Optic Disc Flavoprotein Fluorescence Imaging as a Novel Method to Quantify Disease Burden in Optic Disc Drusen.

PURPOSE: To investigate the ability of flavoprotein fluorescence (FPF) imaging to quantify disease burden in optic disc drusen (ODD).

DESIGN

Cross-sectional study.

PARTICIPANTS

One hundred and fifty-seven ODD eyes (94 participants, ages 7-89 years) and 69 control eyes (53 participants, ages 10-78 years).

METHODS

Comprehensive examination, visual function testing, and multimodal ophthalmic imaging. Statistical analysis was performed using parametric and nonparametric tests, ANOVA, and Spearman correlation.

MAIN OUTCOME MEASURES: LogMAR, static perimetry mean deviation, optic disc and macular FPF, enhanced-depth imaging optical coherence tomography (EDI-OCT), OCT peripapillary retinal nerve fiber layer (pRNFL), and macular ganglion cell complex (mGCC) thickness.

RESULTS

Optic disc FPF signal corresponded with superficial and buried drusen visualized on 97 EDI-OCT B-scans. Compared with controls, ODD eyes have significantly elevated disc FPF (P < .0001) but no difference in macular FPF scores. Examination of age-related changes revealed stable disc FPF in controls over the first 7 decades of life. In contrast, ODD eyes exhibited elevated disc FPF within the first 2 decades of age, which increased over time and remained high after age 40. Sectoral analysis showed significantly elevated disc FPF in all quadrants in ODD compared with controls (P < .001). ODD eyes with visual field loss (mean deviation (MD) < -2 dB) had significantly higher disc FPF and lower pRNFL and mGCC thicknesses compared with ODD eyes without visual field loss (MD ≥ -2 dB) (P < .001 for all). We found a nonlinear relationship between disc FPF and MD (RMSE = 4.4271, R² = 0.4504) and a negative correlation between disc FPF and pRNFL (r = -0.78) and mGCC thicknesses (r = -0.62). Disc FPF, pRNFL, and mGCC had high statistical power in segregating ODD eyes with and without visual field loss.

CONCLUSIONS

Disc FPF is an objective imaging technique to quantify disease burden in ODD, reflecting a combination of drusen autofluorescence signal and metabolic stress from axonopathy. Disc FPF is correlated with structural and functional changes and has high predictive power of visual field loss in ODD, supporting its use as an outcome measure in prospective natural history and treatment studies in ODD.