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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

Long-term morbidity

20 evidence topics · 21 sources

Blindness: leading cause among White adults in the United States

“Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness.” (opens the source at this quote in a new tab)

Blindness: share of severe visual loss in the United States

“Overall, AMD is responsible for an estimated 46% of cases of severe visual loss (visual acuity [VA] 20/200 or worse) in people over age 40 in the United States.” (opens the source at this quote in a new tab)

Blindness and moderate to severe vision impairment: global estimates for 2020

“In 2020, 1.85 million (95%UI: 1.35 to 2.43 million) people were estimated to be blind due to AMD, and another 6.23 million (95%UI: 5.04 to 7.58) with MSVI globally. High-income countries had the highest number of individuals with AMD-related blindness (0.60 million people; 0.46 to 0.77).” (opens the source at this quote in a new tab)

“The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7-18·0]), followed by glaucoma (3·6 million cases [2·8-4·4]), undercorrected refractive error (2·3 million cases [1·8-2·8]), age-related macular degeneration (1·8 million cases [1·3-2·4]), and diabetic retinopathy (0·86 million cases [0·59-1·23]).” (opens the source at this quote in a new tab)

Legal blindness: incidence before and after introduction of anti-VEGF therapy

“The incidence rate of legal blindness attributable to AMD in citizens aged ≥50 years decreased from 52.2 cases per year per 100 000 in 2000 to 25.7 cases per year per 100 000 in 2010, corresponding to a reduction of 50% (95% confidence interval [CI(95)]: 45%-56%, P < .0001, adjusted for age), the bulk of the reduction occurring after 2006.” (opens the source at this quote in a new tab)

Visual acuity after 5 years of anti-VEGF therapy: CATT

“VA was obtained for 647 (71%) of 914 living patients with average follow-up time 5.5 years.” (opens the source at this quote in a new tab)

“At the 5-year visit, 50% of study eyes had VA 20/40 or better and 20% had VA 20/200 or worse. Mean change in VA was −3 letters from baseline and −11 letters from 2 years.” (opens the source at this quote in a new tab)

Visual acuity and macular atrophy 7 years after ranibizumab: SEVEN-UP

“At a mean of 7.3 years (range, 6.3-8.5 years) after entry into ANCHOR or MARINA, 37% of study eyes met the primary end point of 20/70 or better BCVA, with 23% achieving a BCVA of 20/40 or better. Thirty-seven percent of study eyes had BCVA of 20/200 or worse.” (opens the source at this quote in a new tab)

“Active exudative disease was detected by spectral-domain OCT in 68% of study eyes, and 46% were receiving ongoing ocular anti-VEGF treatments. Macular atrophy was detected by FAF in 98% of eyes, with a mean area of 9.4 mm(2); the area of atrophy correlated significantly with poor visual outcome (P<0.0001).” (opens the source at this quote in a new tab)

Visual acuity after up to 7 years of treatment: Fight Retinal Blindness! registry

“After 7 years, mean VA was 2.6 letters lower than baseline for the 131 eyes still being followed; 40% had VA ≥70 (20/40) letters, and 18% had VA ≤35 letters (20/200). Of those with 20/40 VA before treatment, 40% had lost it after 7 years.” (opens the source at this quote in a new tab)

“Treatment was discontinued for 663 eyes (53%) within the first 5 years.” (opens the source at this quote in a new tab)

Visual acuity after 10 years of treatment: real-world meta-analysis

“Our search produced 12 observational studies encompassing 7509 eyes, with 1274 completing 10-years of follow-up.” (opens the source at this quote in a new tab)

“On average, there was a decline of 8.11 letters in VA after 10 years from baseline (95% CI -10.83 to -5.39, p < 0.01).” (opens the source at this quote in a new tab)

Geographic atrophy after anti-VEGF therapy: CATT 5-year incidence

“Among the 1011 participants who did not have GA at baseline and had follow-up images gradable for GA, the cumulative incidence was 12% at 1 year, 17% at 2 years, and 38% at 5 years.” (opens the source at this quote in a new tab)

Macular atrophy after anti-VEGF therapy: IVAN trial and long-term follow-up

“Study eye data were available for 594 of 610 participants; 57 (9.6%) showed intralesional MA at baseline. Incident intralesional MA occurred in 24.4% by the final visit and extralesional MA in only 1.54%.” (opens the source at this quote in a new tab)

“Intralesional macular atrophy was present in 31.8% of the study eyes at IVAN exit (mean follow-up, 1.96 years) and 89.5% at the most recent imaging visit (mean follow-up, 6.18 years).” (opens the source at this quote in a new tab)

