Adaptive optics scanning laser ophthalmoscopy in a heterogenous cohort with Stargardt disease.
ABCA4
AOSLO
Adaptive optics
Adaptive optics scanning laser ophthalmoscope
Retinal imaging
Stargardt disease
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 10 2024
09 10 2024
Historique:
received:
10
05
2024
accepted:
22
09
2024
medline:
10
10
2024
pubmed:
10
10
2024
entrez:
9
10
2024
Statut:
epublish
Résumé
Image based cell-specific biomarkers will play an important role in monitoring treatment outcomes of novel therapies in patients with Stargardt (STGD1) disease and may provide information on the exact mechanism of retinal degeneration. This study reports retinal image features from conventional clinical imaging and from corresponding high-resolution imaging with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) in a heterogenous cohort of patients with Stargardt (STGD1) disease. This is a prospective observational study in which 16 participants with clinically and molecularly confirmed STGD1, and 7 healthy controls underwent clinical assessment and confocal AOSLO imaging. Clinical assessment included short-wavelength and near-infrared fundus autofluorescence, spectral-domain optical coherence tomography, and macular microperimetry. AOSLO images were acquired over a range of retinal eccentricities (0°-20°) and mapped to areas of interest from the clinical images. A regular photoreceptor mosaic was identified in areas of normal or near normal retinal structure on clinical images. Where clinical imaging indicated areas of retinal degeneration, the photoreceptor mosaic was disorganised and lacked unambiguous cones. Discrete hyper-reflective foci were identified in 9 participants with STGD1 within areas of retinal degeneration. A continuous RPE cell mosaic at the fovea was identified in one participant with an optical gap phenotype. The clinical heterogeneity observed in STGD1 is reflected in the findings on confocal AOSLO imaging.
Identifiants
pubmed: 39384610
doi: 10.1038/s41598-024-74088-y
pii: 10.1038/s41598-024-74088-y
doi:
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
23629Informations de copyright
© 2024. The Author(s).
Références
Tanna, P., Strauss, R. W., Fujinami, K. & Michaelides, M. Stargardt disease: Clinical features, molecular genetics, animal models and therapeutic options. Br. J. Ophthalmol.101, 25–30 (2017).
pubmed: 27491360
doi: 10.1136/bjophthalmol-2016-308823
Spiteri Cornish, K. et al. The epidemiology of Stargardt disease in the United Kingdom. Ophthalmol. Retin.1, 508–513 (2017).
doi: 10.1016/j.oret.2017.03.001
Al-Khuzaei, S. et al. An overview of the genetics of ABCA4 retinopathies, an evolving story. Genes12, 1241 (2021).
pubmed: 34440414
pmcid: 8392661
doi: 10.3390/genes12081241
Al-Khuzaei, S. et al. The role of multimodal imaging and vision function testing in ABCA4-related retinopathies and their relevance to future therapeutic interventions. Ther. Adv. Ophthalmol.13, 25158414211056384 (2021).
pubmed: 34988368
pmcid: 8721514
doi: 10.1177/25158414211056384
Schulz, H. L. et al. Mutation spectrum of the ABCA4 gene in 335 stargardt disease patients from a multicenter German cohort—impact of selected deep intronic variants and common SNPs. Investig. Ophthalmol. Vis. Sci.58, 394–403 (2017).
doi: 10.1167/iovs.16-19936
Georgiou, M., Fujinami, K. & Michaelides, M. Inherited retinal diseases: therapeutics, clinical trials and end points—a review. Clin. Exp. Ophthalmol.49, 270–288 (2021).
pubmed: 33686777
doi: 10.1111/ceo.13917
World Medical Association Declaration of Helsinki. JAMA310, 2191 (2013).
