Angiogenesis 2023: Uncovering the mystery surrounding geographic atrophy

Exploratory data analysis from the trial of lampalizumab (Genentech/Roche) has shed new light on the behavior of geographic atrophy (GA), the advanced form of age-related macular degeneration (AMD)

In a presentation at Bascom Palmer’s 2023 Angiogenesis, Exudation, and Degeneration conference in Miami, Usha Chakravarthy, PhD, FRCOphth, CBE, presented details unraveling some of the mystery surrounding geographic atrophy.

Exploratory data analysis from the trial of lampalizumab (Genentech/Roche) has shed new light on the behavior of geographic atrophy (GA), the advanced form of age-related macular degeneration (AMD), according to Chakravarthy, a professor of Ophthalmology and Vision Sciences at Queen’s University Belfast, and ophthalmology consultant, Belfast Health and Social Care Trust; both in Belfast, UK.

The take-home messages from the exploratory analysis are:

• The commonly used clinical measure of visual function, the best-corrected visual acuity (BCVA), has defined relationships with the GA rate of growth.
  
  
• GA lesion location and focality affect the trajectory of the decrease in the BCVA.
  
  
• Understanding the factors that affect the functional loss is critical when conducting, and selecting endpoints for large pragmatic clinical intervention trials to prevent or reduce the progression of GA.
  
  

Chakravarthy explained that seemingly contradictory results have been found previously regarding GA, in that, interventional trials have reported reduced GA growth but without corresponding reduction in the fall effect in BCVA.

GA is highly pleomorphic, and its expansion rate varies and is affected by morphologic factors

Chakravarthy and her colleagues set out to explore the lampalizumab data to determine how baseline clinical factors and GA expansion rates affect the rate of loss of the BCVA.

The clinical trials included patients who were at least 50 years old, with a BCVA of 49 letters or better, and well-demarcated areas of GA secondary to AMD with no active/previous choroidal neovascularization (CNV).

The lesion sizes of the GA in the study eyes were between 2.54 mm2 (1 disc area) and 17.78 mm2 or smaller (7 disc areas). The study eyes also had banded or diffused autofluorescence patterns next to the GA area and sufficiently clear ocular media. The fellow eyes also had GA secondary to AMD with no active or previous CNV, she explained.

The primary observations of the analysis were as follows:

• Over the course of 96 weeks, the size of the GA lesions at baseline was not correlated with the changes in the BCVA.
  
  
• The rate of BCVA loss over the 2 years of FU was similar for all sizes of GA lesions at baseline.
  
  
• Subclassification of the GA lesions by focality and location suggested that unifocal lesions were associated with faster loss of BCVA, while subfoveal and non subfoveal location had similar rates of BCVA loss.
  
  
• The growth rate of the GA lesions was weakly correlated with changes in the BCVA.
  
  
• Change in BCVA classified by growth quartiles of GA showed that the higher growth rate quartiles had steeper decreases in the BCVA.
  
  
• Subclassification based on GA lesion location and focality suggested faster BCVA loss for unifocal/subfoveal lesions in higher growth rate quartiles.
  
  

Chakravarthy concluded that the baseline GA lesion area does not impact the rate of BCVA loss whereas GA lesion growth rate does. The lesion location and focality have specific effects on the rate of BCVA loss.

Finally, contrary to popular clinical opinion, subfoveal lesions remain at very high risk of vision loss over time, especially when lesions are unifocal.