Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye. Choroidal neovascularization is a common cause of neovascular degenerative maculopathy (i.e. 'wet' macular degeneration) [1] commonly exacerbated by extreme myopia, malignant myopic degeneration, or age-related developments.
CNV can occur rapidly in individuals with defects in Bruch's membrane, the innermost layer of the choroid. It is also associated with excessive amounts of vascular endothelial growth factor (VEGF). As well as in wet macular degeneration, CNV can also occur frequently with the rare genetic disease pseudoxanthoma elasticum and rarely with the more common optic disc drusen. CNV has also been associated with extreme myopia or malignant myopic degeneration, where in choroidal neovascularization occurs primarily in the presence of cracks within the retinal (specifically) macular tissue known as lacquer cracks.
CNV can create a sudden deterioration of central vision, noticeable within a few weeks. Other symptoms which can occur include color disturbances, and metamorphopsia (distortions in which straight lines appear wavy). Hemorrhaging of the new blood vessels can accelerate the onset of symptoms of CNV. CNV may also include the feeling of pressure behind your eye.
Using modern optical coherence tomography devices, it is possible to detect non-exudative neovascular membranes, that are typically asymptomatic. [2] [3] [4]
CNV can be detected by using a type of perimetry called preferential hyperacuity perimetry. [5] On the basis of fluorescein angiography, CNV may be described as classic or occult. Two other tests that help identify the condition include indocyanine green angiography and optical coherence tomography. [6]
CNV is conventionally treated with intravitreal injections of angiogenesis inhibitors (also known as "anti-VEGF" drugs) to control neovascularization and reduce the area of fluid below the retinal pigment epithelium. Angiogenesis inhibitors include pegaptanib, ranibizumab and bevacizumab (known by a variety of trade names, such as Macugen, Avastin or Lucentis). These inhibitors slow or stop the formation of new blood vessels (angiogenesis), typically by binding to or deactivating the transmission of vascular endothelial growth factor ('VEGF'), a signal protein produced by cells to stimulate formation of new blood vessels. The effectiveness of angiogenesis inhibitors has been shown to significantly improve visual prognosis with CNV, the recurrence rate for these neovascular areas remains high. [7]
CNV may also be treated with photodynamic therapy (PDT) coupled with a photosensitive drug such as verteporfin (Visudyne). The drug is given intravenously. It is then activated in the eye by a laser light. The drug destroys the new blood vessels, and prevents any new vessels forming by forming thrombi. [8] A Cochrane Review published in 2016 found that people with severe myopia (short-sightedness or near-sightedness) may benefit from being given anti-VEGF treatment. [9]
Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur but these do not represent a mental illness.
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.
Neovascularization is the natural formation of new blood vessels, usually in the form of functional microvascular networks, capable of perfusion by red blood cells, that form to serve as collateral circulation in response to local poor perfusion or ischemia.
Intravitreal is a route of administration of a drug, or other substance, in which the substance is delivered into the vitreous humor of the eye. "Intravitreal" literally means "inside an eye". Intravitreal injections were first introduced in 1911 when Ohm gave an injection of air into the vitreous humor to repair a detached retina. In the mid-1940s, intravitreal injections became a standard way to administer drugs to treat endophthalmitis and cytomegalovirus retinitis.
Rubeosis iridis is a medical condition of the iris of the eye in which new abnormal blood vessels are found on the surface of the iris.
Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related macular degeneration, diabetic retinopathy, and macular edema due to branch retinal vein occlusion or central retinal vein occlusion.
Presumed ocular histoplasmosis syndrome (POHS) is a syndrome affecting the eye, which is characterized by peripheral atrophic chorioretinal scars, atrophy or scarring adjacent to the optic disc and maculopathy.
Pegaptanib sodium injection is an anti-angiogenic medicine for the treatment of neovascular (wet) age-related macular degeneration (AMD). It was discovered by NeXstar Pharmaceuticals and licensed in 2000 to EyeTech Pharmaceuticals, now OSI Pharmaceuticals, for late stage development and marketing in the United States. Gilead Sciences continues to receive royalties from the drugs licensing. Outside the US pegaptanib is marketed by Pfizer. Approval was granted by the U.S. Food and Drug Administration (FDA) in December 2004.
