FPF MAPPING IN DIAGNOSIS OF GLAUCOMA

 

It has been shown that mitochondrial metabolic dysfunction in conditions such as glaucoma, can be used as a marker for the pre-apoptotic cellular state of the eye. Mitochondrial dysfunction and altered energy dynamics drive the production of reactive oxygen species (ROS). This biochemical mechanism is implicated in the apoptosis of retinal ganglion cells (RGCs).

Mitochondrial dysfunction with production of ROS results in conversion of mitochondrial flavoproteins to their oxidized state, which produces an increase in their blue light-stimulated fluorescence. This finding has established flavoprotein fluorescence (FPF) as a potential biomarker for mitochondrial dysfunction. This technology of FPF-mapping could be developed into a non-invasive method to image the eye for pre-perimetric glaucoma.

RGCs, which are highly concentrated within the macula, experience impairment of mitochondrial activity as a result of increased IOP. Studies have shown changes in the macula act as an early marker of glaucoma in a sub-set of patients.

In a study performed at the New York Eye and Ear Infirmary of Mount Sinai, retinal FPF was measured as a surrogate for mitochondrial dysfunction in ocular hypertension (OHT) and open-angle glaucoma (POAG) eyes to investigate its potential as a biomarker for substructural glaucomatous injury.

The study demonstrated significantly increased FPF and FPF/RGC+ thickness of the macula in OHT compared to controls. As OHT eyes demonstrate a lack of cpRNFL thinning or visual field defects, it is notable that that increased mitochondrial dysfunction at the macula can be detected prior to clinical evidence of structural or functional deterioration.

In POAG, the ratio of FPF to RGC+ thickness, representing the FPF per mitochondrion within the ganglion and inner plexiform layers, was found to be significantly increased compared to controls.

FPF maps furthermore demonstrated discrete foci of increased FPF, suggesting that mitochondrial dysfunction may occur in distinct patterns or at particular regions of the macula.

 

FPF-mapping has also been used in diabetic patients.

In the following image, a 65 y/o Hispanic male was diagnosed with PDR and CSME. (a, b) Color fundus picture shows macular edema, hard exudates, and hemorrhages. (c) OCT CMT preinjection (574 μm); (d) OCT CMT postinjection (541 μm). (e) FPF map preinjection shows an increase in green-yellow coloring suggesting greater mitochondrial dysfunction (oxidative stress) compared to the (f) blue-green postinjection FPF map. gsu = grayscale units.