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AXPAXLI (axitinib intravitreal implant)

Neovascular age-related macular degeneration

Also known as OTX-TKI
Manufacturer
Ocular Therapeutix
Last updated
309 sources

Product information and disease descriptionPlace of product in therapyDisease description

Definition and etiology

18 evidence topics · 11 sources

AMD definition: AAO Preferred Practice Pattern

“Age-related macular degeneration (AMD) is a spectrum of disorders of the macula characterized by one or more of the following:” (opens the source at this quote in a new tab)

“Presence of at least medium-size drusen (≥ 63 μm in diameter)” (opens the source at this quote in a new tab)

“Retinal pigment epithelium (RPE) abnormalities such as hypopigmentation or hyperpigmentation” (opens the source at this quote in a new tab)

“Patients are typically aged 50 years or older, with or without visual symptoms.” (opens the source at this quote in a new tab)

AMD definition: CONAN consensus nomenclature

“A condition in patients, typically beyond 50 years of age, in which the structure and function of the macula deteriorates. A salient characteristic is the accumulation of extracellular deposits including subretinal drusenoid deposits, basal linear, and basal laminar deposit. These eyes may demonstrate neovascularization or atrophy.” (opens the source at this quote in a new tab)

“In AMD, the neovascularization may start in the outer retina, and therefore, the term choroidal neovascularization is not appropriate for the class.” (opens the source at this quote in a new tab)

Clinical classification: Beckman Initiative for Macular Research

“Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD.” (opens the source at this quote in a new tab)

“Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a 50% risk for the highest intermediate AMD risk group.” (opens the source at this quote in a new tab)

Clinical classification: AREDS categories used by the AAO Preferred Practice Pattern

“Early AMD (AREDS category 2) is characterized by a combination of multiple small drusen, few intermediate drusen (> 63–124 μm in diameter), or mild RPE abnormalities.” (opens the source at this quote in a new tab)

“Advanced AMD (AREDS category 4) is characterized by one or more of the following (in the absence of other causes) in one eye:” (opens the source at this quote in a new tab)

“Macular neovascularization (MNV) historically referred to as CNV and includes the following:” (opens the source at this quote in a new tab)

Late-stage classification: geographic atrophy and exudative neovascular AMD

“In the late stages of AMD, 2 distinct manifestations emerge. One is the development of confluent areas of atrophy involving photoreceptors and retinal pigment epithelium, known as geographic atrophy. The other is the growth of abnormal blood vessels in the macular region, referred to as neovascular AMD.” (opens the source at this quote in a new tab)

“Neovascular AMD causes visual change when these new blood vessels leak, which may cause subretinal and intraretinal fluid accumulation, hemorrhages, and fibrosis. This condition is known as exudative neovascular AMD.” (opens the source at this quote in a new tab)

Macular neovascularization subtypes: CONAN definitions
TermQuoted definition
Type 1 MNV“Ingrowth of vessels initially from the choriocapillaris into and within the sub-RPE space. Leads to varying types of PEDs.”
Polypoidal choroidal vasculopathy“A variant of type 1 MNV commonly seen in Asian persons. Indocyanine green angiography imaging shows a branching vascular network and aneurysmal dilations of varying number at the outer edge of the expanding lesion.”
Type 2 MNV“Neovascularization that originates from the choroid that traverses Bruch’s membrane and the RPE monolayer and then proliferates in the subretinal space.”
Type 3 MNV“Neovascularization that originates from the retinal circulation, typically the deep capillary plexus, and grows toward the outer retina.”
Macular neovascularization subtypes: AAO Preferred Practice Pattern

“Type 1 MNV: a neovascular complex located in the sub-RPE space originating from the choroid through a defect in Bruch’s membrane” (opens the source at this quote in a new tab)

“Polypoidal choroidal vasculopathy (PCV) lesions, similar to Type 1 MNV, characterized by branching vascular networks with dilated vascular elements (historically referred to as polyps)” (opens the source at this quote in a new tab)

“Type 2 MNV: a neovascular complex located in the subretinal space above the RPE originating from the choroid” (opens the source at this quote in a new tab)

“Type 3 MNV: pathologic angiogenesis originating from the deep retinal capillary plexus and extending to the outer retina (historically referred to as retinal angiomatous proliferation)” (opens the source at this quote in a new tab)

Polypoidal choroidal vasculopathy: frequency by population and presentation

“Although a minority subtype in white populations, it accounts for approximately half of MNV seen in Asia.” (opens the source at this quote in a new tab)

