the same change. […] Early, and sustained treatment has been shown to be the best course of action to preserve as much vision as possible for as long as possible if you have developed wet macular degeneration.

• #72 Wet Macular Degeneration | Signs, Symptoms, and Treatments

  https://www.macular.org/about-macular-degeneration/wet-macular-degeneration

  Current treatment options target controlling bleeding, with the accepted first line of treatment being Anti-VEGF drugs that control bleeding by stopping the growth of new blood vessels that tend to be leaky. […] Anti-VEGF drugs do not restore vision, though some patients may experience a sense of vision restoration due to the body reabsorbing fluid behind the retina after the bleeding is stopped. But anti-VEGF drugs cannot repair retinal scarring, which is the main culprit of vision loss in wet macular degeneration.

• #73

  https://www.aao.org/eye-health/diseases/avastin-eylea-lucentis-difference

  The two newest treatments, Vabysmo and Eylea HD, are unique in that they may allow patients to space out their eye injections to three-to-four times per year rather than requiring visits to the ophthalmologist 6 to 12 times per year. […] Multiple studies have compared these anti-VEGF drugs and found that all are very effective at helping patients retain their ability to see.

• #74

  https://www.aao.org/eye-health/diseases/avastin-eylea-lucentis-difference

  Anti-VEGF drugs can prevent vision loss in patients with wet age-related macular degeneration (AMD), a leading cause of blindness among older Americans. […] Wet AMD is responsible for 90 percent of all AMD-related blindness. […] Today, we have a more positive outlook about wet AMD thanks to the introduction of injectable anti-vascular endothelial growth factor (anti-VEGF) drugs. […] This growth is fueled by a signal protein called vascular endothelial growth factor, or VEGF. Anti-VEGF treatments seek out harmful VEGF molecules and block them. This reduces abnormal growth and leakage, which helps to stabilize vision loss and, in some cases, can improve sight. […] The anti-VEGF medications slow down the disease but do not cure the wet AMD. Therefore, these treatments are typically ongoing.

• #75 Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration | Journal of Translational Medicine | Full Text

  https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03937-7

  Targeting the VEGF/R system has undoubtedly prevented blindness in millions of nAMD patients and improved quality of life and workforce productivity. However, given the shortcomings of current anti-VEGF therapy, there remains a need to identify other types of agents and modalities exploiting this pathway. Despite the promise of reduced treatment burden in nAMD patients brought about by brolucizumab, the future may lie with multi-target interventions. This is because considerable research suggests that factors beyond VEGF, such as other growth factors, chemokines and cytokines, also mediate the pathogenesis of nAMD. Angiogenesis and inflammation underpinning nAMD involves signalling and transcriptional regulation mediated by extracellular signal-regulated kinase-1/2, p-ERK, monocyte chemoattractant protein-1 (MCP-1/CCL2), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-1 (IL-1) and IL-6. This may account for the inadequacy of strategies solely targeting the VEGF system and points to the therapeutic potential for strategies that also target other mediators of nAMD.

• #76 The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment | Eye

  https://www.nature.com/articles/eye2010196

  Conventional therapy that focuses solely on inhibiting angiogenesis may not be optimal because of the inflammatory involvement in AMD. […] Anti-inflammatory therapy also benefits AMD patients who do not respond to conventional anti-VEGF therapy. […] In summary, the inflammatory process exacerbates AMD pathogenesis. Anti-inflammatory agents, which target specific inflammatory pathways and molecules, could be used as promising adjunct agents combined with anti-VEGF and/or PDT therapy for exudative neovascular AMD and potential therapies for GA AMD.

• #77 The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment | Eye

  https://www.nature.com/articles/eye2010196

  Conventional therapy that focuses solely on inhibiting angiogenesis may not be optimal because of the inflammatory involvement in AMD. […] Anti-inflammatory therapy also benefits AMD patients who do not respond to conventional anti-VEGF therapy. […] In summary, the inflammatory process exacerbates AMD pathogenesis. Anti-inflammatory agents, which target specific inflammatory pathways and molecules, could be used as promising adjunct agents combined with anti-VEGF and/or PDT therapy for exudative neovascular AMD and potential therapies for GA AMD.

• #78 A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration | Nature Communications

  https://www.nature.com/articles/s41467-019-11262-1

  The association of APOE variants with AMD was the first indication that a specific gene affected disease risk. […] Current research has focused on understanding the role of specific genes and related pathways that drive AMD pathobiology. […] The integration of genes carrying risk alleles into the framework of complex endophenotypes suggests that AMD risk genes act in multiple molecular pathways and large networks, associate with different anatomical microenvironments in the macula, and affect diverse higher order physiological activities such as Bruchs membrane homeostasis, protein and lipid turnover, energy metabolism, and complement regulation. […] Future directions in dry AMD research should emphasize systems biology approaches that integrate omic, pharmacological, and clinical data into mathematical models that can predict disease onset and progression, identify biomarkers, establish disease causing mechanisms, and monitor response to therapy.

• #79 Age-Related Macular Degeneration – EyeWiki

  https://eyewiki.org/Age-Related_Macular_Degeneration

  The degenerating retina succumbs to the final end point of geographic atrophy, choroidal neovascularization and pigment epithelial detachment. […] Treatments targeting intermediate disease mechanisms or initiating disease factors are in the minority, but may offer a more successful approach to vision preservation than those targeting relatively later steps in AMD pathophysiology (i.e., choroidal neovascularization). […] Complement factor H (CFH) is an important gene in the pathogenesis of AMD. […] Biochemical pathways and genetic association studies have shed light on the possible biochemical pathways that go awry in AMD. […] Activation of the complement system results in cellular damage that is central in the pathogenesis of dry and wet forms of AMD, and this is supported by the presence of many complement system proteins within drusen in patients with AMD.

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