Fundus Autofluorescence in Inherited Retinal Disease: A Review

Abstract

Fundus autofluorescence (FAF) is a non-invasive retinal imaging technique that helps visualize naturally occurring fluorophores, such as lipofuscin, and provides valuable insight into retinal diseases-particularly inherited retinal diseases (IRDs). FAF is especially useful in detecting subclinical or early-stage IRDs and in monitoring disease progression over time. In Stargardt disease, areas of decreased autofluorescence correlate with disease progression and have been proposed as a biomarker for future clinical trials. FAF can also help differentiate Stargardt disease from other macular dystrophies. In retinitis pigmentosa, hyperautofluorescent rings are a common feature on FAF and serve as an important marker for disease monitoring, especially as changes align with those seen on other imaging modalities. FAF is valuable in tracking progression of choroideremia and may help identify disease carrier status. FAF has also improved the characterization of mitochondrial retinopathies such as maternally inherited diabetes and deafness. As a rapid and widely accessible imaging modality, FAF plays a critical role in both diagnosis and longitudinal care of patients with IRDs.

Keywords: fundus autofluorescence; inherited retinal diseases.

Figure 1

Retinoid visual cycle and the origin of fundus autofluorescence signal. An illustration of the retinoid visual cycle that takes place between the retinal pigment epithelium and the outer segments of photoreceptors is shown. Interruption of the visual cycle at any point can lead to the development of inherited retinal degenerations. Accumulation of bisretinoids in retinal pigment epithelium cells as a byproduct of the cycle is the source of fundus autofluorescence signal.

Figure 2

Fundus autofluorescence in Stargardt disease detects features hard to see on color fundus photography. (A) 30° field color fundus photography of a 77-year-old patient with Stargardt disease demonstrates central chorioretinal atrophy and faint gray flecks (green arrows) around central atrophy and along the superior arcades. (B) 30° field fundus autofluorescence better demonstrates hyperautofluorescent flecks and peripapillary sparing around the optic nerve which is nearly imperceptible on fundus photography (cyan arrows). The well-demarcated definitely decreased autofluorescence (DDAF) (red arrow) has been used in multiple clinical trials to assess treatment efficacy in Stargardt disease. The questionably decreased autofluorescence (QDAF) (pink arrow) refers to areas with intermediate autofluorescence signal loss and represents a transitional stage between healthy retina and advanced atrophy. QDAF regions are often poorly demarcated and progress to DDAF over time.

Figure 3

Hyperautofluorescent rings in retinitis pigmentosa seen on fundus autofluorescence compared to color fundus photography. (A) Montage color fundus photographs of a 36-year-old patient with autosomal dominant retinitis pigmentosa due to mutations in RHO demonstrate waxy pallor of the optic nerve, vascular attenuation and nasal and inferior bone spicules. (B) 55° field fundus autofluorescence demonstrates a central hyperautofluorescent ring, smaller in the right eye than the left, which is not seen on color fundus photographs (green arrows). Areas of both definitely decreased autofluorescence (red arrows) and questionably decreased autofluorescence can be seen (pink arrows).

Figure 4

Color fundus photographs and fundus autofluorescence in choroideremia. (A) Montage color fundus photographs of a 49-year-old patient with choroideremia demonstrates diffuse chorioretinal atrophy. (B) 55° field fundus autofluorescence demonstrates a small island of centrally preserved relative hyperautofluorescence that correlates to preserved photoreceptors (green arrows). The area of this central island has been measured as a biomarker of disease progression and is challenging to measure on fundus photography.