High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. Invest Ophthalmol Vis Sci.

Abstract

PURPOSE. To investigate macular photoreceptor structure in patients with inherited retinal degeneration using high-resolution images and to correlate the findings with clinical phenotypes and genetic mutations. METHODS. Adaptive optics scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in 16 eyes: five with retinitis pigmentosa (RP), three with cone-rod dystrophy (CRD), and eight without retinal disease. A quadratic model was used to illustrate cone spacing as a function of retinal eccentricity. Cone spacing at 1°eccentricity was compared with standard measures of central visual function, including best-corrected visual acuity (BCVA), foveal threshold, and multifocal electroretinogram (mfERG) amplitude and timing. Intervisit variations were studied in one patient with RP and one patient with CRD. Screening of candidate disease genes identified mutations in two patients, one with RP (a rhodopsin mutation) and the other with CRD (a novel RPGR-ORF15 mutation). RESULTS. Cone spacing values were significantly different from normal for patients with RP (P ϭ 0.01) and CRD (P Ͻ 0.0001) and demonstrated a statistically significant correlation with foveal threshold (P ϭ 0.0003), BCVA (P ϭ 0.01), and mfERG amplitude (P ϭ 0.008). Although many RP patients showed normal cone spacing within 1°of fixation, cones could not be unambiguously identified in several retinal regions. Cone spacing increased in all CRD patients, even those with early disease. Little variation was observed in cone spacing measured during two sessions fewer than 8 days apart. CONCLUSIONS. AOSLO images can be used to study macular cones with high resolution in patients with retinal degeneration. The authors present the first report of cone structure in vivo in patients with mutations in rhodopsin and RPGR-ORF15 and show that macular cones display distinct characteristics, depending on the underlying disease. AOSLO imaging, therefore, can provide new insight into possible mechanisms of cone vision loss in patients with retinal degeneration. (Invest Ophthalmol Vis Sci. 2007;48:3283-3291 The mechanism of cone death in patients with RP, often caused by rod-specific mutations, remains unclear, 2-4 in part because photoreceptors cannot be easily visualized in living eyes. The blur caused by irregularities of the eye's optics limits the resolution of retinal images with the methods commonly used in clinical practice. 5 Adaptive optics (AO) can compensate for these aberrations and has been used to provide highresolution retinal images. 6 -13 Scanning laser ophthalmoscopy (SLO) provides the ability to record images in real time, to obtain high-contrast retinal images, and to optically section the tissue. 14 The integration of AO into SLO-AOSLO-further improves the resolution and contrast resulting from the superior rejection of light from out-of-focus layers. 15-17 After correcting aberrations, lateral resolutions on the order of 2 m can be achieved, thereby allowing visualization of single-cone photoreceptors. 20,21 The present study was designed to evaluate, with the use of a clinically deployable AOSLO system, a larger number of patients with retinal degeneration and unaffected controls than had been reported previously