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Aim-To describe a new method of evaluating the topographic distribution of fundus autofluorescence in eyes with retinal disease. Methods-Images of fundus autofluorescence were obtained in five patients and 34 normal volunteers using a confocal scanning laser ophthalmoscope (cSLO). To evaluate the topographic distribution of fundus autofluorescence throughout the posterior pole a rectangular box, 10 × 750 pixels, was used as the area of analysis. The box was placed, horizontally, across the macular region. The intensity of fundus autofluorescence of each pixel within the rectangular box was plotted against its degree of eccentricity. Profiles of fundus autofluorescence from patients were compared with those obtained from the age matched control group and with cSLO images. Results-Profiles of fundus autofluorescence appeared to represent the topographic distribution of fundus autofluorescence throughout the posterior pole appreciated in the cSLO images, and allowed rapid identification and quantification of areas of increased or decreased fundus autofluorescence. Conclusions-Fundus autofluorescence profiles appear to be useful to study the spatial distribution of fundus autofluorescence in eyes with retinal disease. (Br J Ophthalmol 2000;84:741-745) The study of accumulation of lipofuscin in the retinal pigment epithelium (RPE) has attracted the attention of many researchers in the past decades. Although still incompletely understood, it is believed that lipofuscin represents the end product of phagocytosed photoreceptor outer segment discs, and to a lesser extent, of autophagy.1-6 "Ex vivo" studies in donor human eyes have shown that lipofuscin accumulates in the RPE with age 7-9 and retinal disease. [10][11][12][13][14][15][16][17][18] Similarly, it has been demonstrated that, in normal subjects, there is a topographic distribution of RPE lipofuscin content throughout the fundus, being higher at the posterior pole, with a localised dip at the fovea, and lower towards the peripheral retina. [7][8][9] Excessive accumulation of lipofuscin in the RPE has been associated with degeneration of RPE cells and photoreceptors. 17 19 Hence, information regarding the distribution of fundus autofluorescence may provide insight on the sequence of events that lead to retina damage in a variety of retinal diseases. Until recently, information regarding the content and spatial distribution of RPE lipofuscin in eyes with retinal disease was limited by the scarce number of eyes available for histopathological evaluation. This problem has been recently overcome with the development of new techniques that allow the study of RPE lipofuscin levels "in vivo". 20-25Using a spectrophotometer 20-22 and a confocal scanning laser ophthalmoscope (cSLO) 23-25 the level of fundus autofluorescence (index of RPE lipofuscin content) has been assessed "in vivo" in a variety of retinal disorders. Previous in vivo studies have quantified fundus autofluorescence in eyes with retinal disease at selected areas of the retina. [20][21][22][2...

, we prospectively examined patients with bull's-eye lesions. Age of onset, duration of symptoms, visual acuity, clinical appearance, and autofluorescence images were recorded, the area of atrophy measured, and electrophysiologic investigations performed. Results: Forty-seven patients, including 6 sibling pairs, met the study entry criteria. On the basis of autofluorescence imaging, 3 distinct groups were identified. Group 1 showed a distinct ring of increased autofluorescence surrounding an area of decreased autofluorescence. In group 2, the ring of increased autofluorescence was not present. Group 3 displayed a speckled appearance within the affected area. All patients had evidence of central sparing in an area of centrally increased autofluorescence. There was significant correlation with the age of onset, visual acuity, and duration of disease. Electrophysiologic tests revealed that 28 patients had macular dysfunction only, 14 had cone-rod dystrophy, 3 had rod-cone dystrophy, and only 2 (monozygotic twins) had cone dystrophy. The correlation between electrophysiologic and autofluorescence data was poor. The sibling pairs had concordant autofluorescence appearance, but electrophysiologic grouping differed in 2 pairs. Conclusions: Bull's-eye maculopathy represents a heterogeneous group of disorders. The clinical appearance was not helpful in assessing the degree of retinal dysfunction. The difference in qualitative characteristics of functional loss between siblings implies that these attributes do not necessarily reflect the influence of the primary mutation.

Aim-To evaluate the reproducibility of the background fundus autofluorescence measurements obtained using a confocal scanning laser ophthalmoscope. Methods-10 normal volunteers and 10 patients with retinal disease were included in the study. One eye per subject was chosen randomly. Five images of the same eye of each individual were obtained, after pupillary dilatation, by two investigators using a confocal scanning laser ophthalmoscope. Background fundus autofluorescence was measured at 7 degrees temporal to the fovea in normal volunteers and between 7 and 15 degrees temporal to the fovea in patients. Within session reproducibility of the measurements obtained by each investigator and interobserver reproducibility were evaluated. Results-For investigator 1 the median values of fundus autofluorescence obtained were 31.9 units for normal volunteers and 27.3 units for patients. The median largest diVerence in readings in normal volunteers was 5.7 units (range 1.4-13.5 units) and in patients 4.2 units (1.5-15.1 units). For investigator 2 the median values of fundus autofluorescence obtained were 28.9 units for normal volunteers and 27.4 units for patients. The median largest diVerence in readings in normal volunteers was 3.6 units (2.7-11.7 units), and in patients 4.1 units (1.5-9.3 units). The median interobserver diVerence in readings in normal volunteers was 3.3 units and for patients 6.6 units. The median greatest interobserver diVerence in measurements obtained for normal volunteers was 8.8 units (8.4-23.0 units) and for patients 11.1 units (7.1-40.8 units). Conclusion-Within session reproducibility of the measurements of background fundus autofluorescence was satisfactory. Although interobserver reproducibility was moderate, the variability of the measurements of fundus autofluorescence between observers appears to be small when compared with variation in fundus autofluorescence with age and disease. (Br J Ophthalmol 1999;83:276-279) It is well recognised that lipofuscin accumulates in the retinal pigment epithelium (RPE) with age.

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