Evicenter
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4D-150

Neovascular age-related macular degeneration

Regulatory submission
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Last updated
180 sources

Product information and disease descriptionPlace of product in therapyDisease description

Natural history, survival, and mortality

12 evidence topics · 9 sources

Natural history: visual acuity loss in untreated eyes

“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)

Natural history: macular atrophy after untreated neovascular AMD

“The cumulative risks of incident macular atrophy after untreated NV were 9.6% (standard error 1.2%), 31.4% (2.2%), 43.1% (2.6%), and 61.5% (4.3%) at two, five, seven, and 10 years, respectively. This corresponded to a linear risk of 6.5%/year.” (opens the source at this quote in a new tab)

Global blindness attributable to AMD

“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 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 at diagnosis in United States clinical practice

“The study included 162,902 eyes. Among all included eyes, 34.3% presented with 20/40 VA or better at diagnosis. Patients with 20/40 vision or better at baseline maintained a mean VA of 20/40 or better for 2 years after treatment initiation.” (opens the source at this quote in a new tab)

Mortality: late AMD and all-cause and cardiovascular mortality

“Late AMD was associated with elevated rates of all-cause (nine studies, hazard ratio (HR) 1.20, 95% confidence interval, CI, 1.02-1.41) and cardiovascular mortality (six studies, HR 1.46, 95% CI 1.13-1.98), but early AMD was not (all-cause mortality, 10 studies, HR 1.06, 95% CI 0.98-1.14; cardiovascular mortality, five studies, HR 1.12, 95% CI 0.96-1.31).” (opens the source at this quote in a new tab)

“The risk of all-cause mortality and cardiovascular mortality associated with early AMD were 1.08 (1.00-1.18) and 1.05 (0.89-1.24), and the associations with late AMD were 1.23 (1.11-1.36) and 1.28 (1.04-1.57), respectively.” (opens the source at this quote in a new tab)

Proportion of untreated eyes with stable and with worsening acuity

“Several studies reported the proportion of patients categorized as stable (defined as improved or unchanging acuity).” (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” (opens the source at this quote in a new tab)

Progression to legal blindness within three months of presentation

“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)

Lesion location and visual prognosis by angiographic subtype in untreated eyes

“In the 41 treatment arms reporting the location of choroidal neovascularization relative to the fovea, most patients had subfoveal disease (81.4%).” (opens the source at this quote in a new tab)

“Based on these studies, at 12 months 33.2% (95% CI, 19.3%–48.7%) of patients with occult choroidal neovascularization had lost between 3 and 6 lines of VA, compared with 43.7% (95% CI, 28.0%–60.1%) of patients with classic choroidal neovascularization.” (opens the source at this quote in a new tab)

“This difference was not significant, as reflected by the overlapping CIs.” (opens the source at this quote in a new tab)

Generalizability of the untreated natural history estimates

“The lack of data on ethnicity and the fact that the vast majority of studies are North American and European limit the generalizability of the data to Western Caucasian populations.” (opens the source at this quote in a new tab)

Mean visual acuity at diagnosis in first and second eyes

“The mean VA at diagnosis was 0.62 ± 0.52 (mean ± standard deviation) logMAR (20/83) for all eyes, 0.63 ± 0.53 (20/85) for first eyes, and 0.60 ± 0.50 (20/79), for second eyes” (opens the source at this quote in a new tab)

Mortality over three and a half years in a treated trial cohort

“Among the 1117 patients alive at the end of the clinical trial (end of Year 2), 203 (18.2%) died before the end of the Follow-up Study.” (opens the source at this quote in a new tab)