Corneal neovascularization (CNV) is the in-growth of new blood vessels from the pericorneal plexus into avascular corneal tissue as a result of oxygen deprivation. Maintaining avascularity of the corneal stroma is an important aspect of corneal pathophysiology as it is required for corneal transparency and optimal vision. A decrease in corneal transparency causes visual acuity deterioration. Corneal tissue is avascular in nature and the presence of vascularization, which can be deep or superficial, is always pathologically related.
Aflibercept, sold under the brand names Eylea and Zaltrap, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals and is approved in the United States and the European Union.
Branch retinal vein occlusion is a common retinal vascular disease of the elderly. It is caused by the occlusion of one of the branches of central retinal vein.
Punctate inner choroiditis (PIC) is an inflammatory choroiditis which occurs mainly in young women. Symptoms include blurred vision and scotomata. Yellow lesions are mainly present in the posterior pole and are between 100 and 300 micrometres in size. PIC is one of the so-called White Dot Syndromes. PIC has only been recognised as a distinct condition as recently as 1984 when Watzke identified 10 patients who appeared to make up a distinct group within the White Dot Syndromes.
Joan Whitten Miller is a Canadian-American ophthalmologist and scientist who has made notable contributions to the treatment and understanding of eye disorders. She is credited for developing photodynamic therapy (PDT) with verteporfin (Visudyne), the first pharmacologic therapy for retinal disease. She also co-discovered the role of vascular endothelial growth factor (VEGF) in eye disease and demonstrated the therapeutic potential of VEGF inhibitors, forming the scientific basis of anti-VEGF therapy for age-related macular degeneration (AMD), diabetic retinopathy, and related conditions.
Anti–vascular endothelial growth factor therapy, also known as anti-VEGF therapy or medication, is the use of medications that block vascular endothelial growth factor. This is done in the treatment of certain cancers and in age-related macular degeneration. They can involve monoclonal antibodies such as bevacizumab, antibody derivatives such as ranibizumab (Lucentis), or orally-available small molecules that inhibit the tyrosine kinases stimulated by VEGF: sunitinib, sorafenib, axitinib, and pazopanib.
Geographic atrophy (GA), also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retinal tissue which can lead to a loss of visual function over time. It is estimated that GA affects >5 million people worldwide and approximately 1 million patients in the US, which is similar to the prevalence of neovascular (wet) AMD, the other advanced form of the disease.
Faricimab, sold under the brand name Vabysmo, is a monoclonal antibody used for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Faricimab is the first bispecific monoclonal antibody, to target both vascular endothelial growth factor (VEGF), and angiopoietin 2 (Ang-2) inhibitor. By targeting these pathways, faricimab stabilizes blood vessels in the retina. It is given by intravitreal injection by an ophthalmologist.
Indocyanine green angiography (ICGA) is a diagnostic procedure used to examine choroidal blood flow and associated pathology. Indocyanine green (ICG) is a water soluble cyanine dye which shows fluorescence in near-infrared range, with peak spectral absorption of 800-810 nm in blood. The near infrared light used in ICGA penetrates ocular pigments such as melanin and xanthophyll, as well as exudates and thin layers of sub-retinal vessels. Age-related macular degeneration is the third main cause of blindness worldwide, and it is the leading cause of blindness in industrialized countries. Indocyanine green angiography is widely used to study choroidal neovascularization in patients with exudative age-related macular degeneration. In nonexudative AMD, ICGA is used in classification of drusen and associated subretinal deposits.
Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.
Conbercept, sold under the commercial name Lumitin, is a novel vascular endothelial growth factor (VEGF) inhibitor used to treat neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). The anti-VEGF was approved for the treatment of neovascular AMD by the China State FDA (CFDA) in December 2013. As of December 2020, conbercept is undergoing phase III clinical trials through the U.S. Food and Drug Administration’s PANDA-1 and PANDA-2 development programs.
Polypoidal choroidal vasculopathy (PCV) is an eye disease primarily affecting the choroid. It may cause sudden blurring of vision or a scotoma in the central field of vision. Since Indocyanine green angiography gives better imaging of choroidal structures, it is more preferred in diagnosing PCV. Treatment options of PCV include careful observation, photodynamic therapy, thermal laser, intravitreal injection of anti-VEGF therapy, or combination therapy.