Fundus autofluorescence and spectral-domain optical coherence tomography characteristics in a rapidly progressing form of geographic atrophy

Abstract

Purpose: To further characterize a previously described phenotypic variant of geographic atrophy (GA) associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence (FAF).

Methods: Thirty-six patients (60 eyes; 72.2% women; mean age, 69.4 ± 10.7 years) with this distinct phenotype were examined by simultaneous confocal scanning laser ophthalmoscopy (cSLO) and spectral-domain optical coherence tomography (SD-OCT) imaging. Images were qualitatively and quantitatively analyzed and compared with 60 eyes (38 patients) with non diffuse-trickling GA.

Results: The atrophic area in the diffuse-trickling phenotype showed a grayish FAF signal and characteristic coalescent lobular configuration at the lesion boundaries. SD-OCT revealed a marked splitting of band 4 (the presumptive retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex) in all 240 analyzed border sections of diffuse-trickling GA eyes (four borders/eye) with a mean distance between the inner and outer parts of band 4 of 23.2 ± 7.5 μm. This finding was present in only 13.8% (33/240) of analyzed border sections in non diffuse-trickling GA.

Conclusions: Patients with the rapidly progressing diffuse-trickling GA phenotype exhibited a characteristic marked separation within the RPE/BM complex on SD-OCT-imaging. The presumed histopathologic correlates are basal laminar deposits. Such deposits may promote RPE cell death and, thus, contribute to rapid GA progression. The persistence of these deposits within the atrophic lesion may account for the distinct grayish FAF appearance, which differs from the markedly reduced signal in other forms of GA. Identification of such alterations based on FAF and SD-OCT imaging may be helpful in future interventional trials directed toward slowing GA progression. (ClinicalTrials.gov number, NCT00393692.).

Figures

Figure 1.

The diffuse-trickling phenotype in GA. Longitudinal course monitored by FAF imaging in two female study patients (A, 68 years of age at first examination; B, 53 years of age at first examination). Both exhibited rapidly progressing lobular atrophy with a grayish appearance on FAF imaging. (A) There is early involvement of the fovea in the right eye; the course of the disease in this patient was asymmetrical. However, after 67 months of follow-up, a large atrophic area in the left eye (similar in size to the one in the right eye) and foveal involvement were observed. (B) Although there were large atrophic areas, the fovea was bilaterally spared until later in the disease course.

Figure 2.

Funduscopic features of the diffuse-trickling phenotype in GA. Dense, granular, hyperpigmentary changes are often observed in the central macula and in fellow eyes without GA (A). The borders of the atrophic lesions appeared hyperpigmented (B).

Figure 3.

Different types of borders as visualized by SD-OCT. (A, B) GA other than diffuse-trickling phenotype. Band 4 (assumed RPE/BM complex) narrows, and an outer layer remains throughout the atrophic area (assumed Bruch's membrane). According to Brar et al., the margin depicted in (A) represents a type 1 border with smooth margins and no alterations of the outer retina, and the margin in (B) represents a type 2 border with severe alterations in the outer retinal layers and irregular margins. (C) In contrast to (A) and (B), the border of GA in the diffuse trickling phenotype is characterized by splitting of band 4 in inner and outer regions.

Figure 4.

(A, B, two different patients) Diffuse-trickling GA phenotype. Fundus autofluorescence imaging, simultaneous infrared reflectance, and SD-OCT. Magnification of the SD-OCT images at the border of GA reveals an obvious splitting of SD-OCT band 4 in inner and outer regions.

Figure 5.

Fellow eyes of the diffuse-trickling GA phenotype. FAF, simultaneous infrared reflectance (top), FA (bottom), and SD-OCT. (A) Fellow eye with increased FAF signal but no GA. Magnification of the SD-OCT image reveals an obvious separation of band 4 (arrow). (B) Fellow eye with choroidal neovascularization (leakage in FA imaging and intraretinal fluid in SD-OCT imaging). Magnification of the SD-OCT image reveals an obvious separation of band 4 (arrow).

Figure 6.

(A) Diffuse-trickling GA shows a coalescent lobular configuration with a grayish appearance in FAF images (left). SD-OCT imaging reveals a thin discontinuous hyperreflective band between the INL and the outer part of band 4 within the atrophy. (B) Representative example (diffuse-fine granular phenotype) for the typical black appearance of the atrophic lesion in FAF imaging in eyes with non diffuse-trickling GA (the choroidal vessels may show a slightly increased FAF signal). In SD-OCT imaging, compared with eyes with the diffuse-trickling phenotype, there was no obvious hyperreflective band between the INL and the outer part of band 4.