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Uma Balakrishnan, Niamh Wynne, Wanda Pfeifer, Joseph Carroll, Arlene V Drack; Disrupted Macular Cone Post-Synaptic Circuitry is Related to Poor Vision in Albinism. Invest. Ophthalmol. Vis. Sci. 2022;63(7):3533.
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© ARVO (1962-2015); The Authors (2016-present)
To examine whether aberrant macular cone post-synaptic circuitry may underly the decreased best corrected visual acuity (BCVA) seen in albinism.
Eight patients with albinism underwent multifocal electroretinography (mfERG, VERIS) and retinal imaging with adaptive optics scanning laser ophthalmoscopy (AOSLO). Pearson correlation of peak cone density (CD) with BCVA, mfERG amplitudes, and mfERG “slope” (rate of amplitude decline between the central Ring [R] 2 and peripheral R6) was performed. Parafoveal CDs and their rate of decline were compared to mfERG slope in 4 subjects. Control data was obtained from our previous studies of healthy individuals with peak CD measurements (n=58 [PMC7746960]), parafoveal CD measurements (n=20 [PMC3348369]), or mfERG (n=18 [PMC6754264]).
All subjects had below average peak CD (mean 62,223±34,153; range 22,611-129,576 cones/mm2 vs. 180,286±25,436; 122,710-247,710 cones/mm2 in controls), decreased BCVA (mean 20/63; range 20/25-20/150), and flattened mfERG topography (R2-R6 slope: 0.239 vs. 0.312 in controls). Higher peak CD correlated with better logMAR BCVA (r=-0.85, p=0.002) and higher mfERG amplitudes in the periphery (r=0.68, p=0.029), but not centrally (r=-0.08). Parafoveal CDs were low compared to controls within the central 2 degrees, and we did not observe an association between higher CD and steeper mfERG topographies. Interestingly, the 2 subjects with 2 confirmed pathogenic mutations in OCA1 had the steepest mfERG topography and BCVA worse than 20/70 (peak CD: 42,100 and 46,400 cones/mm2), while the 5 patients with at least one hypomorphic allele had BCVA better than 20/70 despite having flatter mfERG topography (peak CD range 38,399-129,576 cones/mm2).
Although a wide range of peak foveal cone densities overlapping with the normal range is observed among these patients with albinism, denser cone packing does not result in steeper (more normal) mfERG topography, although it does correlate with better BCVA. Instead, higher cone packing is associated with higher peripheral mfERG amplitudes, suggesting abnormal connections between cone photoreceptors and bipolar cells, which could be similar to the unrefined circuitry seen in fetal retinas. This aberrant post-synaptic circuitry may explain why, even among albinism patients with milder foveal hypoplasia and denser foveal cone packing, optimal visual acuity is often unachievable.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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