Elsevier

Ophthalmology

Volume 115, Issue 1, January 2008, Pages 116-126.e1
Ophthalmology

The Natural History and Prognosis of Neovascular Age-Related Macular Degeneration: A Systematic Review of the Literature and Meta-analysis

https://doi.org/10.1016/j.ophtha.2007.03.008Get rights and content

Purpose

To describe the natural history and progression of visual loss in eyes with untreated neovascular age-related macular degeneration (AMD).

Design

Systematic review and meta-analysis.

Participants

Four thousand three hundred sixty-two untreated neovascular AMD patients from published interventional studies.

Methods

A systematic review of the literature from 1980 to August 2005 was performed. Studies reporting disease progression outcomes for untreated patients with neovascular AMD were included. Outcome measures were summarized using simple counts and means. Random effects meta-analyses were conducted and tests of heterogeneity were performed where appropriate.

Main Outcome Measures

Changes in visual acuity (VA) loss, development of comorbidities, and fellow eye involvement.

Results

Fifty-three primary studies were included. Nearly half of the studies (28) were randomized clinical trials. The quality of the studies was high, with over 80% providing level I or II evidence. Mean baseline VA among study patients was 0.64 logarithm of the minimum angle of resolution (logMAR) (∼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. Neovascular AMD developed in the fellow eye in 12.2% of patients by 12 months and in 26.8% by 4 years. Meta-analyses of vision outcome by subtype of neovascular AMD were not possible.

Conclusions

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. No conclusions can be drawn as to the differences in rates of disease progression by neovascular AMD subtype. The diversity of reporting formats, paucity of long-term natural history data, and heterogeneity among the reported clinical studies impose limits to the clear understanding of long-term prognosis for visual function in neovascular AMD.

Section snippets

Search Strategy to Identify Relevant Studies

We conducted a comprehensive review of all studies published in the English literature involving untreated patients with neovascular AMD, including control arms of clinical trials for treatment-naive patients with neovascular AMD. We performed an electronic search in Medline, Current Contents, and the Cochrane Library for interventional or observational studies published from 1980 through August 15, 2005. Search terms used were macular degeneration (Medical Subject Heading) or maculopathy and

Study Characteristics

Of the 53 eligible studies, 28 were RCTs, an additional 12 were prospective, and 13 were retrospective. In all, 43 of the studies provided level I or II evidence and the remaining studies provided level III or IV evidence. Of the 28 RCTs, 14 had a Jadad quality score of 4 or 5 and 14 had a score of 1 to 3. The majority of the studies were from North America (23) or Europe (24), with 6 from other regions of the world.

Patient Characteristics

From the selected studies, there were 4362 treatment-naive neovascular AMD

Study Utility/Summary of Analyses

To the best of our knowledge, this is the first systematic literature review of the untreated natural history of changes in VA in eyes with neovascular AMD. Our findings confirm a rapid progression to severe central vision loss after the onset and diagnosis of neovascular AMD. Distance VA was the most frequently used marker of disease progression, and there was relatively scarce information and inconsistent reporting on the choroidal neovascularization subtype, development of comorbidities, and

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    Funding provided by Pfizer Inc.

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