Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials

Ophthalmology. 2020 Jun;127(6):769-783. doi: 10.1016/j.ophtha.2019.12.009. Epub 2019 Dec 14.


Purpose: To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD).

Design: Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials.

Participants: Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n = 32).

Methods: Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics.

Main outcome measures: Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA).

Results: At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were -13.88 (1.40) and -7.64 (1.20) in Proxima A, -9.49 (1.29) and -7.57 (1.26) in Proxima B fellow eye CNV cohort, and -11.48 (3.39) and -8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively.

Conclusions: The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Choroidal Neovascularization / complications
  • Choroidal Neovascularization / diagnosis*
  • Choroidal Neovascularization / drug therapy
  • Choroidal Neovascularization / physiopathology
  • Disease Progression
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Geographic Atrophy / diagnosis*
  • Geographic Atrophy / drug therapy
  • Geographic Atrophy / etiology
  • Geographic Atrophy / physiopathology
  • Humans
  • Immunoglobulin Fab Fragments / therapeutic use
  • Macular Degeneration / complications
  • Macular Degeneration / diagnosis*
  • Macular Degeneration / drug therapy
  • Macular Degeneration / physiopathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Vision Disorders / physiopathology
  • Visual Acuity / physiology


  • Immunoglobulin Fab Fragments
  • lampalizumab