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PURPOSE Fluorescence lifetime imaging ophthalmoscopy (FLIO) shows characteristic patterns in macular telangiectasia Type 2 (MacTel). This study investigates FLIO changes over time to better understand disease progression. METHODS Thirty-three patients with MacTel (age 60 ± 15 years) were followed at the Moran Eye Center with a prototype Heidelberg Engineering FLIO. The mean follow-up time was 19 ± 8 months (range 6-34 months). Fundus autofluorescence was excited at 473 nm, and FLIO lifetimes were recorded in in short (498-560 nm) and long (560-720 nm) spectral wavelengths channels. RESULTS Autofluorescence lifetimes imaging ophthalmoscopy lifetimes from the MacTel area prolonged significantly over time (subfield T1, baseline: short spectral channel 210 ± 54 ps, long spectral channel 269 ± 58 ps; follow-up: short spectral channel 225 ± 59 ps, P < 0.001, long spectral channel 282 ± 64 ps, P < 0.01). The average 12-months prolongation of FLIO lifetimes was 9 ps (short spectral channel) and 8 ps (long spectral channel). Autofluorescence lifetimes changes correlated positively with ellipsoid zone loss and negatively with changes in retinal thickness. CONCLUSION Autofluorescence lifetimes in MacTel slowly prolong over time, and temporal patterns progress to full rings. Detailed knowledge about FLIO changes will aid in understanding disease development and progression.