“Regression models showed that the presence of ILMA and HRM was independently associated with BCVA (22 letters worse [95% confidence interval {CI}, -11.2 to -32.8; P < 0.001] and 9.8 letters worse [95% CI, -0.1 to -19.4; P = 0.047], respectively).” (opens the source at this quote in a new tab)

Fibrotic and nonfibrotic scar: CATT through 2 years

“Scar developed in 480 of 1059 eyes (45.3%) by 2 years.” (opens the source at this quote in a new tab)

“Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes.” (opens the source at this quote in a new tab)

Fibrotic scar and associated atrophy: CATT through 5 years

“Cumulative proportion of eyes with scar was 32%, 46% and 56% at year 1, 2 and 5, respectively.” (opens the source at this quote in a new tab)

“Among 68 eyes that developed fibrotic scar at year 1, visual acuity decreased by a mean of additional 13 letters between year 1 and 5.” (opens the source at this quote in a new tab)

Atrophy and fibrosis as causes of long-term vision loss despite treatment

“Long-term follow-up studies have identified that the gains made in the first 2 years are not maintained in the long term” (opens the source at this quote in a new tab)

“Besides patients dropping out of treatment, evidence shows that atrophy and fibrosis are important causes of vision loss despite good early results” (opens the source at this quote in a new tab)

Falls and fractures: population-based cohort in England

“Compared with comparators, there was an increased risk of falls in those with cataract (adjusted hazard ratio [HR], 1.36; 95% CI, 1.35-1.38), AMD (HR, 1.25; 95% CI, 1.23-1.27), and glaucoma (HR, 1.38; 95% CI, 1.35-1.41). Likewise for fractures, there were increased risks in all eye diseases, with an HR of 1.28 (95% CI, 1.27-1.30) in the cataract cohort, an HR of 1.18 (95% CI, 1.15-1.21) for AMD, and an HR of 1.31 (95% CI, 1.27-1.35) for glaucoma.” (opens the source at this quote in a new tab)

Falls and injuries: prospective diary study in older adults with AMD

“Overall, 74% of participants reported having either a fall or a non-fall-related injury. Fifty-four percent of participants reported a fall and 30% reported more than one fall; of the 102 falls reported, 63% resulted in an injury.” (opens the source at this quote in a new tab)

Hip fracture: Medicare beneficiaries with exudative and atrophic AMD

“In adjusted analyses, the risk of hip fractures was similar in cases that were coded with exudative AMD (odds ratio, 1.03; 95% confidence interval (CI), 0.95, 1.12) compared with cases with no AMD but was significantly higher in cases that were coded with atrophic AMD (odds ratio, 1.11; 95% CI, 1.06, 1.16).” (opens the source at this quote in a new tab)

Depression and anxiety: systematic review

“The prevalence estimates, taken from nine cross-sectional and cohort studies, ranged from 15.7%-44% for depressive symptoms and 9.6%-30.1% for anxiety symptoms in people with AMD. The seven case-control studies found that people with AMD were more likely to experience symptoms of depression compared with those without AMD, but not more likely to experience symptoms of anxiety.” (opens the source at this quote in a new tab)

Depression: recent-onset bilateral AMD

“Seventeen patients (33%) were depressed at baseline and had worse visual acuity (P =.04) and greater levels of vision-specific (P =.03) and general (P =.002) physical disability than nondepressed patients.” (opens the source at this quote in a new tab)

AAO Preferred Practice Pattern: falls, depression, and vision rehabilitation

“Loss of VA increases the risk of frequent falls.” (opens the source at this quote in a new tab)

“Depression and visual hallucinations (Charles Bonnet syndrome) frequently accompany severe central vision loss.” (opens the source at this quote in a new tab)

“Patients can be informed that while central visual loss is common, total visual loss is extremely rare.” (opens the source at this quote in a new tab)

PDGF-driven extracellular matrix deposition and macular scarring in neovascular AMD

“In the CATT trial, macular scarring was the most frequent anatomical correlate of impaired visual acuity, affecting every second patient at year two” (opens the source at this quote in a new tab)

“Scar tissue in nAMD has been shown to consist largely of endothelial cells, dedifferentiated RPE, fibrin, and extracellular matrix (ECM)” (opens the source at this quote in a new tab)

“This notion is also supported by the fact that a longer time interval between diagnosis and start of treatment is associated with more fibrosis, and invasion of the supra-RPE space by classic CNV is associated with a six times higher hazard ratio of developing macular scarring when compared to minimally classic or occult CNV” (opens the source at this quote in a new tab)