Progression of Non-geographic Atrophy Common in NAMD

By Reuters Staff

March 30, 2020

NEW YORK (Reuters Health) - Most eyes with neovascular age-related macular degeneration (nAMD) will develop non-geographic atrophy (NGA) after two years of treatment with anti-vascular endothelial growth factor (anti-VEGF), according to new findings.

And about half of eyes that develop NGA progress to geographic atrophy (GA) within four years, Dr. Ebenezer Daniel of the University of Pennsylvania in Philadelphia and colleagues report in JAMA Ophthalmology.

NGA, or hypopigmentation and hyperpigmentation of the retina on color images, is a risk factor for drusen-associated or nascent GA, Dr. Daniel and his team write. NGA, GA and both fibrotic and nonfibrotic scars occur in eyes with nAMD treated with anti-VEGF, they add, but it is not clear whether NGA developing inside or overlapping the original choroidal neovascularization (CNV) lesion will progress to GA and whether it adversely affects VA.

To investigate, the authors performed a secondary analysis of the incidence and progression of NGA in the Comparison of Age-Related Treatments Trials (CATT) study, which included 1,107 patients who were randomly assigned to ranibizumab or bevacizumab for either two years of monthly or as-needed injections or monthly injections for a year with as-needed injections the following year.

The prevalence of NGA was 35% at one year, 59% at two years and 81% at five years, the authors found. NGA risk factors included worse VA (20/200-20/320, adjusted risk ratio, 1.74 .compared to 20/40 or better), larger area of neovascularization (more than four disc areas vs. one disc area or less, aRR, 1.31) and switched drug regimen versus as-needed injections (aRR, 1.28).

Having a thicker sub-retinal pigment epithelium was associated with a reduced risk of NGA (more than 275 um vs. 75 um or less, aRR, 0.59).

Risk of progression from NGA to GA was 29% at one year, 43% at three years and 50% at four years. Worse visual acuity in the treated eye (aRR, 2.75), the fellow eye (aRR, 1.77) and pseudodrusen (aRR, 1.65, either eye) were some of the factors significantly associated with an increased risk of progression. Eyes with subretinal fluid were at significantly lower risk of progression (aRR, 0.42).

"Poor VA at baseline was a risk factor for developing NGA and was previously reported as a risk factor for GA; thus, factors responsible for initially poor VA may contribute to the development of both NGA and GA," Dr. Daniel and colleagues note.

"While large sub-RPE thicknesses (>275 um) are associated with an increased risk of scars, they appear to substantially reduce the risk of developing NGA," they add. "These risk factors provide the ophthalmologist with some prognostic knowledge of the likely morphological outcomes."

Dr. Daniel was not available for an interview by press time.

SOURCE: JAMA Ophthalmology, online March 19, 2020.