Adaptive Optics Scanning Laser Ophthalmoscopy Images in a Family with the Mitochondrial DNA T8993C Mutation
ABSTRACT This study was designed to assess the effect of mitochondrial DNA (mtDNA) mutation T8993C on cone structure in a family expressing neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) syndrome.
Five family members were studied, using clinical examination, nerve conduction studies, perimetry, optical coherence tomography (OCT) measures of central retinal thickness, and electroretinography. High-resolution images of cone structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) were obtained in four subjects with stable fixation. Cone spacing was compared to 18 age-similar normal subjects and converted to z-scores at each location where unambiguous cones were identified. Tissue levels of T8993C mutant heteroplasmy in blood and hair follicles were quantified using real-time allele-refractory mutations system (ARMS) quantitative polymerase chain reaction (qPCR).
Subjects expressing the T8993C mutation showed varying levels of disease severity. The subject with the lowest mutant load (42%-54%) showed no neurologic or retinal abnormalities. The remaining four subjects with over 77% mutant load all expressed severe neurologic and/or retinal abnormalities. AOSLO images revealed three patterns of cone spacing: pattern 1, normal; pattern 2, increased cone spacing within a contiguous cone mosaic; and pattern 3, patchy cone loss with increased cone spacing. Visual function was most severely affected in pattern 3.
High levels of T8993C mutant load were associated with severe neurologic or visual dysfunction, while lower levels caused no detectable abnormalities. Visual function was better in patients with a contiguous and regular cone mosaic. Patients expressing high levels of the mtDNA T8993C mutation show abnormal cone structure, suggesting normal mitochondrial DNA is necessary for normal waveguiding by cones.
SourceAvailable from: Masanori Hangai[Show abstract] [Hide abstract]
ABSTRACT: To assess macular photoreceptor abnormalities in eyes with retinitis pigmentosa (RP) with preserved central vision using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Fourteen eyes of 14 patients with RP (best-corrected visual acuity 20/20 or better) and 12 eyes of 12 volunteers underwent a full ophthalmologic examination, fundus autofluorescence, spectral-domain optical coherence tomography (SD-OCT), and imaging with a prototype AO-SLO system. Cone density and spatial organization of the cone mosaic were assessed using AO-SLO images. In 3 eyes with RP and preserved central vision, cones formed a mostly regular mosaic pattern with small patchy dark areas, and in 10 eyes, the cone mosaic patterns were less regular, and large dark regions with missing cones were apparent. Only one eye with RP demonstrated a normal, regular cone mosaic pattern. In eyes with RP, cone density was significantly lower at 0.5 mm and 1.0 mm from the center of the fovea compared to normal eyes (P<0.001 and 0.021, respectively). At 0.5 mm and 1.0 mm from the center of the fovea, a decreased number of cones had 6 neighbors in eyes with RP (P = 0.002 for both). Greater decrease in cone density was related to disruption of the photoreceptor inner segment (IS) ellipsoid band on SD-OCT images (P = 0.044); however, dark regions were seen on AO-SLO even in areas of continuous IS ellipsoid on SD-OCT. Decreased cone density correlated thinner outer nuclear layer (P = 0.029) and thinner inner segment and outer segment thickness (P = 0.011) on SD-OCT. Cone density is decreased and the regularity of the cone mosaic spatial arrangement is disrupted in eyes with RP, even when visual acuity and foveal sensitivity are good. AO-SLO imaging is a sensitive quantitative tool for detecting photoreceptor abnormalities in eyes with RP.PLoS ONE 11/2013; 8(11):e79447. DOI:10.1371/journal.pone.0079447 · 3.53 Impact Factor
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ABSTRACT: The authors report the use of adaptive-optics scanning laser ophthalmoscopy (AO-SLO) to investigate RHO, D190N autosomal-dominant retinitis pigmentosa in two siblings (11 and 16 years old, respectively). Each patient exhibited distinct hyperautofluorescence patterns in which the outer borders corresponded to inner segment ellipsoid band disruption. Areas within the hyperautofluorescence patterns exhibited normal photoreceptor outer segments and retinal pigment epithelium. However, AO-SLO imaging revealed noticeable spacing irregularities in the cone mosaic. AO-SLO allows researchers to characterize retinal structural abnormalities with precision so that early structural changes in retinitis pigmentosa can be identified and reconciled with genetic findings. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:xxx-xxx.].09/2014; 45(5):1-5. DOI:10.3928/23258160-20140908-01
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ABSTRACT: PURPOSE. To assess photoreceptor structure in macular microholes by using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and spectral-domain optical coherence tomography (SD-OCT) and compare with visual acuity. METHODS. Fourteen eyes from 12 patients with macular microholes underwent a full ophthalmologic examination and imaging with a fundus camera, SD-OCT, and an original prototype AO-SLO system at each visit. RESULTS. All eyes had a cone outer segment tip line disruption and a normal retinal pigment epithelium line on SD-OCT images. Adaptive optics scanning laser ophthalmoscopy revealed foveal cone disruption (13 eyes, round or oval; 1 eye, T-shaped) in all eyes. Cone disruption area (mean = 14,805 +/- 9120 mu m(2); range, 3495-35,901 mu m(2)) positively correlated with logMAR visual acuity at the first visit (P = 0.015, r(s) = 0.679). During the follow-up period, cone disruption area increased in two eyes, was stable in seven eyes, and decreased in five eyes. At the last visit, cone disruption area (mean = 8717 +/- 7432 mu m(2); range, 0-25,746 mu m(2)) also positively correlated with logMAR visual acuity (P = 0.035, r(s) = 0.610). In one patient with bilateral microholes and no apparent vitreous traction, lesion size gradually increased. Cone disruption area decreased and visual acuity improved following oral prednisone therapy. CONCLUSIONS. Cone disruption occurs in eyes with macular microholes and a larger cone disruption area translates into a poorer visual acuity. Macular microholes, which are commonly observed as foveal cone inner and outer segment disruptions, may occur in eyes with or without vitreofoveal traction.Investigative Ophthalmology & Visual Science 08/2014; 55(9). DOI:10.1167/iovs.13-13792 · 3.66 Impact Factor