Fundus autofluorescence characteristics of nascent geographic atrophy in age-related macular degeneration

Abstract

Purpose: We examined the fundus autofluorescence (FAF) characteristics of nascent geographic atrophy (nGA), pathological features preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) that can be visualized using high-resolution optical coherence tomography (OCT).

Methods: Spectral-domain OCT (SD-OCT) and FAF imaging were performed longitudinally in 221 eyes with intermediate AMD (having at least drusen >125 μm), and seven areas that developed drusen-associated atrophy in five eyes were examined and categorized with respect to FAF characteristics. These categories then were used to characterize 49 areas of nGA or drusen-associated atrophy on SD-OCT identified in a cross-sectional study with 230 participants with bilateral intermediate AMD.

Results: Sequential imaging revealed that FAF characteristics in the atrophic areas could be grouped into three categories: predominantly hyperautofluorescent (hyperAF), presence of both hyper- and hypoautofluorescence (mixed AF), or predominantly hypoautofluorescent (hypoAF). In the cross-sectional study, the FAF characteristics were significantly dependent on the type of atrophic area (P = 0.002), where areas of nGA appeared most commonly as being mixed AF (63%), while areas of drusen-associated atrophy most commonly as hypoAF (86%).

Conclusions: Fundus autofluorescence imaging revealed that areas of nGA were most commonly characterized by both hyper- and hypoautofluorescent changes, which differs from areas of drusen-associated atrophy that most often appeared hypoautofluorescent. These findings provide important insights into the FAF characteristics of areas undergoing atrophic changes in eyes still considered to be in the early stages of AMD by current methods, and thus assist in the characterization of disease severity in these early stages.

Keywords: age-related macular degeneration; drusen; fundus autofluorescence; geographic atrophy; spectral-domain optical coherence tomography.

Figure 1

Characteristics of nGA and drusen-associated atrophy detected on SD-OCT, shown for an area that was examined longitudinally. The presence of nGA is defined as the presence of the subsidence of the INL and OPL, and/or the presence of a hyporeflective wedge-shaped band (outlined by black solid lines) within the limits of the OPL (top row). For subsidence of the INL and OPL (top row), the solid black line outlines the border between the INL and OPL from this scan, while the dashed black line outlines its border at the previous visit. Other features also typically present with nGA include a break in the ELM and disruption of the ISe and RPE bands (top row). Drusen-associated atrophy detected on SD-OCT is characterized by the loss of the RPE and photoreceptor (ISe) bands, resulting in a definite area of increased signal transmission below BM (bottom row).

Figure 2

Fundus autofluorescence characteristics in atrophic areas (nGA or drusen-associated atrophy detected on SD-OCT) were classified into three different categories: areas that were predominantly hyperautofluorescent (Category 1, HyperAF), areas that were characterized by both hyperautofluorescence and hypoautofluorescence (Category 2, Mixed AF), and areas that were predominantly hypoautofluorescent (Category 3, HypoAF). Note that all SD-OCT scans (bottom) show areas of nGA.

Figure 3

Example of the longitudinal changes in FAF characteristics preceding the development of atrophy. Top row shows CFPs for the baseline (0 months) and final visit (42 months), where an area of GA is only visible by the final visit (indicated by the black dashed box at 42 months). Middle row shows FAF images that are magnified from the areas outlined by the black dashed boxes in the CFPs at various time intervals, where the corresponding SD-OCT scans are shown (bottom row; the location of these scans are also outlined on the CFPs as dashed black lines) for the development of nGA at 18 months and drusen-associated atrophy detected on SD-OCT at 36 months. The FAF imaging revealed that the area of nGA (18 months) was characterized by predominantly hyperautofluorescent changes, while the area of drusen-associated atrophy (36 months) was characterized by the presence of hyper- and hypoautofluorescent changes, which also is unlike the area of GA (42 months) that appears as a clearly demarcated area of hypoautofluorescence.