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

Natural history, survival, and mortality

9 evidence topics · 5 sources

Summary: natural history and mortality

In a meta-analysis of 53 studies including 4,362 participants with untreated neovascular AMD, mean visual acuity loss was 1 line at 3 months, 2.7 lines at 12 months, and 4 lines at 24 months; severe vision loss (more than 6 lines) occurred in 21.3% at 6 months and 41.9% by 3 years, and the proportion with visual acuity worse than 20/200 rose from 19.7% at baseline to 75.7% by 3 years. In the sham arm of the MARINA trial, 62.2% of participants lost fewer than 15 letters at 12 months and mean visual acuity decreased by 10.4 letters. The AAO attributes nearly 90% of AMD-related severe visual acuity loss (20/200 or worse) to the neovascular form. The AAO cites Salisbury Eye Study data linking visual acuity loss to activities of daily living and mortality risk, and a US cost-utility model estimated that 11 years of anti-VEGF therapy averts a 1.0 year-of-life loss.

Untreated neovascular AMD: systematic review and meta-analysis

“Four thousand three hundred sixty-two untreated neovascular AMD patients from published interventional studies.” (opens the source at this quote in a new tab)
“Mean baseline VA among study patients was 0.64 logarithm of the minimum angle of resolution (logMAR) (approximately 20/87 Snellen). The mean VA change in logMAR progressed from 0.1 (1 line lost) at 3 months to 0.3 (2.7 lines lost) after 12 months and 0.4 (4 lines lost) after 24 months. The proportion of patients who developed severe vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% by 3 years. The proportion of patients with VA worse than logMAR 1.0 (20/200 Snellen) increased from 19.7% at baseline to 75.7% by 3 years.” (opens the source at this quote in a new tab)
“A doubling of the visual angle of presenting VA may be expected to occur in the year after initial presentation in eyes with untreated neovascular AMD.” (opens the source at this quote in a new tab)

Sham-injection arm of the MARINA trial

“At 12 months, 94.5% of the group given 0.3 mg of ranibizumab and 94.6% of those given 0.5 mg lost fewer than 15 letters, as compared with 62.2% of patients receiving sham injections (P<0.001 for both comparisons).” (opens the source at this quote in a new tab)
“Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons).” (opens the source at this quote in a new tab)

Contribution of neovascular AMD to severe vision loss

“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)
“the neovascular form is responsible for nearly 90% of the severe VA loss (20/200 or worse) from AMD because of its natural history.” (opens the source at this quote in a new tab)
“Severe VA loss occurs more slowly in patients with GA than in patients with neovascular AMD.” (opens the source at this quote in a new tab)

Visual acuity loss, activities of daily living, and mortality

“The Salisbury Eye Study reported that VA loss adversely affected activities of daily living, which subsequently increased mortality risk in older adults. Further calculations estimated that treating AMD with anti-VEGF agents saves 1 to 2 years of life.” (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)

Modeled year-of-life loss without treatment

“Eleven-year therapies saved a 1.0 year-of-life loss without treatment from the 11.0-year life expectancy.” (opens the source at this quote in a new tab)

Long-term course after anti-VEGF treatment: atrophy and fibrosis

“Long-term follow-up studies have identified that the gains made in the first 2 years are not maintained in the long term238. In many instances, this loss can be attributed to under-treatment for a variety of reasons, including inability to access ongoing regular treatment, inappropriate treatment protocols and the burden of treatment for the clinician and patient. Besides patients dropping out of treatment, evidence shows that atrophy and fibrosis are important causes of vision loss despite good early results13.” (opens the source at this quote in a new tab)

Untreated neovascular AMD: proportion in each visual acuity loss stratum over time

“The percentage of patients with severe loss of vision (at least 6 lines of VA loss from the baseline visit) increased from 19.8% (14 studies with 1235 patients) at 6 months to 43.3% (9 studies with 743 patients) by 3 years.” (opens the source at this quote in a new tab)
“Likewise, the proportion losing fewer than 3 lines decreased from 65.0% to 43.6% over the same period (Table 5).” (opens the source at this quote in a new tab)
“The proportion of patients losing between 3 and 6 lines at 3 months was 14.1%. This percentage peaked at 27.0% by 1 year and decreased to 18.2% at the 3-year time point.” (opens the source at this quote in a new tab)

Untreated neovascular AMD: progression to visual acuity worse than 20/200

“In 19.7%, VA was worse than 20/200 (legal blindness) at study inception, and this proportion increased to 50.3% by 3 months and to 77.6% by 3 years” (opens the source at this quote in a new tab)
“For example, at the 3-month time point the lower range of the confidence interval (CI) around the proportion of patients with vision worse than 20/200 was 26.2%.” (opens the source at this quote in a new tab)
“The proportion of patients whose VA worsened (defined generally as any deterioration from baseline) increased from 45.0% at 3 months to 81.1% by 2 years (Fig 3).” (opens the source at this quote in a new tab)