Steinman, R. M. Effect of target size, luminance, and color on monocular fixation. J. Opt. Soc. Am.55, 1158 (1965).
doi: 10.1364/JOSA.55.001158
Young, L. K., Morris, T. J., Saunter, C. D. & Smithson, H. E. Compact, modular and in-plane AOSLO for high-resolution retinal imaging. Biomed. Opt. Express9, 4275 (2018).
pubmed: 30615719
pmcid: 6157778
doi: 10.1364/BOE.9.004275
Hirsch, J. & Curcio, C. A. The spatial resolution capacity of human foveal retina. Vis. Res.29, 1095–1101 (1989).
pubmed: 2617858
doi: 10.1016/0042-6989(89)90058-8
Mallen, E. A. H. & Kashyap, P. Technical note: Measurement of retinal contour and supine axial length using the Zeiss IOLMaster. Ophthalmic Physiol. Opt.27, 404–411 (2007).
pubmed: 17584293
doi: 10.1111/j.1475-1313.2007.00490.x
Nõupuu, K., Lee, W., Zernant, J., Tsang, S. H. & Allikmets, R. Structural and genetic assessment of the ABCA4-associated optical gap phenotype. Invest. Ophthalmol. Vis. Sci.55, 7217–7226 (2014).
pubmed: 25301883
pmcid: 4228863
doi: 10.1167/iovs.14-14674
Song, H. et al. Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy. JAMA Ophthalmol.133, 1198–1203 (2015).
pubmed: 26247787
pmcid: 4600048
doi: 10.1001/jamaophthalmol.2015.2443
Song, H. et al. High-resolution adaptive optics in vivo autofluorescence imaging in Stargardt disease. JAMA Ophthalmol.137, 603–609 (2019).
pubmed: 30896765
pmcid: 6567847
doi: 10.1001/jamaophthalmol.2019.0299
Razeen, M. M. et al. Correlating photoreceptor mosaic structure to clinical findings in Stargardt disease. Transl. Vis. Sci. Technol.5, 6 (2016).
pubmed: 26981328
pmcid: 4790429
doi: 10.1167/tvst.5.2.6
Chen, Y. et al. Cone photoreceptor abnormalities correlate with vision loss in patients with Stargardt disease. Investig. Ophthalmol. Vis. Sci.52, 3281–3292 (2011).
doi: 10.1167/iovs.10-6538
Michaelides, M. et al. High-resolution imaging in Stargardt disease: Preliminary observations in preparation for intervention. Invest. Ophthalmol. Vis. Sci.55, 5016 (2014).
Zakka, F. R. et al. Disambiguation of photoreceptor structure in transition zones of retinal degenerative diseases. Invest. Ophthalmol. Vis. Sci.55, 1591 (2014).
Razeen, M. M. et al. Correlating photoreceptor abnormalities on adaptive optics scanning light ophthalmoscopy to conventional clinical findings in patients with Stargardt disease. Invest. Ophthalmol. Vis. Sci.56, 2781 (2015).
Han, G. et al. Adaptive optics imaging of ABCA4 retinal degeneration. ARVO Abstr.55, 2616 (2014).
Audo, I. S. et al. Early findings in a phase I/IIa clinical program for Stargardt disease (STGD1, MIM #248200). In Investig. Ophthalmol. Vis. Sci. Conf. 2015 Annu. Meet. Assoc. Res. Vis. Ophthalmol. ARVO 2015. United States, vol. 56 3819 (2015).
Kasilian, M. et al. Reliability of cone density measurements on adaptive optics images in Stargardt disease. Invest. Ophthalmol. Vis. Sci.56, 4928 (2015).
Reback, M. A., Song, H., Latchney, L. R. & Chung, M. M. Longitudinal adaptive optics imaging reveals regional variation in cone and rod loss in Stargardt disease. Invest. Ophthalmol. Vis. Sci.56, 4929 (2015).
Favazza, T. L. et al. AO-SLO imaging of diseased retina using offset and confocal apertures. Invest. Ophthalmol. Vis. Sci.57, 1662 (2016).
Song, H., Rossi, E. A., Latchney, L. & Chung, M. M. Autofluorescence of the photoreceptors in Stargardt disease (SD) identified using fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO). Invest. Ophthalmol. Vis. Sci.59, 4635 (2018).
Song, H. et al. Adaptive optics scanning laser ophthalmoscopy in stargardt disease reveals decreased cone and rod densities. Invest. Ophthalmol. Vis. Sci.54, 1743 (2013).
Shah, M., Young, L. K., Downes, S. M. & Smithson, H. Investigating the clinical use of adaptive optics scanning laser ophthalmoscopy in patients with Stargardt disease. In Investigative Ophthalmology & Visual Science vol. 60 4580 (2019).
