Abstract
Purpose :
Fundus autofluorescence (AF) is a valuable imaging tool in the diagnosis of inherited retinal degenerations (IRDs). Previously, short-wavelength AF (SW-AF) was noted to appear low in patients with biallelic mutations in RPE65. We hypothesize that this dark AF appearance is a feature common to all patients with mutations in the visual cycle (VC) and may be used as a diagnostic tool and a therapeutic outcome measurement.
Methods :
Retrospective review of patients diagnosed with IRDs over the past 9 years was performed. Patients who did not receive quantitative AF (qAF) or near-infrared AF (NIR-AF) imaging were excluded. A cohort of 10 patients with mutations in the VC genes (RPE65, LRAT, RLBP1, RDH5, RDH11) was identified. A similarly aged cohort of 19 patients with mutations in phototransduction (PT) genes (RHO, CNGB1, PDE6A, PDE6B, GUCA1A, GUCY2D, PRPF31, PRPF8, TULP1) was selected for comparison. qAF was acquired using a Spectralis HRA+OCT equipped with an internal fluorescent reference. Non-normalized NIR-AF images were acquired using an HRA2 at a fixed sensitivity of 96. Gray levels of qAF images were analyzed in three concentric rings around the fovea using IGOR software. Gray levels of NIR-AF images were analyzed in ImageJ as a function of distance from the fovea. Welch’s t-test was used for statistical analysis.
Results :
Both qAF and NIR-AF signal intensities were found to be significantly lower in all patients with mutations in VC genes as compared to those with mutations in PT genes (p<0.001). Mean qAF values were 4.8±14.6 in the VC cohort and 175±81 in the PT cohort (Figure 1). Mean foveal NIR-AF values were 22.6±6.6 in the VC cohort and 31.6±11.4 in the PT cohort (Figure 2). The values in the PT cohort fall between the mean and the -95% confidence interval of normal reference values while those in the VC cohort were found to be below the -95% confidence interval. One of the patients with biallelic RPE65 mutations was re-imaged after treatment with voretigene neparvovec and was found to have some improvement of qAF, but levels remained below the -95% confidence interval.
Conclusions :
Dark qAF and NIR-AF are defining features of patients with deficiencies in the VC as compared to patients with deficiencies in PT. Improvement of qAF following treatment of VC gene mutations suggests that these imaging modalities may serve as valuable outcome measurements in future treatment of these diseases.
This is a 2020 ARVO Annual Meeting abstract.