Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update

Abstract

Purpose: To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies.

Methods: Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), "cone dystrophy with supernormal rod ERG" (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM).

Results: In patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change.

Conclusions: Parafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention.

Fig. 1

Full-field ERGs, PERGs and AF in 3 patients with rod-cone dystrophy (a–c) including a patient with RP18 (a) and Usher syndrome (b). Row D shows full-field ERGs and AF in a case of Leber congenital amaurosis; ERGs and the AF image were obtained in the presence of nystagmus and are consequently noisy. Normal examples are shown for comparison (e). LU indicates log units greater (+) or less (−) than the ISCEV standard flash

Fig. 2

Full-field ERGs, PERGs and AF in cone rod-dystrophy consequent upon mutation in RPGR (a), RIMS1 (b), “cone dystrophy with supernormal rod ERG” (c) and in a case of X-linked retinoschisis (RS1; d). Normal examples are shown for comparison (e). LU indicates log units greater (+) or less (−) than the ISCEV standard flash

Fig. 3

Comparison of mean ring radius with PERG P50 in 62 patients with rod-cone dystrophy (RP; broken linear regression line) and normal visual acuity and in 19 patients with other retinal dystrophies, including 4 cone or cone-rod dystrophy cases in which there was a detectable PERG (solid regression line)

Fig. 4

Multifocal ERGs (a), small field PERGs (b), Humphrey visual field (c) and photopic (d) and scotopic (e) fine matrix mapping in a patient with a clinical diagnosis of RP. Diamonds and error bars in (b) show mean values and standard deviations for 8 normal subjects; triangles and squares show patient data from right and left eyes. Contour plots (d and e) show sensitivity gradients over tested retinal locations; corresponding 3-D plots show retinal location (abscissa, degrees) and thresholds (ordinate, log units). Labelling (x) shows correspondence between the orientation of contour and threshold plots. Normal photopic and scotopic values are plotted in Fig. 5a and d

Fig. 5

Contour sensitivity plots (rows 1 and 3) and 3-D threshold plots (rows 2 and 4) obtained in representative normal subjects (a, d) and in 3 RP patients (b, e and c, f). Subjects were tested under photopic (a–c) and/or scotopic conditions (d–f). Labelling (x) shows correspondence between the orientation of contour and threshold plots. Abscissa shows retinal location (degrees), ordinate axes show threshold (log units). Corresponding photopic FMM in individual (e) has been published elsewhere [18]. Normal 3-D plots show averaged data from 14 (a) or 12 (d) normal subjects

Fig. 6

AF images, mfERGs and corresponding Humphrey visual fields in 3 patients with RP and normal visual acuity

Fig. 7

Multifocal ERGs (a), Humphrey visual field (b) and photopic (c, d) and scotopic (e, f) fine matrix mapping in a patient with cone-rod dystrophy consequent upon RIMS1 mutation. Labelling (x) shows correspondence between the orientation of contour and 3-D threshold plots. Abscissa shows retinal location (degrees), ordinate axes show threshold (log units). Threshold values for half the tested area have been removed from c and e, to expose the foveal values that would otherwise be obscured

Fig. 8

Contour sensitivity plots (rows 1 and 3) and 3-D threshold plots (rows 2 and 4) obtained in 3 patients with cone-rod dystrophy consequent upon RPGR (column 1) or RIMS1 mutations (columns 2 and 3). Subjects were tested under photopic (a–c) and scotopic conditions (d–f). Labelling (x) shows correspondence between the orientation of contour and threshold plots. Abscissa shows retinal location (degrees), ordinate axes show threshold (log units)