Pedersen, H. R. et al. Multimodal in-vivo maps as a tool to characterize retinal structural biomarkers for progression in adult-onset Stargardt disease. Front. Ophthalmol.4, 1384473 (2024).
doi: 10.3389/fopht.2024.1384473
Birnbach, C. D., Järveläínen, M., Possin, D. E. & Milam, A. H. Histopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus. Ophthalmology101, 1211–1219 (1994).
pubmed: 8035984
doi: 10.1016/S0161-6420(13)31725-4
Tanna, P. et al. Reliability and repeatability of cone density measurements in patients with Stargardt disease and RPGR-associated retinopathy. Investig. Ophthalmol. Vis. Sci.58, 3608–3615 (2017).
doi: 10.1167/iovs.17-21904
Davidson, B. et al. Automatic cone photoreceptor localisation in healthy and Stargardt afflicted retinas using deep learning. Sci. Rep.8, 1–13 (2018).
doi: 10.1038/s41598-018-26350-3
Bergeles, C. et al. Unsupervised identification of cone photoreceptors in non-confocal adaptive optics scanning light ophthalmoscope images. Biomed. Opt. Express8, 3081 (2017).
pubmed: 28663928
pmcid: 5480451
doi: 10.1364/BOE.8.003081
Yamaguchi, M. et al. High-resolution imaging by adaptive optics scanning laser ophthalmoscopy reveals two morphologically distinct types of retinal hard exudates. Sci. Rep.6, 1–14 (2016).
Karst, S. G. et al. Characterization of in vivo retinal lesions of diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy. Int. J. Endocrinol.2018, 7492946 (2018).
pubmed: 29853882
pmcid: 5954931
doi: 10.1155/2018/7492946
Vogel, R. N. et al. High-resolution imaging of intraretinal structures in active and resolved central serous chorioretinopathy. Investig. Ophthalmol. Vis. Sci.58, 42–49 (2017).
doi: 10.1167/iovs.16-20351
Khan, K. N. et al. Early patterns of macular degeneration in ABCA4-associated retinopathy. Ophthalmology125, 735–746 (2018).
pubmed: 29310964
doi: 10.1016/j.ophtha.2017.11.020
Battaglia Parodi, M., Sacconi, R., Romano, F. & Bandello, F. Hyperreflective foci in Stargardt disease: 1-Year follow-up. Graefe’s Arch. Clin. Exp. Ophthalmol.257, 41–48 (2019).
doi: 10.1007/s00417-018-4167-6
Piri, N., Nesmith, B. L. W. & Schaal, S. Choroidal hyperreflective foci in Stargardt disease shown by spectral-domain optical coherence tomography imaging: Correlation with disease severity. JAMA Ophthalmol.133, 398–405 (2015).
pubmed: 25590640
doi: 10.1001/jamaophthalmol.2014.5604
Coscas, G. et al. Hyperreflective dots: A new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration. Ophthalmologica229, 32–37 (2012).
pubmed: 23006969
doi: 10.1159/000342159
Uji, A. et al. Association between hyperreflective foci in the outer retina, status of photoreceptor layer, and visual acuity in diabetic macular edema. Am. J. Ophthalmol.153, 710-717.e1 (2012).
pubmed: 22137207
doi: 10.1016/j.ajo.2011.08.041
Framme, C., Wolf, S. & Wolf-Schnurrbusch, U. Small dense particles in the retina observable by spectral-domain optical coherence tomography in age-related macular degeneration. Investig. Ophthalmol. Vis. Sci.51, 5965–5969 (2010).
doi: 10.1167/iovs.10-5779
Dorey, C. K., Wu, G., Ebenstein, D., Garsd, A. & Weiter, J. J. Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration. Investig. Ophthalmol. Vis. Sci.30, 1691–1699 (1989).
Ts’o, M. O. M. & Friedman, E. The retinal pigment epithelium: III. Growth and development. Arch. Ophthalmol.80, 214–216 (1968).
pubmed: 5661888
doi: 10.1001/archopht.1968.00980050216012
Krombach, F. et al. Cell size of alveolar macrophages: An interspecies comparison. Environ. Health Perspect.105, 1261 (1997).
pubmed: 9400735
pmcid: 1470168
Heitkotter, H. et al. Extracting spacing-derived estimates of rod density in healthy retinae. Biomed. Opt. Express14, 1 (2023).
pubmed: 36698662
doi: 10.1364/BOE.473101