Age-related Accumulation and Spatial Distribution of Lipofuscin in RPE of Normal Subjects

Purpose: To characterize the age-related accumulation of lipofuscin in a population of normal subjects, resolve differences in estimated accumulation rates obtained in previous studies, and characterize the spatial distribution of lipofuscin in the normal fundus.

Methods: Spectrophotometric measurements were made at the fovea and 7 degrees temporal to the fovea in 145 normal subjects (age range, 15-80 years). Spatial distribution along the four cardinal meridians was measured in selected subjects by both spectrophotometry and autofluorescence imaging. To minimize contributions of extraneous fluorophores, macular pigment, and melanin, all measurements used excitation at 550 nm, integrating emission between 650 and 750 nm.

Results: Lipofuscin fluorescence increased linearly until age 70, then declined. The rate of accumulation was significantly slower in the fovea than at the temporal site; accumulation rates in vivo were greater than previously observed in microscopic studies. Fluorescence was approximately 40% lower in the fovea than at 7 degrees eccentricity and was asymmetrically distributed around the fovea. The fluorescence was maximal at approximately 11 degrees temporally, approximately 7 degrees nasally, approximately 13 degrees superiorly, and approximately 9 degrees inferiorly. At the same eccentricity, fluorescence was always less along the inferior meridian than along any other.

Conclusions: Light absorption by RPE melanin can explain differences between the in vivo and ex vivo estimates of the rate of lipofuscin accumulation. Declining fluorescence at old age may represent removal of atrophic RPE cells. The spatial distribution of lipofuscin generally matches that of rods and reflects, rather than predicts, the pattern of age-related loss of rod photoreceptors.