New Therapies Needed to Address Key Contributors to AMD Vision Loss

Glenn Jaffe, MD

Utilizing data and images gathered in the Comparison of Age-related Macular Degeneration (AMD) and Treatments Trials (CATT), investigators have determined that certain morphological features of AMD are associated with greater risk of declining visual acuity (VA) patients over time.

Presence, incidence, and worsening of these pathological features, according Glenn J. Jaffee, MD, with the Department of Ophthalmology at Duke University, and fellow researchers from the University of Pennsylvania and Cole Eye Institute at the Cleveland Clinic, are directly associated with greater loss of VA in patients receiving treatment with anti-vascular endothelial growth factor (anti-VEGF) agents, and suggest that there is "a significant need to develop therapies to address these adverse pathological features."

Using data and imaging collected from 523 CATT follow-up study participants—from the two-year study which focused on the results of treatment of AMD-related choroidal neovascularization (CNV) with intraviteral anti-VEGF agents bevacizumab and ranibizumab— Jaffee and colleagues assessed the associations between macular morphology and VA and explored the retinal anatomic factors that contributed to year 5 VA. They reported that specific adverse morphological characteristics had greater association with reduced VA, including "area of CNV lesion, area of GA [geographic atrophy], new foveal GA, new foveal scar, new foveal CNV, new SHRM [subretinal hyper-reflective material] within the center 1mm, new foveal intraretinal fluid [IRF]" and new retinal thinning."

Eyes with more macular fluid saw slightly greater mean reduction in GA (VA = 63 letters) compared to those without macular fluid (VA = 59), but that the mean VA differed "depending on the specific type of fluid." Investigators noted that, relative to the mean VA in eyes with no IRF (68 letters), mean VA was worse for eyes with extrafoveal IRF (VA = 5) and worse for those with foveal IRF (VA= 44). Data also revealed trends towards better VA in eyes with no SHRM (VA= 72, p<0.001) in comparison to eyes without foveal SHRM or with extrafoveal SHRM (VA= 41; 63, respectively), and better VA in eyes without outer retinal tubulations (ORTs) (VA= 63) in comparison to eyes with ORTs (VA= 52, All P < .001).

Thickness of certain morphological features recorded by optical coherence tomography (OCT) also revealed associations with better or worse VA over time. Jaffee wrote that at year 5, eyes with total thickness >550 μm had “markedly worse mean VA (46 letters) than the 192 eyes with < 550 μm (mean 61-65 letters) (all P < .05).”

Other morphological features which were associated with worsening VA were neovascular lesions of greater than 20 mm² (mean VA = 49), presence of GA or scarring (fibrotic and non fibrotic) in the foveal center (mean VA = 46).

Study eyes with 2 or more of the features Jaffee and colleagues labeled "adverse morphological features" saw a greater mean decrease in VA than those eyes with only one or none of these features.

“The mean VA declined more between year 2 to year 5 when there were abnormal features, but the average VA at each time point was worse from year 1 to year 5, as the number of adverse features increased," Jaffee wrote. Even with anti-VEGF treatment, the data showed that VA tended to worsen below baseline by year 5, dependent on associated adverse pathological features.

Jaffee and colleagues believed their findings reveal a significant unmet need to develop treatments that limit or protect against scar formation, GA development, retinal thinning, fluid increase, and lesions, as an accompaniment to anti-VEGF treatments.

Understanding how these morphological features are connected to AMD disease progression and changes in VA even in patients treated with anti-VEGF agents, could lead to the development of alternative or complementary AMD treatment and save patient sight.

The study, "Macular Morphology and Visual Acuity in Year Five of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT)” was published online in Ophthalmology.