Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity

Abstract

Aim: To characterise and monitor abnormal fundus autofluorescence (AF) in patients with retinitis pigmentosa (RP) who have good visual acuity. Methods: 21 patients with a clinical diagnosis of RP were examined. All had rod-cone dystrophy (ISCEV standard electroretinograms (ERGs)), visual acuity of 6/9 or better, and manifested a parafoveal ring of high density fundus AF. Repeat AF imaging was performed after periods of between 2 years and 5 years in 12 patients. Pattern ERG (PERG) and multifocal ERG (mfERG) were performed in 20 cases. Visual fields (VF), photopic and scotopic fine matrix mapping and small field PERGs were performed in representative cases.Results: The rings of high density AF varied in size between patients (from 4˚-16˚diameter). MfERGs showed relative preservation over the central macular area, correlating with the size of AF ring and with PERG and psychophysical data. Progressive constriction of the AF ring was demonstrated at follow up in three patients. Serial PERG, mfERG, and VFs, performed in one of these cases, showed evidence of deterioration concordant with ring constriction. Conclusions: High density rings of AF, seen in some patients with RP with good visual acuity, demarcate areas of preserved central photopic function. MfERGs correlate with the area encircled by high density AF and the PERG data. The size of the ring of AF can show progressive constriction accompanied by increasing macular dysfunction.F undus autofluorescence (AF) imaging using a scanning laser ophthalmoscope is a non-invasive technique that has proved useful in numerous recent studies of inherited and acquired retinal disease in humans. 1-8 The major fluorophore (lipofuscin) accumulates in pigment epithelial cells and is derived from photoreceptor outer segments. Some patients with retinitis pigmentosa (RP) have abnormal fundus AF in the form of a parafoveal ring of high density that is not visible on routine ophthalmoscopic examination and that varies in size between patients. [9][10][11] The size of the high density ring correlates with the amplitude of the pattern electroretinogram (PERG) P50 component in patients with good visual acuity, 9 12 indicating differing degrees of cone system preservation over areas of central macula. Psychophysically determined sensitivity losses are consistent with the distribution of these high density annuli of fundus AF and with PERG data. Hyperautofluorescent areas represent a transition between abnormal paracentral and normal central cone system function 10 11 and correspond with the internal edge of visual field loss. The question of whether the ring is stationary or may represent a progressive phenomenon has not yet been satisfactorily addressed.Multifocal ERGs (mfERG) are mathematically derived cone driven responses associated with localised retinal areas across the posterior pole. Stimulus elements within a hexagonal array are activated according to a rapid pseudo-random binary sequence (m-sequence) and the resultant continuous ERG signal is cross correlated with the area s...

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

“…2,51 On the basis of these histological findings, we assume that the increased NIA reflects the presence of melanin and melanolysosomes in areas with preserved cone function. The functional findings in our patients and earlier studies on FAF and retinal function 11,13,14 are in agreement with the histological findings. The area within the rings of increased FAF and NIA are identical with the area of preserved cone function.…”

“…This is consistent with OCT findings indicating loss of the outer nuclear layer and corresponding visual field loss in areas peripheral to the perifoveal ring of increased NIA. 22,24 During disease progression, a reduction of size has been observed for the ring of increased FAF, 14 and correlates to the decline of the diameter of areas of preserved autofluorescence with age in the present series.…”

“…41 This ring of increased FAF demarcates the area of preserved cone function, 11,13,14 whereas rod function can be severely affected in areas within the ring. 12 This is puzzling, as FAF intensity at both sides of the ring of increased FAF appears to be similar, and thus FAF intensity does not correspond to photoreceptor function.…”

“…10 Characteristic patterns of FAF abnormalities have been reported in RP, and their association with retinal function has been demonstrated. [11][12][13][14] In contrast, melanin is the major protective agent in the RPE cells sheltering the RPE from exposure to light scattering, radiation, oxidative stress, and light damage. 9,15,16 Melanin granules accumulate in the apical part of the RPE cells undergoing a moderate decrease in numbers with age.…”

Mathematical models of retinitis pigmentosa: The oxygen toxicity hypothesis

“…In all cases the central visual field is preserved, being lost only at the end stage of the disease. Studies by Escher et al (2012); Lima et al (2009Lima et al ( , 2012; Murakami et al (2008); Popović et al (2005); Robson et al (2003Robson et al ( , 2004Robson et al ( , 2006Robson et al ( , 2008Robson et al ( , 2011 describe similar patterns of degeneration.…”