“In Asian persons, the typical presentation comprises isolated macular involvement, unilateral, and male preponderance, whereas in white persons, bilateral involvement, female preponderance, and the neovascular lesion originating from the peripapillary region are more common.” (opens the source at this quote in a new tab)

Type 3 neovascularization: origin and terminology

“The neovascularization in RAP may originate not only from deep retinal capillaries but also from the choroid. We therefore propose the more descriptive term "Type 3 neovascularization" for this entity to emphasize the intraretinal location of the vascular complex and distinguish this type from the two types of neovascularization previously described by J. Donald Gass in his classic text.” (opens the source at this quote in a new tab)

Distribution of neovascular subtypes at diagnosis: US single-physician cohort

“A total of 232 patients (266 eyes) fit the inclusion criteria. Mean age was 86.3 years; 67.7% of eyes (180/266) were from female patients, and 95.5% (254/266) were from white patients.” (opens the source at this quote in a new tab)

“With FA+OCT, 39.9% (106/266), 9.0% (24/266), 34.2% (91/266), and 16.9% (45/266) were type 1 (sub-retinal pigment epithelium), type 2 (subretinal), type 3 (intraretinal), and mixed neovascularization (NV), respectively.” (opens the source at this quote in a new tab)

Etiology: multifactorial disease

“AMD is a multifactorial disease related to aging, genetic susceptibility, and environmental risk factors such as cigarette smoking; it develops as a consequence of disruption of the normal homeostatic mechanisms of the retina.” (opens the source at this quote in a new tab)

“Age-related macular degeneration is a multifactorial disorder, with dysregulation in the complement, lipid, angiogenic, inflammatory, and extracellular matrix pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci have been identified, of which the most important are in the CFH and ARMS2 genes. The major non-genetic risk factors are smoking and low dietary intake of antioxidants (zinc and carotenoids).” (opens the source at this quote in a new tab)

Risk factors: AAO Preferred Practice Pattern summary

“Risk factors for the development of advanced AMD include smoking, increasing age, northern European ancestry, and genetic factors. Cigarette smoking has been identified as the primary modifiable risk factor in numerous studies on advanced AMD. It is strongly recommended to advise patients with AMD or those at risk for AMD to stop smoking. Routine genetic testing is not currently recommended.” (opens the source at this quote in a new tab)

Risk factors: age

“A meta-analysis of AMD incidence in 10 populations of White individuals from Europe, Australia, and the United States with approximately 135 000 person-years of follow-up reported that late-stage AMD was associated with an incidence of 0.3 per 1000 in those aged 55to 59 years, 5.7 per 1000 in those aged 75 to 79 years, and 36.7 per 1000 in those aged 90 years or older.” (opens the source at this quote in a new tab)

Risk factors: cigarette smoking

“Cigarette smoking is an independent risk factor for AMD” (opens the source at this quote in a new tab)

“increasing the risk of AMD by twofold to fourfold” (opens the source at this quote in a new tab)

“Smoking cessation reduces the risk of AMD, and after 20 years of cessation, the risk of AMD is similar to that in non-smokers” (opens the source at this quote in a new tab)

“In a large prospective cohort study of 61 862 women over a 12-year follow-up period, 1 case of AMD developed per 1708 person-years among women who currently smoked 25 or more cigarettes per day compared with 1 case per 3740 person-years among those who had never smoked.” (opens the source at this quote in a new tab)

Risk factors: meta-analysis of clinical risk factors for late AMD

“A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors.” (opens the source at this quote in a new tab)

“Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen.” (opens the source at this quote in a new tab)

Risk factors: heritability and major genetic loci (CFH and ARMS2-HTRA1)

“Estimated heritability of late-stage AMD is approximately 71% (estimate for additive risk, 0.71 [95% CI, 0.18-0.88] in 840 participants from a US twin study of AMD” (opens the source at this quote in a new tab)

“indicating that approximately 71% of the risk of AMD is genetic.” (opens the source at this quote in a new tab)

“Patients who are homozygous for the Y402H risk allele of CFH possess a 7.4-fold increased risk of AMD.” (opens the source at this quote in a new tab)

“Strong linkage disequilibrium has been shown across the ARMS2-HTRA1 region, and these two genes are also strongly associated with AMD.” (opens the source at this quote in a new tab)

Risk factors: genome-wide association study and a genetic signal specific to neovascular AMD

“Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants” (opens the source at this quote in a new tab)

“While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9” (opens the source at this quote in a new tab)

Risk factors: race and ancestry

“Findings from the Multi-ethnic Study of Atherosclerosis also suggest that neovascular AMD may be more common in Caucasian individuals than in African American individuals.” (opens the source at this quote in a new tab)