Advances in Retinal Imaging of Achromatopsia Joseph Carroll, PhD Departments of Ophthalmology, Biophysics, and Cell Biology, Neurobiology, & Anatomy Medical College of Wisconsin Achromatopsia Convention August 2, 2011
Acknowledgements Medical College of Wisconsin Kim Stepien, MD Alf Dubra, PhD JungtaeRha, PhD Robert Cooper Adam Dubis Brett Schroeder Phyllis Summerfelt Chicago Lighthouse/UIC Gerald Fishman, MD Mohamed Genead, MD University of Washington Jay Neitz, PhD Maureen Neitz, PhD $$$$ - NIH EY017607, EY001931, Research to Prevent Blindness, E. Matilda Ziegler Foundation for the Blind, Kirchgessner Foundation, Gene & Ruth Posner Foundation, RD & Linda Peters Foundation, Hope for Vision, Vision for Tomorrow Foundation, & Fight for Sight
Complex layered structure which is made up of different types of cells. Picture from Webvision: The Organization of the Retina and Visual System
In achromatopsia, we are interested in studying photoreceptor structure – as this is likely to be helpful in the translation of gene-based therapies to the condition. Two imaging techniques have emerged that allow us to directly assess photoreceptor structure in patients with achromatopsia and other retinal disorders…
Histology data varies: from suggesting normal peripheral cones (Larsen, 1921), reduced numbers throughout (Harrison et al., 1960; Glickstein & Heath, 1975), or normal numbers in the fovea (Falls et al., 1965).
OCT data suggests progressive loss of cone layers (Thiadens et al. 2010)…
OCT reveals foveal hypoplasia in a number of patients. Unclear what the link is to the pathophysiology of achromatopsia is.
OCT reveals significant variation in the disruption of the IS/OS, and variable thinning of the ONL – suggesting variable degrees of photoreceptor loss.
Imaging with AO reveals significant cone structure in most patients, with some even retaining both an inner and outer segment to the cone. These cones are not functioning normally, but appear to be intact structurally, at least in part.
by an absence of L- and M-cone function. - (L + M) = ~95% of all cones
Individuals with BCM present with poor
color discrimination, reduced central vision, nystagmus, & myopia, but otherwise normal fundus findings.
Two primary genetic pathways in BCM – “one-step” involve a deletion of the LCR whereas “two-step” include a reduction in gene number to 1 and incorporation of a missense mutation in the remaining opsin gene.
- Accumulating evidence for macular atrophy and progressive loss of visual function in BCM (Ayyagari et al., 1999, 2000; Kellner et al., 2004; Michaelides et al., 2004; Mizrahi-Meissonnier et al., 2010). Hofer et al. (2005)
JC_0183 JC_0184 Curcio et al. (1991) 2,626 cones/mm2 4,116 cones/mm2 2,000 – 5,000 cones/mm2 S-Cone Free Zone - Data is consistent with the S-cone free zone being variable in size (Williams et al., 1981; de Monasterioet al., 1985; Norket al., 1990; Curcio et al., 1991). - Residual packing density of S-cones may contribute to phenotypic heterogeneity.
Peripheral BCM Mosaic Rods begin to appear. Large, bright S cones no longer visible, rather cones appear dark (inner segment). Fewer in number than AHCM.