Abstract
Purpose :
Waardenburg syndrome type two is an autosomal dominant syndrome associated with auditory and pigmentary defects. Reduced or absent melanin pigmentation has been associated with foveal hypoplasia in oculocutaneous albinism (OCA) arising from other etiologies. Here we examined foveal anatomical specialization in individuals with melanocyte inducing transcription factor (MITF)-related Waardenburg syndrome type 2A (WS2A) and compared this to data from individuals with OCA.
Methods :
Adaptive optics (AO) retinal imaging was used to assess the cone photoreceptor mosaic of 7 eyes (4 individuals) from two families with molecularly confirmed WS2A, as well as 3 eyes (3 individuals) from three families with molecularly confirmed OCA1B. A total of 231 (116 WS2A and 115 OCA) regions of interest (ROIs) containing ~100 cones each were selected from the AO images for further quantification of cone density at the fovea and temporal to the fovea. The fovea was defined as location of estimated highest cone density. Foveal hypoplasia grading (PMID 21529956) was performed using optical coherence tomography (OCT) and evaluated alongside peak cone density in 5 of the 10 eyes. Motion contrast enhancement (PMID 19907024) was used to visualize the parafoveal vasculature in one eye of one individual.
Results :
Cone density in WS2A deviated from normative histologic values (PMID 2324310) to a greater extent near the fovea <1.0 mm (36±32%, n=87 ROIs; Mean±SD of the absolute % difference) when compared to more eccentric locations >1.0 mm (13±10%, n=29). The overall pattern of cone density in WS2A was similar to measurements obtained in OCA1B (<1.0 mm: 38±15%, n=85; >1.0 mm 25±12%, n=30) and also in agreement with previous studies quantifying cones in OCA (PMIDs 24845642, 27887888, 30398625, 32543650). Although peak cone density in WS2A was variable at the fovea (ranging from 49,749 to 76,296 cells/mm2), peak cone density decreased with increasing foveal hypoplasia grade (ranging from 2 to 3) in a manner that was also similar to what has been reported for OCA. Finally, as would be expected for foveal hypoplasia, the parafoveal vasculature was abnormal with an absent foveal avascular zone.
Conclusions :
The fovea in WS2A shares similarities with foveal structure in OCA and may provide new insights into the contribution of MITF and ocular pigment cells during foveal development.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.